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t128 | t128_6 | yes | This usually takes the form of a progressive rehabilitation programme that includes exercises aimed at improving strength and balance. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_7 | no | We aimed to assess the effects of surgical versus conservative interventions for treating ACL injuries. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_8 | yes | Results of the search We performed a systematic literature search (up to 18 January 2016) for studies that compared surgery and conservative interventions for treating ACL injuries. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_9 | yes | This review identified one study of 121 young, active adults with an ACL injury in the preceding four weeks. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_10 | no | The study compared surgery (ACL reconstruction followed by structured rehabilitation) with conservative treatment (structured rehabilitation alone). | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_11 | no | The study found there was no difference between surgery and conservative treatment in patient‐reported knee scores at two or five years. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_12 | yes | The study failed to report on the number of participants in each group who had any type of serious or non‐serious complications. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_13 | yes | However, surgery‐related complications included three cases of graft rupture in the surgery group and several participants of the conservative treatment group had unstable knees. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_14 | yes | Twenty‐three of the 59 participants in the conservative treatment group (39%) had either reconstruction of the ACL or repair of a meniscus tear within two years and 30 (51%) underwent surgery within five years. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_15 | no | There was some evidence that similar numbers of participants in the two groups had surgical treatment of knee meniscal injuries at five years. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t129 | t129_1 | yes | Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) Amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) is a fatal neurological disease which produces paralysis of the limb, swallowing and breathing muscles. | Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. Objectives To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. Selection criteria Types of studies: randomized controlled trials Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events. Data collection and analysis One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible. The four trials examining tracheostomy‐free survival included a total of 974 riluzole‐treated patients and 503 placebo‐treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three‐fold increase in serum alanine transferase was more frequent in riluzole‐treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31). Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. |
t129 | t129_2 | yes | There is no available treatment to stop or reverse its progressive course. | Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. Objectives To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. Selection criteria Types of studies: randomized controlled trials Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events. Data collection and analysis One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible. The four trials examining tracheostomy‐free survival included a total of 974 riluzole‐treated patients and 503 placebo‐treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three‐fold increase in serum alanine transferase was more frequent in riluzole‐treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31). Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. |
t129 | t129_3 | no | In this review, we examine the evidence from four randomized clinical trials involving 1477 people with ALS. | Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. Objectives To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. Selection criteria Types of studies: randomized controlled trials Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events. Data collection and analysis One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible. The four trials examining tracheostomy‐free survival included a total of 974 riluzole‐treated patients and 503 placebo‐treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three‐fold increase in serum alanine transferase was more frequent in riluzole‐treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31). Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. |
t129 | t129_4 | no | The methodological quality of the trials was acceptable and three of the trials were easily comparable (although one of them included older patients with more advanced ALS). | Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. Objectives To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. Selection criteria Types of studies: randomized controlled trials Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events. Data collection and analysis One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible. The four trials examining tracheostomy‐free survival included a total of 974 riluzole‐treated patients and 503 placebo‐treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three‐fold increase in serum alanine transferase was more frequent in riluzole‐treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31). Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. |
t129 | t129_5 | no | The results indicate that riluzole 100 mg probably prolongs median survival in people with ALS by two to three months and the safety of the drug is not a major concern. | Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. Objectives To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. Selection criteria Types of studies: randomized controlled trials Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events. Data collection and analysis One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible. The four trials examining tracheostomy‐free survival included a total of 974 riluzole‐treated patients and 503 placebo‐treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three‐fold increase in serum alanine transferase was more frequent in riluzole‐treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31). Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. |
t129 | t129_6 | no | The evidence from randomized controlled trials indicates that participants taking riluzole probably survive longer than participants taking placebo. | Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. Objectives To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. Selection criteria Types of studies: randomized controlled trials Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events. Data collection and analysis One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible. The four trials examining tracheostomy‐free survival included a total of 974 riluzole‐treated patients and 503 placebo‐treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three‐fold increase in serum alanine transferase was more frequent in riluzole‐treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31). Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. |
t129 | t129_7 | yes | The beneficial effects are very modest and the drug is expensive. | Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. Objectives To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. Selection criteria Types of studies: randomized controlled trials Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events. Data collection and analysis One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible. The four trials examining tracheostomy‐free survival included a total of 974 riluzole‐treated patients and 503 placebo‐treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three‐fold increase in serum alanine transferase was more frequent in riluzole‐treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31). Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. |
t129 | t129_8 | no | There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. | Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. Objectives To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. Selection criteria Types of studies: randomized controlled trials Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events. Data collection and analysis One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible. The four trials examining tracheostomy‐free survival included a total of 974 riluzole‐treated patients and 503 placebo‐treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three‐fold increase in serum alanine transferase was more frequent in riluzole‐treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31). Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. |
t129 | t129_9 | yes | Adverse effects from riluzole are relatively minor and for the most part reversible after stopping the drug. | Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. Objectives To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. Selection criteria Types of studies: randomized controlled trials Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events. Data collection and analysis One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible. The four trials examining tracheostomy‐free survival included a total of 974 riluzole‐treated patients and 503 placebo‐treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three‐fold increase in serum alanine transferase was more frequent in riluzole‐treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31). Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. |
t130 | t130_1 | no | Fixation devices secured across the fracture that are placed either directly or externally for treating hip fractures located outside the hip joint Hip fractures located outside the hip joint capsule (extracapsular hip fractures) may be surgically fixed using metal implants. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t130 | t130_2 | yes | Often these are extramedullary devices consisting of a screw or rod, inserted in the upper part of the thigh bone (femur) to bridge (fix) the fracture, connected to a plate secured to the femur. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t130 | t130_3 | no | Sometimes external fixators are used. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t130 | t130_4 | no | In these, the stabilising component is held outside the thigh by pins or screws driven into the bone on either side of the fracture. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t130 | t130_5 | no | The 18 randomised controlled trials included in this review tested seven comparisons in a total of 2615 mainly female and older participants. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t130 | t130_6 | yes | All trials had methodological flaws that may affect the validity of their results and there was a general lack of evidence on long‐term effects and functional recovery. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t130 | t130_7 | yes | Some extramedullary implants appeared to be associated with an increased risk of fixation complications and reoperation. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t130 | t130_8 | no | In particular, three trials comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (the 'standard' extramedullary device for these fractures) found an increased risk of fixation failure for fixed nail plates. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t130 | t130_9 | yes | Less invasive implants, such as the external fixator, which require smaller incisions resulted in less blood loss and often quicker operations than the sliding hip screw. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t130 | t130_10 | no | We concluded that the sliding hip screw seems preferable to older types of fixed nail plates given their high rate of implant and fixation failure. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t131 | t131_1 | yes | Conventionally, recuperation after bowel surgery followed the patients progress. | In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo‐)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo‐)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo‐) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD ‐2.94 days; 95% CI ‐3.69 to ‐2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta‐analysis, but seemed to favour ERAS. The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed. |
t131 | t131_2 | yes | Mobilisation and expansion of diet after surgery was progressed slowly in a stepwise manner following patients progression. | In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo‐)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo‐)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo‐) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD ‐2.94 days; 95% CI ‐3.69 to ‐2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta‐analysis, but seemed to favour ERAS. The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed. |
t131 | t131_3 | yes | This is because it was believed that faster recovery would be unwise. | In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo‐)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo‐)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo‐) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD ‐2.94 days; 95% CI ‐3.69 to ‐2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta‐analysis, but seemed to favour ERAS. The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed. |
t131 | t131_4 | no | In recent years, however, a new concept has been introduced, called Enhanced Recovery after surgery (ERAS) or fast track. | In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo‐)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo‐)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo‐) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD ‐2.94 days; 95% CI ‐3.69 to ‐2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta‐analysis, but seemed to favour ERAS. The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed. |
t131 | t131_5 | yes | This program, introduced by Kehlet et al, is based on the principle that reducing the body's stress response after surgery reduces the time needed to recuperate. | In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo‐)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo‐)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo‐) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD ‐2.94 days; 95% CI ‐3.69 to ‐2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta‐analysis, but seemed to favour ERAS. The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed. |
t131 | t131_6 | yes | This is achieved by interventions around the operation, involving good information, better feeding before the operation and better pain treatment, so patients can get out of bed earlier and start a normal diet earlier and thereby reducing the risk of complications. | In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo‐)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo‐)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo‐) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD ‐2.94 days; 95% CI ‐3.69 to ‐2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta‐analysis, but seemed to favour ERAS. The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed. |
t131 | t131_7 | no | This review investigated whether this intervention is safe and whether it is more effective than the traditional treatment. | In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo‐)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo‐)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo‐) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD ‐2.94 days; 95% CI ‐3.69 to ‐2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta‐analysis, but seemed to favour ERAS. The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed. |
t131 | t131_8 | no | In order to answer this question, 4 randomised trials were found, comparing these two interventions. | In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo‐)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo‐)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo‐) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD ‐2.94 days; 95% CI ‐3.69 to ‐2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta‐analysis, but seemed to favour ERAS. The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed. |
t131 | t131_9 | no | We found that ERAS can be viewed as safe, i.e. not resulting in more complications or deaths, and at the same time decreases the days spent in hospital following major bowel surgery. | In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo‐)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo‐)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo‐) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD ‐2.94 days; 95% CI ‐3.69 to ‐2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta‐analysis, but seemed to favour ERAS. The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed. |
t132 | t132_1 | no | This review aimed to find out which type of treatment works best for preventing future stroke and other blood clotting (thrombotic) events, in people with antiphospholipid syndrome (APS). | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_2 | no | APS is a disease where the immune system produces antibodies directed against the proteins attached to their own cells. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_3 | yes | The presence of such antibodies may increase the risk of developing blood clots (thrombosis) in the blood vessels, or causing pregnancy‐related complications (such as recurrent miscarriage, death of a baby in womb, premature birth, poor growth of the baby, or serious illness in a pregnant women). | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_4 | yes | Blood clots in the arteries can cause strokes, resulting in brain damage or reversible nerve symptoms. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_5 | yes | Blood clots in veins are associated with pain and limb swelling, and if they move they can block blood flow to the lungs. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_6 | no | Two types of drugs are commonly used to prevent blood clots in people with APS: anticoagulants and antiplatelets. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_7 | yes | Anticoagulants prevent blood clot formation by interfering with the activity of proteins involved in blood clotting (clotting factors); while antiplatelets, usually aspirin, prevent platelets from sticking together and impair clot formation. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_8 | yes | Treatment with some anticoagulants (such as warfarin) requires regular blood tests to ensure their adequate action, and a balanced diet in terms of vitamin K intake, mainly in green leafy vegetables. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_9 | no | We looked for studies that randomly allocated people with APS to different treatments, including anticoagulants, antiplatelets, or both. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_10 | no | We identified five studies involving 419 participants. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_11 | yes | The average age of the participants was between 41 and 50 years, and the studies included people with previous stroke or previous blood clots in large veins or arteries. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_12 | yes | Studies took place in eight different countries and had a variety of funding sources. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_13 | no | One trial compared a novel anticoagulant (rivaroxaban) with the standard anticoagulant (warfarin). | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_14 | no | Two studies compared a high dose versus standard dose of warfarin , and two studies compared combinations of antiplatelets, anticoagulants, or both. | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_15 | no | Interventions lasted from 180 days to an average of 3.9 years (SD 2.0). | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_16 | yes | In one study with an anticoagulant (rivaroxaban), participants had no episodes of blood clotting, and there was no difference in the risk of bleeding (moderate‐quality evidence). | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t132 | t132_17 | no | In the two studies comparing higher and lower doses of anticoagulant (warfarin), similar proportions of participants had blood clotting and major bleeding problems (low‐quality evidence), but the higher dose warfarin group had a greater risk of minor bleeding problems and any bleeding problems (low‐quality evidence). | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t133 | t133_1 | yes | Of all the gynaecological cancers, ovarian cancer has the highest death rate and epithelial ovarian cancer accounts for about 90% of all cases. | This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2010, Issue 9 and 2013, Issue 6). Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum‐based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer. Objectives To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL). Search methods In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trails (CENTRAL, the Cochrane Library 2009, Issue 1), MEDLINE, Embase, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For the first update the searches were extended to October 2012 and for this update to February 2017. Selection criteria Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy. Data collection and analysis Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression‐free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention‐to‐treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs. No new studies were found for inclusion in this update from the latest searches. We included eight trials (1644 women). When all chemotherapy regimens were combined, meta‐analysis indicated no significant difference in three‐, five‐ and 10‐year OS or PFS. For five‐year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10; 4 studies, 899 participants; moderate‐certainly evidence) and for the five‐year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17; 3 studies, 761 participants; moderate‐certainly evidence). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10‐year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three‐ and five‐year OS rates have no significant difference between the two groups. There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required. |
t133 | t133_2 | yes | Surgery and six courses of platinum‐based chemotherapy is the standard treatment and 75% of the women may not have any evidence of disease at the end of this treatment. | This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2010, Issue 9 and 2013, Issue 6). Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum‐based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer. Objectives To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL). Search methods In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trails (CENTRAL, the Cochrane Library 2009, Issue 1), MEDLINE, Embase, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For the first update the searches were extended to October 2012 and for this update to February 2017. Selection criteria Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy. Data collection and analysis Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression‐free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention‐to‐treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs. No new studies were found for inclusion in this update from the latest searches. We included eight trials (1644 women). When all chemotherapy regimens were combined, meta‐analysis indicated no significant difference in three‐, five‐ and 10‐year OS or PFS. For five‐year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10; 4 studies, 899 participants; moderate‐certainly evidence) and for the five‐year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17; 3 studies, 761 participants; moderate‐certainly evidence). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10‐year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three‐ and five‐year OS rates have no significant difference between the two groups. There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required. |
t133 | t133_3 | no | However, 75% of the women who respond to initial treatment will relapse within 18 to 28 months and only 20% to 40% of all women will survive beyond five years.Some doctors suggest giving maintenance chemotherapy for epithelial ovarian cancer. | This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2010, Issue 9 and 2013, Issue 6). Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum‐based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer. Objectives To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL). Search methods In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trails (CENTRAL, the Cochrane Library 2009, Issue 1), MEDLINE, Embase, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For the first update the searches were extended to October 2012 and for this update to February 2017. Selection criteria Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy. Data collection and analysis Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression‐free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention‐to‐treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs. No new studies were found for inclusion in this update from the latest searches. We included eight trials (1644 women). When all chemotherapy regimens were combined, meta‐analysis indicated no significant difference in three‐, five‐ and 10‐year OS or PFS. For five‐year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10; 4 studies, 899 participants; moderate‐certainly evidence) and for the five‐year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17; 3 studies, 761 participants; moderate‐certainly evidence). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10‐year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three‐ and five‐year OS rates have no significant difference between the two groups. There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required. |
t133 | t133_4 | no | Maintenance chemotherapy refers to the chemotherapy given to women who have achieved remission after initial surgery and induction chemotherapy.The aim of maintenance chemotherapy is to prolong the duration of remission and improve the overall length of survival. | This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2010, Issue 9 and 2013, Issue 6). Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum‐based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer. Objectives To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL). Search methods In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trails (CENTRAL, the Cochrane Library 2009, Issue 1), MEDLINE, Embase, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For the first update the searches were extended to October 2012 and for this update to February 2017. Selection criteria Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy. Data collection and analysis Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression‐free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention‐to‐treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs. No new studies were found for inclusion in this update from the latest searches. We included eight trials (1644 women). When all chemotherapy regimens were combined, meta‐analysis indicated no significant difference in three‐, five‐ and 10‐year OS or PFS. For five‐year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10; 4 studies, 899 participants; moderate‐certainly evidence) and for the five‐year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17; 3 studies, 761 participants; moderate‐certainly evidence). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10‐year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three‐ and five‐year OS rates have no significant difference between the two groups. There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required. |
t133 | t133_5 | yes | Some studies indicate that maintenance chemotherapy can improve the time without cancer progression, while others do not show any effect. | This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2010, Issue 9 and 2013, Issue 6). Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum‐based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer. Objectives To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL). Search methods In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trails (CENTRAL, the Cochrane Library 2009, Issue 1), MEDLINE, Embase, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For the first update the searches were extended to October 2012 and for this update to February 2017. Selection criteria Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy. Data collection and analysis Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression‐free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention‐to‐treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs. No new studies were found for inclusion in this update from the latest searches. We included eight trials (1644 women). When all chemotherapy regimens were combined, meta‐analysis indicated no significant difference in three‐, five‐ and 10‐year OS or PFS. For five‐year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10; 4 studies, 899 participants; moderate‐certainly evidence) and for the five‐year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17; 3 studies, 761 participants; moderate‐certainly evidence). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10‐year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three‐ and five‐year OS rates have no significant difference between the two groups. There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required. |
t133 | t133_6 | yes | The aim of this review was to estimate whether using maintenance chemotherapy is better than observation alone for women with epithelial ovarian cancer. | This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2010, Issue 9 and 2013, Issue 6). Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum‐based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer. Objectives To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL). Search methods In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trails (CENTRAL, the Cochrane Library 2009, Issue 1), MEDLINE, Embase, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For the first update the searches were extended to October 2012 and for this update to February 2017. Selection criteria Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy. Data collection and analysis Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression‐free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention‐to‐treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs. No new studies were found for inclusion in this update from the latest searches. We included eight trials (1644 women). When all chemotherapy regimens were combined, meta‐analysis indicated no significant difference in three‐, five‐ and 10‐year OS or PFS. For five‐year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10; 4 studies, 899 participants; moderate‐certainly evidence) and for the five‐year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17; 3 studies, 761 participants; moderate‐certainly evidence). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10‐year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three‐ and five‐year OS rates have no significant difference between the two groups. There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required. |
t133 | t133_7 | yes | We identified eight trials that used different types of chemotherapy (e.g. platinum agents, doxorubicin, topotecan or paclitaxel) but there was not sufficient evidence to prove any of the drugs were better than observation alone. | This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2010, Issue 9 and 2013, Issue 6). Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum‐based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer. Objectives To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL). Search methods In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trails (CENTRAL, the Cochrane Library 2009, Issue 1), MEDLINE, Embase, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For the first update the searches were extended to October 2012 and for this update to February 2017. Selection criteria Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy. Data collection and analysis Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression‐free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention‐to‐treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs. No new studies were found for inclusion in this update from the latest searches. We included eight trials (1644 women). When all chemotherapy regimens were combined, meta‐analysis indicated no significant difference in three‐, five‐ and 10‐year OS or PFS. For five‐year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10; 4 studies, 899 participants; moderate‐certainly evidence) and for the five‐year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17; 3 studies, 761 participants; moderate‐certainly evidence). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10‐year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three‐ and five‐year OS rates have no significant difference between the two groups. There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required. |
t133 | t133_8 | yes | An important consideration for women with advanced disease is the balance between the benefit of treatment and the harms or adverse effects that these treatments may cause. | This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2010, Issue 9 and 2013, Issue 6). Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum‐based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer. Objectives To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL). Search methods In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trails (CENTRAL, the Cochrane Library 2009, Issue 1), MEDLINE, Embase, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For the first update the searches were extended to October 2012 and for this update to February 2017. Selection criteria Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy. Data collection and analysis Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression‐free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention‐to‐treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs. No new studies were found for inclusion in this update from the latest searches. We included eight trials (1644 women). When all chemotherapy regimens were combined, meta‐analysis indicated no significant difference in three‐, five‐ and 10‐year OS or PFS. For five‐year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10; 4 studies, 899 participants; moderate‐certainly evidence) and for the five‐year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17; 3 studies, 761 participants; moderate‐certainly evidence). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10‐year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three‐ and five‐year OS rates have no significant difference between the two groups. There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required. |
t134 | t134_1 | no | A cramp is a sudden, involuntary painful contraction of a muscle. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_2 | no | Many people with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), experience cramps during the course of the disease. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_3 | yes | These range from mild cramps that do not affect daily activities and sleep, through to very severe, painful cramps. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_4 | no | Some medications that are used to treat cramps in people with no medical condition or with conditions other than ALS have been tested in ALS clinical trials. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_5 | no | These medicines include vitamin E, creatine, quinidine, and gabapentin. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_6 | yes | Other medications such as quinine sulfate, magnesium, lioresal, dantrolene, clonazepam, diphenylhydantoin, and gabapentin have been used to treat cramps in people with ALS but their effectiveness is unknown. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_7 | yes | In 2006 and 2010 the US Food and Drugs Administration issued warnings concerning the use of quinine sulfate, which was the previously most widely prescribed medication for cramps in the US. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_8 | no | This review sought to find out how effective medications and physical treatments for cramps are for people with ALS. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_9 | no | The reviewers identified 20 randomised controlled trials in people with ALS comprising a total of 4789 participants. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_10 | no | Only one trial, of the drug tetrahydrocannabinol (THC), directly investigated the effectiveness of an intervention for cramps. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_11 | no | Thirteen randomised controlled ALS trials investigated cramps secondarily among other variables. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_12 | no | The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_13 | no | Six randomised controlled ALS trials investigated cramps as adverse events. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t134 | t134_14 | no | The medications comprised creatine, gabapentin, dextromethorphan, quinidine and lithium. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t135 | t135_1 | yes | Granulosa cell tumours (GCTs) of the ovary are rare ovarian tumours (2% to 5% of all ovarian cancers). | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_2 | yes | Most ovarian tumours arise from the outer surface layer of the ovary, but GCTs arise from granulosa cells (sex cord cells) within the ovaries that produce oestrogen (primary female sex hormones). | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_3 | yes | These tumours grow relatively slowly and can recur 10 to 15 years after primary treatment. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_4 | yes | If women with these tumours want to have children, the surgeon usually removes only the diseased ovary. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_5 | yes | However, standard treatment has consisted of surgery to remove tubes, ovaries and uterus, as most women develop GCTs around the time of the menopause, when fertility is no longer a matter of concern. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_6 | yes | Previous studies have assessed chemotherapy (different combination regimens) with or without radiotherapy following surgery. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_7 | yes | This review aimed to examine the effects of various treatment methods, including fertility‐sparing surgery, on the survival of women with GCT of the ovary. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_8 | no | Five retrospective studies (including 535 women with a diagnosis of GCT) met our inclusion criteria. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_9 | yes | Two studies, which attempted to identify factors associated with better outcomes (in terms of overall survival), suggested that no apparent evidence could be found of differences in overall survival between surgical approaches (including whether the surgery was keyhole or open) whether a patient underwent lymphadenectomy (removal of lymph nodes) or received adjuvant chemotherapy or radiotherapy. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_10 | no | Only percentage of survival for all women combined was reported in two trials and was not reported at all in one study. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_11 | no | One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent only surgery. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_12 | no | In three studies, no apparent evidence to suggest that disease recurrence was associated with type of adjuvant chemotherapy or type of surgery, although surgical staging may be important. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_13 | no | In one study, disease recurrence was not noted to be different between patients who underwent fertility‐sparing surgery, where only the affected fallopian tube and ovary were removed, and those treated with conventional surgery, in which both tubes and ovaries were removed. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_14 | yes | Given the high overall survival rate, fertility‐sparing surgery may be an important treatment option for young patients wishing to have children in the future. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_15 | no | Toxicity and adverse event data were incompletely reported in the five studies. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_16 | no | All five studies were retrospective (looked at past findings) and were at very high risk of bias (low quality); therefore future studies should look at current evidence in randomised studies on adult GCT of the ovary. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_17 | yes | Three randomised studies comparing chemotherapy are ongoing. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_18 | no | The study that may be able to answer the question regarding best choice of chemotherapy in sex cord stromal tumours is an ongoing randomised study comparing the efficacy of two drugs (carboplatin and paclitaxel) versus standard chemotherapy (BEP ‐ bleomycin, etoposide, cisplatin). | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_19 | no | The effectiveness and safety of different ways of treating patients with adult‐onset granulosa cell tumour of the ovary have not yet been assessed by high‐quality studies. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t135 | t135_20 | no | Such trials are required to assess toxicity and quality of life associated with different treatments and to assess the safety of the types of surgery used. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t136 | t136_1 | yes | Tuberculosis causes more deaths in people living with HIV than any other disease. | The lateral flow urine lipoarabinomannan (LF‐LAM) assay Alere Determine™ TB LAM Ag is recommended by the World Health Organization (WHO) to help detect active tuberculosis in HIV‐positive people with severe HIV disease. This review update asks the question, "does new evidence justify the use of LF‐LAM in a broader group of people?”, and is part of the WHO process for updating guidance on the use of LF‐LAM. Objectives To assess the accuracy of LF‐LAM for the diagnosis of active tuberculosis among HIV‐positive adults with signs and symptoms of tuberculosis (symptomatic participants) and among HIV‐positive adults irrespective of signs and symptoms of tuberculosis (unselected participants not assessed for tuberculosis signs and symptoms). The proposed role for LF‐LAM is as an add on to clinical judgement and with other tests to assist in diagnosing tuberculosis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, without language restriction to 11 May 2018. Selection criteria Randomized trials, cross‐sectional, and observational cohort studies that evaluated LF‐LAM for active tuberculosis (pulmonary and extrapulmonary) in HIV‐positive adults. We included studies that used the manufacturer's recommended threshold for test positivity, either the updated reference card with four bands (grade 1 of 4) or the corresponding prior reference card grade with five bands (grade 2 of 5). The reference standard was culture or nucleic acid amplification test from any body site (microbiological). We considered a higher quality reference standard to be one in which two or more specimen types were evaluated for tuberculosis diagnosis and a lower quality reference standard to be one in which only one specimen type was evaluated. Data collection and analysis Two review authors independently extracted data using a standardized form and REDCap electronic data capture tools. We appraised the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool and performed meta‐analyses to estimate pooled sensitivity and specificity using a bivariate random‐effects model and a Bayesian approach. We analyzed studies enrolling strictly symptomatic participants separately from those enrolling unselected participants. We investigated pre‐defined sources of heterogeneity including the influence of CD4 count and clinical setting on the accuracy estimates. We assessed the certainty of the evidence using the GRADE approach. We included 15 unique studies (nine new studies and six studies from the original review that met the inclusion criteria): eight studies among symptomatic adults and seven studies among unselected adults. All studies were conducted in low‐ or middle‐income countries. Risk of bias was high in the patient selection and reference standard domains, mainly because studies excluded participants unable to produce sputum and used a lower quality reference standard. Participants with tuberculosis symptoms LF‐LAM pooled sensitivity (95% credible interval (CrI) ) was 42% (31% to 55%) (moderate‐certainty evidence) and pooled specificity was 91% (85% to 95%) (very low‐certainty evidence), (8 studies, 3449 participants, 37% with tuberculosis). For a population of 1000 people where 300 have microbiologically‐confirmed tuberculosis, the utilization of LF‐LAM would result in: 189 to be LF‐LAM positive: of these, 63 (33%) would not have tuberculosis (false‐positives); and 811 to be LF‐LAM negative: of these, 174 (21%) would have tuberculosis (false‐negatives). By clinical setting, pooled sensitivity was 52% (40% to 64%) among inpatients versus 29% (17% to 47%) among outpatients; and pooled specificity was 87% (78% to 93%) among inpatients versus 96% (91% to 99%) among outpatients. Stratified by CD4 cell count, pooled sensitivity increased, and specificity decreased with lower CD4 cell count. Unselected participants not assessed for signs and symptoms of tuberculosis LF‐LAM pooled sensitivity was 35% (22% to 50%), (moderate‐certainty evidence) and pooled specificity was 95% (89% to 96%), (low‐certainty evidence), (7 studies, 3365 participants, 13% with tuberculosis). For a population of 1000 people where 100 have microbiologically‐confirmed tuberculosis, the utilization of LF‐LAM would result in: 80 to be LF‐LAM positive: of these, 45 (56%) would not have tuberculosis (false‐positives); and 920 to be LF‐LAM negative: of these, 65 (7%) would have tuberculosis (false‐negatives). By clinical setting, pooled sensitivity was 62% (41% to 83%) among inpatients versus 31% (18% to 47%) among outpatients; pooled specificity was 84% (48% to 96%) among inpatients versus 95% (87% to 99%) among outpatients. Stratified by CD4 cell count, pooled sensitivity increased, and specificity decreased with lower CD4 cell count. We found that LF‐LAM has a sensitivity of 42% to diagnose tuberculosis in HIV‐positive individuals with tuberculosis symptoms and 35% in HIV‐positive individuals not assessed for tuberculosis symptoms, consistent with findings reported previously. Regardless of how people are enrolled, sensitivity is higher in inpatients and those with lower CD4 cell, but a concomitant lower specificity. As a simple point‐of‐care test that does not depend upon sputum evaluation, LF‐LAM may assist with the diagnosis of tuberculosis, particularly when a sputum specimen cannot be produced. 17 October 2019 Up to date All studies incorporated from most recent search All studies identified during the most recent search (11 May, 2018) have been incorporated in the review, and no ongoing studies identified. |
t136 | t136_2 | no | The lateral flow urine lipoarabinomannan assay (LF‐LAM, Alere Determine™ TB LAM Ag assay) is a World Health Organization‐recommended rapid test to assist in detection of active tuberculosis in HIV‐positive people with severe HIV disease. | The lateral flow urine lipoarabinomannan (LF‐LAM) assay Alere Determine™ TB LAM Ag is recommended by the World Health Organization (WHO) to help detect active tuberculosis in HIV‐positive people with severe HIV disease. This review update asks the question, "does new evidence justify the use of LF‐LAM in a broader group of people?”, and is part of the WHO process for updating guidance on the use of LF‐LAM. Objectives To assess the accuracy of LF‐LAM for the diagnosis of active tuberculosis among HIV‐positive adults with signs and symptoms of tuberculosis (symptomatic participants) and among HIV‐positive adults irrespective of signs and symptoms of tuberculosis (unselected participants not assessed for tuberculosis signs and symptoms). The proposed role for LF‐LAM is as an add on to clinical judgement and with other tests to assist in diagnosing tuberculosis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, without language restriction to 11 May 2018. Selection criteria Randomized trials, cross‐sectional, and observational cohort studies that evaluated LF‐LAM for active tuberculosis (pulmonary and extrapulmonary) in HIV‐positive adults. We included studies that used the manufacturer's recommended threshold for test positivity, either the updated reference card with four bands (grade 1 of 4) or the corresponding prior reference card grade with five bands (grade 2 of 5). The reference standard was culture or nucleic acid amplification test from any body site (microbiological). We considered a higher quality reference standard to be one in which two or more specimen types were evaluated for tuberculosis diagnosis and a lower quality reference standard to be one in which only one specimen type was evaluated. Data collection and analysis Two review authors independently extracted data using a standardized form and REDCap electronic data capture tools. We appraised the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool and performed meta‐analyses to estimate pooled sensitivity and specificity using a bivariate random‐effects model and a Bayesian approach. We analyzed studies enrolling strictly symptomatic participants separately from those enrolling unselected participants. We investigated pre‐defined sources of heterogeneity including the influence of CD4 count and clinical setting on the accuracy estimates. We assessed the certainty of the evidence using the GRADE approach. We included 15 unique studies (nine new studies and six studies from the original review that met the inclusion criteria): eight studies among symptomatic adults and seven studies among unselected adults. All studies were conducted in low‐ or middle‐income countries. Risk of bias was high in the patient selection and reference standard domains, mainly because studies excluded participants unable to produce sputum and used a lower quality reference standard. Participants with tuberculosis symptoms LF‐LAM pooled sensitivity (95% credible interval (CrI) ) was 42% (31% to 55%) (moderate‐certainty evidence) and pooled specificity was 91% (85% to 95%) (very low‐certainty evidence), (8 studies, 3449 participants, 37% with tuberculosis). For a population of 1000 people where 300 have microbiologically‐confirmed tuberculosis, the utilization of LF‐LAM would result in: 189 to be LF‐LAM positive: of these, 63 (33%) would not have tuberculosis (false‐positives); and 811 to be LF‐LAM negative: of these, 174 (21%) would have tuberculosis (false‐negatives). By clinical setting, pooled sensitivity was 52% (40% to 64%) among inpatients versus 29% (17% to 47%) among outpatients; and pooled specificity was 87% (78% to 93%) among inpatients versus 96% (91% to 99%) among outpatients. Stratified by CD4 cell count, pooled sensitivity increased, and specificity decreased with lower CD4 cell count. Unselected participants not assessed for signs and symptoms of tuberculosis LF‐LAM pooled sensitivity was 35% (22% to 50%), (moderate‐certainty evidence) and pooled specificity was 95% (89% to 96%), (low‐certainty evidence), (7 studies, 3365 participants, 13% with tuberculosis). For a population of 1000 people where 100 have microbiologically‐confirmed tuberculosis, the utilization of LF‐LAM would result in: 80 to be LF‐LAM positive: of these, 45 (56%) would not have tuberculosis (false‐positives); and 920 to be LF‐LAM negative: of these, 65 (7%) would have tuberculosis (false‐negatives). By clinical setting, pooled sensitivity was 62% (41% to 83%) among inpatients versus 31% (18% to 47%) among outpatients; pooled specificity was 84% (48% to 96%) among inpatients versus 95% (87% to 99%) among outpatients. Stratified by CD4 cell count, pooled sensitivity increased, and specificity decreased with lower CD4 cell count. We found that LF‐LAM has a sensitivity of 42% to diagnose tuberculosis in HIV‐positive individuals with tuberculosis symptoms and 35% in HIV‐positive individuals not assessed for tuberculosis symptoms, consistent with findings reported previously. Regardless of how people are enrolled, sensitivity is higher in inpatients and those with lower CD4 cell, but a concomitant lower specificity. As a simple point‐of‐care test that does not depend upon sputum evaluation, LF‐LAM may assist with the diagnosis of tuberculosis, particularly when a sputum specimen cannot be produced. 17 October 2019 Up to date All studies incorporated from most recent search All studies identified during the most recent search (11 May, 2018) have been incorporated in the review, and no ongoing studies identified. |
t136 | t136_3 | yes | Rapid and early tuberculosis diagnosis may allow for prompt treatment and alleviate severe illness and death. | The lateral flow urine lipoarabinomannan (LF‐LAM) assay Alere Determine™ TB LAM Ag is recommended by the World Health Organization (WHO) to help detect active tuberculosis in HIV‐positive people with severe HIV disease. This review update asks the question, "does new evidence justify the use of LF‐LAM in a broader group of people?”, and is part of the WHO process for updating guidance on the use of LF‐LAM. Objectives To assess the accuracy of LF‐LAM for the diagnosis of active tuberculosis among HIV‐positive adults with signs and symptoms of tuberculosis (symptomatic participants) and among HIV‐positive adults irrespective of signs and symptoms of tuberculosis (unselected participants not assessed for tuberculosis signs and symptoms). The proposed role for LF‐LAM is as an add on to clinical judgement and with other tests to assist in diagnosing tuberculosis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, without language restriction to 11 May 2018. Selection criteria Randomized trials, cross‐sectional, and observational cohort studies that evaluated LF‐LAM for active tuberculosis (pulmonary and extrapulmonary) in HIV‐positive adults. We included studies that used the manufacturer's recommended threshold for test positivity, either the updated reference card with four bands (grade 1 of 4) or the corresponding prior reference card grade with five bands (grade 2 of 5). The reference standard was culture or nucleic acid amplification test from any body site (microbiological). We considered a higher quality reference standard to be one in which two or more specimen types were evaluated for tuberculosis diagnosis and a lower quality reference standard to be one in which only one specimen type was evaluated. Data collection and analysis Two review authors independently extracted data using a standardized form and REDCap electronic data capture tools. We appraised the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool and performed meta‐analyses to estimate pooled sensitivity and specificity using a bivariate random‐effects model and a Bayesian approach. We analyzed studies enrolling strictly symptomatic participants separately from those enrolling unselected participants. We investigated pre‐defined sources of heterogeneity including the influence of CD4 count and clinical setting on the accuracy estimates. We assessed the certainty of the evidence using the GRADE approach. We included 15 unique studies (nine new studies and six studies from the original review that met the inclusion criteria): eight studies among symptomatic adults and seven studies among unselected adults. All studies were conducted in low‐ or middle‐income countries. Risk of bias was high in the patient selection and reference standard domains, mainly because studies excluded participants unable to produce sputum and used a lower quality reference standard. Participants with tuberculosis symptoms LF‐LAM pooled sensitivity (95% credible interval (CrI) ) was 42% (31% to 55%) (moderate‐certainty evidence) and pooled specificity was 91% (85% to 95%) (very low‐certainty evidence), (8 studies, 3449 participants, 37% with tuberculosis). For a population of 1000 people where 300 have microbiologically‐confirmed tuberculosis, the utilization of LF‐LAM would result in: 189 to be LF‐LAM positive: of these, 63 (33%) would not have tuberculosis (false‐positives); and 811 to be LF‐LAM negative: of these, 174 (21%) would have tuberculosis (false‐negatives). By clinical setting, pooled sensitivity was 52% (40% to 64%) among inpatients versus 29% (17% to 47%) among outpatients; and pooled specificity was 87% (78% to 93%) among inpatients versus 96% (91% to 99%) among outpatients. Stratified by CD4 cell count, pooled sensitivity increased, and specificity decreased with lower CD4 cell count. Unselected participants not assessed for signs and symptoms of tuberculosis LF‐LAM pooled sensitivity was 35% (22% to 50%), (moderate‐certainty evidence) and pooled specificity was 95% (89% to 96%), (low‐certainty evidence), (7 studies, 3365 participants, 13% with tuberculosis). For a population of 1000 people where 100 have microbiologically‐confirmed tuberculosis, the utilization of LF‐LAM would result in: 80 to be LF‐LAM positive: of these, 45 (56%) would not have tuberculosis (false‐positives); and 920 to be LF‐LAM negative: of these, 65 (7%) would have tuberculosis (false‐negatives). By clinical setting, pooled sensitivity was 62% (41% to 83%) among inpatients versus 31% (18% to 47%) among outpatients; pooled specificity was 84% (48% to 96%) among inpatients versus 95% (87% to 99%) among outpatients. Stratified by CD4 cell count, pooled sensitivity increased, and specificity decreased with lower CD4 cell count. We found that LF‐LAM has a sensitivity of 42% to diagnose tuberculosis in HIV‐positive individuals with tuberculosis symptoms and 35% in HIV‐positive individuals not assessed for tuberculosis symptoms, consistent with findings reported previously. Regardless of how people are enrolled, sensitivity is higher in inpatients and those with lower CD4 cell, but a concomitant lower specificity. As a simple point‐of‐care test that does not depend upon sputum evaluation, LF‐LAM may assist with the diagnosis of tuberculosis, particularly when a sputum specimen cannot be produced. 17 October 2019 Up to date All studies incorporated from most recent search All studies identified during the most recent search (11 May, 2018) have been incorporated in the review, and no ongoing studies identified. |
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