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BACKGROUND This post hoc analysis aim ed to determine whether neuraxial block was associated with a composite of cardiovascular death , non-fatal myocardial infa rct ion ( MI ) and non-fatal cardiac arrest within 30 days of r and omization in POISE trial patients . METHODS A total of 8351 non-cardiac surgical patients at high risk of cardiovascular complications were r and omized  to β-blocker or placebo . Neuraxial block was defined as spinal , lumbar or thoracic epidural anaesthesia . Logistic regression , with weighting using estimated propensity scores , was used to determine the association between neuraxial block and primary and secondary outcomes . RESULTS Neuraxial block was associated with an increased risk of the primary outcome [ 287 ( 7.3 % ) vs 229 ( 5.7 % ) ; odds ratio ( OR ) , 1.24 ; 95 % confidence interval ( CI ) , 1.02 - 1.49 ; P=0.03 ] and MI [ 230 ( 5.9 % ) vs 177 ( 4.4 % ) ; OR , 1.32 ; 95 % CI , 1.07 - 1.64 ; P=0.009 ] but not stroke [ 23 ( 0.6 % ) vs 32 ( 0.8 % ) ; OR , 0.76 ; 95 % CI , 0.44 - 1.33 ; P=0.34 ] , death [ 96 ( 2.5 % ) vs 111 ( 2.8 % ) ; OR , 0.87 ; 95 % CI , 0.65 - 1.17 ; P=0.37 ] or clinical ly significant hypotension [ 522 ( 13.4 % ) vs 484 ( 12.1 % ) ; OR , 1.13 ; 95 % CI , 0.99 - 1.30 ; P=0.08 ] . Thoracic epidural with general anaesthesia was associated with a worse primary outcome than general anaesthesia alone [ 86 ( 12.1 % ) vs 119 ( 5.4 % ) ; OR , 2.95 ; 95 % CI , 2.00 - 4.35 ; P<0.001 ] . CONCLUSIONS In patients at high risk of cardiovascular morbidity , neuraxial block was associated with an increased risk of adverse cardiovascular outcomes , which could be causal or because of residual confounding The actual incidence of neurologic dysfunction result ing from hemorrhagic complications associated with neuraxial blockade is unknown . Although the incidence cited in the literature is estimated to be less than 1 in 150,000 epidural and less than 1 in 220,000 spinal anesthetics , recent epidemiologic surveys suggest that the frequency is increasing and may be as high as 1 in 3000 in some patient population s. Overall , the risk of clinical ly significant bleeding increase with age , associated abnormalities of the spinal cord or vertebral column , the presence of an underlying coagulopathy , difficulty during needle placement , and an indwelling neuraxial catheter during sustained anticoagulation ( particularly with st and ard heparin or low-molecular weight heparin ) . The need for prompt diagnosis and intervention to optimize is also consistently reported . In response to these patient safety issues , the American Society of Regional Anesthesia and Pain Medicine ( ASRA ) convened its Third Consensus Conference on Regional Anesthesia and Anticoagulation . Practice guidelines or recommendations summarize evidence -based review s. However , the rarity of spinal hematoma defies a prospect i ve r and omized study , and there is no current laboratory model . As a result , the ASRA consensus statements represent the collective experience of recognized experts in the field of neuraxial anesthesia and anticoagulation . These are based on case reports , clinical series , pharmacology , hematology , and risk factors for surgical bleeding . An underst and ing of the complexity of this issue is essential to patient management BACKGROUND : In this post hoc sub analysis of the Perioperative Ischemic Evaluation ( POISE ) trial , we sought to determine whether nitrous oxide was associated with the primary composite outcome of cardiovascular death , nonfatal myocardial infa rct ion ( MI ) , and nonfatal cardiac arrest within 30 days of r and omization . METHODS : The POISE trial of perioperative & bgr;-blockade was undertaken in 8351 patients .  Nitrous oxide anesthesia was defined as the coadministration of nitrous oxide in patients receiving general anesthesia  , with or without additional neuraxial blockade or peripheral nerve blockade . Logistic regression , with inverse probability weighting using estimated propensity scores , was used to determine the association of nitrous oxide with the primary outcome , MI , stroke , death , and clinical ly significant hypotension . RESULTS :  Nitrous oxide was administered to 1489 ( 29 % ) of the 5133 patients included in this analysis . Nitrous oxide had no significant effect on the risk of the primary outcome ( 112 [ 7.5 % ] vs 248 [ 6.9 % ] ; odds ratio [ OR ] , 1.08 ; 95 % confidence interval [ CI ] , 0.82–1.44 ; 99 % CI , 0.75–1.57 ; P = 0.58 ) , MI ( 89 [ 6.0 ] vs 204 [ 5.6 ] ; OR , 0.99 ; 95 % CI , 0.75–1.31 ; 99 % CI , 0.69–1.42 ; P = 0.94 ) , stroke ( 6 [ 0.4 % ] vs 28 [ 0.8 % ] ; OR , 0.85 ; 95 % CI , 0.26–2.82 ; 99 % CI , 0.17–4.11 ; P = 0.79 ) , death ( 40 [ 2.7 % ] vs 100 [ 2.8 % ] ; OR , 1.04 ; 95 % CI , 0.6–1.81 ; 99 % CI , 0.51–2.15 ; P = 0.88 ) or clinical ly significant hypotension ( 219 [ 14.7 % ] vs 544 [ 15.0 % ] ; OR , 0.92 ; 95 % CI , 0.74–1.15 ; 99 % CI , 0.70–1.23 ; P = 0.48 ) . CONCLUSIONS : In this post hoc sub analysis , nitrous oxide was not associated with an increased risk of adverse outcomes in the POISE trial patients . This analysis was limited by the observational nature of the data and the lack of information on the concentration and duration of nitrous oxide administration . Further r and omized controlled trial evidence is required Introduction Bemiparin has shown to be effective and safe in clinical trials in total knee or hip replacement . Material s and methods We conducted a prospect i ve , open , multicentre , uncontrolled study to audit the utilisation patterns of bemiparin 3,500 IU/day , first dose administered 6 h after surgery , in 1,009 patients undergoing total hip or knee replacement surgery in st and ard clinical practice . We analysed rates of documented symptomatic venous thromboembolism ( VTE ) [ deep-vein thrombosis ( DVT ) and pulmonary embolism ( PE ) ] confirmed by objective methods , major bleeding , death , thrombocytopaenia and other adverse events up to 6 weeks . Results Rate of documented symptomatic DVT was 0.3 % ( 95 % CI , 0.1–0.9 % ) . No cases of documented PE were reported . There were 14 ( 1.4 % ) major bleedings ( 95 % CI , 0.8–2.3 % ) . Neuraxial anaesthesia was used in 937 ( 92.9 % ) patients . There were no cases of spinal haematoma , fatal bleeding or bleeding in critical organs . There were 6 ( 0.6 % ) cases of mild thrombocytopaenia , which did not require treatment discontinuation . No cases of severe type II heparin-induced thrombocytopaenia were observed . There were no deaths during bemiparin prophylaxis . The median length of hospitalisation was 9 days and 92.5 % of patients continued prophylaxis post-hospitalisation for a total median time of 38 days . There were no thromboembolic or bleeding complications during post-hospitalisation prophylaxis . Postoperative start of prophylaxis with bemiparin permitted that 29.3 % of patients could be admitted to hospital the same day of the intervention . Conclusion Bemiparin prophylaxis , started 6 h after surgery and given for 5–6 weeks after total hip or knee replacement , was associated with low rates of VTE , major bleeding and other adverse events in normal clinical practice . Bemiparin thromboprophylaxis started 6 h after surgery makes neuraxial anaesthesia/analgesia procedures easier , without compromising efficacy Abstract The role of anesthesia techniques on perioperative outcomes on a population level has recently gained widespread interest . Although mainly neuraxial vs general anesthesia has been addressed , population -level data on the impact of peripheral nerve blocks ( PNBs ) are still lacking . Therefore , we investigated the association between PNB use and outcomes using retrospective data on 1,062,152 recipients of hip and knee arthroplasties ( total hip arthroplasty [THA]/total knee arthroplasty [ TKA ] ) from the national Premier Perspective data base ( 2006 - 2013 ) . Multilevel multivariable logistic regression models measured associations between PNB use and outcomes . Complications included cardiac , pulmonary , gastrointestinal and renal complications , cerebrovascular events , infections , wound complications , thromboembolic complications , inpatient falls , and mortality . Re source utilization variables included blood transfusions , intensive care unit admissions , opioid consumption , cost , and length of stay . Overall , 12.5 % of patients received a PNB , with an increase over time particularly among TKAs . Peripheral nerve block use was associated with lower odds for most adverse outcomes mainly among patients with THA . Notable beneficial effects were seen for wound complications ( odds ratio 0.60 [ 95 % confidence interval , 0.49 - 0.74 ] ) among THA recipients and pulmonary complications ( odds ratio 0.83 [ 95 % confidence interval , 0.72 - 0.94 ] ) in patients with TKA . Peripheral nerve block use was significantly ( P < 0.0001 ) associated with a −16.2 % and −12.7 % reduction in opioid consumption for patients with THA and TKA , respectively . In conclusion , our results indicate that PNBs might be associated with superior perioperative population -level outcomes . In light of the inability to establish a causal relationship and the presence of residual confounding , we strongly advocate for further prospect i ve investigation , ideally in multicenter , r and omized trials , to establish the potential impact of PNBs on outcomes on a population level BACKGROUND : The benefit-risk ratio of extended fondaparinux therapy has not been assessed in patients undergoing major lower limb joint arthroplasty . Few data on the concomitant use of fondaparinux and continuous neuraxial or deep peripheral nerve blockade are available . We performed a prospect i ve intervention study in patients undergoing major orthopedic surgery primarily design ed to assess the efficacy of fondaparinux when drug administration was withheld for 48 h to permit removal of a neuraxial or deep peripheral nerve catheter . The safety and efficacy of extended fondaparinux therapy for the prevention of venous thromboembolism were also evaluated . METHODS : Patients received a daily subcutaneous injection of 2.5 mg fondaparinux for 3 to 5 wk postoperatively . In patients with a neuraxial or deep peripheral nerve catheter , the catheter was removed 36 h after the last fondaparinux dose . The next fondaparinux dose was administered 12 h after catheter removal . The primary end points were symptomatic venous thromboembolism and major bleeding up to 4–6 wk after surgery . RESULTS : We recruited 5704 patients . A neuraxial or deep peripheral nerve catheter was inserted in 1553 ( 27 % ) patients and 78 ( 1.4 % ) patients , respectively . The rate of venous thromboembolism was 1.0 % ( 54 of 5387 ) . There was no difference between patients without ( 1.1 % ) or with ( 0.8 % ) a catheter ( the upper limit of the 95 % confidence interval of the odds ratio , 1.49 , being below the predetermined noninferiority margin of 1.75 ) . The incidence of major bleeding was 0.8 % ( 42 of 5382 ) . No neuraxial or perineural hematoma was reported . CONCLUSIONS : Once-daily subcutaneous injection of 2.5 mg fondaparinux given for 3 to 5 wk was effective and safe for prevention of venous thromboembolism after major orthopedic surgery . Temporary discontinuation of fondaparinux for 48 h permitted safe removal of a neuraxial or deep peripheral nerve catheter without decreasing thromboprophylatic efficacy This systematic review and meta- analysis summarizes the clinical effects of increasing perioperative blood flow using fluids with or without inotropes/vasoactive drugs to explicit defined goals in adults . We included r and omized controlled trials of adult patients ( aged 16 years or older ) undergoing surgery . We included 31 studies of 5292 participants . There was no difference in mortality at the longest follow-up : 282/2615 ( 10.8 % ) died in the control group and 238/2677 ( 8.9 % ) in the treatment group , RR of 0.89 ( 95 % CI : 0.76 - 1.05 ; P=0.18 ) . However , the results were sensitive to analytical methods and withdrawal of studies with method ological limitations . The intervention reduced the rate of three morbidities ( renal failure , respiratory failure , and wound infections ) but not the rates of arrhythmia , myocardial infa rct ion , congestive cardiac failure , venous thrombosis , and other types of infections . The number of patients with complications was also reduced by the intervention . Hospital length of stay was reduced in the treatment group by 1.16 days . There was no difference in critical care length of stay . The primary analysis of this review showed no difference between groups but this result was sensitive to the method of analysis , withdrawal of studies with method ological limitations , and was dominated by a single large study . Patients receiving this intervention stayed in hospital 1 day less with fewer complications . It is unlikely that the intervention causes harm . The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced BACKGROUND Recent studies have shown that ultrasound guidance for paediatric regional anaesthesia can improve the quality of upper extremity and neuraxial blocks . We therefore investigated whether ultrasound guidance for sciatic and femoral nerve blocks prolongs sensory blockade in comparison with nerve stimulator guidance in children . METHODS Forty-six children scheduled for surgery of one lower extremity were r and omized to receive a sciatic and femoral nerve block under either ultrasound or nerve stimulator guidance . After induction of general anaesthesia , the blocks were performed using an ultrasound-guided multiple injection technique until the nerves were surrounded by levobupivacaine , or by nerve stimulator guidance using a predefined dose of 0.3 ml kg(-1 ) of levobupivacaine . An increase in heart rate of more than 15 % of baseline during surgery defined a failed block . The duration of the block was determined from the injection of local anaesthetic to the time when the patient received the first postoperative analgesic . RESULTS Two blocks in the nerve stimulator group failed . There were no failures in the ultrasound group . The duration of analgesia was longer in the ultrasound group mean ( sd ) 508 ( 178 ) vs 335 ( 169 ) min ( P < 0.05 ) . The volume of local anaesthetic in sciatic and femoral nerve blocks was reduced with ultrasound compared with nerve stimulator guidance [ 0.2 ( 0.06 ) vs 0.3 ml kg(-1 ) ( P < 0.001 ) and 0.15 ( 0.04 ) vs 0.3 ml kg(-1 ) ( P < 0.001 ) , respectively ] . CONCLUSIONS Ultrasound guidance for sciatic and femoral nerve blocks in children increased the duration of sensory blockade in comparison with nerve stimulator guidance . Prolonged sensory blockade was achieved with smaller volumes of local anaesthetic when using ultrasound guidance Abstract Objectives To evaluate the long term effects of perioperative β blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery . Design R and omised placebo controlled and blinded multicentre trial . Analyses were by intention to treat . Setting University anaesthesia and surgical centres and one coordinating centre . Participants 921 patients aged > 39 scheduled for major non-cardiac surgery . Interventions 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days . Main outcome measures The composite primary outcome measure was time to all cause mortality , acute myocardial infa rct ion , unstable angina , or congestive heart failure . Secondary outcome measures were time to all cause mortality , cardiac mortality , and non-fatal cardiac morbidity . Results Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group . Metoprolol significantly reduced the mean heart rate by 11 % ( 95 % confidence interval 9 % to 13 % ) and mean blood pressure by 3 % ( 1 % to 5 % ) . The primary outcome occurred in 99 of 462 patients in the metoprolol group ( 21 % ) and 93 of 459 patients in the placebo group ( 20 % ) ( hazard ratio 1.06 , 0.80 to 1.41 ) during a median follow-up of 18 months ( range 6 - 30 ) . All cause mortality was 16 % ( 74/462 ) in the metoprolol group and 16 % ( 72/459 ) in the placebo group ( 1.03 , 0.74 to 1.42 ) . The difference in risk for the proportion of patients with serious adverse events was 2.4 % ( − 0.8 % to 5.6 % ) . Conclusions Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes . Confidence intervals , however , were wide , and the issue needs re assessment . Trial registration Current Controlled Trials IS RCT N58485613 [ controlled-trials.com BACKGROUND Cardiovascular complications are the most important causes of perioperative morbidity and mortality among patients undergoing major vascular surgery . METHODS We performed a r and omized , multicenter trial to assess the effect of perioperative blockade of beta-adrenergic receptors on the incidence of death from cardiac causes and nonfatal myocardial infa rct ion within 30 days after major vascular surgery in patients at high risk for these events . High-risk patients were identified by the presence of both clinical risk factors and positive results on dobutamine echocardiography . Eligible patients were r and omly assigned to receive st and ard perioperative care or st and ard care plus perioperative beta-blockade with bisoprolol . RESULTS A total of 1351 patients were screened , and 846 were found to have one or more cardiac risk factors . Of these 846 patients , 173 had positive results on dobutamine echocardiography . Fifty-nine patients were r and omly assigned to receive bisoprolol , and 53 to receive st and ard care .  Fifty-three patients were excluded from r and omization because they were already taking a beta-blocker , and eight were excluded because they had extensive wall-motion abnormalities either at rest or during stress testing . Two patients in the bisoprolol group died of cardiac causes ( 3.4 percent ) , as compared with nine patients in the st and ard-care group ( 17 percent , P=0.02 ) . Nonfatal myocardial infa rct ion occurred in nine patients given st and ard care only ( 17 percent ) and in none of those given st and ard care plus bisoprolol ( P<0.001 ) . Thus , the primary study end point of death from cardiac causes or nonfatal myocardial infa rct ion occurred in 2 patients in the bisoprolol group ( 3.4 percent ) and 18 patients in the st and ard-care group ( 34 percent , P<0.001 ) . CONCLUSIONS Bisoprolol reduces the perioperative incidence of death from cardiac causes and nonfatal myocardial infa rct ion in high-risk patients who are undergoing major vascular surgery AIM To produce dietetic guidelines summarizing the systematic review evidence on dietary advice for secondary prevention of cardiovascular disease . METHODS The Cochrane Library , MEDLINE and EMBASE were comprehensively search ed for systematic review s on aspects of diet and heart health . Review s were included if they search ed systematic ally for r and omised controlled trials relating to diet and secondary prevention of cardiovascular disease . Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review . The quality and results of each review were discussed and summarized in a whole group meeting . The guidelines were trialled in seven dietetic departments and modified where necessary . RESULTS Providing evidence -based dietary information ( including increasing omega-3 fat plus fruit and vegetable intake ) to all people after myocardial infa rct ion will save more lives than concentrating dietary advice on those in need of weight loss or lipid lowering . The practice of prioritizing dietetic time to those with raised lipids is out of date since the advent of statin therapy . CONCLUSION There is good systematic review evidence that dietary advice to those with cardiovascular disease can reduce mortality and morbidity as well as modify risk factors .  Dietary advice that does this most effectively should be prioritized Purpose Real-world data on the use of rivaroxaban in the perioperative period in patients undergoing major orthopedic surgery are limited . Subsets of data from the Phase IV , non-interventional XAMOS study were analyzed to explore the potential influence of timing of the first thrombo prophylactic dose , type of anesthesia , and concomitant mechanical prophylaxis on clinical outcomes in patients undergoing major orthopedic surgery in routine clinical practice . Patients and methods In XAMOS , 8,778 patients received rivaroxaban ( 10 mg once daily ) and 8,635 received st and ard-of-care ( SOC ) pharmacological prophylaxis  ( safety population ) . Crude incidences of symptomatic thromboembolic and treatment-emergent bleeding events were analyzed according to timing of the first postoperative thromboprophylactic dose , use of general or neuraxial anesthesia , and use of mechanical prophylaxis with pharmacological thromboprophylaxis . Results In the rivaroxaban group , the incidences of symptomatic thromboembolic events were 0.7 % , 1.0 % , and 0.7 % in patients receiving the first thromboprophylactic dose at ≤6 hours , > 6 hours to ≤10 hours , and > 10 hours to ≤24 hours after surgery , respectively . In the SOC group , the incidence of symptomatic thromboembolic events was slightly higher when the postoperative dose was given at > 10 hours to ≤24 hours ( 1.8 % vs 1.1 % at ≤6 hours and 1.3 % at > 6 hours to ≤10 hours ) . The antithrombotic effect of rivaroxaban was maintained in comparison to the SOC group . The incidence of major bleeding ( RECORD trial definition ) was low and similar between the two treatment groups and was not influenced by timing of the first thromboprophylactic dose . Neuraxial anesthesia was used more than any other form of anesthesia for both hip and knee surgery ; the effectiveness of rivaroxaban was not influenced by the type of anesthesia used . No spinal hematomas were reported in patients receiving neuraxial anesthesia in either treatment group . Use of mechanical thromboprophylaxis in addition to rivaroxaban or SOC pharmacological prophylaxis did not reduce the risk of thromboembolic events further . Conclusion The effectiveness and safety of rivaroxaban in patients undergoing major orthopedic surgery in routine clinical practice were maintained irrespective of timing of the first postoperative dose within 24 hours after surgery , the type of anesthesia , and the additional use of mechanical thromboprophylaxis BACKGROUND Peripheral neural blockade appears to provide effective analgesia with potentially less morbidity than central neuraxial techniques . We compared the relative benefits of combined femoral ( 3-in-1 ) and sciatic nerve block with epidural blockade for postoperative knee arthroplasty analgesia . METHODS Sixty patients , ASA I-III , undergoing unilateral knee replacement were prospect ively r and omized to receive either a lumbar epidural infusion or combined single-shot femoral ( 3-in-1 ) and sciatic blocks ( combined blocks ) . All patients received st and ard general anaesthesia .  Visual analogue pain scores and rescue opioid requirements were recorded at four time points postoperatively . Patient satisfaction , morbidity , block insertion time , perioperative blood loss and rehabilitation indices were also assessed . RESULTS In both groups , pain on movement was well controlled at discharge from recovery and 6 h postoperatively but increased at 24 and 48 h. Median ( 95 % CI ) analogue scale scores were 0 ( 0 - 0 ) , 15 ( 0 - 30 ) , 55 ( 38 - 75 ) and 54 ( 30 - 67 ) mm for epidural block and 0.5 ( 0 - 22 ) , 21.5 ( 10 - 28 ) , 40 ( 20 - 50 ) and 34.5 ( 21 - 55 ) mm for combined block . VAS pain scores with the combined blocks were significantly lower at 24 h ( P=0.004 ) . Total morphine usage was low in both groups : median epidural group 17 mg ( 8 - 32 ) versus combined blocks 13 mg ( 7.8 - 27.5 ) . Patient satisfaction was high in both groups with median ( 95 % CI ) scores of 100 ( 85 - 100 ) , 83 ( 70 - 100 ) and 82 ( 57 - 90 ) mm for epidural and 90 ( 73 - 100 ) , 100 ( 77 - 100 ) and 97 ( 80 - 100 ) mm for combined blocks ( not significant ) . Perioperative blood loss and rehabilitation indices were also similar . CONCLUSIONS Combined femoral ( 3-in-1 ) and sciatic blocks offer a practical alternative to epidural analgesia for unilateral knee replacements This study explored whether patients ’ preference for particular types of anaesthesia  could be influenced pre‐operatively by giving them the addresses of various relevant websites . Patients at an orthopaedic pre‐ assessment education clinic completed a question naire , which included a short multiple‐choice general knowledge quiz about anaesthesia , and also question ed them as to their choice of anaesthesia ( general or neuraxial ) . Patients were r and omly assigned to intervention or control groups . Intervention group members were given the addresses of three relevant anaesthesia and health related websites to access at home . All patients were asked to complete the question naires on a second occasion , before surgery . Initially , most patients stated a preference for general anaesthesia . Subsequently , the intervention group altered their preference towards neuraxial anaesthesia compared to the control group ( p ≤ 0.0001 ) . The increase in median ( IQR [ range ] ) anaesthesia knowledge test score was greater in the intervention group ( from 10.0 ( 9.0–12.0 [ 5.0–14.0 ] ) to 13.0 ( 11.0–14.0 [ 6.0–14.0 ] ) ) than in the control group ( from 10.0 ( 9.0–11.5 [ 3.0–13.0 ] ) to 11.0 ( 9.0–12.0 [ 4.0–14.0 ] ) ; p = 0.0068 ) OBJECTIVE To assess whether a pragmatic policy of perioperative beta-blockade , with metoprolol , reduced the 30-day cardiovascular morbidity and mortality and reduced the length of hospital stay in average patients undergoing infrarenal vascular surgery . METHODS This was a double-blind r and omized placebo-controlled trial that occurred in vascular surgical units in four UK hospitals . Participants were 103 patients without previous myocardial infa rct ion who had infrarenal vascular surgery between July 2001 and March 2004 . Interventions were oral metoprolol ( 50 mg twice daily , supplemented by intravenous doses when necessary ) or placebo from admission until 7 days after surgery . Holter monitors were kept in place for 72 hours after surgery . RESULTS Eighty men and 23 women ( median age , 73 years ) were r and omized , 55 to  metoprolol  and 48 to placebo , and 97 ( 94 % ) underwent surgery during the trial . The most common operations were aortic aneurysm repair ( 38 % ) and distal bypass ( 29 % ) . Intraoperative inotropic support was required in 64 % and 92 % of patients in the placebo and metoprolol groups , respectively . Within 30 days , cardiovascular events occurred in 32 patients , including myocardial infa rct ion ( 8 % ) , unstable angina ( 9 % ) , ventricular tachycardia ( 19 % ) , and stroke ( 1 % ) . Four ( 4 % ) deaths were reported . Cardiovascular events occurred in 15 ( 34 % ) and 17 ( 32 % ) patients in the placebo and metoprolol groups , respectively ( unadjusted relative risk , 0.94 ; 95 % confidence interval , 0.53 - 1.66 ; adjusted [ for age , sex , statin use , and aortic cross-clamping ] relative risk , 0.87 ; 95 % confidence interval , 0.48 - 1.55 ) . Time from operation to discharge was reduced from a median of 12 days ( 95 % confidence interval , 9 - 19 days ) in the placebo group to 10 days ( 95 % confidence interval , 8 - 12 days ) in the metoprolol group ( adjusted hazard ratio , 1.71 ; 95 % confidence interval , 1.09 - 2.66 ; P < .02 ) . CONCLUSIONS Myocardial ischemia was evident in a high proportion ( one third ) of the patients after surgery . A pragmatic regimen of perioperative beta-blockade with metoprolol did not seem to reduce 30-day cardiovascular events , but it did decrease the time from surgery to discharge Patients receiving anticoagulants could be at higher risk of compressive haematoma with neuraxial anaesthesia use . The phase III RECORD programme compared rivaroxaban with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement surgery in more than 12,500 patients . This observational analysis evaluated the risk of neuraxial haematoma after neuraxial anaesthesia in patients receiving rivaroxaban or enoxaparin  using pooled RECORD1–4 data BACKGROUND Data are scarce on the advantage of ultrasound-guided spinal anaesthesia in patients with easily identifiable bony l and marks . In this study , we compared the use of ultrasound to the l and mark method in patients with no anticipated technical difficulty , presenting for caesarean delivery under spinal anaesthesia . METHODS A total of 150 pregnant women were recruited in this r and omized , controlled study . Ultrasound examination and spinal anaesthesia were performed by three anaesthetists with experience in ultrasound-guided neuraxial block . Patients were r and omized to either the Ultrasound Group ( n=75 ) or the L and mark Group ( n=75 ) . In both groups the level of L3 - 4 or L4 - 5 was identified by ultrasound ( transverse and longitudinal approach ) or palpation . The primary outcome was the procedure time , measured from the time of skin puncture by the introducer to the time of viewing cerebrospinal fluid at the hub of the spinal needle . Secondary outcomes were the number of skin punctures , number of passes , and incidence of successful spinal blockade . RESULTS The average procedure time , number of skin punctures and needle passes , were similar in both groups . The number of patients with successful spinal anaesthesia after one puncture was not statistically different between the groups . CONCLUSION The present results indicate that when performed by anaesthetists experienced in both ultrasound and l and mark techniques , the use of ultrasound does not appear to increase the success rate of spinal anaesthesia , or reduce the procedure time or number of attempts in obstetric patients with easily palpable spines Ultrasound assistance for neuraxial techniques may improve technical performance ; however , it is unclear which population s benefit most . Our study aim ed to investigate the efficacy of neuraxial ultrasound in women having caesarean section with combined spinal‐epidural anaesthesia , and to identify factors associated with improved technical performance . Two‐hundred and eighteen women were r and omly allocated to ultrasound‐assisted or control groups . All the women had a pre‐procedure ultrasound , but only women in the  ultrasound group had this information conveyed to the anaesthetist . Primary outcomes were first‐pass success ( a single needle insertion with no redirections ) and procedure difficulty . Secondary outcomes were block quality , patient experience and complications . Exploratory sub‐group analysis and regression analysis were used to identify factors associated with success . Data from 215 women were analysed .  First‐pass success was achieved in 67 ( 63.8 % ) and 42 ( 38.2 % ) women in the ultrasound and control groups , respectively ( adjusted p = 0.001 ) . Combined spinal‐epidural anaesthesia was ‘ difficult ’ in 19 ( 18.1 % ) and 33 ( 30.0 % ) women in the ultrasound and control groups , respectively ( adjusted p = 0.09 ) . Secondary outcomes did not differ significantly . Anaesthetists misidentified the intervertebral level by two or more spaces in 23 ( 10.7 % ) women . Sub‐group analysis demonstrated a benefit for ultrasound in women with easily palpable spinous processes ( adjusted p = 0.027 ) . Regression analysis identified use of ultrasound and easily palpable spinous processes to be associated with first‐pass success Background Despite evidence that regional anesthesia may be associated with fewer perioperative complications than general anesthesia , most studies that have compared cardiac outcome after general or regional anesthesia alone have not shown major differences . This study examines the impact of anesthetic choice on cardiac outcome in patients undergoing peripheral vascular surgery who have a high likelihood of associated coronary artery disease . Methods Four hundred twenty‐three patients , between 1988 and 1991 , were r and omly assigned to receive general ( n = 138 ) , epidural ( n = 149 ) , or spinal anesthesia ( n = 136 ) for femoral to distal artery bypass surgery . All patients were monitored with radial artery and pulmonary artery catheters . Postoperatively , patients were in a monitored setting for 48–72 h and had daily electrocardiograms for 4–5 days and creatine phosphokinase/isoenzymes every 8 h x 3 , then daily for 4 days . Cardiac outcomes recorded were myocardial infa rct ion , angina , and congestive heart failure . Results Baseline clinical characteristics were not different between anesthetic groups . Overall , the patient population included 86 % who were diabetic , 69 % with hypertension , 36 % with a history of a prior myocardial infa rct ion , and 41 % with a history of smoking . Cardiovascular morbidity and overall mortality were not significantly different between groups when analyzed by either intention to treat or type of anesthesia received . In the intention to treat analysis , incidences of cardiac event or death for general , spinal , and epidural groups were 16.7 % , 21.3 % , and 15.4 % , respectively . The absolute risk difference observed between general and all regional anesthesia groups for cardiac event or death was ‐1.6 % ( 95 % confidence interval ‐9.2 % , 6.1 % ) This reflected a nonsignificant trend for lower risk of postoperative events with general anesthesia . Conclusions The choice of anesthesia , when delivered as described , does not significantly influence cardiac morbidity and overall mortality in patients undergoing peripheral vascular surgery Background : Two wounds are created after abdominal surgery . The surgical insult to the peritoneal cavity and viscera has not been emphasized as a target for interventions . In animal models vagotomy blunts the intraperitoneal response to induced inflammation . This is not feasible in humans . However a transient chemical afferentectomy after colectomy by using neuraxial blockade ( epidural ) and intraperitoneal blockade may be possible . We investigated the effects of intraoperative instillation and postoperative infusion of intraperitoneal local anesthetic ( IPLA ) on recovery parameters after colectomy , in the setting of an established enhanced recovery after surgery ( ERAS ) program . Methods : Double blinded , r and omized , placebo controlled design . The study group ( IPLA ) received instillation of intraperitoneal ropivacaine ( 75 mg ) before dissection and postoperative infusion of 0.2 % solution at 4 mL/hour for 3 days continuously . The placebo group ( NS ) was treated as above with 0.9 % saline solution . All patients were cared for under ERAS st and ardized perioperative care . Epidural infusion was stopped on day 2 . Patients were discharged from day 3 onwards once criteria met . Perioperative data , surgical recovery score ( SRS ) , complications , and length of stay were recorded . Systemic cytokines response , neuroendocrine parameters , pain measures and opioid use data were collected . Patients were followed up for 60 days . Results : Sixty patients were recruited . Patients were equivalently matched at baseline . There were no local anesthetic related adverse events . The complication rate , including anastomotic leak rate , was equivalent between groups . IPLA group had better SRS scores for the duration of intraperitoneal infusion . Pain and opioid use was reduced in the IPLA group . Systemic cytokine and cortisol response was diminished in the IPLA group . IPLA group had consistently higher systemic ropivacaine levels than placebo group . Conclusion : Instillation and infusion of intraperitoneal ropivacaine after colectomy improves early surgical recovery . This was associated with a blunting of postsurgical systemic cytokines and cortisol . Patients also had significantly reduced pain and opioid use over and above the effect of an epidural infusion . Therefore a transient chemical afferentectomy with clinical benefit is possible with this method . A longer IPLA infusion duration needs to be studied . This study is registered at clinical trials.gov and carries the ID number NCT00722709 Although the protein-sparing effect of neuraxial blockade after abdominal surgery is well established , its metabolic effect after operations on the lower extremities remains unclear . In this study , we tested the hypothesis that combined spinal and epidural blockade ( CSE ) inhibits amino acid oxidation after hip surgery . Sixteen patients undergoing hip replacement surgery received either general anesthesia followed by IV patient-controlled analgesia with piritramide ( control ; n = 8) or CSE using bupivacaine 0.5 % for spinal anesthesia and ropivacaine 0.2 % with 0.5 & mgr;g/mL of sufentanil for postoperative epidural analgesia ( CSE ; n = 8) . Glucose and protein kinetics were assessed by stable isotope tracer technique ( [6,6 - 2H2]glucose , L-[1 - 13C]leucine ) on the day before and one day after surgery . Plasma concentrations of glucose , lactate , free fatty acids , cortisol , glucagon , and insulin were also determined . CSE prevented the increase in plasma glucose concentration during and immediately after the operation ( 60 min after skin incision : CSE 4.9 ± 0.7 versus control 6.2 ± 0.7 mmol/L ; P < 0.05 ; postanesthesia care unit : CSE 5.0 ± 0.9 versus control 7.3 ± 1.1 mmol/L ; P < 0.05 ) . Intraoperative cortisol plasma concentrations were smaller in the CSE group than in the control group . One day after the operation , however , glucose plasma concentration , glucose production , and glucose clearance were comparable in both groups . CSE inhibited the postoperative increase in leucine oxidation rate ( CSE 30 ± 12 versus control 43 ± 8 & mgr;mol·kg−1·h−1 ; P < 0.05 ) . There were no differences between the groups in protein breakdown , whole body protein synthesis , and plasma concentrations of lactate , free fatty acids , insulin , and glucagon . In conclusion , CSE prevents hyperglycemia during hip surgery and inhibits protein catabolism thereafter BACKGROUND Nitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk . We aim ed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk . METHODS We did an international , r and omised , assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery . Patients were r and omly assigned via automated telephone service , stratified by site , to receive a general anaesthetic with or without nitrous oxide . Attending anaesthetists were aware of patients ' group assignments , but patients and assessors were not . The primary outcome measure was a composite of death and cardiovascular complications ( non-fatal myocardial infa rct ion , stroke , pulmonary embolism , or cardiac arrest ) within 30 days of surgery . Our modified intention-to-treat population included all patients r and omly assigned to groups and undergoing induction of general anaesthesia for surgery . This trial is registered at Clinical Trials.gov , number NCT00430989 . FINDINGS Of 10,102 eligible patients , we enrolled 7112 patients between May 30 , 2008 , and Sept 28 , 2013 . 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide . 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome . The primary outcome occurred in 283 ( 8 % ) patients receiving nitrous oxide and in 296 ( 8 % ) patients not receiving nitrous oxide ( relative risk 0·96 , 95 % CI 0·83–1·12 ; p=0·64 ) . Surgical site infection occurred in 321 ( 9 % ) patients assigned to nitrous oxide , and in 311 ( 9 % ) patients in the no-nitrous oxide group ( p=0·61 ) , and severe nausea and vomiting occurred in 506 patients ( 15 % ) assigned to nitrous oxide and 378 patients ( 11 % ) not assigned to nitrous oxide ( p<0·0001 ) . INTERPRETATION Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery . Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection , the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis , and a desired effect of reduced volatile agent use was shown . FUNDING Australian National Health and Medical Research Council ; Australian and New Zeal and College of Anaesthetists ; Heart and Stroke Foundation of Quebec , Heart and Stroke Foundation of Ontario , Canada ; General Research Fund of the Research Grant Council , Hong Kong Special Administrative Region , China Forced-air warming is commonly used to warm patients intraoperatively , but may not achieve normothermia during a short procedure . Comparative trials of a new radiant warming device in general anaesthesia ( Suntouch ™ , Fisher and Paykel , Auckl and , New Zeal and ) have had conflicting results . We conducted a r and omized controlled trial to compare the efficacy and thermal comfort of the Suntouch ™ radiant warmer and forced-air warming in patients at high risk of hypothermia during neuraxial blockade . With ethics committee approval , 60 patients having transurethral resection of the prostate under spinal were r and omized to either radiant warming or forced-air warming . All intravenous and irrigation fluids were warmed but pre-warming was not used . The final intraoperative rectal temperatures for the radiant warming and forced-air warming groups were 36.1 ° C and 36.4 ° C respectively ( P=0.03 ) . A large proportion of patients in both groups ( 46 % and 33 % respectively , P=0.3 ) were hypothermic ( < 36 ° C ) on arrival in the post-anaesthesia care unit . No other patient variables were significantly different . Neither warming device reliably prevented hypothermia , although forced-air warming was slightly superior Background : Current knowledge of the risk for  postoperative pulmonary complications ( PPCs  ) rests on studies that narrowly selected patients and procedures . Hypothesizing that PPC occurrence could be predicted from a reduced set of perioperative variables , we aim ed to develop a predictive index for a broad surgical population . Methods : Patients undergoing surgical procedures given general , neuraxial , or regional anesthesia in 59 hospitals were r and omly selected for this prospect i ve , multicenter study . The main outcome was the development of at least one of the following : respiratory infection , respiratory failure , bronchospasm , atelectasis , pleural effusion , pneumothorax , or aspiration pneumonitis . The cohort was r and omly divided into a development sub sample to construct a logistic regression model and a validation sub sample . A PPC predictive index was constructed . Results : Of 2,464 patients studied , 252 events were observed in 123 ( 5 % ) . Thirty-day mortality was higher in patients with a PPC ( 19.5 % ; 95 % [ CI ] , 12.5–26.5 % ) than in those without a PPC ( 0.5 % ; 95 % CI , 0.2–0.8 % ) . Regression modeling identified seven independent risk factors : low preoperative arterial oxygen saturation , acute respiratory infection during the previous month , age , preoperative anemia , upper abdominal or intrathoracic surgery , surgical duration of at least 2 h , and emergency surgery . The area under the receiver operating characteristic curve was 90 % ( 95 % CI , 85–94 % ) for the development sub sample and 88 % ( 95 % CI , 84–93 % ) for the validation sub sample . Conclusion : The risk index based on seven objective , easily assessed factors has excellent discriminative ability . The index can be used to assess individual risk of PPC and focus further research on measures to improve patient care IT is widely accepted that the r and omized controlled trial is the optimal method to evaluate the efficacy of an intervention . Clinical research aim ing to inform and improve patient care should evaluate outcomes rated as important by our patients . Unfortunately , many trials focus on surrogate outcomes that are of question able significance . Given that 5 to 10 % of trial patients will suffer a serious postoperative complication , and that perioperative treatments are likely to have only a moderate effect on outcome , large numbers of patients are required to have sufficient trial power to detect a modest but clinical ly important effect . A systematic review of head injury trials published before December 1998 identified 203 studies in which 16,613 patients were enrolled . Thus , the average number of patients in each trial was 82 . Only 4 % of these trials were large enough to detect a clinical ly important difference . We believe similar problems with underpowered studies exist in the anesthesia , perioperative , and pain medicine literature . Large trials can provide definitive evidence to guide clinical practice . They provide insights in a broad range of clinical setting s and offer an opportunity to identify patient , clinician , and institutional factors that may influence outcome . They should have sufficient power to address clinical ly important questions , balance a range of known and unknown confounding factors , and provide precise estimates of effect — the latter being indicated by narrow confidence intervals . However , large multicenter trials take a lot of time and effort to establish and can be expensive to run . The required sample size needed to reliably demonstrate a clinical ly important effect should be based on the nominated primary endpoint of the study ; this is sometimes lacking in anesthesia trials . There may be several secondary study outcomes , and each of these typically relates to mechanisms of action , specific organ effects , and potential adverse effects of therapy . If the primary endpoint of the trial is a serious complication ( e.g. , death ) , it may only occur in 1 to 2 % of patients , which greatly increases the sample size required to detect a clinical ly useful effect . For this reason , some investigators combine several outcomes into a single composite , or pooled , endpoint . For example , antithrombotic treatments may reduce nonfatal myocardial infa rct ion ( MI ) , nonfatal stroke , and death . Similar approaches have or are being used in perioperative anesthesia trials . A summary measure of each of these effects can be defined . The composite endpoint will have a higher incidence than each of the individual outcomes , and as long as there is a reasonably similar effect across the individual components of the composite , this will reduce the sample size requirement for the trial . Because of the higher event rate , composite endpoints can provide increased statistical precision and efficiency . Clinical trials can be smaller , less costly , completed earlier , and the results made available sooner . However composite endpoints have an inherent assumption in that each component of the endpoint has a similar burden on health . This is often not the case . Endpoints of least importance to patients , such as a single episode of angina , as opposed to MI-induced heart failure , stroke , or death , typically contribute most to trial events . A recent systematic review found that in approximately half the trials review ed , there were large or moderate gradients in both importance to patients and magnitude of effect across components . The most serious and highly rated events typically occurred least often , so they provided the least information ( in terms of numerical value ) to the composite endpoint . This may lead to misleading impressions of the true clinical value of the treatment . Should endpoints be weighted , and if so , how ? We believe this should be guided by the perceived clinical importance of each individual endpoint , and emphasis should be placed on patient values . Objective justification can assist in this regard , using patient and clinician surveys , disability scores , and eventual health care utilization . There may be competing risks between endpoints ; a positive composite endpoint may conceal a negative individual ( more serious ) outcome such as death . The most extreme example of this is when early death prevents the possibility of other less serious outcomes , such as sub clinical MI or prolonged hospital stay . Clinicians should be wary of post hoc definition of composite endpoints as secondary measures when the primary outcome fails to show a treatment effect . This is one of several reasons why findings from the ENIGMA trial are being followed up with a larger , more specifically design ed trial focusing on cardiovascular outcomes . Cardiovascular trials commonly use major adverse cardiac events as a composite primary endpoint . But there is no st and ard definition for major adverse cardiac events . Most include MI , stroke , and death ; others include revascularizaAccepted for publication June 2 , 2010 . The authors are not supported by , nor maintain any financial interest in , any commercial activity that may be associated with the topic of this article OBJECTIVE To evaluate the suitability of spinal and general anaesthesia for cesarean section . METHODS The prospect i ve , double-blinded study , done between March and December 2009 , at Central Education and Research Hospital , Erzurum , Turkey , involved 60 patients undergoing elective cesarean surgery .  They were grouped according to the kind of anaesthesia , with each group having 30 patients each . Postoperative pain scores , opioid requirement , side effects and patient satisfaction were compared through statistical analysis using SPSS version 10 . RESULTS Patient demographics were similar in both groups . Patients in the general anaesthesia group consumed 638.4 + /- 179.10 microg fentanyl , while patients in the spinal anaesthesia group consumed 356.3 + /- 87.1 microg . The number of patients requiring opioid via Patient Controlled Analgesia in the first 24 hours was significantly higher in the general anaesthesia group . Patient satisfaction was significantly higher in the spinal anaesthesia group . CONCLUSION Type of anaesthesia for elective cesarean section is important to provide sufficient post-operative analgesia and patient satisfaction In a controlled multicentre trial carried out to assess the value of long-term practolol treatment  after myocardial infa rct ion the provisional results showed a significant reduction in mortality , though some of the data were lacking . These have now been included and the results up date d. The final figures for all  deaths  were 78 in the placebo group of 1533 patients and 48 in the practolol group of 1520 patients . The reduction in mortality ( 38 % ) was significant at the 1 % level . The figures for non-fatal reinfa rct ion ( 97 in the placebo group , and 75 in the practolol group ) were not significantly different . Patients with pre-entry anterior infa rct ion , and especially those with a diastolic blood pressure equal to or below the mean ( 78 mm Hg ) at entry to the trial , were at high risk but benefited particularly well from beta-adrenoceptor blockade . After pre-entry inferior infa rct ion the percentage reduction in deaths occurring within two hours after symptoms of a new event was similar to that after anterior infa rct ion , but the incidence of death more than two hours after the event was greater in the practolol-treated group . Thus the difference between groups in total deaths after pretrial inferior infa rct ion was marginal . Until the results of further trials are reported long-term beta-adrenoceptor blockade ( possibly up to two years ) is recommended after uncomplicated anterior myocardial infa rct ion BACKGROUND Recent trials suggest that perioperative beta-blockade reduces the risk of cardiac events in patients with a risk of myocardial ischemia who are undergoing noncardiac surgery . Patients with diabetes mellitus are at a high-risk for postoperative cardiac morbidity and mortality . They may , therefore , benefit from perioperative beta-blockade . METHODS The Diabetic Postoperative Mortality and Morbidity ( DIPOM ) trial is an investigator-initiated and -controlled , central ly r and omized , double-blind , placebo-controlled , multicenter trial . We compared the effect of metoprolol with placebo on mortality and cardiovascular morbidity rates in patients with diabetes mellitus who were beta-blocker naive , > or=40 years old , and undergoing noncardiac surgery . The study drug was given during hospitalization for a maximum of 7 days beginning the evening before surgery . The primary outcome measure is the composite of all-cause mortality , acute myocardial infa rct ion , unstable angina , or congestive heart failure leading to hospitalization or discovered or aggravated during hospitalization . Follow-up involves re-examination of patients at 6 months and collection of mortality and morbidity data via linkage to public data bases . The study was powered on the basis of an estimated 30 % 1-year event rate in the placebo arm and a 33 % relative risk reduction in the metoprolol arm . The median follow-up period was 18 months . RESULTS Enrollment started in July 2000 and ended in June 2002 . A total of 921 patients were r and omized , and 54 % of these patients had known cardiac disease , hypertension , or both . CONCLUSION The results of this study may have implication s for reduction of perioperative and postoperative risk in patients with diabetes mellitus who are undergoing major noncardiac surgery Abstract Background : The smoking cessation medicine varenicline has been associated with an increased risk of cardiovascular adverse events compared with placebo in clinical trials . Cases of cardiovascular events , including myocardial infa rct ion ( MI ) and cardiac dysrhythmias , have been noted from spontaneous reporting systems . Objective : The aim of this study was to summarize and describe cardiovascular adverse reactions identified in a general population during intensive postmarketing surveillance of varenicline in New Zeal and . Methods : Observational prospect i ve cohort study using prescription event monitoring methods . The patient cohort was established from pharmacy dispensing data sent directly to the Intensive Medicines Monitoring Programme ( IMMP ) for all New Zeal and patients prescribed varenicline .  Adverse cardiovascular events were identified from follow-up question naires completed by doctors , spontaneous reports and by record linkage to national data sets . Cardiovascular events were organized into clinical groupings for further clinical assessment , and key cases were identified . Results : All New Zeal and patients dispensed a prescription for varenicline from 1 April 2007 to 30 November 2010 were included in this study . At 31 January 2011 , the IMMP varenicline events data set included a total of 172 adverse events in the IMMP circulatory System Organ Class . There were 48 reports of myocardial ischaemia , including 12 reports of MI and 8 reports of angina . Two key cases of myocardial ischaemia suggested that this may have been induced by coronary artery spasm secondary to varenicline treatment . There were 50 reports of hypotensive events , with two key cases having documented hypotension associated with chest pain/tightness , and a further 27 reports of dysrhythmia events , including two unexplained sudden deaths . Conclusions : This paper presents a series of cases of cardiovascular events in patients taking varenicline .  Whilst there were multiple confounding factors in some patients , key cases were identified that suggested a possible mechanism of dysregulation of blood pressure leading to vasospasm or hypotension BACKGROUND : Patients undergoing abdominal hysterectomy often have significant postoperative pain despite the use of concurrent multimodal pain strategies . Neuraxial anesthesia has opioid-sparing effects and may provide better postoperative recovery to patients when compared with general anesthesia . Our main objective in this study was to compare the effects of neuraxial and general anesthesia on postoperative quality of recovery after abdominal hysterectomy . METHODS : The study was a prospect i ve , r and omized , controlled clinical trial . Seventy healthy females were recruited and r and omized to a general anesthesia or neuraxial technique  as their primary anesthetic regimen . The primary outcome was the global quality of recovery—40 question naire ( QoR–40 ) at 24 hours after the surgical procedure . Other data collected included postoperative pain scores and opioid consumption . Data were analyzed using the Mann – Whitney U test , Fisher 's exact test , and linear regression . A P value < 0.05 was considered statistically significant . RESULTS : The median difference ( 95 % confidence interval [ CI ] ) in the global QoR–40 score at 24 hours between the neuraxial and general anesthesia groups was 17 ( 11 to 21.5 ) ( P < 0.001 ) . Patients in the neuraxial anesthesia group had better quality of recovery scores in all the QoR–40 subcomponents than did the general anesthesia group ( all P < 0.005 ) . The median difference in global QoR–40 scores at 48 hours between the neuraxial anesthesia and the general anesthesia groups was 8 ( 6–10 ) ( P < 0.001 ) . Postoperative opioid consumption and pain scores were higher in the general anesthesia group than in the neuraxial anesthesia group . There was an inverse linear relationship between opioid consumption and postoperative quality of recovery at 24 hours , r 2 = 0.67 ( P < 0.0001 , 95 % CI of 0.77 to 0.51 ) , and at 48 hours , r 2 = 0.58 ( P < 0.0001 , 95 % CI of 0.72 to 0.42 ) . CONCLUSION : Neuraxial anesthesia provides better quality of recovery than does general anesthesia for patients undergoing abdominal hysterectomy . The opioid-sparing effects of neuraxial anesthesia were associated with a better quality of recovery in patients after the surgical procedure . In the absence of contraindications , neuraxial anesthesia seems to be a better anesthetic plan for those patients BACKGROUND Perioperative respiratory adverse events in children are one of the major causes of morbidity and mortality during paediatric anaesthesia .  We aim ed to identify associations between family history , anaesthesia management , and occurrence of perioperative respiratory adverse events . METHODS We prospect ively included all children who had general anaesthesia for surgical or medical interventions , elective or urgent procedures at Princess Margaret Hospital for Children , Perth , Australia , from Feb 1 , 2007 , to Jan 31 , 2008 . On the day of surgery , anaesthetists in charge of paediatric patients completed an adapted version of the International Study Group for Asthma and Allergies in Childhood question naire . We collected data on family medical history of asthma , atopy , allergy , upper respiratory tract infection , and passive smoking . Anaesthesia management and all perioperative respiratory adverse events were recorded . FINDINGS 9297 question naires were available for analysis . A positive respiratory history ( nocturnal dry cough , wheezing during exercise , wheezing more than three times in the past 12 months , or a history of present or past eczema ) was associated with an increased risk for bronchospasm ( relative risk [ RR ] 8.46 , 95 % CI 6.18 - 11.59 ; p<0.0001 ) , laryngospasm ( 4.13 , 3.37 - 5.08 ; p<0.0001 ) , and perioperative cough , desaturation , or airway obstruction ( 3.05 , 2.76 - 3.37 ; p<0.0001 ) . Upper respiratory tract infection was associated with an increased risk for perioperative respiratory adverse events only when symptoms were present ( RR 2.05 , 95 % CI 1.82 - 2.31 ; p<0.0001 ) or less than 2 weeks before the procedure ( 2.34 , 2.07 - 2.66 ; p<0.0001 ) , whereas symptoms of upper respiratory tract infection 2 - 4 weeks before the procedure significantly lowered the incidence of perioperative respiratory adverse events ( 0.66 , 0.53 - 0.81 ; p<0.0001 ) . A history of at least two family members having asthma , atopy , or smoking increased the risk for perioperative respiratory adverse events ( all p<0.0001 ) . Risk was lower with intravenous induction compared with inhalational induction ( all p<0.0001 ) , inhalational compared with intravenous maintenance of anaesthesia ( all p<0.0001 ) , airway management by a specialist paediatric anaesthetist compared with a registrar ( all p<0.0001 ) , and use of face mask compared with tracheal intubation ( all p<0.0001 ) . INTERPRETATION Children at high risk for perioperative respiratory adverse events could be systematic ally identified at the preanaesthetic assessment and thus can benefit from a specifically targeted anaesthesia management . FUNDING Department of Anaesthesia , Princess Margaret Hospital for Children , Swiss Foundation for Grants in Biology and Medicine , and the Voluntary Academic Society Basel BACKGROUND : Dexmedetomidine , an & agr;2-receptor agonist , prolongs analgesia when used in neuraxial and IV blocks . We evaluated the effect of dexmedetomidine added to ropivacaine for tibial nerve block on the duration of the sensory blockade . METHODS : For this prospect i ve , r and omized , controlled , double-blind , crossover trial , 14 healthy volunteers were allocated to 2 groups . All volunteers received an ultrasound-guided tibial nerve block  4 to 5 cm proximally to the medial malleolus . In group R , 10 mL of 0.5 % ropivacaine was injected for the block ; in group RD , 10 mL of a solution containing 0.5 % ropivacaine with 1 & mgr;g/kg of dexmedetomidine was administered . After the injection , monitoring of vital signs , evaluation of onset and resolution of sensory block , and level of sedation ( Observer 's Assessment of Alertness/Sedation scale ) were performed . Three weeks later , the same procedure was repeated , but the study subjects were allocated to the other group in a crossover fashion . The primary end point was the duration of sensory blockade . The time and carryover effects were also evaluated . Secondary outcomes were the onset time and the presence of adverse effects such as hypotension , bradycardia , hypoxia , and sedation . RESULTS : Sensory blocks lasted longer in group RD than in group R ( 21.5 vs 16.2 hours ; mean pairwise difference 5.3 hours [ 95 % confidence interval : 3.9–6.7 hours ] ; P < 0.0001 ) . Onset times were similar between groups . The mean systolic and diastolic blood pressure levels were stable throughout the study period in group R. In group RD , a noticeable decrease in systolic and diastolic blood pressure was observed between 60 and 480 minutes ( P < 0.05 ) ; 2 volunteers experienced a 30 % decrease in systolic blood pressure when compared with the baseline value as compared with none in group R. Heart rate was similar between groups except at 60 minutes ( P < 0.01 ) . CONCLUSION : Dexmedetomidine added to ropivacaine for tibial nerve block prolongs the duration of sensory blockade with similar onset time . However , patients should be monitored for potential adverse effects such as hypotension , bradycardia , and sedation BACKGROUND The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery . We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia . METHODS We undertook a parallel group , multicentre , r and omised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries . Participants were r and omly assigned to surgery under general ( n=1753 ) or local ( n=1773 ) anaesthesia  between June , 1999 and October , 2007 . The primary outcome was the proportion of patients with stroke ( including retinal infa rct ion ) , myocardial infa rct ion , or death between r and omisation and 30 days after surgery . Analysis was by intention to treat . The trial is registered with Current Control Trials number IS RCT N00525237 . FINDINGS A primary outcome occurred in 84 ( 4.8 % ) patients assigned to surgery under general anaesthesia and 80 ( 4.5 % ) of those assigned to surgery under local anaesthesia ; three events per 1000 treated were prevented with local anaesthesia ( 95 % CI -11 to 17 ; risk ratio [ RR ] 0.94 [ 95 % CI 0.70 to 1.27 ] ) . The two groups did not significantly differ for quality of life , length of hospital stay , or the primary outcome in the prespecified subgroups of age , contralateral carotid occlusion , and baseline surgical risk . INTERPRETATION We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery . The anaesthetist and surgeon , in consultation with the patient , should decide which anaesthetic technique to use on an individual basis . FUNDING The Health Foundation ( UK ) and European Society of Vascular Surgery Percutaneous transluminal coronary angioplasty ( PTCA ) for acute myocardial infa rct ion is an attractive alternative to thrombolysis , but is still limited by recurrent ischemia and restenosis . We determined whether adjunctive platelet glycoprotein IIb/IIIa receptor blockade improved outcomes in patients undergoing direct and rescue PTCA in the Evaluation of c7E3 for Prevention of Ischemic Complications ( EPIC ) trial . Of the 2,099 patients undergoing percutaneous intervention who r and omly received chimeric 7E3 Fab ( c7E3 ) as a bolus , a bolus and 12-hour infusion , or placebo , 42 underwent direct PTCA for acute myocardial infa rct ion and 22 patients had rescue PTCA after failed thrombolysis .  The primary composite end point comprised death , reinfa rct ion , repeat intervention , or bypass surgery . Outcomes were assessed at 30 days and 6 months . Baseline characteristics were similar in direct and rescue PTCA patients . Pooling the 2 groups , c7E3 bolus and infusion reduced the primary composite end point by 83 % ( 26.1 % placebo vs 4.5 % c7E3 bolus and infusion , p = 0.06 ) . No reinfa rct ions or repeat urgent interventions occurred in c7E3 bolus and infusion patients at 30 days , although there was a trend toward more deaths in c7E3-treated patients . Major bleeding was increased with c7E3 ( 24 % vs 13 % , p = 0.28 ) . At 6 months , ischemic events were reduced from 47.8 % with placebo to 4.5 % with c7E3 bolus and infusion ( p = 0.002 ) , particularly reinfa rct ion ( p = 0.05 ) and repeat revascularization ( p = 0.002 ) . We conclude that adjunctive c7E3 therapy during direct and rescue PTCA decreased acute ischemic events and clinical restenosis in the EPIC trial . These data provide initial evidence of benefit for glycoprotein IIb/IIIa receptor blockade during PTCA for acute myocardial infa rct ion Background Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion . Previous trials have shown that carotid endarterectomy improves long-term outcomes , particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke . However , complications may occur during or soon after surgery , the most serious of which is stroke , which can be fatal . It has been suggested that performing the operation under local anaesthesia , rather than general anaesthesia , may be safer . Therefore , a prospect i ve , r and omised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality , quality of life and longer term outcome in terms of stroke-free survival . Methods / design A two-arm , parallel group , multicentre r and omised controlled trial with a recruitment target of 5000 patients . For entry into the study , in the opinion of the responsible clinician , the patient requiring an endarterectomy must be suitable for either local or general anaesthesia , and have no clear indication for either type . All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible . There is no upper age limit . Exclusion criteria are : no informed consent ; definite preference for local or general anaesthetic by the clinician or patient ; patient unlikely to be able to co-operate with awake testing during local anaesthesia ; patient requiring simultaneous bilateral carotid endarterectomy ; carotid endarterectomy combined with another operation such as coronary bypass surgery ; and , the patient has been r and omised into the trial previously . Patients are r and omised to local or general anaesthesia by the central trial office . The primary outcome is the proportion of patients alive , stroke free ( including retinal infa rct ion ) and without myocardial infa rct ion 30 days post-surgery . Secondary outcomes include the proportion of patients alive and stroke free at one year ; health related quality of life at 30 days ; surgical adverse events , re-operation and re-admission rates ; the relative cost of the two methods of anaesthesia ; length of stay and intensive and high dependency bed occupancy . Trial registration Current Controlled Trials IS RCT BACKGROUND Combined spinal-epidural anaesthesia is commonly used for elective caesarean section . Intrathecal injection produces rapid onset with minimal doses of local anaesthetic and epidural administration can be used to prolong the block . Our study examined the effects of adding magnesium sulphate to epidural bupivacaine and fentanyl in patients undergoing elective caesarean section using combined spinal-epidural anaesthesia . METHODS Women ASA physical status I or II at term were recruited . All received 2 mL intrathecal 0.5 % hyperbaric bupivacaine , 10 mL epidural 0.25 % plain bupivacaine with fentanyl 100 μg , and were r and omly allocated to receive either 10 mL of epidural 0.9 % sodium chloride or 10 mL epidural 5 % magnesium sulphate .  The quality of surgical anaesthesia , incidence of hypotension , Apgar scores , intraoperative pain assessment , onset of postoperative pain , sedation scores and side effects were recorded in the postoperative period . RESULTS Ninety women were recruited . There was no difference in the time taken for the block to reach T4 sensory level , time to reach the highest level of sensory block , time interval between first neuraxial injection and onset of surgery between the groups . Women who received magnesium had greater motor block and muscle relaxation ( P<0.05 ) . Apgar scores were 7 or more in almost all neonates in both groups . There was no significant difference in the incidence of hypotension , nausea and vomiting and duration of motor blockade between the groups . Women who received magnesium showed less shivering and later onset of post operative pain ( P<0.05 ) . CONCLUSION The addition of magnesium to epidural bupivacaine and fentanyl in women undergoing elective caesarean section with combined spinal-epidural anaesthesia improved intraoperative conditions and the quality of postoperative analgesia Background : A growing body of evidence suggests that hyperglycemia is an independent predictor of increased cardiovascular risk . Aggressive glycemic control in the intensive care decreases mortality . The benefit of glycemic control in noncardiac surgery is unknown . Methods : In a single-center , prospect i ve , unblinded , active-control study , 236 patients were r and omly assigned to continuous insulin infusion ( target glucose 100–150 mg/dl ) or to a st and ard intermittent insulin bolus ( treat glucose > 150 mg/dl ) in patients undergoing peripheral vascular bypass , abdominal aortic aneurysm repair , or below- or above-knee amputation . The treatments began at the start of surgery and continued for 48 h. The primary endpoint was a composite of all-cause death , myocardial infa rct ion , and acute congestive heart failure . The secondary endpoints were blood glucose concentrations , rates of hypoglycemia ( < 60 mg/dl ) and hyperglycemia ( > 150 mg/dl ) , graft failure or reintervention , wound infection , acute renal insufficiency , and duration of stay . Results : The groups were well balanced for baseline characteristics , except for older age in the intervention group . There was a significant reduction in primary endpoint ( 3.5 % ) in the intervention group compared with the control group ( 12.3 % ) ( relative risk , 0.29 ; 95 % confidence interval , 0.10–0.83 ; P = 0.013 ) . The secondary endpoints were similar . Hypoglycemia occurred in 8.8 % of the intervention group compared with 4.1 % of the control group ( P = 0.14 ) . Multivariate analysis demonstrated that continuous insulin infusion was a negative independent predictor ( odds ratio , 0.28 ; 95 % confidence interval , 0.09–0.87 ; P = 0.027 ) , whereas previous coronary artery disease was a positive predictor of adverse events . Conclusion : Continuous insulin infusion reduces perioperative myocardial infa rct ion after vascular surgery This systematic overview summarizes the relevant evidence from multiple systematic review s of the benefits of nonpharmacological interventions for preventing  type 2 diabetes mellitus ( T2MD ) in women diagnosed with gestational diabetes mellitus ( GDM ) . A comprehensive search using the Cochrane Library , CINAHL , EMBASE and MEDLINE via Ovid SP , and PubMed data bases was completed on 18 November 2015 . Any systematic review s that evaluated r and omized controlled trials ( RCTs ) with defined nonpharmacological interventions for preventing T2DM in women diagnosed with GDM were eligible for inclusion . The authors independently performed critical appraisal s and quality assessment s of the included review s using the AMSTAR tool , and extracted data were converted to coherent values for tabular summarization . Six eligible review s of diet and /or exercise , breastfeeding , and reminder interventions were identified ; however , the method ologies of the review s varied greatly , and the majority of the evidence suggested unclear bias . We found inconsistent reporting on the rates at which diet and exercise interventions reduced the risk of T2DM progression , but these interventions were found to be effective at reducing glycemic load . Combined diet , exercise , and breastfeeding interventions proved to be effective at returning women to their postpartum weight . Neither diet alone nor exercise alone proved to be effective at lowering the risk of T2DM . Overall , there was no robust evidence to support the hypothesis that nonpharmacological interventions are effective at lowering the risk of T2DM in women diagnosed with GDM , and there was no consistent evidence showing that these interventions improved the predictor outcomes of T2DM , such as glycemic load or anthropometric changes Objectives : Myocardial infa rct ion after major surgery is frequent , drives outcome , and consumes health re sources . Specific prediction and detection of perioperative myocardial infa rct ion is an unmet clinical need . With the widespread use of high-sensitive cardiac troponin T assays , positive tests become frequent , but their diagnostic or prognostic impact is arguable . We , therefore , studied the association of routinely determined pre- and postoperative high-sensitive cardiac troponin T with the occurrence of major adverse cardiac events . Design : This study was a prospect i ve noninterventional trial . Setting : This study was conducted at Hannover Medical School in Germany . Patients : A total of 455 patients undergoing open vascular surgery  were followed for 30 days for the occurrence of major adverse cardiac events . Interventions : None . Measurements and Main Results : Preoperative and 24-hour postoperative high-sensitive cardiac troponin T measurements and the respective changes were correlated to medical history and the occurrence of major adverse cardiac events ( cardiovascular death , myocardial infa rct ion , and ischemia ) . Pre- and postoperative high-sensitive cardiac troponin T measurements demonstrated a majority of patients with detectable troponin levels preoperatively and an increase over the 24 hours after surgery . The level of high-sensitive cardiac troponin T was significantly associated with preexisting diseases that constitute the Lee ’s Revised Cardiac Risk Index . A preoperative high-sensitive cardiac troponin T greater than or equal to 17.8 ng/L and a perioperative high-sensitive cardiac troponin T  change greater than or equal to 6.3 ng/L are independently associated with the occurrence of major adverse cardiac events . Adding high-sensitive cardiac troponin T absolute change to the Revised Cardiac Risk Index improves the risk predictive accuracy of the score as evidence d by increased area under receiver operating characteristic and significant reclassification effects . Conclusions : The risk predictive power of high-sensitive cardiac troponin T change in addition to the Revised Cardiac Risk Index could facilitate 1 ) detection of patients at highest risk for perioperative myocardial ischemia , 2 ) evaluation and development of cardioprotective therapeutic strategies , and 3 ) decisions for admission to and discharge from high-density care units Supraventricular arrhythmia after noncardiac surgery is common [ 1 , 2 ] . Much of the data on the epidemiology and consequences of perioperative supraventricular arrhythmia in patients undergoing noncardiac surgery were collected before recent advances in anesthetic and monitoring techniques were made [ 3 ] . This clinical syndrome may have been influenced by such trends as the aging of the general population and the increased use of -blockers and calcium-channel blockers . To test the hypothesis that supraventricular arrhythmia remains a frequent event that is associated with major adverse outcomes after surgery , we studied a consecutive sample of 4181 patients who underwent major , nonemergency , noncardiac procedures and were in sinus rhythm at the preoperative evaluation . Our findings provide insight into the contemporary epidemiology and natural history of perioperative supraventricular arrhythmia . Methods Patients All patients 50 years of age or older who underwent major , nonemergency , noncardiac procedures at Brigham and Women 's Hospital , Boston , Massachusetts , from 18 July 1989 to 28 February 1994 were eligible for the study . Major noncardiac procedures were defined as those associated with an expected length of stay of 2 or more days . Procedures were electively scheduled or were done during inpatient admissions . The Brigham and Women 's Hospital Human Research Committee approved the enrollment and clinical data collection protocol s. Patients were included in this analysis if they were in sinus rhythm at the preoperative evaluation . Of the 4315 consecutive patients enrolled in the overall study , 4181 ( 97 % ) met this criterion and constituted the study sample for this analysis . Data Collection The data collection protocol is described elsewhere ( [ 4 ] ; Lee TH , Marcantonio ER , Mangione CM , Thomas EJ , Cook EF , Sugarbaker DJ , et al. Derivation and prospect i ve validation of a simple index for prediction of cardiac risk of major noncardiac surgery . In preparation ) . In brief , patients who provided informed consent for the full study protocol had preoperative evaluations done by study personnel , who used a structured data form . These evaluations included detailed medical histories , physical examinations , and laboratory testing . Intraoperative data were obtained from anesthesia flow sheets and surgeons ' notes . For patients who did not have this evaluation because they could not be approached or because they refused to participate in the interview portion of the study , clinical data were obtained from the structured evaluation performed by the anesthesiologist noted in the medical record . This data source was also used to obtain American Society of Anesthesiologists ( ASA ) classifications for all patients . Consenting patients agreed to postoperative sampling of creatine kinase . If total creatine kinase levels were elevated , creatine kinase-MB levels were measured immediately after surgery , at 8 p.m. on the evening of surgery , and on the next two mornings . For other enrolled patients , creatine kinase-MB testing was done according to the physician 's orders . Electrocardiography was performed in the recovery room and 1 , 3 , and 5 days after surgery if the patient remained hospitalized . Study personnel review ed charts daily for the occurrence of complications . Classification of Outcome The perioperative period was divided into two parts : the intraoperative period , which ended at the patient 's departure from the operating room , and the postoperative period . A perioperative supraventricular arrhythmia was diagnosed whenever a patient was noted by his or her physicians or by the study 's research personnel to have new onset of atrial fibrillation , atrial flutter , paroxysmal atrial tachycardia , multifocal atrial tachycardia , or regular supraventricular tachyarrhythmia without discernible P waves . For the purpose of this study , only episodes of supraventricular arrhythmia that were reported to be persistent or were treated with specific therapies were considered in the analysis . Review of records for a r and omly selected subset of 60 patients with supraventricular arrhythmia revealed that 87 % received specific treatment ( cardioversion or antiarrhythmic therapy ) . The postoperative occurrence of major cardiac events was classified by a single review er [ who was blinded to preoperative clinical data ] on the basis of postoperative clinical information , including cardiac enzyme measurements , electrocardiograms , and clinical events . Criteria for perioperative myocardial infa rct ion were 1 ) a new Q wave lasting 0.04 seconds or longer , 2 ) creatine kinase-MB levels greater than 5 % of an elevated total creatine kinase level with a typical increase and decrease in creatine kinase-MB levels , and 3 ) creatine kinase-MB levels greater than 3 % of an elevated total creatine kinase level in the setting of electrocardiographic changes consistent with ischemia [ 4 ] . Major cardiac events were myocardial infa rct ion , cardiogenic pulmonary edema , ventricular fibrillation or primary cardiac arrest , and sustained complete heart block . Intermediate cardiac events , recorded by study research personnel on the basis of record review , were congestive heart failure without pulmonary edema , myocardial ischemia with documented electrocardiographic changes , and documented ventricular tachycardia . Noncardiac events were pulmonary embolism , cerebrovascular accident , noncardiac pulmonary edema , respiratory failure requiring intubation , renal failure requiring dialysis , gastrointestinal bleeding , bacteremia , pneumonia , urinary tract infection , and wound infection . Statistical Analysis Univariate analyses of the correlation between clinical characteristics and the occurrence of perioperative supraventricular arrhythmia were performed by using a chi-square test and the Fisher exact test for categorical variables and a t-test or Wilcoxon test for continuous variables . Variables with a P value less than 0.10 were then entered into the multiple regression analysis . Stepwise logistic regression analysis was used to determine independent correlates of supraventricular arrhythmia . A two-sided P value less than 0.05 was considered statistically significant . Clinical ly relevant variables from the regression model were analyzed for potential interactions . Potentially significant interaction terms were considered in the regression models . In the analysis of the association between intraoperative events and the occurrence of supraventricular arrhythmia , only postoperative episodes of supraventricular arrhythmia were included ( n = 256 ) . A clinical ly significant hypotensive episode during surgery was defined as a decrease of one third in the original systolic blood pressure or a systolic blood pressure less than 90 mm Hg . Linear regression models were used to estimate the independent variation in length of stay attributable to supraventricular arrhythmia ; these models controlled for age , sex , preoperative clinical characteristics , ASA classification , type of procedure , and postoperative events ( major and intermediate cardiac events and noncardiac events ) . The log transformation of length of stay was used because of the non-normal distribution of this variable . The adjusted hospital days attributable to supraventricular arrhythmia were estimated from the percentage change in length of stay by using the geometric mean of length of stay from the final model . Results The patients ' mean age ( SD ) was 66 9 years . A total of 2244 patients ( 54 % ) were male , 563 ( 14 % ) were diabetic , 609 ( 15 % ) had a history of myocardial infa rct ion , 244 ( 6 % ) had congestive heart failure , and 1366 ( 33 % ) had evidence of ischemic heart disease . The types of procedures performed were orthopedic ( 35 % ) , thoracic ( 12 % ) , abdominal ( 12 % ) , abdominal aortic aneurysm ( 5 % ) , other vascular ( 16 % ) , and other general surgical ( 20 % ) procedures . A new perioperative supraventricular arrhythmia developed in 317 patients ( 7.6 % ) ( Table 1 ) . Less than 25 % of patients who had supraventricular arrhythmia had more than one episode of arrhythmia . Atrial fibrillation and supraventricular tachycardia without discernible P waves were the most frequent types of supraventricular arrhythmia and usually occurred in the postoperative period . The time of occurrence of postoperative supraventricular arrhythmia peaked during the first 3 days after surgery ( Figure 1 ) . This pattern of occurrence after surgery was similar for all types of supraventricular arrhythmia . Table 1 . Prevalence of Perioperative Supraventricular Arrhythmia  in 4181 Patients Undergoing Noncardiac Surgery *  Figure 1 . Distribution of  supraventricular arrhythmias ( SVA ) according to the time of first occurrence among the 256 patients who developed arrhythmias after surgery . Correlates of Supraventricular Arrhythmia Compared with patients who did not develop supraventricular arrhythmia , patients who developed this arrhythmia were significantly older and were more likely to be male ; to have a history of myocardial infa rct ion , congestive heart failure , diabetes , chronic lung disease , cancer , or arrhythmia ; to have evidence of clinical ly significant valvular disease ( such as systolic murmurs of grade III or higher ) on physical examination ; and to have premature atrial complexes on preoperative electrocardiography ( Table 2 ) . Table 2 . Univariate Analysis of Preoperative Correlates of Perioperative Supraventricular Arrhythmia * Preoperative use of calcium-channel blockers , digoxin , procainamide , and quinidine was more common in patients who developed supraventricular arrhythmia . Use of -blockers did not differ between the two groups . Patients with ASA classification III or IV were more likely to develop supraventricular arrhythmia . The most significant univariate correlate of supraventricular arrhythmia was the type of procedure performed . Patients who had abdominal aortic aneurysm repair or an intrathoracic , abdominal , or other vascular procedure had an increased risk for perioperative Objectives : The SCORE model predicts the ten-year risk of cardiovascular mortality but it is still unknown whether applying the SCORE in clinical practice subsequently improves cardiovascular disease ( CVD ) outcomes . The objective of this study is to assess the effect of total cardiovascular risk estimation using the SCORE in preventing serious cardiovascular events in European adults without prior CVD . Methods and results : Data sources : eight bibliographical data bases ( 2003 – August 2015 ) , other internet sources and reference lists of articles were checked . This was supplemented by contact with the board members of the European Society of Cardiology ( ESC ) and the authors of the SCORE model . Study eligibility criteria : all prospect i ve studies in any language investigating the effect of using the SCORE on the clinical outcome ( CVD death , major events and adverse outcomes ) in an adult population were examined . Two review ers assessed the studies independently ( titles , abstract s , full texts ) . After removal of duplicates , 5,256 records were screened and 14 full text papers considered . No eligible studies were identified . An extensive literature search revealed no r and omized control trial or other prospect i ve study comparing significant clinical outcomes between groups that used the SCORE and those who did not . Conclusions : The effect of using the SCORE ( with or without subsequent intervention ) on CVD death , all-cause mortality , major CVD events like myocardial infa rct ion and stroke , as well as adverse outcomes , is still unknown . A cluster r and omised controlled trial is warranted to evaluate the use of the SCORE on important outcomes Context Residual paralysis is associated with post-operative pulmonary complications , including critical respiratory events . Objective We determined the incidence of critical respiratory events , such as hypoxaemia , in patients with minimal residual neuromuscular blockade and compared these data with those from patients with full recovery of blockade . Design R and omised , prospect i ve , placebo-controlled trial . Setting Single centre ; Rostock , Germany , from January 2007 to February 2008 . Patients One hundred and thirty-two adult patients , aged 18–80 years , with the American Society of Anesthesiology I – III physical status , undergoing orthopaedic surgery under general anaesthesia , including rocuronium to produce neuromuscular blockade ; 114 patients were r and omised to one of two groups : neostigmine group ( neostigmine 20 & mgr;g kg−1 ) or placebo group ( saline ) . Interventions In the patients in the neostigmine group , the tracheal tube was removed at a train-of-four ( TOF ) ratio of 1.0 ; in the patients in the placebo group , the trachea was extubated at a TOF ratio less than 1.0 , but without fade in TOF and double-burst stimulation ( DBS ) . Neuromuscular monitoring was assessed simultaneously with qualitative TOF/DBS monitoring , and with quantitative calibrated acceleromyography . Critical respiratory events , such as hypoxaemia , were assessed in the post-anaesthesia care unit . Main outcome measures Forty-five patients ( 39.5 % ) became hypoxaemic ( SaO2 < 93 % ) ; there was a significant difference between the groups ( 29 patients in the placebo group versus 16 in the neostigmine group ; P = 0.021 ) . Results In the neostigmine group , all patients were extubated at a TOF ratio of 1.0 . In the placebo group , the median TOF ratio was 0.7 ( range : 0.46–0.9 ; P < 0.001 ) . The median time for spontaneous recovery in the placebo group was 16 min ( range 3–49 min ) . Neostigmine 20 & mgr;g kg−1 was effective in antagonising rocuronium-induced blockade without fade in TOF and DBS . Conclusion In this r and omised , prospect i ve , placebo-controlled trial , minimal residual block was associated with hypoxaemia in the post-anaesthesia care unit . Neostigmine 20 & mgr;g kg−1 was effective in antagonising rocuronium-induced ( minimal ) blockade Background and Objectives Pregabalin is often used as a perioperative analgesic adjunct ; some studies show benefit , but others do not . Adverse effects , such as confusion and sedation , have been attributed to perioperative use of pregabalin . We tested the hypothesis that pregabalin , when used as part of a multimodal analgesic regimen , reduces the duration of moderate to severe pain in the first 24 hrs following foot or ankle surgery . Secondary outcomes included measures of opioid and pregabalin adverse effects . Methods Sixty patients scheduled for hospital admission after foot or ankle surgery entered this r and omized , double-blind , placebo-controlled trial . Patients received a neuraxial anesthetic , a popliteal fossa sciatic nerve block using 30 mL 0.375 % bupivacaine with clonidine 100 µg and epinephrine , a saphenous nerve block , postoperative hydromorphone intravenous patient-controlled analgesia , and oral analgesics ( oxycodone/acetaminophen ) . Patients were r and omized to receive pregabalin ( 100 mg preoperatively , then 50 mg every 12 hrs ) or a placebo for 3 days . The primary outcome was the number of hours that patients reported moderate to severe pain . Results Both groups reported a similar number of hours of moderate to severe pain during the first 24 hrs : 4.1 ( SD , 4.1 ) hrs ( pregabalin ) versus 4.5 ( SD , 3.5 ) hrs  ( placebo ) . Pain scores , opioid use , and adverse effects were also similar in both groups . Conclusions No clinical benefit was obtained from perioperative administration of pregabalin ( 100 mg preoperative , then 50 mg every 12 hrs ) as part of a multimodal postoperative analgesic regimen following foot and ankle surgery BACKGROUND Blockade of the platelet glycoprotein IIb/IIIa receptor with the monoclonal antibody fragment abciximab was shown in a placebo-controlled r and omized trial to reduce the incidence of acute ischemic complications within 30 days among a broad spectrum of patients undergoing percutaneous coronary revascularization . The durability of clinical benefit in this setting has not been established . METHODS AND RESULTS A total of 2792 patients enrolled in the Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade ( EPILOG ) trial were followed with maintenance of double-blinding for 1 year . Patients had been assigned at the time of their index coronary interventional procedure to receive placebo with st and ard-dose , weight-adjusted heparin ( 100 U/kg initial bolus ) , abciximab with st and ard-dose , weight-adjusted heparin , or abciximab with low-dose , weight-adjusted heparin ( 70 U/kg initial bolus ) . The primary outcome was the composite of death , myocardial infa rct ion , or urgent repeat revascularization by 30 days ; this composite end point and its individual components were also assessed at 6 months and 1 year . Rates of any repeat revascularization ( urgent or elective ) , target vessel revascularization , and a composite of death , myocardial infa rct ion , or any repeat revascularization were also reported . Follow-up at 1 year was 99 % complete for survival status and 97 % complete for other end points . By 1 year , the incidence of the primary composite end point was 16.1 % in the placebo group , 9.6 % in the abciximab with low-dose heparin group ( P<0.001 ) , and 9.5 % in the abciximab with st and ard-dose heparin group ( P<0.001 ) . Each of the components of this composite end point was reduced to a similar extent . Nonurgent or target vessel repeat revascularization rates were not significantly decreased by abciximab therapy . Mortality rates over 1 year increased with increasing levels of periprocedural creatine kinase MB fraction elevation . CONCLUSIONS Acute reductions in ischemic events after percutaneous coronary intervention by abciximab are sustained over follow-up to at least 1 year . Early periprocedural myocardial infa rct ions suppressed by this therapy are associated with long-term mortality rates BACKGROUND Although guidelines recommend the use of beta-adrenoceptor blocking drugs to reduce cardiac events ( CEs ) after major noncardiac surgery , trial results have varied between showing benefit , ineffectiveness , and harm . We sought whether optimizing beta-blockade ( BB ) delivery could make them more effective . METHODS Intermediate risk patients undergoing major noncardiac surgery ( n = 400 ) were r and omized to 2 strategies of BB therapy : universal BB ( UBB ; n = 197 ) comprising an algorithm-based , nurse-led strategy to optimize dosing and adherence to bisoprolol titration over > or = 1 week preoperatively versus usual care ( UC ; n = 203 ) , whereby BB are continued in those already taking them or prescribed for patients identified as high risk based on ischemia ( new or inducible wall motion abnormalities ) at dobutamine echocardiography ( DbE ) . Daily electrocardiogram and troponin levels were obtained on 3 postoperative days . The primary end point was a major CE ( cardiac death or myocardial infa rct ion ) within 30 days . RESULTS There were 25 major CEs ( 6.3 % ) , occurring in 13 ( 6.6 % ) of 197 UBB and 12 ( 5.9 % ) of 203 UC patients ( OR 1.12 , 95 % CI 0.52 - 2.39 ) . Independent predictors of CEs were baseline systolic blood pressure ( beta 1.02 , P = .005 ) and postoperative hypotension ( beta 1.02 , P = .03 ) but not treatment strategy . Those r and omized to UBB had significantly better heart rate control perioperatively , at the cost of bradycardia and hypotension . The negative predictive value of DbE in this study was 95 % . CONCLUSIONS These data confirm a persistent CE rate after major noncardiac surgery despite nurse-led dose titration of bisoprolol . Cardiac events were equivalent to a UC strategy based on DbE results The original Norwegian Multicenter Study on  Timolol after Myocardial Infa rct ion was a double-blind , r and omized study comparing the effect of timolol with that of placebo for up to 33 months after acute myocardial infa rct ion . The initial results showed that the cumulated mortality rate was 39.4 per cent lower among 945 patients r and omly assigned to  timolol  treatment than among 939 patients r and omly assigned to  placebo  ( P = 0.0003 ) . After the end of the double-blind period the majority of participating patients in the timolol group continued to receive beta-adrenergic blockade , whereas the majority of  placebo-treated patients continued without such blockade . During an extended follow-up of participating patients up to 72 months after r and omization , the mortality curves of the two groups continued to rise in parallel . Cumulated mortality rates were 32.3 per cent in the placebo group and 26.4 per cent in the timolol group ( P = 0.0028 ) . We conclude that the previously observed early beneficial effect of beta-adrenergic blocking therapy is maintained for at least six years after infa rct ion BACKGROUND Ultrasound can facilitate neuraxial blockade in patients with poorly defined anatomical surface l and marks , but there are no studies comparing an ultrasound-guided technique with l and mark palpation for spinal anaesthesia . The objective of this study was to compare pre-procedural lumbar ultrasonography with l and mark palpation to locate the needle insertion point in women with impalpable lumbar spinous processes presenting for caesarean delivery . METHODS After institutional ethics committee approval , 20 women with impalpable lumbar spinous processes presenting for elective caesarean delivery were recruited . Patients were r and omised to palpation or ultrasound . The primary outcome of the study was the number of needle passes to achieve lumbar puncture . Secondary outcomes were the overall procedural time and patient satisfaction score . RESULTS There was no difference in mean ( ±SD ) body mass index of both groups ( ultrasound 39.1 ± 5.02kg/m2 vs. palpation 38.3±3.77kg/m2 ) . There were significantly fewer needle passes in the ultrasound group ( median 3 [ IQR 1.8 - 3.2 ] ) compared to the palpation group ( median 5.5 [ IQR 3.2 - 7.2 ] ( P=0.03 ) ) . More time was required to locate the needle insertion point in the ultrasound group ( ultrasound 91.8±30.8s vs. palpation 32.6±11.4s , P<0.001 ) . There was no difference in the total procedural time between groups ( ultrasound 191.8±49.4s vs. palpation 192±110.9s , P=0.99 ) . CONCLUSION The use of ultrasonography to locate the needle insertion point reduced the number of needle passes in women with impalpable lumbar spinous processes undergoing elective caesarean delivery under spinal anaesthesia . Its use did not prolong overall procedural time Objectives In general population s , the adverse effects of smoking on coronary risk have been demonstrated to be greater in women than in men ; whether this is true for individuals with diabetes is unclear . Design Cohort study . Setting 20 countries worldwide participating in the ADVANCE ( Action in Diabetes and Vascular Disease : Preterax and Diamicron modified release Controlled Evaluation ) trial . Participants 11 140 patients with type 2 diabetes aged ≥55 years and in cardiovascular risk at the time of r and omisation . Primary and secondary outcome measures Major cardiovascular events ( death from cardiovascular disease , non-fatal stroke or non-fatal myocardial infa rct ion ( MI ) ) , all cardiovascular events ( major cardiovascular event or peripheral arterial disease or transient ischaemic attack ) , and all-cause mortality . Secondary outcome measures were major coronary events ( fatal and non-fatal MI ) , major cerebrovascular events ( fatal and non-fatal stroke ) , nephropathy ( new or worsening renal disease ) , and all cancer . Results At baseline , 6466 ( 56 % women ) participants were never-smokers , 1550 ( 28 % women ) were daily smokers and 3124 ( 21 % women ) were former smokers . Median follow-up time was 5 years . In Cox regression models after multiple adjustments , compared with never smoking , daily smoking was associated with increased risk of all primary and secondary outcomes with the exception of major cerebrovascular disease . Only for major coronary events was there any evidence of a stronger effect in women than in men ( ratio of the adjusted HRs women : men ; 1.64 ( 0.83 to 3.26 ) p=0.08 ) . For all other outcomes considered , the hazards of smoking were similar in men and women . Quitting smoking was associated with a 30 % reduction in all-cause mortality ( p=0.001 ) in both sexes . Conclusions In individuals with diabetes , the effects of smoking on all major forms of cardiovascular disease are equally as hazardous in women and men with the possible exception of major coronary events where there was some evidence of a greater hazard in women . Trial registration number NCT00145925 BACKGROUND Increased long-term mortality was found in patients exposed to perioperative hyperoxia in the PROXI trial , where patients undergoing laparotomy were r and omised to 80 % versus 30 % oxygen during and after surgery . This post hoc follow-up study assessed the impact of perioperative hyperoxia on long-term risk of cardiovascular events . METHODS A total of 1386 patients undergoing either elective or emergency laparotomy  were r and omised to 80 % versus 30 % oxygen during and two hours after surgery . At follow-up , the primary outcome of acute coronary syndrome was assessed . Secondary outcomes included myocardial infa rct ion , other heart disease , and acute coronary syndrome or death . Data were analysed in the Cox proportional hazards model . RESULTS The primary outcome , acute coronary syndrome , occurred in 2.5 % versus 1.3 % in the 80 % versus 30 % oxygen group ; HR 2.15 ( 95 % CI 0.96 - 4.84 ) . Patients in the 80 % oxygen group had significantly increased risk of myocardial infa rct ion ; HR 2.86 ( 95 % CI 1.10 - 7.44 ) , other heart disease ; HR 1.40 ( 95 % 1.06 - 1.83 ) , and acute coronary syndrome or death ; HR 1.22 ( 95 % CI 1.01 - 1.49 ) . CONCLUSIONS Perioperative hyperoxia may be associated with an increased long-term risk of myocardial infa rct ion and other heart disease Background : Poor surface anatomic l and marks are highly predictive of technical difficulty in neuraxial blockade . The authors examined the use of ultrasound imaging to reduce this difficulty . Methods : The authors recruited 120 orthopedic patients with one of the following : body mass index more than 35 kg/m2 and poorly palpable spinous processes ; moderate to severe lumbar scoliosis ; or previous lumbar spine surgery . Patients were r and omized to receive spinal anesthetic by the conventional surface l and mark-guided technique ( group LM ) or by an ultrasound-guided technique ( group US ) . Patients in group US had a preprocedural ultrasound scan to locate and mark a suitable needle insertion point . The primary outcome was the rate of successful dural puncture on the first needle insertion attempt . Normally distributed data were summarized as mean ± SD and nonnormally distributed data were summarized as median [ interquartile range ] . Results : The first-attempt success rate was twice as high in group US than in group LM ( 65 % vs. 32 % ; P < 0.001 ) . There was a twofold difference between groups in the number of needle insertion attempts ( group US , 1 [ 1–2 ] vs. group LM , 2 [ 1–4 ] ; P < 0.001 ) and number of needle passes ( group US , 6 [ 1–10 ] vs. group LM , 13 [ 5–21 ] ; P = 0.003 ) . More time was required to establish l and marks in group US ( 6.7 ± 3.1 ; group LM , 0.6 ± 0.5 min ; P < 0.001 ) , but this was partially offset by a shorter spinal anesthesia performance time ( group US , 5.0 ± 4.9 vs. group LM , 7.3 ± 7.6 min ; P = 0.038 ) . Similar results were seen in subgroup analyses of patients with body mass index more than 35 kg/m2 and patients with poorly palpable l and marks . Conclusion : Preprocedural ultrasound imaging facilitates the performance of spinal anesthesia in the nonobstetric patient population with difficult anatomic l and marks BACKGROUND It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management . METHODS We did a r and omised , multicentre , superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infa rct ion who were about to undergo coronary angiography and percutaneous coronary intervention . Patients were r and omly allocated ( 1:1 ) to radial or femoral access with a web-based system . The r and omisation sequence was computer generated , blocked , and stratified by use of ticagrelor or prasugrel , type of acute coronary syndrome ( ST-segment elevation myocardial infa rct ion , troponin positive or negative , non-ST-segment elevation acute coronary syndrome ) , and anticipated use of immediate percutaneous coronary intervention . Outcome assessors were masked to treatment allocation . The 30-day co primary outcomes were major adverse cardiovascular events , defined as death , myocardial infa rct ion , or stroke , and net adverse clinical events , defined as major adverse cardiovascular events or Bleeding Academic Research Consortium ( BARC ) major bleeding unrelated to coronary artery bypass graft surgery . The analysis was by intention to treat . The two-sided α was prespecified at 0·025 . The trial is registered at Clinical Trials.gov , number NCT01433627 . FINDINGS We r and omly assigned 8404 patients with acute coronary syndrome , with or without ST-segment elevation , to radial ( 4197 ) or femoral ( 4207 ) access for coronary angiography and percutaneous coronary intervention . 369 ( 8·8 % ) patients with radial access had major adverse cardiovascular events , compared with 429 ( 10·3 % ) patients with femoral access ( rate ratio [ RR ] 0·85 , 95 % CI 0·74 - 0·99 ; p=0·0307 ) , non-significant at α of 0·025 . 410 ( 9·8 % ) patients with radial access had net adverse clinical events compared with 486 ( 11·7 % ) patients with femoral access ( 0·83 , 95 % CI 0·73 - 0·96 ; p=0·0092 ) . The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery ( 1·6 % vs 2·3 % , RR 0·67 , 95 % CI 0·49 - 0·92 ; p=0·013 ) and all-cause mortality ( 1·6 % vs 2·2 % , RR 0·72 , 95 % CI 0·53 - 0·99 ; p=0·045 ) . INTERPRETATION In patients with acute coronary syndrome undergoing invasive management , radial as compared with femoral access reduces net adverse clinical events , through a reduction in major bleeding and all-cause mortality . FUNDING The Medicines Company and Terumo The relation across anemia , hemorrhagic complications , and mortality associated with  percutaneous coronary intervention ( PCI )  is unclear . We review ed the R and omized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 Trial , which compared bivalirudin plus provisional glycoprotein IIb/IIIa blockade with heparin plus planned glycoprotein IIb/IIIa blockade in patients undergoing urgent or elective PCI . Of the 6,010 patients r and omized in REPLACE-2 , 1,371 ( 23 % ) were anemic .  Major bleeding was more common in anemic than in nonanemic patients ( 4.9 % vs 2.8 % , p = 0.0001 ) . In anemic patients , treatment with bivalirudin ( n = 678 ) result ed in a lower risk of major bleeding versus heparin plus glycoprotein IIb/IIIa blockade ( n = 693 , 3.5 % vs 6.2 % , p = 0.0221 ) . Mortality was higher in anemic patients than in nonanemic patients at 30 days ( 0.9 % vs 0.2 % , p < 0.0001 ) , 6 months ( 2.6 % vs 0.7 % , p < 0.0001 ) , and 1 year ( 4.3 % vs 1.5 % , p < 0.0001 ) . There were no differences between anemic and nonanemic patients with regard to ischemic complications at 30 days . Although anemic patients had higher mortality rates , proportions of cardiovascular and noncardiovascular mortalities were equal in anemic and nonanemic patients . In conclusion , anemic patients undergoing PCI have an increased risk of mortality and major bleeding , but not of ischemic events , and the use of bivalirudin with provisional glycoprotein IIb/IIIa blockade decreases the risk of hemorrhagic complications compared with heparin plus planned glycoprotein IIb/IIIa blockade OBJECTIVES The purpose of this study was to investigate the effects of angiotensin II receptor blockers on the prevention of cardiovascular events in patients with coronary artery disease ( CAD ) . BACKGROUND Angiotensin II may contribute to the pathogenesis of CAD . Long-term clinical trials have shown that blockade of the renin-angiotensin system can reduce cardiovascular events in patients with acute myocardial infa rct ion complicated by heart failure . METHODS Patients with a history of coronary intervention and no significant coronary stenosis on follow-up angiography 6 months after intervention were r and omly assigned into a c and esartan group ( n = 203 ; baseline treatment plus c and esartan 4 mg/d ) or a control group ( n = 203 ; baseline treatment alone ) . The primary end point was a composite of revascularization , nonfatal myocardial infa rct ion , or cardiovascular death . The secondary end point was hospitalization for cardiovascular causes . RESULTS There were no changes in blood pressure and in other coronary risk factors in either group during a mean follow-up of 24 months . Primary end point risk was significantly lower in the c and esartan group ( n = 12 ) than in control group patients ( n = 25 ) ( P = .03 ) . C and esartan treatment reduced primary end point risk ( 5.9 % vs 12.3 % for control subjects ; relative risk , 0.47 ; 95 % CI , 0.24 to 0.93 ) . The incidence of all events including secondary end points and noncardiovascular death was significantly lower in the c and esartan group than in control group patients ( 23 vs 40 cases ) ( P = .02 ) . CONCLUSIONS Relatively low-dose c and esartan , which did not alter blood pressure levels , reduces cardiovascular risk in high-risk patients with CAD At the end of a long week in the office , you sink back into your chair , reflecting on some of the more memorable patients you cared for and counseled . Through gentle history taking , you discovered that urinary incontinence is the underlying cause of an elderly patient 's increasing social isolation . During a careful physical examination , you detected bruising on the torso of a woman with chronic headaches and began to explore the longst and ing abusive relationship between the woman and her alcoholic partner . You discontinued procainamide therapy in a 72-year-old man who had asymptomatic premature ventricular contractions after myocardial infa rct ion . To prevent bleeding from esophageal varices , you started -blocker therapy in a woman with long-st and ing cryptogenic cirrhosis and portal hypertension . In couples ' therapy , discussing the future quality of life of a middle-aged gay man with human immunodeficiency virus infection , you journeyed through emotionally intense dialogue about advance directives . You presented the risk factors for major and minor bleeding to a 39-year-old woman who was considering warfarin therapy because of recently diagnosed atrial fibrillation and valvular heart disease . You listened to , made diagnoses for , treated , advised , and comforted many patients . Yet there were some hiccoughs in your practice along the way . You stumbled while debating the pros and cons of breast cancer screening with a healthy 48-year-old woman who has been staying current with information on the Internet . You question ed the merits of a personalized walking program suggested to you by a motivated 66-year-old man with severe claudication . Explaining that you wanted to review the best current evidence on these issues , you resolved to address your uncertainties before these patients made their next office visits , in a week 's time . Sighing deeply , you acknowledge that you have little time to read . You subscribe to three journals , which you browse months after they arrive-either when your journal stack becomes precariously high or when your guilt is sufficiently motivational . You sometimes find the conclusions of individual articles conflicting or confusing . You know that some of the decisions and suggestions you made this week , specifically your decisions about stopping procainamide therapy and starting -blocker therapy and your advice about bleeding risks from anticoagulant therapy , were based on the best current research evidence [ 1 - 3 ] . On the other h and , your patients ' inquiries about breast cancer screening and exercise treatment for claudication highlight your need for a concise , current , rigorous synthesis of the best available evidence on each of these topics : in brief , a systematic review [ 4 , 5 ] . Incorporating Research Evidence into Clinical Decision Making The foregoing scenario is familiar to practitioners . In a typical week , we encounter patients with diverse problems ; exercise numerous clinical , interpersonal , and technical skills ; and make many decisions . The factors that affect these decisions and their outcomes are complex . For instance , each patient has unique sociodemographic characteristics , cultural circumstances , and personal preferences . Each physician has unique knowledge , experiences , and values . Moreover , practitioners and their patients make decisions within the context of a rapidly changing health care system that influences the availability , accessibility , and cost of diagnostic tests and therapies [ 6 ] . Timely , useful evidence from the biomedical literature should be an integral component of clinical decision making . If one treatment has been shown to be better than another , we need to know , so that we can recommend the treatment to the appropriate patients . The worldwide effort to develop new tests and treatments , and to determine their usefulness , has never been stronger , and our patients and their families expect us to be fonts of the knowledge that results from this effort [ 7 ] . Unfortunately , it is easy for current best research evidence to pass us by [ 8 ] . We may lack the time , motivation , and basic skills needed to find , critically appraise , and synthesize information , all of which we must do if we are to integrate the results of original studies into our practice . Fortunately , several potent methods are emerging that can greatly enhance our ability to interpret and apply research evidence ; foremost among them is the systematic review . This article begins a series in Annals that will examine systematic review s in detail and explore their many applications . Systematic review s represent the best chance that most practitioners will have to underst and and accurately apply the key signals arising from the robust and increasingly productive search for solutions to medical problems . A properly conducted systematic review faithfully summarizes the evidence from all relevant studies on the topic of interest , and it does so concisely and transparently . What Is a Systematic Review ? Systematic review s are scientific investigations in themselves , with pre-planned methods and an assembly of original studies as their subjects . They synthesize the results of multiple primary investigations by using strategies that limit bias and r and om error [ 9 , 10 ] . These strategies include a comprehensive search of all potentially relevant articles and the use of explicit , reproducible criteria in the selection of articles for review . Primary research design s and study characteristics are appraised , data are synthesized , and results are interpreted . When the results of primary studies are summarized but not statistically combined , the review may be called a qualitative systematic review . A quantitative systematic review , or meta- analysis , is a systematic review that uses statistical methods to combine the results of two or more studies . The term overview is sometimes used to denote a systematic review , whether quantitative or qualitative . Summaries of research that lack explicit descriptions of systematic methods are often called narrative review s. Review articles are one type of integrative publication ; practice guidelines , economic evaluations , and clinical decision analyses are others . These other types of integrative articles often incorporate the results of systematic review s. For example , practice guidelines are systematic ally developed statements intended to assist practitioners and patients with decisions about appropriate health care for specific clinical circumstances [ 11 ] . Evidence -based practice guidelines are based on systematic review s of the literature , appropriately adapted to local circumstances and values . Economic evaluations compare both the costs and the consequences of different courses of action ; the knowledge of consequences that are considered in these evaluations is often generated by systematic review s of primary studies . Decision analyses quantify both the likelihood and the valuation of the expected outcomes associated with competing alternatives . Differences between Systematic and Narrative Review s All review s , narrative and systematic alike , are retrospective , observational research studies and are therefore subject to systematic and r and om error . Accordingly , the quality of a review - and thus its worth-depends on the extent to which scientific review methods have been used to minimize error and bias . This is the key feature that distinguishes traditional narrative review s from systematic review s ( Table 1 ) . If a review is prepared according to the steps outlined in the right column of Table 1 , it is more likely to be systematic and to provide unbiased conclusions . If review methods approximate those found in the middle column of Table 1 , the article is more likely to be a narrative review , and the conclusions are less likely to be based on an unbiased summary of all relevant evidence . Table 1 . Differences between Narrative Review s and Systematic Review s Systematic review s are generated to answer specific , often narrow , clinical questions in depth . These questions can be formulated explicitly according to four variables : a specific population and setting ( such as elderly out patients ) , the condition of interest ( for example , hypertension ) , an exposure to a test or treatment ( such as pharmacologic management ) , and one or more specific outcomes ( such as cardiovascular and cerebrovascular events and mortality ) [ 12 ] . Thus , an example of a well-formulated , clinical ly relevant question is , Does pharmacologic treatment of hypertension in the elderly prevent strokes and myocardial infa rct ions or delay death ? If the question that is driving the review is not clear from the title , abstract , or introduction , or if no methods section is included , the paper is more likely to be a narrative review than a systematic review [ 13 ] . Most narrative review articles deal with a broad range of issues related to a given topic rather than addressing a particular issue in depth [ 9 ] . For example , a narrative review on diabetes ( such as that which might be found in a textbook chapter ) might include sections on the physiology and pathophysiology of carbohydrate , lipid , and protein metabolism ; the epidemiology of and prognosis associated with diabetes ; diagnostic and screening approaches ; and preventive , therapeutic , rehabilitative , and palliative interventions . Thus , narrative review s may be most useful for obtaining a broad perspective on a topic ; they are less often useful in furnishing quantitative answers to specific clinical questions . Narrative review s are appropriate for describing the history or development of a problem and its management . Narrative review s may better describe cutting-edge developments if research is scant or preliminary or if studies are very limited by flawed design or execution [ 13 ] . They may be particularly useful for discussing data in light of underlying theory and context . Narrative review s can draw analogies and can conceptually integrate two independent fields of research , such as OBJECTIVE : To determine whether early initiation of neuraxial analgesia ( anesthetic[s ] placed around the nerves of the central nervous system ) compared with systemic opioid analgesia , followed later in labor by epidural analgesia , increases the rate of cesarean delivery in nulliparas undergoing induction of labor . METHODS : Nulliparas undergoing induction of labor who requested analgesia when cervical dilation was less than 4 cm participated in the study . Patients were r and omized to neuraxial ( early ) or systemic opioid ( late ) analgesia at the first analgesia request . Patient-controlled epidural analgesia was initiated in the early group at the second analgesia request and in the late group at cervical dilation of 4 cm or greater or at the third analgesia request . The primary outcome was the rate of cesarean delivery . RESULTS : The rate of cesarean delivery was not different between groups ( neuraxial [ early ] 32.7 % compared with systemic [ late ] 31.5 % , 95 % confidence interval of the difference -3 % to 6 % , P=.65 ) . A sample size of 30,500 would be required to detect a difference at the observed rate . There were no differences in the mode of vaginal delivery or Apgar scores . Pain scores were significantly lower ( median 1 compared with 5 on a 0–10 scale , P<.001 ) and labor duration shorter ( median 528 minutes compared with 569 minutes , P=.047 ) in the early group . The incidence of reassuring fetal heart rate tracings after analgesia was not different between groups . CONCLUSION : Early-labor neuraxial analgesia does not increase the cesarean delivery rate compared with late epidural analgesia in nulliparas undergoing induction of labor . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00380978 LEVEL OF EVIDENCE : Background Systematic review s of the effects of healthcare interventions frequently include non-r and omized studies . These are subject to confounding and a range of other biases that are seldom considered in detail when synthesizing and interpreting the results . Our aims were to assess the reliability and usability of a new Cochrane risk of bias ( RoB ) tool for non-r and omized studies of interventions and to determine whether restricting analysis to studies with low or moderate RoB made a material difference to the results of the review s. Methods and Findings We selected two systematic review s of population -based , controlled non-r and omized studies of the relationship between the use of thiazolidinediones ( TZDs ) and cyclooxygenase-2 ( COX-2 ) inhibitors and major cardiovascular events . Two epidemiologists applied the Cochrane RoB tool and made assessment s across the seven specified domains of bias for each of 37 component studies . Inter-rater agreement was measured using the weighted Kappa statistic . We grouped studies according to overall RoB and performed statistical pooling for ( a ) all studies and ( b ) only studies with low or moderate RoB. Kappa scores across the seven bias domains ranged from 0.50 to 1.0 . In the COX-2 inhibitor review , two studies had low overall RoB , 14 had moderate RoB , and five had serious RoB. In the TZD review , six studies had low RoB , four had moderate RoB , four had serious RoB , and two had critical RoB. The pooled odds ratios for myocardial infa rct ion , heart failure , and death for rosiglitazone versus pioglitazone remained significantly elevated when analyses were confined to studies with low or moderate RoB. However , the estimate for myocardial infa rct ion declined from 1.14 ( 95 % CI 1.07–1.24 ) to 1.06 ( 95 % CI 0.99–1.13 ) when analysis was confined to studies with low RoB. Estimates of pooled relative risks of cardiovascular events with COX-2 inhibitors compared with no nonsteroidal anti-inflammatory drug changed little when analyses were confined to studies with low or moderate RoB. The exception was a rise in the relative risk associated with ibuprofen from 1.07 ( 95 % CI 0.97–1.18 ) to 1.14 ( 95 % CI 1.03–1.26 ) . The main limitation of our study was testing the instrument on a narrow range of pharmacoepidemiological studies ; we can not assume our findings extend to a broader range of interventions and setting s. Conclusions The Cochrane RoB tool highlighted a wide range of risks of bias in studies included in two widely cited review s and had the potential to change the conclusions of the review s. Systematic review s that incorporate non-r and omized studies of medical interventions should include a detailed assessment of RoB for each included study BACKGROUND Perioperative beta blockade has been shown to reduce mortality after major elective surgery . The aim of this study was to determine whether it could reduce the rate of death and morbidity from cardiac complications in high risk patients undergoing emergency surgery . METHODS Over a one-year interval all patients undergoing major non-elective orthopaedic or general surgery were screened to identify those at high risk of cardiac complications . Consenting , high risk patients were r and omly allocated atenolol or placebo for seven days , commencing at anaesthetic induction . Deaths and cardiac complications within 30 days were recorded . RESULTS Some 2351 patients had an emergency operation ; 145 were at high risk and eligible for the study . Of 89 patients approached , 57 initially consented . Only 38 patients , however , completed the study protocol , 19 were withdrawn . Of those who completed the study , 5/20 patients in the placebo group and 3/18 in the treatment group died before hospital discharge ( p=0.520 ) . Four others in the placebo group and two in the atenolol group had post-operative non-fatal cardiac events ( positive troponin T ) , p=0.311 . CONCLUSIONS This study of emergency surgery proved more difficult than similar trials in elective surgery . The final study groups were small and there were no significant differences in outcomes . A much larger study is required for a definitive answer BACKGROUND Abdominal aortic clamping during aneurysm repair may cause a decrease in splanchnic blood flow and deterioration of gut barrier integrity . Epidural blocks have beneficial effects on vital organs during abdominal surgery , but sparse data are available on the influence on gut permeability during open aortic surgery . The aim of this study was to verify the hypothesis that epidural blocks may have beneficial effects on intestine permeability changes . METHODS Seventy individuals undergoing elective open abdominal aortic aneurysm repair were r and omly assigned to receive either balanced anaesthesia ( continuous epidural and general anaesthesia , group E&G ) or only general anaesthesia ( group G ) . For group E&G , an epidural catheter was inserted into the epidural space before the induction of general anaesthesia . Ropivacaine was used for intraoperative and postoperative blocks . For both groups general anaesthesia was maintained with sevoflurane . For group G , analgesia was provided with remifentanil . The assessment s of gut function were based on measurements of the absorption and percentages of urinary excretion of four sugars ( m 3-O-methyl-D-glucose , D-xylose , L-rhamnose and lactulose ) and the lactulose/rhamnose ( L/R ) ratio . RESULTS No intergroup differences were observed for sugar recovery or L/R ratio . Significant decreases in 3-O-methyl-D-glucose , D-xylose , and L-rhamnose recoveries were revealed in both examined groups when comparing the results obtained at 12 and 24 hours following the administration of anaesthesia . The rate of blood pressure decrease was significantly higher in group E&G. CONCLUSIONS Aortic clamping during open abdominal aortic repair led to unfavorable changes in intestinal permeability . Epidural block did not attenuate this deterioration OBJECTIVE Statin therapy in ambulatory population s is associated with a significant reduction in adverse cardiovascular events , including death and myocardial infa rct ion . Much less is known about the beneficial effects of statins on acute perioperative cardiovascular events . The purpose of this study was to determine whether preoperative statin therapy is associated with a reduced risk of early cardiac death or nonfatal , in-hospital postoperative myocardial infa rct ion after primary , elective coronary artery bypass graft surgery requiring cardiopulmonary bypass . METHODS The Multicenter Study of Perioperative Ischemia ( McSPI ) Epidemiology II Study was a prospect i ve , longitudinal study of 5436 patients undergoing coronary artery bypass graft surgery between November 1996 and June 2000 at 70 centers in 17 countries . The present study consisted of a pre-specified subset of these subjects divided into patients receiving ( n = 1352 ) and not receiving ( n = 1314 ) preoperative statin therapy . To control for potential bias related to use of statin therapy , the study estimated propensity scores by logistic regression to determine the predicted probability of inclusion in the " statin " group . Multivariate , stepwise logistic regression was then performed , controlling for patient demographics , medical history , operative characteristics , and propensity score to determine whether preoperative statin therapy was independently associated with a reduction in the risk of early ( DOS-POD3 ) cardiac death and /or nonfatal , in-hospital postoperative myocardial infa rct ion . RESULTS Preoperative statin therapy was independently associated with a significant reduction ( adjusted odds ratio [ OR ] 0.25 ; 95 % confidence intervals [ CI ] 0.07 - 0.87 ) in the risk of early cardiac death after primary , elective coronary bypass surgery ( 0.3 % vs 1.4 % ; P < .03 ) , but was not associated with a reduced risk of postoperative nonfatal , in-hospital myocardial infa rct ion ( 7.9 % vs 6.2 % ; P = not significant ) . Discontinuation of statin therapy after surgery was independently associated with a significant increase in late ( POD4-discharge ) all-cause mortality ( adjusted OR 2.64 ; 95 % CI 1.32 - 5.26 ) compared with continuation of statin therapy ( 2.64 % vs 0.60 % ; P < .01 ) . This was true even when controlling for the postoperative discontinuation of aspirin , beta-blocker , or angiotensin-converting enzyme inhibitor therapy . Discontinuation of statin therapy after surgery was also independently associated with a significant increase in late cardiac mortality ( adjusted OR 2.95 ; 95 % CI 1.31 - 6.66 ) compared with continuation of statin therapy ( 1.91 % vs 0.45 % ; P < 0.01 ) . CONCLUSIONS Preoperative statin use is associated with reduced cardiac mortality  after primary , elective coronary artery bypass grafting . Postoperative statin discontinuation is associated with increased in-hospital mortality . Although further r and omized trials are needed to confirm these findings , these data suggest the importance of perioperative statin administration Clinical trial evidence exists that supports a role for the omega-3 polyunsaturated fatty acids in coronary heart disease prevention . However , the results from these clinical trials have varied and were conducted in diverse population groups using several different types of omega-3 polyunsaturated fatty acids , including eicosapentaenoic acid , docosahexaenoic acid , and alpha-linolenic acid ( ALA ) . Thus , we systematic ally review ed previously published reports assessing the different types of omega-3 polyunsaturated fatty acid interventions and cardiovascular outcomes . Fourteen r and omized clinical trials were included in the review . Six trials were included with fish oil , with 1 large trial ( 10,000 patients ) dominating the analysis . In aggregate , the fish oil trials demonstrated a reduction in total mortality and sudden death without a clinical ly significant reduction in nonfatal myocardial infa rct ion . The 6 trials with ALA supplements or an ALA-enriched diet were of poorer design than the fish oil trials and had limited power . Many of the trials with ALA involved other changes in dietary components . In aggregate , the ALA trials demonstrated possible benefits in reducing sudden death and nonfatal myocardial infa rct ion , but with wider confidence intervals than in the fish oil trials . In conclusion , the evidence suggests a role for fish oil ( eicosapentaenoic acid , docosahexaenoic acid ) or fish in secondary prevention because recent clinical trial data have demonstrated a significant reduction in total mortality , coronary heart disease death , and sudden death . The data on ALA have been limited by studies of smaller sample size and limited quality BACKGROUND Patients undergoing vascular surgery comprise the highest risk group for perioperative cardiac mortality and morbidity after noncardiac procedures . Many current guidelines recommend the use of beta-blockers in all patients undergoing vascular surgery . We report a trial of the perioperative administration of metoprolol and its effects on the incidence of cardiac complications at 30 days and 6 months after vascular surgery . METHODS Patients undergoing abdominal aortic surgery and infrainguinal or axillofemoral revascularizations were recruited to a double-blind r and omized controlled trial of perioperative metoprolol versus placebo . Patients were r and omized to receive study medication , starting 2 hours preoperatively until hospital discharge or maximum of 5 days postoperatively . Primary outcome were postoperative 30-day composite incidence of nonfatal myocardial infa rct ion , unstable angina , new congestive heart failure , new atrial or ventricular dysrhythmia requiring treatment , or cardiac death . RESULTS Patients were r and omized to receive either metoprolol ( n = 246 ) or placebo ( n = 250 ) . Primary outcome events at 30 days postoperative occurred in 25 ( 10.2 % ) versus 30 ( 12.0 % ) ( P = .57 ) in metoprolol and placebo groups , respectively ( relative risk reduction 15.3 % , 95 % CI -38.3 % to 48.2 % ) . Observed effects at 6 months were not significantly different ( P = .81 ) ( relative risk reduction 6.2 % , 95 % CI% -58.4 % to 43.8 % ) . Intraoperative bradycardia requiring treatment was more frequent in the metoprolol group ( 53/246 vs 19/250 , P = .00001 ) , as was intraoperative hypotension requiring treatment ( 114/246 vs 84/250 , P = .0045 ) . CONCLUSION Our results showed metoprolol was not effective in reducing the 30-day and 6-month postoperative cardiac event rates . Prophylactic use of perioperative beta-blockers in all vascular patients is not indicated Objective Cardiovascular complications are important causes of morbidity and mortality in elective non-cardiac surgery . Although difficult to diagnose , perioperative myocardial infa rct ion ( MI ) remains prognostically important . High-sensitivity troponin T ( hs-TnT ) assays allow detection of very minor damage to cardiac muscle . These assays are yet to be fully evaluated in the perioperative setting . Our aim was to determine the incidence and predictors of myocardial necrosis in patients at high cardiovascular risk undergoing elective non-cardiac surgery using hs-TnT.  Design Prospect i ve observational cohort study . Patients 352 consecutive patients undergoing elective major non-cardiac surgery prescribed antiplatelet therapy for primary or secondary cardiovascular event prevention . Main outcome measure The incidence of elevated preoperative hs-TnT ( ≥14 ng/litre ) , hs-TnT-defined perioperative myocardial necrosis ( ≥ 14ng/litre and 50 % increase from preoperative level ) , and perioperative MI were determined in relation to patient and surgical factors . Results Preoperative hs-TnT was elevated in 31 % and postoperative myocardial necrosis occurred in 22 % of patients . Predictors of elevated baseline hs-TnT included age ( OR 1.10 , p<0.001 ) , male gender ( OR 2.91 , p<0.001 ) , diabetes requiring insulin therapy ( OR 4.85 , p=0.004 ) and chronic kidney disease ( OR 3.60 , p<0.001 ) . Independent predictors of perioperative myocardial necrosis were age ( OR 1.07 , p<0.001 ) , intraoperative hypotension ( OR 3.67 , p=0.001 ) and orthopaedic surgery ( OR 2.46 , p=0.005 ) . Only 2 % of patients suffered clinical ly apparent MI . Elevated preoperative hs-TnT did not predict perioperative myocardial necrosis or MI . Conclusions Perioperative myocardial damage occurs frequently in patients undergoing elective non-cardiac surgery , although the majority of events are clinical ly undetected . Age and intraoperative hypotension are independent predictors of myocardial necrosis in this setting BACKGROUND Most patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infa rct ion , stroke , and death .  Aspirin poses a risk of bleeding in patients undergoing surgery , but it is unclear whether aspirin should be stopped before coronary artery surgery . METHODS We used a 2-by-2 factorial trial design to r and omly assign patients who were scheduled to undergo coronary artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo . The results of the aspirin trial are reported here . Patients were r and omly assigned to receive 100 mg of aspirin or matched placebo preoperatively . The primary outcome was a composite of death and thrombotic complications ( nonfatal myocardial infa rct ion , stroke , pulmonary embolism , renal failure , or bowel infa rct ion ) within 30 days after surgery . RESULTS Among 5784 eligible patients , 2100 were enrolled ; 1047 were r and omly assigned to receive aspirin and 1053 to receive placebo .  A primary outcome event occurred in 202 patients in the aspirin group ( 19.3 % ) and in 215 patients in the placebo group ( 20.4 % ) ( relative risk , 0.94 ; 95 % confidence interval , 0.80 to 1.12 ; P=0.55 ) . Major hemorrhage leading to reoperation occurred in 1.8 % of patients in the aspirin group and in 2.1 % of patients in the placebo group ( P=0.75 ) , and cardiac tamponade occurred at rates of 1.1 % and 0.4 % , respectively ( P=0.08 ) . CONCLUSIONS Among patients undergoing coronary artery surgery , the administration of preoperative aspirin result ed in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo . ( Funded by the Australian National Health and Medical Research Council and others ; Australia New Zeal and Clinical Trials Registry number , ACTRN12605000557639 . ) BACKGROUND Adverse cardiac events are common after vascular surgery . We hypothesized that perioperative statin therapy would improve postoperative outcomes . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned patients who had not previously been treated with a statin  to receive , in addition to a beta-blocker , either 80 mg of extended-release fluvastatin or placebo once daily before undergoing vascular surgery .  Lipid , interleukin-6 , and C-reactive protein levels were measured at the time of r and omization and before surgery . The primary end point was the occurrence of myocardial ischemia , defined as transient electrocardiographic abnormalities , release of troponin T , or both , within 30 days after surgery . The secondary end point was the composite of death from cardiovascular causes and myocardial infa rct ion . RESULTS A total of 250 patients were assigned to fluvastatin  , and 247 to placebo , a median of 37 days before vascular surgery . Levels of total cholesterol , low-density lipoprotein cholesterol , interleukin-6 , and C-reactive protein were significantly decreased in the fluvastatin group but were unchanged in the placebo group . Postoperative myocardial ischemia occurred in 27 patients ( 10.8 % ) in the fluvastatin group and in 47 ( 19.0 % ) in the placebo group ( hazard ratio , 0.55 ; 95 % confidence interval [ CI ] , 0.34 to 0.88 ; P=0.01 ) . Death from cardiovascular causes or myocardial infa rct ion occurred in 12 patients ( 4.8 % ) in the fluvastatin group and 25 patients ( 10.1 % ) in the placebo group ( hazard ratio , 0.47 ; 95 % CI , 0.24 to 0.94 ; P=0.03 ) . Fluvastatin therapy was not associated with a significant increase in the rate of adverse events . CONCLUSIONS In patients undergoing vascular surgery , perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome . ( Current Controlled Trials number , IS RCT N83738615 . Background and Context : Different adjuvants been tried out for neuraxial anesthesia in emergency caesarean section so that the dose of the local anesthetic can be reduced and hypotension thereby prevented . Aims and Objectives : The present study was carried out in patients presenting for emergency lower segment caesarean section ( LSCS ) to establish the dose of intrathecal clonidine that would allow reduction of the dose of local anesthetic ( thereby reducing the incidence and magnitude of hypotension ) while at the same time providing clinical ly relevant prolongation of spinal anesthesia without significant side effects . Material s and Methods : This r and omized clinical study was carried out in our institution among 100 pregnant females who underwent emergency caesarean section .  The participants were divided r and omly into four groups : A , B , C , and D , each comprising 25 parturients . Subarachnoid block was performed using a 26 G Quincke needle , with 12 mg of hyperbaric bupivacaine ( LA ) in group A , 9 mg of LA + 30 μg of clonidine in group B , LA + 37.5 μg of clonidine in group C , and LA + 45 μg of clonidine in group D. The solution was uniformly made up to 2.2 mL with normal saline in all the groups . Onset of analgesia at T10 level , sensory and motor blockade levels , maternal heart rate and blood pressure , neonatal Apgar scores , postoperative block characteristics , and adverse events were looked for and recorded . Statistical analysis was carried out with SPSS ® version 10.0 for Windows ® , using the ANOVA test with post hoc significance , the Chi-square test , and the Mann-Whitney U test . P<.05 was considered significant and P<.0001 as highly significant . Results : One hundred patients were enrolled for this study . The four groups were comparable with regard to demographic data and neonatal Apgar scores . Onset and establishment of sensory and motor analgesia was significantly shorter in groups C and D , while hypotension ( and the use of vasopressors ) was significantly higher in groups A and D. Perioperative shivering , nausea , and vomiting were significantly higher in groups A and D , while incidence of dry mouth was significantly higher in group D. Conclusions : The addition of 45 μg , 37.5 μg , and 30 μg of clonidine to hyperbaric bupivacaine results in more prolonged complete and effective analgesia , allowing reduction of up to 18 % of the total dose of hyperbaric bupivacaine . From the results of this study , 37.5 μg of clonidine seems to be the optimal dose Background Delirium is a common complication in elderly patients after surgery and associated with increased morbidity and mortality . Studies suggest that deep anesthesia and intense pain are important precipitating factors of postoperative delirium . Neuraxial block is frequently used in combination with general anesthesia for patients undergoing major thoracic and abdominal surgery . Compared with general anesthesia alone and postoperative intravenous analgesia , combined epidural-general anesthesia and postoperative epidural analgesia decreases the requirement of general anesthetics during surgery and provided better pain relief after surgery . However , whether combined epidural-general anesthesia plus epidural analgesia is superior to general anesthesia plus intravenous analgesia in decreasing the incidence of postoperative delirium remains unknown . Methods / design This is a multicenter , open-label , r and omized , parallel-controlled clinical trial . One thous and eight hundred elderly patients ( age range 60–90 years ) who are scheduled to undergo major thoracic or abdominal surgery are r and omized to receive either general anesthesia plus postoperative intravenous analgesia or combined epidural-general anesthesia plus postoperative epidural analgesia . The primary outcome is the 7-day incidence of postoperative delirium . Secondary outcomes include the duration of postoperative delirium , the intensity of pain during the first three days after surgery , the 30-day incidences of postoperative non-delirium complications , the length of stay in hospital after surgery and 30-day all-cause mortality . Discussion Results of the present study will provide information to guide clinical practice in choosing appropriate anesthesia-analgesia method for elderly patients undergoing major thoracic and abdominal surgery . Trial registration The study is registered on Clinical Trials.gov NCT01661907 and Chinese Clinical Trial Registry ChiCTR-TRC-12002371 BACKGROUND Globally there are > 200 million major surgical procedures undertaken annually , and about 20 % of these involve patients who have coronary artery disease . Many receive nitrous oxide , which impairs methionine synthase , thus inhibiting folate synthesis and increasing postoperative homocysteine levels . Nitrous oxide anesthesia leads to postoperative endothelial dysfunction , and there is some evidence that it increases myocardial ischemia and , possibly , myocardial infa rct ion . We have initiated the Nitrous oxide and perioperative cardiac morbidity ( ENIGMA-II ) Trial to test the hypothesis that in in patients undergoing anesthesia for major noncardiac surgery , avoidance of nitrous oxide will reduce the incidence of death and major cardiovascular events . METHODS ENIGMA-II is a 7,000-patient , international r and omized trial involving patients at risk of coronary artery disease undergoing noncardiac surgery . The patients , health care providers ( except for the anesthesiologists ) , data collectors , and outcome adjudicators are blinded to whether patients receive nitrous oxide-containing or nitrous oxide-free anesthetic . The primary outcome is a composite of death and major nonfatal events ( ie , myocardial infa rct ion , cardiac arrest , pulmonary embolism , and stroke ) at 30 days after surgery . RESULTS At present , ENIGMA-II has r and omized > 1,000 patients in 22 hospitals in 5 countries . To date , patients ' mean age is 70 years , 66 % are men , 38 % have a history of coronary artery disease , 19 % have a history of cerebrovascular disease , and 84 % have a history of hypertension . Most patients have undergone intra-abdominal 28 % , vascular 32 % , and orthopedic 16 % surgery . CONCLUSIONS The ENIGMA-II Trial will be the largest study yet conducted to ascertain the benefits and risks of removing nitrous oxide from the gas mixture in anesthesia . The results of this large international trial will guide the clinical care of the hundreds of millions of adults undergoing noncardiac surgery annually Findings of systematic review s incorporating meta analysis are by nature hypothesis generating and should be carefully and judiciously interpreted . This need is epitomized by two of the largest review s of interventions to support risk factor reduction after a diagnosis of coronary heart disease ( Table 1 ) . These review s both included r and omized trials published in a similar timeframe ( up to 2003 or 2004 ) that compared the effects of various risk factor reduction programmes for patients with confirmed coronary heart disease to usual care . In 2004 , a Cochrane review found that supervised and unsupervised exercise-based cardiac rehabilitation provided to patients with different forms of coronary heart disease lowered all cause total mortality by 20 % and cardiac mortality by 26 % in 48 trials of 8940 patients . The review ers concluded that there was ‘ no difference in mortality effect between exercise-only cardiac rehabilitation and comprehensive cardiac rehabilitation , or by exercise dose or duration of followup ’ . Also , the exercise-based programmes did not reduce recurrent myocardial infa rct ion and the need for repeat coronary revascularization to statistically significant levels . Around the same time , a second review of 63 trials involving 21,295 patients who had undergone secondary cardiac prevention programmes found reductions of total mortality of 15 % and of acute myocardial infa rct ion of 17 % . However , in contrast to the previous review , the secondary prevention programmes significantly reduced the rate of recurrent heart attacks . Also , benefits did not differ between programmes ‘ that incorporated education and counselling about coronary risk factors with a supervised exercise programme , those that included risk factor education or counselling but no exercise component , and those that consisted of only a structured exercise programme ’ . On first reading , these review s appear to offer different conclusions on effects on cardiovascular morbidity and regarding the benefits of supervised exercise . Either could be cited selectively to support or refute the benefits of exercise programmes for morbidity or to support or refute the incorporation of supervised exercise into services . Why might these different conclusions have come about and how should they be interpreted ? Firstly , it is unlikely that the different conclusions arise from differences in quality as both review s were of high quality as defined by PRISMA criteria and included many of the same trials : 37 of the 48 ( 77 % ) exercise-based trials were included in the 63 ( 59 % ) secondary prevention trials . Rather , issues of statistical power can explain the differences noted in morbidity . The forest plot analyses showed that , although exercise-based programmes in the Cochrane review did not reach statistically significant headline ‘ effect sizes ’ , there was a tendency towards reduced recurrent myocardial infa rct ion and the need for repeat coronary revascularization . The larger review of secondary prevention programmes considered over twice the number of events in the analysis of recurrent myocardial infa rct ion and found that secondary prevention programmes significantly reduced the rate of recurrent heart attacks . Hence , focusing only on the presence or absence of Background : Perioperative morbidity may be modifiable in high risk patients by the anesthesiologist 's choice of either regional or general anesthesia . This clinical trial compared outcomes between epidural ( EA ) and general ( GA ) anesthesia/analgesia regimens In a group of patients at high risk for cardiac and other morbidity who were undergoing similarly stressful surgical procedures . Methods : One hundred patients scheduled for elective vascular reconstruction of the lower extremities were r and omized to receive either EA for surgery followed by epidural analgesia , or GA for surgery followed by intravenous patient-controlled analgesia .  Hemodynamic monitoring , blood pressure , and heart rate limits were determined prior to r and omization . Management of anesthesia in the immediate postoperative period was st and ardized . The data collected included continuous electrocardiographic monitoring from the day before surgery through the third postoperative day , serial electrocardiograms , and cardiac enzymes . Cardiac ischemia , myocardial infa rct ion , unstable angina , and cardiac death were identified by a cardiologist blinded to the type of anesthesia received . Other major morbidity was determined at the time of hospital discharge and at 1 and 6 months after surgery . Results : Eleven patients who received GA required regrafting or an embolectomy during their hospital stay , compared with two patients who received EA . This association of GA with reoperation remained significant after adjustment for baseline differences . Cardiac outcomes were similar in the two groups with respect to perioperative death ( 1 EA and 1 GA ) , death within 6 months ( 4 EA and 3 GA ) , nonfatal myocardial infa rct ion within 7 days ( 2 EA and 2 GA ) , unstable angina ( 0 EA and 2 GA ) , and myocardial ischemia following r and omization ( 17 EA and 23 GA ) . Rates of major infections in the two groups ( 1 EA and 2 GA ) , renal failure ( 3 EA and 3 GA ) , and pulmonary complications ( 3 EA and 7 GA ) also were similar . Conclusions : Carefully conducted epidural and general anesthesia appear to be associated with comparable rates of cardiac and most other morbidity in patients undergoing lower extremity vascular surgery . However , compared with general anesthesia , epidural anesthesia is associated with a lower incidence of reoperatlon for inadequate tissue perfusion and , therefore , may be advantageous for this surgical population A previous article ( Part I ) described the patient population and operative management of 666 patients who had surgery for nonruptured abdominal aortic aneurysms . This article details the perioperative complications and , by chi-square and logistic regression analysis , identifies the variables that are associated with each complication . In summarizing the results ( below ) the incidence of each complication is listed , along with the predictive risk factors in parentheses that have significance levels less than 0.05 . Vascular morbidity data are as follows : intraoperative bleeding , 4.8 % ; postoperative bleeding requiring transfusion , 2.3 % or repeat operation , 1.4 % ( large volume of blood transfusion and /or use of an autotransfusion device ) ; intraoperative limb ischemia , 3.5 % ; graft thrombosis , 0.9 % ( femoropopliteal disease and /or distal anastomosis at the femoral level ) ; distal thromboembolism , 3.3 % ( male sex , femoral popliteal disease , and /or intraoperative graft thrombosis ) ; amputation , 1.2 % ; graft infection , 1 case . General morbidity data are as follows : cerebrovascular event , 0.6 % ; paraplegia , 1 case ; cardiac event , 15.1 % ( age , previous episode of congestive heart failure , and /or electrocardiogram [ ECG ] evidence of a previous myocardial infa rct ion ) ; myocardial infa rct ion , 5.2 % ( advancing age , angina , and /or prolonged aortic cross-clamp time ) ; congestive heart failure , 8.9 % ( previous history of congestive heart failure , ECG evidence of ischemia , and /or chronic obstructive lung disease ) ; arrhythmia requiring treatment , 10.5 % ( preoperative ventricular premature beats and /or respiratory failure requiring ventilation for more than 48 hours ) ; new arrhythmia , 8.4 % ( angina and /or chronic obstructive lung disease ) ; respiratory failure , 8.4 % ( chronic obstructive lung disease , large volume of blood transfused , and /or occurrence of postoperative bleeding , cerebrovascular accident , congestive heart failure , or myocardial infa rct ion ) ; renal damage with rise in creatinine or blood urea nitrogen , 5.4 % and /or renal failure requiring dialysis , 0.6 % ( elevated preoperative creatinine , suprarenal aortic cross-clamping , and /or renal vein ligation ) ; diarrhea without evidence of ischemia colitis , 7.1 % and ischemic colitis , 0.6 % ( pelvic flow interrupted ) ; prolonged ileus , 11.0 % ( aortoiliac occlusive disease , deterioration of renal function , prolonged ventilation , and /or preoperative history of angina ) ; superficial wound infection , 1.5 % and deep infection , 0.5 % ( femoral anastomosis and /or female sex ) ; coagulopathy , 1.1 % ( large volume of blood transfused ) . ( ABSTRACT TRUNCATED AT 400 WORDS BACKGROUND Adverse cardiac events are a major cause of morbidity and mortality after noncardiac surgery . It is necessary to determine the predictors of these outcomes in order to focus efforts on prevention and treatment . Patients undergoing noncardiac surgery  sometimes have postoperative cardiac events . It would be helpful to know which patients are at highest risk . METHODS We prospect ively studied 474 men with coronary artery disease ( 243 ) or at high risk for it ( 231 ) who were undergoing elective noncardiac surgery .  We gathered historical , clinical , laboratory , and physiologic data during hospitalization and for 6 to 24 months after surgery . Myocardial ischemia was assessed by continuous electrocardiographic monitoring , beginning two days before surgery and continuing for two days after . RESULTS Eighty-three patients ( 18 percent ) had postoperative cardiac events in the hospital that were classified as ischemic events ( cardiac death , myocardial infa rct ion , or unstable angina ) ( 15 patients ) , congestive heart failure ( 30 ) , or ventricular tachycardia ( 38 ) . Postoperative myocardial ischemia occurred in 41 percent of the monitored patients and was associated with a 2.8-fold increase in the odds of all adverse cardiac outcomes ( 95 percent confidence interval , 1.6 to 4.9 ; P less than 0.0002 ) and a 9.2-fold increase in the odds of an ischemic event ( 95 percent confidence interval , 2.0 to 42.0 ; P less than 0.004 ) . Multivariate analysis showed no other clinical , historical , or perioperative variable to be independently associated with ischemic events , including cardiac-risk index , a history of previous myocardial infa rct ion or congestive heart failure , or the occurrence of ischemia before or during surgery . CONCLUSIONS In high-risk patients undergoing noncardiac surgery , early postoperative myocardial ischemia is an important correlate of adverse cardiac outcomes Objective The aim of this article is to summarize the relevant findings that inform the 2017 International Consultation on Incontinence pathway for surgical treatment of pelvic organ prolapse ( POP ) . Methods We conducted an evidence -based review of the English- language peer- review ed literature relating to POP surgery published prior to December 2016 . Level 1 evidence ( r and omized controlled trials [ RCTs ] or systematic review s of RCTs ) was preferred ; however , level 2 ( poor- quality RCT , prospect i ve cohort studies ) or 3 evidence ( case series or retrospective studies ) has been included if level 1 data were lacking . The committee evaluated the literature and made recommendations based on the Oxford grading system summarized as follows : grade A recommendation usually depends on consistent level 1 evidence ; grade B recommendation usually depends on consistent level 2 and /or 3 studies , or “ majority evidence ” from RCTs ; grade C recommendation usually depends on level 3 studies or “ majority evidence ” from level 2/3 studies or Delphi-processed expert opinion ; grade D , “ no recommendation possible , ” would be used where the evidence is inadequate or conflicting . Results The recommendations from each chapter of the review are presented and serve to inform an evidence -based pathway for the surgical treatment of prolapse . A Web-based interactive application of the pathway is presented . Conclusions The 2017 International Consultation on Incontinence pathway on surgery for POP is design ed as an adjunct to transparent consultation and consent relating to POP surgery . The final decision regarding surgical intervention can be made only after a shared decision-making process between the patient and the clinician that will evaluate a variety of individual factors that can not be assessed in the pathway This issue of JAMA contains the latest US Preventive Services Task Force ( USPSTF ) recommendation statement on statins for prevention of cardiovascular disease in adults,1 along with the accompanying evidence report and systematic review 2 on which the recommendations are based . The evidence report summarized data from 19 trials including a total of 71 344 patients and concluded that statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and cardiovascular disease ( CVD ) events . Thus , the task force recommended “ initiating use of lowto moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 10 % or greater ( B recommendation ) ” or “ 7.5 % to 10 % ( C recommendation ) .”1 Although the task force did their usual careful job of review ing the evidence , the evidence for treating asymptomatic persons with statins does not appear to merit a grade B or even a grade C recommendation . The task force evidence report estimated an absolute benefit for use of statins of 0.40 % for all-cause mortality and 0.43 % for cardiovascular mortality and indicated that the absolute benefit was greater for patients at greater baseline risk.2 Notably , the evidence report did not exclude studies that included patients taking statins for secondary prevention , who have a higher baseline risk of cardiac events and death and thus are more likely to benefit from therapy that inflates the benefit attributed to a primary prevention population . The task force did perform a sensitivity analysis that excluded 3 trials with persons for whom there were prior “ hard ” cardiovascular events and obtained similar results of benefits ( eTable 5 in the article by Chou et al2 ) . This sensitivity analysis did not exclude WOSCOPS , which included patients receiving statins for secondary prevention—5 % had angina and 3 % had intermittent claudication,3 accounting for 15 % of the total weight in the meta- analysis . In contrast , a meta- analysis of 11 studies and 65 229 patients receiving statins for primary prevention , in which patients receiving statins for secondary prevention were excluded , found no benefit of statins for reducing all-cause mortality.4 The confidence intervals of these 2 analyses overlap , and the difference between these findings likely reflects differences in studies included . The USPSTF and authors of the evidence report did not have access to the primary data ( clinical study reports and anonymized patient-level data ) from the statin clinical trials . Rather , they had to rely on peer- review ed published reports as the basis for these recommendations . Exacerbating the potential bias , all of the trials included in the task force evidence report2 were industry-sponsored except 1 trial,5 and that trial contributed 0.2 % of the weight to the mortality calculation . Industry-sponsored studies have been shown to report greater benefit and lesser adverse effects than noncommercially sponsored trials of the same drugs.6 Whether this is true for statins and primary prevention of CVD is unknown . Among the 19 r and omized clinical trials of statins vs placebo or no statin included in the evidence report for the task force recommendations , only 15 reported all-cause mortality , 10 reported cardiovascular mortality , 12 reported fatal and nonfatal myocardial infa rct ion  , and 13 reported fatal and nonfatal stroke.2,7  Reliance on selective reporting of the most important outcomes , which are likely included in the clinical trial data , makes reporting bias possible . Furthermore , after allcause mortality , the comparative incidence of serious adverse events between treatment and control groups is arguably the second most important measure of the effect of active therapy in r and omized clinical trials . Underst and ing the evidence base in evaluating harms of statin therapy is also critically important . Although the benefits of any preventive therapy accrue according to risk of disease ( greater benefit in higher-risk patients ) , the harms of therapy usually distribute equally over all risk levels . Thus , persons at low risk have little chance of benefit but equal chance of harms and thus are more likely to have a net harm . The evidence base for harms of statins , despite the introduction of these drugs more than 20 years ago , is incomplete . Many of the trials did not ask about commonly reported statin effects , such as muscle pains and weakness , and only recorded myopathy , for which an increase in creatine kinase levels was required . Because most muscle problems do not involve an increase in creatine kinase levels , this leads to a significant underestimate of muscle problems . Other studies have estimated that closer to 20 % of statin users have muscle problems.8 Additionally , the actual trial data are largely held by the Cholesterol Treatment Trialists ’ Collaboration on behalf of the industry sponsor and have not been made available to other research ers , despite multiple requests over many years.9 Although reported rates of adverse events in clinical trials are low , this does not reflect the experience of clinicians who see patients who are taking statins . For instance , the experience of an NPR reporter with a calculated 2.9 % risk of heart disease over 10 years using the recommended American College of Cardiology/American Heart Association ( ACC/AHA ) risk calculator,10 but still prescribed a statin , and experiencing adverse effects from the medication , is typical of what many Related articles at jama.com STUDY OBJECTIVE To determine whether bilateral iliohypogastric and ilioinguinal ( IHII ) peripheral nerve blocks , given in conjunction with neuraxial morphine , reduce postcesarean analgesic requirements and side effects , result ing in improved maternal satisfaction . DESIGN R and omized , prospect i ve , double-blinded , placebo-controlled study . SETTING Labor and delivery suite at Johns Hopkins Hospital . PATIENTS 34 women scheduled for elective cesarean delivery . INTERVENTIONS Patients were r and omized to receive IHII nerve blocks bilaterally , with either total 24 mL of 0.5 % bupivacaine or normal saline , following cesarean delivery via Pfannensteil incision with a st and ard intrathecal dose of 12 mg of 0.75 % bupivacaine with 10 µg of fentanyl and 200 µg of preservative-free morphine . MEASUREMENTS Patients were assessed at 0 , 6 , 12 , 18 , and 24 hours postoperatively . Visual analog scale ( VAS ) pain scores at rest were recorded at each time period . Analgesic use , patients ' perception of nausea , vomiting , pruritus , and their overall satisfaction with their analgesia were recorded for the first 24 hours . MAIN RESULTS Lower VAS pain scores were seen in the bupivacaine group at 6 , 12 , 18 , and 24 hours postoperatively ( P = 0.01 , P < 0.01 , 0.02 , and 0.04 , respectively ) . A longer mean time to first rescue dose of ketorolac was noted in the bupivacaine group ( 14.3 ± 1.8 hrs ) than the saline group ( mean 5.6 ±1.1 hrs ) , ( P < 0.01 ) . Fewer patients in the bupivacaine group made requests for acetaminophen 500 mg/oxycodone 5 mg in the first 24 hours . Satisfaction was greater in the bupivacaine group . No difference in side effects was noted between groups . CONCLUSIONS Bilateral multilevel injection IHII nerve blocks result in lower resting VAS pain scores , lower analgesic requirements , and greater satisfaction following cesarean delivery in patients who received neuraxial morphine BACKGROUND Cytokines are significant mediators of the immune response to surgery and also play a role in parturition . The aim of the study was to investigate the impact of the anesthetic technique for cesarean section on plasma levels of cytokines IL-6 and TNF-alpha . METHODS Thirty-five parturients scheduled for elective cesarean section were r and omly assigned to  general ( n=18 ) or neuraxial ( n=17 ) anesthesia . The general anesthesia group received thiopental 4 mg/kg , succinylcholine 1 - 1.5 mg/kg and 1 % end-tidal concentration of sevoflurane in nitrous oxide and 50 % oxygen . The neuraxial anesthesia group received intrathecal 0.5 % levobupivacaine 1.8 - 2.2 mL and epidural fentanyl 1 microg/kg . Blood sample s were taken for IL-6 and TNF-alpha immediately after positioning the parturient on the operating table , after uterine incision and before the umbilical cord clamping and 24h after surgery ( T(1 ) , T(2 ) and T(3 ) respectively ) . RESULTS The two groups did not differ in IL-6 ( P=0.15 ) or TNF-alpha ( P=0.73 ) serum concentrations at any time point . In the general and neuraxial anesthesia groups , IL-6 serum concentrations were significantly higher in the third blood sample , T(3 ) ( 12.2+/-5.0 and 15.2+/-4.3 pg/mL ) , than in T(1 ) ( 0.41+/-0.38 and 0.29+/-0.10 pg/mL ) and T(2 ) ( 0.37+/-0.47 and 0.24+/-0.05 ) respectively ( P<0.001 ) . Within each group , serum TNF-alpha concentrations did not differ significantly over time ( P=0.44 ) . CONCLUSIONS Under the present study design anesthetic technique did not affect IL-6 or TNF-alpha concentrations in parturients undergoing elective cesarean section . Serum IL-6 levels increased 24 h postoperatively independently of anesthetic technique Fear of losing cognitive ability to Alzheimer disease and related dementias drives a growing industry of over-the-counter ( OTC ) supplements intended to boost brain health and prevent or slow cognitive decline . The Alzheimer 's Research and Prevention Foundation recommends that people be sure to take [ their ] vitamins and memory-specific nutrients and suggests optimal dosages for an array of vitamins and nutrients ( 1 ) . An estimated 63 % of older adults use OTC supplements ( 2 ) . In 2015 , Americans spent $ 37 billion on OTC supplements and $ 91 million on ginkgo bilobajust one of a growing number of supplements marketed to boost memory ( 3 ) . Whether any dietary or herbal supplement or specific food can prevent or delay cognitive decline is unclear . This review summarizes the evidence on efficacy and harms of OTC supplements to prevent or delay cognitive decline , mild cognitive impairment ( MCI ) , or clinical Alzheimer-type dementia . Methods We developed and followed a st and ard protocol ( https://effectivehealthcare.ahrq.gov/topics/cognitive-decline/ research - protocol ) . Data Sources and Search es We search ed Ovid MEDLINE , PsycINFO , EMBASE , and the Cochrane Central Register of Controlled Trials for relevant literature published between 2009 and July 2017 ( see Part A of the Supplement for search strategies ) . We identified studies published before 2009 by search ing citations in systematic review s and pertinent studies ( 48 ) . Supplement . Supplementary Material Study Selection Two investigators independently review ed titles and abstract s and screened the full text of potentially eligible references . We included r and omized and nonr and omized controlled trials of any OTC supplements  that enrolled adults with normal cognition or MCI . Because the review focused on prevention , we excluded studies of adults with dementia . We included only studies that followed participants for at least 6 months , reported incident MCI or dementia ( our main outcome of interest ) or cognitive performance outcomes , and were published in English . There were no restrictions on sample size or comparator type . Disagreements about eligibility were resolved by consensus . Data Extraction and Quality Assessment One review er extracted information on study design , population , intervention , comparator , setting , and funding source from eligible studies . For each study , 2 review ers read the full text and independently rated risk of bias for the overall study and for each outcome and time point as low , medium , or high according to Agency for Healthcare Research and Quality ( AHRQ ) guidance ( 9 ) . Outcomes and adverse events were extracted from studies with low to medium risk of bias . A second review er checked the quality of all data . Data Synthesis and Analysis We summarized results for studies with low to medium risk of bias by intervention , baseline cognitive status ( presumed normal cognition or MCI ) , and outcome . Because studies used highly variable outcome measures , neuropsychological tests were categorized according to the following 4 specific cognitive domains to facilitate analysis : executive function , attention , and processing speed ; memory ; language ; and visuospatial abilities ( see Supplement Table A1 for the list of cognitive outcomes that were used and Supplement Table A2 for measurement properties , including change indices , of neuropsychological tests that were used ) . We grouped executive function , attention , and processing speed because a large number of cognitive tests frequently measure all 3 of these related domains . Our preliminary work found that studies analyzed and reported cognitive test results in widely varying ways , frequently making it impossible to determine effect size or assess whether between-group differences in scores or subscores were clinical ly meaningful . We instead analyzed and report cognitive test results by direction of effect and statistical significance . When there were at least 2 studies or 1 large study ( > 500 participants ) for a treatment comparison , 2 review ers grade d strength of evidence for each outcome on the basis of study limitations , directness , consistency , and precision ; otherwise , strength of evidence was grade d as insufficient ( 10 ) . Assessment s were confirmed by consensus . Role of the Funding Source This review was funded by the National Institute on Aging and the AHRQ . These agencies and members of the National Academies Committee on Preventing Dementia and Cognitive Impairment helped refine the scope and review ed a draft report of findings . The authors are solely responsible for the content , preparation , and writing of the manuscript and the decision to su bmi t it for publication . Results We identified 63 publications of 56 unique studies covering 13 categories of OTC treatments ( Appendix Figure ) . A third of the studies were at least partially funded by industry . Eighteen were assessed as having high risk of bias and were not further analyzed . Table 1 depicts the interventions and population s of the 38 studies judged as having low or medium risk of bias . Detailed evidence tables and risk-of-bias assessment s are presented for studies involving adults with normal cognition in Part B of the Supplement and for studies involving adults with MCI in Part C of the Supplement ; these tables are also available in the parent technical report ( 11 ) . Table 2 summarizes the strength of evidence for the findings . Appendix Figure . Evidence search and selection . Table 1 . Number of Studies With Low or Moderate Risk of Bias , by Intervention Type and Population Table 2 . Effect of OTC Supplement Interventions Versus Control on Cognitive Outcomes in Adults With Normal Cognition and MCI * Table . Continued . -3 Fatty Acids Normal Cognition Seven r and omized trials with low to medium risk of bias ( n= 21027 ) that enrolled adults with presumed normal cognition compared -3 fatty acids with placebo ( 1218 ) . Interventions lasted from 6 months to more than 6 years . Five trials reported cognitive exclusion criteria , including a Mini-Mental State Examination ( MMSE ) score less than 22 ( 14 , 15 ) , less than 24 ( 13 ) , or less than 26 ( 16 , 17 ) out of a possible 30 points . One study used only docosahexaenoic acid ( DHA ) ( 17 ) ; all others used some combination of eicosapentaenoic acid ( EPA ) plus DHA . The largest study ( n= 15077 ) allowed participation of adults who were already using -3 supplementation  ( 18 ) . Population s varied in baseline health and risk for cognitive decline . Participants included patients with diabetes or impaired glucose tolerance ( 18 ) , patients with a history of ischemic heart disease ( 12 ) or coronary artery disease ( 14 ) , and healthy adults ( 13 , 1517 ) . None of the studies reported on incident Alzheimer-type dementia or MCI . A large multinational study of adults with diabetes or impaired glucose tolerance ( n= 15077 ) used a combination of clinical diagnosis or an MMSE score less than 24 and found no difference in probable dementia incidence between the EPA/DHA group and the placebo group at a median follow-up of 6.2 years ( hazard ratio [ HR ] , 0.93 [ 95 % CI , 0.86 to 1.0 ] ) ( 18 ) . Overall , studies provided low-strength evidence suggesting that -3 fatty acids do not improve cognitive performance in adults with normal cognition compared with placebo . Of 67 reported cognitive testsincluding 9 brief cognitive tests ( 12 , 14 , 17 , 18 ) ; 1 test of multidomain neuropsychological performance ( 13 ) ; 32 tests of executive function , attention , and processing speed ( 13 , 1518 ) ; and 25 memory tests ( 13 , 1517)only 5 showed scores that were statistically significantly better in -3treated groups than in control groups . These 5 tests were administered in 2 studies that had relatively short follow-up ( 6 months ) and included fewer than 5 % of the total participants in the 7 studies ( 16 , 17 ) . Four studies did not report adverse events , and no studies reported statistically significant differences in adverse events between the -3 and placebo groups . The parent technical report provides details on adverse events ( 11 ) . Subgroups were examined in 4 studies . No statistically significant differences in effect were found by age ( 12 , 14 , 15 , 18 ) , sex ( 14 , 15 , 18 ) , time since myocardial infa rct ion ( 14 ) , or diabetes status ( 18 ) . One study ( n= 884 ) with 4-year follow-up examined the comparative effectiveness of -3 fatty acids and B vitamins on cognition ( 12 ) . No between-group differences were found for any cognitive outcome between -3 fatty acids ( alone or in combination with B vitamins ) and B vitamins alone . Adverse events were not reported . MCI Evidence was insufficient for benefits of -3 fatty acids on cognitive outcomes compared with placebo after 1 year in the single small study of adults with MCI that we identified ( n= 36 ) ( 19 ) . No serious adverse events were reported . Soy Normal Cognition  Five r and omized trials with low to medium risk of bias that enrolled 35 to 350 participants ( n= 829 ) and lasted 6 months to 2.5 years compared soy supplementation with placebo ( 2025 ) . Population s included older adults without dementia ( 20 ) and generally healthy postmenopausal women ( 21 , 2325 ) . Baseline testing excluded persons with cognitive impairment in 2 of the studies ( 20 , 21 ) . Mean reported baseline MMSE scores  ranged from 28 to 29 ( 2023 ) . None of the trials reported MCI or Alzheimer-type dementia outcomes . Evidence was deemed insufficient to determine soy 's effect on brief cognitive test performance ( 21 , 25 ) and multidomain neuropsychological test performance ( 21 , 24 ) and low-strength for soy having no effect on executive function , attention , and processing speed ( 20 , 21 , 2325 ) or memory ( 2025 ) for up to 2.5 years . Two studies reported no serious adverse events and no statistically significant differences in adverse events between the soy and placebo groups ( 21 , 25 ) . MCI Evidence was insufficient to determine any beneficial effect on cognitive outcomes from soybean-derived phosphatidylserine at 2 doses ( 100 and 300 mg daily ) compared with placebo after 9 months in a single small study of adults Much interest is being shown in fibrinogen as a possible cardiovascular risk factor . ' The concept that fibrinogen is causally related to cardiovascular events is supported by several lines of evidence . Perhaps the strongest indication stems from seven prospect i ve epidemiological trials2all of which showed that fibrinogen predicts major cardiovascular events such as stroke and myocardial infa rct ion . Clinical trials on survivors of a first myocardial infa rct ion9 or stroke'0 also showed that fibrinogen was a risk factor for further cardiovascular disasters . Several plausible pathological mechanisms could explain this association ' : fibrinogen is an important clotting factor and it determines the flow properties of blood , represents a co-factor for platelet aggregation , and may cause atherosclerosis by direct effects on the arterial wall . Acceptance that fibrinogen is a major cardiovascular risk factor will lead to attempts to lower its plasma concentration . Methods to achieve this are still in their infancy . Though dietary influences seem to be small , ' there is a striking association between body weight and fibrinogen . I will review the data suggesting that weight loss might be one practical way of influencing fibrinogen concentrations General anaesthesia was induced with , and maintained by , an infusion of either propofol or methohexitone , in patients undergoing surgery with the aid of regional blockade .  Both agents provided satisfactory and controllable anaesthesia . Complications were few with a similar incidence for the two drugs . Recovery from anaesthesia was significantly faster following propofol Purpose of review To review the risk of cardiovascular complications in HIV-infected patients receiving combination antiretroviral treatment .  Recent findings Recent data suggest that patients with chronic HIV infection will require continuous lifelong combination antiretroviral treatment , which may increase the risk of cardiovascular disease in all population s by substantial amounts . Simple , safe and effective interventions to reduce cardiovascular complications in HIV-infected patients will be required . Studies in the general population suggest that the primary prevention of cardiovascular disease with a pill combining blood-pressure-lowering , cholesterol-lowering and antiplatelet treatments ( a polypill ) might decrease cardiovascular events . An HIV polypill study with 8000 HIV-infected patients with a moderate risk of cardiovascular disease r and omized to either a polypill of low-dose pravastatin , aspirin , hydrochlorothiazide and lisinopril or to placebo is described . The primary clinical endpoint would be a composite of cardiovascular mortality , non-fatal myocardial infa rct ion and stroke .  A vanguard study of 400 patients could assess changes in cholesterol , blood pressure and other risk factors . The clinical endpoint study described would have 80 % power to detect a 23 % reduction in the rate of cardiovascular events in the polypill arm . Summary A study of a polypill like that proposed for the general population will provide crucial information on the risks and benefits of primary cardiovascular prevention in HIV-infected patients short-term prognosis of perioperative myocardial infa rct ion in patients undergoing noncardiac surgery : a cohort study . Ann Intern Med 2011 ; 154 : 523–8 5 . Botto F , Alonso-Coello P , Chan MT , et al. Myocardial injury after noncardiac surgery : a large , international , prospect i ve cohort study establishing diagnostic criteria , characteristics , predictors , and 30-day outcomes . Anesthesiology 2014 ; 120 : 564–78 6 . Wa sowicz M , Syed S , Wijeysundera DN , et al. Effectiveness of platelet inhibition on major adverse cardiac events in noncardiac surgery after percutaneous coronary intervention : a prospect i ve cohort study . Br J Anaesth 2016 ; 116 : 493–500 7 . Kubo T , Imanishi T , Takarada S , et al. Assessment of culprit lesionmorphology in acutemyocardial infa rct ion : ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy . J Am Coll Cardiol 2007 ; 50 : 933–9 8 . Ino Y , Kubo T , Tanaka A , et al. Difference of culprit lesion morphologies between ST-segment elevation myocardial infa rct ion and non-ST-segment elevation acute coronary syndrome : an optical coherence tomography study . JACC Cardiovasc Interv 2011 ; 4 : 76–82 9 . Devereaux PJ , Mrkobrada M , Sessler DI , et al. Aspirin in patients undergoing noncardiac surgery . N Engl J Med 2014 ; 370 : 1494–503 10 . Kamel H , Johnston SC , Kirkham JC , et al. Association between major perioperative hemorrhage and stroke or Q-wave myocardial infa rct ion . Circulation 2012 ; 126 : 207–12 11 . Fleisher LA , Fleischmann KE , Auerbach AD , et al. 2014 ACC/ AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery : executive summary : a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines . Circulation 2014 ; 130 : 2215–45 12 . collaborators C-t , Shakur H , Roberts I , et al. Effects of tranexamic acid  on death , vascular occlusive events , and blood transfusion in trauma patients with significant haemorrhage ( CRASH-2 ) : a r and omised , placebo-controlled trial . Lancet 2010 ; 376 : 23–32 13 . Roberts I , Perel P , Prieto-Merino D , et al. Effect of tranexamic acid onmortality in patients with traumatic bleeding :  prespecified analysis of data from r and omised controlled trial . BMJ 2012 ; 345 : e5839 14 . Kaluza GL , Joseph J , Lee JR , Raizner ME , Raizner AE . Catastrophic outcomes of noncardiac surgery soon after coronary stenting . J Am Coll Cardiol 2000 ; 35 : 1288–94 15 . Devereaux PJ , Yang H , Yusuf S , et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery ( POISE trial ) : a r and omised controlled trial . Lancet 2008 ; 371 : 1839–47 16 . Devereaux PJ , Sessler DI , Leslie K , et al.  Clonidine  in patients undergoing noncardiac surgery . N Engl J Med 2014 ; 370 : 1504–13 17 . Myles PS , Leslie K , ChanMT , et al. The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery ( ENIGMA-II ) : a r and omised , single-blind trial . Lancet 2014 ; 384 : Background : Perioperative myocardial injury ( PMI ) seems to be a contributor to mortality after noncardiac surgery . Because the vast majority of PMIs are asymptomatic , PMI usually is missed in the absence of systematic screening . Methods : We performed a prospect i ve diagnostic study enrolling consecutive patients undergoing noncardiac surgery who had a planned postoperative stay of ≥24 hours and were considered at increased cardiovascular risk . All patients received a systematic screening using serial measurements of high-sensitivity cardiac troponin T in clinical routine . PMI was defined as an absolute high-sensitivity cardiac troponin T increase of ≥14 ng/L from preoperative to postoperative measurements . Furthermore , mortality was compared among patients with PMI not fulfilling additional criteria ( ischemic symptoms , new ECG changes , or imaging evidence of loss of viable myocardium ) required for the diagnosis of spontaneous acute myocardial infa rct ion versus those that did . Results : From 2014 to 2015 we included 2018 consecutive patients undergoing 2546 surgeries . Patients had a median age of 74 years and 42 % were women . PMI occurred after 397 of 2546 surgeries ( 16 % ; 95 % confidence interval , 14%–17 % ) and was accompanied by typical chest pain in 24 of 397 patients ( 6 % ) and any ischemic symptoms in 72 of 397 ( 18 % ) . Crude 30-day mortality was 8.9 % ( 95 % confidence interval [ CI ] , 5.7–12.0 ) in patients with PMI versus 1.5 % ( 95 % CI , 0.9–2.0 ) in patients without PMI ( P<0.001 ) . Multivariable regression analysis showed an adjusted hazard ratio of 2.7 ( 95 % CI , 1.5–4.8 ) for 30-day mortality . The difference was retained at 1 year with mortality rates of 22.5 % ( 95 % CI , 17.6–27.4 ) versus 9.3 % ( 95 % CI , 7.9–10.7 ) . Thirty-day mortality was comparable among patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infa rct ion ( 280/397 , 71 % ) versus those with at least 1 additional criterion ( 10.4 % ; 95 % CI , 6.7–15.7 , versus 8.7 % ; 95 % CI , 4.2–16.7 ; P=0.684 ) . Conclusions : PMI is a common complication after noncardiac surgery and , despite early detection during routine clinical screening , is associated with substantial short- and long-term mortality . Mortality seems comparable in patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infa rct ion versus those patients who do . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT02573532 Each year , 600 000 patients undergo myocardial revascularization with cardiopulmonary bypass  and sustain profound physiologic perturbations that precipitate ischemia and infa rct ion in several organ systems [ 1 - 3 ] . Although medical re sources have been redirected to address perioperative cardiac and neurologic illness , the clinical effect of cardiac surgery on renal function has not been studied rigorously . Nonpulsatile blood flow , increases in levels of circulating catecholamines and inflammatory mediators , macroembolic and microembolic insults to the kidney , and release of free hemoglobin from traumatized erythrocytes result in numerous pathophysiologic renal responses [ 4 - 6 ] . Many studies [ 7 - 9 ] have shown that patients who have undergone cardiac surgery developed maldistributed renal blood flow , increases in renal vascular resistance , and substantive decreases ( 25 % to 75 % ) in renal blood flow and glomerular filtration rate . The effect of these phenomena on clinical outcome is not well known but is thought to be considerable . Studies have reported incidences of oliguric renal failure requiring dialysis as high as 5 % and mortality rates as great as 89 % . Previous studies [ 10 - 19 ] have many limitations because of a wide variability ( threefold or more ) in estimates of adverse renal outcomes : All of the studies were conducted at a single center , most were retrospective , and most were done more than a decade ago . No previous study provided adjusted estimates of risk factors ; in addition , the definition chosen for renal dysfunction was arbitrary , or the study sample consisted only of patients requiring dialysis [ 11 , 13 , 15 - 17 ] . Finally , few studies have investigated re source utilization in patients with renal dysfunction or failure . We therefore studied 2400 patients who underwent myocardial revascularization with cardiopulmonary bypass .  Our goals were to determine 1 ) the incidence and characteristics of postoperative renal dysfunction and failure , 2 ) the predictors of renal dysfunction [ determined by the use of multivariate modeling techniques ] , and 3 ) the effect of renal dysfunction on in-hospital re source utilization and patient disposition after discharge . Methods Patients The Multicenter Study for Perioperative Ischemia ( McSPI ) Research Group studied 2417 patients undergoing myocardial revascularization between 1991 and 1993 . Twenty-four diverse U.S. health care facilities-small and large academic institutions , private medical centers , health maintenance organization groups , and Veterans Affairs hospitals-participated in this study . Most patients were representative of consecutive patients seen at a given medical center . We enrolled every nth patient on the basis of a proportion of the site-specific expected annual caseload ( n = 2 through 30 in 24 centers ) . Comprehensive data were collected from preoperative cardiac , surgical , and medical histories ; invasive and noninvasive cardiologic testing ; surgical procedures and techniques ; perioperative hemodynamic events ; postoperative in-hospital events ( illness and death ) ; and hospital re source utilization . In addition , serial preoperative and postoperative 12-lead electrocardiograms were obtained and were central ly analyzed by a consensus panel of cardiologists . Serum creatinine values were recorded before and after surgery . Of the 2417 patients enrolled , 195 were excluded from analysis because of preexisting renal failure ( n = 99 ) or dysfunction ( serum creatinine level > 177 mol/L [ n = 81 ] ) or lack of perioperative serum creatinine measurements ( n = 68 ) . The latter group included patients who died before a postoperative sample could be obtained . Definitions of Renal Failure , Renal Dysfunction , and Comorbid Events Postoperative renal failure was defined by the need for dialysis after surgery . Renal dysfunction was defined as a postoperative serum creatinine level of 177 mol/L or greater and an increase in serum creatinine level of 62 mol/L or greater from preoperative to maximum postoperative values . The criteria for dysfunction were derived from the distribution of serum creatinine values in an uncomplicated patient subset . This subset excluded patients with preoperative renal disease ( serum creatinine level > 124 mol/L ) or medical risk factors ( age > 70 years ; history of congestive heart failure or type 1 diabetes mellitus ) , or a complicated postsurgical course ( in-hospital death ; concomitant valvular surgery ; intraaortic balloon pump insertion ; administration of at least three nonroutine inotropic drugs ; measures of hemodynamic instability ; ventricular fibrillation or dysrhythmia requiring a pacemaker ; complications necessitating a return to cardiopulmonary bypass , the intensive care unit , or the operating room ; or chest tube output exceeding 1 L/d ) . Less than 1 % of patients meeting these criteria had a maximum postoperative creatinine level greater than 177 mol/L and a maximum preoperative-to-postoperative change in creatinine level of 62 mol/L. Comorbid events , assessed through the first postoperative day , consisted of postoperative myocardial infa rct ion , congestive heart failure ( hemodynamic or clinical ) , use of an intraaortic balloon pump or other mechanical circulatory assist device , administration of three or more inotropic drugs , and hemorrhage . A myocardial infa rct ion was defined as either a Q-wave or a non-Q-wave infa rct ion . A Q-wave myocardial infa rct ion was diagnosed central ly by the presence of a new Q wave on each of two postoperative 12-lead electrocardiograms , as defined by Minnesota Code criteria , that were scored by a consensus panel of cardiologists . A non-Q-wave myocardial infa rct ion was determined by an elevated creatine kinase-MB level , a new wall-motion abnormality detected by echocardiography , or a new perfusion defect on a scintigraphy scan . Low output state [ an ordered , categorical variable ] was defined as one of the following : 1 ) severe ventricular dysfunction-intraaortic balloon pump counterpulsation required , 2 ) moderate ventricular dysfunction-hemodynamic congestive heart failure or at least three nonroutine inotropic drugs prescribed after surgery , and 3 ) mild ventricular dysfunction- clinical congestive heart failure . We defined hemodynamic congestive heart failure on the basis of a cardiac index less than 1.5 L/min per m2 body surface area for at least 30 minutes , a central venous pressure greater than 12 mm Hg , or a pulmonary artery occlusion pressure/left ventricular end diastolic pressure greater than 18 mm Hg . Clinical congestive heart failure was defined according to the presence of pulmonary rales , S3 gallop , or chest radiographic findings suggestive of heart failure . We defined hemorrhage as 1 ) chest tube output of at least 1 L/d , 2 ) return to the critical care unit or operating room within the first postoperative day because of bleeding , or 3 ) administration of three or more units of blood products in the operating room or critical care unit within 48 hours of surgery . Statistical Analysis Distributions and univariate measures of preoperative , postoperative , and preoperative-to-postoperative changes in serum creatinine values were examined . Unadjusted relative risks and 95 % CIs were calculated for all perioperative factors . Adjusted relative risk estimates were derived from multivariate logistic regression models because an 8 % incidence of renal dysfunction is relatively rare . Models were analyzed in a piece-wise fashion ( separate models were developed for each preoperative , operative , and postoperative period from the significant unadjusted factors in each period ) . A final model with adjusted estimates of relative risk was derived with factors that remained significant ( P 0.05 ) in the three time period models . Operative and postoperative variables were entered into the model in a forward stepwise fashion after adjustment for preoperative variables . No appreciable differences were noted when all perioperative factors were allowed to enter into the model in forward or backward stepwise selection procedures . The best-fitting models were selected from evaluation of the Hosmer-Lemeshow goodness-of-fit test statistic and the smallest values of the Akaike Information Criterion . The predictive ability of the models of preoperative risk factors alone , as well as the final model , were also evaluated with the area under the receiver-operating characteristic curve ( the concordance or c-index ) . The c-index was also derived from a validation process that involved comparison of the c-index derived from a r and om sample of half of the patients from each site and a computed c-index derived from modeling the remaining sample 's predicted probability of renal dysfunction calculated from the variable estimates from the original 50 % r and om sample . In other words , a predicted probability was derived from variable estimates from those obtained from the 50 % within-center sample ; these estimates were applied to the patients ' combination of risk factors in the remaining sample . The c-index was then calculated from modeling the remaining sample 's predicted probabilities as a single predictor . From the final model of preoperative risk factors , both observed and predicted probabilities were described and the sensitivity and specificity of the preoperative model were reported . The sensitivity and specificity were determined by selecting the highest sensitivity and specificity from a classification table of observed and predicted events ( this occurred with a probability of renal dysfunction 6 % ) . Theoretically , each of the 24 medical centers in the study sample may have characteristics that were not measured and could have influenced patients ' outcomes . To address potential within-center correlation , ancillary analyses were conducted . Logistic regression models using generalized estimating equations with an exchangeable correlation matrix were used to account for within-center correlation . Estimates of SEs are considered corrected for potential within-center Background The role of vitamin D in management of depression is unclear . Results from observational and emerging r and omized controlled trials ( RCTs ) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association . Methods / Design The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors ’ original definition . Secondary aims include assessing the change in quality of life , adverse events and treatment discontinuation . We will conduct the systematic review and meta- analysis according to the recommendations of the Cochrane H and book for Systematic Review s of Interventions . We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE ( 1966 to present ) , EMBASE ( 1980 to present ) , CINAHL ( 1982 to present ) , PsychINFO ( 1967 to present ) and Clinical Trials.gov . Unpublished work will be identified by search ing two major conferences : the International Vitamin Conference , the Anxiety Disorders and Depression Conference , while grey literature will be acquired by contacting authors of included studies . We will use the r and om-effects meta- analysis to synthesize the data by pooling the results of included studies . Discussion The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant setting s. Study registration Unique identifier : CRD42013003849 IMPORTANCE Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm . OBJECTIVE To evaluate the clinical effectiveness of a perioperative , cardiac output-guided hemodynamic therapy algorithm . DESIGN , SETTING , AND PARTICIPANTS OPTIMISE was a pragmatic , multicenter , r and omized , observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom . An up date d systematic review and meta- analysis were also conducted including r and omized trials published from 1966 to February 2014 . INTERVENTIONS Patients were r and omly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope ( dopexamine ) infusion during and 6 hours following surgery ( n=368 ) or to usual care ( n=366 ) . MAIN OUTCOMES AND MEASURES The primary outcome was a composite of predefined 30-day moderate or major complications and mortality . Secondary outcomes were morbidity on day 7 ; infection , critical care-free days , and all-cause mortality at 30 days ; all-cause mortality at 180 days ; and length of hospital stay . RESULTS Baseline patient characteristics , clinical care , and volumes of intravenous fluid were similar between groups . Care was nonadherent to the allocated treatment for less than 10 % of patients in each group . The primary outcome occurred in 36.6 % of intervention and 43.4 % of usual care participants ( relative risk [ RR ] , 0.84 [ 95 % CI , 0.71 - 1.01 ] ; absolute risk reduction , 6.8 % [ 95 % CI , -0.3 % to 13.9 % ] ; P = .07 ) . There was no significant difference between groups for any secondary outcomes . Five intervention patients ( 1.4 % ) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group . Findings of the meta- analysis of 38 trials , including data from this study , suggest that the intervention is associated with fewer complications ( intervention , 488/1548 [ 31.5 % ] vs control , 614/1476 [ 41.6 % ] ; RR , 0.77 [ 95 % CI , 0.71 - 0.83 ] ) and a nonsignificant reduction in hospital , 28-day , or 30-day mortality ( intervention , 159/3215 deaths [ 4.9 % ] vs control , 206/3160 deaths [ 6.5 % ] ; RR , 0.82 [ 95 % CI , 0.67 - 1.01 ] ) and mortality at longest follow-up ( intervention , 267/3215 deaths [ 8.3 % ] vs control , 327/3160 deaths [ 10.3 % ] ; RR , 0.86 [ 95 % CI , 0.74 - 1.00 ] ) . CONCLUSIONS AND RELEVANCE In a r and omized trial of high-risk patients undergoing major gastrointestinal surgery , use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality . However , inclusion of these data in an up date d meta- analysis indicates that the intervention was associated with a reduction in complication rates . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N04386758 Background The optimization of preventive strategies in patients at high risk of cardiovascular events and the evaluation of bottlenecks and limitations of transferring current guidelines to the real world of clinical practice are important limiting steps to cardiovascular prevention . Treatment with n-3 polyunsaturated fatty acids improves prognosis after myocardial infa rct ion , but evidence of this benefit is lacking in patients at high cardiovascular risk , but without a history of myocardial infa rct ion . Methods / design Patients were eligible if their general practitioner ( GP ) considered them at high cardiovascular risk because of a cardiovascular disease other than myocardial infa rct ion , or multiple risk factors ( at least four major risk factors in non-diabetic patients and one in diabetics ) . Patients were r and omly allocated to treatment with n-3 polyunsaturated fatty acids ( 1 g daily ) or placebo in a double-blind study and followed up for five years by their GPs to assess the efficacy of the treatment in preventing cardiovascular mortality ( including sudden death ) and hospitalization for cardiovascular reasons . The secondary , epidemiological , aim of the study is to assess whether it is feasible to adopt current guidelines in everyday clinical practice , with a view to optimizing all the available preventive strategies in people at high cardiovascular risk . A nation-wide network of 860 GPs admitted 12,513 patients to the study between February 2004 and March 2007 . The mean age was 64 years and 62 % were males . Diabetes mellitus plus one or more cardiovascular risk factors was the main inclusion criterion ( 47 % ) . About 30 % of patients were included because of a history of atherosclerotic cardiovascular disease , 21 % for four or more risk factors , and less than 1 % for other reasons . Discussion The Rischio and Prevenzione ( R&P ) project provides a feasible model to test the efficacy of n-3 polyunsaturated fatty acid therapy in patients at high cardiovascular risk with no history of myocardial infa rct ion , and to assess how to implement recommended preventive strategies in general practice .Trial registration Clinical Trials.gov BACKGROUND The r and omized controlled trial ( RCT ) is the least biased measure of the effectiveness of interventions , including surgical interventions . The aim was to review the available evidence base in gynaecologic surgery , to assess what progress has been made and to determine gaps in the evidence for clinical decision-making . METHODS Systematic review s involving gynaecological surgery interventions were extracted from the Cochrane Data base of Systematic Review s ( Issue 2 , 2007 ) and data were extracted for key primary outcomes from each of the r and omized trials in the review s. The review s were categorized as to whether they had provided evidence of effectiveness for pre-defined outcomes of most relevance to patients . RESULTS Of 371 review s or protocol s published on the Cochrane Data base of Systematic Review s ( Issue 2 , 2007 ) , only 30 were completed review s assessing surgical interventions . Seven review s concluded there was evidence of a significant effect ( whether beneficial or harmful ) of the interventions studied for pre-defined primary outcomes ; 11 review s concluded there was some evidence of significant effects for primary outcomes along with some gaps for primary outcomes ; 12 review s concluded insufficient evidence of effectiveness . Common themes of unique method ological challenges and pitfalls with trials of surgical interventions were apparent . CONCLUSIONS Cochrane review s have gone a long way to establishing a sound evidence base in gynaecologic surgery : some gaps in the evidence have been eliminated and others highlighted . In general , gynaecology has been a specialty where surgical interventions have been well exposed to the scrutiny of RCTs compared with other surgical specialties PURPOSE Although early death from perioperative myocardial infa rct ion ( PMI ) after vascular surgery is well established , long-term outcome in patients surviving PMI is unknown . This prospect i ve study was design ed to determine cardiac outcome and survival rates in patients with symptomatic and asymptomatic nonfatal PMI associated with peripheral vascular surgery . METHODS During a 36-month period for 1989 to 1992 , all patients undergoing vascular surgery at our institution were monitored for PMI with serial creatine kinase and myocardial b and isoenzymes and electrocardiography . PMIs were classified as symptomatic ( associated with chest pain , arrhythmia , congestive heart failure , or hypotension ) or asymptomatic ( electrocardiographic changes and /or elevated creatine kinase and myocardial b and isoenzymes ) . Patients with PMI were then prospect ively monitored and compared for late survival , with control patients undergoing vascular surgery without PMI during the same interval . RESULTS During the study period 1561 major peripheral vascular procedures were performed . There were 47 PMIs ( 3.0 % ) . Eleven ( 0.7 % ) PMIs were fatal , 31 were nonfatal , and five other patients with PMI died during operation of non-heart-related causes . Eight of 31 patients with nonfatal PMI had a " chemical PMI " with creatine kinase and myocardial b and isoenzyme elevation as the sole indicator of PMI . During follow-up ( mean 27.7 months ) , there was a higher incidence of both subsequent myocardial infa rct ion and coronary artery revascularization among the patients with nonfatal PMI compared with control subjects ( p < 0.05 ) ; however , survival for patients with nonfatal PMI at 1 and 4 years ( 80 % and 51 % ) did not differ from that of control patients ( 90 % and 60 % ) ( p > 0.05 ) . Patients with " chemical PMI " had similar patterns of subsequent myocardial infa rct ion and coronary intervention as control patients . CONCLUSIONS Patients surviving nonfatal PMI after peripheral vascular surgery have a higher incidence of subsequent adverse cardiac events and coronary artery revascularization than patients undergoing vascular surgery without PMI , but they have similar survival rates at 1 and 4 years . Patients in the enzyme-only PMI group have a similar outcome compared with control subjects suggesting that a perioperative " chemical MI " may not be a significant clinical event Atherosclerotic cardiovascular disease ( ASCVD ) is the leading cause of death , decreased quality of life , and medical costs in the United States . Nearly 1 in 3 Americans die of heart disease and stroke ( 1 ) . Most ASCVD is preventable through a healthy lifestyle and effective treatment of cholesterol and blood pressure . The 2013 Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults from the American College of Cardiology and American Heart Association ( ACC/AHA ) provides an evidence -based approach to reducing ASCVD risk ( 2 ) . Guideline Development Process In 2008 , the National Heart , Lung , and Blood Institute ( NHLBI ) convened the Adult Treatment Panel ( ATP ) IV to up date the 2001 ATP-III cholesterol guidelines using a rigorous systematic process to identify and review r and omized , controlled trials ( RCTs ) with cardiovascular outcomes and meta-analyses of these RCTs . The panel comprised experts and clinicians from the fields of cardiology , epidemiology , primary care , and endocrinology ( 2 ) and received support from the Lifestyle Management and Risk Assessment Work Groups ( 3 , 4 ) . Systematic evidence review s conducted according to principles recommended by the Institute of Medicine ( 5 ) were performed to answer 3 questions relevant to clinical care . Two questions focused on the evidence supporting low-density lipoprotein cholesterol ( LDL-C ) and nonhigh-density lipoprotein cholesterol ( HDL-C ) levels as targets of treatment . One question examined the reduction in ASCVD events and adverse effects for each cholesterol-lowering drug class . The panel synthesized the evidence from these 3 review s as well as from Lifestyle Management and Risk Assessment Work Groups review s ( 3 , 4 ) that addressed 5 additional critical questions . Systematic electronic search es of relevant data bases of the peer- review ed English- language literature published from 1 January 1995 through 1 December 2009 for each critical question were conducted by an NHLBI-selected independent contractor and focused on RCTs and systematic review s and meta-analyses of RCTs assessed as fair to good quality . In addition , RCTs with ASCVD outcomes that included coronary heart disease , stroke , and cardiovascular deaths published after that date were eligible for consideration through July 2013 . Evidence tables were constructed , and the strength of evidence was rated according to the NHLBI ( Table 1 of the Supplement ) . Recommendations were grade d according to criteria from the NHLBI ( Table 2 of the Supplement ) and ACC/AHA ( Table 3 of the Supplement ) . Because of the inherent differences in grading systems and the clinical questions driving the recommendations , alignment between the NHLBI and ACC/AHA formats was imperfect . A complete description of the methods used and results of the evidence review are provided in the guideline ( 2 ) and the NHLBI evidence report ( www.nhlbi.nih.gov/ guidelines /cholesterol/ser/index.htm ) . Supplement . NHLBI and ACC/AHA Criteria for Rating Strength of Evidence To help clinicians estimate ASCVD risk , the risk assessment working group developed the Pooled Cohort Equations using data from 5 NHLBI-sponsored longitudinal , population -based cohorts of African American and non-Hispanic white men and women to estimate risk for a first myocardial infa rct ion , coronary heart disease death , or fatal or nonfatal stroke on the basis of age , sex , race , smoking status , total cholesterol level , HDL-C level , systolic blood pressure , antihypertensive therapy , and diabetes ( 4 , 6 ) . These equations significantly advance ASCVD risk estimation by providing sex- and race-specific estimates and including stroke as an outcome . The earlier Framingham equations calculated only coronary heart disease risk for non-Hispanic whites . The draft recommendations were review ed by 23 experts and representatives of federal agencies identified by the NHLBI . In September 2013 , the recommendations developed by the panel were transitioned to the ACC/AHA and had additional review by 4 experts nominated by the ACC Foundation and the AHA . The governing bodies of the ACC and AHA approved the guideline , which also received endorsement from the American Association of Cardiovascular and Pulmonary Rehabilitation , American Pharmacists Association , American Society for Preventive Cardiology , Association of Black Cardiologists , Preventive Cardiovascular Nurses Association , and WomenHeart : The National Coalition for Women with Heart Disease . Recommendations The guideline focuses on treatment of blood cholesterol to reduce ASCVD risk in adults . Major recommendations are summarized here and in Table 1 . The guideline report provides a complete listing of recommendations and supporting evidence behind each recommendation ( 2 ) . Table 1 . Major Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults * 1 . Encourage Adherence to a Healthy Lifestyle A healthy lifestyle is the foundation for cardiovascular health . The panel endorsed the 2013 ACC/AHA Lifestyle Management Guideline ( 3 ) for a diet that is low in saturated fat , trans fat , and sodium ; emphasizes vegetables , fruits , whole grains , low-fat dairy products , poultry , fish , legumes , nontropical vegetable oils , and nuts ; and limits sweets , sugar-sweetened beverages , and red meats and engage in regular aerobic physical activity . Adults also should maintain a healthy body weight , avoid smoking , and control hypertension and diabetes when present . 2 . Statin Therapy Is Recommended for Adults in Groups Demonstrated to Benefit Strong RCT evidence shows that reduction in ASCVD events from statin therapy exceeds adverse events for 4 patient groups : those with clinical ASCVD ( acute coronary syndromes , myocardial infa rct ion , stable angina , coronary or other arterial revascularization , stroke , transient ischemic attack , or peripheral arterial disease of atherosclerotic origin ) when  statins are used for secondary prevention , and those with LDL-C levels 190 mg/dL ; those aged 40 to 75 years with diabetes and LDL-C levels 70 to 189 mg/dL ; and those aged 40 to 75 years without diabetes and with a 10-year ASCVD risk 7.5 % when statins are used for primary prevention . Moderate evidence supports consideration of statin therapy for primary prevention in individuals with a 10-year ASCVD risk of 5 % to < 7.5 % . Routine initiation of statin therapy is not recommended in adults with New York Heart Association heart failure class II to IV or those receiving maintenance hemodialysis . R and omized , controlled trials in these groups showed no reduction in ASCVD . 3 . Statins have an Acceptable Margin of Safety When Used in Properly Selected Individuals and Appropriately Monitored Strong RCT evidence supports safety of statins when they are used as directed in conjunction with regular follow-up assessment s in properly selected patients . Adjustment of statin intensity is recommended in individuals older than 75 years with a history of statin intolerance or other characteristics ( 2 ) or those receiving drug therapy that may increase statin adverse events . Routine monitoring of hepatic aminotransferase level or creatine kinase level is not recommended unless clinical ly indicated by symptoms suggesting hepatotoxicity or myopathy . Given the potential for decreasing ASCVD events and death , the relationship of muscle and other symptoms to statin treatment must be confirmed . Therefore , eliciting a history of muscle symptoms before statin initiation and carefully monitoring symptoms during statin discontinuation and rechallenge is recommended . Severe myopathy , rhabdomyolysis , and possibly hemorrhagic stroke are rare complications of statin therapy . Although statin therapy modestly increases the risk for type 2 diabetes , ASCVD risk reduction outweighs the excess risk for diabetes for high-intensity statins in secondary prevention or for 10-year ASCVD risk 7.5 % . Similarly , ASCVD risk reduction outweighs the excess risk for diabetes for moderate-intensity statin therapy in adults with a 10-year ASCVD risk 5 % . 4 . Engage in a ClinicianPatient Discussion Before Initiating Statin Therapy , Especially for Primary Prevention in Patients With Lower ASCVD Risk Decisions to initiate statin therapy in primary prevention should be based on clinical judgment and preferences of informed patients . In adults without clinical ASCVD or diabetes whose LDL-C level is < 190 mg/dL , calculating the estimated 10-year ASCVD risk should be the start of the clinicianpatient discussion and should not automatically lead to statin initiation . As the absolute risk for ASCVD events decreases , so does the net benefit of the intervention . Therefore , discussion of the potential for ASCVD event reduction , adverse effects , drugdrug interactions , and patient preferences is especially important for lower-risk primary prevention . The discussion provides the opportunity to encourage healthy lifestyle habits and control other risk factors . Additional factors may be considered when a risk-based decision is uncertain , including LDL-C levels 160 mg/dL , family history of premature ASCVD , elevated  lifetime ASCVD risk  , high-sensitivity C-reactive protein level 2.0 mg/L ,  coronary artery calcification score  > 300 Agatston units , and anklebrachial index < 0.9 . After age 75 years , comorbid conditions , anticipated longevity , safety considerations , and patient preferences should play a large role in decision making . 5 . Use the Newly Developed Pooled Cohort Equations for Estimating 10-Year ASCVD Risk The Pooled Cohort Equations are currently the best available method for estimating 10-year ASCVD risk to guide statin initiation ( 4 , 6 ) . Application of the inclusion and exclusion criteria from RCTs is cumbersome and results in underidentifying high-risk and overidentifying low-risk individuals for statin treatment . The Pooled Cohort Equations were developed using recent data from 5 NHLBI-sponsored , longitudinal , population -based cohorts of African American and white men and women ( ARIC [ Background and objective Sugammadex , a modified γ-cyclodextrin , is a selective relaxant-binding agent design ed to reverse the effects of the steroidal neuromuscular blocking agents rocuronium or vecuronium . This study compared the efficacy of sugammadex and neostigmine for reversal of neuromuscular blockade induced by rocuronium for facilitating elective surgery . Methods This r and omised , multicentre , parallel-group trial included 98 adult patients . Patients received intravenous propofol for induction followed by sevoflurane maintenance anaesthesia . Neuromuscular blockade was monitored using acceleromyography and a train-of-four ( TOF ) mode of stimulation . Patients were r and omly allocated to receive sugammadex 2.0 mg kg−1 or neostigmine 50 μg kg−1 ( with glycopyrrolate 10 μg kg−1 ) at reappearance of the second response of the TOF ( mean 16 % twitch height of first response ) after the last dose of rocuronium . Safety was evaluated by assessing adverse events , laboratory variables and vital signs . Results Time to recovery of the TOF ratio of 0.9 after sugammadex compared with neostigmine was significantly shorter ( P < 0.0001 ) , being 1.5 versus 18.6 min ( geometric means ) . Predictability of response was greater with sugammadex than neostigmine : with 98 % of sugammadex patients versus 11 % of neostigmine patients recovering to a TOF ratio of 0.9 within 5 min . There were no clinical events related to residual neuromuscular blockade or reoccurrence of blockade . Serious adverse events were observed in two sugammadex-treated patients and in three neostigmine-treated patients , respectively , but none were considered related to study drugs . Conclusion Sugammadex achieved significantly faster recovery of neuromuscular function after rocuronium to a TOF ratio of 0.9 compared with neostigmine ( Clinical trials.gov identifier : NCT00451217 )
Compared with general anaesthesia , a central neuraxial block may reduce the zero to 30-day mortality for patients undergoing surgery with intermediate to high cardiac risk ( level of evidence , moderate ) .
BACKGROUND Various beneficial effects derived from neuraxial blocks have been reported .
However , it is unclear whether these effects have an influence on perioperative mortality and major pulmonary/cardiovascular complications .
OBJECTIVES Our primary objective was to summarize Cochrane systematic review s that assess the effects of neuraxial blockade on perioperative rates of death , chest infection and myocardial infa rct ion by integrating the evidence from all such review s that have compared neuraxial blockade with or without general anaesthesia versus general anaesthesia alone for different types of surgery in various population s. Our secondary objective was to summarize the evidence on adverse effects ( an adverse event for which a causal relation between the intervention and the event is at least a reasonable possibility ) of neuraxial blockade .