CONTROVERSIES IN ENDODONTICS. Antidepressants in bipolar depression: The clinical debate Long‐term treatment with aspirin desensitization: a prospective clinical trial comparing 100 and 300 mg aspirin daily Hydroxyethyl starches: what do we still know? Analgesic effect of intraarticular morphine. A controlled, randomised and double‐blind study Increase of bone mineral density by calcium supplement with oyster shell electrolysate. An inhibitor persistently decreased enteric methane emission from dairy cows with no negative effect on milk production Antimicrobial Prophylaxis in Laparoscopic Gynecologic Surgery: A Prospective Randomized Study Comparing Amoxicillin-Clavulanic Acid with Cefazolin [Optimization of calcium intake for the prevention of osteoporosis and osteoporotic fractures: a review of the evidence]. Erythropoietin plus granulocyte colony-stimulating factor is better than erythropoietin alone to treat anemia in low-risk myelodysplastic syndromes: results from a randomized single-centre study Tight Stapes Prosthesis Fixation Leads to Better Functional Results in Otosclerosis Surgery Musculoskeletal disorders and occupational exposures: How should we judge the evidence concerning the causal association? Dairy Products and Prevention of Type 2 Diabetes: Implications for Research and Practice Oral Specific Desensitization in Food-Allergic Children ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Recombinant human activated protein C for adults with septic shock: a randomized controlled trial. Use of high-dose methylprednisolone pulse therapy in patients with progressive and stable vitiligo. Association between dairy food consumption and risk of myocardial infarction in women differs by type of dairy food. Impact of timing of follow-up upon outcome in the TOPKAT trial TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION: Relevance of Stimulation Parameters to Neurophysiological and Hypoalgesic Effects Chocolate and Prevention of Cardiovascular Disease: A Systematic Review Portal vein thrombosis relevance on liver cirrhosis: Italian Venous Thrombotic Events Registry Intent-to-treat analysis and preventive vaccine efficacy. Manipulating dietary anions and cations for prepartum dairy cows to reduce incidence of milk fever. Celecoxib for the treatment of mild-to-moderate depression due to acute brucellosis: a double-blind, placebo-controlled, randomized trial. Heroin-assisted treatment in Switzerland: a case study in policy change.
Diseases of the dental pulp often have an infectious origin , and treatments are aim ed to control infections of the root canal system . Endodontic treatment principles originally evolved on the basis of trial and error , and only in recent decades have scientific methods been adopted to support clinical strategies . Yet , relevant research on the disease processes , their diagnoses , and efficient treatment are rare in the endodontic literature . Hence , the advancement of biologically based knowledge significant to clinical endodontics has been slow . Therefore , many differences of opinion still prevail in this field of dentistry . This review highlights and analyzes the background of some of the more heavily debated issues in recent years . Specifically , it deals with disagreements regarding the clinical management of pulpal exposures by caries in the adult dentition , definitions of success and failure of endodontic therapy  , and causes of and measures to control infections of the root canal system . Clearly , a most apparent gap in the published endodontic literature is the lack of r and omized clinical trials that address the more significant controversial matters relating to the management of pulpal wounds , medication , and the number of appointments required for the treatment of infected root canals . However , trials in endodontics require extremely long follow-up periods if valid conclusions are to be generated . Therefore , it is not to be expected that there will be rapid solutions to these issues in the foreseeable future There are scientific , clinical and cultural aspects to the debate about antidepressants in bipolar depression . In prior communications I ’ve focused on scientific aspects . Over time , as I realized how the scientific evidence seemed unconvincing , I concluded that clinical and cultural aspects were important . Here , besides briefly recapitulating the scientific evidence , I will also comment on clinical and cultural factors . To begin with some rules of clinical research worth making explicit : r and omized data are more valid than observational data , because factors that influence the results besides what we are study ing ( confounding factors ) are only removed by r and omization . Sample size is less relevant ; a large observational study does not contradict a smaller r and omized study . Let ’s keep in mind this basic fact of science ( one can call it evidence -based medicine , EBM , if one wants ) . Given that background , risks and benefits of antidepressants need to be assessed in four categories : acute efficacy , maintenance efficacy , acute manic switch and long-term mood destabilization . These different groupings often overlap and are mixed , leading to confusion Background : The daily dose of aspirin in desensitization in aspirin‐sensitive asthmatics with nasal polyps is still a matter of debate The choice of fluids for intravascular volume replacement has been debated for decades . As early as 1919 , Benjamin Moore eloquently commented on the relative merits of colloids and crystalloids in different types of shock . More recently , this debate has focused not only on colloids versus crystalloids , but more specifically on the choice of colloid solutions . Hydroxyethyl starch ( HES ) solutions were developed as less-expensive alternatives to albumin . HES solutions vary in their median molecular weight , molecular weight distribution , ratio between C2:C6 hydroxyethylation , and the type of diluent used . The goal to reduce side effects was an important motivation for the different compositions , but clinical evidence for their improved safety is inadequate . Today , the safety of HES solutions is still debated , with the additional complicating factor of commercial interests attempting to influence the argument . On October 28 , 2010 , Anesthesia & Analgesia retracted a recent publication of Joachim Boldt et al. based on an inference of fraudulent research and after an official inquiry by the L and esärztekammer Rheinl and -Pfalz ( the Rheinl and -Pfalz State Medical Board ) . Because of the widespread use of HES solutions and the fact that their use may have increased as a result of research described in the retracted paper , it is important to address just how retraction of this paper may influence the debate on HES . The recent retraction of a series of fraudulent publications by Scott Reuben profoundly shook the anesthesia community . Steven Shafer , Editor-in-Chief of Anesthesia & Analgesia , compared these events to ripping a thread from the interwoven tapestry of human underst and ing . At first glance , the now-retracted single-center report of 50 patients seems trivial in the context of the overall debate on efficacy of HES . Unfortunately , any scientific misconduct , no matter how trivial , casts a long shadow on the scientific work of all involved . In this particular case , a shadow is cast on a bulk of literature on HES safety and efficacy . According to the ISI Web of Science data base , 85 of 346 publications authored by Dr. Boldt deal with  intravascular volume therapy .  Of these , 30 studies and 2 review s were included in recent meta-analyses and consensus guidelines ( Table 1 ) . Because of the shadow cast on Dr. Boldt ’s publications by the recent retraction , we need to ask what evidence on the safety and efficacy of HES remains if his publications were not taken into account . Cochrane meta-analyses on the effectiveness of crystalloid versus colloid fluid resuscitation  in critically ill patients and on  colloid versus colloid fluids  in acute hypovolemia concluded that “ there is no evidence from r and omized controlled trials that resuscitation with colloids , instead of crystalloids , reduces the risk of death in patients with trauma , burns , or following surgery ” and that “ despite finding 70 trials we can not make any conclusions about the relative effectiveness of different colloid solutions . ” Excluding the studies of Boldt et al. from these meta-analyses is unlikely to change these conclusions . In the current debate on HES , safety is of major concern . Another recent Cochrane meta- analysis on the safety of HES versus other fluid therapies on kidney function concluded that “ medical practitioners should consider the potential for adverse kidney effects , including acute kidney injury and increased risk of renal replacement therapy when using HES for volume resuscitation , particularly in septic patients . ” A recent systematic review and meta analysis from the Canadian Critical Care Trials Group concluded that critically ill patients receiving HES  were more likely to receive renal replacement therapy , and identified a trend toward increased risk of death in association with HES for patients with severe sepsis . Because most of the studies by Boldt et al. included in these meta-analyses favored HES , their exclusion would increase the safety concerns of HES . For those whose clinical practice is strongly influenced by the available evidence , the approach to fluid therapy in hypovolemia is likely to remain largely unchanged despite the retraction of the article by Boldt et al. However , recent consensus guidelines on fluid therapy draw somewhat mixed conclusions on choice of fluid for volume therapy . For instance , the American Thoracic Society Guidelines urge a cautious approach in the use of HES and synthetic colloids in critically ill patients , whereas the British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients ( GIFTASUP ) caution against the use of older starches in patients at risk of renal dysfunction but not against the use of low-molecular-weight thirdgeneration HES ( Table 1 ) . The shadow of doubt now cast From the * Klinik für Anästhesiologie und Intensivtherapie , Universitätsklinikum Jena , Jena , Germany ; and †Department of Intensive Care Medicine , Bern University Hospital ( Inselspital ) and University of Bern , Bern , Switzerl and Background : Opioids produce antinociceptive effect by acting on receptors on peripheral nerves . The clinical relevance of this effect is still debated . The aim of the study was to compare the analgesic effect of morphine intraarticularly with the intramuscular route of administration after knee surgery The effect of calcium supplementation , in patients with osteoporosis is still a matter of controversy . Oyster shell electrolysate ( OSE ) was reported to raise serum calcium and increase urinary calcium excretion in vitamin D-deficient states more readily than calcium carbonate . Since the effect of calcium salts on osteoporosis depends heavily on its bioavailability , the effect of 900 mg/day calcium as OSE was tested in 12 elderly osteoporotic females , using radial bone mineral density measured by single photon absorptiometry and spinal trabecular bone density measured by quantitative computed tomography ( QCT ) as indicated , in comparison with 21 untreated controls in the same geriatric hospital .  Radial bone mineral density significantly increased from the pre-test value after 12 and 24 months in subjects given OSE by paired t-test , whereas it fell significantly in the controls . The spinal QCT value on OSE  did not change significantly in either the subjects under treatment with OSE , or the controls . Thus OSE may favorably influence osteoporosis by providing a readily available source of calcium Significance Methane from enteric fermentation in the ruminant digestive system is a major contributor to anthropogenic greenhouse gas emissions in the United States and worldwide . Methane is also a net loss of feed energy to the animal . This study was undertaken to investigate the effect of a methane inhibitor on enteric methane emissions from lactating dairy cows . The experiment demonstrated that , under industry-relevant conditions , the inhibitor persistently decreased by 30 % enteric methane emissions , without negatively affecting animal productivity . The spared methane energy was partially used for tissue synthesis , which led to a greater body weight gain by the inhibitor-treated cows . If adopted , this mitigation practice could lead to a substantial reduction of greenhouse gas emissions from the ruminant livestock sector . A quarter of all anthropogenic methane emissions in the United States are from enteric fermentation , primarily from ruminant livestock . This study was undertaken to test the effect of a methane inhibitor , 3-nitrooxypropanol ( 3NOP ) , on enteric methane emission in lactating Holstein cows . An experiment was conducted using 48 cows in a r and omized block design with a 2-wk covariate period and a 12-wk data collection period . Feed intake , milk production , and fiber digestibility were not affected by the inhibitor . Milk protein and lactose yields were increased by 3NOP . Rumen methane emission was linearly decreased by 3NOP , averaging about 30 % lower than the control . Methane emission per unit of feed dry matter intake or per unit of energy-corrected milk were also about 30 % less for the 3NOP-treated cows . On average , the body weight gain of 3NOP-treated cows was 80 % greater than control cows during the 12-wk experiment . The experiment demonstrated that the methane inhibitor 3NOP , applied at 40 to 80 mg/kg feed dry matter , decreased methane emissions from high-producing dairy cows by 30 % and increased body weight gain without negatively affecting feed intake or milk production and composition . The inhibitory effect persisted over 12 wk of treatment , thus offering an effective methane mitigation practice for the livestock industries Abstract Numerous studies have been published in recent years about antimicrobial prophylaxis in gynecologic surgery , but the optimal drug and schedule for the different surgical procedures is still a matter of debate . The aim of the present study was to compare two ultra-short term antimicrobial prophylaxis regimens ( amoxicillin-clavulanic acid and cefazolin ) in preventing infections following laparoscopic gynecologic operations . Three hundred sixty women hospitalized for a laparoscopic gynecologic surgery procedure were included in the study between January 1999 , and December 2001 . Patients were r and omly allocated to receive amoxicillin-clavulanic acid ( 2.2 g ) [ Group A ] or cefazolin ( 2 g ) [ Group B ] as a single dose 30 minutes before surgery . Each patient was assessed daily until discharge to evidence febrile status and the presence of infections at the operative site , urinary tract and respiratory tract . In the amoxicillin-clavulanic acid ( Group A ) and cefazolin ( Group B ) groups , overall 164 and 172 patients , respectively , were evaluable for prophylactic efficacy at hospital discharge . Infectious complications were infrequent in both groups with febrile morbidity occurring in only one patient ( 0.6 % ) in the amoxicillin- clavulanic group . No sign of infections at the surgical site , urinary tract and respiratory tract was observed in either group . No death due to sepsis was recorded . It is concluded that ultra-short term prophylaxis with both amoxicillin-clavulanic acid and cefazolin is safe and effective in elective laparoscopic gynecologic surgery One of the main focuses of lifestyle modification for the prevention of osteoporosis and osteoporotic fractures  in Japan is improvement in dietary calcium intake . However , virtually no r and omized controlled trial to assess the preventive effects of administration of calcium on the risk of fractures has been conducted in Japan . In this study , we review ed all the scientific papers currently available from medical literature data bases to propose evidence -based recommendations on the preventive procedures for osteoporosis . The result of the present systematic review gives the evidence showing that calcium supplementation or optimal dietary calcium intake increases bone density in childhood and adolescence and reduces the risk of fracture due to osteoporosis in the elderly people regardless of the gender . The evidence also supports the current health policy guiding the elderly to increase their dietary calcium intake in daily life Haemopoietic growth factors ( HGF ) , i.e. erythropoietin [ recombinant human erythropoietin ( rHEPO ) ] or granulocyte colony stimulating factor ( G-CSF ) , alone or in combination , have largely been used to treat anemia in myelodysplastic syndromes ( MDS ) , but whether combined rHEPO and G-CSF is really superior to rHEPO alone is still under debate . In particular , r and omized studies comparing front-line rHEPO vs rHEPO+G-CSF are still lacking . The aim of this study was to compare the effects of “ st and ard ” doses of rHEPO with the combination of rHEPO and G-CSF in the treatment of anemic patients with low-risk MDS in a prospect i ve r and omized trial . Anemic patients with low-risk MDS were r and omly assigned to receive either rHEPO ( 10,000 IU s.c . three times a week ) or the same dosage of rHEPO+G-CSF ( 300 μg s.c . twice a week ) for a minimum of 8 weeks . Patients who were unresponsive to rHEPO were offered the combination therapy for another 8 weeks , whereas non-responders to rHEPO+G-CSF were considered “ off study ” . Responders continued the treatment indefinitely . Both haematological response and changes in quality -of-life ( QoL ) scores ( Functional Assessment of Cancer Therapy-Anemia ) were recorded and evaluated . Thirty consecutive patients [ 10 refractory anemia ( RA ) , 5 RA with ringed sideroblasts , 7 refractory cytopenia with multilineage dysplasia , 5 RA with less than 10 % blasts and 3 5q-syndrome ] were enrolled in the study . All of them ( 15 in the rHEPO arm and 15 in the rHEPO+G-CSF arm ) were valuable after the first 8 weeks of treatment . Erythroid response was observed in 6/15 ( 40 % ) patients in the rHEPO arm and in 11/15 ( 73.3 % ) patients in the rHEPO+G-CSF arm . In 4/9 ( 44.4 % ) patients who were unresponsive to rHEPO , the addition of G-CSF induced erythroid response at 16 weeks . No relevant adverse effects were recorded for either treatment in any of the study patients . Erythroid response to HGF was associated with a relevant improvement in QoL.Twenty responders continued the treatment . Afterwards , 8/20 ( 40 % ) discontinued therapy because of the following : losing response ( 2 ) , progression to high-risk MDS ( 3 ) and death due to other causes ( 3 ) . The remaining 12 are still responding and continuing treatment , with a median follow-up of 28 months . Progression to acute leukemia was cumulatively observed in 4/30 ( 13.3 % ) patients ( 2 in each arm).Although our data were obtained from a relatively small cohort of patients , they indicate that the rHEPO+G-CSF treatment is more effective than rHEPO alone for correcting anemia in low-risk MDS patients and for making a relevant improvement in their Tight fixation of stapes prostheses  yields better functional results because sound transmission from the incus to the prosthesis is improved . Background : The optimal prosthesis to use for otosclerosis surgery is still a matter of debate . It has been proposed that using prostheses made of Nitinol , a shape-memory metal , produces better functional results with less variability and reduced risk for middle and inner ear damage . This is thought to be because heat activation rather than manual crimping of the prosthesis loop forms a tighter fixation . Methods : Functional results of two groups were compared 1 year after surgery . In one group were 75 cases of stapedotomy performed using Nitinol prostheses .  Results were analyzed prospect ively and compared with 75 retrospectively analyzed matched controls with conventional stapes prostheses .  Crimping quality was measured in 23 patients by intraoperative laser Doppler interferometry ( LDI ) . Causality was assessed by correlating results of intraoperative LDI and postoperative pure-tone thresholds . Results : Nitinol and conventional prostheses yielded postoperative air-bone gaps ( ABGs ) of 8.0 and 11.6 dB with 71 and 43 % ABG closure within 10 dB , respectively . Intraoperatively , sound transmission was improved by 2.5 dB with the Nitinol prostheses as compared with conventional prostheses . These differences were statistically significant . Intraoperative fixation quality was positively correlated to functional outcome , but results were not statistically significant . Conclusion : Tight fixation , as provided by Nitinol prostheses leads to improved functional results because of better sound transmission properties at the incus-prosthesis interface . The improvement in ABG closure is in the range of 3 dB pure-tone average and more pronounced at higher frequencies . Nitinol prostheses provide an effective treatment option in otosclerosis surgery Musculoskeletal disorders ( MSDs ) affecting the back , upper and lower extremities are widespread in the general population , implying a variety of causal factors . Multiple causes are not mutually exclusive , and a high background rate does not preclude associations with specific factors that are uncommon in the general population . MSDs have well-documented associations with occupational ergonomic stressors such as repetitive motion , heavy lifting , non-neutral postures , and vibration . Organizational features of the work environment , such as time pressure and low decision latitude , may also play a role , at least by potentiating the effects of physical loading . Numerous systematic review s have mostly concurred with these overall findings . Nevertheless , some continue to debate whether MSDs are sometimes work-related , even for those performing jobs with repetitive and routinized tasks , heavy lifting , and /or pronounced postural strain . This article discusses ( 1 ) some epidemiologic features of MSDs that underlie that debate ; and ( 2 ) the question of what should appropriately be considered a gold st and ard for scientific evidence on an etiological question such as the health effects of a non-voluntary exposure , such as an occupational or environmental agent . In particular , r and omized clinical trials have little relevance for determining the health effects of non-therapeutic risk factors A growing body of scientific evidence has linked dairy intake to a reduced  type 2 diabetes ( T2D ) risk . Using an evidence -based approach , we review ed the most recent and strongest evidence on the relationship between dairy intake and the risk of T2D . Evidence indicates that dairy intake is significantly associated with a reduced T2D risk , and likely in a dose-response manner . The association between low-fat dairy and T2D risk reduction appears consistent . A beneficial impact is suggested for regular-fat dairy . The role of specific dairy products needs to be clarified . Potential underlying mechanisms include the role of dairy products in obesity and metabolic syndrome , as well as several dairy components , such as calcium , vitamin D , dairy fat , and specifically trans-palmitoleic acid . To conclude , there is strong , consistent , and accumulating evidence that dairy intake reduces the risk of T2D . More research is needed to better underst and the role of regular-fat and specific dairy products . Well- design ed r and omized controlled trials and mechanistic studies are needed to support these findings . Efforts to translate this evidence into clinical practice and public health guidance are needed The possibility of obtaining oral desensitization in patients with food allergy is still a matter of debate . We decided to evaluate the safety and efficacy of st and ardized protocol s for oral desensitization with the most common food allergens . Forty-two children ( ages up to 16 years ) diagnosed as affected by food allergy ( on the basis of clinical history , skin prick tests , measurement of specific IgE , and double-blind , placebo-controlled food challenge ) underwent a sublingual-oral desensitizing treatment according to new st and ardized protocol s. The control group consisted of 10 patients who followed an elimination diet .  The treatment was successfully completed by 85.7 % of the patients . Specific IgE showed a significant decrease , while specific IgG4 showed a significant increase , in all treated patients . The immunological modifications observed in our patients lead us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory and insect sting allergy BACKGROUND Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma . However , recent clinical trials have failed to confirm BEACOPP  overall survival ( OS ) superiority over ABVD . In addition , the gain in low-risk patients is still a matter of debate . PATIENTS AND METHODS We r and omly compared ABVD ( 8 cycles ) with BEACOPP ( escalated 4 cycles ≥ baseline 4 cycles ) in low-risk patients with an International Prognostic Score ( IPS ) of 0 - 2 . The primary end point was event-free survival ( EFS ) . This parallel group , open-label phase 3 trial was registered under # RECF0219 at French National Cancer Institute . RESULTS One hundred and fifty patients were r and omized in this trial ( ABVD 80 , BEACOPP 70 ) : 28 years was the median age , 50 % were male and IPS was 0 - 1 for 64 % . Complete remission rate was 85 % for ABVD and 90 % for BEACOPP  . Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients ( 17 versus 5 patients ) . With a median follow-up period of 5.5 years , seven patients died : six in the ABVD arm and one in the BEACOPP arm ( HL 3 and 0 , 2nd cancer 2 and 1 , accident 1 and 0 ) . The EFS at 5 years was estimated at 62 % for ABVD versus 77 % , for BEACOPP [ hazards ratio ( HR ) = 0.6 , P = 0.07 ] . The progression-free survival ( PFS ) at 5 years was 75 % versus 93 % ( HR = 0.3 , P = 0.007 ) . The OS at 5 years was 92 % versus 99 % ( HR = 0.18 , P = 0.06 ) . CONCLUSION Fewer progressions/relapses were observed with BEACOPP , demonstrating the high efficacy of the more intensive regimen , even in low-risk patients . However , additional considerations , balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP RATIONALE A decade after drotrecogin alfa ( activated ) ( DAA ) was released on the market worldwide , its benefit-to-risk ratio remains a matter of debate . OBJECTIVES The current investigator-led trial was design ed to evaluate the efficacy and safety of DAA , in combination with low-dose steroids , in adults with persistent septic shock . METHODS This was a multicenter ( 24 intensive care units ) , placebo-controlled , double-blind , 2 × 2 factorial design trial in which adults with persistent septic shock and no contraindication to DAA  were r and omly assigned to DAA alone ( 24 μg/kg/h for 96 h ) , hydrocortisone and fludrocortisone alone , their respective combinations , or their respective placebos . Primary outcome was mortality rate on Day 90 . MEASUREMENTS AND MAIN RESULTS On October 25 , 2011 , the trial was suspended after the withdrawal from the market of DAA . The Scientific Committee decided to continue the trial according to a two parallel group design comparing low-dose steroids with their placebos and to analyze the effects of DAA on patients included before trial suspension . At the time trial was suspended , 411 patients had been recruited , 208 had received DAA , and 203 had received its placebo . There was no significant interaction between DAA and low-dose steroids ( P = 0.47 ) . On Day 90 , there were 99 deaths ( 47.6 % ) among the 208 patients receiving DAA and 94 deaths ( 46.3 % ) among the 203 patients receiving placebo ( P = 0.79 ) . There was no evidence of a difference between DAA and its placebo for any secondary outcomes or serious adverse events . CONCLUSIONS In adults with established and severe septic shock , DAA showed no evidence of benefit or harm . Clinical trial registered with www . clinical trials.gov ( NCT00625209 ) BACKGROUND Although there are several treatment options available for patients with generalized vitiligo , their efficacy is still a matter of debate . Although shown to be effective , corticosteroids applied either systemically or topically carry the risk of significant side-effects in long-term therapy . We evaluated the effectiveness of intravenous methylprednisolone ( 8 mg/kg body weight ) administered on three consecutive days in patients with generalized vitiligo . MATERIAL S AND METHODS A total of 14 patients with progressive or static vitiligo were included in a prospect i ve , open , clinical study . RESULTS Eighty-five per cent of the patients presenting with progressive disease showed cessation of disease progression after the infusion therapy . Repigmentation was observed in 71 % of patients with progressive vitiligo . None of the six patients presenting with static disease showed any repigmentation in response to this form of treatment . The therapy was well tolerated in all but one patient who developed intermittent arterial hypertension during therapy . CONCLUSIONS High-dose glucocorticoid pulse therapy may represent a therapeutic option in patients with generalized progressive vitiligo , and should be further evaluated in a prospect i ve , r and omized , clinical trial The relation between dairy foods , particularly specific foods , and risk of cardiovascular disease ( CVD ) remains unclear . We examined the association between total , as well as specific , dairy food intakes and incidence of  myocardial infa rct ion ( MI )  in a prospect i ve population -based cohort . We followed 33,636 women ( aged 48 - 83 y ) , free from CVD , cancer , and diabetes at baseline ( 1997 ) , in the Swedish Mammography Cohort .  Consumption of milk , cultured milk/yogurt , cheese , cream , crème fraiche , and butter was obtained from a vali date d self-administered FFQ at baseline . We used Cox proportional hazards regression models to estimate HRs and 95 % CIs , adjusted for relevant CVD risk factors . MI incidence was ascertained from national registries . Over 11.6 y of follow-up , we ascertained 1392 cases of MI . When the highest quintile was compared with the lowest quintile , total dairy food intake was inversely associated with MI risk [ multivariable adjusted HR : 0.77 ( 95 % CI : 0.63 , 0.95 ) ] . Among specific dairy food products , total cheese was inversely associated [ HR : 0.74 ( 95 % CI : 0.60 , 0.91 ) ] and butter used on bread but not on cooking was positively associated [ HR : 1.34 ( 95 % CI : 1.02 , 1.75 ) ] with MI risk . Other specific dairy food products were not significantly associated with MI risk . No differences were observed between consumption of specific low-fat and high-fat dairy foods , expressed as either absolute intakes or intakes relative to the total , and MI risk . Failure to consider dairy foods as a heterogeneous group in future studies could hamper important insights of relevance for the development of dietary guidelines Due to the practicalities of recruitment , r and omisation of participants in surgical trials may need to take place prior to the day of surgery . However , substantial post-r and omisation delays in receiving surgery due to limited capacity may then occur . This can create a tension between timing the follow-up from r and omisation ( scientifically most desirable ) and surgery ( clinical ly most relevant ) . It is unclear what impact alternative follow-up timings have upon the outcome Although Transcutaneous Electrical Nerve Stimulation ( TENS ) has become a popular modality in pain management over the past 20 yr , there is still debate over its mechanisms of action and the precise relevance of stimulation parameters to its hypoalgesic effects . Thus , confusion still surrounds the selection of optimal stimulation parameters . Two separate studies ( total n=88 ) were carried out to investigate the effect of four combinations of TENS pulse duration s ( 50 ( µ.s & 200 µ.s ) and frequencies ( 4 Hz and 110 Hz ) on nerve conduction in the human superficial radial nerve and on Mechanical Pain Threshold ( MPT ) within the associated sensory distribution of the nerve over the dorsum of the h and . Results showed that application of one combination of TENS parameters ( 110 Hz , 200 µ,s ) directly over the course of the nerve produced a significant increase in both peripheral nerve conduction latency ( P < 0.05 ; analysis of variance ( ANOVA ) ) and MPT ( P < 0.01 ) . In addition , there was a high correlation ( r=0.9 ) between shifts in MPT and negative peak latency for the groups treated with this combination of TENS parameters . The results of this study thus illustrate that combinations of TENS parameters are important to the peripheral neurophysiological effects of this modality and , further , its associated hypoalgesic effects , at least on the model of pain used here Background Consumption of chocolate has been often hypothesized to reduce the risk of cardiovascular disease ( CVD ) due to chocolate 's high levels of stearic acid and antioxidant flavonoids . However , debate still lingers regarding the true long term beneficial cardiovascular effects of chocolate overall . Methods We review ed English- language MEDLINE publications from 1966 through January 2005 for experimental , observational , and clinical studies of relations between cocoa , cacao , chocolate , stearic acid , flavonoids ( including flavonols , flavanols , catechins , epicatechins , and procynadins ) and the risk of cardiovascular disease ( coronary heart disease ( CHD ) , stroke ) . A total of 136 publications were selected based on relevance , and quality of design and methods . An up date d meta- analysis of flavonoid intake and CHD mortality was also conducted . Results The body of short-term r and omized feeding trials suggests cocoa and chocolate may exert beneficial effects on cardiovascular risk via effects on lowering blood pressure , anti-inflammation , anti-platelet function , higher HDL , decreased LDL oxidation . Additionally , a large body of trials of stearic acid suggests it is indeed cholesterol-neutral . However , epidemiologic studies of serum and dietary stearic acid are inconclusive due to many method ologic limitations . Meanwhile , the large body of prospect i ve studies of flavonoids suggests the flavonoid content of chocolate may reduce risk of cardiovascular mortality . Our up date d meta- analysis indicates that intake of flavonoids may lower risk of CHD mortality , RR = 0.81 ( 95 % CI : 0.71–0.92 ) comparing highest and lowest tertiles . Conclusion Multiple lines of evidence from laboratory experiments and r and omized trials suggest stearic acid may be neutral , while flavonoids are likely protective against CHD mortality . The highest priority now is to conduct larger r and omized trials to definitively investigate the impact of chocolate consumption on long-term cardiovascular outcomes Abstract Portal vein thrombosis may occur in cirrhosis ; nevertheless , its prevalence , and predictors are still elusive . To investigate this issue , the Italian Society of Internal Medicine undertook the “ Portal vein thrombosis Relevance On Liver cirrhosis : Italian Venous thrombotic Events Registry ” ( PRO-LIVER ) . This prospect i ve multicenter study includes consecutive cirrhotic patients undergoing Doppler ultrasound examination of the portal area to evaluate the prevalence and incidence of portal vein thrombosis over a 2-year scheduled follow-up . Seven hundred and fifty-three ( 68 % men ; 64 ± 12 years ) patients were included in the present analysis . Fifty percent of the cases were cirrhotic out patients . Viral ( 44 % ) etiology was predominant . Around half of the patients had a  mild-severity disease  according to the Child – Pugh score ; hepatocellular carcinoma was present in 20 % . The prevalence of ultrasound-detected portal vein thrombosis was 17 % ( n = 126 ) ; it was asymptomatic in 43 % of the cases . Notably , more than half of the portal vein thrombosis patients ( n = 81 ) were not treated with anticoagulant therapy . Logistic step-forward multivariate analysis demonstrated that previous portal vein thrombosis ( p < 0.001 ) , Child – Pugh Class B + C ( p < 0.001 ) , hepatocellular carcinoma ( p = 0.01 ) , previous upper gastrointestinal bleeding ( p = 0.030 ) and older age ( p = 0.012 ) were independently associated with portal vein thrombosis . Portal vein thrombosis is a frequent complication of cirrhosis , particularly in patients with moderate – severe liver failure . The apparent undertreatment of patients with portal vein thrombosis is a matter of concern and debate , which should be addressed by planning interventional trials especially with newer oral anticoagulants . Clinical trials.gov identifier NCT01470547 While the intent-to-treat ( ITT ) concept has often been discussed and debated in the literature with respect to r and omized , placebo-controlled therapeutic trials , there has been little discussion of this issue in the context of preventive vaccine efficacy trials .  ITT analysis has traditionally played a minor role ( if any ) in the latter trials . This paper discusses the ITT approach to analysis in r and omized superiority trials of preventive vaccine efficacy , using clinical endpoints . Data are presented from published literature as well as from a simple mathematical model . The data suggest that when compliance and efficacy are high , both ITT and " per- protocol " approaches generally lead to similar conclusions regarding the acceptability of a vaccine for use in a population . However , when compliance is low , the ITT and per- protocol estimates of vaccine efficacy can be widely disparate . ITT and per- protocol analyses address unique and relevant scientific questions , and often both will be informative in evaluating preventive vaccines Twenty preparturient dairy cows were in a 2-yr switchover design to test effects of dietary ions on incidence of milk fever .  In yr 1 , cows were blocked and assigned r and omly 45 days prepartum to one of two diets ; one diet contained an excess of anions , and the second diet contained an excess of cations . In yr 2 , cows were changed to the opposite diet . Both diets were equivalent for crude protein ( 11 % ) , calcium ( .65 % ) , phosphorus ( .25 % ) , and energy on a dry basis but differed for quantities of chlorine , sulfur , and sodium . Both diets were chopped alfalfa hay , corn silage , high moisture corn , and vitamin-mineral mix . Diets were available ad libitum as complete rations . There were no differences in dry matter intake of the diets . Cows consuming the anionic diet had no milk fever , but cows consuming the canionic diet had 47.4 % incidence . Sample s of blood plasma showed that cows consuming the anionic diet maintained calcium and phosphorus through parturition , whereas cows consuming the cationic diet decreased in these minerals around calving . Hydroxyproline was higher for cows consuming the anionic diet during the peripartal period compared to cows consuming the cationic diet .  Milk produced in the lactation subsequent to prepartum treatment was 6.8 % less for cows offered the cationic diet . When milk production of paretic and nonparetic cows offered the cationic diet was compared , milk was reduced 14 % with milk fever WHAT IS KNOWN AND OBJECTIVE Depression is a debilitating complication of brucellosis and how best to treat this is a matter of debate . Inflammatory processes are involved in the pathogenesis of both brucellosis and depression . Therefore , we hypothesized that celecoxib could be beneficial for the treatment of depression due to brucellosis . METHODS Forty out patients with depression due to brucellosis with a Hamilton Depression Rating Scale score ( HDRS ) < 19 participated in a r and omized , double-blind , placebo-controlled trial and underwent 8 weeks of treatment with either celecoxib ( 200 mg bid ) or placebo as an adjunctive to antibiotic therapy . Patients were evaluated using HDRS at baseline and weeks 4 and 8 . RESULT AND DISCUSSION Repeated- measures analysis demonstrated significant effect for time × treatment interaction on the HDRS score [ F ( 1·43 , 57·41 ) = 37·22 , P < 0·001 ] . Significantly greater response to treatment occurred in the celecoxib group than in the placebo group at the study end [ 10 patients ( 50 % ) vs. no patient ( 0 % ) , respectively , P < 0·001 ] . No serious adverse event was observed . WHAT IS NEW AND CONCLUSION Celecoxib is a safe and effective treatment for depression due to brucellosis when compared with placebo BACKGROUND Switzerl and introduced a pragmatic national drug policy when the former conservative abstinence-orientated politics proved unable to cope with an escalating number of users and related negative consequences for public health and public order . The high visibility of ' needle parks ' and the size of the acquired immune deficiency disorder ( AIDS ) epidemic called for a new approach and for national leadership . AIMS To describe the intentions , the process and the results of setting up the new treatment approach of prescribing heroin to treatment resistant heroin addicts , as an example of drug policy change . MATERIAL S AND METHODS A systematic collection of relevant documents is analysed and used as evidence for describing the process of policy change . RESULTS Measures to reduce the negative consequences of continued use and to prevent the spread of AIDS were started mainly by private initiatives and soon taken up officially in the ' four-pillar ' drug policy ( including harm reduction , prevention , treatment and law enforcement ) . Medical prescription of heroin to chronic , treatment-resistant heroin addicts was one of the innovations , based on extensive scientific and political preparation . Detailed documentation and evaluation , ample communication of results , adaptations made on the basis of results and extensive public debate helped to consoli date the new policy and heroin-assisted treatment , in spite of its limitations as an observational cohort study . All necessary steps were taken to proceed from a scientific experiment to a routine procedure . DISCUSSION Comparable policy changes have been observed in a few other countries , such as The Netherl and s and Germany , based on the Swiss experience , with equally positive results of heroin-assisted treatment . These experiments were design ed as r and omised controlled trials , comparing intravenous heroin against oral methadone , thereby demonstrating the specific value of pharmaceutical diamorphine for maintenance treatment in opiate dependence . The positive impact of policy change and the positive outcomes of heroin-assisted treatment were acknowledged increasingly nationally and internationally , but made it difficult to continue the process of adapting policy to new challenges , due to the low visibility of present drug problems and to changing political priorities . CONCLUSION A major change in drug policy was effectively realised under typical conditions of a federalist country with a longst and ing tradition of democratic consensus building . Facilitating factors were the size and visibility of the heroin problem , the rise of the Aids epidemic , and a pragmatic attitude of tolerating private initiatives opening the way to official policy change
In conclusion , the role of dairy products for BMC or BMD has been sufficiently established in Chinese and Caucasian girls and women .
In Caucasian women , drinking milk also reduces fracture risk .
The relevance of dairy produce for the diminishment of osteoporotic risk is still a matter of scientific debate due to the outcome of a few single observational studies .