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In 2004, one of us (PJV) wrote a discussion paper entitled ‘Religion, spirituality and psychiatry: A field wide open for discussion and research’ [1] and in 2005, on behalf of the World Psychiatric Association (WPA) Section on Religion, Spirituality and Psychiatry (SRSP), this was circulated amongst colleagues around the world as a basis for discussion. Amongst other groups, this paper was sent to the Spirituality and Psychiatry Special Interest Group (SIG) of the Royal College of Psychiatrists in London, United Kingdom. It was agreed by the SIG and the SRSP that there might be benefit in agreement by WPA on a shorter position paper on the same theme. In November 2006 the SIG and the SRSP agreed towork together on this important project. A position paper was duly drafted, also by one of us (CCHC), and approved by the Executive Committee of the SIG.

[86609-17-8] C20H16CuMn2N4O8 (MW 613.79) InChI = 1S/2C10H8N2.Cu.2Mn.8O/c2*1-3-7-11-9(5-1)10-6-2-4-8-12-10;;;;;;;;;;;/h2*1-8H;;;;;;;;;;;/q;;+2;;;;;;;;;2*-1 InChIKey = MFJBERCSDXBHFL-UHFFFAOYSA-N (oxidant, used for the oxidation of thiols to disulfides,1 benzylic alcohols to carbonyl compounds,2 aromatic amines to azo compounds,2 benzylamine and oximes to the corresponding carbonyl compounds2) Alternate Name: bis(2,2-bipyridine-N,N′)copper(2+) permanganate. Physical Data: purple solid; decomposes at 105–110 °C.2 Solubility: sol water, acetone, and methylene chloride.2 Analysis of Reagent Purity: λmax (log e) (H2O): 290 nm (4.50), 296 (4.59), 306 (4.58), 458, (3.23), 474 (3.28), 491 (3.38), 510 (3.49), 529 (3.57), 552 (3.54), 576 (3.35). Preparative Method: Potassium Permanganate (0.01 mol) dissolved in a minimum of water is added to bis(2,2′-bipyridyl)copper(II) chloride (0.02 mol) in water (25 mL). On cooling a purple precipitate is collected and air dried.2 The yield is 95%. Handling, Storage, and Precautions: oxidant, store in a glass vessel at or below rt. The reagent should be filtered and dried on a filter paper, not on a sintered glass funnel. It should be transferred with nonmetallic spatulas; if metallic spatulas are used the reagent may burst into flame.1

Background Dementia is a collective name for different degenerative brain syndromes which, according to Alzheimer's Disease International, affects approximately 35.6 million people worldwide. The latest NICE guideline for dementia highlights the value of diverse treatment options for the different stages and symptoms of dementia including non-pharmacological treatments. Relevant literature also argues for the value of interventions that acknowledge the complexity of the condition and address the person as a whole, including their physical, emotional, social and cognitive processes. At the same time, there is growing literature that highlights the capacity of the arts and embodied practices to address this complexity. Dance movement therapy is an embodied psychological intervention that can address complexity and thus, may be useful for people with dementia, but its effectiveness remains unclear. Objectives To assess the effects of dance movement therapy on behavioural, social, cognitive and emotional symptoms of people with dementia in comparison to no treatment, standard care or any other treatment. Also, to compare different forms of dance movement therapy (e.g. Laban-based dance movement therapy, Chacian dance movement therapy or Authentic Movement). Search methods Searches took place up to March 2016 through ALOIS, Cochrane Dementia and Cognitive Improvement’s Specialized Register, which covers CENTRAL, a number of major healthcare databases and trial registers, and grey literature sources. We checked bibliographies of relevant studies and reviews, and contacted professional associations, educational programmes and experts from around the world. Selection criteria We considered randomised controlled trials (RCTs) in any language, including cross-over design and cluster-RCTs for inclusion. Studies considered had to include people with dementia, in any age group and in any setting, with interventions delivered by a dance movement therapy practitioner who (i) had received formal training (ii) was a dance movement therapist in training or (iii) was otherwise recognised as a dance movement therapist in the country in which the study was conducted. Data collection and analysis The two review authors independently reviewed studies on an abstract/title level and again after reading the full paper, and we independently evaluated methodological quality. Main results Of the 102 studies identified through electronic searches and personal communication, after de-duplication we screened 80 at title/abstract level. We then reviewed 19 full papers, none of which met the inclusion criteria. Although three studies mentioned dance movement therapy as their intervention, they were excluded because they were not delivered by a qualified dance movement therapy practitioner. As a result, no studies were included in this review. Authors' conclusions Trials of high methodological quality, large sample sizes and clarity in the way the intervention is put together and delivered are needed to assess whether dance movement therapy is an effective intervention for dementia.

Background Dysfunctional breathing is described as chronic or recurrent changes in breathing pattern causing respiratory and non-respiratory symptoms. It is an umbrella term that encompasses hyperventilation syndrome and vocal cord dysfunction. Dysfunctional breathing affects 10% of the general population. Symptoms include dyspnoea, chest tightness, sighing and chest pain which arise secondary to alterations in respiratory pattern and rate. Little is known about dysfunctional breathing in children. Preliminary data suggest 5.3% or more of children with asthma have dysfunctional breathing and that, unlike in adults, it is associated with poorer asthma control. It is not known what proportion of the general paediatric population is affected. Breathing training is recommended as a first-line treatment for adults with dysfunctional breathing (with or without asthma) but no similar recommendations are available for the management of children. As such, breathing retraining is adapted from adult regimens based on the age and ability of the child. Objectives To determine whether breathing retraining in children with dysfunctional breathing has beneficial effects as measured by quality of life indices.To determine whether there are any adverse effects of breathing retraining in young people with dysfunctional breathing. Search methods We identified trials for consideration using both electronic and manual search strategies. We searched CENTRAL, MEDLINE and EMBASE. We searched the National Research Register (NRR) Archive, Health Services Research Projects in Progress (HSRProj), Current Controlled Trials register (incorporating the metaRegister of Controlled Trials and the International Standard Randomised Controlled Trial Number (ISRCTN) to identify research in progress and unpublished research. The latest search was undertaken in October 2013. Selection criteria We planned to include randomised, quasi-randomised or cluster-randomised controlled trials. We excluded observational studies, case studies and studies utilising a cross-over design. The cross-over design was considered inappropriate due to the purported long-lasting effects of breathing retraining. Children up to the age of 18 years with a clinical diagnosis of dysfunctional breathing were eligible for inclusion. We planned to include children with a primary diagnosis of asthma with the intention of undertaking a subgroup analysis. Children with symptoms secondary to cardiac or metabolic disease were excluded.We considered any type of breathing retraining exercise for inclusion in this review, such as breathing control, diaphragmatic breathing, yoga breathing, Buteyko breathing, biofeedback-guided breathing modification and yawn/sigh suppression. We considered programmes where exercises were either supervised (by parents or a health professional, or both) or unsupervised. We also considered relaxation techniques and acute episode management as long as it was clear that breathing exercises were a component of the intervention.Any intervention without breathing exercises or where breathing exercises were not key to the intervention were excluded. Data collection and analysis We planned that two authors (NJB and MJ) would extract data independently using a standardised form. Any discrepancies would be resolved by consensus. Where agreement could not be reached a third review author (MLE) would have considered the paper. Main results We identified 264 potential trials and reviews from the search. Following removal of duplicates, we screened 224 papers based on title and abstract. We retrieved six full-text papers and further evaluated them but they did not meet the inclusion criteria. There were, therefore, no studies suitable for inclusion in this review. Authors' conclusions The results of this systematic review cannot inform clinical practice as no suitable trials were identified for inclusion. Therefore, it is currently unknown whether these interventions offer any added value in this patient group or whether specific types of breathing exercise demonstrate superiority over others. Given that breathing exercises are frequently used to treat dysfunctional breathing/hyperventilation syndrome, there is an urgent need for well-designed clinical trials in this area. Future trials should conform to the CONSORT statement for standards of reporting and use validated outcome measures. Trial reports should also ensure full disclosure of data for all important clinical outcomes.

Background Guillain-Barre syndrome is an acute symmetric, usually ascending and usually paralysing illness, due to inflammation of peripheral nerves. It is thought to be caused by autoimmune factors, such as antibodies. Plasma exchange removes antibodies and other potentially injurious factors from the blood stream. It involves connecting the patient's blood circulation to a machine which exchanges the plasma for a substitute solution, usually albumin. Several studies have evaluated plasma exchange for Guillain-Barre syndrome. Objectives To systematically review the evidence concerning the efficacy of plasma exchange for treating Guillain-Barre syndrome. Search strategy Search of the Cochrane Neuromuscular Disease Trial Register for randomised trials concerning plasma exchange in Guillain-Barre syndrome, search of the bibliographies of identified papers and enquiry from the authors of the papers. Selection criteria Randomised and quasi-randomised trials of plasma exchange versus sham exchange or supportive treatment. Data collection and analysis Potentially relevant papers were scrutinised by two reviewers and the selection of eligible studies was agreed by them and a third reviewer. Data were extracted by one reviewer and checked by a second reviewer. Some missing data were obtained from the authors of studies. Main results Six eligible trials concerning 649 patients were identified, all comparing plasma exchange versus supportive treatment alone. Primary outcome measures ~bullet~Time to recover walking with aid In the only two trials for which this measure was reported, the median time to recover this ability was faster in the plasma exchange than the control group. ~bullet~Time to onset of motor recovery in mildly affected patients In the one trial for which this measure was available, the time was significantly shortened in the plasma exchange group. Secondary outcome measures ~bullet~Improvement in disability grade at four weeks In five trials, there were significantly more patients who had improved by one disability grade or more in the plasma exchange group as compared to the control group. Patients treated with plasma exchange fared significantly better in the following secondary outcome measures: time to recover walking without aid, percentage of patients requiring artificial ventilation, duration of ventilation, full muscle strength recovery after one year, and severe sequelae after one year. There were less patients with infectious events and cardiac arrhythmias in the plasma exchange than the control group. Subgroup analyses Plasma exchange was beneficial in patients with mild, moderate and severe (needing ventilation) Guillain-Barre syndrome. It was beneficial in patients with a disease duration of seven or less days and also in those with disease lasting more than seven days. However, in the only trial that enrolled patients up to 30 days from disease onset, the benefit of plasma exchange in patients treated after seven days was less apparent. Type of treatment Single studies showed that two plasma exchanges were significantly superior to none for mild Guillain-Barre syndrome and four to two for moderate Guillain-Barre syndrome, but that six were not superior to four for severe Guillain-Barre syndrome requiring ventilation. One study suggested that continuous flow plasma exchange was significantly superior to intermittent flow. Another study found no significant difference between the two techniques. The same study found a significantly higher rate of adverse events with fresh frozen plasma as the replacement fluid than albumin. Plasma exchange compared with cerebrospinal fluid filtration A single trial comparing these two treatments did not show any difference in outcomes but was too small to demonstrate equivalence. Reviewer's conclusions Plasma exchange is the first and only treatment that has been proven to be superior to supportive treatment alone in Guillain-Barre syndrome. Consequently, plasma exchange should be regarded as the treatment against which new treatments, such as intravenous immunoglobulin, should be judged. In mild Guillain-Barre syndrome two sessions of plasma exchange are superior to none. In moderate Guillain-Barre syndrome four sessions are superior to two. In severe Guillain-Barre syndrome six sessions are no better than four. Continuous flow plasma exchange machines may be superior to intermittent flow machines and albumin to fresh frozen plasma as the exchange fluid. Plasma exchange is more beneficial when started within seven days after disease onset rather than later, but was still beneficial in patients treated up to 30 days after disease onset. The value of plasma exchange in children less than 12 years old is not known. There is insufficient evidence to determine whether cerebrospinal fluid filtration is equivalent to plasma exchange.

BACKGROUND: Clinical research affecting how doctors practice medicine is increasingly sponsored by companies that make drugs and medical devices. Previous systematic reviews have found that pharmaceutical-industry sponsored studies are more often favorable to the sponsor's product compared with studies with other sources of sponsorship. A similar association between sponsorship and outcomes have been found for device studies, but the body of evidence is not as strong as for sponsorship of drug studies. This review is an update of a previous Cochrane review and includes empirical studies on the association between sponsorship and research outcome.OBJECTIVES: To investigate whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship.SEARCH METHODS: In this update we searched MEDLINE (2010 to February 2015), Embase (2010 to February 2015), the Cochrane Methodology Register (2015, Issue 2) and Web of Science (June 2015). In addition, we searched reference lists of included papers, previous systematic reviews and author files.SELECTION CRITERIA: Cross-sectional studies, cohort studies, systematic reviews and meta-analyses that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. We had no language restrictions.DATA COLLECTION AND ANALYSIS: Two assessors screened abstracts and identified and included relevant papers. Two assessors extracted data, and we contacted authors of included papers for additional unpublished data. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether the conclusions agreed with the study results. Two assessors assessed risk of bias of included papers. We calculated pooled risk ratios (RR) for dichotomous data (with 95% confidence intervals (CIs)).MAIN RESULTS: Twenty-seven new papers were included in this update and in total the review contains 75 included papers. Industry sponsored studies more often had favorable efficacy results, RR: 1.27 (95% CI: 1.17 to 1.37) (25 papers) (moderate quality evidence), similar harms results RR: 1.37 (95% CI: 0.64 to 2.93) (four papers) (very low quality evidence) and more often favorable conclusions RR: 1.34 (95% CI: 1.19 to 1.51) (29 papers) (low quality evidence) compared with non-industry sponsored studies. Nineteen papers reported on sponsorship and efficacy effect size, but could not be pooled due to differences in their reporting of data and the results were heterogeneous. We did not find a difference between drug and device studies in the association between sponsorship and conclusions (test for interaction, P = 0.98) (four papers). Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment, follow-up and selective outcome reporting. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.25 (95% CI: 1.05 to 1.50) (13 papers), compared with non-industry sponsored studies. In industry sponsored studies, there was less agreement between the results and the conclusions than in non-industry sponsored studies, RR: 0.83 (95% CI: 0.70 to 0.98) (six papers).AUTHORS' CONCLUSIONS: Sponsorship of drug and device studies by the manufacturing company leads to more favorable efficacy results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.

Background There are a limited number of treatment options for patients with ulcerative colitis (UC). An increased risk of thrombosis in UC coupled with an observation that UC patients being treated with anticoagulant therapy for thrombotic events had an improvement in their bowel symptoms led to trials examining the use of unfractionated heparin (UFH) and low molecular weight heparins (LMWH) in patients with active UC. Objectives To review randomized trials examining the efficacy of unfractionated heparin (UFH) or low molecular weight heparins (LMWH) for remission induction in patients with ulcerative colitis. Search strategy The MEDLINE (PUBMED), and EMBASE databases, The Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD group specialized trials register, review papers on ulcerative colitis, and references from identified papers were searched in an effort to identify all randomized trials studying UFH or LMWH use in patients with ulcerative colitis. Abstracts from major gastroenterological meetings were searched to identify research published in abstract form only. Selection criteria Each author independently reviewed potentially relevant trials to determine their eligibility for inclusion based on the criteria identified above. The Jadad scale was used to assess study quality. Studies published in abstract form only were included if the authors could be contacted for further information. Data collection and analysis A data extraction form was developed and used to extract data from included studies. At least 2 authors independently extracted data. Any disagreements were resolved by consensus. Data were analyzed using Review Manager (RevMan 4.2.9). Data were analyzed on an intention-to-treat basis, and treated dichotomously. In cross-over studies, only data from the first arm were included. The primary endpoint was induction of remission, as defined by the studies. Data were combined for analysis if they assessed the same treatments (UFH or LMWH versus placebo or other therapy). If a comparison was only assessed in a single trial, P-values were derived using the chi-square test. If the comparison was assessed in more than one trial, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals (95% CI). The presence of heterogeneity among studies was assessed using the chi-square test (a P value of 0.10 was regarded as statistically significant). If statistically significant heterogeneity was identified the odds ratio and 95% CI were calculated using a random effects model. Main results There were 2 randomized, double-blind studies assessing LMWH versus placebo for the treatment of mild-moderate active UC. Various outcomes were assessed in the 2 studies. LMWH showed no benefit over placebo in any outcome, including clinical remission (OR 1.09; 95% CI 0.26 to 4.63; P = 0.91), clinical improvement (OR 0.73; 95% CI 0.32 to 1.66; P = 0.45 and OR 1.09; 95% CI 0.18 to 6.58; P = 0.92 in the two studies, respectively), endoscopic improvement (OR 1.35; 95% CI 0.29 to 6.18; P = 0.70), or histological improvement (OR 2.00; 95% CI 0.45 to 8.96; P = 0.37). LMWH was also not beneficial when added to standard therapy in a randomized open-label trial in which the outcome measures included clinical remission (OR 0.71; 95% CI 0.17 to 2.95; P = 0.64), clinical improvement (OR 2.00; 95% CI 0.31 to 12.75; P = 0.46), endoscopic remission (OR 0.71; 95% CI 0.17 to 2.95; P = 0.64), or endoscopic improvement (OR 1.40; 95% CI 0.34 to 5.79; P = 0.64). LMWH was well-tolerated and provided no significant benefit for quality of life. One study examining UFH versus corticosteroids in the treatment of severe UC demonstrated inferiority of UFH in clinical improvement as an outcome measure (OR 0.02; 95% CI 0 to 0.40; P = 0.01). Patients assigned to UFH did not improve clinically. More patients assigned to UFH had rectal hemorrhage as an adverse event. Authors' conclusions There is no evidence to support the use of UFH or LMWH for the treatment of active UC. No further trials examining these drugs for patients with UC are warranted, except perhaps a trial of UFH in patients with mild disease. Any benefit found would need to be weighed against a possible increased risk of rectal bleeding in patients with active UC.

Background Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a global threat. Antiviral drugs and vaccinations may be insufficient to prevent their spread. Objectives To review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Search methods We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL 2010, Issue 3), which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to October 2010), OLDMEDLINE (1950 to 1965), EMBASE (1990 to October 2010), CINAHL (1982 to October 2010), LILACS (2008 to October 2010), Indian MEDLARS (2008 to October 2010) and IMSEAR (2008 to October 2010). Selection criteria In this update, two review authors independently applied the inclusion criteria to all identified and retrieved articles and extracted data. We scanned 3775 titles, excluded 3560 and retrieved full papers of 215 studies, to include 66 papers of 67 studies. We included physical interventions (screening at entry ports, isolation, quarantine, social distancing, barriers, personal protection, hand hygiene) to prevent respiratory virus transmission. We included randomised controlled trials (RCTs), cohorts, case-controls, before-after and time series studies. Data collection and analysis We used a standardised form to assess trial eligibility. We assessed RCTs by randomisation method, allocation generation, concealment, blinding and follow up. We assessed non-RCTs for potential confounders and classified them as low, medium and high risk of bias. Main results We included 67 studies including randomised controlled trials and observational studies with a mixed risk of bias. A total number of participants is not included as the total would be made up of a heterogenous set of observations (participant people, observations on participants and countries (object of some studies)). The risk of bias for five RCTs and most cluster-RCTs was high. Observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis. The highest quality cluster-RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Benefit from reduced transmission from children to household members is broadly supported also in other study designs where the potential for confounding is greater. Nine case-control studies suggested implementing transmission barriers, isolation and hygienic measures are effective at containing respiratory virus epidemics. Surgical masks or N95 respirators were the most consistent and comprehensive supportive measures. N95 respirators were non-inferior to simple surgical masks but more expensive, uncomfortable and irritating to skin. Adding virucidals or antiseptics to normal handwashing to decrease respiratory disease transmission remains uncertain. Global measures, such as screening at entry ports, led to a non-significant marginal delay in spread. There was limited evidence that social distancing was effective, especially if related to the risk of exposure. Authors' conclusions Simple and low-cost interventions would be useful for reducing transmission of epidemic respiratory viruses. Routine long-term implementation of some measures assessed might be difficult without the threat of an epidemic.

BACKGROUND: Recurrent chest pain in the absence of coronary artery disease is a common problem which sometimes leads to excess use of medical care. Although many studies have examined the causes of pain in these patients, few clinical trials have evaluated treatment. This is an update of a Cochrane review originally published in 2005 and last updated in 2010. The studies reviewed in this paper provide an insight into the effectiveness of psychological interventions for this group of patients. OBJECTIVES: To assess the effects of psychological interventions for chest pain, quality of life and psychological parameters in people with non‐specific chest pain. SEARCH METHODS: We searched the Cochrane Library (CENTRAL, Issue 4 of 12, 2014 and DARE Issue 2 of 4, 2014), MEDLINE (OVID, 1966 to April week 4 2014), EMBASE (OVID, 1980 to week 18 2014), CINAHL (EBSCO, 1982 to April 2014), PsycINFO (OVID, 1887 to April week 5 2014) and BIOSIS Previews (Web of Knowledge, 1969 to 2 May 2014). We also searched citation lists and contacted study authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) with standardised outcome methodology that tested any form of psychotherapy for chest pain with normal anatomy. Diagnoses included non‐specific chest pain (NSCP), atypical chest pain, syndrome X or chest pain with normal coronary anatomy (as either inpatients or outpatients). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data and assessed quality of studies. We contacted trial authors for further information about the included RCTs. MAIN RESULTS: We included two new papers, one of which was an update of a previously included study. Therefore, a total of 17 RCTs with 1006 randomised participants met the inclusion criteria, with the one new study contributing an additional 113 participants. There was a significant reduction in reports of chest pain in the first three months following the intervention: random‐effects relative risk = 0.70 (95% CI 0.53 to 0.92). This was maintained from three to nine months afterwards: relative risk 0.59 (95% CI 0.45 to 0.76). There was also a significant increase in the number of chest pain‐free days up to three months following the intervention: mean difference (MD) 3.00 (95% CI 0.23 to 5.77). This was associated with reduced chest pain frequency (random‐effects MD ‐2.26, 95% CI ‐4.41 to ‐0.12) but there was no evidence of effect of treatment on chest pain frequency from three to twelve months (random‐effects MD ‐0.81, 95% CI ‐2.35 to 0.74). There was no effect on severity (random‐effects MD ‐4.64 (95% CI ‐12.18 to 2.89) up to three months after the intervention. Due to the nature of the main interventions of interest, it was impossible to blind the therapists as to whether the participant was in the intervention or control arm. In addition, in three studies the blinding of participants was expressly forbidden by the local ethics committee because of issues in obtaining fully informed consent . For this reason, all studies had a high risk of performance bias. In addition, three studies were thought to have a high risk of outcome bias. In general, there was a low risk of bias in the other domains. However, there was high heterogeneity and caution is required in interpreting these results. The wide variability in secondary outcome measures made it difficult to integrate findings from studies. AUTHORS' CONCLUSIONS: This Cochrane review suggests a modest to moderate benefit for psychological interventions, particularly those using a cognitive‐behavioural framework, which was largely restricted to the first three months after the intervention. Hypnotherapy is also a possible alternative. However, these conclusions are limited by high heterogeneity in many of the results and low numbers of participants in individual studies. The evidence for other brief interventions was less clear. Further RCTs of psychological interventions for NSCP with follow‐up periods of at least 12 months are needed.

Background The inequitable distribution of health professionals, within countries, poses an important obstacle to the optimal functioning of health services. Objectives To assess the effectiveness of interventions aimed at increasing the proportion of health professionals working in rural and other underserved areas. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, including specialised register of the Cochrane Effective Practice and Organisation of Care Group; March 2014), MEDLINE (1966 to March 2014), EMBASE (1988 to March 2014), CINAHL (1982 to March 2014), LILACS (February 2014), Science Citation Index and Social Sciences Citation Index (up to April 2014), Global Health (March 2014) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (June 2013). We also searched reference lists of all papers and relevant reviews identified, and contacted authors of relevant papers regarding any further published or unpublished work. Selection criteria Randomised trials, non-randomised trials, controlled before-and-after studies and interrupted time series studies evaluating the effects of various interventions (e.g. educational, financial, regulatory or support strategies) on the recruitment or retention, or both, of health professionals in underserved areas. Data collection and analysis Two review authors independently screened titles and abstracts and assessed full texts of potentially relevant studies for eligibility. Two review authors independently extracted data from eligible studies. Main results For this first update of the original review, we screened 8945 records for eligibility. We retrieved and assessed the full text of 125 studies. Only one study met the inclusion criteria of the review. This interrupted time series study, conducted in Taiwan, found that the implementation of a National Health Insurance scheme in 1995 was associated with improved equity in the geographic distribution of physicians and dentists. We judged the certainty of the evidence provided by this one study very low. Authors' conclusions There is currently limited reliable evidence regarding the effects of interventions aimed at addressing the inequitable distribution of health professionals. Well-designed studies are needed to confirm or refute findings of observational studies of educational, financial, regulatory and supportive interventions that might influence healthcare professionals' decisions to practice in underserved areas. Governments and medical schools should ensure that when interventions are implemented, their impacts are evaluated using scientifically rigorous methods to establish the true effects of these measures on healthcare professional recruitment and retention in rural and other underserved settings.

Background This is an update of a review previously published in 2009. Chronic angina and advanced forms of coronary disease are increasingly more frequent. In spite of the improvement in the efficacy of available revascularization treatments, a subgroup of patients continue suffering from refractory angina. Transmyocardial laser revascularization (TMLR) has been proposed to improve the clinical situation of these patients. Objectives To assess the effects (both benefits and harms) of TMLR versus optimal medical treatment in people with refractory angina who are not candidates for percutaneous coronary angioplasty or coronary artery bypass graft, in alleviating angina severity, reducing mortality and improving ejection fraction. Search methods We searched the following resources up to June 2014: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the metaRegister of Controlled Trials database, ClinicalTrials.gov, and the WHO International Clinical Trials Registry. We applied no languages restrictions. We also checked reference lists of relevant papers. Selection criteria We selected studies if they fulfilled the following criteria: randomized controlled trials (RCTs) of TMLR, by thoracotomy, in patients with Canadian Cardiovascular Society or New York Heart Association angina grade III-IV who were excluded from other revascularization procedures. Data collection and analysis Three authors independently extracted data for each trial about the population and interventions compared and assessed the risk of bias of the studies, evaluating randomisation sequence generation, allocation concealment, blinding (of participants, personnel and outcome assessors), incomplete outcome data, selective outcome reporting, and other potential sources of bias. Main results From a total of 502 references, we retrieved 47 papers for more detailed evaluation. We selected 20 papers, reporting data from seven studies, which included 1137 participants, of which 559 were randomized to TMLR. Participants and professionals were not blinded, which suggests high risk of performance bias. Overall, 43.8% of participants in the treatment group decreased two angina classes, as compared with 14.8% in the control group: odds ratio (OR) 4.63, 95% confidence interval (CI) 3.43 to 6.25), and heterogeneity was present. Mortality by intention-to-treat analysis was similar in both groups at 30 days (4.0% in the TMLR group and 3.5% in the control group), and one year (12.2% in the TMLR group and 11.9% in the control group). However, the 30-day mortality as-treated was 6.8% in the TMLR group and 0.8% in the control group (pooled OR was 3.76, 95% CI 1.63 to 8.66), mainly due to a higher mortality in participants crossing from standard treatment to TMLR. The assessment of subjective outcomes, such as improvement in angina, was affected by a high risk of bias and this may explain the differences found. Other adverse events such as myocardial infarction, arrhythmias or heart failure, were not considered in this review, as they were not predefined outcomes in trials design and they show a high inconsistency across studies. No new trials on transmyocardial laser revascularization have been published in the last ten years and it is very unlikely that new research will be undertaken in this field. Authors' conclusions This review shows that risks associated with TMLR outweigh the potential clinical benefits. Subjective outcomes are subject to high risk of bias and no differences were found in survival, but a significant increase in postoperative mortality and other safety outcomes suggests that the procedure may pose unacceptable risks.

The biological limitations to cardiac regenerative growth create a clinical need to promote more efficient cardiac repair. Experimental studies and early-phase clinical trials indicate that progenitor cells may be useful as a therapeutic tool to improve heart function after myocardial ischaemia. This paper will summarize experimental studies to determine (1) the mechanisms underlying progenitor cell homing to ischaemic tissue and (2) to define transcription factors involved in endothelial maturation of progenitor cells. Homing seems to be assisted by a proteolytic enzyme, cathepsin L, which degrades the extracellular matrix. In an in vitro assay, a cathepsin inhibitor prevented different progenitor cell populations from passing through a matrigel layer. In vivo, progenitor cells lacking cathepsin L had an impaired capacity to promote neovascularization in ischaemic mouse limbs compared with normal, wild-type cells. Differentiation of progenitor cells towards the endothelial phenotype involves a member of the homeobox gene family, HoxA9. HoxA9 regulates endothelial gene expression (eNOS, KDR, VE-cadherin). Moreover, HoxA9-deficient mice have a severe impairment of neovascularization capacity after ischaemia. In the second part of the paper, we describe clinical studies using bone marrow or the peripheral blood-derived cells for functional recovery of patients with acute and chronic heart failure (TOPCARE-AMI, TOPCARE-CHF). Whereas blood-derived and bone marrow-derived progenitor cells were equally effective in patients with acute myocardial infarction, bone marrow-derived cells were significantly better than blood-derived progenitor cells in patients with chronic ischaemic heart disease.

BACKGROUND: Printed educational materials are widely used passive dissemination strategies to improve the quality of clinical practice and patient outcomes. Traditionally they are presented in paper formats such as monographs, publication in peer‐reviewed journals and clinical guidelines. OBJECTIVES: To assess the effect of printed educational materials on the practice of healthcare professionals and patient health outcomes. To explore the influence of some of the characteristics of the printed educational materials (e.g. source, content, format) on their effect on professional practice and patient outcomes. SEARCH METHODS: For this update, search strategies were rewritten and substantially changed from those published in the original review in order to refocus the search from published material to printed material and to expand terminology describing printed materials. Given the significant changes, all databases were searched from start date to June 2011. We searched: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), HealthStar, CINAHL, ERIC, CAB Abstracts, Global Health, and the EPOC Register. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi‐randomised trials, controlled before and after studies (CBAs) and interrupted time series (ITS) analyses that evaluated the impact of printed educational materials (PEMs) on healthcare professionals' practice or patient outcomes, or both. We included three types of comparisons: (1) PEM versus no intervention, (2) PEM versus single intervention, (3) multifaceted intervention where PEM is included versus multifaceted intervention without PEM. There was no language restriction. Any objective measure of professional practice (e.g. number of tests ordered, prescriptions for a particular drug), or patient health outcomes (e.g. blood pressure) were included. DATA COLLECTION AND ANALYSIS: Two review authors undertook data extraction independently, and any disagreement was resolved by discussion among the review authors. For analyses, the included studies were grouped according to study design, type of outcome (professional practice or patient outcome, continuous or dichotomous) and type of comparison. For controlled trials, we reported the median effect size for each outcome within each study, the median effect size across outcomes for each study and the median of these effect sizes across studies. Where the data were available, we re‐analysed the ITS studies and reported median differences in slope and in level for each outcome, across outcomes for each study, and then across studies. We categorised each PEM according to potential effects modifiers related to the source of the PEMs, the channel used for their delivery, their content, and their format. MAIN RESULTS: The review includes 45 studies: 14 RCTs and 31 ITS studies. Almost all the included studies (44/45) compared the effectiveness of PEM to no intervention. One single study compared paper‐based PEM to the same document delivered on CD‐ROM. Based on seven RCTs and 54 outcomes, the median absolute risk difference in categorical practice outcomes was 0.02 when PEMs were compared to no intervention (range from 0 to +0.11). Based on three RCTs and eight outcomes, the median improvement in standardised mean difference for continuous profession practice outcomes was 0.13 when PEMs were compared to no intervention (range from ‐0.16 to +0.36). Only two RCTs and two ITS studies reported patient outcomes. In addition, we re‐analysed 54 outcomes from 25 ITS studies, using time series regression and observed statistically significant improvement in level or in slope in 27 outcomes. From the ITS studies, we calculated improvements in professional practice outcomes across studies after PEM dissemination (standardised median change in level = 1.69). From the data gathered, we could not comment on which PEM characteristic influenced their effectiveness. AUTHORS' CONCLUSIONS: The results of this review suggest that when used alone and compared to no intervention, PEMs may have a small beneficial effect on professional practice outcomes. There is insufficient information to reliably estimate the effect of PEMs on patient outcomes, and clinical significance of the observed effect sizes is not known. The effectiveness of PEMs compared to other interventions, or of PEMs as part of a multifaceted intervention, is uncertain.

Background Occlusal interventions may be used in adults with periodontitis. At present there is little consensus regarding the indications and effectiveness of occlusal interventions in periodontal patients. Objectives To identify and analyse the evidence for the effect of occlusal interventions on adults who have periodontitis in relation to tooth loss, probing depths, clinical attachment level, adverse effects and patient-centred outcomes. Search methods The search was last conducted in April 2008. We searched the Cochrane Oral Health Group's Trials Register (to 30th April 2008); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 1); MEDLINE (1966 to 30th April 2008); and EMBASE (1980 to 30th April 2008). There were no language restrictions. Selection criteria We included randomised controlled trials (RCTs) assessing occlusal interventions in patients with periodontitis with a follow up of at least 3 months. Data collection and analysis Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. Any disagreements between the review authors were resolved by discussion. The main investigator of the included trial was contacted to obtain missing information. The Cochrane Collaboration statistical guidelines were to be followed for data synthesis. Main results Abstracts of 54 papers were identified by the search. One paper was eligible for inclusion. This paper studied the effect of occlusal adjustment against no occlusal adjustment in patients who were treated with non-surgical and surgical periodontal therapy. Methodological quality assessment of the included paper revealed that randomisation of the patients into the treatment groups was adequate. Allocation concealment, masking of patients and clinicians were not reported and no response to author contact was received.Mean change in attachment level and mean pocket depth were reported in the included trial. Mean difference in clinical attachment level between occlusal intervention and control in the non-surgical group amounted to 0.38 mm (95% confidence interval (CI) 0.04 to 0.72) favouring the occlusal intervention group and was statistically significant. In the surgical group the mean difference in clinical attachment level between occlusal intervention and control amounted to 0.40 mm (95% CI 0.05 to 0.75) favouring the occlusal intervention group and was also statistically significant. The difference in mean pocket depth reduction between the occlusal intervention and control in both the surgical and non-surgical groups was less than 0.1 mm and was not statistically significant. Tooth loss, patient-centred affects and adverse effects were not reported. Meta-analysis was not possible due to the inclusion of only one study. Authors' conclusions There is only one randomised trial that has addressed this question. The data from this study are inconclusive. We therefore conclude there is no evidence for or against the use of occlusal interventions in clinical practice. This question can only be addressed by adequately powered bias-protected randomised controlled trials.

Background Viral epidemics or pandemics such as of influenza or severe acute respiratory syndrome (SARS) pose a significant threat. Antiviral drugs and vaccination may not be adequate to prevent catastrophe in such an event. Objectives To systematically review the evidence of effectiveness of interventions to interrupt or reduce the spread of respiratory viruses (excluding vaccines and antiviral drugs, which have been previously reviewed). Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to November 2006); OLDMEDLINE (1950 to 1965); EMBASE (1990 to November 2006); and CINAHL (1982 to November 2006). Selection criteria We scanned 2300 titles, excluded 2162 and retrieved the full papers of 138 trials, including 49 papers of 51 studies. The quality of three randomised controlled trials (RCTs) was poor; as were most cluster RCTs. The observational studies were of mixed quality. We were only able to meta-analyse case-control data. We searched for any interventions to prevent viral transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection and hygiene). Study design included RCTs, cohort studies, case-control studies, cross-over studies, before-after, and time series studies. Data collection and analysis We scanned the titles, abstracts and full text articles using a standardised form to assess eligibility. RCTs were assessed according to randomisation method, allocation generation, concealment, blinding, and follow up. Non-RCTs were assessed for the presence of potential confounders and classified as low, medium, and high risk of bias. Main results The highest quality cluster RCTs suggest respiratory virus spread can be prevented by hygienic measures around younger children. Additional benefit from reduced transmission from children to other household members is broadly supported in results of other study designs, where the potential for confounding is greater. The six case-control studies suggested that implementing barriers to transmission, isolation, and hygienic measures are effective at containing respiratory virus epidemics. We found limited evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks. The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease respiratory disease remains uncertain. The lack of proper evaluation of global measures such as screening at entry ports and social distancing prevent firm conclusions about these measures. Authors' conclusions Many simple and probably low-cost interventions would be useful for reducing the transmission of epidemic respiratory viruses. Routine long-term implementation of some of the measures assessed might be difficult without the threat of a looming epidemic.

Background Various methods of sedation and analgesia have been used for pain relief during oocyte recovery in IVF/ICSI procedures. The choice of agents has also been influenced by quality of analgesia as well as by concern about possible detrimental effects on reproductive outcome. Objectives To assess the efficacy of conscious sedation and analgesia versus alternative methods on pregnancy outcomes and pain relief in patients undergoing transvaginal oocyte retrieval. Search strategy We searched the Specialised Register of the Menstrual Disorders and Subfertility Group, The Central Register of Controlled Trials (CENTRAL) , MEDLINE (1966 to present), EMBASE (1980 to present), CINAHL (1982 to present), the National Research Register, and Current Controlled Trials. There was no language restriction. All references in the identified trials and background papers were checked and authors contacted to identify relevant published and unpublished data. Selection criteria Only randomised controlled trials comparing conscious sedation and analgesia versus alternative methods for pain relief during oocyte recovery were included. Data collection and analysis Two reviewers independently scanned abstracts of the reports identified by electronic searching to identify relevant papers, extracted data and assessed trial quality. Interventions were classified and analysed under broad categories/strategies of pain relief comparing conscious sedation/analgesia with alternative methods and administration protocols. Main results Our search strategy identified 390 potentially eligible reports and 12 papers met our inclusion criteria. There were no significant differences in clinical pregnancy rates per woman and patient satisfaction between the methods compared. Women's perception of pain showed conflicting results. Due to considerable heterogeneity, in terms of types and dosages of sedation or analgesia used, and tools used to assess the principal outcomes of pain and satisfaction, a meta-analysis of all the studies was not attempted. Of the three trials which compared the effect of conventional medical analgesia plus paracervical block versus electro-acupuncture plus paracervical block, there was no significant difference in clinical pregnancy rates per woman in the two groups (OR 1.01; 95% CI 0.73 to 1.4). For intra-operative pain score as measured by visual analogue scale (VAS), there was a significant difference (WMD -4.95; 95% CI -7.84 to -2.07), favouring conventional medical analgesia plus paracervical block . There was also a significant difference in intra-operative pain by VAS between patient-controlled sedation and physician-administered sedation (WMD 5.98; 95% CI 1.63 to 10.33), favouring physician -administered sedation. However, as different types and dosages of sedative and analgesic agents were used in these trials, these data should be interpreted with caution. For the rest of the trials, a descriptive summary of the outcomes was presented. Authors' conclusions There is insufficient evidence to determine the effect of different methods of pain relief when compared with conscious sedation and analgesia used during oocyte recovery. In this review, no one particular pain relief method or delivery system appeared to be better than the other. In future, greater consensus is needed to determine both the tools used to evaluate pain and the timing of pain evaluation during and after the procedure. Pain assessment using both subjective and objective measures may merit consideration. In addition, future trials should include intra- and post-operative adverse respiratory and cardiovascular events as outcomes.

Background NSAIDs are widely applied to treat cancer pain and are frequently combined with opioids in combination preparations for this purpose. However, it is unclear which agent is most clinically efficacious for relieving cancer-related pain, or even what may be the additional benefit of combining an NSAID with an opioid in this setting. Objectives To assess the effects of NSAIDs, alone or combined with opioids, for the treatment of cancer pain. Search methods CENTRAL (Issue 2, 2002), MEDLINE (January 1966 to March 2003), EMBASE (January 1980 to December 2001), LILACS (January 1984 to December 2001) were searched. Selection criteria Randomized controlled trials (RCTs) and controlled clinical trials that compared NSAID versus placebo; NSAID versus NSAID; NSAID versus NSAID plus opioid; opioid versus opioid plus NSAID; or NSAID versus opioid. Data collection and analysis Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse event information was collected from trials. Where there was disagreement between reviewers, the opinion of an additional reviewer was sought to resolve the issue. Main results Forty-two trials involving 3084 patients were included. Clinical heterogeneity of study methods and outcomes precluded meta-analyses and only supported a qualitative systematic review. Seven of eight papers that compared NSAID with placebo demonstrated superior efficacy of NSAID with no difference in side effects. Thirteen papers compared one NSAID with another; four reported increased efficacy of one NSAID over another. Four different studies found that one NSAID had fewer side effects than one or more others. Twenty-three studies compared NSAIDs and opioids in combination or alone with NSAID/opioid combinations. Thirteen out of 14 studies found no difference, or low clinical difference, when combining an NSAID plus an opioid versus either drug alone. Comparisons between various NSAID/opioid combinations were inconclusive. Nine studies assessed the association between dose and efficacy and safety. Four papers demonstrated increased efficacy with increased dose, but no dose-dependent increase in side effects within the dose ranges studied. Study duration ranged from single dose studies performed over six hours to crossover studies lasting six weeks; however, the majority of studies were of less than seven days duration. Authors' conclusions Based upon limited data, NSAIDs appear to be more effective than placebo for cancer pain; clear evidence to support superior safety or efficacy of one NSAID over another is lacking; and trials of combinations of an NSAID with an opioid have disclosed either no difference (4 out of 14 papers), a statistically insignificant trend towards superiority (1 out of 14 papers), or at most a slight but statistically significant advantage (9 out of 14 papers), compared with either single entity. The short duration of studies undermines generalization of their findings on efficacy and safety of NSAIDs for cancer pain.

Background The improvement of renal allograft survival by pre-transplantation transfusions alerted the medical community to the potential detrimental effect of transfusions in patients being treated for cancer. Objectives The present meta-analysis aims to evaluate the role of perioperative blood transfusions (PBT) on colorectal cancer recurrence. This is accomplished by validating the results of a previously published meta-analysis (Amato 1998); and by updating it to December 2004. Search strategy Published papers were retrieved using Medline, EMBASE, the Cochrane Library, controlled trials web-based registries, or the CCG Trial Database. The search strategy used was: {colon OR rectal OR colorectal} WITH {cancer OR tumor OR neoplasm} AND transfusion. The tendency not to publish negative trials was balanced by inspecting the proceedings of international congresses. Selection criteria Patients undergoing curative resection of colorectal cancer (classified either as Dukes stages A-C, Astler-Coller stages A-C2, or TNM stages T1-3a/N0-1/M0) were included if they had received any amount of blood products within one month of surgery. Excluded were patients with distant metastases at surgery, and studies with short follow-up or with no data. Data collection and analysis A specific form was developed for data collection. Data extraction was cross-checked, using the most recent publication in case of repetitive ones. Papers' quality was ranked using the method by Evans and Pollock. Odds ratios (OR, with 95% confidence intervals) were computed for each study, and pooled estimates were generated by RevMan (version 4.2). When available, data were stratified for risk factors of cancer recurrence. Main results The findings of the 1998 meta-analysis were confirmed, with small variations in some estimates. Updating it through December 2004 led to the identification of 237 references. Two-hundred and one of them were excluded because they analyzed survival (n=22), were repetitive (n=26), letters/reviews (n=66) or had no data (n=87). Thirty-six studies on 12,127 patients were included: 23 showed a detrimental effect of PBT; 22 used also multivariable analyses, and 14 found PBT to be an independent prognostic factor. Pooled estimates of PBT effect on colorectal cancer recurrence yielded overall OR of 1.42 (95% CI, 1.20 to 1.67) against transfused patients in randomized controlled studies. Stratified meta-analyses confirmed these findings, also when stratifying patients by site and stage of disease. The PBT effect was observed regardless of timing, type, and in a dose-related fashion, although heterogeneity was detected. Data on surgical techniques was not available for further analysis. Authors' conclusions This updated meta-analysis confirms the previous findings. All analyses support the hypothesis that PBT have a detrimental effect on the recurrence of curable colorectal cancers. However, since heterogeneity was detected and conclusions on the effect of surgical technique could not be drawn, a causal relationship cannot still be claimed. Carefully restricted indications for PBT seems necessary.

Background Panic disorder is characterised by repeated, unexpected panic attacks, which represent a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes, and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. It is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, the National Institute for Health and Care Excellence (NICE) and the British Association for Psychopharmacology consider antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Several classes of antidepressants have been studied and compared, but it is still unclear which antidepressants have a more or less favourable profile in terms of effectiveness and acceptability in the treatment of this condition. Objectives To assess the effects of antidepressants for panic disorder in adults, specifically: 1. to determine the efficacy of antidepressants in alleviating symptoms of panic disorder, with or without agoraphobia, in comparison to placebo; 2. to review the acceptability of antidepressants in panic disorder, with or without agoraphobia, in comparison with placebo; and 3. to investigate the adverse effects of antidepressants in panic disorder, with or without agoraphobia, including the general prevalence of adverse effects, compared to placebo. Search methods We searched the Cochrane Common Mental Disorders' (CCMD) Specialised Register, and CENTRAL, MEDLINE, EMBASE and PsycINFO up to May 2017. We handsearched reference lists of relevant papers and previous systematic reviews. Selection criteria All double-blind, randomised, controlled trials (RCTs) allocating adults with panic disorder to antidepressants or placebo. Data collection and analysis Two review authors independently checked eligibility and extracted data using a standard form. We entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details and settings. Primary outcomes included failure to respond, measured by a range of response scales, and treatment acceptability, measured by total number of dropouts for any reason. Secondary outcomes included failure to remit, panic symptom scales, frequency of panic attacks, agoraphobia, general anxiety, depression, social functioning, quality of life and patient satisfaction, measured by various scales as defined in individual studies. We used GRADE to assess the quality of the evidence for each outcome Main results Forty-one unique RCTs including 9377 participants overall, of whom we included 8252 in the 49 placebo-controlled arms of interest (antidepressant as monotherapy and placebo alone) in this review. The majority of studies were of moderate to low quality due to inconsistency, imprecision and unclear risk of selection and performance bias. We found low-quality evidence that revealed a benefit for antidepressants as a group in comparison with placebo in terms of efficacy measured as failure to respond (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.66 to 0.79; participants = 6500; studies = 30). The magnitude of effect corresponds to a number needed to treat for an additional beneficial outcome (NNTB) of 7 (95% CI 6 to 9): that means seven people would need to be treated with antidepressants in order for one to benefit. We observed the same finding when classes of antidepressants were compared with placebo. Moderate-quality evidence suggested a benefit for antidepressants compared to placebo when looking at number of dropouts due to any cause (RR 0.88, 95% CI 0.81 to 0.97; participants = 7850; studies = 30). The magnitude of effect corresponds to a NNTB of 27 (95% CI 17 to 105); treating 27 people will result in one person fewer dropping out. Considering antidepressant classes, TCAs showed a benefit over placebo, while for SSRIs and serotonin-norepinephrine reuptake inhibitor (SNRIs) we observed no difference. When looking at dropouts due to adverse effects, which can be considered as a measure of tolerability, we found moderate-quality evidence showing that antidepressants as a whole are less well tolerated than placebo. In particular, TCAs and SSRIs produced more dropouts due to adverse effects in comparison with placebo, while the confidence interval for SNRI, noradrenergic reuptake inhibitors (NRI) and other antidepressants were wide and included the possibility of no difference. Authors' conclusions The identified studies comprehensively address the objectives of the present review. Based on these results, antidepressants may be more effective than placebo in treating panic disorder. Efficacy can be quantified as a NNTB of 7, implying that seven people need to be treated with antidepressants in order for one to benefit. Antidepressants may also have benefit in comparison with placebo in terms of number of dropouts, but a less favourable profile in terms of dropout due to adverse effects. However, the tolerability profile varied between different classes of antidepressants. The choice of whether antidepressants should be prescribed in clinical practice cannot be made on the basis of this review. Limitations in results include funding of some studies by pharmaceutical companies, and only assessing short-term outcomes. Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.

Pain on biting or chewing can originate from the temporomandibular joints, muscles of mastication, teeth or soft tissues of the oral cavity. The most common cause is a periapical infection associated with a tooth with a necrotic pulp. The patient can identify the tooth; the tooth is tender to percussion; there is a negative response to pulp sensibility testing; there may be a previous history of pulpitis; and frequently there are associated radiographic changes. Teeth in traumatic occlusion can be sensitive to biting forces. Some teeth are in traumatic occlusion only over a small range of a complete excursive movement. Careful testing with articulating paper will usually identify the exact location or spot of the traumatic interference. The pain may be from any of a large number of sources both in and outside the oral cavity. Submandibular pain and eating are frequently associated with a pathosis of the submandibular gland.

Background Morbidity and mortality in patients with symptomatic chronic heart failure is high, it predisposes to stroke and thromboembolism which in turn contribute to high mortality in heart failure. Objectives To determine effect of antiplatelet agents when compared to placebo or anticoagulant therapy on death and/or major thromboembolic events in adults with heart failure who are in sinus rhythm. Search strategy Systematic search of electronic databases (MEDLINE, EMBASE, DARE). Abstracts from cardiology meetings and reference lists of relevant papers were searched. Authors of studies were contacted for further information. Selection criteria Randomised parallel group placebo or controlled trials comparing antiplatelet therapy with control or anticoagulation in adults with chronic heart failure in sinus rhythm. Treatment for at least 1 month. To assess any adverse effects cohort study & non-randomised controlled studies were assessed. Orally administered antiplatelet agents e.g. non-steroidal anti-inflammatory agents, TICLOPIDINE, CLOPIDOGREL, DIPYRIDAMOLE, ASPIRIN compared with anticoagulant agents e.g. COUMARINS, WARFARIN or placebo. Data collection and analysis Data were extracted by two reviewers independently. No meta-analyses were performed as no data were available from randomised comparisons. The data extracted included data relating to the complexities of the topic area, such as patient characteristics and concomitant treatments, as well as data relating to study eligibility, quality, and outcomes. Non-randomised studies were used to identify side-effects caused by anticoagulants. Main results One RCT of warfarin, aspirin versus no antithrombotic therapy was found but no definitive data have yet been published. Three retrospective, non-randomised cohort studies from the V-HeFT, SOLVD and SAVE trials examining the role of ACE inhibitors have examined the role of aspirin therapy +/- anticoagulant therapy in patients with heart failure and/or left ventricular systolic dysfunction. The results from these trials were conflicting. Reviewer's conclusions At present there is no evidence from long term RCTs to recommend use of aspirin to prevent thromboembolism in patients with heart failure in sinus rhythm. A possible interaction with ACE inhibitors may reduce the efficacy of aspirin, although this evidence is from retrospective analyses of trial cohorts. There is also no evidence to indicate superior effects from oral anticoagulation, when compared to aspirin, in patients with heart failure in sinus rhythm.

Increasingly, researchers are turning their attention to the issue of aggression and violence perpetrated by girls and women. This reflects mounting evidence from several related fields of research including: criminal justice, corrections, forensic psychology and psychiatry, domestic violence, child and elder abuse, and delinquency and juvenile justice. Together, this research supports several broad conclusions: (i) the assumption of female nonviolence is untenable; (ii) rates of female-perpetrated aggression are escalating; (iii) aggression by females often has serious negative implications for victims; and (iv) there is insufficient research of risk and protective factors, developmental trajectories, and clinical programs to prevent and reduce female aggression. In this paper, we report the prevalence and incidence of aggression among females; document sex differences and similarities in aggressive and violent behavior; and examine sex-specific versus common risk factors. We conclude with clinical implications for prevention and intervention and reflect on gaps in knowledge and directions for future research. Keywords: female; gender; women; girls; violence; aggression

Background Cardiovascular disease, which includes coronary artery disease, stroke and peripheral vascular disease, is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor for cardiovascular disease is an elevated circulating total homocysteine level. The impact of homocysteine-lowering interventions, given to patients in the form of vitamins B6, B9 or B12 supplements, on cardiovascular events has been investigated. This is an update of a review previously published in 2009, 2013, and 2015. Objectives To determine whether homocysteine-lowering interventions, provided to patients with and without pre-existing cardiovascular disease are effective in preventing cardiovascular events, as well as reducing all-cause mortality, and to evaluate their safety. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 5), MEDLINE (1946 to 1 June 2017), Embase (1980 to 2017 week 22) and LILACS (1986 to 1 June 2017). We also searched Web of Science (1970 to 1 June 2017). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. Selection criteria We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. Data collection and analysis We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We calculated the number needed to treat for an additional beneficial outcome (NNTB). We measured statistical heterogeneity using the I2 statistic. We used a random-effects model. We conducted trial sequential analyses, Bayes factor, and fragility indices where appropriate. Main results In this third update, we identified three new randomised controlled trials, for a total of 15 randomised controlled trials involving 71,422 participants. Nine trials (60%) had low risk of bias, length of follow-up ranged from one to 7.3 years. Compared with placebo, there were no differences in effects of homocysteine-lowering interventions on myocardial infarction (homocysteine-lowering = 7.1% versus placebo = 6.0%; RR 1.02, 95% confidence interval (CI) 0.95 to 1.10, I2 = 0%, 12 trials; N = 46,699; Bayes factor 1.04, high-quality evidence), death from any cause (homocysteine-lowering = 11.7% versus placebo = 12.3%, RR 1.01, 95% CI 0.96 to 1.06, I2 = 0%, 11 trials, N = 44,817; Bayes factor = 1.05, high-quality evidence), or serious adverse events (homocysteine-lowering = 8.3% versus comparator = 8.5%, RR 1.07, 95% CI 1.00 to 1.14, I2 = 0%, eight trials, N = 35,788; high-quality evidence). Compared with placebo, homocysteine-lowering interventions were associated with reduced stroke outcome (homocysteine-lowering = 4.3% versus comparator = 5.1%, RR 0.90, 95% CI 0.82 to 0.99, I2 = 8%, 10 trials, N = 44,224; high-quality evidence). Compared with low doses, there were uncertain effects of high doses of homocysteine-lowering interventions on stroke (high = 10.8% versus low = 11.2%, RR 0.90, 95% CI 0.66 to 1.22, I2 = 72%, two trials, N = 3929; very low-quality evidence). We found no evidence of publication bias. Authors' conclusions In this third update of the Cochrane review, there were no differences in effects of homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo on myocardial infarction, death from any cause or adverse events. In terms of stroke, this review found a small difference in effect favouring to homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo. There were uncertain effects of enalapril plus folic acid compared with enalapril on stroke; approximately 143 (95% CI 85 to 428) people would need to be treated for 5.4 years to prevent 1 stroke, this evidence emerged from one mega-trial. Trial sequential analyses showed that additional trials are unlikely to increase the certainty about the findings of this issue regarding homocysteine-lowering interventions versus placebo. There is a need for additional trials comparing homocysteine-lowering interventions combined with antihypertensive medication versus antihypertensive medication, and homocysteine-lowering interventions at high doses versus homocysteine-lowering interventions at low doses. Potential trials should be large and co-operative.

Background Palliative radiotherapy to the chest is often used in patients with lung cancer, but radiotherapy regimens are more often based on tradition than research results. This is an update of a Cochrane review first published in 2001 and previously updated in 2006. Objectives The two objectives of this review were: 1. To assess the effects of different palliative radiotherapy regimens on improving thoracic symptoms in patients with locally advanced or metastatic non-small cell lung cancer who are not suitable for radical RT given with curative intent. 2. To assess the effects of radiotherapy dose on overall survival in patients with locally advanced or metastatic non-small cell lung cancer who are not suitable for radical RT given with curative intent. Search methods The electronic databases MEDLINE (1966 - Jan 2014), EMBASE and the Cochrane Central Register of Controlled Trials, reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished. Two authors (FM and RS) independently identified all studies that may be suitable for inclusion in the review. We updated the search up to January 2014. Selection criteria Randomised controlled clinical trials comparing different regimens of palliative thoracic radiotherapy in patients with non-small cell lung cancer. Data collection and analysis The reviewers assessed search results independently and possible studies were highlighted and the full text obtained. Data were extracted and attempts were made to contact the original authors for missing information. The primary outcome measure was improvement in major thoracic symptoms (degree and duration). Secondary outcome measures were short and long term toxicities, effect on quality of life and overall survival. Patient reported outcomes were reported descriptively. Quantitative data such as survival and toxicity were analysed as dichotomous variables and reported using relative risks (RR). For this update of the review a meta-analysis of the survival data was carried out. Main results Fourteen randomised controlled trials (3576 patients) were included, with no new studies added in this update. There were important differences in the doses of radiotherapy investigated, the patient characteristics including disease stage and performance status and the outcome measures.The doses of RT investigated ranged from 10 Gy in 1 fraction (10Gy/1F) to 60 Gy/30F over six weeks, with a total of 19 different dose/ fractionation regimens. Potential biases were identified in some studies. Methods of randomisation, assessment of symptoms and statistical methods used were unclear in some papers. Withdrawal and drop-outs were accounted for in all but one study. All 13 studies that investigated symptoms reported that major thoracic symptoms improved following RT.There is no strong evidence that any regimen gives greater palliation. Higher dose regimens may give more acute toxicity and some regimens are associated with an increased risk of radiation myelitis. Variation in reporting of toxicities, in particular the absence of clear grading, means results of the meta-analysis should be treated with caution. Meta-analysis of overall survival broken down by performance status, a key variable, is included in this update. Further information was sought from all the original authors if stratified data was not included in the original publication. Three published studies contained sufficient data and seven authors were able to provide further information which represented 1992 patients (56% of all patients). The absence of data for nearly half of the patients has affected the quality of evidence. The meta-analysis showed no significant difference in 1-year overall survival between regimens with fewer radiotherapy fractions compared with regimens with more when patients were stratified by performance status. The results of the meta-analysis of 1-year overall survival for patients with good performance status (WHO performance status 0-1) showed moderately high heterogeneity and a summary result was not thought meaningful. The results of 1-year overall survival for patients with poor performance status was RR 0.96 (95% CI 0.91 to 1.02; moderate quality of evidence). Authors' conclusions Radiotherapy for patients with incurable non-small cell lung cancer can improve thoracic symptoms. Care should be taken with the dose to the spinal cord to reduce the risk of radiation myelopathy. The higher dose, more fractionated palliative radiotherapy regimens do not provide better or more durable palliation and their use to prolong survival is not supported by strong evidence. More research is needed into reducing the acute toxicity of large fraction regimens and into the role of radical compared to high dose palliative radiotherapy. In the future, large trials comparing different RT regimens may be difficult to set up because of the increasing use of systemic chemotherapy. Trials looking at how best to integrate these two modalities, particularly in good PS patients, need to be carried out.

Imaging of hyperpolarized nuclei provides significant new insights into previously inaccessible aspects of disease biology. Many of the biomolecules crucial for understanding and monitoring metabolism are present in low concentration and are often beyond the detection threshold of traditional magnetic resonance spectroscopy and imaging. A solution is to improve sensitivity by a factor of 10 000 or more by temporarily redistributing the populations of nuclear spins in a magnetic field, a process termed hyperpolarization. Nuclei such as 13C in metabolically active biomolecules can be hyperpolarized, providing unprecedented gains in sensitivity for imaging biologic compounds. Although the first US National Cancer Institute-sponsored white paper describing the potential of this new molecular imaging technique was published only 3 years ago, over 60 biomolecules have been polarized and tested in preclinical studies. Moreover, a phase 1 clinical trial of hyperpolarized [1-13C]pyruvate in prostate cancer patients has demonstrated that this powerful technology can be translated to the clinic. This review is focused on the dissolution dynamic nuclear polarization (DNP)-based polarization technique and summarizes the acquisition techniques used for hyperpolarized 13C imaging, in vivo applications of some of the most promising hyperpolarized 13C labeled biomolecules, and its clinical translation. Keywords: hyperpolarized dissolution dynamic nuclear polarization (DNP); carbon-13 magnetic resonance imaging (MRI); 13C magnetic resonance spectroscopic imaging (MRSI); pyruvate; lactate; metabolic imaging; molecular imaging

Background A range of health workforce strategies are needed to address health service demands in low-, middle- and high-income countries. Non-medical prescribing involves nurses, pharmacists, allied health professionals, and physician assistants substituting for doctors in a prescribing role, and this is one approach to improve access to medicines. Objectives To assess clinical, patient-reported, and resource use outcomes of non-medical prescribing for managing acute and chronic health conditions in primary and secondary care settings compared with medical prescribing (usual care). Search methods We searched databases including CENTRAL, MEDLINE, Embase, and five other databases on 19 July 2016. We also searched the grey literature and handsearched bibliographies of relevant papers and publications. Selection criteria Randomised controlled trials (RCTs), cluster-RCTs, controlled before-and-after (CBA) studies (with at least two intervention and two control sites) and interrupted time series analysis (with at least three observations before and after the intervention) comparing: 1. non-medical prescribing versus medical prescribing in acute care; 2. non-medical prescribing versus medical prescribing in chronic care; 3. non-medical prescribing versus medical prescribing in secondary care; 4 non-medical prescribing versus medical prescribing in primary care; 5. comparisons between different non-medical prescriber groups; and 6. non-medical healthcare providers with formal prescribing training versus those without formal prescribing training. Data collection and analysis We used standard methodological procedures expected by Cochrane. Two review authors independently reviewed studies for inclusion, extracted data, and assessed study quality with discrepancies resolved by discussion. Two review authors independently assessed risk of bias for the included studies according to EPOC criteria. We undertook meta-analyses using the fixed-effect model where studies were examining the same treatment effect and to account for small sample sizes. We compared outcomes to a random-effects model where clinical or statistical heterogeneity existed. Main results We included 46 studies (37,337 participants); non-medical prescribing was undertaken by nurses in 26 studies and pharmacists in 20 studies. In 45 studies non-medical prescribing as a component of care was compared with usual care medical prescribing. A further study compared nurse prescribing supported by guidelines with usual nurse prescribing care. No studies were found with non-medical prescribing being undertaken by other health professionals. The education requirement for non-medical prescribing varied with country and location. A meta-analysis of surrogate markers of chronic disease (systolic blood pressure, glycated haemoglobin, and low-density lipoprotein) showed positive intervention group effects. There was a moderate-certainty of evidence for studies of blood pressure at 12 months (mean difference (MD) -5.31 mmHg, 95% confidence interval (CI) -6.46 to -4.16; 12 studies, 4229 participants) and low-density lipoprotein (MD -0.21, 95% CI -0.29 to -0.14; 7 studies, 1469 participants); we downgraded the certainty of evidence from high due to considerations of serious inconsistency (considerable heterogeneity), multifaceted interventions, and variable prescribing autonomy. A high-certainty of evidence existed for comparative studies of glycated haemoglobin management at 12 months (MD -0.62, 95% CI -0.85 to -0.38; 6 studies, 775 participants). While there appeared little difference in medication adherence across studies, a meta-analysis of continuous outcome data from four studies showed an effect favouring patient adherence in the non-medical prescribing group (MD 0.15, 95% CI 0.00 to 0.30; 4 studies, 700 participants). We downgraded the certainty of evidence for adherence to moderate due to the serious risk of performance bias. While little difference was seen in patient-related adverse events between treatment groups, we downgraded the certainty of evidence to low due to indirectness, as the range of adverse events may not be related to the intervention and selective reporting failed to adequately report adverse events in many studies. Patients were generally satisfied with non-medical prescriber care (14 studies, 7514 participants). We downgraded the certainty of evidence from high to moderate due to indirectness, in that satisfaction with the prescribing component of care was only addressed in one study, and there was variability of satisfaction measures with little use of validated tools. A meta-analysis of health-related quality of life scores (SF-12 and SF-36) found a difference favouring non-medical prescriber care for the physical component score (MD 1.17, 95% CI 0.16 to 2.17), and the mental component score (MD 0.58, 95% CI -0.40 to 1.55). However, the quality of life measurement may more appropriately reflect composite care rather than the prescribing component of care, and for this reason we downgraded the certainty of evidence to moderate due to indirectness of the measure of effect. A wide variety of resource use measures were reported across studies with little difference between groups for hospitalisations, emergency department visits, and outpatient visits. In the majority of studies reporting medication use, non-medical prescribers prescribed more drugs, intensified drug doses, and used a greater variety of drugs compared to usual care medical prescribers. The risk of bias across studies was generally low for selection bias (random sequence generation), detection bias (blinding of outcome assessment), attrition bias (incomplete outcome data), and reporting bias (selective reporting). There was an unclear risk of selection bias (allocation concealment) and for other biases. A high risk of performance bias (blinding of participants and personnel) existed. Authors' conclusions The findings suggest that non-medical prescribers, practising with varying but high levels of prescribing autonomy, in a range of settings, were as effective as usual care medical prescribers. Non-medical prescribers can deliver comparable outcomes for systolic blood pressure, glycated haemoglobin, low-density lipoprotein, medication adherence, patient satisfaction, and health-related quality of life. It was difficult to determine the impact of non-medical prescribing compared to medical prescribing for adverse events and resource use outcomes due to the inconsistency and variability in reporting across studies. Future efforts should be directed towards more rigorous studies that can clearly identify the clinical, patient-reported, resource use, and economic outcomes of non-medical prescribing, in both high-income and low-income countries.

BACKGROUND: Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. The efficacy of levetiracetam for relief of neuropathic pain has not previously been reviewed. OBJECTIVES: To assess the analgesic efficacy and adverse events of levetiracetam in chronic neuropathic pain conditions in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6) (via the Cochrane Library), MEDLINE, EMBASE, and two clinical trials databases (ClinicalTrials.gov. and the World Health Organisation Clinical Trials Registry Platform) to 3 July 2014, together with reference lists of retrieved papers and reviews. SELECTION CRITERIA: We included randomised, double‐blind studies of two weeks duration or longer, comparing levetiracetam with placebo or another active treatment in adults with chronic neuropathic pain conditions. Studies had to have a minimum of 10 participants per treatments arm. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction; intention‐to‐treat analysis without imputation for dropouts; at least 200 participants in the comparison; 8 to 12 weeks duration; parallel design); second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with at least 200 participants in the comparison; and third tier evidence from data involving fewer than 200 participants that was considered very likely to be biased or used outcomes of limited clinical utility, or both. MAIN RESULTS: We included six studies: five small, cross‐over studies with 174 participants, and one parallel group study with 170 participants. Participants were treated with levetiracetam (2000 mg to 3000 mg daily) or placebo for between four and 14 weeks. Each study included participants with a different type of neuropathic pain; central pain due to multiple sclerosis, pain following spinal cord injury, painful polyneuropathy, central post‐stroke pain, postherpetic neuralgia, and post‐mastectomy pain. None of the included studies provided first or second tier evidence. The evidence was very low quality, downgraded because of the small size of the treatment arms, and because studies reported results using last observation carried forward (LOCF) imputation for withdrawals or using only participants who completed the study according to the protocol, where there were greater than 10% withdrawals. There were insufficient data for a pooled efficacy analysis in particular neuropathic pain conditions, but individual studies did not show any analgesic effect of levetiracetam compared with placebo. We did pool results for any outcome considered substantial pain relief (≥ 50% pain intensity reduction or ‘complete’ or ‘good’ responses on the verbal rating scale) for four studies with dichotomous data; response rates across different types of neuropathic pain was similar with levetiracetam (10%) and placebo (12%), with no statistical difference (risk ratio 0.9; 95% confidence interval (CI) 0.4 to1.7). We pooled data across different conditions for adverse events and withdrawals. Based on very limited data, significantly more participants experienced an adverse event with levetiracetam than with placebo (number needed to treat for an additional harmful event (NNH) 8.0 (95% CI 4.6 to 32)). There were significantly more adverse event withdrawals with levetiracetam (NNH 9.7 (6.7 to 18)). AUTHORS' CONCLUSIONS: The amount of evidence for levetiracetam in neuropathic pain conditions was very small and potentially biased because of the methods of analysis used in the studies. There was no indication that levetiracetam was effective in reducing neuropathic pain, but it was associated with an increase in participants who experienced adverse events and who withdrew due to adverse events.

BACKGROUND: Dual-method contraception refers to using condoms as well as another modern method of contraception. The latter (usually non-barrier) method is commonly hormonal (e.g. oral contraceptives) or a non-hormonal intrauterine device. Use of two methods can better prevent pregnancy and the transmission of HIV and other sexually transmitted infections (STIs) compared to single-method use. Unprotected sex increases risk for disease disability and mortality in many areas due to the prevalence and incidence of HIV/STI. Millions of women especially in lower-resource areas also have an unmet need for protection against unintended pregnancy. OBJECTIVES: We examined comparative studies of behavioral interventions for improving use of dual methods of contraception. Dual-method use refers to using condoms as well as another modern contraceptive method. Our intent was to identify effective interventions for preventing pregnancy as well as HIV/STI transmission. SEARCH METHODS: Through January 2014 we searched MEDLINE CENTRAL POPLINE EMBASE COPAC and Open Grey. In addition we searched ClinicalTrials.gov and ICTRP for current trials and trials with relevant data or reports. We examined reference lists of pertinent papers including review articles for additional reports. SELECTION CRITERIA: Studies could be either randomized or non-randomized. They examined a behavioral intervention with an educational or counseling component to encourage or improve the use of dual methods i.e. condoms and another modern contraceptive. The intervention had to address preventing pregnancy as well as the transmission of HIV/STI. The program or service could be targeted to individuals couples or communities. The comparison condition could be another behavioral intervention to improve contraceptive use usual care other health education or no intervention.Studies had to report use of dual methods i.e. condoms plus another modern contraceptive method. We focused on the investigators assessment of consistent dual-method use or use at last sex. Outcomes had to be measured at least three months after the behavioral intervention began. DATA COLLECTION AND ANALYSIS: Two authors evaluated abstracts for eligibility and extracted data from included studies. For the dichotomous outcomes the Mantel-Haenszel odds ratio (OR) with 95% CI was calculated using a fixed-effect model. Where studies used adjusted analysis we presented the results as reported by the investigators. No meta-analysis was conducted due to differences in interventions and outcome measures. MAIN RESULTS: We identified four studies that met the inclusion criteria: three randomized controlled trials and a pilot study for one of the included trials. The interventions differed markedly: computer-delivered individually tailored sessions; phone counseling added to clinic counseling; and case management plus a peer-leadership program. The latter study which addressed multiple risks showed an effect on contraceptive use. Compared to the control group the intervention group was more likely to report consistent dual-method use i.e. oral contraceptives and condoms. The reported relative risk was 1.58 at 12 months (95% CI 1.03 to 2.43) and 1.36 at 24 months (95% CI 1.01 to 1.85). The related pilot study showed more reporting of consistent dual-method use for the intervention group compared to the control group (reported P value = 0.06); the investigators used a higher alpha (P < 0.10) for this pilot study. The other two trials did not show any significant difference between the study groups in reported dual-method use or in test results for pregnancy or STIs at 12 or 24 months. AUTHORS CONCLUSIONS: We found few behavioral interventions for improving dual-method contraceptive use and little evidence of effectiveness. A multifaceted program showed some effect but only had self-reported outcomes. Two trials were more applicable to clinical settings and had objective outcomes measures but neither showed any effect. The included studies had adequate information on intervention fidelity and sufficient follow-up periods for change to occur. However the overall quality of evidence was considered low. Two trials had design limitations and two had high losses to follow up as often occurs in contraceptive trials. Good quality studies are still needed of carefully designed and implemented programs or services.

Background Antidepressants are widely used to treat chronic neuropathic pain (pain due to nerve damage), usually in doses below those at which they exert antidepressant effects. An earlier review that included all antidepressants for neuropathic pain is being replaced by new reviews of individual drugs examining individual neuropathic pain conditions. Desipramine is a tricyclic antidepressant that is occasionally used for treating neuropathic pain. Objectives To assess the analgesic efficacy of desipramine for chronic neuropathic pain in adults, and to assess the associated adverse events. Search methods We searched CENTRAL, MEDLINE, and EMBASE from inception to 29 April 2014, and the reference lists of retrieved papers and other reviews. We also used our own hand searched database to identify older studies, and two clinical trials databases for ongoing or unpublished studies. Selection criteria We included randomised, double-blind studies of at least two weeks duration comparing desipramine with placebo or another active treatment in chronic neuropathic pain. Participants were adults aged 18 years and over. We included only full journal publication articles. Data collection and analysis Two review authors independently extracted the efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts, at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design); second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison; and third tier from data involving small numbers of participants and considered very likely to be biased or that used outcomes of limited clinical utility, or both. Main results Five studies treated 177 participants with painful diabetic neuropathy (104) or postherpetic neuralgia (73). The mean or median ages in the studies were 55 to 72 years. Four studies used a cross-over, and one a parallel group design; 145 participants were randomised to receive desipramine 12.5 mg to 250 mg daily, with most taking 100 mg to 150 mg daily following titration. Comparators were placebo in three studies (an 'active placebo' in two studies), fluoxetine, clomipramine (one study each), and amitriptyline (two studies), and treatment was for two to six weeks. All studies had one or more sources of potential major bias. No study provided first or second tier evidence for any outcome. No data were available on the proportion of people with at least 50% or 30% reduction in pain, but data were available from three studies for our other primary outcome of Patient Global Impression of Change, reported as patient evaluation of pain relief that was 'complete' or 'a lot'. No pooling of data was possible, but third tier evidence in individual studies indicated some improvement in pain relief with desipramine compared with placebo, although this was very low quality evidence, derived mainly from group mean data and completer analyses in small, short duration studies where major bias was possible. There were too few participants in comparisons of desipramine with another active treatment to draw any conclusions. All studies reported some information about adverse events, but reporting was inconsistent and fragmented. Participants taking desipramine experienced more adverse events, and a higher rate of withdrawal due to adverse events, than did participants taking placebo (very low quality evidence). Authors' conclusions This review found little evidence to support the use of desipramine to treat neuropathic pain. There was very low quality evidence of benefit and harm, but this came from studies that were methodologically flawed and potentially subject to major bias. Effective medicines with much greater supportive evidence are available. There may be a role for desipramine in patients who have not obtained pain relief from other treatments.

Family members play an important role in the lives of those who experience dementia. Culture is an important factor in the discussions of family dementia caregiving in Asian American families. Unfortunately, little attention has been placed on understating dementia among Asian Americans partly due to the fact that dementia is still hidden in many communities. The purpose of this paper is to explore the issues related to dementia care in the Asian American community. Keywords: acculturation; cross-cultural; immigration; mental health; stress

Background Research suggests that measurable change in cerebrospinal fluid (CSF) biomarkers occurs years in advance of the onset of clinical symptoms (Beckett 2010). In this review, we aimed to assess the ability of CSF tau biomarkers (t-tau and p-tau) and the CSF tau (t-tau or p-tau)/ABeta ratio to enable the detection of Alzheimer’s disease pathology in patients with mild cognitive impairment (MCI). These biomarkers have been proposed as important in new criteria for Alzheimer's disease dementia that incorporate biomarker abnormalities. Objectives To determine the diagnostic accuracy of 1) CSF t-tau, 2) CSF p-tau, 3) the CSF t-tau/ABeta ratio and 4) the CSF p-tau/ABeta ratio index tests for detecting people with MCI at baseline who would clinically convert to Alzheimer’s disease dementia or other forms of dementia at follow-up. Search methods The most recent search for this review was performed in January 2013. We searched MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection, including Conference Proceedings Citation Index (Thomson Reuters Web of Science), PsycINFO (OvidSP), and LILACS (BIREME). We searched specialized sources of diagnostic test accuracy studies and reviews. We checked reference lists of relevant studies and reviews for additional studies. We contacted researchers for possible relevant but unpublished data. We did not apply any language or data restriction to the electronic searches. We did not use any methodological filters as a method to restrict the search overall. Selection criteria We selected those studies that had prospectively well-defined cohorts with any accepted definition of MCI and with CSF t-tau or p-tau and CSF tau (t-tau or p-tau)/ABeta ratio values, documented at or around the time the MCI diagnosis was made. We also included studies which looked at data from those cohorts retrospectively, and which contained sufficient data to construct two by two tables expressing those biomarker results by disease status. Moreover, studies were only selected if they applied a reference standard for Alzheimer's disease dementia diagnosis, for example, the NINCDS-ADRDA or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Data collection and analysis We screened all titles generated by the electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies, and the full papers for eligibility. Two independent assessors performed data extraction and quality assessment. Where data allowed, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic (ROC) curve. Main results In total, 1282 participants with MCI at baseline were identified in the 15 included studies of which 1172 had analysable data; 430 participants converted to Alzheimer’s disease dementia and 130 participants to other forms of dementia. Follow-up ranged from less than one year to over four years for some participants, but in the majority of studies was in the range one to three years. Conversion to Alzheimer’s disease dementia The accuracy of the CSF t-tau was evaluated in seven studies (291 cases and 418 non-cases).The sensitivity values ranged from 51% to 90% while the specificity values ranged from 48% to 88%. At the median specificity of 72%, the estimated sensitivity was 75% (95% CI 67 to 85), the positive likelihood ratio was 2.72 (95% CI 2.43 to 3.04), and the negative likelihood ratio was 0.32 (95% CI 0.22 to 0.47). Six studies (164 cases and 328 non-cases) evaluated the accuracy of the CSF p-tau. The sensitivities were between 40% and 100% while the specificities were between 22% and 86%. At the median specificity of 47.5%, the estimated sensitivity was 81% (95% CI: 64 to 91), the positive likelihood ratio was 1.55 (CI 1.31 to 1.84), and the negative likelihood ratio was 0.39 (CI: 0.19 to 0.82). Five studies (140 cases and 293 non-cases) evaluated the accuracy of the CSF p-tau/ABeta ratio. The sensitivities were between 80% and 96% while the specificities were between 33% and 95%. We did not conduct a meta-analysis because the studies were few and small. Only one study reported the accuracy of CSF t-tau/ABeta ratio. Our findings are based on studies with poor reporting. A significant number of studies had unclear risk of bias for the reference standard, participant selection and flow and timing domains. According to the assessment of index test domain, eight of 15 studies were of poor methodological quality. The accuracy of these CSF biomarkers for ‘other dementias’ had not been investigated in the included primary studies. Investigation of heterogeneity The main sources of heterogeneity were thought likely to be reference standards used for the target disorders, sources of recruitment, participant sampling, index test methodology and aspects of study quality (particularly, inadequate blinding). We were not able to formally assess the effect of each potential source of heterogeneity as planned, due to the small number of studies available to be included. Authors' conclusions The insufficiency and heterogeneity of research to date primarily leads to a state of uncertainty regarding the value of CSF testing of t-tau, p-tau or p-tau/ABeta ratio for the diagnosis of Alzheimer's disease in current clinical practice. Particular attention should be paid to the risk of misdiagnosis and overdiagnosis of dementia (and therefore over-treatment) in clinical practice. These tests, like other biomarker tests which have been subject to Cochrane DTA reviews, appear to have better sensitivity than specificity and therefore might have greater utility in ruling out Alzheimer's disease as the aetiology to the individual's evident cognitive impairment, as opposed to ruling it in. The heterogeneity observed in the few studies awaiting classification suggests our initial summary will remain valid. However, these tests may have limited clinical value until uncertainties have been addressed. Future studies with more uniformed approaches to thresholds, analysis and study conduct may provide a more homogenous estimate than the one that has been available from the included studies we have identified.

Background Dementia is a progressive global cognitive impairment syndrome. In 2010, more than 35 million people worldwide were estimated to be living with dementia. Some people with mild cognitive impairment (MCI) will progress to dementia but others remain stable or recover full function. There is great interest in finding good predictors of dementia in people with MCI. The Mini-Mental State Examination (MMSE) is the best-known and the most often used short screening tool for providing an overall measure of cognitive impairment in clinical, research and community settings. Objectives To determine the diagnostic accuracy of the MMSE at various thresholds for detecting individuals with baseline MCI who would clinically convert to dementia in general, Alzheimer’s disease dementia or other forms of dementia at follow-up. Search methods We searched ALOIS (Cochrane Dementia and Cognitive Improvement Specialized Register of diagnostic and intervention studies (inception to May 2014); MEDLINE (OvidSP) (1946 to May 2014); EMBASE (OvidSP) (1980 to May 2014); BIOSIS (Web of Science) (inception to May 2014); Web of Science Core Collection, including the Conference Proceedings Citation Index (ISI Web of Science) (inception to May 2014); PsycINFO (OvidSP) (inception to May 2014), and LILACS (BIREME) (1982 to May 2014). We also searched specialized sources of diagnostic test accuracy studies and reviews, most recently in May 2014: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of Abstracts of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). No language or date restrictions were applied to the electronic searches and methodological filters were not used as a method to restrict the search overall so as to maximize sensitivity. We also checked reference lists of relevant studies and reviews, tracked citations in Scopus and Science Citation Index, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on MMSE for dementia diagnosis to try to locate possibly relevant but unpublished data. Selection criteria We considered longitudinal studies in which results of the MMSE administered to MCI participants at baseline were obtained and the reference standard was obtained by follow-up over time. We included participants recruited and clinically classified as individuals with MCI under Petersen and revised Petersen criteria, Matthews criteria, or a Clinical Dementia Rating = 0.5. We used acceptable and commonly used reference standards for dementia in general, Alzheimer’s dementia, Lewy body dementia, vascular dementia and frontotemporal dementia. Data collection and analysis We screened all titles generated by the electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies. We assessed the identified full papers for eligibility and extracted data to create two by two tables for dementia in general and other dementias. Two authors independently performed quality assessment using the QUADAS-2 tool. Due to high heterogeneity and scarcity of data, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic curve. Main results In this review, we included 11 heterogeneous studies with a total number of 1569 MCI patients followed for conversion to dementia. Four studies assessed the role of baseline scores of the MMSE in conversion from MCI to all-cause dementia and eight studies assessed this test in conversion from MCI to Alzheimer´s disease dementia. Only one study provided information about the MMSE and conversion from MCI to vascular dementia. For conversion from MCI to dementia in general, the accuracy of baseline MMSE scores ranged from sensitivities of 23% to 76% and specificities from 40% to 94%. In relationship to conversion from MCI to Alzheimer’s disease dementia, the accuracy of baseline MMSE scores ranged from sensitivities of 27% to 89% and specificities from 32% to 90%. Only one study provided information about conversion from MCI to vascular dementia, presenting a sensitivity of 36% and a specificity of 80% with an incidence of vascular dementia of 6.2%. Although we had planned to explore possible sources of heterogeneity, this was not undertaken due to the scarcity of studies included in our analysis. Authors' conclusions Our review did not find evidence supporting a substantial role of MMSE as a stand-alone single-administration test in the identification of MCI patients who could develop dementia. Clinicians could prefer to request additional and extensive tests to be sure about the management of these patients. An important aspect to assess in future updates is if conversion to dementia from MCI stages could be predicted better by MMSE changes over time instead of single measurements. It is also important to assess if a set of tests, rather than an isolated one, may be more successful in predicting conversion from MCI to dementia.

Background Remote and web 2.0 interventions for promoting physical activity (PA) are becoming increasingly popular but their ability to achieve long term changes are unknown. Objectives To compare the effectiveness of remote and web 2.0 interventions for PA promotion in community dwelling adults (aged 16 years and above) with a control group exposed to placebo or no or minimal intervention. Search methods We searched CENTRAL, MEDLINE, EMBASE, CINAHL, and some other databases (from earliest dates available to October 2012). Reference lists of relevant articles were checked. No language restrictions were applied. Selection criteria Randomised controlled trials (RCTs) that compared remote and web 2.0 PA interventions for community dwelling adults with a placebo or no or minimal intervention control group. We included studies if the principal component of the intervention was delivered using remote or web 2.0 technologies (for example the internet, smart phones) or more traditional methods (for example telephone, mail-outs), or both. To assess behavioural change over time, the included studies had a minimum of 12 months follow-up from the start of the intervention to the final results. We excluded studies that had more than a 20% loss to follow-up if they did not apply an intention-to-treat analysis. Data collection and analysis At least two authors independently assessed the quality of each study and extracted the data. Non-English language papers were reviewed with the assistance of an interpreter who was an epidemiologist. Study authors were contacted for additional information where necessary. Standardised mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for the continuous measures of self-reported PA and cardio-respiratory fitness. For studies with dichotomous outcomes, odds ratios and 95% CIs were calculated. Main results A total of 11 studies recruiting 5862 apparently healthy adults met the inclusion criteria. All of the studies took place in high-income countries. The effect of the interventions on cardiovascular fitness at one year (two studies; 444 participants) was positive and moderate with significant heterogeneity of the observed effects (SMD 0.40; 95% CI 0.04 to 0.76; high quality evidence). The effect of the interventions on self-reported PA at one year (nine studies; 4547 participants) was positive and moderate (SMD 0.20; 95% CI 0.11 to 0.28; moderate quality evidence) with heterogeneity (I2 = 37%) in the observed effects. One study reported positive results at two years (SMD 0.20; 95% CI 0.08 to 0.32; moderate quality evidence). When studies were stratified by risk of bias, the studies at low risk of bias (eight studies; 3403 participants) had an increased effect (SMD 0.28; 95% CI 0.16 to 0.40; moderate quality evidence). The most effective interventions applied a tailored approach to the type of PA and used telephone contact to provide feedback and to support changes in PA levels. There was no evidence of an increased risk of adverse events (seven studies; 2892 participants). Risk of bias was assessed as low (eight studies; 3060 participants) or moderate (three studies; 2677 participants). There were no differences in effectiveness between studies using different types of professionals delivering the intervention (for example health professional, exercise specialist). There was no difference in pooled estimates between studies that generated the prescribed PA using an automated computer programme versus a human, nor between studies that used pedometers as part of their intervention compared to studies that did not. Authors' conclusions We found consistent evidence to support the effectiveness of remote and web 2.0 interventions for promoting PA. These interventions have positive, moderate sized effects on increasing self-reported PA and measured cardio-respiratory fitness, at least at 12 months. The effectiveness of these interventions was supported by moderate and high quality studies. However, there continues to be a paucity of cost effectiveness data and studies that include participants from varying socioeconomic or ethnic groups. To better understand the independent effect of individual programme components, longer term studies, with at least one year follow-up, are required.

Background This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. The use of complementary therapies is increasing and some women look to complementary therapies during pregnancy and childbirth to be used alongside conventional medical practice. Acupuncture involves the insertion of very fine needles into specific points of the body. The limited observational studies to date suggest acupuncture for induction of labour appears safe, has no known adverse effects to the fetus, and may be effective. However, the evidence regarding the clinical effectiveness of this technique is limited. Objectives To determine the effectiveness and safety of acupuncture for third trimester cervical ripening or induction of labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 November 2012), PubMed (1966 to 23 November 2012), Embase (1980 to 23 November 2012), Dissertation Abstracts (1861 to 23 November 2012), CINAHL (1982 to 23 November 2012), the WHO International Clinical Trials Registry Portal (ICTRP) (23 November 2012) and bibliographies of relevant papers. Selection criteria Clinical trials comparing acupuncture used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. Data collection and analysis Two review authors independently assessed trials for inclusion, evaluated methodological quality and extracted data. Main results The original review included three trials and seven trials were excluded. This updated review includes 14 trials, and excludes eight trials. Three trials previously excluded due to no clinically relevant outcomes are now included. Eight new trials were included, and four new trials were excluded. We included 14 trials with data reporting on 2220 women. Trials reported on three primary outcomes only caesarean section, serious neonatal morbidity and maternal mortality. No trial reported on vaginal delivery not achieved within 24 hours; and uterine hyperstimulation with fetal heart rate (FHR) changes. There was no difference in caesarean deliveries between acupuncture and the sham control (average risk ratio (RR) 0.95, 95% confidence interval (CI) 0.69 to 1.30, six trials, 654 women), and acupuncture versus usual care (average RR 0.69, 95% CI 0.40, 1.20, six trials, 361 women). There was no difference in neonatal seizures between acupuncture and the sham group (RR 1.01, 95% CI 0.06 to 16.04, one trial, 364 women). There was some evidence of a change in cervical maturation for women receiving acupuncture compared with the sham control, (mean difference (MD) 0.40. 95%CI 0.11 to 0.69, one trial, 125 women), and when compared with usual care (MD 1.30, 95% CI 0.11 to 2.49, one trial, 67 women). The length of labour was shorter in the usual care group compared with acupuncture (average standardised mean difference (SMD) 0.67, 95% CI 0.18 to 1.17, one trial 68 women). There were no other statistically significant differences between groups. Few studies reported on many clinically relevant outcomes. One trial was at a low risk of bias on all domains. Authors' conclusions Overall, there have been few studies assessing the role of acupuncture for induction of labour. Before implications for clinical practice can be made there is a need for well-designed randomised controlled trials to evaluate the role of acupuncture to induce labour and for trials to assess clinically meaningful outcomes.

Background People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013. Objectives To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016. Selection criteria We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA. Data collection and analysis Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data. Main results We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA. Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology. Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity. We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) -0.37 to 3.77: consolidation; 18 participants; MD -1.50 bleeding events, 95% CI -3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies. Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence). All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD -5.60 platelet units, 95% CI -9.02 to -2.18: induction; 38 participants, MD -1.00 platelet units, 95% CI -9.11 to 7.11; very low-quality evidence). Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence). None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL). Authors' conclusions Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020.

Background Please see Appendix 4 for a glossary of terms. The outcome of patients with esophageal cancer is generally poor. Although multimodal therapy is standard, there is conflicting evidence regarding the addition of esophagectomy to chemoradiotherapy. Objectives To compare the effectiveness and safety of chemoradiotherapy plus surgery with that of chemoradiotherapy alone in people with nonmetastatic esophageal carcinoma. Search methods We performed a computerized search for relevant studies, up to Feburary 2017, on the CENTRAL, MEDLINE, and Embase databases using MeSH headings and keywords. We searched five online databases of clinical trials, handsearched conference proceedings, and screened reference lists of retrieved papers. Selection criteria We included randomized controlled trials (RCTs) comparing chemoradiotherapy plus esophagectomy with chemoradiotherapy alone for localized esophageal carcinoma. We excluded RCTs comparing chemotherapy or radiotherapy alone with esophagectomy. Data collection and analysis Two authors independently selected studies, extracted data, and assessed risk of bias and the quality of the evidence, using standardized Cochrane methodological procedures. The primary outcome was overall survival (OS), estimated with Hazard Ratio (HR). Secondary outcomes, estimated with risk ratio (RR), were local and distant progression-free survival (PFS), quality of life (QoL), treatment-related mortality and morbidity, and use of salvage procedures for dysphagia. Data were analyzed using a random effects model in Review Manager 5.3 software. Main results From 2667 references, we identified two randomized studies, in six reports, that included 431 participants. All participants were clinically staged to have at least T3 and/or node positive thoracic esophageal carcinoma, 93% of which was squamous cell histology. The risk of methodological bias of the included studies was low to moderate. High-quality evidence found the addition of esophagectomy had little or no difference on overall survival (HR 0.99, 95% CI 0.79 to 1.24; P = 0.92; I² = 0%; two trials). Neither study reported PFS, therefore, freedom from loco-regional relapse was used as a proxy. Moderate-quality evidence suggested that the addition of esophagectomy probably improved freedom from locoregional relapse (HR 0.55, 95% CI 0.39 to 0.76; P = 0.0004; I² = 0%; two trials), but low-quality evidence suggested it may increase the risk of treatment-related mortality (RR 5.11, 95% CI 1.74 to 15.02; P = 0.003; I² = 2%; two trials). The other pre-specified outcomes (quality of life, treatment-related toxicity, and use of salvage procedures for dysphagia) were reported by only one study, which found very low-quality evidence that use of esophagectomy was associated with reduced short-term QoL (MD 0.93, 95% CI 0.24 to 1.62), and low-quality evidence that it reduced use of salvage procedures for dysphagia (HR 0.52, 95% CI 0.36 to 0.75). Neither study compared treatment-related morbidity between treatment groups. Authors' conclusions Based on the available evidence, the addition of esophagectomy to chemoradiotherapy in locally advanced esophageal squamous cell carcinoma, provides little or no difference on overall survival, and may be associated with higher treatment-related mortality. The addition of esophagectomy probably delays locoregional relapse, however, this end point was not well defined in the included studies. It is undetermined whether these results can be applied to the treatment of adenocarcinomas, tumors involving the distal esophagus and gastro-esophageal junction, and to people with poor response to chemoradiation.

BACKGROUND: Malabsorption and deficiency of fat‐soluble vitamins K may occur in cystic fibrosis, a genetic disorder affecting multiple organs. Vitamin K is known to play an important role in both blood coagulation and bone formation, hence the role of supplementation of vitamin K in this category needs to be reviewed. This is an updated version of the review. OBJECTIVES: To assess the effects of vitamin K supplementation in people with cystic fibrosis and to investigate the hypotheses that vitamin K will decrease deficiency‐related coagulopathy, increase bone mineral density, decrease risk of fractures and improve quality of life in people with CF. Also to determine the optimal dose and route of administration of vitamin K for people with CF (for both routine and therapeutic use). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 12 August 2019. SELECTION CRITERIA: Randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently screened papers, extracted trial details and assessed their risk of bias. The quality of the evidence was assessed using the GRADE criteria. MAIN RESULTS: Three trials (total 70 participants, aged 8 to 46 years) assessed as having a moderate risk of bias were included. One trial compared vitamin K to placebo, a second to no supplementation and the third compared two doses of vitamin K. No trial in either comparison reported our primary outcomes of coagulation and quality of life or the secondary outcomes of nutritional parameters and adverse events. Vitamin K versus control Two trials compared vitamin K to control, but data were not available for analysis. One 12‐month trial (n = 38) compared 10 mg vitamin K daily or placebo in a parallel design and one trial (n = 18) was of cross‐over design with no washout period and compared 5 mg vitamin K/week for four‐weeks to no supplementation for four‐weeks. Only the 12‐month trial reported on the primary outcome of bone formation; we are very uncertain whether vitamin K supplementation has any effect on bone mineral density at the femoral hip or lumbar spine (very low‐quality evidence). Both trials reported an increase in serum vitamin K levels and a decrease in undercarboxylated osteocalcin levels. The cross‐over trial also reported that levels of proteins induced by vitamin K absence (PIVKA) showed a decrease and a return to normal following supplementation, but due to the very low‐quality evidence we are not certain that this is due to the intervention. High‐dose versus low‐dose vitamin K One parallel trial (n = 14) compared 1 mg vitamin K/day to 5 mg vitamin K/day for four weeks. The trial did report that there did not appear to be any difference in serum undercarboxylated osteocalcin or vitamin K levels (very low‐quality evidence). While the trial reported that serum vitamin K levels improved with supplementation, there was no difference between the high‐dose and low‐dose groups. AUTHORS' CONCLUSIONS: There is very low‐quality evidence of any effect of vitamin K in people with cystic fibrosis. While there is no evidence of harm, until better evidence is available the ongoing recommendations by national CF guidelines should be followed.

Background Surgical site infection has been estimated to occur in about 15% of clean surgery and 30% of contaminated surgery cases. Using plastic adhesive drapes to protect the wound from organisms that may be present on the surrounding skin during surgery is one strategy used to prevent surgical site infection. Results from non-randomised studies have produced conflicting results about the efficacy of this approach. A systematic review was required to guide clinical practice. Objectives To assess the effect of adhesive drapes used during surgery on surgical site infection, cost, mortality and morbidity. Search methods For this fourth update we searched the Cochrane Wounds Group Specialised Register (searched 4th March 2015); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 2); Ovid MEDLINE (2012 to 3rd March 2015); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, 2012 to 3rd March 2015); Ovid EMBASE (2012 to 3rd March 2015); and EBSCO CINAHL (2012 to 4th March 2015). Selection criteria Randomised controlled trials comparing any plastic adhesive drape with no plastic adhesive drape, used alone or in combination with woven (material) drapes or disposable (paper) drapes, in patients undergoing any type of surgery. Ring drapes were excluded. Data collection and analysis Two review authors independently selected and assessed studies for trial quality and both independently extracted data. We contacted study authors for additional information. Main results We identified no new studies for this fourth update. The review includes five studies involving 3082 participants comparing plastic adhesive drapes with no drapes and two studies involving 1113 participants comparing iodine-impregnated adhesive drapes with no drapes. A significantly higher proportion of patients in the adhesive drape group developed a surgical site infection when compared with no drapes (risk ratio (RR) 1.23, 95% confidence interval (CI) 1.02 to 1.48, P = 0.03). Iodine-impregnated adhesive drapes had no effect on the surgical site infection rate (RR 1.03, 95% CI 0.06 to 1.66, P = 0.89). Length of hospital stay was similar in the adhesive drape and non-adhesive drape groups. Authors' conclusions There was no evidence from the seven trials that plastic adhesive drapes reduce surgical site infection rates, and some evidence that they increase infection rates. Further trials may be justified, using blinded outcome assessment to examine the effect of adhesive drapes on surgical site infection, based on different wound classifications.

Magnetic Resonance Electrical Impedance Tomography(MREIT) is a new medical imaging technique for the cross-sectional conductivity distribution of a human body using both EIT(Electrical Impedance Tomography) and MRI(Magnetic Resonance Imaging) system. MREIT system was designed to enhance EIT imaging system which has inherent low sensitivity of boundary measurements to any changes of internal tissue conductivity values. MREIT utilizes a recent CDI (Current Density Imaging) technique of measuring the internal current density by means of MRI technique. In this paper, a mathematical modeling for MREIT and image reconstruction method called the alternating J-substitution algorithm are presented. Computer simulations show that the alternating J-substitution algorithm provides accurate high-resolution conductivity images.

BACKGROUND: Severe traumatic brain injury is a significant cause of morbidity and mortality. Treatment strategies in management of such injuries are directed to the prevention of secondary brain ischaemia, as a consequence of disturbed post-traumatic cerebral blood flow. They are usually concerned with avoiding high intracranial pressure (ICP) or adequate cerebral perfusion pressure (CPP). An alternative to this conventional treatment is the Lund concept, which emphasises a reduction in microvascular pressures. OBJECTIVES: To assess the role of the Lund concept versus other treatment modalities such as ICP-targeted therapy, CPP-targeted therapy or other possible treatment strategies in the management of severe traumatic brain injury. SEARCH METHODS: We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 10, 2013), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL Plus (EBSCO Host), ISI Web of Science (SCI-EXPANDED and CPCI-S) and trials registries. We searched the reference lists of relevant studies and published reviews found with our search. The most recent search was 5 November 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs, level 1 evidence) exploring the efficacy of the Lund concept in the treatment of traumatic brain injury. DATA COLLECTION AND ANALYSIS: Two review authors independently selected papers and made decisions about the eligibility of potentially relevant studies. MAIN RESULTS: We found no studies that met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: There is no evidence that the Lund concept is a preferable treatment option in the management of severe traumatic brain injury. Language: en

Background There is ongoing debate about whether fusion or arthroplasty is superior in the treatment of single level cervical degenerative disc disease. Mainly because the intended advantage of arthroplasty over fusion, that is, the prevention of symptoms due to adjacent segment degeneration in the long term, is not confirmed yet. Until sufficient long‐term results become available, it is important to know whether results of one of the two treatments are superior to the other in the first one to two years. Objectives To assess the effects of arthroplasty versus fusion for radiculopathy or myelopathy, or both due to single level cervical degenerative disc disease. Search methods We searched the following databases for randomised controlled trials (RCTs): CENTRAL (The Cochrane Library 2011, Issue 2), MEDLINE, EMBASE, and EBMR. Additionally, we searched the System for Information on Grey Literature (SIGLE), subheading Biological and Medical Sciences, the US Food and Drug Administration (FDA) database on medical devices, and Clinicaltrials.gov to identify trials in progress. We also screened the reference list of all selected papers. Date of search: 25 May 2011. Selection criteria We included RCTs that directly compared any type of cervical fusion with any type of arthroplasty, with at least one year of follow‐up. Primary outcomes were arm pain, neck pain, neck‐related functional status, patient satisfaction, neurological outcome, and global health status. Secondary outcomes were the presence of (radiological) fusion, revision surgery at the treated level, secondary surgery on adjacent levels, segmental mobility of treated and adjacent levels, and work status. Data collection and analysis Study selection was performed independently by three review authors, and 'Risk of bias' assessment and data extraction were performed by two review authors. In case of missing data or insufficient information for a judgement about risk of bias, we tried to contact the study authors or the study sponsor. The data were entered into RevMan by one review author and subsequently checked by a second review author. We assessed the quality of evidence using GRADE. We analysed heterogeneity and performed sensitivity analyses for the pooled analyses. Main results We included nine studies (2400 participants), five of which had a low risk of bias. Eight of these studies were industry sponsored. The most important results showed low‐quality evidence for a small but significant difference in alleviation of arm pain at one to two years in favour of arthroplasty (mean difference (MD) ‐1.54; 95% confidence interval (CI) ‐2.86 to ‐0.22; 100‐point scale). A small study effect could not be ruled out for this outcome in the sensitivity analyses. This means that smaller studies (or small published subsets of larger studies) showed larger differences for this outcome, which may indicate publication bias. Also, moderate‐quality evidence showed a small difference in neck‐related functional status at one to two years in favour of arthroplasty (MD ‐2.79; 95% CI ‐4.73 to ‐0.85; 100‐point scale) and a small difference in neurological outcome in favour of arthroplasty (risk ratio (RR) 1.05; 95% CI 1.01 to 1.09). These two outcomes were robust to sensitivity analyses. For none of the primary outcomes, was a clinically relevant difference shown. Additionally, there was high‐quality evidence for a large, statistically significant difference in segmental mobility at one to two years (measured as degrees segmental range of motion) at the treated level (MD 6.90; 95% CI 5.45 to 8.35). There was low‐quality evidence that there was no statistically significant difference in secondary surgery at the adjacent levels at one to two years (RR 0.60; 95% CI 0.35 to 1.02). The latter was not robust to sensitivity analyses. Authors' conclusions There was a tendency for clinical results to be in favour of arthroplasty; often these were statistically significant. However, differences in effect size were invariably small and not clinically relevant for all primary outcomes. Significance was often gained or lost in the varying sensitivity analyses, probably owing to the relatively small number of studies, in combination with the small differences that were found. Given the fact that all of the included studies were not blinded, this could be due to patient or carer expectations. However, at this time both treatments can be seen as valid options with respect to results at a maximum of one to two years. Given the current absence of truly long‐term results, use of these mobile disc prostheses should still be limited to clinical trials. There was high‐quality evidence that the goal of preservation of segmental mobility in arthroplasty was met. A statistically significant effect on the incidence of secondary symptoms at adjacent levels, the primary goal of arthroplasty over fusion, was not found at one to two years. If there was a protective effect, this should become clearer over time. A future update, when studies with 'truly long‐term' results (five years or more) become available, should focus on this issue.

BACKGROUND: Emergency contraception (EC) is using a drug or copper intrauterine device (Cu‐IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. This is an update of a review previously published in 2009 and 2012. OBJECTIVES: To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy. SEARCH METHODS: In February 2017 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database. We also searched ICTRP and ClinicalTrials.gov as well as contacting content experts and pharmaceutical companies, and searching reference lists of appropriate papers. SELECTION CRITERIA: Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcome was observed number of pregnancies. Side effects and changes of menses were secondary outcomes. MAIN RESULTS: We included 115 trials with 60,479 women in this review. The quality of the evidence for the primary outcome ranged from moderate to high, and for other outcomes ranged from very low to high. The main limitations were risk of bias (associated with poor reporting of methods), imprecision and inconsistency. Comparative effectiveness of different emergency contraceptive pills (ECP) Levonorgestrel was associated with fewer pregnancies than Yuzpe (estradiol‐levonorgestrel combination) (RR 0.57, 95% CI 0.39 to 0.84, 6 RCTs, n = 4750, I(2) = 23%, high‐quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000. Mifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I(2) = 0%, high‐quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000. Both low‐dose mifepristone (less than 25 mg) and mid‐dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I(2) = 0%, high‐quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I(2) = 0%, moderate‐quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low‐dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid‐dose mifepristone would be between 16 and 29 women per 1000. Ulipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I(2) = 0%, high‐quality evidence). Comparative effectiveness of different ECP doses It was unclear whether there was any difference in pregnancy rate between single‐dose levonorgestrel (1.5 mg) and the standard two‐dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I(2) = 0%, moderate‐quality evidence). Mid‐dose mifepristone was associated with fewer pregnancies than low‐dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I(2) = 0%, high‐quality evidence). Comparative effectiveness of Cu‐IUD versus mifepristone There was no conclusive evidence of a difference in the risk of pregnancy between the Cu‐IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low‐quality evidence). Adverse effects Nausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I(2) = 59%, moderate‐quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I(2) = 0%, high‐quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I(2) = 82%, moderate‐quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I(2) = 78%, moderate‐quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high‐quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I(2) = 0%, high‐quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose‐related. Cu‐IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu‐IUD versus no events in 190 women using mifepristone, low‐quality evidence). AUTHORS' CONCLUSIONS: Levonorgestrel and mid‐dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid‐dose (25 mg to 50 mg) and low‐dose mifepristone(less than 25 mg) were probably more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25 mg) was less effective than mid‐dose mifepristone. UPA may be more effective than levonorgestrel. Levonorgestrel users had fewer side effects than Yuzpe users, and appeared to be more likely to have a menstrual return before the expected date. UPA users were probably more likely to have a menstrual return after the expected date. Menstrual delay was probably the main adverse effect of mifepristone and seemed to be dose‐related. Cu‐IUD may be associated with higher risks of abdominal pain than ECPs.

Background Many patients with metastatic spinal cord compression (MSCC) have spinal instability but are determined, by their clinician, to be unsuitable for surgical internal fixation due to their advanced disease. Mobilisation may be hazardous in the presence of spinal instability as further vertebral collapse can occur. Current guidance on positioning (or mobilisation) and spinal bracing is contradictory. Objectives To investigate the correct positioning (or mobilisation) and examine the effects of spinal bracing to relieve pain or to prevent further vertebral collapse in patients with MSCC. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, CANCERLIT, NICE, SIGN, AMED, TRIP, National Guideline Clearinghouse and PEDro database were searched; the last search was run in February 2012. Selection criteria We selected randomised controlled trials (RCTs) of adults with MSCC of interventions on positioning or mobilisation and bracing. Data collection and analysis Two review authors independently assessed each possible study for inclusion and quality. Main results One thousand, six hundred and eleven potentially relevant studies were screened. No studies met the inclusion criteria. Many papers identified the importance of mobilisation but no RCTs have been undertaken. No RCTs of bracing in MSCC were identified. Authors' conclusions There is lack of evidence based guidance around how to correctly position and when to mobilise patients with MSCC or if spinal bracing is an effective technique for reducing pain or improving quality of life. RCTs are required in this important area.

BACKGROUND: Chronic heart failure is a major cause of morbidity and mortality worldwide. Diuretics are regarded as the first‐line treatment for patients with congestive heart failure since they provide symptomatic relief. The effects of diuretics on disease progression and survival remain unclear. OBJECTIVES: To assess the harms and benefits of diuretics for chronic heart failure SEARCH METHODS: Updated searches were run in the Cochrane Central Register of Controlled Trials in The Cochrane Library (CENTRAL Issue 1 of 4, 2011), MEDLINE (1966 to 22 February 2011), EMBASE (1980 to 2011 Week 07) and HERDIN database (1990 to February 2011). We hand searched pertinent journals and reference lists of papers were inspected. We also contacted manufacturers and researchers in the field. No language restrictions were applied. SELECTION CRITERIA: Double‐blinded randomised controlled trials of diuretic therapy comparing one diuretic with placebo, or one diuretic with another active agent (e.g. ACE inhibitors, digoxin) in patients with chronic heart failure. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted the data and assessed the eligibility and methodological quality of each trial. Extracted data were analysed by determining the odds ratio for dichotomous data, and difference in means for continuous data, of the treated group compared with controls. The likelihood of heterogeneity of the study population was assessed by the Chi‐square test. If there was no evidence of statistical heterogeneity and pooling of results was clinically appropriate, a combined estimate was obtained using the fixed‐effects model. MAIN RESULTS: This update has not identified any new studies for inclusion. The review includes 14 trials (525 participants), 7 were placebo‐controlled, and 7 compared diuretics against other agents such as ACE inhibitors or digoxin. We analysed the data for mortality and for worsening heart failure. Mortality data were available in 3 of the placebo‐controlled trials (202 participants). Mortality was lower for participants treated with diuretics than for placebo, odds ratio (OR) for death 0.24, 95% confidence interval (CI) 0.07 to 0.83; P = 0.02. Admission for worsening heart failure was reduced in those taking diuretics in two trials (169 participants), OR 0.07 (95% CI 0.01 to 0.52; P = 0.01). In four trials comparing diuretics to active control (91 participants), diuretics improved exercise capacity in participants with CHF, difference in means WMD 0.72 , 95% CI 0.40 to 1.04; P < 0.0001. AUTHORS' CONCLUSIONS: The available data from several small trials show that in patients with chronic heart failure, conventional diuretics appear to reduce the risk of death and worsening heart failure compared to placebo. Compared to active control, diuretics appear to improve exercise capacity.