Post-herpetic neuralgia Raising the standard of applied dementia care research: addressing the implementation error Medication development for agitation and aggression in Alzheimer disease: review and discussion of recent randomized clinical trial design. Clinical trials in restless legs syndrome--recommendations of the European RLS Study Group (EURLSSG). Lithium in the treatment of mania: comparisons with neuroleptics. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition) Vitamin D: do we get enough? Art therapy for relief of symptoms associated with HIV/AIDS Nevasic audio program for the prevention of chemotherapy induced nausea and vomiting: A feasibility study using a randomized controlled trial design. Theory of Mind and Emotional Functioning in Fibromyalgia Syndrome: An Investigation of the Relationship between Social Cognition and Executive Function Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany. Estimating live birth rates after ovulation induction in polycystic ovary syndrome: sample size calculations for the pregnancy in polycystic ovary syndrome trial. Commentary: Replication of influential trial helps international policy Randomised controlled trial of welfare rights advice accessed via primary health care: pilot study [ISRCTN61522618] New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Drugs in aggressive behavior. Missing data: our view of the state of the art. Statistical methodologies to pool across multiple intervention studies Monitoring awareness of and attitudes to depression in Australia. Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome Exercise training and music therapy in elderly with depressive syndrome: a pilot study. Considerations on Designing Clinical Trials to Evaluate the Place of New Antiepileptic Drugs in the Treatment of Newly Diagnosed and Chronic Patients with Epilepsy Efficacy of a dilemma-focused intervention for unipolar depression: study protocol for a multicenter randomized controlled trial
Background In spite of the large body of evidence available in the literature , definition and treatment of  Post-Herpetic Neuralgia ( PHN )  are still lacking a consistent and universally recognized st and ardization . Furthermore , many issues concerning diagnosis , prediction and prevention of PHN need to be clarified in view of recent contributions . Objectives To assess whether PHN may be better defined , predicted , treated and prevented in light of recent data , and whether available alternative or adjunctive therapies may improve pain relief in treatment recalcitrant PHN . Methods Systematic review s , meta-analyses , r and omized controlled trials , cohort studies and protocol s were search ed ; the search sources included PubMed , Cochrane Library , NICE , and DARE . More than 130 papers were selected and evaluated . Results Diagnosis of PHN is essentially clinical , but it can be improved by resorting to the many tools available , including some practical and accessible question naires . Prediction of PHN can be now much more accurate , taking into consideration a few well vali date d clinical and anamnestic variables . Treatment of PHN is presently based on a well characterized array of drugs and drug associations , including , among others , tricyclic antidepressants , gabapentinoids , opioids and many topical formulations . It is still unsatisfactory , however , in a substantial proportion of patients , especially those with many comorbidities and intense pain at herpes zoster ( HZ ) presentation , so that this frequent complication of HZ still strongly impacts on the quality of life of affected patients . Conclusion Further efforts are needed to improve the management of PHN . Potentially relevant interventions may include early antiviral therapy of acute HZ , prevention of HZ by adult vaccination , as well as new therapeutic approaches for patients experiencing PHN Current methodology has made popular the pragmatic r and omized trial ( Foster & Little , 2012 ) and has led to an acknowledged growth of high- quality research in the ‘ new generation ’ of psychosocial interventions in dementia care ( Orrell , 2012 ) . However , many trials of psychosocial interventions in dementia lack impact . It is not clear whether this reflects a genuine ineffectiveness , since the methodology used in dementia care research is at present weak in addressing the important distinction between genuine ineffectiveness and an implementation error . Therefore , potentially effective dementia care interventions that may have a positive impact on patient experience can fail to show effectiveness , thereby reducing treatment options and wasting research money . Method ological discussion s about the success and failure of interventions in dementia care within the European INTERDEM group of multi-professional research ers on psychosocial dementia care ( www.interdem.org/ ) led to a critical analysis of the suitability of the current methodology . This has often relied on the Medical Research Council ’s ( MRC ) Framework for complex interventions and its iterations ( Campbell et al. , 2000 ; Craig et al. , 2008 ; Craig & Petticrew , 2013 ) . Foster and Little ( 2012 ) pinpoint an important obstacle to improving clinical practice as the legacy of ‘ simple ’ drug therapy evaluations which are engrained in the design and conduct of the pragmatic trial , a view that can also be extended more generally to the interpretation and conduct of the MRC framework for complex interventions and its method ologies . The advantage of pragmatic trials is their proximity to daily practice in routine health care setting s. This has particular implication s for the design and conduct of psychosocial intervention research in dementia , where the important distinction between poor attention to implementation and genuine ineffectiveness is often overlooked . Furthermore , better attention to the implication s of this proximity in the design and conduct of psychosocial intervention research trials may reduce the need for a separate large-scale implementation study phase in the way that this is currently conceived within the MRC approach to complex interventions ( Craig et al. , 2008 ; Craig & Petticrew , 2013 ) . This is an urgent issue for psychosocial intervention research in dementia care as today 35.6 million people and families worldwide live with dementia ( Prince et al. , 2013 ) , whilst major pharmaceutical advances in prevention and cure remain elusive ( Miller , 2012 ) . The predicted future growth of dementia cases over the next decade will undoubtedly raise the already high costs of care , estimated at US$ 604 billion in 2010 ( Wimo et al. , 2013 ) , in an illness that is most feared people over the age of 55 years ( Le Couteur , Doust , Creasey , & Brayne , 2013 ) , since it can undermine core human capacities result ing in decline in quality of life ( Selkoe , 2012 ) . Although cure for dementia is not available for dementia patients , we are not empty h and ed . Psychosocial intervention research has emerged as today ’s forerunner , given its aim to improve daily practice among professionals who provide support to people and families living with dementia .  Psychosocial interventions in dementia involve interactions between people to improve psychological and social functioning ( Moniz-Cook , Vernooij-Dassen , Woods , & Orrell , 2011 ; Rabins et al. , 2007 ) , such as cognitive stimulation therapy ( Woods , Aguirre , Spector , & Orrell , 2012 ) , occupational therapy ( Graff et al. , 2006 ) and support programmes for family carers ( Vernooij-Dassen , Draskovic , McCleery , & Downs , 2011 ) . This paper outlines the rationale for a paradigm shift in the design and methodology for evaluation of complex interventions in applied dementia care research . We use  psychosocial intervention research as an exemplar of how research ers and their funders may achieve better value for money ABSTRACT Background : The management of disruptive neuropsychiatric symptom ( NPS ) such as agitation and aggression ( A/A ) is a major priority in caring for people with Alzheimer 's disease ( AD ) . Few effective pharmacological or non-pharmacological options are available . Results of r and omized clinical trials ( RCTs ) of drugs for A/A have been disappointing . This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to method ological issues such as the choice of outcomes . The aim of this review was to highlight key method ological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD . Methods : We search ed PubMed / Medline , Cochrane Central Register of Controlled Trials , and Clinical Trials.gov for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD , between January 2008 and December 2013 . Results : We identified a total of 18 RCTs ; of these , 11 were completed and 7 ongoing . Of the ongoing RCTs , only one is in Phase III . Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo . Each of the completed RCTs used a different definition of " clinical ly significant A/A. " There was considerable heterogeneity in study design . The primary endpoints were largely proxy-based but a variety of scales were used . The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous . Placebo response was notable in all trials . Conclusions : This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key method ological issues such as definition of A/A , choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design The European Restless Legs Syndrome ( RLS ) Study Group ( EURLSSG ) is an association of European RLS experts who are actively involved in RLS research . A major aim of the Study Group is the development and continuous improvement of st and ards for diagnosis and treatment of RLS . Several members developed study design s and evaluation methods in investigator-initiated trials early in the 1990s , and all members have since contributed to many pivotal and nonpivotal drug trials for the treatment of RLS . The recommendations on clinical investigations of pharmacological treatment of RLS patients summarize the group 's expertise and knowledge acquired through clinical trials . The recommendations primarily address how to plan and conduct confirmatory , r and omized clinical studies in patients with idiopathic RLS . Advice is presented for the diagnosis of RLS and clinical and polysomnographic inclusion and exclusion criteria . Primary and secondary endpoints for an evaluation of efficacy are based on a critical description of vali date d methods for both short- and long-term trials , also in special population s ( children , pregnant women , elderly patients ) . The recommendations include the assessment of augmentation . Finally , general issues including the evaluation of safety and tolerability , as well as specific neurological and cardiovascular risks and sleep attacks/daytime somnolence , are discussed . The aim of these recommendations is to support research groups or pharmaceutical companies in the design of optimized study protocol Since the original discovery of the antimanic properties of lithium nearly 30 years ago , 1 a large number of studies , as well as extensive clinical experience , have confirmed the efficacy of this drug for the treatment of the manic phase of manic-depressive illness . The recent focus of questions concerning the role of lithium in the treatment of mania has shifted from efficacy per se to comparisons with other drug treatments and the related issue of specificity . This review will , therefore , focus on controlled studies comparing lithium with neuroleptics , following a brief historical review of the earlier studies . The studies comparing lithium with neuroleptics are of special importance not only from a practical point of view but also theoretically , in that they bear on the question of the specificity of  lithium  against the manic syndrome — a question with implication for the underlying pathophysiology of mania . OPEN SINGLE-BLIND STUDIES Table 1 summarizes The actual incidence of neurologic dysfunction result ing from hemorrhagic complications associated with neuraxial blockade is unknown . Although the incidence cited in the literature is estimated to be less than 1 in 150,000 epidural and less than 1 in 220,000 spinal anesthetics , recent epidemiologic surveys suggest that the frequency is increasing and may be as high as 1 in 3000 in some patient population s. Overall , the risk of clinical ly significant bleeding increase with age , associated abnormalities of the spinal cord or vertebral column , the presence of an underlying coagulopathy , difficulty during needle placement , and an indwelling neuraxial catheter during sustained anticoagulation ( particularly with st and ard heparin or low-molecular weight heparin ) . The need for prompt diagnosis and intervention to optimize is also consistently reported . In response to these patient safety issues , the American Society of Regional Anesthesia and Pain Medicine ( ASRA ) convened its Third Consensus Conference on Regional Anesthesia and Anticoagulation . Practice guidelines or recommendations summarize evidence -based review s. However , the rarity of spinal hematoma defies a prospect i ve r and omized study , and there is no current laboratory model . As a result , the ASRA consensus statements represent the collective experience of recognized experts in the field of neuraxial anesthesia and anticoagulation . These are based on case reports , clinical series , pharmacology , hematology , and risk factors for surgical bleeding . An underst and ing of the complexity of this issue is essential to patient management Summary On September 29 , 2011 , acknowledged experts in the field of vitamin D , mainly European , were brought together in order to discuss the recent scientific advances in relation to vitamin D : the current requirements and associations with various health outcomes . In this article , the discussion s result ing from the meeting are summarized . Introduction Several groups at risk for developing vitamin D insufficiency have been identified . Accordingly , review s indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l . In addition to the role of vitamin D in bone health , recent studies suggest that it may play a pivotal role in other systems , e.g. , the cardiovascular system , pancreas , muscle , immune system and brain . Most evidence , however , is obtained from observational studies and yet inconclusive . Methods To exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes , a workshop entitled “ Vitamin D Expert Meeting : Do we get enough ? ” , was organized . Results Despite low vitamin D levels worldwide , consensus on the definition of deficiency is not yet reached . In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects , r and omized controlled trials in these fields are warranted . The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation , in most studies co-administered with calcium , reduces fracture risk in the senior population . Conclusion To reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged ≥65 years are therefore recommended to meet a mean daily vitamin D intake of 20 μg ( 800 IU ) , which is best achieved with a supplement Abstract Symptom management for persons living with HIV/AIDS is an extremely important component of care management . The importance of pharmacologic interventions for management of symptoms is well recognized , and non-pharmacologic strategies such as art therapy are gaining interest in lay and professional communities . The aim of this research project was to test the feasibility and effectiveness of art therapy  for relief of symptoms experienced by people living with HIV/AIDS . In this r and omized clinical trial of art therapy , the primary objective was to assess change in physical and psychological symptoms .  Participants were recruited from a large urban hospital 's inpatient population and outpatient HIV clinic . Seventy-nine people with a diagnosis of HIV infection provided socio-demographic information , participated in either a one-hour art therapy session or viewed a videotape about art therapy , and completed pre- and posttest measures of psychological and physical symptoms . Two separate analysis of covariance models were used to identify if the treatment condition influenced psychological and physical symptoms , after adjusting for pretest score , age , gender , and race/ethnicity . The analyses showed that physical symptom mean scores were better for those who participated in the art therapy compared to those who viewed the videotape , and this difference between conditions was statistically significant ( p<0.05 ) . Thus , the study demonstrated the potential benefits of one session of art therapy in relation to symptoms associated with HIV/AIDS PURPOSE Pharmacological therapy is only partially effective in preventing or treating chemotherapy induced nausea and vomiting ( CINV ) . Therefore , exploring the complementary role of non-pharmacological approaches used in addition to pharmacological agents is important . Nevasic uses specially constructed audio signals hypothesized to generate an antiemetic reaction . The aim of this study was to examine the feasibility of conducting a r and omized controlled trial ( RCT ) to evaluate the effectiveness of Nevasic  to control CINV . METHODS A mixed methods design incorporating an RCT and focus group interviews . For the RCT , female breast cancer patients were r and omized to receive either Nevasic plus usual care , music plus usual care , or usual care only . Data were analysed using descriptive statistics and linear mixed-effects models . Five focus group interviews were conducted to obtain participants ' views regarding the acceptability of the interventions in the trial . RESULTS 99 participants were recruited to the RCT and 15 participated in focus group interviews . Recruitment targets were achieved . Issues of Nevasic acceptability were highlighted as weaknesses of the program . This study did not detect any evidence for the effectiveness of Nevasic ;  however , the results showed statistically significant less use of anti-emetics ( p = 0.003 ) and borderline non-significant improvement in quality of life ( p = 0.06 ) . CONCLUSIONS Conducting a non-pharmacological intervention using such an audio program is feasible , although difficulties and limitations exist with its use . Further studies are required to investigate the effectiveness of Nevasic from perspectives such as anti-emetic use , as well as its overall effect on the levels of nausea and vomiting Background Fibromyalgia ( FM ) is a syndrome primarily characterised by chronic , widespread musculoskeletal pain . In the aetiology of this syndrome a crucial role is played by complex interactions among biological , genetic , psychological , and socio-cultural factors . Recently , research ers have started to explore emotional functioning in FM , with their attention focused on alexithymia , a personality construct that affects the regulation of a person ’s own emotions . On the other h and , the detection and experience of emotional signals from other people have only been sparsely investigated in FM syndrome and no studies have investigated the ability to represent other people ’s mental states ( i.e. Theory of Mind , ToM ) in these patients . Here we present the first study investigating a large set of social-cognitive abilities , and the possible relationships between these abilities and the performance on executive-function tasks , in a homogenous sample of patients with FM . Methodology Forty women with FM and forty-one healthy women matched for education and age were involved in the study .  Social cognition was assessed with a set of vali date d experimental tasks .  Measures of executive function were used to test the correlations between this dimension and the social-cognitive profile of patients with FM . Relationships between social-cognitive abilities and demographic , clinical and psychological variables were also investigated . Principal Findings Patients with FM have impairments both in the regulation of their own affect and in the recognition of other ’s emotions , as well as in representing other people ’s mental states . No significant correlations were found between social cognition tasks and the subcomponents of the executive function that were analysed . Conclusions The results show the presence of several impairments in social cognition skills in patients with FM , which are largely independent of both executive function deficits and symptoms of psychological distress . The impairments reported highlight the importance of adequately assessing ToM and emotional functioning in clinical practice AIMS Drug-induced long QT syndrome ( diLQTS ) leading to Torsade de Pointes ( TdP ) is a potentially lethal condition , which has led to several post-marketing drug withdrawals in the past decade . The true incidence of diLQTS/TdP is largely unknown . One explanation is under-reporting of this potentially life-threatening adverse event by physicians and other medical staff to pharmacovigilance agencies . To gain more insight into the incidence of diLQTS and TdP , the Berlin Pharmacovigilance Center ( PVZ-FAKOS ) has actively and prospect ively identified patients who developed this particular type of drug-induced adverse event . Here , the basic characteristics of the affected patients are summarized and suspected drugs are discussed . Furthermore , an extrapolation of the Berlin incidence rates to the German St and ard Population is presented . METHODS AND RESULTS Using a Berlin-wide network of 51 collaborating hospitals ( > 180 clinical departments ) , adult patients presenting with long QT syndrome ( LQTS/TdP ) between 2008 and 2011 were identified by active surveillance of these hospitals . Drug exposures as well as other possible risk factors were obtained from the patient 's files and in a face-to-face interview with the patient . One-hundred and seventy patients of possible LQTS/TdP were reported to the Pharmacovigilance Center of whom 58 cases were confirmed in a thorough validation process . The majority ( 66 % ) of these cases were female and 60 % had developed LQTS/TdP in the outpatient setting . Thirty-five ( 60 % ) of 58 confirmed cases were assessed as drug-related based on a st and ardized causality assessment applying the criteria of the World Health Organization . Drugs assessed as related in more than two cases were metoclopramide , amiodarone , melperone , citalopram , and levomethadone . The age-st and ardized incidence of diLQTS/TdP in Berlin was estimated to be 2.5 per million per year for males and 4.0 per million per year for females . CONCLUSION While European annual reporting rates based on spontaneous reports suggest an annual diLQTS/TdP incidence of 0.26 per million in Germany , we estimated a considerably higher incidence of diLQTS/TdP in an active surveillance approach . Further measures are warranted to better sensitize physicians against this potentially life-threatening drug-induced adverse event Polycystic ovary syndrome ( PCOS ) affects approximately 5 % of the female population , and is a leading cause of infertility , primarily secondary to anovulation . Clomiphene citrate has been st and ard therapy for ovulation induction in patients seeking pregnancy , but recent evidence suggests that insulin sensitizing agents such as metformin may also be effective . The National Institute of Child Health and Human Development 's Reproductive Medicine Network has begun a r and omized , double-blind trial of clomiphene vs. metformin vs. clomiphene plus metformin for the induction of ovulation in patients with PCOS seeking pregnancy , with live birth rate as the primary outcome . Because the available literature was largely limited to surrogate outcomes such as ovulation and pregnancy rates , we created a Markov model to derive estimates of likely live birth rates in each arm . Using these estimates , we then constructed an algorithm that allowed only two formal comparisons between the three arms . First , we assumed that combination therapy would have to be superior to the next best single-agent therapy in order to be preferred , because of complexity , costs , increased side effects , etc . If combination therapy is not superior to the next best single agent , then the only other comparison of interest is between the two single agent therapies . Because the third possible comparison , between the best and worst of the three therapies , is not clinical ly relevant , it can be eliminated from formal statistical consideration , with subsequent reduction in sample size . Based on the opinion of the Network Steering Committee that a 15 % absolute difference in live birth rates would be clinical ly relevant , our methodology result ed in a sample size of 226 per arm , or a total of 678 subjects . The PPCOS trial should definitively answer the question of the relative efficacy of metformin , clomiphene , and combination therapy  in the treatment of infertile women with PCOS The World Bank , the Gates Foundation and the World Health Organization promote national child deworming programmes in developing countries.1 They assert these programmes will improve nutritional status , health and school performance , and hence contribute to economic growth . Indeed , the World Health Organization states that deworming contributed to Japan ’s economic boom in the 1950s,2 and Nobel Laureates meeting in Copenhagen ranked deworming as the fourth most important intervention to solve the health problems of the whole world.3 Surprisingly , the evidence base for these cl aims from controlled studies is limited . Critically , according to the Cochrane review which two of us author , there is quite good evidence of no effect for the main biomedical outcomes in deworming , making the broader societal benefits on economic development barely credible ( Figure 1).4 Nevertheless , the advocates increasingly rely on a single large quasi-r and omized trial carried out in Kenya , published in 2004 in Econometrica,5 which reports school attendance . Figure 1 . Conceptual framework used to underpin the effects of deworming programmes on economic growth  in developing countries . Contemporary evidence questions this model , as there is now quite good contemporary evidence , summarized in the Cochrane review , that ... This study has been highly influential . The International Initiative for Impact Evaluation commissioned the London School of Hygiene and Tropical Medicine ( LSHTM ) to replicate the analysis , as the original analysis is ‘ based on econometric approaches and used a language and format that would be unfamiliar to many health care research ers’.6 The replication aim ed to provide detail of the methods and reporting in line with the CONSORT statement . The team are internationally recognized , independent and meticulous in their approach . They agreed a protocol , carefully checked and corrected the raw data , and then re-ran their prespecified analysis .6 Their first paper is a pure replication,7 exactly repeating the authors ’ original analysis . This paper clarifies some method ological details not provided in the original paper , but it also uncovers a series of important coding and analysis errors . Some of the corrected results are consistent with the original findings , but others are quite different . Most notably , the much quoted ‘ positive externalities’—where the benefits of treating children in one school ‘ spill over ’ to benefit children in adjacent schools — vanish in their corrected analysis . Their second paper uses approaches more familiar to epidemiologists , and allows a more thorough exploration of the data .8 There are substantial amounts of missing information , and some unexpected patterns that are difficult to explain . For example , there is a correlation between the number of observations in each school and the reported attendance , with more observations associated with lower attendance reported — except in some of the intervention groups , where more frequent observation is associated with better attendance . This raises the possibility that the process of observation influenced outcome reporting and this was different in control and intervention groups . The second paper confirms an association with higher attendance in the deworming schools when stratified by year , but found the combined estimate across years was much larger , and the authors caution the validity of the combined year estimate : this may be due to the stepped-wedge design where the combined year estimate includes a before and after comparison ; or it may be due to the problems with secular and group effects of the number of observations of school attendance varying . To further complicate matters , there was also a concurrent ‘ School Assistance Program ’ ( SAP ) evaluating five other interventions in 27/75 of the study schools , which was not part of the r and omized intervention . Attendance patterns differed on the basis of involvement in the SAP , which the authors suggest could well lead to bias.8 One of the critical points the LSHTM papers make is that the administration of the deworming drugs was part of a ‘ complex health education and drug treatment intervention’.8 The intervention schools also received regular public health lectures , wall charts and teacher training on worm prevention . Interestingly , the pure replication shows very similar impacts of the intervention on children in the intervention schools irrespective of whether they took the deworming medicine or not.7 For Miguel and colleagues , they term this as ‘ indirect within-school effects ’ of deworming , but equally the effects could be due to the non-specific effects of the health promotion interventions in the intervention schools . So where does this take us ? There is a small effect on school attendance for sure , but this should not be over-interpreted , as the LSHTM authors say , given the concerns raised regarding the risk of bias , and the independent effects on school attendance of the programme of health promotion . In addition , the study shows that allocation to the deworming group does not influence student progress , as the re- analysis shows clearly no evidence of a difference in examination performance between deworming and control groups.7,8 In the context of the global evidence base , there is only one other study that has examined school attendance with no obvious effect shown.4 Given all these uncertainties , we simply do n’t know if there is truly an effect on school attendance from the data , in taking all these factors into account formally in a GRADE analysis .4 But what weakens the case of deworming still further is that there is now quite good evidence of no effect for most of the main outcomes ( Figure 1 ) , including nutritional status , haemoglobin , cognition and school performance . This is important because without these effects it seems implausible that deworming itself would have an independent effect on school attendance or economic development . Obviously children infected with worms should be treated . Trials from over 20 years ago in an area of Kenya where all the children were heavily infected showed benefit . Another trial in India showed benefit , but subsequent trials in the same area failed to show an effect.4,9 So deworming may have helped in these exceptional , heavily infected , untreated population s from another decade , but this is scarcely a solid base for contemporary policy : public health nutrition has changed , worm burden has declined and this probably accounts for the lack of effect on biomedical outcomes in contemporary studies .10 We have been perplexed by the un question ing belief behind deworming in the advocates , and have found it is deep rooted in American history . The Rockefeller Sanitary Commission in 1909 sought to eradicate hookworm in the Southern USA population , where it was seen as a cause of ‘ some of the proverbial laziness of the poorer classes ’ and to improve worker productivity ; these were extended with the Rockefeller International Health Commission established in 1913.11 The beliefs and assumptions appear to continue , with ‘ Deworm the World ’ aim ing to deworm 220 million children in India during 2015.12 What have we learned from this ? Certainly that replication is a valuable process , not least for errors that have the potential to mislead , but also to provide a much better interpretation of the potential biases in studies . In terms of policies in deworming , it suggests donors and Nobel Prize winners need to be aware of their prior assumptions , and base decisions on the all the evidence from reliable studies within a systematic review , not just select a single study . They need to look at all relevant outcomes , not just one . They need to consider bias and confounding . Our view is that current promotion of community deworming is certainly a panacea : a single solution to multiple problems in low- and middle-income countries , and that the belief that deworming will impact substantially on economic development seems delusional when you look at the results of reliable controlled trials . This is a view , based on over 15 years of engagement with critically appraising the literature in this field.13 We recommend anyone responsible for public or philanthropic money going to large scale deworming to read these replication studies , the original publication , the authors ’ responses to the replication and the 2015 version of the Cochrane review that includes corrections from these replications plus data from five further studies , including the recently published DEVTA study of 2 million children.4,14 Then make up your own mind . Conflict of interest : PG and DTR are authors of a Cochrane review of community deworming programmes . PG is funded by the Department for International Development to provide reliable independent systematic review s for the benefit of developing countries ; PG receives salary support from Countdown , a DFID-supported research grant in programmatic implementation of neglected tropical disease programmes Background Little research has directly evaluated the impact of increasing financial or material re sources on health . One way of assessing this lies with assisting people to obtain full welfare benefit entitlements . In 2000–1 , 2.3 million pensioners were living in poverty in the UK and estimates suggest that around one million do not cl aim the financial support to which they are entitled . The effectiveness of welfare rights advice services delivered via primary health care to promote health and reduce health inequalities is unknown . Methods The main objectives of this study were to assess the feasibility and acceptability of a r and omised controlled trial of welfare rights advice in a community setting and identify appropriate health and social outcome measures in order to plan a definitive trial . This was a single blind , community-based , pilot r and omised controlled trial . 126 men and women aged 60 years and over , recruited from 4 general practice s in Newcastle upon Tyne , UK , participated . The intervention comprised a structured welfare rights assessment followed by active assistance with welfare benefit cl aims over the following 24 months . The control group received the intervention after a six month delay . A range of socio-economic , health , behavioural and psycho-social outcomes were measured . Results 126 out of 400 people invited agreed to participate and 109 were followed up at 24 months . Both the intervention and research procedures were feasible and acceptable to participants and professionals involved . 68 ( 58 % ) of all participants received a welfare benefit award  ( 31 financial , 16 non-financial and 21 both ) . Median time to receipt of benefits from initial assessment was 14 ( range 1 to 78 ) weeks and median financial award was £ 55 ( € 81 , $ 98 ) per household per week . There was little evidence of health-related differences between groups or over time , which could be due to limitations of the study design . Conclusion Modification of the study design , including selection of study participants , timing of interventions and length of follow up are recommended for a definitive trial . More appropriate health and psycho-social outcome measures relevant to the elderly population should be sought , particularly focussing on those issues highlighted in the accompanying qualitative study BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies The role of pharmacotherapy in the management of  severe aggressive behavior in children is review ed . An overview of the relevant literature , a discussion of method ological issues , and a description of a pilot study of the comparative efficacy of lithium , haloperidol , and chlorpromazine are presented . It is concluded that this area has not been studied systematic ally and that , in the future , research must be directed toward assessing the value of current and new pharmacological agents by using well-defined patient population s and attempting to identify subgroups of responders and nonresponders . Equally important are studies concerned with an evaluation of pharmacotherapy combined with psychosocial treatments . Lithium and haloperidol appear worthy of critical examination as adjuncts in the treatment of children for whom the long-term prognosis is poor . Journal of the American Academy of Child Psychiatry , 21 , 2:107–117 , 1982 Statistical procedures for  missing data have vastly improved , yet misconception and unsound practice still abound . The authors frame the missing- data problem , review methods , offer advice , and raise issues that remain unresolved . They clear up common misunderst and ings regarding the missing at r and om ( MAR ) concept . They summarize the evidence against older procedures and , with few exceptions , discourage their use . They present , in both technical and practical language , 2 general approaches that come highly recommended : maximum likelihood ( ML ) and Bayesian multiple imputation ( MI ) . Newer developments are discussed , including some for dealing with missing data that are not MAR . Although not yet in the mainstream , these procedures may eventually extend the ML and MI methods that currently represent the state of the art Combining and analyzing data from heterogeneous r and omized controlled trials of complex multiple-component intervention studies , or discussing them in a systematic review , is not straightforward . The present article describes certain issues to be considered when combining data across studies , based on discussion s in an NIH-sponsored workshop on pooling issues across studies in consortia ( see Belle et al. in Psychol Aging , 18(3):396–405 , 2003 ) . Several statistical method ologies are described and their advantages and limitations are explored . Whether weighting the different studies data differently , or via employing r and om effects , one must recognize that different pooling method ologies may yield different results . Pooling can be used for comprehensive exploratory analyses of data from RCTs and should not be viewed as replacing the st and ard analysis plan for each study . Pooling may help to identify intervention components that may be more effective especially for subsets of participants with certain behavioral characteristics . Pooling , when supported by statistical tests , can allow exploratory investigation of potential hypotheses and for the design of future interventions OBJECTIVES To determine the degree of recognition and underst and ing of depression and its treatments in Australia in 2001 , and detail factors and personal experiences that influence awareness of and attitudes to depression . DESIGN AND SETTING Cross-sectional survey of a representative community sample ( 900 r and omly selected respondents ) , via telephone interview , conducted 5 - 7 October 2001 . MAIN OUTCOME MEASURES Reports of community awareness , knowledge and attitudes to depression and its treatments in Australia . RESULTS The Australian community does not view mental health as a major general health issue . When asked specifically , depression was recognised as the most common mental health problem . Recognition of depression was greater among women and younger people . Most people ( 58 % ; 508/879 ) reported that they or a family member had experienced depression .  People younger than 55 years and people with personal or family experiences of depression viewed depression as more disabling than other chronic medical conditions . Half the respondents differentiated depression from normal sadness . Awareness of common risk versus protective factors was limited . Most people endorsed a preference for self-help and non-pharmacological treatments , but community views of antidepressant drugs were less negative than expected . General practitioners were identified as the preferred point of first contact among healthcare professionals . CONCLUSIONS Although mental health is still not highlighted as a major health issue , Australians do recognise depression as the major mental health problem . Women and younger people have more substantial knowledge about key aspects of depression and its treatments Background : Despite intensive research , there are no universally accepted clinical definitions for acute lung injury ( ALI ) or the acute respiratory distress syndrome ( ARDS ) . A recent joint American-European Consensus Conference on ARDS formally defined the difference between ALI and ARDS based on the degree of oxygenation impairment . However , this definition may not reflect the true prevalence , severity and prognosis of these syndromes . Methods : During a 22-month period , 56 consecutive mechanically ventilated patients who met the American-European Consensus definition for ARDS [ arterial oxygen tension/fractional inspired oxygen ( PaO2/FIO2≤ 200 mmHg regardless of the level of positive end-expiratory pressure ( PEEP ) , bilateral pulmonary infiltrates , and no evidence of left heart failure ] were admitted into the intensive care units ( ICU ) of the Hospital del Pino , Las Palmas , Spain , and prospect ively studied . The diagnosis of ALI and ARDS was made by a PEEP-FIO2 trial , 24 h after patients met the Consensus inclusion criteria . Patients were classified as having ALI–24 h if the PaO2/FIO2 was > 150 mmHg with PEEP = 5 cmH2O , and ARDS–24 h if the PaO2 /FIO2 was ≤ 150 mmHg with PEEP ≥ 5 cmH2O . Results : Overall mortality was 43 % ( 24 of 56 ) . However , 24 h after inclusion , PaO2 response to PEEP 5 cmH2O allowed the separation of our patients into two different groups : 31 patients met our ALI–24 h criteria ( PaO2/FIO2 > 150 mmHg ) and their mortality was 22.6 % ; 25 patients met our ARDS–24 h criteria ( PaO2/FIO2≤ 150 mmHg ) and their mortality was 68 % ( p = 0.0016 ) . The differences in the respiratory severity index during the first 24 h of inclusion , PaO2/FIO2 ratio at baseline and at 24 h , maximum plateau airway pressure , maximum level of PEEP , and number of organ system failures during the ICU stay were statistically significant . Conclusions : Since the use of PEEP in the American-European Consensus criteria for ARDS is not m and atory , that definition does not reflect the true severity of lung damage and outcome . Our data support the need for guidelines based on a specific method of evaluating oxygenation status before the American-European Consensus definition is adopted OBJECTIVE Recent studies have thrown doubt on the true effectiveness of anti-depressants in light and moderate depression . The aim of this study is to evaluate the impact of physical training and music therapy on a sample group of subjects affected by light to moderate depression versus subjects treated with pharmacological therapy only . DESIGN AND SETTING R and omized controlled study . Patients were r and omized into two groups . Subjects in the pharmacotherapy group received a therapy with antidepressant drugs ; the exercise/music therapy group was assigned to receive physical exercise training combined with listening to music . The effects of interventions were assessed by differences in changes in mood state between the two groups . MAIN OUTCOME MEASURES Medically eligible patients were screened with the Hamilton Anxiety Scale and with the Geriatric Depression Scale . We used plasmatic cytokine dosage as a stress marker . RESULTS We recruited 24 subjects ( mean age : 75.5 ± 7.4 , 11 M/13 F ) . In the pharmacotherapy group there was a significant improvement in anxiety only ( p<0.05 ) at 6-months . In the exercise/music therapy was a reduction in anxiety and in depression at 3-months and at 6-months ( p<0.05 ) . We noted an average reduction of the level of TNF-a from 57.67 ( ± 39.37 ) pg/ml to 35.80 ( ± 26.18 ) pg/ml . CONCLUSIONS Our training may potentially play a role in the treatment of subjects with mild to moderate depression . Further research should be carried out to obtain more evidence on effects of physical training and music therapy in depressed subjects The Fifth Commission on Antiepileptic Drugs of the International League Against Epilepsy was asked to advise the ILAE Executive on the place of new drugs in the treatment of patients with newly diagnosed or chronic epilepsy . With the licensing of a significant number of new antiepileptic drugs ( AEDs ) in the last 5 - 10 years , there is an obvious need for these new treatments to be introduced efficiently and effectively to benefit the care and management of people with epilepsy . Implicit in this will be a determination of the comparative efficacy , tolerability , and overall effectiveness against st and ard ( existing ) AEDs and against other new drugs . Although many of the issues relating to comparative studies were addressed in Guidelines for the Clinical Evaluation of Antiepileptic Drugs , produced by the Fourth Commission , several complex ethical and method ological problems remain that would benefit from further discussion aim ed at the establishment of some form of consensus . Although determination of the relative risks of rare but potentially serious idiosyncratic adverse reactions and teratogenicity can be determined only by adequate postmarketing surveillance , other issues concerning the efficacy , tolerability , and effectiveness of new drugs can best be determined within the context of well- design ed r and omized ( or otherwise controlled ) clinical trials ( RCTs ) . It is the design , structure , and outcomes of such comparative RCTs that dem and further consideration . Many of the difficulties arise because the most meaningful and satisfactory comparative studies will essentially be those that compare monotherapy with a new agent with monotherapy with alternative agents . The Commission recognizes that several different parties have interests in comparative studies . First and foremost patients and their doctors require adequate information to guide daily practice in an “ evidence -based ” way so that patients can make fully informed decisions about their drug treatment . Individual pharmaceutical manufacturers need to know how their drug compares with other products so that a drug can be appropriately positioned in the market . Licensing authorities have traditionally ignored issues of comparative Background Depression is one of the more severe and serious health problems because of its morbidity , disabling effects and for its societal and economic burden . Despite the variety of existing pharmacological and psychological treatments , most of the cases evolve with only partial remission , relapse and recurrence . Cognitive models have contributed significantly to the underst and ing of unipolar depression and its psychological treatment . However , success is only partial and many authors affirm the need to improve those models and also the treatment programs derived from them . One of the issues that requires further elaboration is the difficulty these patients experience in responding to treatment and in maintaining therapeutic gains across time without relapse or recurrence . Our research group has been working on the notion of cognitive conflict viewed as personal dilemmas according to personal construct theory . We use a novel method for identifying those conflicts using the repertory grid technique ( RGT ) . Preliminary results with depressive patients show that about 90 % of them have one or more of those conflicts . This fact might explain the blockage and the difficult progress of these patients , especially the more severe and /or chronic . These results justify the need for specific interventions focused on the resolution of these internal conflicts . This study aims to empirically test the hypothesis that an intervention focused on the dilemma(s ) specifically detected for each patient will enhance the efficacy of cognitive behavioral therapy ( CBT ) for depression . Design A therapy manual for a dilemma-focused intervention will be tested using a r and omized clinical trial by comparing the outcome of two treatment conditions : combined group CBT ( eight , 2-hour weekly sessions ) plus individual dilemma-focused therapy ( eight , 1-hour weekly sessions ) and CBT alone ( eight , 2-hour group weekly sessions plus eight , 1-hour individual weekly sessions ) . Method Participants are patients aged over 18 years meeting diagnostic criteria for major depressive disorder or dysthymic disorder , with a score of 19 or above on the Beck depression inventory , second edition ( BDI-II ) and presenting at least one cognitive conflict ( implicative dilemma or dilemmatic construct ) as assessed using the RGT . The BDI-II is the primary outcome measure , collected at baseline , at the end of therapy , and at 3- and 12-month follow-up ; other secondary measures are also used . Discussion We expect that adding a dilemma-focused intervention to CBT will increase the efficacy of one of the more prestigious therapies for depression , thus result ing in a significant contribution to the psychological treatment of depression . Trial registration IS RCT N92443999 ; Clinical Trials.gov Identifier : NCT01542957
Paroxetine , sertraline , citalopram , escitalopram , and clomipramine showed the most consistent results , while fluvoxamine , fluoxetine , and imipramine showed limited efficacy .
Preliminary results suggested the potential efficacy of inositol ; D-cycloserine showed mixed results for its ability to improve the outcome of exposure-based cognitive behavioral therapy .
No studies have been specifically oriented toward evaluating the effect of drugs on AG ; in the available studies , the improvement of AG might have been the consequence of the reduction of panic attacks .
BACKGROUND Although there are controversial issues ( the " American view " and the " European view " ) regarding the construct and definition of agoraphobia ( AG ) , this syndrome is well recognized and it is a burden in the lives of millions of people worldwide .
To better clarify the role of drug therapy in AG , the authors summarized and discussed recent evidence on pharmacological treatments , based on clinical trials available from 2000 , with the aim of highlighting pharmacotherapies that may improve this complex syndrome .