New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis.

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community-including patients, carers, clinicians, researchers and funders-to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world.

Vaccines for preventing rotavirus diarrhoea: vaccines in use.

BACKGROUND: Rotavirus is a common cause of diarrhoea, diarrhoea-related hospital admissions, and diarrhoea-related deaths worldwide. Rotavirus vaccines prequalified by the World Health Organization (WHO) include Rotarix (GlaxoSmithKline), RotaTeq (Merck), and, more recently, Rotasiil (Serum Institute of India Ltd.), and Rotavac (Bharat Biotech Ltd.). OBJECTIVES: To evaluate rotavirus vaccines prequalified by the WHO for their efficacy and safety in children. SEARCH METHODS: On 30 November 2020, we searched PubMed, the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, Science Citation Index Expanded, Social Sciences Citation Index, Conference Proceedings Citation Index-Science, Conference Proceedings Citation Index-Social Science & Humanities. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies, and relevant systematic reviews. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) conducted in children that compared rotavirus vaccines prequalified for use by the WHO with either placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and assessed risk of bias. One author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analyses by under-five country mortality rate and used GRADE to evaluate evidence certainty. MAIN RESULTS: Sixty trials met the inclusion criteria and enrolled a total of 228,233 participants. Thirty-six trials (119,114 participants) assessed Rotarix, 15 trials RotaTeq (88,934 participants), five trials Rotasiil (11,753 participants), and four trials Rotavac (8432 participants). Rotarix Infants vaccinated and followed up for the first year of life In low-mortality countries, Rotarix prevented 93% of severe rotavirus diarrhoea cases (14,976 participants, 4 trials; high-certainty evidence), and 52% of severe all-cause diarrhoea cases (3874 participants, 1 trial; moderate-certainty evidence).  In medium-mortality countries, Rotarix prevented 79% of severe rotavirus diarrhoea cases (31,671 participants, 4 trials; high-certainty evidence), and 36% of severe all-cause diarrhoea cases (26,479 participants, 2 trials; high-certainty evidence).  In high-mortality countries, Rotarix prevented 58% of severe rotavirus diarrhoea cases (15,882 participants, 4 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (5639 participants, 2 trials; high-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, Rotarix prevented 90% of severe rotavirus diarrhoea cases (18,145 participants, 6 trials; high-certainty evidence), and 51% of severe all-cause diarrhoea episodes (6269 participants, 2 trials; moderate-certainty evidence).   In medium-mortality countries, Rotarix prevented 77% of severe rotavirus diarrhoea cases (28,834 participants, 3 trials; high-certainty evidence), and 26% of severe all-cause diarrhoea cases (23,317 participants, 2 trials; moderate-certainty evidence).  In high-mortality countries, Rotarix prevented 35% of severe rotavirus diarrhoea cases (13,768 participants, 2 trials; moderate-certainty evidence), and 17% of severe all-cause diarrhoea cases (2764 participants, 1 trial; high-certainty evidence). RotaTeq Infants vaccinated and followed up for the first year of life In low-mortality countries, RotaTeq prevented 97% of severe rotavirus diarrhoea cases (5442 participants, 2 trials; high-certainty evidence).  In medium-mortality countries, RotaTeq prevented 79% of severe rotavirus diarrhoea cases (3863 participants, 1 trial; low-certainty evidence).  In high-mortality countries, RotaTeq prevented 57% of severe rotavirus diarrhoea cases (6775 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (1 trial, 4085 participants; moderate-certainty evidence).  Children vaccinated and followed up for two years In low-mortality countries, RotaTeq prevented 96% of severe rotavirus diarrhoea cases (5442 participants, 2 trials; high-certainty evidence).  In medium-mortality countries, RotaTeq prevented 79% of severe rotavirus diarrhoea cases (3863 participants, 1 trial; low-certainty evidence).  In high-mortality countries, RotaTeq prevented 44% of severe rotavirus diarrhoea cases (6744 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (5977 participants, 2 trials; high-certainty evidence).  We did not identify RotaTeq studies reporting on severe all-cause diarrhoea in low- or medium-mortality countries. Rotasiil Rotasiil has not been assessed in any RCT in countries with low or medium child mortality. Infants vaccinated and followed up for the first year of life In high-mortality countries, Rotasiil prevented 48% of severe rotavirus diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence), and resulted in little to no difference in severe all-cause diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence). Children vaccinated and followed up for two years In high-mortality countries, Rotasiil prevented 44% of severe rotavirus diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence), and resulted in little to no difference in severe all-cause diarrhoea cases (11,008 participants, 2 trials; high-certainty evidence). Rotavac Rotavac has not been assessed in any RCT in countries with low or medium child mortality.  Infants vaccinated and followed up for the first year of life In high-mortality countries, Rotavac prevented 57% of severe rotavirus diarrhoea cases (6799 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (6799 participants, 1 trial; moderate-certainty evidence). Children vaccinated and followed up for two years In high-mortality countries, Rotavac prevented 54% of severe rotavirus diarrhoea cases (6541 participants, 1 trial; moderate-certainty evidence); no Rotavac studies have reported on severe all-cause diarrhoea at two-years follow-up. Safety No increased risk of serious adverse events (SAEs) was detected with Rotarix (103,714 participants, 31 trials; high-certainty evidence), RotaTeq (82,502 participants, 14 trials; moderate to high-certainty evidence), Rotasiil (11,646 participants, 3 trials; high-certainty evidence), or Rotavac (8210 participants, 3 trials; moderate-certainty evidence). Deaths were infrequent and the analysis had insufficient evidence to show an effect on all-cause mortality. Intussusception was rare.  AUTHORS' CONCLUSIONS: Rotarix, RotaTeq, Rotasiil, and Rotavac prevent episodes of rotavirus diarrhoea. The relative effect estimate is smaller in high-mortality than in low-mortality countries, but more episodes are prevented in high-mortality settings as the baseline risk is higher. In high-mortality countries some results suggest lower efficacy in the second year. We found no increased risk of serious adverse events, including intussusception, from any of the prequalified rotavirus vaccines.

Vaccines for preventing rotavirus diarrhoea: vaccines in use.

BACKGROUND: Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a common cause of diarrhoea-related hospital admissions in countries with low childhood mortality. Rotavirus vaccines that have been prequalified by the World Health Organization (WHO) include a monovalent vaccine (RV1; Rotarix, GlaxoSmithKline), a pentavalent vaccine (RV5; RotaTeq, Merck), and, more recently, another monovalent vaccine (Rotavac, Bharat Biotech). OBJECTIVES: To evaluate rotavirus vaccines prequalified by the WHO (RV1, RV5, and Rotavac) for their efficacy and safety in children. SEARCH METHODS: On 4 April 2018 we searched MEDLINE (via PubMed), the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, and BIOSIS. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies and relevant systematic reviews. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) in children comparing rotavirus vaccines prequalified for use by the WHO versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and assessed risks of bias. One review author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analysis by country mortality rate and used GRADE to evaluate evidence certainty. MAIN RESULTS: Fifty-five trials met the inclusion criteria and enrolled a total of 216,480 participants. Thirty-six trials (119,114 participants) assessed RV1, 15 trials (88,934 participants) RV5, and four trials (8432 participants) Rotavac. RV1 Children vaccinated and followed up the first year of life In low-mortality countries, RV1 prevents 84% of severe rotavirus diarrhoea cases (RR 0.16, 95% CI 0.09 to 0.26; 43,779 participants, 7 trials; high-certainty evidence), and probably prevents 41% of cases of severe all-cause diarrhoea (RR 0.59, 95% CI 0.47 to 0.74; 28,051 participants, 3 trials; moderate-certainty evidence). In high-mortality countries, RV1 prevents 63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.23 to 0.60; 6114 participants, 3 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (RR 0.73, 95% CI 0.56 to 0.95; 5639 participants, 2 trials; high-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, RV1 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.14 to 0.23; 36,002 participants, 9 trials; high-certainty evidence), and probably prevents 37% of severe all-cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71; 39,091 participants, 2 trials; moderate-certainty evidence). In high-mortality countries RV1 probably prevents 35% of severe rotavirus diarrhoea cases (RR 0.65, 95% CI 0.51 to 0.83; 13,768 participants, 2 trials; high-certainty evidence), and 17% of severe all-cause diarrhoea cases (RR 0.83, 95% CI 0.72 to 0.96; 2764 participants, 1 trial; moderate-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.88 95% CI 0.83 to 0.93; high-certainty evidence). There were 30 cases of intussusception reported in 53,032 children after RV1 vaccination and 28 cases in 44,214 children after placebo or no intervention (RR 0.70, 95% CI 0.46 to 1.05; low-certainty evidence). RV5 Children vaccinated and followed up the first year of life In low-mortality countries, RV5 probably prevents 92% of severe rotavirus diarrhoea cases (RR 0.08, 95% CI 0.03 to 0.22; 4132 participants, 5 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 57% of severe rotavirus diarrhoea (RR 0.43, 95% CI 0.29 to 0.62; 5916 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (RR 0.80, 95% CI 0.58 to 1.11; 1 trial, 4085 participants; moderate-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, RV5 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.08 to 0.39; 7318 participants, 4 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82; 5885 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, 2 trials; high-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.86 to 1.01; moderate to high-certainty evidence). There were 16 cases of intussusception in 43,629 children after RV5 vaccination and 20 cases in 41,866 children after placebo (RR 0.77, 95% CI 0.41 to 1.45; low-certainty evidence). Rotavac Children vaccinated and followed up the first year of life Rotavac has not been assessed in any RCT in countries with low child mortality. In India, a high-mortality country, Rotavac probably prevents 57% of severe rotavirus diarrhoea cases (RR 0.43, 95% CI 0.30 to 0.60; 6799 participants, moderate-certainty evidence); the trial did not report on severe all-cause diarrhoea at one-year follow-up. Children vaccinated and followed up for two years Rotavac probably prevents 54% of severe rotavirus diarrhoea cases in India (RR 0.46, 95% CI 0.35 to 0.60; 6541 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (RR 0.84, 95% CI 0.71 to 0.98; 6799 participants, 1 trial; moderate-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.85 to 1.02; moderate-certainty evidence). There were eight cases of intussusception in 5764 children after Rotavac vaccination and three cases in 2818 children after placebo (RR 1.33, 95% CI 0.35 to 5.02; very low-certainty evidence). There was insufficient evidence of an effect on mortality from any rotavirus vaccine (198,381 participants, 44 trials; low- to very low-certainty evidence), as the trials were not powered to detect an effect at this endpoint. AUTHORS' CONCLUSIONS: RV1, RV5, and Rotavac prevent episodes of rotavirus diarrhoea. Whilst the relative effect estimate is smaller in high-mortality than in low-mortality countries, there is a greater number of episodes prevented in these settings as the baseline risk is much higher. We found no increased risk of serious adverse events. 21 October 2019 Up to date All studies incorporated from most recent search All published trials found in the last search (4 Apr, 2018) were included and 15 ongoing studies are currently awaiting completion (see 'Characteristics of ongoing studies').

CONTEXTE: Le rotavirus entraîne plus de décès liés à la diarrhée chez les enfants de moins de cinq ans que tout autre agent unique dans les pays où la mortalité infantile est élevée. C'est également une cause fréquente d'hospitalisations liées à la diarrhée dans les pays où la mortalité infantile est faible. Les vaccins antirotavirus préqualifiés par l'Organisation mondiale de la santé (OMS) comprennent un vaccin monovalent (RV1 ; Rotarix, GlaxoSmithKline), un vaccin pentavalent (RV5 ; RotaTeq, Merck) et plus récemment un autre vaccin monovalent (Rotavac, Bharat Biotech). OBJECTIFS: Évaluer les vaccins antirotavirus préqualifiés par l'OMS (RV1, RV5 et Rotavac) pour leur efficacité et leur innocuité chez les enfants. STRATÉGIE DE RECHERCHE DOCUMENTAIRE: Le 4 avril 2018, nous avons effectué une recherche dans MEDLINE (via PubMed), le registre spécialisé du groupe de travail Cochrane sur les maladies infectieuses (the Cochrane Infectious Diseases Group), CENTRAL (publié dans la Bibliothèque Cochrane), Embase, LILACS, et BIOSIS. Nous avons également effectué des recherches dans le système d'enregistrement international des essais cliniques (ICTRP) de l'OMS, ClinicalTrials.gov, les rapports d'essais cliniques trouvés sur les sites Web des fabricants, les références des études incluses et les revues systématiques pertinentes. CRITÈRES DE SÉLECTION: Nous avons sélectionné des essais cliniques contrôlés randomisés (ECR) chez des enfants comparant des vaccins antirotavirus préqualifiés pour utilisation par l'OMS à un placebo ou à aucune intervention. RECUEIL ET ANALYSE DES DONNÉES: Deux auteurs de la revue ont évalué de façon indépendante l'éligibilité à l'essai et évalué les risques de biais. Un auteur de la revue a extrait les données et un deuxième auteur les a vérifiées par recoupement. Nous avons combiné des données dichotomiques en utilisant le risque relatif (RR) et l'intervalle de confiance à 95 % (IC). Nous avons stratifié l'analyse par taux de mortalité par pays et utilisé GRADE pour évaluer la valeur probante des données. RÉSULTATS PRINCIPAUX: Cinquante­cinq essais ont satisfait aux critères d'inclusion et enrôlé 216 480 participants au total. Trente­six essais cliniques (119 114 participants) ont évalué le RV1, 15 essais cliniques (88 934 participants) le RV5 et quatre essais cliniques (8432 participants) le Rotavac. RV1 Enfants vaccinés et suivis au cours de leur première année de vie Dans les pays à faible mortalité, le RV1 prévient 84 % des cas graves de diarrhée à rotavirus (RR 0,16, IC à 95 % : 0,09 à 0,26 ; 43 779 participants, 7 essais ; données de bonne valeur probante) et probablement 41 % des cas de diarrhée sévère toutes causes confondues (RR 0,59, IC à 95 % : 0,47 à 0,74 ; 28 051 participants, 3 essais ; données de valeur probante moyenne). Dans les pays à forte mortalité, le RV1 prévient 63 % des cas graves de diarrhée à rotavirus (RR 0,37, IC à 95 % : 0,23 à 0,60 ; 6114 participants, 3 essais ; données de bonne valeur probante) et 27 % des cas graves de diarrhée toutes causes confondues (RR 0,73, IC à 95 % : 0,56 à 0,95 ; 5639 participants, 2 essais ; données de bonne valeur probante). Enfants vaccinés et suivis pendant deux ans Dans les pays à faible mortalité, le RV1 prévient 82 % des cas graves de diarrhée à rotavirus (RR 0,18, IC à 95 % : 0,14 à 0,23 ; 36 002 participants, 9 essais ; données de bonne valeur probante) et probablement 37 % des épisodes graves de diarrhée toutes causes confondues (rapport des taux 0,63, IC à 95 % : 0,56 à 0,71 ; 39 091 participants, 2 essais ; données de valeur probante moyenne). Dans les pays à forte mortalité, le RV1 prévient probablement 35 % des cas graves de diarrhée à rotavirus (RR 0,65, IC à 95 % : 0,51 à 0,83 ; 13 768 participants, 2 essais ; données de bonne valeur probante) et 17 % des cas graves de diarrhée toutes causes confondues (RR 0,83, IC à 95 % : 0,72 à 0,96 ; 2764 participants, 1 essai ; données de valeur probante moyenne). Aucune augmentation du risque d'événements indésirables graves (EIG) n'a été décelée (RR 0,88 IC à 95 % 0,83 à 0,93 ; données de bonne valeur probante). On a signalé 30 cas d'invagination (intussusception) intestinale chez 53 032 enfants après la vaccination RV1 et 28 cas chez 44 214 enfants après l'administration d'un placebo ou l'absence d'intervention (RR 0,70, IC à 95 % : 0,46 à 1,05 ; données de faible valeur probante). RV5 Enfants vaccinés et suivis au cours de leur première année de vie Dans les pays à faible mortalité, le RV5 prévient probablement 92 % des cas graves de diarrhée à rotavirus (RR 0,08, IC à 95 % : 0,03 à 0,22 ; 4 132 participants, 5 essais ; données de valeur probante moyenne). Nous n'avons pas identifié d'études sur les diarrhées graves toutes causes confondues dans les pays à faible mortalité. Dans les pays à forte mortalité, le RV5 prévient 57 % des cas de diarrhée à rotavirus grave (RR 0,43, IC à 95 % : 0,29 à 0,62 ; 5916 participants, 2 essais ; données de bonne valeur probante), mais il n'y a probablement que peu voire pas de différence entre vaccin et placebo pour la diarrhée grave toutes causes confondues (RR 0,80, IC à 95 % : 0,58 à 1,11 ; 1 essai, 4085 participants ; données de valeur probante moyenne). Enfants vaccinés et suivis pendant deux ans Dans les pays à faible mortalité, le RV5 prévient 82 % des cas graves de diarrhée à rotavirus (RR 0,18, IC à 95 % : 0,08 à 0,39 ; 7318 participants, 4 essais ; données de valeur probante moyenne). Nous n'avons pas identifié d'études sur les diarrhées graves toutes causes confondues dans les pays à faible mortalité. Dans les pays à forte mortalité, le RV5 prévient 41 % des cas graves de diarrhée à rotavirus (RR 0,59, IC à 95 % : 0,43 à 0,82 ; 5 885 participants, 2 essais ; données de bonne valeur probante) et 15 % des cas graves de diarrhée toutes causes confondues (RR 0,85, IC à 95 % : 0,75 à 0,98 ; 5977 participants, 2 essais ; données de bonne valeur probante). Aucune augmentation du risque d'évènements indésirables graves (EIG) n'a été décelée (RR 0,93 IC à 95 % 0,86 à 1,01 ; données de valeur probante moyenne à bonne). Il y a eu 16 cas d'invagination chez 43 629 enfants après la vaccination RV5 et 20 cas chez 41 866 enfants après le placebo (RR 0,77, IC à 95 % : 0,41 à 1,45 ; données de faible valeur probante). Rotavac Enfants vaccinés et suivis au cours de leur première année de vie Le Rotavac n'a fait l'objet d'aucun ECR dans les pays à faible mortalité infantile. En Inde, pays à forte mortalité, le Rotavac prévient probablement 57 % des cas graves de diarrhée à rotavirus (RR 0,43, IC à 95 % : 0,30 à 0,60 ; 6799 participants, données de valeur probante moyenne) ; l'essai n'a pas fait état de diarrhée grave toutes causes confondues à un an de suivi. Enfants vaccinés et suivis pendant deux ans Le Rotavac prévient probablement 54 % des cas graves de diarrhée à rotavirus en Inde (RR 0,46, IC à 95 % : 0,35 à 0,60 ; 6541 participants, 1 essai ; données de valeur probante moyenne) et 16 % des cas graves de diarrhée toutes causes confondues (RR 0,84, IC à 95 % : 0,71 à 0,98 ; 6799 participants, 1 essai ; données de valeur probante moyenne). Aucune augmentation du risque d'évènements indésirables graves (EIG) n'a été décelée (RR 0,93 95 % IC 0,85 à 1,02 ; données de valeur probante moyenne). Il y a eu huit cas d'invagination intestinale chez 5 764 enfants après la vaccination par Rotavac et trois cas chez 2 818 enfants après le placebo (RR 1,33, IC à 95 % : 0,35 à 5,02 ; données de très faible valeur probante). Il n'y avait pas suffisamment de données probante indiquant un effet sur la mortalité attribuable à un vaccin antirotavirus (198 381 participants, 44 essais ; données de valeur probante faible à très faible), car les essais n'étaient pas assez puissants pour détecter un effet à ce paramètre. CONCLUSIONS DES AUTEURS: Les vaccins RV1, RV5 et Rotavac préviennent les épisodes de diarrhée à rotavirus. Bien que l'estimation de l'effet relatif soit plus faible dans les pays à forte mortalité que dans les pays à faible mortalité, le nombre d'épisodes évités est plus élevé dans ces pays car le risque de base est beaucoup plus élevé. Nous n'avons trouvé aucun risque accru d'événements indésirables graves.

A rapid research needs appraisal methodology to identify evidence gaps to inform clinical research priorities in response to outbreaks-results from the Lassa fever pilot.

BACKGROUND: Infectious disease epidemics are a constant threat, and while we can strengthen preparedness in advance, inevitably, we will sometimes be caught unaware by novel outbreaks. To address the challenge of rapidly identifying clinical research priorities in those circumstances, we developed and piloted a protocol for carrying out a systematic, rapid research needs appraisal (RRNA) of existing evidence within 5 days in response to outbreaks globally, with the aim to inform clinical research prioritization. METHODS: The protocol was derived from rapid review methodologies and optimized through effective use of pre-defined templates and global time zones. It was piloted using a Lassa fever (LF) outbreak scenario. Databases were searched from 1969 to July 2017. Systematic reviewers based in Canada, the UK, and the Philippines screened and extracted data using a systematic review software. The pilot was evaluated through internal analysis and by comparing the research priorities identified from the data, with those identified by an external LF expert panel. RESULTS: The RRNA pilot was completed within 5 days. To accommodate the high number of articles identified, data extraction was prioritized by study design and year, and the clinical research prioritization done post-day 5. Of 118 potentially eligible articles, 52 met the data extraction criteria, of which 46 were extracted within the 5-day time frame. The RRNA team identified 19 clinical research priorities; the expert panel independently identified 21, of which 11 priorities overlapped. Each method identified a unique set of priorities, showing that combining both methods for clinical research prioritization is more robust than using either method alone. CONCLUSIONS: This pilot study shows that it is feasible to carry out a systematic RRNA within 5 days in response to a (re-) emerging outbreak to identify gaps in existing evidence, as long as sufficient resources are identified, and reviewers are experienced and trained in advance. Use of an online systematic review software and global time zones effectively optimized resources. Another 3 to 5 days are recommended for review of the extracted data and to formulate clinical research priorities. The RRNA can be used for a "Disease X" scenario and should optimally be combined with an expert panel to ensure breadth and depth of coverage of clinical research priorities.

Vaccines for preventing rotavirus diarrhoea: vaccines in use.

BACKGROUND: Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a common cause of diarrhoea-related hospital admissions in countries with low childhood mortality. Rotavirus vaccines that have been prequalified by the World Health Organization (WHO) include a monovalent vaccine (RV1; Rotarix, GlaxoSmithKline), a pentavalent vaccine (RV5; RotaTeq, Merck), and, more recently, another monovalent vaccine (Rotavac, Bharat Biotech). OBJECTIVES: To evaluate rotavirus vaccines prequalified by the WHO (RV1, RV5, and Rotavac) for their efficacy and safety in children. SEARCH METHODS: On 4 April 2018 we searched MEDLINE (via PubMed), the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, and BIOSIS. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies and relevant systematic reviews. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) in children comparing rotavirus vaccines prequalified for use by the WHO versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and assessed risks of bias. One review author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analysis by country mortality rate and used GRADE to evaluate evidence certainty. MAIN RESULTS: Fifty-five trials met the inclusion criteria and enrolled a total of 216,480 participants. Thirty-six trials (119,114 participants) assessed RV1, 15 trials (88,934 participants) RV5, and four trials (8432 participants) Rotavac.RV1 Children vaccinated and followed up the first year of life In low-mortality countries, RV1 prevents 84% of severe rotavirus diarrhoea cases (RR 0.16, 95% CI 0.09 to 0.26; 43,779 participants, 7 trials; high-certainty evidence), and probably prevents 41% of cases of severe all-cause diarrhoea (RR 0.59, 95% CI 0.47 to 0.74; 28,051 participants, 3 trials; moderate-certainty evidence). In high-mortality countries, RV1 prevents 63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.23 to 0.60; 6114 participants, 3 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (RR 0.73, 95% CI 0.56 to 0.95; 5639 participants, 2 trials; high-certainty evidence).Children vaccinated and followed up for two yearsIn low-mortality countries, RV1 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.14 to 0.23; 36,002 participants, 9 trials; high-certainty evidence), and probably prevents 37% of severe all-cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71; 39,091 participants, 2 trials; moderate-certainty evidence). In high-mortality countries RV1 probably prevents 35% of severe rotavirus diarrhoea cases (RR 0.65, 95% CI 0.51 to 0.83; 13,768 participants, 2 trials; high-certainty evidence), and 17% of severe all-cause diarrhoea cases (RR 0.83, 95% CI 0.72 to 0.96; 2764 participants, 1 trial; moderate-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.88 95% CI 0.83 to 0.93; high-certainty evidence). There were 30 cases of intussusception reported in 53,032 children after RV1 vaccination and 28 cases in 44,214 children after placebo or no intervention (RR 0.70, 95% CI 0.46 to 1.05; low-certainty evidence).RV5 Children vaccinated and followed up the first year of life In low-mortality countries, RV5 probably prevents 92% of severe rotavirus diarrhoea cases (RR 0.08, 95% CI 0.03 to 0.22; 4132 participants, 5 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 57% of severe rotavirus diarrhoea (RR 0.43, 95% CI 0.29 to 0.62; 5916 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (RR 0.80, 95% CI 0.58 to 1.11; 1 trial, 4085 participants; moderate-certainty evidence).Children vaccinated and followed up for two yearsIn low-mortality countries, RV5 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.08 to 0.39; 7318 participants, 4 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82; 5885 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, 2 trials; high-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.86 to 1.01; moderate to high-certainty evidence). There were 16 cases of intussusception in 43,629 children after RV5 vaccination and 20 cases in 41,866 children after placebo (RR 0.77, 95% CI 0.41 to 1.45; low-certainty evidence).Rotavac Children vaccinated and followed up the first year of life Rotavac has not been assessed in any RCT in countries with low child mortality. In India, a high-mortality country, Rotavac probably prevents 57% of severe rotavirus diarrhoea cases (RR 0.43, 95% CI 0.30 to 0.60; 6799 participants, moderate-certainty evidence); the trial did not report on severe all-cause diarrhoea at one-year follow-up.Children vaccinated and followed up for two yearsRotavac probably prevents 54% of severe rotavirus diarrhoea cases in India (RR 0.46, 95% CI 0.35 to 0.60; 6541 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (RR 0.84, 95% CI 0.71 to 0.98; 6799 participants, 1 trial; moderate-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.85 to 1.02; moderate-certainty evidence). There were eight cases of intussusception in 5764 children after Rotavac vaccination and three cases in 2818 children after placebo (RR 1.33, 95% CI 0.35 to 5.02; very low-certainty evidence).There was insufficient evidence of an effect on mortality from any rotavirus vaccine (198,381 participants, 44 trials; low- to very low-certainty evidence), as the trials were not powered to detect an effect at this endpoint. AUTHORS' CONCLUSIONS: RV1, RV5, and Rotavac prevent episodes of rotavirus diarrhoea. Whilst the relative effect estimate is smaller in high-mortality than in low-mortality countries, there is a greater number of episodes prevented in these settings as the baseline risk is much higher. We found no increased risk of serious adverse events.

PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation.

Scoping reviews, a type of knowledge synthesis, follow a systematic approach to map evidence on a topic and identify main concepts, theories, sources, and knowledge gaps. Although more scoping reviews are being done, their methodological and reporting quality need improvement. This document presents the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist and explanation. The checklist was developed by a 24-member expert panel and 2 research leads following published guidance from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. The final checklist contains 20 essential reporting items and 2 optional items. The authors provide a rationale and an example of good reporting for each item. The intent of the PRISMA-ScR is to help readers (including researchers, publishers, commissioners, policymakers, health care providers, guideline developers, and patients or consumers) develop a greater understanding of relevant terminology, core concepts, and key items to report for scoping reviews.

Client feedback in psychological therapy for children and adolescents with mental health problems.

BACKGROUND: Childhood and adolescent mental health problems are a serious and growing concern worldwide. Research suggests that psychotherapy can have a significant and positive impact on children and adolescents with mental health problems, such as anxiety disorders, depression and conduct disorders. Client feedback tools serve as a method of monitoring clients' progress and providing feedback from clients to therapists during the therapeutic process. These tools may help to enhance clinicians' decision-making by allowing them to adapt their treatment plans as the therapy progresses, resulting in a reduction of treatment failures. Research has shown that client feedback tools have a positive effect on adults' psychotherapy. This review addresses whether feedback tools in child and adolescent therapy could help therapists to better treat their young clients. OBJECTIVES: To assess the effects of client feedback in psychological therapy on child and adolescent mental health outcomes. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR, Studies and References), the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1946-), Embase (1974-) and PsycINFO (1967-) to 3 April 2018. We did not apply any restriction on date, language or publication status to the search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared client feedback to no client feedback in psychological therapies for children and adolescents. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed references for inclusion eligibility and extracted outcome, risk of bias and study characteristics data into customised forms. We contacted study authors to obtain missing data. We analysed dichotomous data using risk ratios (RRs) and calculated their 95% confidence intervals (CIs). For continuous data, we calculated mean differences (MDs), or standardised mean differences (SMDs) if different scales were used to measure the same outcome. We used a random-effects model for all analyses. MAIN RESULTS: We included six published RCTs, conducted in the USA (5 RCTs) and Israel (1 RCT), with 1097 children and adolescents (11 to 18 years old), in the review.We are very uncertain about the effect of client feedback on improvement of symptoms, as reported by youth in the short term because we considered evidence to be of very low-certainty due to high risk of bias and very serious inconsistency in the effect estimates from the different studies. Similarly, we are very uncertain about the effect of client feedback on treatment acceptability, due to high risk of bias, imprecision in the results, and indirectness of measuring the outcome (RR 1.08, 95% CI 0.73 to 1.61; 2 studies, 237 participants; very low-certainty).Overall, most studies reported and carried out randomisation and allocation concealment adequately. None of the studies were blinded or attempted to blind participants and personnel and were at high risk of performance bias, and only one study had blind outcome assessors. All of the studies were at high or unclear risk of attrition bias mainly due to poor, non-transparent reporting of participants' flow through the studies. AUTHORS' CONCLUSIONS: Due to the paucity of high-quality data and considerable inconsistency in results from different studies, there is currently insufficient evidence to reach any firm conclusions regarding the role of client feedback in psychological therapies for children and adolescents with mental health problems, and further research on this important topic is needed.Future studies should avoid risks of performance, detection and attrition biases, as seen in the studies included in this review. Studies from countries other than the USA are needed, as well as studies including children younger than 10 years.

Miscellaneous treatments for antipsychotic-induced tardive dyskinesia.

BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. This review, one in a series examining the treatment of TD, covers miscellaneous treatments not covered elsewhere. OBJECTIVES: To determine whether drugs, hormone-, dietary-, or herb-supplements not covered in other Cochrane reviews on TD treatments, surgical interventions, electroconvulsive therapy, and mind-body therapies were effective and safe for people with antipsychotic-induced TD. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including trial registers (16 July 2015 and 26 April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA: We included reports if they were randomised controlled trials (RCTs) dealing with people with antipsychotic-induced TD and schizophrenia or other chronic mental illnesses who remained on their antipsychotic medication and had been randomly allocated to the interventions listed above versus placebo, no intervention, or any other intervention. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created 'Summary of findings' tables using GRADE. MAIN RESULTS: We included 31 RCTs of 24 interventions with 1278 participants; 22 of these trials were newly included in this 2017 update. Five trials are awaiting classification and seven trials are ongoing. All participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. Studies were primarily of short (three to six6 weeks) duration with small samples size (10 to 157 participants), and most (61%) were published more than 20 years ago. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment, generation of the sequence, and blinding.Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found moderate-quality evidence of a benefit of the intervention compared with placebo: valbenazine (RR 0.63, 95% CI 0.46 to 0.86, 1 RCT, n = 92) and extract of Ginkgo biloba (RR 0.88, 95% CI 0.81 to 0.96, 1 RCT, n = 157), respectively. However, due to small sample sizes we cannot be certain of these effects.We consider the results for the remaining interventions to be inconclusive: Low- to very low-quality evidence of a benefit was found for buspirone (RR 0.53, 95% CI 0.33 to 0.84, 1 RCT, n = 42), dihydrogenated ergot alkaloids (RR 0.45, 95% CI 0.21 to 0.97, 1 RCT, n = 28), hypnosis or relaxation, (RR 0.45, 95% CI 0.21 to 0.94, 1 study, n = 15), pemoline (RR 0.48, 95% CI 0.29 to 0.77, 1 RCT, n = 46), promethazine (RR 0.24, 95% CI 0.11 to 0.55, 1 RCT, n = 34), insulin (RR 0.52, 95% CI 0.29 to 0.96, 1 RCT, n = 20), branched chain amino acids (RR 0.79, 95% CI 0.63 to 1.00, 1 RCT, n = 52), and isocarboxazid (RR 0.24, 95% CI 0.08 to 0.71, 1 RCT, n = 20). There was low- to very low-certainty evidence of no difference between intervention and placebo or no treatment for the following interventions: melatonin (RR 0.89, 95% CI 0.71 to 1.12, 2 RCTs, n = 32), lithium (RR 1.59, 95% CI 0.79 to 3.23, 1 RCT, n = 11), ritanserin (RR 1.00, 95% CI 0.70 to 1.43, 1 RCT, n = 10), selegiline (RR 1.37, 95% CI 0.96 to 1.94, 1 RCT, n = 33), oestrogen (RR 1.18, 95% CI 0.76 to 1.83, 1 RCT, n = 12), and gamma-linolenic acid (RR 1.00, 95% CI 0.69 to 1.45, 1 RCT, n = 16).None of the included studies reported on the other primary outcome, 'no clinically significant extrapyramidal adverse effects'. AUTHORS' CONCLUSIONS: This review has found that the use of valbenazine or extract of Ginkgo biloba may be effective in relieving the symptoms of tardive dyskinesia. However, since only one RCT has investigated each one of these compounds, we are awaiting results from ongoing trials to confirm these results. Results for the remaining interventions covered in this review must be considered inconclusive and these compounds probably should only be used within the context of a well-designed evaluative study.

Cholinergic medication for antipsychotic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) remains a troublesome adverse effect of conventional antipsychotic (neuroleptic) medication. It has been proposed that TD could have a component of central cholinergic deficiency. Cholinergic drugs have been used to treat TD. OBJECTIVES: To determine the effects of cholinergic drugs (arecoline, choline, deanol, lecithin, meclofenoxate, physostigmine, RS 86, tacrine, metoxytacrine, galantamine, ipidacrine, donepezil, rivastigmine, eptastigmine, metrifonate, xanomeline, cevimeline) for treating antipsychotic-induced TD in people with schizophrenia or other chronic mental illness. SEARCH METHODS: An electronic search of the Cochrane Schizophrenia Group's Study-Based Register of Trials (16 July 2015 and April 2017) was undertaken. This register is assembled by extensive searches for randomised controlled trials in many electronic databases, registers of trials, conference proceedings and dissertations. References of all identified studies were searched for further trial citations. SELECTION CRITERIA: We included reports identified by the search if they were of controlled trials involving people with antipsychotic-induced TD and chronic mental illness, who had been randomly allocated to either a cholinergic agent or to a placebo or no intervention. Two review authors independently assessed the methodological quality of the trials. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and, where possible, estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We analysed data on an intention-to-treat basis, with the assumption that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE. MAIN RESULTS: We included 14 studies investigating the use of cholinergic drugs compared with placebo published between 1976 and 2014. All studies involved small numbers of participants (five to 60 people). Three studies that investigated the new cholinergic Alzheimer drugs for the treatment of TD are new to this update. Overall, the risk of bias in the included studies was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, we are unsure if data are incomplete, and data were often poorly or selectively reported.We are uncertain about the effect of new or old cholinergic drugs on no clinically important improvement in TD symptoms when compared with placebo; the quality of evidence was very low (RR 0.89, 95% CI 0.65 to 1.23; 27 people, 4 RCTs). Eight trials found that cholinergic drugs may make little or no difference to deterioration of TD symptoms (low-quality evidence, RR 1.11, 95% CI 0.55 to 2.24; 147 people). Again, due to very low-quality evidence, we are uncertain about the effects on mental state (RR 0.50, 95% CI 0.10 to 2.61; 77 people, 5 RCTs), adverse events (RR 0.56, 95% CI 0.15 to 2.14; 106 people, 4 RCTs), and leaving the study early (RR 1.09,95% CI 0.56 to 2.10; 288 people 12 RCTs). No study reported on social confidence, social inclusion, social networks, or personalised quality of life. AUTHORS' CONCLUSIONS: TD remains a major public health problem. The clinical effects of both older cholinergic drugs and new cholinergic agents, now used for treating Alzheimer's disease, are unclear, as too few, too small studies leave many questions unanswered. Cholinergic drugs should remain of interest to researchers and currently have little place in routine clinical work. However, with the advent of new cholinergic agents now used for treating Alzheimer's disease, scope exists for more informative trials. If these new cholinergic agents are to be investigated for treating people with TD, their effects should be demonstrated in large well-designed, conducted and reported randomised trials.

Calcium channel blockers for antipsychotic-induced tardive dyskinesia.

BACKGROUND: Schizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic medications are associated with a variety of adverse effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil, flunarizine) have been among these experimental treatments. OBJECTIVES: To determine the effects of calcium channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA: We selected randomised controlled trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness who remained on their antipsychotic medication. DATA COLLECTION AND ANALYSIS: We independently extracted data and estimated risk ratios of dichotomous data or mean differences (MD) of continuous data, with 95% confidence intervals (CI). We assumed that people who left the trials early had no improvement. We also created a 'Summary of findings' table using GRADE. MAIN RESULTS: Previous versions of this review included no trials. From the 2015 search, we identified three cross-over trials that could be included. The 2017 search found no new studies relevant to this review. The included trials randomised 47 inpatients with chronic mental illnesses in the USA and China. Trials were published in the 1990s and were of short duration (six to 10 weeks). Overall, the risk of bias was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, and attrition and outcome data were not fully reported. Findings were sparse, no study reported on the primary outcome 'no clinically important improvement in tardive dyskinesia symptoms,' but two small studies (37 participants) found no difference on the tardive dyskinesia symptoms scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or flunarizine and placebo after three to four weeks' treatment (MD -0.71, 95% CI -2.68 to 1.26, very low quality evidence). Only one study randomising 20 participants reported on adverse events, and reported that there were no adverse events with flunarizine or with placebo (very low quality evidence). One study with 18 participants reported no events of deterioration in mental state with diltiazem or with placebo (very low quality evidence). No studies reported on acceptability of treatment or on social confidence, social inclusion, social networks or personalised quality of life outcomes designated important to patients. AUTHORS' CONCLUSIONS: Available evidence from randomised controlled trials is extremely limited and very low quality, conclusions cannot be drawn. The effects of calcium channel blockers for antipsychotic-induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well-designed randomised trials.

Antipsychotic reduction and/or cessation and antipsychotics as specific treatments for tardive dyskinesia.

BACKGROUND: Since the 1950s antipsychotic medication has been extensively used to treat people with chronic mental illnesses such as schizophrenia. These drugs, however, have also been associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. Various strategies have been examined to reduce a person's cumulative exposure to antipsychotics. These strategies include dose reduction, intermittent dosing strategies such as drug holidays, and antipsychotic cessation. OBJECTIVES: To determine whether a reduction or cessation of antipsychotic drugs is associated with a reduction in TD for people with schizophrenia (or other chronic mental illnesses) who have existing TD. Our secondary objective was to determine whether the use of specific antipsychotics for similar groups of people could be a treatment for TD that was already established. SEARCH METHODS: We updated previous searches of Cochrane Schizophrenia's study-based Register of Trials including the registers of clinical trials (16 July 2015 and 26 April 2017). We searched references of all identified studies for further trial citations. We also contacted authors of trials for additional information. SELECTION CRITERIA: We included reports if they assessed people with schizophrenia or other chronic mental illnesses who had established antipsychotic-induced TD, and had been randomly allocated to (a) antipsychotic maintenance versus antipsychotic cessation (placebo or no intervention), (b) antipsychotic maintenance versus antipsychotic reduction (including intermittent strategies), (c) specific antipsychotics for the treatment of TD versus placebo or no intervention, and (d) specific antipsychotics versus other antipsychotics or versus any other drugs for the treatment of TD. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who dropped out had no improvement. MAIN RESULTS: We included 13 RCTs with 711 participants; eight of these studies were newly included in this 2017 update. One trial is ongoing.There was low-quality evidence of a clear difference on no clinically important improvement in TD favouring switch to risperidone compared with antipsychotic cessation (with placebo) (1 RCT, 42 people, RR 0.45 CI 0.23 to 0.89, low-quality evidence). Because evidence was of very low quality for antipsychotic dose reduction versus antipsychotic maintenance (2 RCTs, 17 people, RR 0.42 95% CI 0.17 to 1.04, very low-quality evidence), and for switch to a new antipsychotic versus switch to another new antipsychotic (5 comparisons, 5 RCTs, 140 people, no meta-analysis, effects for all comparisons equivocal), we are uncertain about these effects. There was low-quality evidence of a significant difference on extrapyramidal symptoms: use of antiparkinsonism medication favouring switch to quetiapine compared with switch to haloperidol (1 RCT, 45 people, RR 0.45 CI 0.21 to 0.96, low-quality evidence). There was no evidence of a difference for switch to risperidone or haloperidol compared with antipsychotic cessation (with placebo) (RR 1 RCT, 48 people, RR 2.08 95% CI 0.74 to 5.86, low-quality evidence) and switch to risperidone compared with switch to haloperidol (RR 1 RCT, 37 people, RR 0.68 95% CI 0.34 to 1.35, very low-quality evidence).Trials also reported on secondary outcomes such as other TD symptom outcomes, other adverse events outcomes, mental state, and leaving the study early, but the quality of the evidence for all these outcomes was very low due mainly to small sample sizes, very wide 95% CIs, and risk of bias. No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, outcomes that we designated as being important to patients. AUTHORS' CONCLUSIONS: Limited data from small studies using antipsychotic reduction or specific antipsychotic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches. There is a need for larger trials of a longer duration to fully investigate this area.

Global health trials methodological research agenda: results from a priority setting exercise.

BACKGROUND: Methodological research into the design, conduct, analysis and reporting of trials is essential to optimise the process. UK specialists in the field have established a set of top priorities in aid of this research. These priorities, however, may not be reflected in the needs of similar research in low- to middle-income countries (LMICs) with different healthcare provision, resources and research infrastructure. The aim of the study was to identify the top priorities for methodological research in LMICs to inform further research and ultimately to improve clinical trials in these regions. METHODS: An online, two-round survey was conducted from December 2016 to April 2017 amongst researchers and methodologists working on trials in LMICs. The first round required participants to suggest between three and six topics which they felt were priorities for trial methodological research in LMICs. The second round invited participants to grade the importance of a compulsory list of topics suggested by four or more individuals, and an optional list of the remaining topics. FINDINGS: Rounds 1 and 2 were completed by 412 and 314 participants, respectively. A wide spread of years of experience, discipline, current country of residence, origin of trials training and area of involvement in trials was reported. The topics deemed most important for methodological research were: choosing appropriate outcomes to measure and training of research staff. CONCLUSION: By presenting these top priorities we have the foundations of a global health trials methodological research agenda which we hope will foster future research in specific areas in order to increase and improve trials in LMICs.

Vitamin E for antipsychotic-induced tardive dyskinesia.

BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. Vitamin E has been proposed as a treatment to prevent or decrease TD. OBJECTIVES: The primary objective was to determine the clinical effects of vitamin E in people with schizophrenia or other chronic mental illness who had developed antipsychotic-induced TD.The secondary objectives were:1. to examine whether the effect of vitamin E was maintained as duration of follow-up increased;2. to test the hypothesis that the use of vitamin E is most effective for those with early onset TD (less than five years) SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA: We included reports if they were controlled trials dealing with people with antipsychotic-induced TD and schizophrenia who remained on their antipsychotic medication and had been randomly allocated to either vitamin E or to a placebo, no intervention, or any other intervention. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE. MAIN RESULTS: The review now includes 13 poorly reported randomised trials (total 478 people), all participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. There was no clear difference between vitamin E and placebo for the outcome of TD: not improved to a clinically important extent (6 RCTs, N = 264, RR 0.95, 95% CI 0.89 to 1.01, low-quality evidence). However, people allocated to placebo may show more deterioration of their symptoms compared with those given vitamin E (5 RCTs, N = 85, RR 0.23, 95% CI 0.07 to 0.76, low-quality evidence). There was no evidence of a difference in the incidence of any adverse effects (9 RCTs, N = 205, RR 1.21, 95% CI 0.35 to 4.15, very low-quality evidence), extrapyramidal adverse effects (1 RCT, N = 104, MD 1.10, 95% CI -1.02 to 3.22, very low-quality evidence), or acceptability of treatment (measured by participants leaving the study early) (medium term, 8 RCTs, N = 232, RR 1.07, 95% CI 0.64 to 1.80, very low-quality evidence). No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, outcomes designated important to patients. There is no trial-based information regarding the effect of vitamin E for those with early onset of TD. AUTHORS' CONCLUSIONS: Small trials of limited quality suggest that vitamin E may protect against deterioration of TD. There is no evidence that vitamin E improves symptoms of this problematic and disfiguring condition once established. New and better trials are indicated in this under-researched area, and, of the many adjunctive treatments that have been given for TD, vitamin E would be a good choice for further evaluation.