Virtual wards for people with frailty: what works, for whom, how and why-a rapid realist review.

BACKGROUND: Virtual wards (VWs) deliver multidisciplinary care at home to people with frailty who are at high risk of a crisis or in crisis, aiming to mitigate the risk of acute hospital admission. Different VW models exist, and evidence of effectiveness is inconsistent. AIM: We conducted a rapid realist review to identify different VW models and to develop explanations for how and why VWs could deliver effective frailty management. METHODS: We searched published and grey literature to identify evidence on multidisciplinary VWs. Information on how and why VWs might 'work' was extracted and synthesised into context-mechanism-outcome configurations with input from clinicians and patient/public contributors. RESULTS: We included 17 peer-reviewed and 11 grey literature documents. VWs could be short-term and acute (1-21 days), or longer-term and preventative (typically 3-7 months). Effective VW operation requires common standards agreements, information sharing processes, an appropriate multidisciplinary team that plans patient care remotely, and good co-ordination. VWs may enable delivery of frailty interventions through appropriate selection of patients, comprehensive assessment including medication review, integrated case management and proactive care. Important components for patients and caregivers are good communication with the VW, their experience of care at home, and feeling involved, safe and empowered to manage their condition. CONCLUSIONS: Insights gained from this review could inform implementation or evaluation of VWs for frailty. A combination of acute and longer-term VWs may be needed within a whole system approach. Proactive care is recommended to avoid frailty-related crises.

Physical activity interventions in European primary schools: a scoping review to create a framework for the design of tailored interventions in European countries.

Introduction: Schools provide a unique environment to facilitate physical activity for children. However, many school-based physical activity interventions have not been effective. We propose a new approach, which allows schools to tailor interventions to their specific context. This scoping review aimed to identify intervention components from previous school-based physical activity interventions to form the basis of a tailored approach in a European setting. Methods: Joanna Briggs Institute guidelines for conducting scoping reviews were followed. European school-based intervention studies aimed at increasing physical activity in children aged 7-11 years published in English since 2015 were included. Databases searched were Ovid Medline, Embase, PsycINFO, Web of Science Social Sciences Citation Index, ERIC and British Education Index. Data was extracted on intervention components, context-related factors (geographical location, school size, child socioeconomic status and ethnicity), feasibility, acceptability and cost-effectiveness. A data-driven framework was developed to summarize the identified intervention components. Results: 79 articles were included, constituting 45 intervention studies. We identified 177 intervention components, which were synthesized into a framework of 60 intervention component types across 11 activity opportunities: six within the school day, three within the extended school day and two within the wider school environment. Interventions most frequently targeted physical education (21%), active and outdoor learning (16%), active breaks (15%), and school-level environmewnt (12%). Of the intervention components, 41% were delivered by school staff, 31% by the research team, and 24% by external organizations. Only 19% of intervention studies reported geographical location and only 10% reported school size. Participant ethnicity and socioeconomic information was reported by 15% and 25%, respectively. Intervention acceptability was reported in 51% of studies, feasibility in 49%, and cost effectiveness in 2%. Discussion: This review offers a first step in developing a future framework to help schools to develop context-specific, tailored interventions. However, there was a lack of reporting of contextual factors within the included studies, making it difficult to understand the role of context. Future research should seek to measure and report contextual factors, and to better understand the important aspects of context within school-based physical activity.

Vaginal birth core information set: study protocol for a Delphi study to achieve a consensus on a 'core information set' for vaginal birth.

INTRODUCTION: Studies have shown that women are often underinformed about potential benefits and risks of vaginal birth. This is in contrast to other modes of birth, such as caesarean birth, for which the risks/benefits are often conveyed prior to undergoing the procedure. A core information set (CIS) is an agreed set of information points that should be discussed with all patients prior to undergoing a procedure or intervention. This CIS could improve the quality of information given regarding mode of birth options, as women will be given information prioritised by patients and stakeholders regarding vaginal birth, empowering them to make informed decisions about their birth. We aim to describe the protocol for the development of this vaginal birth CIS. METHODS AND ANALYSIS: We will develop the CIS by: (1) Compiling a 'long-list' of information points about vaginal birth by: undertaking a scoping review of studies and patient information leaflets; interviews with antenatal/postnatal women, an online survey of stakeholders. (2) Collating the 'long-list' of information points and developing the Delphi survey. Think-aloud interviews will refine the survey. (3) Conducting a two-round Delphi survey. 200 stakeholder participants will be recruited. Items rated critically important by ≥80% of participants in one stakeholder group, or with no consensus, will be carried through to a stakeholder consensus meeting to decide the final CIS. Planned start date is 1 June 2022. Planned end date is 31 August 2023. ETHICS AND DISSEMINATION: This project has been given a favourable ethics opinion by the University of Bristol Research Ethics Committee (Ref: 10530). Approval from the ethics committee will be sought for any protocol amendments, and the principal investigator will be responsible for these changes. Findings will be presented at relevant conferences and published in a high-impact journal. We will disseminate the CIS, via Policy Bristol, to clinical policy and guideline developers.

Factors related to adverse long-term outcomes after mild traumatic brain injury in children: a scoping review.

OBJECTIVE: To identify demographic, premorbid and injury-related factors, or biomarkers associated with long-term (≥3 months) adverse outcomes in children after mild traumatic brain injury (mTBI). DESIGN: Scoping review of literature. PATIENTS: Children and adolescents with mTBI. RISK FACTORS: Any demographic, premorbid and injury-related factors, or biomarkers were included. We excluded genetic and treatment-related factors. MAIN OUTCOME MEASURES: Postconcussion syndrome (PCS), recovery. RESULTS: Seventy-three publications were included, reporting 12 long-term adverse outcomes, including PCS in 12 studies and recovery in 29 studies. Additional outcomes studied were symptom scores/severity (n=22), quality of life (n=9) and cognitive function (n=9). Forty-nine risk factors were identified across studies. Risk factors most often assessed were sex (n=28), followed by age (n=23), injury mechanism = (n=22) and prior mTBI (n=18). The influence of these and other risk factors on outcomes of mTBI were inconsistent across the reviewed literature. CONCLUSIONS: The most researched risk factors are sex, age and mechanism of injury, but their effects have been estimated inconsistently and did not show a clear pattern. The most studied outcomes are recovery patterns and symptom severity. However, these may not be the most important outcomes for clinicians and patients. Future primary studies in this area should focus on patient-important outcomes. Population-based prospective studies are needed that address prespecified hypotheses on the relationship of risk factors with given outcomes to enable reliable prediction of long-term adverse outcomes for childhood mTBI.

Educational interventions to prevent paediatric abusive head trauma in babies younger than one year old: A systematic review and meta-analyses.

BACKGROUND: Paediatric abusive head trauma (AHT) occurs in young children due to violent shaking or blunt impact. Educational and behavioural programmes modifying parent/infant interactions may aid primary prevention. This systematic review aims to assess the effectiveness of such interventions to prevent AHT in infants. METHODS: We searched Embase, MEDLINE, PsycINFO, The Cochrane library, CINAHL databases and trial registries to September 2021, for studies assessing the effectiveness of educational and behavioural interventions in preventing AHT. Eligible interventions had to include messaging about avoiding or dangers of infant shaking. Randomised controlled trials (RCTs) reporting results for primary (AHT, infant shaking) or secondary outcomes (including parental responses to infant crying, mental wellbeing), and non-randomised studies (NRSs) reporting primary outcomes were included. Evidence from combinable studies was synthesised using random-effects meta-analyses. Certainty of evidence was assessed using GRADE framework. PROSPERO registration CRD42020195644. FINDINGS: Of 25 identified studies, 16 were included in meta-analyses. Five NRSs reported results for AHT, of which four were meta-analysed (summary odds ratio [OR] 0.95, 95 % confidence intervals [CI] 0.80-1.13). Two studies assessed self-reported shaking (one cluster-RCT, OR 0.11, 95 % CI 0.02-0.53; one cohort study, OR 0.36, 95 % CI 0.20-0.64, not pooled). Meta-analyses of secondary outcomes demonstrated marginal improvements in parental response to inconsolable crying (summary mean difference 1.58, 95 % CI 0.11-3.06, on a 100-point scale) and weak evidence that interventions increased walking away from crying infants (summary incidence rate ratio 1.52, 95 % CI 0.94-2.45). No intervention effects were found in meta-analyses of parental mental wellbeing or other responses to crying. INTERPRETATION: Low certainty evidence suggests that educational programmes for AHT prevention are not effective in preventing AHT. There is low to moderate certainty evidence that educational interventions have no effect or only marginally improve some parental responses to infant crying.

Variations in policies for accessing elective musculoskeletal procedures in the English National Health Service: A documentary analysis.

OBJECTIVE: The overall aim of this study was to investigate how commissioning policies for accessing clinical procedures compare in the context of the English National Health Service. Our primary objective was to compare policy wording and categorise any variations identified. Our secondary objective was to explore how any points of variation relate to national guidance. METHODS: This study entailed documentary analysis of commissioning policies that stipulated criteria for accessing eight elective musculoskeletal procedures. For each procedure, we retrieved policies held by regions with higher and lower rates of clinical activity relative to the national average. Policies were subjected to content and thematic analysis, using constant comparison techniques. Matrices and descriptive reports were used to compare themes across policies for each procedure and derive categories of variation that arose across two or more procedures. National guidance relating to each procedure were identified and scrutinised, to explore whether these provided context for explaining the policy variations. RESULTS: Thirty-five policy documents held by 14 geographic regions were included in the analysis. Policies either focused on a single procedure/treatment or covered several procedures/treatments in an all-encompassing document. All policies stipulated criteria that needed to be fulfilled prior to accessing treatment, but there were inconsistences in the evidence cited. Policies varied in recurring ways, with respect to specification of non-surgical treatments and management, requirements around time spent using non-surgical approaches, diagnostic requirements, requirements around symptom severity and disease progression, and use of language, in the form of terms and phrases ('threshold modifiers') which could open up or restrict access to care. National guidance was identified for seven of the procedures, but this guidance did not specify criteria for accessing the procedures in question, making direct comparisons with regional policies difficult. CONCLUSIONS: This, to our knowledge, is the first study to identify recurring ways in which policies for accessing treatment can vary within a single-payer system with universal coverage. The findings raise questions around whether formulation of commissioning policies should receive more central support to promote greater consistency - especially where evidence is uncertain, variable or lacking.

Preventing Childhood Obesity in Primary Schools: A Realist Review from UK Perspective.

Childhood obesity is a global public health concern. While evidence from a recent comprehensive Cochrane review indicates school-based interventions can prevent obesity, we still do not know how or for whom these work best. We aimed to identify the contextual and mechanistic factors associated with obesity prevention interventions implementable in primary schools. A realist synthesis following the Realist And Meta-narrative Evidence Syntheses-Evolving Standards (RAMESES) guidance was with eligible studies from the 2019 Cochrane review on interventions in primary schools. The initial programme theory was developed through expert consensus and stakeholder input and refined with data from included studies to produce a final programme theory including all of the context-mechanism-outcome configurations. We included 24 studies (71 documents) in our synthesis. We found that baseline standardised body mass index (BMIz) affects intervention mechanisms variably as a contextual factor. Girls, older children and those with higher parental education consistently benefitted more from school-based interventions. The key mechanisms associated with beneficial effect were sufficient intervention dose, environmental modification and the intervention components working together as a whole. Education alone was not associated with favourable outcomes. Future interventions should go beyond education and incorporate a sufficient dose to trigger change in BMIz. Contextual factors deserve consideration when commissioning interventions to avoid widening health inequalities.

Quality of reporting and risk of bias: a review of randomised trials in occupational health.

OBJECTIVES: To assess the reporting quality of randomisation and allocation methods in occupational health and safety (OHS) trials in relation to Consolidated Standards of Reporting Trials (CONSORT) requirements of journals, risk of bias (RoB) and publication year. METHODS: We systematically searched for randomised controlled trials (RCTs) in PubMed between 2010 and May 2019 in 18 OHS journals. We measured reporting quality as percentage compliance with the CONSORT 2010 checklist (items 8-10) and RoB with the ROB V.2.0 tool (first domain). We tested the mean difference (MD) in % in reporting quality between CONSORT-requiring and non-requiring journals, trials with low, some concern and high RoB and publications before and after 2015. RESULTS: In 135 articles reporting on 129 RCTs, average reporting quality was at 37.4% compliance (95% CI 31.9% to 43.0%), with 10% of articles reaching 100% compliance. Reporting quality was significantly better in CONSORT-requiring journals than non-requiring journals (MD 31.0% (95% CI 21.4% to 40.7%)), for studies at low RoB than high RoB (MD 33.1% (95% CI 16.1% to 50.2%)) and with RoB of some concern (MD 39.8% (95% CI 30.0% to 49.7%)). Reporting quality did not improve over time (MD -5.7% (95% CI -16.8% to 5.4%). CONCLUSIONS: Articles in CONSORT-requiring journals and of low RoB studies show better reporting quality. Low reporting quality is linked to unclear RoB judgements (some concern). Reporting quality did not improve over the last 10 years and CONSORT is insufficiently implemented. Concerted efforts by editors and authors are needed to improve CONSORT implementation.

Evidence of detrimental effects of prenatal alcohol exposure on offspring birthweight and neurodevelopment from a systematic review of quasi-experimental studies.

BACKGROUND: Systematic reviews of prenatal alcohol exposure effects generally only include conventional observational studies. However, estimates from such studies are prone to confounding and other biases. OBJECTIVES: To systematically review the evidence on the effects of prenatal alcohol exposure from randomized controlled trials (RCTs) and observational designs using alternative analytical approaches to improve causal inference. SEARCH STRATEGY: Medline, Embase, Web of Science, PsychINFO from inception to 21 June 2018. Manual searches of reference lists of retrieved papers. SELECTION CRITERIA: RCTs of interventions to stop/reduce drinking in pregnancy and observational studies using alternative analytical methods (quasi-experimental studies e.g. Mendelian randomization and natural experiments, negative control comparisons) to determine the causal effects of prenatal alcohol exposure on pregnancy and longer-term offspring outcomes in human studies. DATA COLLECTION AND ANALYSIS: One reviewer extracted data and another checked extracted data. Risk of bias was assessed using customized risk of bias tools. A narrative synthesis of findings was carried out and a meta-analysis for one outcome. MAIN RESULTS: Twenty-three studies were included, representing five types of study design, including 1 RCT, 9 Mendelian randomization and 7 natural experiment studies, and reporting on over 30 outcomes. One study design-outcome combination included enough independent results to meta-analyse. Based on evidence from several studies, we found a likely causal detrimental role of prenatal alcohol exposure on cognitive outcomes, and weaker evidence for a role in low birthweight. CONCLUSION: None of the included studies was judged to be at low risk of bias in all domains, results should therefore be interpreted with caution. SYSTEMATIC REVIEW REGISTRATION: This study is registered with PROSPERO, registration number CRD42015015941.

Antipsychotic Polypharmacy and Metabolic Syndrome in Schizophrenia: A Review of Systematic Reviews.

(Reprinted with permission from BMC Psychiatry (2018) 18:275).

Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff.

BACKGROUND: In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. OBJECTIVES: To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. SELECTION CRITERIA: We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. MAIN RESULTS: Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants) coveralls were more difficult to doff than isolation gowns (very low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). According to three studies that tested more recently introduced full-body PPE ensembles, there may be no difference in contamination. Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. AUTHORS' CONCLUSIONS: We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.

Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff.

BACKGROUND: In epidemics of highly infectious diseases, such as Ebola, severe acute respiratory syndrome (SARS), or coronavirus (COVID-19), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Personal protective equipment (PPE) can reduce the risk by covering exposed body parts. It is unclear which type of PPE protects best, what is the best way to put PPE on (i.e. donning) or to remove PPE (i.e. doffing), and how to train HCWs to use PPE as instructed. OBJECTIVES: To evaluate which type of full-body PPE and which method of donning or doffing PPE have the least risk of contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to 20 March 2020. SELECTION CRITERIA: We included all controlled studies that evaluated the effect of full-body PPE used by HCW exposed to highly infectious diseases, on the risk of infection, contamination, or noncompliance with protocols. We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training on the same outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed the risk of bias in included trials. We conducted random-effects meta-analyses were appropriate. MAIN RESULTS: Earlier versions of this review were published in 2016 and 2019. In this update, we included 24 studies with 2278 participants, of which 14 were randomised controlled trials (RCT), one was a quasi-RCT and nine had a non-randomised design. Eight studies compared types of PPE. Six studies evaluated adapted PPE. Eight studies compared donning and doffing processes and three studies evaluated types of training. Eighteen studies used simulated exposure with fluorescent markers or harmless microbes. In simulation studies, median contamination rates were 25% for the intervention and 67% for the control groups. Evidence for all outcomes is of very low certainty unless otherwise stated because it is based on one or two studies, the indirectness of the evidence in simulation studies and because of risk of bias. Types of PPE The use of a powered, air-purifying respirator with coverall may protect against the risk of contamination better than a N95 mask and gown (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.17 to 0.43) but was more difficult to don (non-compliance: RR 7.5, 95% CI 1.81 to 31.1). In one RCT (59 participants), people with a long gown had less contamination than those with a coverall, and coveralls were more difficult to doff (low-certainty evidence). Gowns may protect better against contamination than aprons (small patches: mean difference (MD) -10.28, 95% CI -14.77 to -5.79). PPE made of more breathable material may lead to a similar number of spots on the trunk (MD 1.60, 95% CI -0.15 to 3.35) compared to more water-repellent material but may have greater user satisfaction (MD -0.46, 95% CI -0.84 to -0.08, scale of 1 to 5). Modified PPE versus standard PPE The following modifications to PPE design may lead to less contamination compared to standard PPE: sealed gown and glove combination (RR 0.27, 95% CI 0.09 to 0.78), a better fitting gown around the neck, wrists and hands (RR 0.08, 95% CI 0.01 to 0.55), a better cover of the gown-wrist interface (RR 0.45, 95% CI 0.26 to 0.78, low-certainty evidence), added tabs to grab to facilitate doffing of masks (RR 0.33, 95% CI 0.14 to 0.80) or gloves (RR 0.22, 95% CI 0.15 to 0.31). Donning and doffing Using Centers for Disease Control and Prevention (CDC) recommendations for doffing may lead to less contamination compared to no guidance (small patches: MD -5.44, 95% CI -7.43 to -3.45). One-step removal of gloves and gown may lead to less bacterial contamination (RR 0.20, 95% CI 0.05 to 0.77) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28) than separate removal. Double-gloving may lead to less viral or bacterial contamination compared to single gloving (RR 0.34, 95% CI 0.17 to 0.66) but not to less fluorescent contamination (RR 0.98, 95% CI 0.75 to 1.28). Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4) and to fewer contamination spots (MD -5, 95% CI -8.08 to -1.92). Extra sanitation of gloves before doffing with quaternary ammonium or bleach may decrease contamination, but not alcohol-based hand rub. Training The use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7). A video lecture on donning PPE may lead to better skills scores (MD 30.70, 95% CI 20.14 to 41.26) than a traditional lecture. Face-to-face instruction may reduce noncompliance with doffing guidance more (odds ratio 0.45, 95% CI 0.21 to 0.98) than providing folders or videos only. AUTHORS' CONCLUSIONS: We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort, and may therefore even lead to more contamination. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction. Modifications to PPE design, such as tabs to grab, may decrease the risk of contamination. For donning and doffing procedures, following CDC doffing guidance, a one-step glove and gown removal, double-gloving, spoken instructions during doffing, and using glove disinfection may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than folder-based training. We still need RCTs of training with long-term follow-up. We need simulation studies with more participants to find out which combinations of PPE and which doffing procedure protects best. Consensus on simulation of exposure and assessment of outcome is urgently needed. We also need more real-life evidence. Therefore, the use of PPE of HCW exposed to highly infectious diseases should be registered and the HCW should be prospectively followed for their risk of infection.

Pharmacological interventions for treatment-resistant depression in adults.

BACKGROUND: Although antidepressants are often a first-line treatment for adults with moderate to severe depression, many people do not respond adequately to medication, and are said to have treatment-resistant depression (TRD). Little evidence exists to inform the most appropriate 'next step' treatment for these people. OBJECTIVES: To assess the effectiveness of standard pharmacological treatments for adults with TRD. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (March 2016), CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science (31 December 2018), the World Health Organization trials portal and ClinicalTrials.gov for unpublished and ongoing studies, and screened bibliographies of included studies and relevant systematic reviews without date or language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) with participants aged 18 to 74 years with unipolar depression (based on criteria from DSM-IV-TR or earlier versions, International Classification of Diseases (ICD)-10, Feighner criteria or Research Diagnostic Criteria) who had not responded to a minimum of four weeks of antidepressant treatment at a recommended dose. Interventions were: (1) increasing the dose of antidepressant monotherapy; (2) switching to a different antidepressant monotherapy; (3) augmenting treatment with another antidepressant; (4) augmenting treatment with a non-antidepressant. All were compared with continuing antidepressant monotherapy. We excluded studies of non-standard pharmacological treatments (e.g. sex hormones, vitamins, herbal medicines and food supplements). DATA COLLECTION AND ANALYSIS: Two reviewers used standard Cochrane methods to extract data, assess risk of bias, and resolve disagreements. We analysed continuous outcomes with mean difference (MD) or standardised mean difference (SMD) and 95% confidence interval (CI). For dichotomous outcomes, we calculated a relative risk (RR) and 95% CI. Where sufficient data existed, we conducted meta-analyses using random-effects models. MAIN RESULTS: We included 10 RCTs (2731 participants). Nine were conducted in outpatient settings and one in both in- and outpatients. Mean age of participants ranged from 42 - 50.2 years, and most were female. One study investigated switching to, or augmenting current antidepressant treatment with, another antidepressant (mianserin). Another augmented current antidepressant treatment with the antidepressant mirtazapine. Eight studies augmented current antidepressant treatment with a non-antidepressant (either an anxiolytic (buspirone) or an antipsychotic (cariprazine; olanzapine; quetiapine (3 studies); or ziprasidone (2 studies)). We judged most studies to be at a low or unclear risk of bias. Only one of the included studies was not industry-sponsored. There was no evidence of a difference in depression severity when current treatment was switched to mianserin (MD on Hamilton Rating Scale for Depression (HAM-D) = -1.8, 95% CI -5.22 to 1.62, low-quality evidence)) compared with continuing on antidepressant monotherapy. Nor was there evidence of a difference in numbers dropping out of treatment (RR 2.08, 95% CI 0.94 to 4.59, low-quality evidence; dropouts 38% in the mianserin switch group; 18% in the control). Augmenting current antidepressant treatment with mianserin was associated with an improvement in depression symptoms severity scores from baseline (MD on HAM-D -4.8, 95% CI -8.18 to -1.42; moderate-quality evidence). There was no evidence of a difference in numbers dropping out (RR 1.02, 95% CI 0.38 to 2.72; low-quality evidence; 19% dropouts in the mianserin-augmented group; 38% in the control). When current antidepressant treatment was augmented with mirtazapine, there was little difference in depressive symptoms (MD on Beck Depression Inventory (BDI-II) -1.7, 95% CI -4.03 to 0.63; high-quality evidence) and no evidence of a difference in dropout numbers (RR 0.50, 95% CI 0.15 to 1.62; dropouts 2% in mirtazapine-augmented group; 3% in the control). Augmentation with buspirone provided no evidence of a benefit in terms of a reduction in depressive symptoms (MD on Montgomery and Asberg Depression Rating Scale (MADRS) -0.30, 95% CI -9.48 to 8.88; low-quality evidence) or numbers of drop-outs (RR 0.60, 95% CI 0.23 to 1.53; low-quality evidence; dropouts 11% in buspirone-augmented group; 19% in the control). Severity of depressive symptoms reduced when current treatment was augmented with cariprazine (MD on MADRS -1.50, 95% CI -2.74 to -0.25; high-quality evidence), olanzapine (MD on HAM-D -7.9, 95% CI -16.76 to 0.96; low-quality evidence; MD on MADRS -12.4, 95% CI -22.44 to -2.36; low-quality evidence), quetiapine (SMD -0.32, 95% CI -0.46 to -0.18; I2 = 6%, high-quality evidence), or ziprasidone (MD on HAM-D -2.73, 95% CI -4.53 to -0.93; I2 = 0, moderate-quality evidence) compared with continuing on antidepressant monotherapy. However, a greater number of participants dropped out when antidepressant monotherapy was augmented with an antipsychotic (cariprazine RR 1.68, 95% CI 1.16 to 2.41; quetiapine RR 1.57, 95% CI: 1.14 to 2.17; ziprasidone RR 1.60, 95% CI 1.01 to 2.55) compared with antidepressant monotherapy, although estimates for olanzapine augmentation were imprecise (RR 0.33, 95% CI 0.04 to 2.69). Dropout rates ranged from 10% to 39% in the groups augmented with an antipsychotic, and from 12% to 23% in the comparison groups. The most common reasons for dropping out were side effects or adverse events. We also summarised data about response and remission rates (based on changes in depressive symptoms) for included studies, along with data on social adjustment and social functioning, quality of life, economic outcomes and adverse events. AUTHORS' CONCLUSIONS: A small body of evidence shows that augmenting current antidepressant therapy with mianserin or with an antipsychotic (cariprazine, olanzapine, quetiapine or ziprasidone) improves depressive symptoms over the short-term (8 to 12 weeks). However, this evidence is mostly of low or moderate quality due to imprecision of the estimates of effects. Improvements with antipsychotics need to be balanced against the increased likelihood of dropping out of treatment or experiencing an adverse event. Augmentation of current antidepressant therapy with a second antidepressant, mirtazapine, does not produce a clinically important benefit in reduction of depressive symptoms (high-quality evidence). The evidence regarding the effects of augmenting current antidepressant therapy with buspirone or switching current antidepressant treatment to mianserin is currently insufficient. Further trials are needed to increase the certainty of these findings and to examine long-term effects of treatment, as well as the effectiveness of other pharmacological treatment strategies.

Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff.

BACKGROUND: In epidemics of highly infectious diseases, such as Ebola Virus Disease (EVD) or Severe Acute Respiratory Syndrome (SARS), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Contact precautions by means of personal protective equipment (PPE) can reduce the risk. It is unclear which type of PPE protects best, what is the best way to remove PPE, and how to make sure HCW use PPE as instructed. OBJECTIVES: To evaluate which type of full body PPE and which method of donning or doffing PPE have the least risk of self-contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS: We searched MEDLINE (PubMed up to 15 July 2018), Cochrane Central Register of Trials (CENTRAL up to 18 June 2019), Scopus (Scopus 18 June 2019), CINAHL (EBSCOhost 31 July 2018), and OSH-Update (up to 31 December 2018). We also screened reference lists of included trials and relevant reviews, and contacted NGOs and manufacturers of PPE. SELECTION CRITERIA: We included all controlled studies that compared the effects of PPE used by HCW exposed to highly infectious diseases with serious consequences, such as Ebola or SARS, on the risk of infection, contamination, or noncompliance with protocols. This included studies that used simulated contamination with fluorescent markers or a non-pathogenic virus.We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training in PPE use on the same outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We planned to perform meta-analyses but did not find sufficiently similar studies to combine their results. MAIN RESULTS: We included 17 studies with 1950 participants evaluating 21 interventions. Ten studies are Randomised Controlled Trials (RCTs), one is a quasi RCT and six have a non-randomised controlled design. Two studies are awaiting assessment.Ten studies compared types of PPE but only six of these reported sufficient data. Six studies compared different types of donning and doffing and three studies evaluated different types of training. Fifteen studies used simulated exposure with fluorescent markers or harmless viruses. In simulation studies, contamination rates varied from 10% to 100% of participants for all types of PPE. In one study HCW were exposed to Ebola and in another to SARS.Evidence for all outcomes is based on single studies and is very low quality.Different types of PPEPPE made of more breathable material may not lead to more contamination spots on the trunk (Mean Difference (MD) 1.60 (95% Confidence Interval (CI) -0.15 to 3.35) than more water repellent material but may have greater user satisfaction (MD -0.46; 95% CI -0.84 to -0.08, scale of 1 to 5).Gowns may protect better against contamination than aprons (MD large patches -1.36 95% CI -1.78 to -0.94).The use of a powered air-purifying respirator may protect better than a simple ensemble of PPE without such respirator (Relative Risk (RR) 0.27; 95% CI 0.17 to 0.43).Five different PPE ensembles (such as gown vs. coverall, boots with or without covers, hood vs. cap, length and number of gloves) were evaluated in one study, but there were no event data available for compared groups.Alterations to PPE design may lead to less contamination such as added tabs to grab masks (RR 0.33; 95% CI 0.14 to 0.80) or gloves (RR 0.22 95% CI 0.15 to 0.31), a sealed gown and glove combination (RR 0.27; 95% CI 0.09 to 0.78), or a better fitting gown around the neck, wrists and hands (RR 0.08; 95% CI 0.01 to 0.55) compared to standard PPE.Different methods of donning and doffing proceduresDouble gloving may lead to less contamination compared to single gloving (RR 0.36; 95% CI 0.16 to 0.78).Following CDC recommendations for doffing may lead to less contamination compared to no guidance (MD small patches -5.44; 95% CI -7.43 to -3.45).Alcohol-based hand rub used during the doffing process may not lead to less contamination than the use of a hypochlorite based solution (MD 4.00; 95% CI 0.47 to 34.24).Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4).Different types of trainingThe use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7).A video lecture on donning PPE may lead to better skills scores (MD 30.70; 95% CI 20.14,41.26) than a traditional lecture.Face to face instruction may reduce noncompliance with doffing guidance more (OR 0.45; 95% CI 0.21 to 0.98) than providing folders or videos only.There were no studies on effects of training in the long term or on resource use.The quality of the evidence is very low for all comparisons because of high risk of bias in all studies, indirectness of evidence, and small numbers of participants. AUTHORS' CONCLUSIONS: We found very low quality evidence that more breathable types of PPE may not lead to more contamination, but may have greater user satisfaction. Alterations to PPE, such as tabs to grab may decrease contamination. Double gloving, following CDC doffing guidance, and spoken instructions during doffing may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than video or folder based training. Because data come from single small studies with high risk of bias, we are uncertain about the estimates of effects.We still need randomised controlled trials to find out which training works best in the long term. We need better simulation studies conducted with several dozen participants to find out which PPE protects best, and what is the safest way to remove PPE. Consensus on the best way to conduct simulation of exposure and assessment of outcome is urgently needed. HCW exposed to highly infectious diseases should have their use of PPE registered and should be prospectively followed for their risk of infection in the field.

Interventions for preventing obesity in children.

BACKGROUND: Prevention of childhood obesity is an international public health priority given the significant impact of obesity on acute and chronic diseases, general health, development and well-being. The international evidence base for strategies to prevent obesity is very large and is accumulating rapidly. This is an update of a previous review. OBJECTIVES: To determine the effectiveness of a range of interventions that include diet or physical activity components, or both, designed to prevent obesity in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsychINFO and CINAHL in June 2015. We re-ran the search from June 2015 to January 2018 and included a search of trial registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) of diet or physical activity interventions, or combined diet and physical activity interventions, for preventing overweight or obesity in children (0-17 years) that reported outcomes at a minimum of 12 weeks from baseline. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed risk-of-bias and evaluated overall certainty of the evidence using GRADE. We extracted data on adiposity outcomes, sociodemographic characteristics, adverse events, intervention process and costs. We meta-analysed data as guided by the Cochrane Handbook for Systematic Reviews of Interventions and presented separate meta-analyses by age group for child 0 to 5 years, 6 to 12 years, and 13 to 18 years for zBMI and BMI. MAIN RESULTS: We included 153 RCTs, mostly from the USA or Europe. Thirteen studies were based in upper-middle-income countries (UMIC: Brazil, Ecuador, Lebanon, Mexico, Thailand, Turkey, US-Mexico border), and one was based in a lower middle-income country (LMIC: Egypt). The majority (85) targeted children aged 6 to 12 years.Children aged 0-5 years: There is moderate-certainty evidence from 16 RCTs (n = 6261) that diet combined with physical activity interventions, compared with control, reduced BMI (mean difference (MD) -0.07 kg/m2, 95% confidence interval (CI) -0.14 to -0.01), and had a similar effect (11 RCTs, n = 5536) on zBMI (MD -0.11, 95% CI -0.21 to 0.01). Neither diet (moderate-certainty evidence) nor physical activity interventions alone (high-certainty evidence) compared with control reduced BMI (physical activity alone: MD -0.22 kg/m2, 95% CI -0.44 to 0.01) or zBMI (diet alone: MD -0.14, 95% CI -0.32 to 0.04; physical activity alone: MD 0.01, 95% CI -0.10 to 0.13) in children aged 0-5 years.Children aged 6 to 12 years: There is moderate-certainty evidence from 14 RCTs (n = 16,410) that physical activity interventions, compared with control, reduced BMI (MD -0.10 kg/m2, 95% CI -0.14 to -0.05). However, there is moderate-certainty evidence that they had little or no effect on zBMI (MD -0.02, 95% CI -0.06 to 0.02). There is low-certainty evidence from 20 RCTs (n = 24,043) that diet combined with physical activity interventions, compared with control, reduced zBMI (MD -0.05 kg/m2, 95% CI -0.10 to -0.01). There is high-certainty evidence that diet interventions, compared with control, had little impact on zBMI (MD -0.03, 95% CI -0.06 to 0.01) or BMI (-0.02 kg/m2, 95% CI -0.11 to 0.06).Children aged 13 to 18 years: There is very low-certainty evidence that physical activity interventions, compared with control reduced BMI (MD -1.53 kg/m2, 95% CI -2.67 to -0.39; 4 RCTs; n = 720); and low-certainty evidence for a reduction in zBMI (MD -0.2, 95% CI -0.3 to -0.1; 1 RCT; n = 100). There is low-certainty evidence from eight RCTs (n = 16,583) that diet combined with physical activity interventions, compared with control, had no effect on BMI (MD -0.02 kg/m2, 95% CI -0.10 to 0.05); or zBMI (MD 0.01, 95% CI -0.05 to 0.07; 6 RCTs; n = 16,543). Evidence from two RCTs (low-certainty evidence; n = 294) found no effect of diet interventions on BMI.Direct comparisons of interventions: Two RCTs reported data directly comparing diet with either physical activity or diet combined with physical activity interventions for children aged 6 to 12 years and reported no differences.Heterogeneity was apparent in the results from all three age groups, which could not be entirely explained by setting or duration of the interventions. Where reported, interventions did not appear to result in adverse effects (16 RCTs) or increase health inequalities (gender: 30 RCTs; socioeconomic status: 18 RCTs), although relatively few studies examined these factors.Re-running the searches in January 2018 identified 315 records with potential relevance to this review, which will be synthesised in the next update. AUTHORS' CONCLUSIONS: Interventions that include diet combined with physical activity interventions can reduce the risk of obesity (zBMI and BMI) in young children aged 0 to 5 years. There is weaker evidence from a single study that dietary interventions may be beneficial.However, interventions that focus only on physical activity do not appear to be effective in children of this age. In contrast, interventions that only focus on physical activity can reduce the risk of obesity (BMI) in children aged 6 to 12 years, and adolescents aged 13 to 18 years. In these age groups, there is no evidence that interventions that only focus on diet are effective, and some evidence that diet combined with physical activity interventions may be effective. Importantly, this updated review also suggests that interventions to prevent childhood obesity do not appear to result in adverse effects or health inequalities.The review will not be updated in its current form. To manage the growth in RCTs of child obesity prevention interventions, in future, this review will be split into three separate reviews based on child age.

Workplace interventions for reducing sitting at work.

BACKGROUND: A large number of people are employed in sedentary occupations. Physical inactivity and excessive sitting at workplaces have been linked to increased risk of cardiovascular disease, obesity, and all-cause mortality. OBJECTIVES: To evaluate the effectiveness of workplace interventions to reduce sitting at work compared to no intervention or alternative interventions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, OSH UPDATE, PsycINFO, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal up to 9 August 2017. We also screened reference lists of articles and contacted authors to find more studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cross-over RCTs, cluster-randomised controlled trials (cluster-RCTs), and quasi-RCTs of interventions to reduce sitting at work. For changes of workplace arrangements, we also included controlled before-and-after studies. The primary outcome was time spent sitting at work per day, either self-reported or measured using devices such as an accelerometer-inclinometer and duration and number of sitting bouts lasting 30 minutes or more. We considered energy expenditure, total time spent sitting (including sitting at and outside work), time spent standing at work, work productivity and adverse events as secondary outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full-text articles for study eligibility. Two review authors independently extracted data and assessed risk of bias. We contacted authors for additional data where required. MAIN RESULTS: We found 34 studies - including two cross-over RCTs, 17 RCTs, seven cluster-RCTs, and eight controlled before-and-after studies - with a total of 3,397 participants, all from high-income countries. The studies evaluated physical workplace changes (16 studies), workplace policy changes (four studies), information and counselling (11 studies), and multi-component interventions (four studies). One study included both physical workplace changes and information and counselling components. We did not find any studies that specifically investigated the effects of standing meetings or walking meetings on sitting time.Physical workplace changesInterventions using sit-stand desks, either alone or in combination with information and counselling, reduced sitting time at work on average by 100 minutes per workday at short-term follow-up (up to three months) compared to sit-desks (95% confidence interval (CI) -116 to -84, 10 studies, low-quality evidence). The pooled effect of two studies showed sit-stand desks reduced sitting time at medium-term follow-up (3 to 12 months) by an average of 57 minutes per day (95% CI -99 to -15) compared to sit-desks. Total sitting time (including sitting at and outside work) also decreased with sit-stand desks compared to sit-desks (mean difference (MD) -82 minutes/day, 95% CI -124 to -39, two studies) as did the duration of sitting bouts lasting 30 minutes or more (MD -53 minutes/day, 95% CI -79 to -26, two studies, very low-quality evidence).We found no significant difference between the effects of standing desks and sit-stand desks on reducing sitting at work. Active workstations, such as treadmill desks or cycling desks, had unclear or inconsistent effects on sitting time.Workplace policy changesWe found no significant effects for implementing walking strategies on workplace sitting time at short-term (MD -15 minutes per day, 95% CI -50 to 19, low-quality evidence, one study) and medium-term (MD -17 minutes/day, 95% CI -61 to 28, one study) follow-up. Short breaks (one to two minutes every half hour) reduced time spent sitting at work on average by 40 minutes per day (95% CI -66 to -15, one study, low-quality evidence) compared to long breaks (two 15-minute breaks per workday) at short-term follow-up.Information and counsellingProviding information, feedback, counselling, or all of these resulted in no significant change in time spent sitting at work at short-term follow-up (MD -19 minutes per day, 95% CI -57 to 19, two studies, low-quality evidence). However, the reduction was significant at medium-term follow-up (MD -28 minutes per day, 95% CI -51 to -5, two studies, low-quality evidence).Computer prompts combined with information resulted in no significant change in sitting time at work at short-term follow-up (MD -14 minutes per day, 95% CI -39 to 10, three studies, low-quality evidence), but at medium-term follow-up they produced a significant reduction (MD -55 minutes per day, 95% CI -96 to -14, one study). Furthermore, computer prompting resulted in a significant decrease in the average number (MD -1.1, 95% CI -1.9 to -0.3, one study) and duration (MD -74 minutes per day, 95% CI -124 to -24, one study) of sitting bouts lasting 30 minutes or more.Computer prompts with instruction to stand reduced sitting at work on average by 14 minutes per day (95% CI 10 to 19, one study) more than computer prompts with instruction to walk at least 100 steps at short-term follow-up.We found no significant reduction in workplace sitting time at medium-term follow-up following mindfulness training (MD -23 minutes per day, 95% CI -63 to 17, one study, low-quality evidence). Similarly a single study reported no change in sitting time at work following provision of highly personalised or contextualised information and less personalised or contextualised information. One study found no significant effects of activity trackers on sitting time at work.Multi-component interventions Combining multiple interventions had significant but heterogeneous effects on sitting time at work (573 participants, three studies, very low-quality evidence) and on time spent in prolonged sitting bouts (two studies, very low-quality evidence) at short-term follow-up. AUTHORS' CONCLUSIONS: At present there is low-quality evidence that the use of sit-stand desks reduce workplace sitting at short-term and medium-term follow-ups. However, there is no evidence on their effects on sitting over longer follow-up periods. Effects of other types of interventions, including workplace policy changes, provision of information and counselling, and multi-component interventions, are mostly inconsistent. The quality of evidence is low to very low for most interventions, mainly because of limitations in study protocols and small sample sizes. There is a need for larger cluster-RCTs with longer-term follow-ups to determine the effectiveness of different types of interventions to reduce sitting time at work.

Antipsychotic polypharmacy and metabolic syndrome in schizophrenia: a review of systematic reviews.

BACKGROUND: There is conflicting evidence on the association between antipsychotic polypharmacy and metabolic syndrome in schizophrenia. We conducted a review of published systematic reviews to evaluate evidence on the association between metabolic syndrome (diabetes, hypertension, and hyperlipidaemia) and exposure to antipsychotic polypharmacy in schizophrenia. METHODS: We searched five electronic databases, complemented by reference screening, to find systematic reviews that investigated the association of antipsychotic polypharmacy in schizophrenia with hypertension, diabetes, or hyperlipidaemia. Selection of reviews, data extraction and review quality were conducted independently by two people and disagreements resolved by discussion. Results were synthesised narratively. RESULTS: We included 12 systematic reviews, which reported heterogeneous results, mostly with narrative syntheses and without pooled data. The evidence was rated as low quality. There was some indication of a possible protective effect of drug combinations including aripiprazole for diabetes and hyperlipidaemias, compared to other combinations and/or monotherapy. Only one review reported the association between APP and hypertension. The most frequently reported combinations of medication included clozapine, possibly representing a sample of patients with treatment resistant illness. No included review reported results separately by setting (primary or secondary care). CONCLUSIONS: Further robust studies are needed to elucidate the possible protective effect of aripiprazole. Long-term prospective studies are required for accurate appraisal of diabetes risk, hypertension and hyperlipidaemia in patients exposed to antipsychotic polypharmacy.

Workplace interventions for reducing sitting at work.

BACKGROUND: A large number of people are employed in sedentary occupations. Physical inactivity and excessive sitting at workplaces have been linked to increased risk of cardiovascular disease, obesity, and all-cause mortality. OBJECTIVES: To evaluate the effectiveness of workplace interventions to reduce sitting at work compared to no intervention or alternative interventions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, OSH UPDATE, PsycINFO, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal up to 9 August 2017. We also screened reference lists of articles and contacted authors to find more studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cross-over RCTs, cluster-randomised controlled trials (cluster-RCTs), and quasi-RCTs of interventions to reduce sitting at work. For changes of workplace arrangements, we also included controlled before-and-after studies. The primary outcome was time spent sitting at work per day, either self-reported or measured using devices such as an accelerometer-inclinometer and duration and number of sitting bouts lasting 30 minutes or more. We considered energy expenditure, total time spent sitting (including sitting at and outside work), time spent standing at work, work productivity and adverse events as secondary outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full-text articles for study eligibility. Two review authors independently extracted data and assessed risk of bias. We contacted authors for additional data where required. MAIN RESULTS: We found 34 studies - including two cross-over RCTs, 17 RCTs, seven cluster-RCTs, and eight controlled before-and-after studies - with a total of 3,397 participants, all from high-income countries. The studies evaluated physical workplace changes (16 studies), workplace policy changes (four studies), information and counselling (11 studies), and multi-component interventions (four studies). One study included both physical workplace changes and information and counselling components. We did not find any studies that specifically investigated the effects of standing meetings or walking meetings on sitting time.Physical workplace changesInterventions using sit-stand desks, either alone or in combination with information and counselling, reduced sitting time at work on average by 100 minutes per workday at short-term follow-up (up to three months) compared to sit-desks (95% confidence interval (CI) -116 to -84, 10 studies, low-quality evidence). The pooled effect of two studies showed sit-stand desks reduced sitting time at medium-term follow-up (3 to 12 months) by an average of 57 minutes per day (95% CI -99 to -15) compared to sit-desks. Total sitting time (including sitting at and outside work) also decreased with sit-stand desks compared to sit-desks (mean difference (MD) -82 minutes/day, 95% CI -124 to -39, two studies) as did the duration of sitting bouts lasting 30 minutes or more (MD -53 minutes/day, 95% CI -79 to -26, two studies, very low-quality evidence).We found no significant difference between the effects of standing desks and sit-stand desks on reducing sitting at work. Active workstations, such as treadmill desks or cycling desks, had unclear or inconsistent effects on sitting time.Workplace policy changesWe found no significant effects for implementing walking strategies on workplace sitting time at short-term (MD -15 minutes per day, 95% CI -50 to 19, low-quality evidence, one study) and medium-term (MD -17 minutes/day, 95% CI -61 to 28, one study) follow-up. Short breaks (one to two minutes every half hour) reduced time spent sitting at work on average by 40 minutes per day (95% CI -66 to -15, one study, low-quality evidence) compared to long breaks (two 15-minute breaks per workday) at short-term follow-up.Information and counsellingProviding information, feedback, counselling, or all of these resulted in no significant change in time spent sitting at work at short-term follow-up (MD -19 minutes per day, 95% CI -57 to 19, two studies, low-quality evidence). However, the reduction was significant at medium-term follow-up (MD -28 minutes per day, 95% CI -51 to -5, two studies, low-quality evidence).Computer prompts combined with information resulted in no significant change in sitting time at work at short-term follow-up (MD -10 minutes per day, 95% CI -45 to 24, two studies, low-quality evidence), but at medium-term follow-up they produced a significant reduction (MD -55 minutes per day, 95% CI -96 to -14, one study). Furthermore, computer prompting resulted in a significant decrease in the average number (MD -1.1, 95% CI -1.9 to -0.3, one study) and duration (MD -74 minutes per day, 95% CI -124 to -24, one study) of sitting bouts lasting 30 minutes or more.Computer prompts with instruction to stand reduced sitting at work on average by 14 minutes per day (95% CI 10 to 19, one study) more than computer prompts with instruction to walk at least 100 steps at short-term follow-up.We found no significant reduction in workplace sitting time at medium-term follow-up following mindfulness training (MD -23 minutes per day, 95% CI -63 to 17, one study, low-quality evidence). Similarly a single study reported no change in sitting time at work following provision of highly personalised or contextualised information and less personalised or contextualised information. One study found no significant effects of activity trackers on sitting time at work.Multi-component interventions Combining multiple interventions had significant but heterogeneous effects on sitting time at work (573 participants, three studies, very low-quality evidence) and on time spent in prolonged sitting bouts (two studies, very low-quality evidence) at short-term follow-up. AUTHORS' CONCLUSIONS: At present there is low-quality evidence that the use of sit-stand desks reduce workplace sitting at short-term and medium-term follow-ups. However, there is no evidence on their effects on sitting over longer follow-up periods. Effects of other types of interventions, including workplace policy changes, provision of information and counselling, and multi-component interventions, are mostly inconsistent. The quality of evidence is low to very low for most interventions, mainly because of limitations in study protocols and small sample sizes. There is a need for larger cluster-RCTs with longer-term follow-ups to determine the effectiveness of different types of interventions to reduce sitting time at work.