Decision-support tools via mobile devices to improve quality of care in primary healthcare settings.

BACKGROUND: The ubiquity of mobile devices has made it possible for clinical decision-support systems (CDSS) to become available to healthcare providers on handheld devices at the point-of-care, including in low- and middle-income countries. The use of CDSS by providers can potentially improve adherence to treatment protocols and patient outcomes. However, the evidence on the effect of the use of CDSS on mobile devices needs to be synthesized. This review was carried out to support a World Health Organization (WHO) guideline that aimed to inform investments on the use of decision-support tools on digital devices to strengthen primary healthcare. OBJECTIVES: To assess the effects of digital clinical decision-support systems (CDSS) accessible via mobile devices by primary healthcare providers in the context of primary care settings. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Global Index Medicus, POPLINE, and two trial registries from 1 January 2000 to 9 October 2020. We conducted a grey literature search using mHealthevidence.org and issued a call for papers through popular digital health communities of practice. Finally, we conducted citation searches of included studies. SELECTION CRITERIA: Study design: we included randomized trials, including full-text studies, conference abstracts, and unpublished data irrespective of publication status or language of publication.  Types of participants: we included studies of all cadres of healthcare providers, including lay health workers and other individuals (administrative, managerial, and supervisory staff) involved in the delivery of primary healthcare services using clinical decision-support tools; and studies of clients or patients receiving care from primary healthcare providers using digital decision-support tools. Types of interventions: we included studies comparing digital CDSS accessible via mobile devices with non-digital CDSS or no intervention, in the context of primary care. CDSS could include clinical protocols, checklists, and other job-aids which supported risk prioritization of patients. Mobile devices included mobile phones of any type (but not analogue landline telephones), as well as tablets, personal digital assistants, and smartphones. We excluded studies where digital CDSS were used on laptops or integrated with electronic medical records or other types of longitudinal tracking of clients. DATA COLLECTION AND ANALYSIS: A machine learning classifier that gave each record a probability score of being a randomized trial screened all search results. Two review authors screened titles and abstracts of studies with more than 10% probability of being a randomized trial, and one review author screened those with less than 10% probability of being a randomized trial. We followed standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care group. We used the GRADE approach to assess the certainty of the evidence for the most important outcomes. MAIN RESULTS: Eight randomized trials across varying healthcare contexts in the USA,. India, China, Guatemala, Ghana, and Kenya, met our inclusion criteria. A range of healthcare providers (facility and community-based, formally trained, and lay workers) used digital CDSS. Care was provided for the management of specific conditions such as cardiovascular disease, gastrointestinal risk assessment, and maternal and child health. The certainty of evidence ranged from very low to moderate, and we often downgraded evidence for risk of bias and imprecision. We are uncertain of the effect of this intervention on providers' adherence to recommended practice due to the very low certainty evidence (2 studies, 185 participants). The effect of the intervention on patients' and clients' health behaviours such as smoking and treatment adherence is mixed, with substantial variation across outcomes for similar types of behaviour (2 studies, 2262 participants). The intervention probably makes little or no difference to smoking rates among people at risk of cardiovascular disease but probably increases other types of desired behaviour among patients, such as adherence to treatment. The effect of the intervention on patients'/clients' health status and well-being  is also mixed (5 studies, 69,767 participants). It probably makes little or no difference to some types of health outcomes, but we are uncertain about other health outcomes, including maternal and neonatal deaths, due to very low-certainty evidence. The intervention may slightly improve patient or client acceptability and satisfaction (1 study, 187 participants). We found no studies that reported the time between the presentation of an illness and appropriate management, provider acceptability or satisfaction, resource use, or unintended consequences. AUTHORS' CONCLUSIONS: We are uncertain about the effectiveness of mobile phone-based decision-support tools on several outcomes, including adherence to recommended practice. None of the studies had a quality of care framework and focused only on specific health areas.   We need well-designed research that takes a systems lens to assess these issues.

Birth and death notification via mobile devices: a mixed methods systematic review.

BACKGROUND: Ministries of health, donors, and other decision-makers are exploring how they can use mobile technologies to acquire accurate and timely statistics on births and deaths. These stakeholders have called for evidence-based guidance on this topic. This review was carried out to support World Health Organization (WHO) recommendations on digital interventions for health system strengthening. OBJECTIVES: Primary objective: To assess the effects of birth notification and death notification via a mobile device, compared to standard practice. Secondary objectives: To describe the range of strategies used to implement birth and death notification via mobile devices and identify factors influencing the implementation of birth and death notification via mobile devices. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Global Health Library, and POPLINE (August 2, 2019). We searched two trial registries (August 2, 2019). We also searched Epistemonikos for related systematic reviews and potentially eligible primary studies (August 27, 2019). We conducted a grey literature search using mHealthevidence.org (August 15, 2017) and issued a call for papers through popular digital health communities of practice. Finally, we conducted citation searches of included studies in Web of Science and Google Scholar (May 15, 2020). We searched for studies published after 2000 in any language.  SELECTION CRITERIA: For the primary objective, we included individual and cluster-randomised trials; cross-over and stepped-wedge study designs; controlled before-after studies, provided they have at least two intervention sites and two control sites; and interrupted time series studies. For the secondary objectives, we included any study design, either quantitative, qualitative, or descriptive, that aimed to describe current strategies for birth and death notification via mobile devices; or to explore factors that influence the implementation of these strategies, including studies of acceptability or feasibility. For the primary objective, we included studies that compared birth and death notification via mobile devices with standard practice. For the secondary objectives, we included studies of birth and death notification via mobile device as long as we could extract data relevant to our secondary objectives. We included studies of all cadres of healthcare providers, including lay health workers; administrative, managerial, and supervisory staff; focal individuals at the village or community level; children whose births were being notified and their parents/caregivers; and individuals whose deaths were being notified and their relatives/caregivers. DATA COLLECTION AND ANALYSIS: For the primary objective, two authors independently screened all records, extracted data from the included studies and assessed risk of bias. For the analyses of the primary objective, we reported means and proportions, where appropriate. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence and we prepared a 'Summary of Findings' table. For the secondary objectives, two authors screened all records, one author extracted data from the included studies and assessed methodological limitations using the WEIRD tool and a second author checked the data and assessments. We carried out a framework analysis using the Supporting the Use of Research Evidence (SURE) framework to identify themes in the data. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in the evidence and we prepared a 'Summary of Qualitative Findings' table. MAIN RESULTS: For the primary objective, we included one study, which used a controlled before-after study design. The study was conducted in Lao People's Democratic Republic and assessed the effect of using mobile devices for birth notification on outcomes related to coverage and timeliness of Hepatitis B vaccination. However, we are uncertain of the effect of this approach on these outcomes because the certainty of this evidence was assessed as very low. The included study did not assess resource use or unintended consequences. For the primary objective, we did not identify any studies using mobile devices for death notification. For the secondary objective, we included 21 studies. All studies were conducted in low- or middle-income settings. They focussed on identification of births and deaths in rural, remote, or marginalised populations who are typically under-represented in civil registration processes or traditionally seen as having poor access to health services. The review identified several factors that could influence the implementation of birth-death notification via mobile device. These factors were tied to the health system, the person responsible for notifying, the community and families; and include: - Geographic barriers that could prevent people's access to birth-death notification and post-notification services - Access to health workers and other notifiers with enough training, supervision, support, and incentives - Monitoring systems that ensure the quality and timeliness of the birth and death data - Legal frameworks that allow births and deaths to be notified by mobile device and by different types of notifiers - Community awareness of the need to register births and deaths - Socio-cultural norms around birth and death - Government commitment - Cost to the system, to health workers and to families - Access to electricity and network connectivity, and compatibility with existing systems - Systems that protect data confidentiality We have low to moderate confidence in these findings. This was mainly because of concerns about methodological limitations and data adequacy. AUTHORS' CONCLUSIONS: We need more, well-designed studies of the effect of birth and death notification via mobile devices and on factors that may influence its implementation.

Targeted client communication via mobile devices for improving sexual and reproductive health.

BACKGROUND: The burden of poor sexual and reproductive health (SRH) worldwide is substantial, disproportionately affecting those living in low- and middle-income countries. Targeted client communication (TCC) delivered via mobile devices (MD) (TCCMD) may improve the health behaviours and service use important for sexual and reproductive health. OBJECTIVES: To assess the effects of TCC via MD on adolescents' knowledge, and on adolescents' and adults' sexual and reproductive health behaviour, health service use, and health and well-being. SEARCH METHODS: In July/August 2017, we searched five databases including The Cochrane Central Register of Controlled Trials, MEDLINE and Embase. We also searched two trial registries. A search update was carried out in July 2019 and potentially relevant studies are awaiting classification. SELECTION CRITERIA: We included randomised controlled trials of TCC via MD to improve sexual and reproductive health behaviour, health service use, and health and well-being. Eligible comparators were standard care or no intervention, non-digital TCC, and digital non-targeted communication. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane, although data extraction and risk of bias assessments were carried out by one person only and cross-checked by a second. We have presented results separately for adult and adolescent populations, and for each comparison. MAIN RESULTS: We included 40 trials (27 among adult populations and 13 among adolescent populations) with a total of 26,854 participants. All but one of the trials among adolescent populations were conducted in high-income countries. Trials among adult populations were conducted in a range of high- to low-income countries. Among adolescents, nine interventions were delivered solely through text messages; four interventions tested text messages in combination with another communication channel, such as emails, multimedia messaging, or voice calls; and one intervention used voice calls alone. Among adults, 20 interventions were delivered through text messages; two through a combination of text messages and voice calls; and the rest were delivered through other channels such as voice calls, multimedia messaging, interactive voice response, and instant messaging services. Adolescent populations TCCMD versus standard care TCCMD may increase sexual health knowledge (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.23 to 1.71; low-certainty evidence). TCCMD may modestly increase contraception use (RR 1.19, 95% CI 1.05 to 1.35; low-certainty evidence). The effects on condom use, antiretroviral therapy (ART) adherence, and health service use are uncertain due to very low-certainty evidence. The effects on abortion and STI rates are unknown due to lack of studies. TCCMD versus non-digital TCC (e.g. pamphlets) The effects of TCCMD on behaviour (contraception use, condom use, ART adherence), service use, health and wellbeing (abortion and STI rates) are unknown due to lack of studies for this comparison. TCCMD versus digital non-targeted communication The effects on sexual health knowledge, condom and contraceptive use are uncertain due to very low-certainty evidence. Interventions may increase health service use (attendance for STI/HIV testing, RR 1.61, 95% CI 1.08 to 2.40; low-certainty evidence). The intervention may be beneficial for reducing STI rates (RR 0.61, 95% CI 0.28 to 1.33; low-certainty evidence), but the confidence interval encompasses both benefit and harm. The effects on abortion rates and on ART adherence are unknown due to lack of studies. We are uncertain whether TCCMD results in unintended consequences due to lack of evidence. Adult populations TCCMD versus standard care For health behaviours, TCCMD may modestly increase contraception use at 12 months (RR 1.17, 95% CI 0.92 to 1.48) and may reduce repeat abortion (RR 0.68 95% CI 0.28 to 1.66), though the confidence interval encompasses benefit and harm (low-certainty evidence). The effect on condom use is uncertain. No study measured the impact of this intervention on STI rates. TCCMD may modestly increase ART adherence (RR 1.13, 95% CI 0.97 to 1.32, low-certainty evidence, and standardised mean difference 0.44, 95% CI -0.14 to 1.02, low-certainty evidence). TCCMD may modestly increase health service utilisation (RR 1.17, 95% CI 1.04 to 1.31; low-certainty evidence), but there was substantial heterogeneity (I2 = 85%), with mixed results according to type of service utilisation (i.e. attendance for STI testing; HIV treatment; voluntary male medical circumcision (VMMC); VMMC post-operative visit; post-abortion care). For health and well-being outcomes, there may be little or no effect on CD4 count (mean difference 13.99, 95% CI -8.65 to 36.63; low-certainty evidence) and a slight reduction in virological failure (RR 0.86, 95% CI 0.73 to 1.01; low-certainty evidence). TCCMD versus non-digital TCC No studies reported STI rates, condom use, ART adherence, abortion rates, or contraceptive use as outcomes for this comparison. TCCMD may modestly increase in service attendance overall (RR: 1.12, 95% CI 0.92-1.35, low certainty evidence), however the confidence interval encompasses benefit and harm. TCCMD versus digital non-targeted communication No studies reported STI rates, condom use, ART adherence, abortion rates, or contraceptive use as outcomes for this comparison. TCCMD may increase service utilisation overall (RR: 1.71, 95% CI 0.67-4.38, low certainty evidence), however the confidence interval encompasses benefit and harm and there was considerable heterogeneity (I2 = 72%), with mixed results according to type of service utilisation (STI/HIV testing, and VMMC). Few studies reported on unintended consequences. One study reported that a participant withdrew from the intervention as they felt it compromised their undisclosed HIV status. AUTHORS' CONCLUSIONS: TCCMD may improve some outcomes but the evidence is of low certainty. The effect on most outcomes is uncertain/unknown due to very low certainty evidence or lack of evidence. High quality, adequately powered trials and cost effectiveness analyses are required to reliably ascertain the effects and relative benefits of TCC delivered by mobile devices. Given the sensitivity and stigma associated with sexual and reproductive health future studies should measure unintended consequences, such as partner violence or breaches of confidentiality.

Targeted client communication via mobile devices for improving maternal, neonatal, and child health.

BACKGROUND: The global burden of poor maternal, neonatal, and child health (MNCH) accounts for more than a quarter of healthy years of life lost worldwide. Targeted client communication (TCC) via mobile devices (MD) (TCCMD) may be a useful strategy to improve MNCH. OBJECTIVES: To assess the effects of TCC via MD on health behaviour, service use, health, and well-being for MNCH. SEARCH METHODS: In July/August 2017, we searched five databases including The Cochrane Central Register of Controlled Trials, MEDLINE and Embase. We also searched two trial registries. A search update was carried out in July 2019 and potentially relevant studies are awaiting classification. SELECTION CRITERIA: We included randomised controlled trials that assessed TCC via MD to improve MNCH behaviour, service use, health, and well-being. Eligible comparators were usual care/no intervention, non-digital TCC, and digital non-targeted client communication. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane, although data extraction and risk of bias assessments were carried out by one person only and cross-checked by a second. MAIN RESULTS: We included 27 trials (17,463 participants). Trial populations were: pregnant and postpartum women (11 trials conducted in low-, middle- or high-income countries (LMHIC); pregnant and postpartum women living with HIV (three trials carried out in one lower middle-income country); and parents of children under the age of five years (13 trials conducted in LMHIC). Most interventions (18) were delivered via text messages alone, one was delivered through voice calls only, and the rest were delivered through combinations of different communication channels, such as multimedia messages and voice calls. Pregnant and postpartum women TCCMD versus standard care For behaviours, TCCMD may increase exclusive breastfeeding in settings where rates of exclusive breastfeeding are less common (risk ratio (RR) 1.30, 95% confidence intervals (CI) 1.06 to 1.59; low-certainty evidence), but have little or no effect in settings where almost all women breastfeed (low-certainty evidence). For use of health services, TCCMD may increase antenatal appointment attendance (odds ratio (OR) 1.54, 95% CI 0.80 to 2.96; low-certainty evidence); however, the CI encompasses both benefit and harm. The intervention may increase skilled attendants at birth in settings where a lack of skilled attendants at birth is common (though this differed by urban/rural residence), but may make no difference in settings where almost all women already have a skilled attendant at birth (OR 1.00, 95% CI 0.34 to 2.94; low-certainty evidence). There were uncertain effects on maternal and neonatal mortality and morbidity because the certainty of the evidence was assessed as very low. TCCMD versus non-digital TCC (e.g. pamphlets) TCCMD may have little or no effect on exclusive breastfeeding (RR 0.92, 95% CI 0.79 to 1.07; low-certainty evidence). TCCMD may reduce 'any maternal health problem' (RR 0.19, 95% CI 0.04 to 0.79) and 'any newborn health problem' (RR 0.52, 95% CI 0.25 to 1.06) reported up to 10 days postpartum (low-certainty evidence), though the CI for the latter includes benefit and harm. The effect on health service use is unknown due to a lack of studies. TCCMD versus digital non-targeted communication No studies reported behavioural, health, or well-being outcomes for this comparison. For use of health services, there are uncertain effects for the presence of a skilled attendant at birth due to very low-certainty evidence, and the intervention may make little or no difference to attendance for antenatal influenza vaccination (RR 1.05, 95% CI 0.71 to 1.58), though the CI encompasses both benefit and harm (low-certainty evidence). Pregnant and postpartum women living with HIV TCCMD versus standard care For behaviours, TCCMD may make little or no difference to maternal and infant adherence to antiretroviral (ARV) therapy (low-certainty evidence). For health service use, TCC mobile telephone reminders may increase use of antenatal care slightly (mean difference (MD) 1.5, 95% CI -0.36 to 3.36; low-certainty evidence). The effect on the proportion of births occurring in a health facility is uncertain due to very low-certainty evidence. For health and well-being outcomes, there was an uncertain intervention effect on neonatal death or stillbirth, and infant HIV due to very low-certainty evidence. No studies reported on maternal mortality or morbidity. TCCMD versus non-digital TCC The effect is unknown due to lack of studies reporting this comparison. TCCMD versus digital non-targeted communication TCCMD may increase infant ARV/prevention of mother-to-child transmission treatment adherence (RR 1.26, 95% CI 1.07 to 1.48; low-certainty evidence). The effect on other outcomes is unknown due to lack of studies. Parents of children aged less than five years No studies reported on correct treatment, nutritional, or health outcomes. TCCMD versus standard care Based on 10 trials, TCCMD may modestly increase health service use (vaccinations and HIV care) (RR 1.21, 95% CI 1.08 to 1.34; low-certainty evidence); however, the effect estimates varied widely between studies. TCCMD versus non-digital TCC TCCMD may increase attendance for vaccinations (RR 1.13, 95% CI 1.00 to 1.28; low-certainty evidence), and may make little or no difference to oral hygiene practices (low-certainty evidence). TCCMD versus digital non-targeted communication TCCMD may reduce attendance for vaccinations, but the CI encompasses both benefit and harm (RR 0.63, 95% CI 0.33 to 1.20; low-certainty evidence). No trials in any population reported data on unintended consequences. AUTHORS' CONCLUSIONS: The effect of TCCMD for most outcomes is uncertain. There may be improvements for some outcomes using targeted communication but these findings were of low certainty. High-quality, adequately powered trials and cost-effectiveness analyses are required to reliably ascertain the effects and relative benefits of TCCMD. Future studies should measure potential unintended consequences, such as partner violence or breaches of confidentiality.

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.

Public health deworming programmes for soil-transmitted helminths in children living in endemic areas.

BACKGROUND: The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. Global advocacy organizations claim routine deworming has substantive health and societal effects beyond the removal of worms. In this update of the 2015 edition we included six new trials, additional data from included trials, and addressed comments and criticisms. OBJECTIVES: To summarize the effects of public health programmes to regularly treat all children with deworming drugs on child growth, haemoglobin, cognition, school attendance, school performance, physical fitness, and mortality. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; LILACS; the metaRegister of Controlled Trials (mRCT); reference lists; and registers of ongoing and completed trials up to 19 September 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs that compared deworming drugs for soil-transmitted helminths (STHs) with placebo or no treatment in children aged 16 years or less, reporting on weight, height, haemoglobin, and formal tests of cognition. We also sought data on other measures of growth, school attendance, school performance, physical fitness, and mortality. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the trials for inclusion, risk of bias, and extracted data. We analysed continuous data using the mean difference (MD) with 95% confidence intervals (CIs). Where data were missing, we contacted trial authors. We stratified the analysis based on the background burden of STH infection. We used outcomes at time of longest follow-up. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We identified 51 trials, including 10 cluster-RCTs, that met the inclusion criteria. One trial evaluating mortality included over one million children, and the remaining 50 trials included a total of 84,336 participants. Twenty-four trials were in populations categorized as high burden, including nine trials in children selected because they were helminth-stool positive; 18 with intermediate burden; and nine as low burden.First or single dose of deworming drugsFourteen trials reported on weight after a single dose of deworming drugs (4970 participants, 14 RCTs). The effects were variable. There was little or no effect in studies conducted in low and intermediate worm burden groups. In the high-burden group, there was little or no effect in most studies, except for a large effect detected from one study area in Kenya reported in two trials carried out over 30 years ago. These trials result in qualitative heterogeneity and uncertainty in the meta-analysis across all studies (I2 statistic = 90%), with GRADE assessment assessed as very low-certainty, which means we do not know if a first dose or single dose of deworming impacts on weight.For height, most studies showed little or no effect after a single dose, with one of the two trials in Kenya from 30 years ago showing a large average difference (2621 participants, 10 trials, low-certainty evidence). Single dose probably had no effect on average haemoglobin (MD 0.10 g/dL, 95% CI 0.03 lower to 0.22 higher; 1252 participants, five trials, moderate-certainty evidence), or on average cognition (1596 participants, five trials, low-certainty evidence). The data are insufficient to know if there is an effect on school attendance and performance (304 participants, one trial, low-certainty evidence), or on physical fitness (280 participants, three trials, very low-certainty evidence). No trials reported on mortality.Multiple doses of deworming drugsThe effect of regularly treating children with deworming drugs given every three to six months on weight was reported in 18 trials, with follow-up times of between six months and three years; there was little or no effect on average weight in all but two trials, irrespective of worm prevalence-intensity. The two trials with large average weight gain included one in the high burden area in Kenya carried out over 30 years ago, and one study from India in a low prevalence area where subsequent studies in the same area did not show an effect. This heterogeneity causes uncertainty in any meta-analysis (I2 = 78%). Post-hoc analysis excluding trials published prior to 2000 gave an estimate of average difference in weight gain of 0.02 kg (95%CI from 0.04 kg loss to 0.08 gain, I2 = 0%). Thus we conclude that we do not know if repeated doses of deworming drugs impact on average weight, with a fewer older studies showing large gains, and studies since 2000 showing little or no average gain.Regular treatment probably had little or no effect on the following parameters: average height (MD 0.02 cm higher, 95% CI 0.09 lower to 0.13 cm higher; 13,700 participants, 13 trials, moderate-certainty evidence); average haemoglobin (MD 0.01 g/dL lower; 95% CI 0.05 g/dL lower to 0.07 g/dL higher; 5498 participants, nine trials, moderate-certainty evidence); formal tests of cognition (35,394 participants, 8 trials, moderate-certainty evidence); school performance (34,967 participants, four trials, moderate-certainty evidence). The evidence assessing an effect on school attendance is inconsistent, and at risk of bias (mean attendance 2% higher, 95% CI 5% lower to 8% higher; 20,650 participants, three trials, very low-certainty evidence). No trials reported on physical fitness. No effect was shown on mortality (1,005,135 participants, three trials, low-certainty evidence). AUTHORS' CONCLUSIONS: Public health programmes to regularly treat all children with deworming drugs do not appear to improve height, haemoglobin, cognition, school performance, or mortality. We do not know if there is an effect on school attendance, since the evidence is inconsistent and at risk of bias, and there is insufficient data on physical fitness. Studies conducted in two settings over 20 years ago showed large effects on weight gain, but this is not a finding in more recent, larger studies. We would caution against selecting only the evidence from these older studies as a rationale for contemporary mass treatment programmes as this ignores the recent studies that have not shown benefit.The conclusions of the 2015 edition have not changed in this update.

Memantine for dementia.

BACKGROUND: Memantine is a moderate affinity uncompetitive antagonist of glutamate NMDA receptors. It is licensed for use in moderate and severe Alzheimer's disease (AD); in the USA, it is also widely used off-label for mild AD. OBJECTIVES: To determine efficacy and safety of memantine for people with dementia. To assess whether memantine adds benefit for people already taking cholinesterase inhibitors (ChEIs). SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register of trials (http://www.medicine.ox.ac.uk/alois/) up to 25 March 2018. We examined clinical trials registries, press releases and posters of memantine manufacturers; and the web sites of the FDA, EMEA and NICE. We contacted authors and companies for missing information. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomised trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: We pooled and analysed data from four clinical domains across different aetiologies and severities of dementia and for AD with agitation. We assessed the impact of study duration, severity and concomitant use of ChEIs. Consequently, we restricted analyses to the licensed dose (20 mg/day or 28 mg extended release) and data at six to seven months duration of follow-up, and analysed separately results for mild and moderate-to-severe AD.We transformed results for efficacy outcomes into the difference in points on particular outcome scales. MAIN RESULTS: Across all types of dementia, data were available from almost 10,000 participants in 44 included trials, most of which were at low or unclear risk of bias. For nearly half the studies, relevant data were obtained from unpublished sources. The majority of trials (29 in 7885 participants) were conducted in people with AD.1. Moderate-to-severe AD (with or without concomitant ChEIs). High-certainty evidence from up to 14 studies in around 3700 participants consistently shows a small clinical benefit for memantine versus placebo: clinical global rating (CGR): 0.21 CIBIC+ points (95% confidence interval (CI) 0.14 to 0.30); cognitive function (CF): 3.11 Severe Impairment Battery (SIB) points (95% CI 2.42 to 3.92); performance on activities of daily living (ADL): 1.09 ADL19 points (95% CI 0.62 to 1.64); and behaviour and mood (BM): 1.84 Neuropsychiatric Inventory (NPI) points (95% CI 1.05 to 2.76). There may be no difference in the number of people discontinuing memantine compared to placebo: risk ratio (RR) 0.93 (95% CI 0.83 to 1.04) corresponding to 13 fewer people per 1000 (95% CI 31 fewer to 7 more). Although there is moderate-certainty evidence that fewer people taking memantine experience agitation as an adverse event: RR 0.81 (95% CI 0.66 to 0.99) (25 fewer people per 1000, 95% CI 1 to 44 fewer), there is also moderate-certainty evidence, from three additional studies, suggesting that memantine is not beneficial as a treatment for agitation (e.g. Cohen Mansfield Agitation Inventory: clinical benefit of 0.50 CMAI points, 95% CI -3.71 to 4.71) .The presence of concomitant ChEI does not impact on the difference between memantine and placebo, with the possible exceptions of the BM outcome (larger effect in people taking ChEIs) and the CF outcome (smaller effect).2. Mild AD (Mini Mental State Examination (MMSE) 20 to 23): mainly moderate-certainty evidence based on post-hoc subgroups from up to four studies in around 600 participants suggests there is probably no difference between memantine and placebo for CF: 0.21 ADAS-Cog points (95% CI -0.95 to 1.38); performance on ADL: -0.07 ADL 23 points (95% CI -1.80 to 1.66); and BM: -0.29 NPI points (95% CI -2.16 to 1.58). There is less certainty in the CGR evidence, which also suggests there may be no difference: 0.09 CIBIC+ points (95% CI -0.12 to 0.30). Memantine (compared with placebo) may increase the numbers of people discontinuing treatment because of adverse events (RR 2.12, 95% CI 1.03 to 4.39).3. Mild-to-moderate vascular dementia. Moderate- and low-certainty evidence from two studies in around 750 participants indicates there is probably a small clinical benefit for CF: 2.15 ADAS-Cog points (95% CI 1.05 to 3.25); there may be a small clinical benefit for BM: 0.47 NOSGER disturbing behaviour points (95% CI 0.07 to 0.87); there is probably no difference in CGR: 0.03 CIBIC+ points (95% CI -0.28 to 0.34); and there may be no difference in ADL: 0.11 NOSGER II self-care subscale points (95% CI -0.35 to 0.54) or in the numbers of people discontinuing treatment: RR 1.05 (95% CI 0.83 to 1.34).There is limited, mainly low- or very low-certainty efficacy evidence for other types of dementia (Parkinson's disease and dementia Lewy bodies (for which CGR may show a small clinical benefit; four studies in 319 people); frontotemporal dementia (two studies in 133 people); and AIDS-related Dementia Complex (one study in 140 people)).There is high-certainty evidence showing no difference between memantine and placebo in the proportion experiencing at least one adverse event: RR 1.03 (95% CI 1.00 to 1.06); the RR does not differ between aetiologies or severities of dementia. Combining available data from all trials, there is moderate-certainty evidence that memantine is 1.6 times more likely than placebo to result in dizziness (6.1% versus 3.9%), low-certainty evidence of a 1.3-fold increased risk of headache (5.5% versus 4.3%), but high-certainty evidence of no difference in falls. AUTHORS' CONCLUSIONS: We found important differences in the efficacy of memantine in mild AD compared to that in moderate-to-severe AD. There is a small clinical benefit of memantine in people with moderate-to-severe AD, which occurs irrespective of whether they are also taking a ChEI, but no benefit in people with mild AD.Clinical heterogeneity in AD makes it unlikely that any single drug will have a large effect size, and means that the optimal drug treatment may involve multiple drugs, each having an effect size that may be less than the minimum clinically important difference.A definitive long-duration trial in mild AD is needed to establish whether starting memantine earlier would be beneficial over the long term and safe: at present the evidence is against this, despite it being common practice. A long-duration trial in moderate-to-severe AD is needed to establish whether the benefit persists beyond six months.

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.

Community-based supplementary feeding for food insecure, vulnerable and malnourished populations - an overview of systematic reviews.

BACKGROUND: Supplementary feeding may help food insecure and vulnerable people by optimising the nutritional value and adequacy of the diet, improving quality of life and improving various health parameters of disadvantaged families. In low- and middle-income countries (LMIC), the problems supplementary feeding aims to address are entangled with poverty and deprivation, the programmes are expensive and delivery is complicated. OBJECTIVES: 1. To summarise the evidence from systematic reviews of supplementary feeding for food insecure, vulnerable and malnourished populations, including children under five years of age, school-aged children, pregnant and lactating women, people with HIV or tuberculosis (or both), and older populations.2. To describe and explore the effects of supplementary feeding given to people in these groups, and to describe the range of outcomes between reviews and range of effects in the different groups. METHODS: In January 2017, we searched the Cochrane Database of Systematic Reviews, MEDLINE, Embase and nine other databases. We included systematic reviews evaluating community-based supplementary feeding, and concerning food insecure, vulnerable and malnourished populations. Two review authors independently undertook selection of systematic reviews, data extraction and 'Risk of bias' assessment. We assessed review quality using the AMSTAR tool, and used GRADEpro 'Summary of findings' tables from each review to indicate the certainty of the evidence for the main comparisons. We summarised review findings in the text and reported the data for each outcome in additional tables. We also used forest plots to display results graphically. MAIN RESULTS: This overview included eight systematic reviews (with last search dates between May 2006 and February 2016). Seven were Cochrane Reviews evaluating interventions in pregnant women; children (aged from birth to five years) from LMIC; disadvantaged infants and young children (aged three months to five years); children with moderate acute malnutrition (MAM); disadvantaged school children; adults and children who were HIV positive or with active tuberculosis (with or without HIV). One was a non-Cochrane systematic review in older people with Alzheimer's disease. These reviews included 95 trials relevant to this overview, with the majority (74%) of participants from LMIC.The number of included participants varied between 91 and 7940 adults, and 271 and more than 12,595 children. Trials included a wide array of nutritional interventions that varied in duration, frequency and format, with micronutrients often reported as cointerventions. Follow-up ranged from six weeks to two years; three trials investigated outcomes at four to 17 years of age. All reviews were rated as high quality (AMSTAR score between eight and 11). The GRADE certainty ratings ranged from very low to moderate for individual comparisons, with the evidence often comprising only one or two small trials, thereby resulting in many underpowered analyses (too small to detect small but important differences). The main outcome categories reported across reviews were death, anthropometry (adults and children) and other markers of nutritional status, disease-related outcomes, neurocognitive development and psychosocial outcomes, and adverse events.Mortality data were limited and underpowered in meta-analysis in all populations (children with MAM, in children with HIV, and in adults with tuberculosis) with the exception of balanced energy and protein supplementation in pregnancy, which may have reduced the risk of stillbirth (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.39 to 0.94; 5 trials, 3408 women). Supplementation in pregnancy also improved infant birth weight (mean difference (MD) 40.96 g, 95% CI 4.66 to 77.26; 11 trials, 5385 participants) and reduced risk of infants born small-for-gestational age (RR 0.79, 95% CI 0.69 to 0.90; 7 trials, 4408 participants). These effects did not translate into demonstrable long-term benefits for children in terms of growth and neurocognitive development in the one to two trials reporting on longer-term outcomes. In one study (505 participants), high-protein supplementation was associated with increased risk of small-for-gestational age babies.Effects on growth in children were mixed. In children under five years of age from LMIC, one review found that supplementary feeding had a little or no effect on child growth; however, a more recent review in a similar population found that those who received food supplementation gained an average of 0.12 kg more in weight (MD 0.12 kg, 95% CI 0.05 to 0.18; 9 trials, 1057 participants) and 0.27 cm more in height (MD 0.27 cm, 95% CI 0.07 to 0.48; 9 trials, 1463 participants) than those who were not supplemented. Supplementary food was generally more effective for younger children (younger than two years of age) and for those who were poorer or less well-nourished. In children with MAM, the provision of specially formulated food improved their weight, weight-for-height z scores and other key outcomes such as recovery rate (by 29%), as well as reducing the number of participants dropping out (by 70%). In LMIC, school meals seemed to lead to small benefits for children, including improvements in weight z scores, especially in children from lower-income countries, height z scores, cognition or intelligence quotient tests, and maths and spelling performance.Supplementary feeding in adults who were HIV positive increased the daily energy and protein intake compared to nutritional counselling alone. Supplementation led to an initial improvement in weight gain or body mass index but did not seem to confer long-term benefit.In adults with tuberculosis, one small trial found a significant benefit on treatment completion and sputum conversion rate. There were also significant but modest benefits in terms of weight gain (up to 2.60 kg) during active tuberculosis.The one study included in the Alzheimer's disease review found that three months of daily oral nutritional supplements improved nutritional outcomes in the intervention group.There was little or no evidence regarding people's quality of life, adherence to treatment, attendance at clinic or the costs of supplementary feeding programmes. AUTHORS' CONCLUSIONS: Considering the current evidence base included, supplementary food effects are modest at best, with inconsistent and limited mortality evidence. The trials reflected in the reviews mostly reported on short-term outcomes and across the whole of the supplementation trial literature it appears important outcomes, such as quality of life and cost of programmes, are not systematically reported or summarised.

Ribavirin for treating Crimean Congo haemorrhagic fever.

BACKGROUND: Crimean Congo haemorrhagic fever (CCHF) is a tick-borne disease that occurs in parts of Asia, Europe and Africa. Since 2000 the infection has caused epidemics in Turkey, Iran, Russia, Uganda and Pakistan. Good-quality general supportive medical care helps reduce mortality. There is uncertainty and controversy about treating CCHF with the antiviral drug ribavirin. OBJECTIVES: To assess the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (OVID); Science Citation Index-Expanded, Social Sciences Citation index, conference proceedings (Web of Science); and CINAHL (EBSCOHost). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for trials in progress. We conducted all searches up to 16 October 2017. We also contacted experts in the field and obtained further studies from these sources. SELECTION CRITERIA: We evaluated studies assessing the use of ribavirin in people with suspected or confirmed Crimean Congo haemorrhagic fever. We included randomised control trials (RCTs); non-randomised studies (NRSs) that included more than 10 participants designed as cohort studies with comparators; and case-control studies. DATA COLLECTION AND ANALYSIS: Two review authors assessed eligibility, risk of bias, and extracted data. For non-randomized studies we used the ROBINS-I tool to assess risk of bias. The main effects analysis included all studies where we judged the risk of bias to be low, moderate or high. We summarized dichotomous outcomes using risk ratios (RRs) and continuous outcomes using mean differences (MDs), and used meta-analyses where appropriate. We carried out a subsidiary appraisal and analysis of studies with critical risk of bias for the primary outcome, as these are often cited to support using ribavirin. MAIN RESULTS: For the main effects analysis, five studies met our inclusion criteria: one RCT with 136 participants and four non-randomized studies with 612 participants. We excluded 18 non-randomized studies with critical risk of bias, where none had attempted to control for confounding.We do not know if ribavirin reduces mortality (1 RCT; RR 1.13, 95% confidence interval (CI) 0.29 to 4.32; 136 participants; very low-certainty evidence; 3 non-randomized studies; RR 0.72, 95% CI 0.41 to 1.28; 549 participants; very low-certainty evidence). We do not know if ribavirin reduces the length of stay in hospital (1 RCT: mean difference (MD) 0.70 days, 95% CI -0.39 to 1.79; 136 participants; and 1 non-randomized study: MD -0.80, 95% CI -2.70 to 1.10; 50 participants; very low-certainty evidence). We do not know if it reduces the risk of patients needing platelet transfusions (1 RCT: RR 1.23, 95% CI 0.77 to 1.96; 136 participants; very low-certainty evidence). For adverse effects (including haemolytic anaemia and a need to discontinue treatment), we do not know whether there is an increased risk with ribavirin in people with CCHF as data are insufficient.We do not know if adding ribavirin to early supportive care improves outcomes. One non-randomized study assessed mortality in people receiving ribavirin and supportive care within four days or less from symptom onset compared to after four days since symptom onset: mortality was lower in the group receiving early supportive care and ribavirin, but it is not possible to distinguish between the effects of ribavirin and early supportive medical care alone.In the subsidiary analysis, 18 studies compared people receiving ribavirin with those not receiving ribavirin. All had a critical risk of bias due to confounding, reflected in the mortality point estimates favouring ribavirin. AUTHORS' CONCLUSIONS: We do not know if ribavirin is effective for treating Crimean Congo haemorrhagic fever. Non-randomized studies are often cited as evidence of an effect, but the risk of bias in these studies is high.

Mefloquine for preventing malaria during travel to endemic areas.

BACKGROUND: Mefloquine is one of four antimalarial agents commonly recommended for preventing malaria in travellers to malaria-endemic areas. Despite its high efficacy, there is controversy about its psychological side effects. OBJECTIVES: To summarize the efficacy and safety of mefloquine used as prophylaxis for malaria in travellers. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published on the Cochrane Library; MEDLINE; Embase (OVID); TOXLINE (https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm); and LILACS. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; http://www.who.int/ictrp/en/) and ClinicalTrials.gov (https://clinicaltrials.gov/ct2/home) for trials in progress, using 'mefloquine', 'Lariam', and 'malaria' as search terms. The search date was 22 June 2017. SELECTION CRITERIA: We included randomized controlled trials (for efficacy and safety) and non-randomized cohort studies (for safety). We compared prophylactic mefloquine with placebo, no treatment, or an alternative recommended antimalarial agent. Our study populations included all adults and children, including pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and risk of bias of trials, extracted and analysed data. We compared dichotomous outcomes using risk ratios (RR) with 95% confidence intervals (CI). Prespecified adverse outcomes are included in 'Summary of findings' tables, with the best available estimate of the absolute frequency of each outcome in short-term international travellers. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 20 RCTs (11,470 participants); 35 cohort studies (198,493 participants); and four large retrospective analyses of health records (800,652 participants). Nine RCTs explicitly excluded participants with a psychiatric history, and 25 cohort studies stated that the choice of antimalarial agent was based on medical history and personal preference. Most RCTs and cohort studies collected data on self-reported or clinician-assessed symptoms, rather than formal medical diagnoses. Mefloquine efficacyOf 12 trials comparing mefloquine and placebo, none were performed in short-term international travellers, and most populations had a degree of immunity to malaria. The percentage of people developing a malaria episode in the control arm varied from 1% to 82% (median 22%) and 0% to 13% in the mefloquine group (median 1%).In four RCTs that directly compared mefloquine, atovaquone-proguanil and doxycycline in non-immune, short-term international travellers, only one clinical case of malaria occurred (4 trials, 1822 participants). Mefloquine safety versus atovaquone-proguanil Participants receiving mefloquine were more likely to discontinue their medication due to adverse effects than atovaquone-proguanil users (RR 2.86, 95% CI 1.53 to 5.31; 3 RCTs, 1438 participants; high-certainty evidence). There were few serious adverse effects reported with mefloquine (15/2651 travellers) and none with atovaquone-proguanil (940 travellers).One RCT and six cohort studies reported on our prespecified adverse effects. In the RCT with short-term travellers, mefloquine users were more likely to report abnormal dreams (RR 2.04, 95% CI 1.37 to 3.04, moderate-certainty evidence), insomnia (RR 4.42, 95% CI 2.56 to 7.64, moderate-certainty evidence), anxiety (RR 6.12, 95% CI 1.82 to 20.66, moderate-certainty evidence), and depressed mood during travel (RR 5.78, 95% CI 1.71 to 19.61, moderate-certainty evidence). The cohort studies in longer-term travellers were consistent with this finding but most had larger effect sizes. Mefloquine users were also more likely to report nausea (high-certainty evidence) and dizziness (high-certainty evidence).Based on the available evidence, our best estimates of absolute effect sizes for mefloquine versus atovaquone-proguanil are 6% versus 2% for discontinuation of the drug, 13% versus 3% for insomnia, 14% versus 7% for abnormal dreams, 6% versus 1% for anxiety, and 6% versus 1% for depressed mood. Mefloquine safety versus doxycyclineNo difference was found in numbers of serious adverse effects with mefloquine and doxycycline (low-certainty evidence) or numbers of discontinuations due to adverse effects (RR 1.08, 95% CI 0.41 to 2.87; 4 RCTs, 763 participants; low-certainty evidence).Six cohort studies in longer-term occupational travellers reported our prespecified adverse effects; one RCT in military personnel and one cohort study in short-term travellers reported adverse events. Mefloquine users were more likely to report abnormal dreams (RR 10.49, 95% CI 3.79 to 29.10; 4 cohort studies, 2588 participants, very low-certainty evidence), insomnia (RR 4.14, 95% CI 1.19 to 14.44; 4 cohort studies, 3212 participants, very low-certainty evidence), anxiety (RR 18.04, 95% CI 9.32 to 34.93; 3 cohort studies, 2559 participants, very low-certainty evidence), and depressed mood (RR 11.43, 95% CI 5.21 to 25.07; 2 cohort studies, 2445 participants, very low-certainty evidence). The findings of the single cohort study reporting adverse events in short-term international travellers were consistent with this finding but the single RCT in military personnel did not demonstrate a difference between groups in frequencies of abnormal dreams or insomnia.Mefloquine users were less likely to report dyspepsia (RR 0.26, 95% CI 0.09 to 0.74; 5 cohort studies, 5104 participants, low certainty-evidence), photosensitivity (RR 0.08, 95% CI 0.05 to 0.11; 2 cohort studies, 1875 participants, very low-certainty evidence), vomiting (RR 0.18, 95% CI 0.12 to 0.27; 4 cohort studies, 5071 participants, very low-certainty evidence), and vaginal thrush (RR 0.10, 95% CI 0.06 to 0.16; 1 cohort study, 1761 participants, very low-certainty evidence).Based on the available evidence, our best estimates of absolute effect for mefloquine versus doxycyline were: 2% versus 2% for discontinuation, 12% versus 3% for insomnia, 31% versus 3% for abnormal dreams, 18% versus 1% for anxiety, 11% versus 1% for depressed mood, 4% versus 14% for dyspepsia, 2% versus 19% for photosensitivity, 1% versus 5% for vomiting, and 2% versus 16% for vaginal thrush.Additional analyses, including comparisons of mefloquine with chloroquine, added no new information. Subgroup analysis by study design, duration of travel, and military versus non-military participants, provided no conclusive findings. AUTHORS' CONCLUSIONS: The absolute risk of malaria during short-term travel appears low with all three established antimalarial agents (mefloquine, doxycycline, and atovaquone-proguanil).The choice of antimalarial agent depends on how individual travellers assess the importance of specific adverse effects, pill burden, and cost. Some travellers will prefer mefloquine for its once-weekly regimen, but this should be balanced against the increased frequency of abnormal dreams, anxiety, insomnia, and depressed mood.

Antipsychotic combinations for schizophrenia.

BACKGROUND: Many people with schizophrenia do not achieve a satisfactory treatment response with their initial antipsychotic drug treatment. Sometimes a second antipsychotic, in combination with the first, is used in these situations. OBJECTIVES: To examine whether:1. treatment with antipsychotic combinations is effective for schizophrenia; and2. treatment with antipsychotic combinations is safe for the same illness. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's register which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We ran searches in September 2010, August 2012 and January 2016. We checked for additional trials in the reference lists of included trials. SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials comparing antipsychotic combinations with antipsychotic monotherapy for the treatment of schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We independently extracted data from the included studies. We analysed dichotomous data using risk ratios (RR) and the 95% confidence intervals (CI). We analysed continuous data using mean difference (MD) with a 95% CIs. For the meta-analysis we used a random-effects model. We used GRADE to complete a 'Summary of findings' table and assessed risk of bias for included studies. MAIN RESULTS: Sixty-two studies are included in the review, 31 of these compared clozapine monotherapy with clozapine combination. We considered the risk of bias in the included studies to be moderate to high. The majority of trials had unclear allocation concealment, method of randomisation and blinding, and were not free of selective reporting.There is some limited evidence that combination therapy is superior to monotherapy in improving clinical response (RR 0.73, 95% CI 0.63 to 0.85; participants = 2364; studies = 29, very low-quality evidence), although subgroup analyses show that the positive result was due to the studies with clozapine in both the monotherapy and combination groups (RR 0.66, 95% CI 0.53 to 0.83; participants = 1127; studies = 17). Few studies reported on rate of relapse, most likely due to the short length of the studies. Overall, a combination of antipsychotics was not superior or inferior to antipsychotic monotherapy in preventing relapse (RR 0.63, 95% CI 0.31 to 1.29; participants = 512; studies = 3, very low-quality evidence), but the pooled data showed high heterogeneity (I² = 82%). A combination of antipsychotics was not superior or inferior to antipsychotic monotherapy in reducing the number of participants discontinuing treatment early (RR 0.89, 95% CI 0.73 to 1.07; participants = 3103; studies = 43, low-quality evidence). No difference was found between treatment groups in the number of participants hospitalised (RR 0.96, 95% CI 0.36 to 2.55; participants = 202; studies = 3, low-quality evidence) . We did not find evidence of a difference between treatment groups in serious adverse events or those requiring discontinuation (RR 1.05, 95% CI 0.65 to 1.69; participants = 2398; studies = 30, very low-quality evidence). There is as lack of evidence on clinically important change in quality of life, with only four studies reporting average endpoint or change data for this outcome on three different scales, none of which showed a difference between treatment groups. AUTHORS' CONCLUSIONS: Currently, most evidence regarding the use of antipsychotic combinations comes from short-term trials, limiting the assessment of long-term efficacy and safety. We found very low-quality evidence that a combination of antipsychotics may improve the clinical response. We also found low-quality evidence that a combination of antipsychotics is may make no difference at preventing participants from leaving the study early, preventing relapse and/or causing more serious adverse events than monotherapy.

Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance.

BACKGROUND: The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. As the intervention is often claimed to have important health, nutrition, and societal effects beyond the removal of worms, we critically evaluated the evidence on benefits. OBJECTIVES: To summarize the effects of giving deworming drugs to children to treat soil-transmitted helminths on weight, haemoglobin, and cognition; and the evidence of impact on physical well-being, school attendance, school performance, and mortality. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register (14 April 2015); Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2015, Issue 4); MEDLINE (2000 to 14 April 2015); EMBASE (2000 to 14 April 2015); LILACS (2000 to 14 April 2015); the metaRegister of Controlled Trials (mRCT); and reference lists, and registers of ongoing and completed trials up to 14 April 2015. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs comparing deworming drugs for soil-transmitted helminths with placebo or no treatment in children aged 16 years or less, reporting on weight, haemoglobin, and formal tests of intellectual development. We also sought data on school attendance, school performance, and mortality. We included trials that combined health education with deworming programmes. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the trials, evaluated risk of bias, and extracted data. We analysed continuous data using the mean difference (MD) with 95% confidence intervals (CIs). Where data were missing, we contacted trial authors. We used outcomes at time of longest follow-up. The evidence quality was assessed using GRADE. This edition of the Cochrane Review adds the DEVTA trial from India, and draws on an independent analytical replication of a trial from Kenya. MAIN RESULTS: We identified 45 trials, including nine cluster-RCTs, that met the inclusion criteria. One trial evaluating mortality included over one million children, and the remaining 44 trials included a total of 67,672 participants. Eight trials were in children known to be infected, and 37 trials were carried out in endemic areas, including areas of high (15 trials), moderate (12 trials), and low prevalence (10 trials). Treating children known to be infectedTreating children known to be infected with a single dose of deworming drugs (selected by screening, or living in areas where all children are infected) may increase weight gain over the next one to six months (627 participants, five trials, low quality evidence). The effect size varied across trials from an additional 0.2 kg gain to 1.3 kg. There is currently insufficient evidence to know whether treatment has additional effects on haemoglobin (247 participants, two trials, very low quality evidence); school attendance (0 trials); cognitive functioning (103 participants, two trials, very low quality evidence), or physical well-being (280 participants, three trials, very low quality evidence). Community deworming programmesTreating all children living in endemic areas with a dose of deworming drugs probably has little or no effect on average weight gain (MD 0.04 kg less, 95% CI 0.11 kg less to 0.04 kg more; trials 2719 participants, seven trials, moderate quality evidence), even in settings with high prevalence of infection (290 participants, two trials). A single dose also probably has no effect on average haemoglobin (MD 0.06 g/dL, 95% CI -0.05 lower to 0.17 higher; 1005 participants, three trials, moderate quality evidence), or average cognition (1361 participants, two trials, low quality evidence).Similiarly, regularly treating all children in endemic areas with deworming drugs, given every three to six months, may have little or no effect on average weight gain (MD 0.08 kg, 95% CI 0.11 kg less to 0.27 kg more; 38,392 participants, 10 trials, low quality evidence). The effects were variable across trials; one trial from a low prevalence setting carried out in 1995 found an increase in weight, but nine trials carried out since then found no effect, including five from moderate and high prevalence areas.There is also reasonable evidence that regular treatment probably has no effect on average height (MD 0.02 cm higher, 95% CI 0.14 lower to 0.17 cm higher; 7057 participants, seven trials, moderate quality evidence); average haemoglobin (MD 0.02 g/dL lower; 95% CI 0.08 g/dL lower to 0.04 g/dL higher; 3595 participants, seven trials, low quality evidence); formal tests of cognition (32,486 participants, five trials, moderate quality evidence); exam performance (32,659 participants, two trials, moderate quality evidence); or mortality (1,005,135 participants, three trials, low quality evidence). There is very limited evidence assessing an effect on school attendance and the findings are inconsistent, and at risk of bias (mean attendance 2% higher, 95% CI 4% lower to 8% higher; 20,243 participants, two trials, very low quality evidence).In a sensitivity analysis that only included trials with adequate allocation concealment, there was no evidence of any effect for the main outcomes. AUTHORS' CONCLUSIONS: Treating children known to have worm infection may have some nutritional benefits for the individual. However, in mass treatment of all children in endemic areas, there is now substantial evidence that this does not improve average nutritional status, haemoglobin, cognition, school performance, or survival.

Transcranial magnetic stimulation (TMS) for schizophrenia.

BACKGROUND: People with schizophrenia often experience symptoms which fail to fully respond to antipsychotic medication. Transcranial magnetic stimulation (TMS) has been proposed as a new treatment for people with schizophrenia, especially those who experience persistent auditory hallucinations. OBJECTIVES: To estimate the effects of TMS alone, compared with sham TMS or with 'standard management' and any other comparison interventions in reducing psychotic symptoms associated with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (June 2006, June 2008, April 2013). This register is compiled by methodical searches of MEDLINE, EMBASE, BIOSIS, CINAHL, Dissertation abstracts, LILACS, PSYNDEX, PsycINFO, RUSSMED, and Sociofile, and is supplemented with handsearching of relevant journals and numerous conference proceedings. SELECTION CRITERIA: We included all randomised controlled trials recruiting at least five participants and comparing TMS with sham TMS or any other treatment for people with schizophrenia. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RRs) and their 95% confidence intervals (CIs). For continuous data, we calculated mean differences (MD) and 95% CI. We used a fixed-effect model. We assessed overall quality of the evidence using the GRADE approach. MAIN RESULTS: We included 41 studies with 1473 participants in the review. We found significant differences in favour of temporoparietal TMS compared to sham TMS for global state measured on the CGI scale (7 RCTs, n = 224, MD -0.5, 95% CI -0.76 to -0.23, very low-quality evidence) and positive symptoms measured on the PANSS scale (5 RCTs, n = 127, MD -6.09, 95% CI -10.95 to -1.22, very low-quality evidence). Participants experienced significantly more headaches in the temporoparietal TMS group (10 RCTs, n = 392, RR 2.65, 95% CI 1.56 to 4.50, very low-quality evidence). However, no more participants left the study early from the TMS group than from the sham group (very low-quality evidence). Cognitive state was assessed using 39 different measures, and all were equivocal (very low-quality evidence).We included only two trials which compared temporoparietal TMS with standard treatment. In both trials the participants received first- and second-generation antipsychotic medication in both treatment groups, therefore TMS was used an adjunctive therapy to medication. We found no significant differences in the number of participants that showed clinical improvement in global state (1 RCT, n = 100, RR 1.19, 95% CI 0.91 to 1.57) or left the study early (2 RCTs, n = 140, RR 0.33, 95% CI 0.08 to 1.46) (both very low-quality evidence). No studies reported on global state score, mental state, cognitive state and adverse effects.For prefrontal TMS compared to sham TMS, global state was measured on three different scales, all of which presented equivocal results (very low quality evidence). We could not pool data for mental state on the PANSS scale due to high heterogeneity. Cognitive state was assessed using 19 different measures, with 15/19 being equivocal (very low-quality evidence). Prefrontal TMS caused more headaches (6 RCTs, n = 164, RR 2.77, 95% CI 1.22 to 6.26, very low-quality evidence) but there was no difference in the number of participants leaving the study early (very low-quality evidence). No studies reported data for clinical improvement.We found a significant difference in favour of prefrontal theta burst stimulation TMS compared to sham TMS for mental state on the PANNS scale (3 RCTs, n = 108, MD -5.71, 95% CI -9.32 to -2.10, very low evidence). We found no difference for clinical improvement, cognitive state, number of headaches, and leaving the study early (very low-quality evidence).None of the included studies reported satisfaction with care. AUTHORS' CONCLUSIONS: Based on this review, there is insufficient evidence to support or refute the use of TMS to treat symptoms of schizophrenia. Although some evidence suggests that TMS, and in particular temporoparietal TMS, may improve certain symptoms (such as auditory hallucinations and positive symptoms of schizophrenia) compared to sham TMS, the results were not robust enough to be unequivocal across the assessment measures used. There was insufficient evidence to suggest any added benefit with TMS used as an adjunctive therapy to antipsychotic medication.The overall quality of evidence was graded as very low due to risk of bias, and this was accompanied by an imprecision in estimates due to the relatively small number of participants in the studies. Thus, consideration is required in improving the quality of trial processes, as well as the quality of reporting of ongoing and future TMS trials, so as to facilitate accurate future judgements in assessing risk of bias. Differences in TMS techniques in relation to stimulation intensity, stimulation length, brain areas stimulated and variations in the design of sham TMS all contributed to the heterogeneity of study findings and limited the interpretation and applicability of the results. In addition, the trials assessed their outcomes with a variety of scales, and usable data were limited. Therefore, to better evaluate the treatment effects of TMS in people with schizophrenia, we favour the use of standardised treatment protocols and outcome measures.

Supportive therapy for schizophrenia.

BACKGROUND: Supportive therapy is often used in everyday clinical care and in evaluative studies of other treatments. OBJECTIVES: To review the effects of supportive therapy compared with standard care, or other treatments in addition to standard care for people with schizophrenia. SEARCH METHODS: For this update, we searched the Cochrane Schizophrenia Group's register of trials (November 2012). SELECTION CRITERIA: All randomised trials involving people with schizophrenia and comparing supportive therapy with any other treatment or standard care. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated these and extracted data. For dichotomous data, we estimated the risk ratio (RR) using a fixed-effect model with 95% confidence intervals (CIs). Where possible, we undertook intention-to-treat analyses. For continuous data, we estimated the mean difference (MD) fixed-effect with 95% CIs. We estimated heterogeneity (I(2) technique) and publication bias. We used GRADE to rate quality of evidence. MAIN RESULTS: Four new trials were added after the 2012 search. The review now includes 24 relevant studies, with 2126 participants. Overall, the evidence was very low quality.We found no significant differences in the primary outcomes of relapse, hospitalisation and general functioning between supportive therapy and standard care.There were, however, significant differences favouring other psychological or psychosocial treatments over supportive therapy. These included hospitalisation rates (4 RCTs, n = 306, RR 1.82 CI 1.11 to 2.99, very low quality of evidence), clinical improvement in mental state (3 RCTs, n = 194, RR 1.27 CI 1.04 to 1.54, very low quality of evidence) and satisfaction of treatment for the recipient of care (1 RCT, n = 45, RR 3.19 CI 1.01 to 10.7, very low quality of evidence). For this comparison, we found no evidence of significant differences for rate of relapse, leaving the study early and quality of life.When we compared supportive therapy to cognitive behavioural therapy CBT), we again found no significant differences in primary outcomes. There were very limited data to compare supportive therapy with family therapy and psychoeducation, and no studies provided data regarding clinically important change in general functioning, one of our primary outcomes of interest. AUTHORS' CONCLUSIONS: There are insufficient data to identify a difference in outcome between supportive therapy and standard care. There are several outcomes, including hospitalisation and general mental state, indicating advantages for other psychological therapies over supportive therapy but these findings are based on a few small studies where we graded the evidence as very low quality. Future research would benefit from larger trials that use supportive therapy as the main treatment arm rather than the comparator.

Social skills programmes for schizophrenia.

BACKGROUND: Social skills programmes (SSP) are treatment strategies aimed at enhancing the social performance and reducing the distress and difficulty experienced by people with a diagnosis of schizophrenia and can be incorporated as part of the rehabilitation package for people with schizophrenia. OBJECTIVES: The primary objective is to investigate the effects of social skills training programmes, compared to standard care, for people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (November 2006 and December 2011) which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. We inspected references of all identified studies for further trials.A further search for studies has been conducted by the Cochrane Schizophrenia Group in 2015, 37 citations have been found and are currently being assessed by review authors. SELECTION CRITERIA: We included all relevant randomised controlled trials for social skills programmes versus standard care involving people with serious mental illnesses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratios (RRs) and their 95% confidence intervals (CI) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD) and 95% CIs. MAIN RESULTS: We included 13 randomised trials (975 participants). These evaluated social skills programmes versus standard care, or discussion group. We found evidence in favour of social skills programmes compared to standard care on all measures of social functioning. We also found that rates of relapse and rehospitalisation were lower for social skills compared to standard care (relapse: 2 RCTs, n = 263, RR 0.52 CI 0.34 to 0.79, very low quality evidence), (rehospitalisation: 1 RCT, n = 143, RR 0.53 CI 0.30 to 0.93, very low quality evidence) and participants' mental state results (1 RCT, n = 91, MD -4.01 CI -7.52 to -0.50, very low quality evidence) were better in the group receiving social skill programmes. Global state was measured in one trial by numbers not experiencing a clinical improvement, results favoured social skills (1 RCT, n = 67, RR 0.29 CI 0.12 to 0.68, very low quality evidence). Quality of life was also improved in the social skills programme compared to standard care (1 RCT, n = 112, MD -7.60 CI -12.18 to -3.02, very low quality evidence). However, when social skills programmes were compared to a discussion group control, we found no significant differences in the participants social functioning, relapse rates, mental state or quality of life, again the quality of evidence for these outcomes was very low. AUTHORS' CONCLUSIONS: Compared to standard care, social skills training may improve the social skills of people with schizophrenia and reduce relapse rates, but at present, the evidence is very limited with data rated as very low quality. When social skills training was compared to discussion there was no difference on patients outcomes. Cultural differences might limit the applicability of the current results, as most reported studies were conducted in China. Whether social skills training can improve social functioning of people with schizophrenia in different settings remains unclear and should be investigated in a large multi-centre randomised controlled trial.

Voxel-based morphometry for separation of schizophrenia from other types of psychosis in first episode psychosis.

BACKGROUND: Schizophrenia is a psychiatric disorder which involves distortions in thought and perception, blunted affect, and behavioural disturbances. The longer psychosis goes unnoticed and untreated, the more severe the repercussions for relapse and recovery. There is some evidence that early intervention services can help, and diagnostic techniques that could contribute to early intervention may offer clinical utility in these situations. The index test being evaluated in this review is the structural magnetic resonance imaging (MRI) analysis technique known as voxel-based morphometry (VBM) that estimates the distribution of grey matter tissue volume across several brain regions. This review is an exploratory examination of the diagnostic 'potential' of VBM for use as an additional tool in the clinical examination of patients with first episode psychosis to establish whether an individual will progress on to developing schizophrenia as opposed to other types of psychosis. OBJECTIVES: To determine whether VBM applied to the brain can be used to differentiate schizophrenia from other types of psychosis in participants who have received a clinical diagnosis of first episode psychosis. SEARCH METHODS: In December 2013, we updated a previous search (May 2012) of MEDLINE, EMBASE, and PsycInfo using OvidSP. SELECTION CRITERIA: We included retrospective and prospective studies that consecutively or randomly selected adolescent and adult participants (< 45 years) with a first episode of psychosis; and that evaluated the diagnostic accuracy of VBM for differentiating schizophrenia from other psychoses compared with a clinical diagnosis made by a qualified mental health professional, with or without the use of standard operational criteria or symptom checklists. We excluded studies in children, and in adult participants with organic brain disorders or who were at high risk for schizophrenia, such as people with a genetic predisposition. DATA COLLECTION AND ANALYSIS: Two review authors screened all references for inclusion. We assessed the quality of studies using the QUADAS-2 instrument. Due to a lack of data, we were not able to extract 2 x 2 data tables for each study nor undertake any meta-analysis. MAIN RESULTS: We included four studies with a total of 275 participants with first episode psychosis. VBM was not used to diagnose schizophrenia in any of the studies, instead VBM was used to quantify the magnitude of differences in grey matter volume. Therefore, none of the included studies reported data that could be used in the analysis, and we summarised the findings narratively for each study. AUTHORS' CONCLUSIONS: There is no evidence to currently support diagnosing schizophrenia (as opposed to other psychotic disorders) using the pattern of brain changes seen in VBM studies in patients with first episode psychosis. VBM has the potential to discriminate between diagnostic categories but the methods to do this reliably are currently in evolution. In addition, the lack of applicability of the use of VBM to clinical practice in the studies to date limits the usefulness of VBM as a diagnostic aid to differentiate schizophrenia from other types of psychotic presentations in people with first episode of psychosis.

Fluphenazine decanoate (depot) and enanthate for schizophrenia.

BACKGROUND: Intramuscular injections (depot preparations) offer an advantage over oral medication for treating schizophrenia by reducing poor compliance. The benefits gained by long-acting preparations, however, may be offset by a higher incidence of adverse effects. OBJECTIVES: To assess the effects of fluphenazine decanoate and enanthate versus oral anti-psychotics and other depot neuroleptic preparations for individuals with schizophrenia in terms of clinical, social and economic outcomes. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (February 2011 and October 16, 2013), which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. SELECTION CRITERIA: We considered all relevant randomised controlled trials (RCTs) focusing on people with schizophrenia comparing fluphenazine decanoate or enanthate with placebo or oral anti-psychotics or other depot preparations. DATA COLLECTION AND ANALYSIS: We reliably selected, assessed the quality, and extracted data of the included studies. For dichotomous data, we estimated risk ratio (RR) with 95% confidence intervals (CI). Analysis was by intention-to-treat. We used the mean difference (MD) for normal continuous data. We excluded continuous data if loss to follow-up was greater than 50%. Tests of heterogeneity and for publication bias were undertaken. We used a fixed-effect model for all analyses unless there was high heterogeneity. For this update. we assessed risk of bias of included studies and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to create a 'Summary of findings' table. MAIN RESULTS: This review now includes 73 randomised studies, with 4870 participants. Overall, the quality of the evidence is low to very low.Compared with placebo, use of fluphenazine decanoate does not result in any significant differences in death, nor does it reduce relapse over six months to one year, but one longer-term study found that relapse was significantly reduced in the fluphenazine arm (n = 54, 1 RCT, RR 0.35, CI 0.19 to 0.64, very low quality evidence). A very similar number of people left the medium-term studies (six months to one year) early in the fluphenazine decanoate (24%) and placebo (19%) groups, however, a two-year study significantly favoured fluphenazine decanoate (n = 54, 1 RCT, RR 0.47, CI 0.23 to 0.96, very low quality evidence). No significant differences were found in mental state measured on the Brief Psychiatric Rating Scale (BPRS) or in extrapyramidal adverse effects, although these outcomes were only reported in one small study each. No study comparing fluphenazine decanoate with placebo reported clinically significant changes in global state or hospital admissions.Fluphenazine decanoate does not reduce relapse more than oral neuroleptics in the medium term (n = 419, 6 RCTs, RR 1.46 CI 0.75 to 2.83, very low quality evidence). A small study found no difference in clinically significant changes in global state. No difference in the number of participants leaving the study early was found between fluphenazine decanoate (17%) and oral neuroleptics (18%), and no significant differences were found in mental state measured on the BPRS. Extrapyramidal adverse effects were significantly less for people receiving fluphenazine decanoate compared with oral neuroleptics (n = 259, 3 RCTs, RR 0.47 CI 0.24 to 0.91, very low quality evidence). No study comparing fluphenazine decanoate with oral neuroleptics reported death or hospital admissions.No significant difference in relapse rates in the medium term between fluphenazine decanoate and fluphenazine enanthate was found (n = 49, 1 RCT, RR 2.43, CI 0.71 to 8.32, very low quality evidence), immediate- and short-term studies were also equivocal. One small study reported the number of participants leaving the study early (29% versus 12%) and mental state measured on the BPRS and found no significant difference for either outcome. No significant difference was found in extrapyramidal adverse effects between fluphenazine decanoate and fluphenazine enanthate. No study comparing fluphenazine decanoate with fluphenazine enanthate reported death, clinically significant changes in global state or hospital admissions. AUTHORS' CONCLUSIONS: There are more data for fluphenazine decanoate than for the enanthate ester. Both are effective antipsychotic preparations. Fluphenazine decanoate produced fewer movement disorder effects than other oral antipsychotics but data were of low quality, and overall, adverse effect data were equivocal. In the context of trials, there is little advantage of these depots over oral medications in terms of compliance but this is unlikely to be applicable to everyday clinical practice.

First rank symptoms for schizophrenia.

BACKGROUND: Early and accurate diagnosis and treatment of schizophrenia may have long-term advantages for the patient; the longer psychosis goes untreated the more severe the repercussions for relapse and recovery. If the correct diagnosis is not schizophrenia, but another psychotic disorder with some symptoms similar to schizophrenia, appropriate treatment might be delayed, with possible severe repercussions for the person involved and their family. There is widespread uncertainty about the diagnostic accuracy of First Rank Symptoms (FRS); we examined whether they are a useful diagnostic tool to differentiate schizophrenia from other psychotic disorders. OBJECTIVES: To determine the diagnostic accuracy of one or multiple FRS for diagnosing schizophrenia, verified by clinical history and examination by a qualified professional (e.g. psychiatrists, nurses, social workers), with or without the use of operational criteria and checklists, in people thought to have non-organic psychotic symptoms. SEARCH METHODS: We conducted searches in MEDLINE, EMBASE, and PsycInfo using OvidSP in April, June, July 2011 and December 2012. We also searched MEDION in December 2013. SELECTION CRITERIA: We selected studies that consecutively enrolled or randomly selected adults and adolescents with symptoms of psychosis, and assessed the diagnostic accuracy of FRS for schizophrenia compared to history and clinical examination performed by a qualified professional, which may or may not involve the use of symptom checklists or based on operational criteria such as ICD and DSM. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all references for inclusion. Risk of bias in included studies were assessed using the QUADAS-2 instrument. We recorded the number of true positives (TP), true negatives (TN), false positives (FP), and false negatives (FN) for constructing a 2 x 2 table for each study or derived 2 x 2 data from reported summary statistics such as sensitivity, specificity, and/or likelihood ratios. MAIN RESULTS: We included 21 studies with a total of 6253 participants (5515 were included in the analysis). Studies were conducted from 1974 to 2011, with 80% of the studies conducted in the 1970's, 1980's or 1990's. Most studies did not report study methods sufficiently and many had high applicability concerns. In 20 studies, FRS differentiated schizophrenia from all other diagnoses with a sensitivity of 57% (50.4% to 63.3%), and a specificity of 81.4% (74% to 87.1%) In seven studies, FRS differentiated schizophrenia from non-psychotic mental health disorders with a sensitivity of 61.8% (51.7% to 71%) and a specificity of 94.1% (88% to 97.2%). In sixteen studies, FRS differentiated schizophrenia from other types of psychosis with a sensitivity of 58% (50.3% to 65.3%) and a specificity of 74.7% (65.2% to 82.3%). AUTHORS' CONCLUSIONS: The synthesis of old studies of limited quality in this review indicates that FRS correctly identifies people with schizophrenia 75% to 95% of the time. The use of FRS to diagnose schizophrenia in triage will incorrectly diagnose around five to 19 people in every 100 who have FRS as having schizophrenia and specialists will not agree with this diagnosis. These people will still merit specialist assessment and help due to the severity of disturbance in their behaviour and mental state. Again, with a sensitivity of FRS of 60%, reliance on FRS to diagnose schizophrenia in triage will not correctly diagnose around 40% of people that specialists will consider to have schizophrenia. Some of these people may experience a delay in getting appropriate treatment. Others, whom specialists will consider to have schizophrenia, could be prematurely discharged from care, if triage relies on the presence of FRS to diagnose schizophrenia. Empathetic, considerate use of FRS as a diagnostic aid - with known limitations - should avoid a good proportion of these errors.We hope that newer tests - to be included in future Cochrane reviews - will show better results. However, symptoms of first rank can still be helpful where newer tests are not available - a situation which applies to the initial screening of most people with suspected schizophrenia. FRS remain a simple, quick and useful clinical indicator for an illness of enormous clinical variability.

Respite care for people with dementia and their carers.

BACKGROUND: Caring for someone with dementia can be emotionally and physically demanding. Respite care is any intervention designed to give rest or relief to caregivers. It is not clear what positive and negative effects such care may have on them, or on people with dementia. OBJECTIVES: To assess the benefits and harms of respite care for people with dementia and their caregivers, in particular the effect of respite care on rates of institutionalisation. SEARCH METHODS: The trials were identified from a search of ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, using the terms respite* OR daycare OR caregiver* relief. ALOIS contains up-to-date records from all major healthcare databases and many ongoing trial databases. SELECTION CRITERIA: Randomised controlled trials comparing respite care with a control intervention for people with dementia. DATA COLLECTION AND ANALYSIS: Two review authors carried out study selection independently and reached a consensus through discussion. Data were extracted by a single review author. The review authors contacted all investigators for methodological details not reported in the text and for additional data for three studies included in the previous version of the review. MAIN RESULTS: Four trials are now included in the review, with 753 participants. They were different in many ways including the intervention, duration, outcomes and control group so pooling of data was not possible. Overall, the quality of the evidence was rated as very low. Re-analysis of outcomes using data from the published studies found no significant effects of respite care compared to no respite care on any caregiver variable. When respite care was compared to polarity therapy a significant effect was found in favour of polarity therapy for caregiver perceived stress (n = 38, MD 5.80, 95% CI 1.43 to 10.17), but not for other measures of psychological health and other caregiver outcomes. No studies reported evaluable data on outcomes related to the people with dementia. AUTHORS' CONCLUSIONS: Current evidence does not demonstrate any benefits or adverse effects from the use of respite care for people with dementia or their caregivers. These results should be treated with caution, however, as they may reflect the lack of high quality research in this area rather than an actual lack of benefit. Given the frequency with which respite care is advocated and provided, well-designed trials are needed in this area.