Core outcome set for intervention research on snakebite envenomation in South Asia.

BACKGROUND: The 2019 WHO strategy to reduce snakebite burden emphasises the need for fostering research on snakebite treatments. A core outcome set (COS) is a consensus minimal list of outcomes that should be measured in research on a particular condition. We aimed to develop a COS for snakebite research in South Asia, the region with the highest burden. METHODS: We used data from a systematic review of outcomes to develop a long list of outcomes which were rated in two rounds of online Delphi survey with healthcare providers, patients and the public, and potential COS users to develop a COS for intervention research on snakebite treatments in South Asia for five intervention groups. Subsequently, meetings, consultations and workshops were organised to reach further consensus. We defined the consensus criteria a priori. RESULTS: Overall, 72 and 61 people, including patients and the public, participated in round I and round II of the Delphi, respectively. Consensus COSs (including definition and time points) were developed for interventions that prevent adverse reaction to snake antivenom (three outcomes), specifically manage neurotoxic manifestations (five outcomes), specifically manage haematological manifestations (five outcomes) and those that act against snake venom (seven) outcomes. A priori criteria for inclusion in COS were not met for COS on interventions for management of the bitten part. CONCLUSION: The COS contributes to improving research efficiency by standardising outcome measurement in South Asia. It also provides methodological insights for future development of COS, beyond snakebite.

The kidney histopathological spectrum of patients with kidney injury following snakebite envenomation in India: scoping review of five decades.

INTRODUCTION: Snakebite is a public health problem leading to about 58,000 deaths every year in India. Kidney injury subsequent to snakebite envenomation is common with a reported prevalence of up to 32%. The current study aims to elucidate the spectrum of kidney histopathology in acute kidney injury (AKI) cases associated with snake bites. METHODS: We searched seven electronic database studies to identify studies describing the histopathological findings in the kidney with snakebite envenomation. Two reviewers independently conducted titles and abstract screening as well as full-text evaluation for the final inclusion decision. Data were extracted as per the standardized form. We conducted narrative synthesis. Studies done exclusively on autopsy findings, in vitro studies, and case reports were excluded. RESULTS: We retrieved 1464 studies and finally included 28 studies which met the eligibility criteria in the analysis. Most studies were single-centre and the majority were cross-sectional. Overall we included a total of 534 renal biopsies. Russell's viper bite was the most common cause related to AKI. Acute tubular necrosis was the most common finding followed by acute interstitial nephritis, acute cortical necrosis (ACN), and thrombotic microangiopathy (TMA). Vasculitis changes in vessels were rarely reported. Lesions such as ACN and TMA were associated with poor outcomes. CONCLUSION: This analysis supports the notion that renal biopsies are important to guide prognosis and increase our knowledge about post-snake bite AKI pathophysiology.

A Reporting Tool for Adapted Guidelines in Health Care: The RIGHT-Ad@pt Checklist.

BACKGROUND: Adaptation of existing guidelines can be an efficient way to develop contextualized recommendations. Transparent reporting of the adaptation approach can support the transparency and usability of the adapted guidelines. OBJECTIVE: To develop an extension of the RIGHT (Reporting Items for practice Guidelines in HealThcare) statement for the reporting of adapted guidelines (including recommendations that have been adopted, adapted, or developed de novo), the RIGHT-Ad@pt checklist. DESIGN: A multistep process was followed to develop the checklist: establishing a working group, generating an initial checklist, optimizing the checklist (through an initial assessment of adapted guidelines, semistructured interviews, a Delphi consensus survey, an external review, and a final assessment of adapted guidelines), and approval of the final checklist by the working group. SETTING: International collaboration. PARTICIPANTS: A total of 119 professionals participated in the development process. MEASUREMENTS: Participants' consensus on items in the checklist. RESULTS: The RIGHT-Ad@pt checklist contains 34 items grouped in 7 sections: basic information (7 items); scope (6 items); rigor of development (10 items); recommendations (4 items); external review and quality assurance (2 items); funding, declaration, and management of interest (2 items); and other information (3 items). A user guide with explanations and real-world examples for each item was developed to provide a better user experience. LIMITATION: The RIGHT-Ad@pt checklist requires further validation in real-life use. CONCLUSION: The RIGHT-Ad@pt checklist has been developed to improve the reporting of adapted guidelines, focusing on the standardization, rigor, and transparency of the process and the clarity and explicitness of adapted recommendations. PRIMARY FUNDING SOURCE: None.

Embedding rapid reviews in health policy and systems decision-making: Impacts and lessons learned from four low- and middle-income countries.

BACKGROUND: Demand for rapid evidence-based syntheses to inform health policy and systems decision-making has increased worldwide, including in low- and middle-income countries (LMICs). To promote use of rapid syntheses in LMICs, the WHO's Alliance for Health Policy and Systems Research (AHPSR) created the Embedding Rapid Reviews in Health Systems Decision-Making (ERA) Initiative. Following a call for proposals, four LMICs were selected (Georgia, India, Malaysia and Zimbabwe) and supported for 1 year to embed rapid response platforms within a public institution with a health policy or systems decision-making mandate. METHODS: While the selected platforms had experience in health policy and systems research and evidence syntheses, platforms were less confident conducting rapid evidence syntheses. A technical assistance centre (TAC) was created from the outset to develop and lead a capacity-strengthening program for rapid syntheses, tailored to the platforms based on their original proposals and needs as assessed in a baseline questionnaire. The program included training in rapid synthesis methods, as well as generating synthesis demand, engaging knowledge users and ensuring knowledge uptake. Modalities included live training webinars, in-country workshops and support through phone, email and an online platform. LMICs provided regular updates on policy-makers' requests and the rapid products provided, as well as barriers, facilitators and impacts. Post-initiative, platforms were surveyed. RESULTS: Platforms provided rapid syntheses across a range of AHPSR themes, and successfully engaged national- and state-level policy-makers. Examples of substantial policy impact were observed, including for COVID-19. Although the post-initiative survey response rate was low, three quarters of those responding felt confident in their ability to conduct a rapid evidence synthesis. Lessons learned coalesced around three themes - the importance of context-specific expertise in conducting reviews, facilitating cross-platform learning, and planning for platform sustainability. CONCLUSIONS: The ERA initiative successfully established rapid response platforms in four LMICs. The short timeframe limited the number of rapid products produced, but there were examples of substantial impact and growing demand. We emphasize that LMICs can and should be involved not only in identifying and articulating needs but as co-designers in their own capacity-strengthening programs. More time is required to assess whether these platforms will be sustained for the long-term.

Effect of COVID-19 containment measures on access to snakebite care in India.

INTRODUCTION: The extensive spread of COVID-19 meant action to address the pandemic took precedence over routine service delivery, thus impacting access to care for many health conditions, including the effects of snakebite. METHOD: We prospectively collected facility-level data from several health facilities in India, including number of snakebite admissions and snakebite envenoming admissions on modality of transport to reach the health facility. To analyse the effect of a health facility being in cluster-containment zone, we used negative binomial regression analysis. RESULTS: Our findings suggest that that health facilities located within a COVID containment zone saw a significant decrease in total snakebite admissions (incidence rate ratio 0.64 (0.43-0.94), standard error 0.13, p≤0.02)) and envenoming snakebite admissions (incidence rate ratio 0.43 (0.23-0.81), standard error 0.14, p≤0.01) compared to when health facilities were not within a COVID containment zone. There was no statistically significant difference in non-envenoming admissions and modalities of transport used to reach health facilities. CONCLUSION: This article provides the first quantitative estimate of the impact of COVID-19 containment measures on access to snakebite care. More research is needed to understand how containment measures altered care-seeking pathways and the nature of snake-human-environment conflict. Primary healthcare systems need to be safeguarded for snakebite care to mitigate effects of cluster-containment measures.

Determining child drowning mortality in the Sundarbans, India: applying the community knowledge approach.

BACKGROUND: The Sundarbans in India is a rural, forested region where children are exposed to a high risk of drowning due to its waterlogged geography. Current data collection systems capture few drowning deaths in this region. METHODS: A community-based survey was conducted in the Sundarbans to determine the drowning mortality rate for children aged 1 to 4 years and 5 to 9 years. A community knowledge approach was used. Meetings were held with community residents and key informants to identify drowning deaths in the population. Identified deaths were verified by the child's household through a structured survey, inquiring on the circumstances around the drowning death. RESULTS: The drowning mortality rate for children aged 1 to 4 years was 243.8 per 100 000 children and for 5 to 9 years was 38.8 per 100 000 children. 58.0% of deaths were among children aged 1 to 2 years. No differences in rates between boys and girls were found. Most children drowned in ponds within 50 metres of their homes. Children were usually unaccompanied with their primary caretaker engaged in household work. A minority of children were treated by formal health providers. CONCLUSIONS: Drowning is a major cause of death among children in the Sundarbans, particularly those aged 1 to 4 years. Interventions keeping children in safe spaces away from water are urgently required. The results illustrate how routine data collection systems grossly underestimate drowning deaths, emphasising the importance of community-based surveys in capturing these deaths in rural low- and middle-income country contexts. The community knowledge approach provides a low-resource, validated methodology for this purpose.

Facilitators and barriers to child restraint use in motor vehicles: a qualitative evidence synthesis.

BACKGROUND: Road traffic collisions contribute a significant burden of mortality and morbidity to children globally. The improper or non-use of child restraints can result in children sustaining significant injuries in the event of a collision. Systematic reviews on the effectiveness of various interventions to increase the use of child restraints already exist but to the best of our knowledge, there has been no qualitative evidence syntheses on the facilitators and barriers to child restraint usage. This review aims to fill that gap. METHODS: We searched for qualitative studies, which focused on perceptions, values and experiences of children, parents/caregivers or any other relevant stakeholders on the use of restraints for children travelling in motor vehicles in PubMed, EMBASE and Global Health and screened reference lists of all included studies. We assessed the quality of included studies with the Critical Appraisal Skills Programme (CASP) checklist and used the PROGRESS Plus lens for an equity focused analysis. RESULTS: We identified a total of 335 records from searching the databases and five records from other sources. After screening, we identified 17 studies that met our inclusion criteria. All but one study (which had children as participants) focused on the perceptions, attitudes and barriers of parents or caregivers. The included studies were from three high-income (n=14) and one upper-middle income (n=3) country. In addition, although many focused exclusively on participants from culturally and linguistically diverse minorities, the issue of equity was not well addressed. Five major themes emerged from the analysis. (1) perceived risk for injuries and perceived safety benefits of child restraint usage varies in different settings and between different types of caregivers; (2) practical issues around the use of child restraints is a major barrier to its uptake as a child safety measure; (3) restraint use is considered as a mechanism to discipline children rather than as a safety device by parents and as children became older they actively seek opportunities to negotiate the non-usage of restraints; (4) adoption and enforcement of laws shape perceptions and usage in all settings and (5) perceptions and norms of child safety differ among culturally and linguistically diverse groups. CONCLUSION: The results of this systematic review should be considered when designing interventions to promote the uptake of child restraints. However, there is a need to conduct qualitative research around the facilitators and barriers to child restraint usage in low-income and middle-income countries. Furthermore, there is a need for more evidence conducted in semiurban and rural areas and to involve fathers, policy-makers, implementers and enforcement agencies in such studies.

Epidemiology of injuries from fire, heat and hot substances: global, regional and national morbidity and mortality estimates from the Global Burden of Disease 2017 study.

BACKGROUND: Past research has shown how fires, heat and hot substances are important causes of health loss globally. Detailed estimates of the morbidity and mortality from these injuries could help drive preventative measures and improved access to care. METHODS: We used the Global Burden of Disease 2017 framework to produce three main results. First, we produced results on incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years from 1990 to 2017 for 195 countries and territories. Second, we analysed these results to measure mortality-to-incidence ratios by location. Third, we reported the measures above in terms of the cause of fire, heat and hot substances and the types of bodily injuries that result. RESULTS: Globally, there were 8 991 468 (7 481 218 to 10 740 897) new fire, heat and hot substance injuries in 2017 with 120 632 (101 630 to 129 383) deaths. At the global level, the age-standardised mortality caused by fire, heat and hot substances significantly declined from 1990 to 2017, but regionally there was variability in age-standardised incidence with some regions experiencing an increase (eg, Southern Latin America) and others experiencing a significant decrease (eg, High-income North America). CONCLUSIONS: The incidence and mortality of injuries that result from fire, heat and hot substances affect every region of the world but are most concentrated in middle and lower income areas. More resources should be invested in measuring these injuries as well as in improving infrastructure, advancing safety measures and ensuring access to care.

The burden of unintentional drowning: global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study.

BACKGROUND: Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017. METHODS: Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning. RESULTS: Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes. CONCLUSIONS: There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries.

Burden of injury along the development spectrum: associations between the Socio-demographic Index and disability-adjusted life year estimates from the Global Burden of Disease Study 2017.

BACKGROUND: The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. METHODS: Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm-the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. RESULTS: For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. CONCLUSIONS: The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.

Assessing cardiovascular disease risk factor screening inequalities in India using Lot Quality Assurance Sampling.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of mortality in India. India has rolled out Comprehensive Primary Health Care (CPHC) reforms including population based screening for hypertension and diabetes, facilitated by frontline health workers. Our study assessed blood pressure and blood sugar coverage achieved by frontline workers using Lot Quality Assurance Sampling (LQAS). METHODS: LQAS Supervision Areas were defined as catchments covered by frontline workers in primary health centres in two districts each of Uttar Pradesh and Delhi. In each Area, 19 households for each of four sampling universes (males, females, Above Poverty Line (APL) and Below Poverty Line (BPL)) were visited using probability proportional to size sampling. Following written informed consent procedures, a short questionnaire was administered to individuals aged 30 or older using tablets related to screening for diabetes and hypertension. Using the LQAS hand tally method, coverage across Supervision Areas was determined. RESULTS: A sample of 2052 individuals was surveyed, median ages ranging from 42 to 45 years. Caste affiliation, education levels, and occupation varied by location; the sample was largely married and Hindu. Awareness of and interaction with frontline health workers was reported in Uttar Pradesh and mixed in Delhi. Greater coverage of CVD risk factor screening (especially blood pressure) was seen among females, as compared to males. No clear pattern of inequality was seen by poverty status; some SAs did not have adequate BPL samples. Overall, blood pressure and blood sugar screening coverage by frontline health workers fell short of targeted coverage levels at the aggregate level, but in all sites, at least one area was crossing this threshold level. CONCLUSION: CVD screening coverage levels at this early stage are low. More emphasis may be needed on reaching males. Sex and poverty related inequalities must be addressed by more closely studying the local context and models of service delivery where the threshold of screening is being met. LQAS is a pragmatic method for measuring program inequalities, in resource-constrained settings, although possibly not for spatially segregated population sub-groups.

Packed red cells versus whole blood transfusion for severe paediatric anaemia, pregnancy-related anaemia and obstetric bleeding: an analysis of clinical practice guidelines from sub-Saharan Africa and evidence underpinning recommendations.

OBJECTIVE: Blood component transfusion is increasingly promoted in sub-Saharan Africa (SSA), but is resource-intensive so whole blood is often used. We examined SSA recommendations about whole blood and packed red cell transfusions for pregnancy-related bleeding or anaemia, and paediatric anaemia, and evaluated the evidence underpinning these recommendations. METHOD: Relevant SSA guidelines were identified using five electronic databases, websites for SSA Ministries of Health, blood transfusion services and WHO. To facilitate comparisons, indications for transfusing packed red cells or whole blood within these guidelines and reasons given for these recommendations were recorded on a pre-designed matrix. The AGREE II tool was used to appraise guidelines that gave a reason for recommending either packed red cells or whole blood. We systematically searched MEDLINE, CINAHL, Global Health, Cochrane library and NHSBT Transfusion Evidence Library, using PRISMA guidelines, for clinical studies comparing whole blood with packed red cells or combined blood components in obstetric bleeding or anaemia, or paediatric anaemia. Characteristics and findings of included studies were extracted in a standardised format and narratively summarised. RESULTS: 32 English language guidelines from 15 SSA countries mentioned packed red cell or whole blood use for our conditions of interest. Only seven guidelines justified their recommendation for using packed red cells or whole blood. No recommendations or justifications had supporting citations to research evidence. 33 full-text papers, from 11 234 citations, were reviewed but only one study met our inclusion criteria. This was a single-centre study in post-partum haemorrhage. CONCLUSION: Evidence comparing whole blood and packed red cell transfusion for common paediatric and maternal indications is virtually absent in SSA. Therefore, it is unclear whether policies promoting red cells over whole blood transfusion are clinically appropriate. Building a relevant evidence base will help develop effective policies promoting the most appropriate use of blood in African settings.

Reporting guideline for priority setting of health research (REPRISE).

BACKGROUND: Research priority setting with stakeholders can help direct the limited resources for health research toward priority areas of need. Ensuring transparency of the priority setting process can strengthen legitimacy and credibility for influencing the research agenda. This study aims to develop a reporting guideline for priority setting of health research. METHODS: We searched electronic databases and relevant websites for sources (frameworks, guidelines, or models for conducting, appraising, reporting or evaluating health research priority setting, and reviews (including systematic reviews)), and primary studies of research priority setting to July 2019. We inductively developed a list of reporting items and piloted the preliminary guideline with a diverse range of 30 priority setting studies from the records retrieved. RESULTS: From 21,556 records, we included 26 sources for the candidate REPRISE framework and 455 primary research studies. The REporting guideline for PRIority SEtting of health research (REPRISE) has 31 reporting items that cover 10 domains: context and scope, governance and team, framework for priority setting, stakeholders/participants, identification and collection of priorities, prioritization of research topics, output, evaluation and feedback, translation and implementation, and funding and conflict of interest. Each reporting item includes a descriptor and examples. CONCLUSIONS: The REPRISE guideline can facilitate comprehensive reporting of studies of research priority setting. Improved transparency in research priority setting may strengthen the acceptability and implementation of the research priorities identified, so that efforts and funding are invested in generating evidence that is of importance to all stakeholders. TRIAL REGISTRATION: Not applicable.

​Primary closure versus delayed or no closure for traumatic wounds due to mammalian bite.

BACKGROUND: Mammalian bites are a common presentation in emergency and primary healthcare facilities across the world. The World Health Organization recommends postponing the suturing of a bite wound but this has not been evaluated through a systematic review. OBJECTIVES: To assess the effects of primary closure compared with delayed closure or no closure for mammalian bite wounds. SEARCH METHODS: In July 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials which compared primary closure with delayed or no closure for traumatic wounds due to mammalian bite. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full-text publications, applied the inclusion criteria, and extracted data. We pooled data using a random-effects model, as appropriate. We used the Cochrane 'Risk of bias' tool and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We found three trials (878 participants) that compared primary closure with no closure for dog bites and one trial (120 participants) that compared primary closure with delayed closure. No other mammalian bite studies were identified. The trials were from the UK (one trial), Greece (one trial) and China (two trials). Overall, participants from both sexes and all age groups were represented. We are uncertain whether primary closure improves the proportion of wounds which are infection-free compared with no closure, as the certainty of evidence for this outcome was judged to be very low (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.97 to 1.05; 2 studies, 782 participants; I2 = 0%). We downgraded the evidence by one level for high risk of bias and two levels for imprecision. There is no clinically important difference in cosmesis (acceptable physical/cosmetic appearance) of dog bite wounds when primary closure is compared with no closure (mean difference (MD) -1.31, 95% CI -2.03 to -0.59; 1 study, 182 participants). The certainty of evidence for this outcome was judged to be moderate (we downgraded our assessment by one level for imprecision). We are uncertain whether primary closure improves the proportion of dog bite wounds that are infection-free compared with delayed closure, as the evidence for this outcome was judged to be very low (RR 0.98, 95% CI 0.90 to 1.07; 1 study, 120 participants; I2 = 0%). We downgraded the evidence by one level for high risk of bias and two levels for imprecision. None of the four trials reported any adverse outcomes such as death or rabies but they were, in any case, unlikely to have been large enough to have satisfactory power to provide precise estimates for these. Important outcomes like time to complete wound healing, proportion of wounds healed, and length of hospital stay were not evaluated. AUTHORS' CONCLUSIONS: All the studies we identified concerned dog bites. There is no high-certainty evidence to support or refute existing recommendations concerning primary closure for dog bites. The potential benefits and harms of primary closure compared with delayed or no closure for mammalian bites remain uncertain and more robust trials are needed.

Fluid therapy for acute bacterial meningitis.

BACKGROUND: Acute bacterial meningitis remains a disease with high mortality and morbidity rates. However, with prompt and adequate antimicrobial and supportive treatment, the chances for survival have improved, especially among infants and children. Careful management of fluid and electrolyte balance is an important supportive therapy. Both over- and under-hydration are associated with adverse outcomes. This is the latest update of a review first published in 2005 and updated in 2008 and 2014. OBJECTIVES: To evaluate treatment of acute bacterial meningitis with differing volumes of initial fluid administration (up to 72 hours after first presentation) and the effects on death and neurological sequelae. SEARCH METHODS: For this 2016 update we searched the following databases up to March 2016: the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, CINAHL, Global Health, and Web of Science. SELECTION CRITERIA: Randomised controlled trials (RCTs) of differing volumes of fluid given in the initial management of bacterial meningitis were eligible for inclusion. DATA COLLECTION AND ANALYSIS: All four of the original review authors extracted data and assessed trials for quality in the first publication of this review (one author, ROW, has passed away since the original review; see Acknowledgements). The current authors combined data for meta-analysis using risk ratios (RRs) for dichotomous data or mean difference (MD) for continuous data. We used a fixed-effect statistical model. We assessed the overall quality of evidence using the GRADE approach. MAIN RESULTS: We included three trials with a total of 420 children; there were no trials in adult populations. The largest of the three trials was conducted in settings with high mortality rates and was judged to have low risk of bias for all domains, except performance bias which was high risk. The other two smaller trials were not of high quality.The meta-analysis found no significant difference between the maintenance-fluid and restricted-fluid groups in number of deaths (RR 0.82, 95% confidence interval (CI) 0.53 to 1.27; 407 participants; low quality of evidence) or acute severe neurological sequelae (RR 0.67, 95% CI 0.41 to 1.08; 407 participants; low quality of evidence). However, when neurological sequelae were defined further, there was a statistically significant difference in favour of the maintenance-fluid group for spasticity (RR 0.50, 95% CI 0.27 to 0.93; 357 participants); and seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83; 357 participants) and 14 days (RR 0.19, 95% CI 0.04 to 0.88; 357 participants). There was very low quality of evidence favouring maintenance fluid over restrictive fluid for chronic severe neurological sequelae at three months follow-up (RR 0.42, 95% CI 0.20 to 0.89; 351 participants). AUTHORS' CONCLUSIONS: The quality of evidence regarding fluid therapy in children with acute bacterial meningitis is low to very low and more RCTs need to be conducted. There is insufficient evidence to guide practice as to whether maintenance fluids should be chosen over restricted fluids in the treatment of acute bacterial meningitis.

Workplace interventions for reducing sitting at work.

BACKGROUND: Office work has changed considerably over the previous couple of decades and has become sedentary in nature. Physical inactivity at workplaces and particularly increased sitting has been linked to increase in cardiovascular disease, obesity and overall mortality. OBJECTIVES: To evaluate the effects of workplace interventions to reduce sitting at work compared to no intervention or alternative interventions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, OSH UPDATE, PsycINFO, Clinical trials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal up to 2 June, 2015. We also screened reference lists of articles and contacted authors to find more studies to include. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-randomised controlled trials (cRCTs), and quasi-randomised controlled trials of interventions to reduce sitting at work. For changes of workplace arrangements, we also included controlled before-and-after studies (CBAs) with a concurrent control group. The primary outcome was time spent sitting at work per day, either self-reported or objectively measured by means of an accelerometer-inclinometer. We considered energy expenditure, duration and number of sitting episodes lasting 30 minutes or more, work productivity and adverse events as secondary outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full-text articles for study eligibility. Two review authors independently extracted data and assessed risk of bias. We contacted authors for additional data where required. MAIN RESULTS: We included 20 studies, two cross-over RCTs, 11 RCTs, three cRCTs and four CBAs, with a total of 2180 participants from high income nations. The studies evaluated physical workplace changes (nine studies), policy changes (two studies), information and counselling (seven studies) and interventions from multiple categories (two studies). One study had both physical workplace changes and information and counselling components. We did not find any studies that had investigated the effect of periodic breaks or standing or walking meetings. Physical workplace changesA sit-stand desk alone compared to no intervention reduced sitting time at work per workday with between thirty minutes to two hours at short term (up to three months) follow-up (six studies, 218 participants, very low quality evidence). In two studies, sit-stand desks with additional counselling reduced sitting time at work in the same range at short-term follow-up (61 participants, very low quality evidence). One study found a reduction at six months' follow-up of -56 minutes (95% CI -101 to -12, very low quality evidence) compared to no intervention. Also total sitting time at work and outside work decreased with sit-stand desks compared to no intervention (MD -78 minutes, 95% CI -125 to -31, one study) as did the duration of sitting episodes lasting 30 minutes or more (MD -52 minutes, 95% CI -79 to -26, two studies). This is considerably less than the two to four hours recommended by experts. Sit-stand desks did not have a considerable effect on work performance, musculoskeletal symptoms or sick leave. It remains unclear if standing can repair the harms of sitting because there is hardly any extra energy expenditure.The effects of active workstations were inconsistent. Treadmill desks combined with counselling reduced sitting time at work (MD -29 minutes, 95% CI -55 to -2, one study) compared to no intervention at 12 weeks' follow-up. Pedalling workstations combined with information did not reduce inactive sitting at work considerably (MD -12 minutes, 95% CI -24 to 1, one study) compared to information alone at 16 weeks' follow-up. The quality of evidence was low for active workstations. Policy changesTwo studies with 443 participants provided low quality evidence that walking strategies did not have a considerable effect on workplace sitting time at 10 weeks' (MD -16 minutes, 95% CI -54 to 23) or 21 weeks' (MD -17 minutes, 95% CI -58 to 25) follow-up respectively. Information and counsellingCounselling reduced sitting time at work (MD -28 minutes, 95% CI -52 to -5, two studies, low quality evidence) at medium term (three months to 12 months) follow-up. Mindfulness training did not considerably reduce workplace sitting time (MD -2 minutes, 95% CI -22 to 18) at six months' follow-up and at 12 months' follow-up (MD -16 minutes, 95% CI -45 to 12, one study, low quality evidence). There was no considerable increase in work engagement with counselling.There was an inconsistent effect of computer prompting on sitting time at work. One study found no considerable effect on sitting at work (MD -17 minutes, 95% CI -48 to 14, low quality evidence) at 10 days' follow-up, while another study reported a significant reduction in sitting at work (MD -55 minutes, 95% CI -96 to -14, low quality evidence) at 13 weeks' follow-up. Computer prompts to stand reduced sitting at work by 14 minutes more (95% CI 10 to 19, one study) compared to computer prompts to step at six days' follow-up. Computer prompts did not change the number of sitting episodes that last 30 minutes or longer. Interventions from multiple categories Interventions combining multiple categories had an inconsistent effect on sitting time at work, with a reduction in sitting time at 12 weeks' (25 participants, very low quality evidence) and six months' (294 participants, low quality evidence) follow-up in two studies but no considerable effect at 12 months' follow-up in one study (MD -47.98, 95% CI -103 to 7, 294 participants, low quality evidence). AUTHORS' CONCLUSIONS: At present there is very low to low quality evidence that sit-stand desks may decrease workplace sitting between thirty minutes to two hours per day without having adverse effects at the short or medium term. There is no evidence on the effects in the long term. There were no considerable or inconsistent effects of other interventions such as changing work organisation or information and counselling. There is a need for cluster-randomised trials with a sufficient sample size and long term follow-up to determine the effectiveness of different types of interventions to reduce objectively measured sitting time at work.

Fluid therapy for acute bacterial meningitis.

BACKGROUND: Acute bacterial meningitis remains a disease with high mortality and morbidity rates. However, with prompt and adequate antimicrobial and supportive treatment, the chances for survival have improved, especially among infants and children. Careful management of fluid and electrolyte balance is an important supportive therapy. Both over- and under-hydration are associated with adverse outcomes. OBJECTIVES: To evaluate treatment of acute bacterial meningitis with differing volumes of initial fluid administration (up to 72 hours after first presentation) and the effects on death and neurological sequelae. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 10), MEDLINE (1966 to October week 5, 2013), EMBASE (1980 to November 2013), CINAHL (1981 to November 2013), LILACS (1982 to November 2013) and Web of Science (2010 to 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) of differing volumes of fluid given in the initial management of bacterial meningitis were eligible for inclusion. DATA COLLECTION AND ANALYSIS: For this update we identified two abstracts, but after obtaining full texts we excluded them. Previous searches had identified six trials; on careful inspection three trials (415 children) met the inclusion criteria. All four of the original review authors extracted data and assessed trials for quality (one author, ROW, has died since the original review; see Acknowledgements). We combined data for meta-analysis using risk ratios (RRs) for dichotomous data or mean difference (MD) for continuous data. We used a fixed-effect statistical model. We assessed overall evidence quality using the GRADE approach. MAIN RESULTS: There were no trials in adult populations. All included trials were on paediatric patient groups. The largest of the three trials was conducted in settings with high mortality rates. The meta-analysis found no significant difference between the maintenance-fluid and restricted-fluid groups in number of deaths (RR 0.82, 95% confidence interval (CI) 0.53 to 1.27; 407 participants) (moderate trial quality); acute severe neurological sequelae (RR 0.67, 95% CI 0.41 to 1.08; 407 participants) (very low trial quality); or in mild to moderate sequelae (RR 1.24, 95% CI 0.58 to 2.65; 357 participants) (moderate trial quality). However, when neurological sequelae were defined further, there was a statistically significant difference in favour of the maintenance-fluid group for spasticity (RR 0.50, 95% CI 0.27 to 0.93; 357 participants); seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83; 357 participants) and 14 days (RR 0.19, 95% CI 0.04 to 0.88; 357 participants); and chronic severe neurological sequelae at three months follow-up (RR 0.42, 95% CI 0.20 to 0.89; 351 participants). AUTHORS' CONCLUSIONS: The quality of evidence regarding fluid therapy in children with acute bacterial meningitis is not high-grade and there is a need for further research. Some evidence supports maintaining intravenous fluids rather than restricting them in the first 48 hours in settings with high mortality rates and where children present late. However, where children present early and mortality rates are lower, there is insufficient evidence to guide practice.

Community health workers for health systems resilience during COVID-19: protocol for qualitative evidence synthesis.

INTRODUCTION: COVID-19 exposed the fragility of health systems, where even the most basic health services in high-income and low-income and middle-income nations could not withstand the health systems shock due to the pandemic. Community health workers (CHWs) can contribute to improving the resilience of health systems, specifically to withstand shocks and emergencies and to avoid disruptions of routine service delivery. We aim to explore and understand the 'individual' and 'systems-level' resilience factors that shaped the involvement of CHWs in the COVID-19 response. METHODS AND ANALYSIS: We will search five electronic databases (PubMed, Cochrane Library, EMBASE, CINAHL and SciELO (Spanish)) and conduct citation screening to identify studies on CHWs' response during the COVID-19 pandemic. Two review authors will independently screen the studies for inclusion and to extract data. The software Rayyan will be used to assist in screening the relevant literature. A thematic analysis approach will be followed to analyse and synthesise the qualitative evidence. The quality of the included studies will be critically assessed using the Critical Skills Appraisal Programme Tool. We will use the GRADE CERQual(Grading of Recommendations, Assessment, Development, and Evaluations - Confidence in the Evidence from Reviews of Qualitative Research) approach to assess certainty in the synthesised findings of the qualitative evidence. ETHICS AND DISSEMINATION: This study will be conducted on published evidence, with no living participants; thus, no ethical approval is required. The final review will be submitted and published in a peer-reviewed journal. We will also develop a policy brief to communicate the review findings to the stakeholders.