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Objectives. We estimated the relative rate of highly credible gastrointestinal illness (HCGI) per year associated with active versus sham household water filtration devices among older adults in a community receiving tap water meeting current US standards. Methods. We conducted a randomized, triple-blinded, crossover trial in 714 households (988 individuals), which used active and sham water filtration devices for 6 months each. We estimated the annual incidence rate ratio of HCGI episodes and the longitudinal prevalence ratio of HCGI days at population and individual levels with a generalized estimating equation (GEE) and generalized linear mixed models (GLMMs), respectively, adjusted for covariates associated with outcome. Results. The incidence rate ratios (active versus sham) were 0.88 (95% confidence interval [CI]=0.77, 1.00) and 0.85 (95% CI=0.76, 0.94) HCGI episodes per year estimated by GEE and GLMM models, respectively. The corresponding longitudinal prevalence ratios were 0.88 (95% CI=0.74, 1.05) and 0.84 (95% CI=0.78, 0.90) HCGI days per person per year. Conclusions. We observed reductions in population-and individual-level measures of HCGI associated with use of the active filtration device. These findings suggest the need for further research on the impact of drinking water on the health of sensitive subpopulations. [ABSTRACT FROM AUTHOR]

The incidence of acute gastrointestinal illness (AGI) attributable to public drinking water systems in the United States cannot be directly measured but must be estimated based on epidemiologic studies and other information. The randomized trial is one study design used to evaluate risks attributable to drinking water. In this paper, we review all published randomized trials of drinking water interventions in industrialized countries conducted among general immunocompetent populations. We then present an approach to estimating the incidence (number of cases) of AGI attributable annually to drinking water. To develop a national estimate, we integrate trial results with the estimated incidence of AGI using necessary assumptions about the estimated number of residents consuming different sources of drinking water and the relative quality of the water sources under different scenarios. Using this approach we estimate there to be 4.26–11.69 million cases of AGI annually attributable to public drinking water systems in the United States. We believe this preliminary estimate should be updated as new data become available. [ABSTRACT FROM AUTHOR]

Although immunocompromised persons may be at increased risk for gastrointestinal illnesses, no trials investigating drinking water treatment and gastrointestinal illness in such patients have been published. Earlier results from San Francisco suggested an association (OR 6.76) between tap water and cryptosporidiosis among HIV + persons. The authors conducted a randomized, triple-blinded intervention trial of home water treatment in San Francisco, California, from April 2000 to May 2001. Fifty HIV-positive patients were randomized to externally identical active (N = 24) or sham (N = 26) treatment devices. The active device contained a filter and UV light; the sham provided no treatment. Forty-five (90%) of the participants completed the study and were successfully blinded. Illness was measured using `highly credible gastrointestinal illness' (HCGI), a previously published measure. There were 31 episodes of HCGI during 1,797 person-days in the sham group and 16 episodes during 1,478 person-days in the active group. The adjusted relative risk was 3.34 (95% Cl: 0.99-11.21) times greater in those with the sham device. The magnitude of the point estimate of the risk, its consistency with recently published observational data, and its relevance for drinking water choices by immunocompromised individuals support the need for larger trials. [ABSTRACT FROM AUTHOR]

Approximately 1,100 communities in the United States have combined sewer and stormwater systems whose capacity may be exceeded during moderate or heavy rainfall. Outflows may occur that can deposit water with varying concentrations of the components of sewage onto public areas, where contact with residents or workers is possible, potentially resulting in a range of adverse health effects. This study proposes and applies three analytic methods to evaluate the impact of such outflows on public health. [ABSTRACT FROM AUTHOR]

Examines the literature describing the stresses experienced by hospital residents in training, the effects of stresses on residents and methods to reduce job stress. Recognition by the health community of the crisis in residency training due to stress; Failure of residency programs to fill up slots in the matching process; Advocation for legislative changes by staff unions; Need to address the problem of sleep deprivation.

A letter to the editor is presented which is concerned with the health benefits of water filters.

BACKGROUND: The recent global climate agreement in Paris aims to mitigate greenhouse gas emissions while fostering sustainable development and establishes an international trading mechanism to meet this goal. Currently, carbon offset program implementers are allowed to collect their own monitoring data to determine the number of carbon credits to be awarded. OBJECTIVES: We summarize reasons for mandating independent monitoring of greenhouse gas emission reduction projects. In support of our policy recommendations, we describe a case study of a program designed to earn carbon credits by distributing almost one million drinking water filters in rural Kenya to avert the use of fuel for boiling water. We compare results from an assessment conducted by our research team in the program area among households with pregnant women or caregivers in rural villages with low piped water access with the reported program monitoring data and discuss the implications. DISCUSSION: Our assessment in Kenya found lower levels of household water filter usage than the internal program monitoring reported estimates used to determine carbon credits; we found 19% (n = 4,041) of households reported filter usage 2 -- 3 years after filter distribution compared to the program stated usage rate of 81% (n = 14,988) 2.7 years after filter distribution. Although carbon financing could be a financially sustainable approach to scale up water treatment and improve health in low-income settings, these results suggest program effectiveness will remain uncertain in the absence of requiring monitoring data be collected by third-party organizations. CONCLUSION: Independent monitoring should be a key requirement for carbon credit verification in future international carbon trading mechanisms to ensure programs achieve benefits in line with sustainable development goals. CITATION: Pickering AJ, Arnold BF, Dentz HN, Colford JM Jr., Null C. 2017. Climate and health co-benefits in low-income countries: a case study of carbon financed water filters in Kenya and a call for independent monitoring. Environ Health Perspect 125:278 -- 283; http://dx.doi. org/10.1289/EHP342 [ABSTRACT FROM AUTHOR]

Background: Diarrhea and acute respiratory infection (ARI) are leading causes of death in children. The WASH Benefits Bangladesh trial implemented a multicomponent sanitation intervention that led to a 39% reduction in the prevalence of diarrhea among children and a 25% reduction for ARI, measured 1 to 2 years after intervention implementation. We measured longer-term intervention effects on these outcomes between 1 to 3.5 years after intervention implementation, including periods with differing intensity of behavioral promotion.Methods and Findings: WASH Benefits Bangladesh was a cluster-randomized controlled trial of water, sanitation, hygiene, and nutrition interventions (NCT01590095). The sanitation intervention included provision of or upgrades to improved latrines, sani-scoops for feces removal, children's potties, and in-person behavioral promotion. Promotion was intensive up to 2 years after intervention initiation, decreased in intensity between years 2 to 3, and stopped after 3 years. Access to and reported use of latrines was high in both arms, and latrine quality was significantly improved by the intervention, while use of child feces management tools was low. We enrolled a random subset of households from the sanitation and control arms into a longitudinal substudy, which measured child health with quarterly visits between 1 to 3.5 years after intervention implementation. The study period therefore included approximately 1 year of high-intensity promotion, 1 year of low-intensity promotion, and 6 months with no promotion. We assessed intervention effects on diarrhea and ARI prevalence among children <5 years through intention-to-treat analysis using generalized linear models with robust standard errors. Masking was not possible during data collection, but data analysis was masked. We enrolled 720 households (360 per arm) from the parent trial and made 9,800 child observations between June 2014 and December 2016. Over the entire study period, diarrheal prevalence was lower among children in the sanitation arm (11.9%) compared to the control arm (14.5%) (prevalence ratio [PR] = 0.81, 95% CI 0.66, 1.00, p = 0.05; prevalence difference [PD] = -0.027, 95% CI -0.053, 0, p = 0.05). ARI prevalence did not differ between sanitation (21.3%) and control (22.7%) arms (PR = 0.93, 95% CI 0.82, 1.05, p = 0.23; PD = -0.016, 95% CI -0.043, 0.010, p = 0.23). There were no significant differences in intervention effects between periods with high-intensity versus low-intensity/no promotion. Study limitations include use of caregiver-reported symptoms to define health outcomes and limited data collected after promotion ceased.Conclusions: The observed effect of the WASH Benefits Bangladesh sanitation intervention on diarrhea in children appeared to be sustained for at least 3.5 years after implementation, including 1.5 years after heavy promotion ceased. Existing latrine access was high in the study setting, suggesting that improving on-site latrine quality can deliver health benefits when latrine use practices are in place. Further work is needed to understand how latrine adoption can be achieved and sustained in settings with low existing access and how sanitation programs can adopt transformative approaches of excreta management, including safe disposal of child and animal feces, to generate a hygienic home environment.Trial Registration: ClinicalTrials.gov; NCT01590095; https://clinicaltrials.gov/ct2/show/NCT01590095. [ABSTRACT FROM AUTHOR]

Background Children may be at higher risk for swimming-associated illness following exposure to fecally-contaminated recreational waters. We analyzed a pooled data set of over 80,000 beachgoers from 13 beach sites across the United States to compare risks associated with the fecal indicator bacteria Enterococcus spp. (measured by colony forming units, CFU and quantitative polymerase chain reaction cell equivalents, qPCR CE) for different age groups across different exposures, sites and health endpoints. Methods Sites were categorized according to the predominant type of fecal contamination (human or non-human). Swimming exposures of varying intensity were considered according to degree of contact and time spent in the water. Health endpoints included gastrointestinal and respiratory symptoms and skin rashes. Logistic regression models were used to analyze the risk of illness as a function of fecal contamination in water as measured by Enterococcus spp. among the exposed groups. Non-swimmers (those who did not enter the water) were excluded from the models to reduce bias and facilitate comparison across groups. Results Gastrointestinal symptoms were the most sensitive health endpoint and strongest associations were observed with Enterococcus qPCR CE at sites impacted by human fecal contamination. Under several exposure scenarios, associations between illness and Enterococcus spp. levels were significantly higher among children compared to adolescents and adults. Respiratory symptoms were also associated with Enterococcus spp. exposures among young children at sites affected by human fecal sources, although small sample sizes resulted in imprecise estimates for these associations. Conclusion Under many exposure scenarios, children were at higher risk of illness associated with exposure to fecal contamination as measured by the indicator bacteria Enterococcus spp. The source of fecal contamination and the intensity of swimming exposure were also important factors affecting the association between Enterococcus spp. and swimming-associated illness. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend the use of Escherichia coli (EC) or thermotolerant (“fecal”) coliforms (FC) as indicators of fecal contamination in drinking water. Despite their broad use as measures of water quality, there remains limited evidence for an association between EC or FC and diarrheal illness: a previous review found no evidence for a link between diarrhea and these indicators in household drinking water. Objectives: We conducted a systematic review and meta-analysis to update the results of the previous review with newly available evidence, to explore differences between EC and FC indicators, and to assess the quality of available evidence. Methods: We searched major databases using broad terms for household water quality and diarrhea. We extracted study characteristics and relative risks (RR) from relevant studies. We pooled RRs using random effects models with inverse variance weighting, and used standard methods to evaluate heterogeneity and publication bias. Results: We identified 20 relevant studies; 14 studies provided extractable results for meta-analysis. When combining all studies, we found no association between EC or FC and diarrhea (RR 1.26 [95% CI: 0.98, 1.63]). When analyzing EC and FC separately, we found evidence for an association between diarrhea and EC (RR: 1.54 [95% CI: 1.37, 1.74]) but not FC (RR: 1.07 [95% CI: 0.79, 1.45]). Across all studies, we identified several elements of study design and reporting (e.g., timing of outcome and exposure measurement, accounting for correlated outcomes) that could be improved upon in future studies that evaluate the association between drinking water contamination and health. Conclusions: Our findings, based on a review of the published literature, suggest that these two coliform groups have different associations with diarrhea in household drinking water. Our results support the use of EC as a fecal indicator in household drinking water. [ABSTRACT FROM AUTHOR]

Background: Water distribution systems are vulnerable to performance deficiencies that can cause (re)contamination of treated water and plausibly lead to increased risk of gastrointestinal illness (GII) in consumers. Objectives: It is well established that large system disruptions in piped water networks can cause GII outbreaks. We hypothesized that routine network problems can also contribute to background levels of waterborne illness and conducted a systematic review and meta-analysis to assess the impact of distribution system deficiencies on endemic GII. Methods: We reviewed published studies that compared direct tap water consumption to consumption of tap water re‑treated at the point of use (POU) and studies of specific system deficiencies such as breach of physical or hydraulic pipe integrity and lack of disinfectant residual. Results: In settings with network malfunction, consumers of tap water versus POU-treated water had increased GII [incidence density ratio (IDR) = 1.34; 95% CI: 1.00, 1.79]. The subset of nonblinded studies showed a significant association between GII and tap water versus POU-treated water consumption (IDR = 1.52; 95% CI: 1.05, 2.20), but there was no association based on studies that blinded participants to their POU water treatment status (IDR = 0.98; 95% CI: 0.90, 1.08). Among studies focusing on specific network deficiencies, GII was associated with temporary water outages (relative risk = 3.26; 95% CI: 1.48, 7.19) as well as chronic outages in intermittently operated distribution systems (odds ratio = 1.61; 95% CI: 1.26, 2.07). Conclusions: Tap water consumption is associated with GII in malfunctioning distribution networks. System deficiencies such as water outages also are associated with increased GII, suggesting a potential health risk for consumers served by piped water networks. [ABSTRACT FROM AUTHOR]

Background: Drinking water contaminated by chemicals or pathogens is a major public health threat in the developing world. Responses to this threat often require water consumers (households or communities) to improve their own management or treatment of water. One approach hypothesized to increase such positive behaviors is increasing knowledge of the risks of unsafe water through the dissemination of water contamination data. This paper reviews the evidence for this approach in changing behavior and subsequent health outcomes. Methods/Principal Findings: A systematic review was conducted for studies where results of tests for contaminants in drinking water were disseminated to populations whose water supply posed a known health risk. Studies of any design were included where data were available from a contemporaneous comparison or control group. Using multiple sources .14,000 documents were located. Six studies met inclusion criteria (four of arsenic contamination and two of microbiological contamination). Meta-analysis was not possible in most cases due to heterogeneity of outcomes and study designs. Outcomes included water quality, change of water source, treatment of water, knowledge of contamination, and urinary arsenic. Source switching was most frequently reported: of 5 reporting studies 4 report significantly higher rates of switching (26-72%) among those who received a positive test result and a pooled risk difference was calculate for 2 studies (RD = 0.43 [CI0.4.0-0.46] 6-12 months post intervention) suggesting 43% more of those with unsafe wells switched source compared to those with safe wells. Strength of evidence is low since the comparison is between non-equivalent groups. Two studies concerning fecal contamination reported non-significant increases in point-of-use water treatment. Conclusion: Despite the publication of some large cohort studies and some encouraging results the evidence base to support dissemination of contamination data to improve water management is currently equivocal. Rigorous studies on this topic are needed, ideally using common outcome measures. [ABSTRACT FROM AUTHOR]

Background: Estimating the required sample size and statistical power for a study is an integral part of study design. For standard designs, power equations provide an efficient solution to the problem, but they are unavailable for many complex study designs that arise in practice. For such complex study designs, computer simulation is a useful alternative for estimating study power. Although this approach is well known among statisticians, in our experience many epidemiologists and social scientists are unfamiliar with the technique. This article aims to address this knowledge gap. Methods: We review an approach to estimate study power for individual- or cluster-randomized designs using computer simulation. This flexible approach arises naturally from the model used to derive conventional power equations, but extends those methods to accommodate arbitrarily complex designs. The method is universally applicable to a broad range of designs and outcomes, and we present the material in a way that is approachable for quantitative, applied researchers. We illustrate the method using two examples (one simple, one complex) based on sanitation and nutritional interventions to improve child growth. Results: We first show how simulation reproduces conventional power estimates for simple randomized designs over a broad range of sample scenarios to familiarize the reader with the approach. We then demonstrate how to extend the simulation approach to more complex designs. Finally, we discuss extensions to the examples in the article, and provide computer code to efficiently run the example simulations in both R and Stata. Conclusions: Simulation methods offer a flexible option to estimate statistical power for standard and nontraditional study designs and parameters of interest. The approach we have described is universally applicable for evaluating study designs used in epidemiologic and social science research. [ABSTRACT FROM AUTHOR]

The United States Environmental Protection Agency is committed to developing new recreational water quality criteria for coastal waters by 2012 to provide increased protection to swimmers. We review the uncertainties and shortcomings of the current recreational water quality criteria, describe critical research needs for the development of new criteria, as well as recommend a path forward for new criteria development. We believe that among the most needed research needs are the completion of epidemiology studies in tropical waters and in waters adversely impacted by urban runoff and animal feces, as well as studies aimed to validate the use of models for indicator and pathogen concentration and health risk predictions. [ABSTRACT FROM AUTHOR]

During the Escherichia coli O157:H7 outbreak in 2006 in the United States, the primary strategy to prevent illness was to advise consumers not to eat spinach. No widespread warnings were issued about preventing person-to-person (secondary) transmission. A disease transmission model, fitted to the current data, was used to investigate likely reductions in illnesses that could result from interventions to prevent secondary transmission. The model indicates that exposure to contaminated spinach occurred early in the outbreak and that secondary transmission was similar to that in previous E. coli outbreaks (≈12%). The model also suggests that even a modestly effective strategy to interrupt secondary transmission (prevention of only 2%-3% of secondary illnesses) could result in a reduction of ≈5%-11% of symptomatic cases. This analysis supports the use of widespread public health messages during outbreaks of E. coli O157:H7 with specific advice on how to interrupt secondary transmission. [ABSTRACT FROM AUTHOR]

Background: More than 200 studies related to nucleic acid amplification (NAA) tests to detect Mycobacterium tuberculosis directly from clinical specimens have appeared in the world literature since this technology was first introduced. NAA tests come as either commercial kits or as tests designed by the reporting investigators themselves (in-house tests). In-house tests vary widely in their accuracy, and factors that contribute to heterogeneity in test accuracy are not well characterized. Here, we used meta-analytical methods, including meta-regression, to identify factors related to study design and assay protocols that affect test accuracy in order to identify those factors associated with high estimates of accuracy. Results: By searching multiple databases and sources, we identified 2520 potentially relevant citations, and analyzed 84 separate studies from 65 publications that dealt with in-house NAA tests to detect M. tuberculosis in sputum samples. Sources of heterogeneity in test accuracy estimates were determined by subgroup and meta-regression analyses. Among 84 studies analyzed, the sensitivity and specificity estimates varied widely; sensitivity varied from 9.4% to 100%, and specificity estimates ranged from 5.6% to 100%. In the meta-regression analysis, the use of IS6110 as a target, and the use of nested PCR methods appeared to be significantly associated with higher diagnostic accuracy. Conclusion: Estimates of accuracy of in-house NAA tests for tuberculosis are highly heterogeneous. The use of IS6110 as an amplification target, and the use of nested PCR methods appeared to be associated with higher diagnostic accuracy. However, the substantial heterogeneity in both sensitivity and specificity of the in-house NAA tests rendered clinically useful estimates of test accuracy difficult. Future development of NAA-based tests to detect M. tuberculosis from sputum specimens should take into consideration these findings in improving accuracy of in-house NAA tests. [ABSTRACT FROM AUTHOR]

A major challenge in tuberculosis control is the diagnosis and treatment of latent tuberculosis infection. Until recently, there were no alternatives to the tuberculin skin test (TST) for diagnosing latent tuberculosis. However, an alternative has now emerged in the form of a new in-vitro test: the interferon-γ assay. We did a systematic review to assess the performance of interferon-γ assays in the immunodiagnosis of tuberculosis. By searching databases, contacting experts and test manufacturers, we identified 75 relevant studies. The results suggest that interferon-γ assays that use Mycobacterium tuberculosis-specific region of difference 1 (RD1) antigens (such as early secretory antigenic target 6 and culture filtrate protein 10) may have advantages over the TST, in terms of higher specificity, better correlation with exposure to M tuberculosis, and less cross-reactivity due to BCG vaccination and non-tuberculous mycobacterial infection. However, interferon-γ assays that use RD1 antigens in isolation may maximise specificity at the cost of sensitivity. Assays that use cocktails of RD1 antigens seem to overcome this problem, and such assays have the highest accuracy. RD1-based interferon-γ assays can potentially identify those with latent tuberculosis who are at high risk for developing active disease, but this requires confirmation. There is inadequate evidence on the value of interferon-γ assays in the management of immunocompromised individuals, children, patients with extrapulmonary or non-tuberculous mycobacterial disease, and populations in countries where tuberculosis is endemic. Current evidence suggests that interferon-γ assays based on cocktails of RD1 antigens have the potential to become useful diagnostic tools. Whether this potential can be realised in practice remains to be confirmed in well designed, long-term studies. [Copyright &y& Elsevier]

BACKGROUND: Inadequate access to safe drinking water remains a global health problem, particularly in rural areas. Boiling is the most commonly used form of point-of-use household water treatment (HWT) globally, although the use of bottled water in low- and middle-income countries (LMICs) is increasing rapidly. OBJECTIVES: We assessed the regional and seasonal prevalence of HWT practices (including bottled water use) in low-income rural areas in two Chinese provinces, evaluated the microbiological safety of drinking water and associated health outcomes, and estimated the air pollution burden associated with the use of solid fuels for boiling. METHODS: We conducted cross-sectional surveys and collected drinking water samples from 1,033 rural households in Guangxi and Henan provinces. Temperature sensors affixed to pots and electric kettles were used to corroborate self-reported boiling frequencies and durations, which were used to model household air pollution (HAP) in terms of estimated particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5) concentrations. RESULTS: Based on summer data collection in both provinces, after controlling for covariates, boiling with electric kettles was associated with the largest log reduction in thermotolerant coliforms (TTCs) (-0.66log10 TTC most probable number/100mL), followed by boiling with pots (-0.58), and bottled water use (-0.39); all were statistically significant (p<0.001). Boiling with electric kettles was associated with a reduced risk of TTC contamination [risk ratio (RR)=0.25, p<0.001] and reported diarrhea (RR=0.80, p=0.672). TTCs were detected in 51% (p=136) of bottled water samples. For households boiling with biomass, modeled PM2.5 concentrations averaged 79 µg/m³ (standard deviation=21). DISCUSSION: Our findings suggest that where boiling is already common and electricity access is widespread, the promotion of electricity-based boiling may represent a pragmatic stop-gap means of expanding safe water access until centralized, or decentralized, treated drinking water is available; displacing biomass use for water boiling could also reduce HAP concentrations and exposures. Our results also highlight the risks of increasing bottled water use in rural areas, and its potential to displace other sources of safe drinking water, which could in turn hamper efforts in China and other LMICs toward universal and affordable safe water access. [ABSTRACT FROM AUTHOR]

BACKGROUND: The effects of weather on diarrhea could influence the health impacts of climate change. Children have the highest diarrhea incidence, especially in India, where many lack safe water and sanitation. OBJECTIVES: In a prospective cohort of 1,284 children under 5 y of age from 900 households across 25 villages in rural Tamil Nadu, India, we examined whether high temperature and heavy rainfall was associated with increased all-cause diarrhea and water contamination. METHODS: Seven-day prevalence of diarrhea was assessed monthly for up to 12 visits from January 2008 to April 2009, and hydrogen sulfide (H2S) presence in drinking water, a fecal contamination indicator, was tested in a subset of households. We estimated associations between temperature and rainfall exposures and diarrhea and H2S using binomial regressions, adjusting for potential confounders, random effects for village, and autoregressive-1 error terms for study week. RESULTS: There were 259 cases of diarrhea. The prevalence of diarrhea during the 7 d before visits was 2.95 times higher (95% CI: 1.99, 4.39) when mean temperature in the week before the 7-d recall was in the hottest versus the coolest quartile of weekly mean temperature during 1 December 2007 to 15 April 2009. Diarrhea prevalence was 1.50 times higher when the 3 weeks before the diarrhea recall period included ≥1 d (vs. 0 d) with rainfall of >16:82 mm (95% CI: 1.12, 2.02), and 2.60 times higher (95% CI: 1.55, 4.36) for heavy rain weeks following a 60-d dry period. The H2S prevalence in household water was not associated with heavy rain prior to sample collection. CONCLUSIONS: The results suggest that, in rural Tamil Nadu, heavy rainfall may wash pathogens that accumulate during dry weather into child contact. Higher temperatures were positively associated with diarrhea 1-3 weeks later. Our findings suggest that diarrhea morbidity could worsen under climate change without interventions to reduce enteric pathogen transmission through multiple pathways. [ABSTRACT FROM AUTHOR]

Background: Shorter childhood telomere length (TL) and more rapid TL attrition are widely regarded as manifestations of stress. However, the potential effects of health interventions on child TL are unknown. We hypothesized that a water, sanitation, handwashing (WSH), and nutritional intervention would slow TL attrition during the first two years of life. Methods: In a trial in rural Bangladesh (ClinicalTrials.gov, NCT01590095), we randomized geographical clusters of pregnant women into individual water treatment, sanitation, handwashing, nutrition, combined WSH, combined nutrition plus WSH (N + WSH), or control arms. We conducted a substudy enrolling children from the control arm and the N + WSH intervention arm. Participants and outcome assessors were not masked; analyses were masked. Relative TL was measured at 1 and 2 years after intervention, and the change in relative TL was reported. Analysis was intention-to-treat. Findings: Between May 2012 and July 2013, in the overall trial, we randomized 720 geographical clusters of 5551 pregnant women to a control or an intervention arm. In this substudy, after 1 year of intervention, we assessed a total of 662 children (341 intervention and 321 control) and 713 children after 2 years of intervention (383 intervention and 330 control). Children in the intervention arm had significantly shorter relative TL compared with controls after 1 year of intervention (difference -163 base pairs (bp), p=0.001). Between years 1 and 2, TL increased in the intervention arm (+76 bp) and decreased in the controls (-23 bp) (p=0.050). After 2 years, there was no difference between the arms (p=0.305). Interpretation: Our unexpected finding of increased telomere attrition during the first year of life in the intervention group suggests that rapid telomere attrition during this critical period could reflect the improved growth in the intervention group, rather than accumulated stress. Funding: The Bill and Melinda Gates Foundation [ABSTRACT FROM AUTHOR]

Rainstorms increase levels of fecal indicator bacteria in urban coastal waters, but it is unknown whether exposure to seawater after rainstorms increases rates of acute illness. Our objective was to provide the first estimates of rates of acute illness after seawater exposure during both dry- and wet-weather periods and to determine the relationship between levels of indicator bacteria and illness among surfers, a population with a high potential for exposure after rain. We enrolled 654 surfers in San Diego, California, and followed them longitudinally during the 2013--2014 and 2014--2015 winters (33,377 days of observation, 10,081 surf sessions). We measured daily surf activities and illness symptoms (gastrointestinal illness, sinus infections, ear infections, infected wounds). Compared with no exposure, exposure to seawater during dry weather increased incidence rates of all outcomes (e.g., for earache or infection, adjusted incidence rate ratio (IRR) = 1.86, 95% confidence interval (CI): 1.27, 2.71; for infected wounds, IRR = 3.04, 95% CI: 1.54, 5.98); exposure during wet weather further increased rates (e.g., for earache or infection, IRR = 3.28, 95% CI: 1.95, 5.51; for infected wounds, IRR = 4.96, 95% CI: 2.18, 11.29). Fecal indicator bacteria measured in seawater (Enterococcus species, fecal coliforms, total coliforms) were strongly associated with incident illness only during wet weather. Urban coastal seawater exposure increases the incidence rates of many acute illnesses among surfers, with higher incidence rates after rainstorms. [ABSTRACT FROM AUTHOR]

Background: Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity. Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects.Methods: We searched 19 electronic databases for articles published before 2014 and hand-searched titles from 2010 to 2013 in five relevant journals. We adapted the Cochrane Collaboration's quality grading tool for spillover estimation and rated the quality of evidence.Results: A total of 54 studies met inclusion criteria. We found a wide range of terminology used to describe spillovers, a lack of standardization among spillover methods and poor reporting of spillovers in many studies. We identified three primary mechanisms of spillovers: reduced disease transmission, social proximity and substitution of resources within households. We found the strongest evidence for spillovers through reduced disease transmission, particularly vaccines and mass drug administration. In general, the proportion of a population receiving an intervention was associated with improved health. Most studies were of moderate or low quality. We found evidence of publication bias for certain spillover estimates but not for total or direct effects. To facilitate improved reporting and standardization in future studies, we developed a reporting checklist adapted from the CONSORT framework specific to reporting spillover effects.Conclusions: We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease. There was little high quality evidence of spillovers for other interventions. [ABSTRACT FROM AUTHOR]

Approximately two billion people drink unsafe water. Boiling is the most commonly used household water treatment (HWT) method globally and in China. HWT can make water safer, but sustained adoption is rare and bottled water consumption is growing. To successfully promote HWT, an understanding of associated socioeconomic factors is critical. We collected survey data and water samples from 450 rural households in Guangxi Province, China. Covariates were grouped into blocks to hierarchically construct modified Poisson models and estimate risk ratios (RR) associated with boiling methods, bottled water, and untreated water. Female-headed households were most likely to boil (RR = 1.36, p < 0.01), and among boilers those using electric kettles rather than pots had higher income proxies (e.g., per capita TV ownership RR = 1.42, p < 0.01). Higher-income households with younger, literate, and male heads were more likely to purchase (frequently contaminated) bottled water, or use electric kettles if they boiled. Our findings show that boiling is not an undifferentiated practice, but one with different methods of varying effectiveness, environmental impact, and adoption across socioeconomic strata. Our results can inform programs to promote safer and more efficient boiling using electric kettles, and suggest that if rural China's economy continues to grow then bottled water use will increase. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate whether the quality of implementation of a water, sanitation, and hygiene program called SHEWA-B and delivered by UNICEF to 20 million people in rural Bangladesh was associated with health behaviors and sanitation infrastructure access. Methods. We surveyed 33 027 households targeted by SHEWA-B and 1110 SHEWA-B hygiene promoters in 2011 and 2012. We developed an implementation quality index and compared the probability of health behaviors and sanitation infrastructure access in counterfactual scenarios over the range of implementation quality. Results. Forty-seven percent of households (n = 14 622) had met a SHEWA-B hygiene promoter, and 47% of hygiene promoters (n = 527) could recall all key program messages. The frequency of hygiene promoter visits was not associated with improved outcomes. Higher implementation quality was not associated with better health behaviors or infrastructure access. Outcomes differed by only 1% to 3% in scenarios in which all clusters received low versus high implementation quality. Conclusions. SHEWA-B did not meet UNICEF's ideal implementation quality in any area. Improved implementation quality would have resulted in marginal changes in health behaviors or infrastructure access. This suggests that SHEWA-B's design was suboptimal for improving these outcomes. [ABSTRACT FROM AUTHOR]

Objectives. To provide summary estimates of gastroenteritis risks and illness burden associated with recreational water exposure and determine whether children have higher risks and burden. Methods. We combined individual participant data from 13 prospective cohorts at marine and freshwater beaches throughout the United States (n = 84 411). We measured incident outcomes within 10 days of exposure: diarrhea, gastrointestinal illness, missed daily activity (work, school, vacation), and medical visits. We estimated the relationship between outcomes and 2 exposures: body immersion swimming and Enterococcus spp. fecal indicator bacteria levels in the water. We also estimated the population-attributable risk associated with these exposures. Results. Water exposure accounted for 21% of diarrhea episodes and 9% of missed daily activities but was unassociated with gastroenteritis leading to medical consultation. Children aged 0 to 4 and 5 to 10 years had the most water exposure, exhibited stronger associations between levels of water quality and illness, and accounted for the largest attributable illness burden. Conclusions. The higher gastroenteritis risk and associated burden in young children presents important new information to inform future recreational water quality guidelines designed to protect public health. [ABSTRACT FROM AUTHOR]

Background: Breast milk vitamin B-12 concentration may be inadequate in regions in which animal-source food consumption is low or infrequent. Vitamin B-12 deficiency causes megaloblastic anemia and impairs growth and development in children.Objective: We measured vitamin B-12 in breast milk and examined its associations with household hunger, recent animal-source food consumption, and vitamin B-12 intake.Methods: In a cross-sectional substudy nested within a cluster-randomized trial assessing water, sanitation, hygiene, and nutrition interventions in Kenya, we sampled 286 women 1-6 mo postpartum. Mothers hand-expressed breast milk 1 min into a feeding after 90 min observed nonbreastfeeding. The Household Hunger Scale was used to measure hunger, food intake in the previous week was measured with the use of a food-frequency questionnaire (FFQ), and vitamin B-12 intake was estimated by using 24-h dietary recall. An animal-source food score was based on 10 items from the FFQ (range: 0-70). Breast milk vitamin B-12 concentration was measured with the use of a solid-phase competitive chemiluminescent enzyme immunoassay and was modeled with linear regression. Generalized estimating equations were used to account for correlated observations at the cluster level.Results: Median (IQR) vitamin B-12 intake was 1.5 μg/d (0.3, 9.7 μg/d), and 60% of women consumed <2.4 μg/d, the estimated average requirement during lactation. Median (IQR) breast milk vitamin B-12 concentration was 113 pmol/L (61, 199 pmol/L); 89% had concentrations <310 pmol/L, the estimated adequate concentration. Moderate or severe hunger prevalence was 27%; the animal-source food score ranged from 0 to 30 item-d/wk. Hunger and recent animal-source food and vitamin B-12 intake were not associated with breast milk vitamin B-12 concentrations. Maternal age was negatively associated with breast milk vitamin B-12 concentrations.Conclusion: Most lactating Kenyan women consumed less than the estimated average requirement of vitamin B-12 and had low breast milk vitamin B-12 concentrations. We recommend interventions that improve vitamin B-12 intake in lactating Kenyan women to foster maternal health and child development. The main trial was registered at clinicaltrials.gov as NCT01704105. [ABSTRACT FROM AUTHOR]

Background The combination of deworming and improved sanitation or hygiene may result in greater reductions in soil-transmitted helminth (STH) infection than any single intervention on its own. We measured STH prevalence in rural Bangladesh and assessed potential interactions among deworming, hygienic latrines, and household finished floors. Methodology We conducted a cross-sectional survey (n = 1,630) in 100 villages in rural Bangladesh to measure three exposures: self-reported deworming consumption in the past 6 months, access to a hygienic latrine, and household flooring material. We collected stool samples from children 1-4 years, 5-12 years, and women 15-49 years. We performed mini-FLOTAC on preserved stool samples to detect Ascaris lumbricoides, Enterobius vermicularis, hookworm, and Trichuris trichiura ova. Approximately one-third (32%) of all individuals and 40%of school-aged children had an STH infection. Less than 2%of the sample had moderate/heavy intensity infections. Deworming was associated with lower Ascaris prevalence (adjusted prevalence ratio (PR) = 0.53; 95% CI 0.40, 0.71), but there was no significant association with hookworm (PR = 0.93, 95%CI 0.60, 1.44) or Trichuris (PR = 0.90, 95%CI 0.74, 1.08). PRs for hygienic latrine access were 0.91 (95% CI 0.67,1.24), 0.73 (95%CI 0.43,1.24), and 1.03 (95%CI 0.84,1.27) for Ascaris, hookworm, and Trichuris, respectively. Finished floors were associated with lower Ascaris prevalence (PR = 0.56, 95%CI 0.32, 0.97) but not associated with hookworm (PR = 0.48 95%CI 0.16,1.45) or Trichuris (PR = 0.98, 95%CI 0.72,1.33). Across helminths and combinations of exposures, adjusted prevalence ratios for joint exposures were consistently more protective than those for individual exposures. Conclusions We found moderate STH prevalence in rural Bangladesh among children and women of childbearing age. This study is one of the first to examine independent and combined associations with deworming, sanitation, and hygiene. Our results suggest that coupling deworming with sanitation and flooring interventions may yield more sustained reductions in STH prevalence. [ABSTRACT FROM AUTHOR]

Background: Shallow tubewells are the primary drinking water source for most rural Bangladeshis. Fecal contamination has been detected in tubewells, at low concentrations at the source and at higher levels at the point of use. We conducted a randomized controlled trial to assess whether improving the microbiological quality of tubewell drinking water by household water treatment and safe storage would reduce diarrhea in children <2 years in rural Bangladesh. Methods: We randomly assigned 1800 households with a child aged 6-18 months (index child) into one of three arms: chlorine plus safe storage, safe storage and control. We followed households with monthly visits for one year to promote the interventions, track their uptake, test participants’ source and stored water for fecal contamination, and record caregiver-reported child diarrhea prevalence (primary outcome). To assess reporting bias, we also collected data on health outcomes that are not expected to be impacted by our interventions. Findings: Both interventions had high uptake. Safe storage, alone or combined with chlorination, reduced heavy contamination of stored water. Compared to controls, diarrhea in index children was reduced by 36% in the chlorine plus safe storage arm (prevalence ratio, PR = 0.64, 0.55-0.73) and 31% in the safe storage arm (PR = 0.69, 0.60-0.80), with no difference between the two intervention arms. One limitation of the study was the non-blinded design with self-reported outcomes. However, the prevalence of health outcomes not expected to be impacted by water interventions did not differ between study arms, suggesting minimal reporting bias. Conclusions: Safe storage significantly improved drinking water quality at the point of use and reduced child diarrhea in rural Bangladesh. There was no added benefit from combining safe storage with chlorination. Efforts should be undertaken to implement and evaluate long-term efforts for safe water storage in Bangladesh. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of inadequate water and sanitation on diarrhoeal disease in low- and middle-income settings.Methods: The search strategy used Cochrane Library, MEDLINE & PubMed, Global Health, Embase and BIOSIS supplemented by screening of reference lists from previously published systematic reviews, to identify studies reporting on interventions examining the effect of drinking water and sanitation improvements in low- and middle-income settings published between 1970 and May 2013. Studies including randomised controlled trials, quasi-randomised trials with control group, observational studies using matching techniques and observational studies with a control group where the intervention was well defined were eligible. Risk of bias was assessed using a modified Ottawa-Newcastle scale. Study results were combined using meta-analysis and meta-regression to derive overall and intervention-specific risk estimates.Results: Of 6819 records identified for drinking water, 61 studies met the inclusion criteria, and of 12,515 records identified for sanitation, 11 studies were included. Overall, improvements in drinking water and sanitation were associated with decreased risks of diarrhoea. Specific improvements, such as the use of water filters, provision of high-quality piped water and sewer connections, were associated with greater reductions in diarrhoea compared with other interventions.Conclusions: The results show that inadequate water and sanitation are associated with considerable risks of diarrhoeal disease and that there are notable differences in illness reduction according to the type of improved water and sanitation implemented. [ABSTRACT FROM AUTHOR]

: Sumeet Patil and colleagues conduct a cluster randomized controlled trial to measure the effect of India's Total Sanitation Campaign in Madhya Pradesh on the availability of individual household latrines, defecation behaviors, and child health. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Background: Efforts to monitor malaria transmission increasingly use cross-sectional surveys to estimate transmission intensity from seroprevalence data using malarial antibodies. To date, seroconversion rates estimated from cross-sectional surveys have not been compared to rates estimated in prospective cohorts. Our objective was to compare seroconversion rates estimated in a prospective cohort with those from a cross-sectional survey in a low-transmission population. Methods and Findings: The analysis included two studies from Haiti: a prospective cohort of 142 children ages ≤11 years followed for up to 9 years, and a concurrent cross-sectional survey of 383 individuals ages 0–90 years old. From all individuals, we analyzed 1,154 blood spot specimens for the malaria antibody MSP-119 using a multiplex bead antigen assay. We classified individuals as positive for malaria using a cutoff derived from the mean plus 3 standard deviations in antibody responses from a negative control set of unexposed individuals. We estimated prospective seroconversion rates from the longitudinal cohort based on 13 incident seroconversions among 646 person-years at risk. We also estimated seroconversion rates from the cross-sectional survey using a reversible catalytic model fit with maximum likelihood. We found the two approaches provided consistent results: the seroconversion rate for ages ≤11 years was 0.020 (0.010, 0.032) estimated prospectively versus 0.023 (0.001, 0.052) in the cross-sectional survey. Conclusions: The estimation of seroconversion rates using cross-sectional data is a widespread and generalizable problem for many infectious diseases that can be measured using antibody titers. The consistency between these two estimates lends credibility to model-based estimates of malaria seroconversion rates using cross-sectional surveys. This study also demonstrates the utility of including malaria antibody measures in multiplex assays alongside targets for vaccine coverage and other neglected tropical diseases, which together could comprise an integrated, large-scale serological surveillance platform. [ABSTRACT FROM AUTHOR]

Background: Acute encephalitis syndrome (AES) is a constellation of symptoms that includes fever and altered mental status. Most cases are attributed to viral encephalitis (VE), occurring either in outbreaks or sporadically. We conducted hospital-based surveillance for sporadic adult-AES in rural Central India in order to describe its incidence, spatial and temporal distribution, clinical profile, etiology and predictors of mortality. Methods: All consecutive hospital admissions during the study period were screened to identify adult- AES cases and were followed until 30-days of hospitalization. We estimated incidence by administrative sub-division of residence and described the temporal distribution of cases. We performed viral diagnostic studies on cerebrospinal fluid (CSF) samples to determine the etiology of AES. The diagnostic tests included RT-PCR (for enteroviruses, HSV 1 and 2), conventional PCR (for flaviviruses), CSF IgM capture ELISA (for Japanese encephalitis virus, dengue, West Nile virus, Varicella zoster virus, measles, and mumps). We compared demographic and clinical variables across etiologic subtypes and estimated predictors of 30-day mortality. Results: A total of 183 AES cases were identified between January and October 2007, representing 2.38% of all admissions. The incidence of adult AES in the administrative subdivisions closest to the hospital was 16 per 100,000. Of the 183 cases, a non-viral etiology was confirmed in 31 (16.9%) and the remaining 152 were considered as VE suspects. Of the VE suspects, we could confirm a viral etiology in 31 cases: 17 (11.2%) enterovirus; 8(5.2%)flavivirus; 3 (1.9%) Varicella zoster; 1 (0.6%) herpesvirus; and 2 (1.3%) mixed etiology); the etiology remained unknown in remaining 121 (79.6%) cases. 53 (36%) of the AES patients died; the case fatality proportion was similar in patients with a confirmed and unknown viral etiology (45.1 and 33.6% respectively). A requirement for assisted ventilation significantly increased mortality (HR 2.14 (95% CI 1.0-4.77)), while a high Glasgow coma score (HR 0.76 (95% CI 0.69-0.83)), and longer duration of hospitalization (HR 0.88 (95% CI 0.83-0.94)) were protective. Conclusion: This study is the first description of the etiology of adult-AES in India, and provides a framework for future surveillance programs in India. [ABSTRACT FROM AUTHOR]

Field studies often use caregiver-reported diarrhoea and related symptoms to measure child morbidity. There are various vernacular terms to define diarrhoea that vary across the local cultural contexts. The relationship between vernacular definitions of diarrhoea and symptoms-based definitions is not well-documented. This paper describes the association of the vernacular Quechua term k'echalera with the symptoms-based standard definition of diarrhoea in rural Bolivian settings. During a cluster randomized trial in rural Bolivia, both signs and symptoms of diarrhoea and reports of k'echalera were collected for children aged less than five years. Reported k'echalera were found to be associated with important changes in stool frequency, consistency, and presence of blood and mucus. Reported k'echalera were highly related to three of four recorded categories of watery stool. The intermediate (milk-rice) stool consistency, which fits into the definition of watery stool, was not strongly related to k'echalera. Mucus in the stool was also associated with k'echalera; however, its presence in k'echalera-free days accounted for at least 50% of the possible false negatives. The sensitivity and specificity of the term k'echalera were estimated by Bayesian methods, allowing for both symptoms of diarrhoea and reports of k'echalera to be subject to diagnosis error. An average specificity of at least 97% and the sensitivity of at least 50% were obtained. The findings suggest that the use of k'echalera would identify fewer cases of diarrhoea than a symptom-based definition in rural Bolivia. [ABSTRACT FROM AUTHOR]

Empirical measurement of interventions to address significant global health and development problems is necessary to ensure that resources are applied appropriately. Such intervention programs are often deployed at the group or community level. The gold standard design to measure the effectiveness of community-level interventions is the community-randomized trial, but the conditions of these trials often make it difficult to assess their external validity and sustainability. The sheer number of community interventions, relative to randomized studies, speaks to a need for rigorous observational methods to measure their impact. In this article, we use the potential outcomes model for causal inference to motivate a matched cohort design to study the impact and sustainability of nonrandomized, preexisting interventions. We illustrate the method using a sanitation mobilization, water supply, and hygiene intervention in rural India. In a matched sample of 25 villages, we enrolled 1,284 children <5 y old and measured outcomes over 12 mo. Although we found a 33 percentage point difference in new toilet construction [95% confidence interval (Cl) = 28%, 39%), we found no impacts on height-for-age Z scores (adjusted difference = 0.01. 95% Cl= -0.15,0.19) or diarrhea (adjusted longitudinal prevalence difference = 0.003, 95% Cl = -0.001, 0.008) among children <5 y old. This study demonstrates that matched cohort designs can estimate impacts from nonrandomized, preexistirig interventions that are used widely in development efforts. Interpreting the impacts as causal, however, requires stronger assumptions than prospective, randomized studies. [ABSTRACT FROM AUTHOR]

Background: The promotion of household water treatment and handwashing with soap has led to large reductions in child diarrhoea in randomized efficacy trials. Currently, we know little about the health effectiveness of behaviour-based water and hygiene interventions after the conclusion of intervention activities.Methods: We present an extension of previously published design (propensity score matching) and analysis (targeted maximum likelihood estimation) methods to evaluate the behavioural and health impacts of a pre-existing but non-randomized intervention (a 3-year, combined household water treatment and handwashing campaign in rural Guatemala). Six months after the intervention, we conducted a cross-sectional cohort study in 30 villages (15 intervention and 15 control) that included 600 households, and 929 children <5 years of age.Results: The study design created a sample of intervention and control villages that were comparable across more than 30 potentially confounding characteristics. The intervention led to modest gains in confirmed water treatment behaviour [risk difference = 0.05, 95% confidence interval (CI) 0.02-0.09]. We found, however, no difference between the intervention and control villages in self-reported handwashing behaviour, spot-check hygiene conditions, or the prevalence of child diarrhoea, clinical acute lower respiratory infections or child growth.Conclusions: To our knowledge this is the first post-intervention follow-up study of a combined household water treatment and handwashing behaviour change intervention, and the first post-intervention follow-up of either intervention type to include child health measurement. The lack of child health impacts is consistent with unsustained behaviour adoption. Our findings highlight the difficulty of implementing behaviour-based household water treatment and handwashing outside of intensive efficacy trials. [ABSTRACT FROM AUTHOR]

Background: Solar drinking water disinfection (SODIS) is a low-cost, point-of-use water purification method that has been disseminated globally. Laboratory studies suggest that SODIS is highly efficacious in inactivating waterborne pathogens. Previous field studies provided limited evidence for its effectiveness in reducing diarrhoea. Methods and Findings: We conducted a cluster-randomized controlled trial in 22 rural communities in Bolivia to evaluate the effect of SODIS in reducing diarrhoea among children under the age of 5 y. A local nongovernmental organisation conducted a standardised interactive SODIS-promotion campaign in 11 communities targeting households, communities, and primary schools. Mothers completed a daily child health diary for 1 y. Within the intervention arm 225 households (376 children) were trained to expose water-filled polyethyleneteraphtalate bottles to sunlight. Eleven communities (200 households, 349 children) served as a control. We recorded 166,971 person-days of observation during the trial representing 79.9% and 78.9% of the total possible person-days of child observation in intervention and control arms, respectively. Mean compliance with SODIS was 32.1%. The reported incidence rate of gastrointestinal illness in children in the intervention arm was 3.6 compared to 4.3 episodes/year at risk in the control arm. The relative rate of diarrhoea adjusted for intracluster correlation was 0.81 (95% confidence interval 0.59-1.12). The median length of diarrhoea was 3 d in both groups. Conclusions: Despite an extensive SODIS promotion campaign we found only moderate compliance with the intervention and no strong evidence for a substantive reduction in diarrhoea among children. These results suggest that there is a need for better evidence of how the well-established laboratory efficacy of this home-based water treatment method translates into field effectiveness under various cultural settings and intervention intensities. Further global promotion of SODIS for general use should be undertaken with care until such evidence is available. [ABSTRACT FROM AUTHOR]

Background: Fractures of the femoral shaft are common and have potentially serious consequences in patients with multiple injuries. The appropriate timing of fracture repair is controversial. The purpose of the present study was to assess the effect of timing of internal fixation on mortality in patients with multisystem trauma. Methods: We performed a retrospective cohort study with use of data from public and private trauma centers throughout the United States that were reported to the National Trauma Data Bank (version 5.0 for 2000 through 2004). The study included 3069 patients with multisystem trauma (Injury Severity Score, ≥15) who underwent internal fixation of a femoral shaft fracture. The time to treatment was defined in categories as the time from admission to internal fixation: to (twelve hours or less), t1 (more than twelve hours to twenty-four hours), t2 (more than twenty-four hours to forty-eight hours), t3 (more than forty-eight hours to 120 hours), and t4 (more than 120 hours). The relative risk of in-hospital mortality when the four later periods were compared with the earliest one was estimated with inverse probability of treatment-weighted analysis. Subgroups with serious head or neck, chest, abdominal, and additional extremity injury were investigated. Results: When compared with that during the first twelve hours after admission, the estimated mortality risk was significantly lower in three time categories: t1 (relative risk, 0.45; 95% confidence interval, 0.15 to 0.98; p = 0.03), t3 (relative risk, 0.58; 95% confidence interval, 0.28 to 0.93; p = 0.03), and t4 (relative risk, 0.43; 95% confidence interval, 0.10 to 0.94; p = 0.03). Patients with serious abdominal trauma (Abbreviated Injury Score, ≥3) experienced the greatest benefit from a delay of internal fixation beyond twelve hours (relative risk, 0.82 [95% confidence interval, 0.54 to 1.35] for patients with an Abbreviated Injury Score of <3, compared with 0.36 [95% confidence interval, 0.13 to 0.87] for those with an Abbreviated Injury Score of ≥3) (p value for effect modification, 0.09). Conclusions: Delayed repair of femoral shaft fracture beyond twelve hours in patients with multisystem trauma, which may allow time for appropriate resuscitation, reduces mortality by approximately 50%. Patients with serious abdominal injury benefit most from delayed treatment. These results support delaying definitive treatment of long-bone injuries in patients with multisystem trauma as a means of so-called damage-control in order to reduce adverse outcomes. Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although the U.S. Environmental Protection Agency has a long history of using risk-based approaches for regulatory purposes, pollutant limits for pathogens in biosolids are not currently based on quantitative risk assessments. OBJECTIVES: We developed and demonstrated a risk-based methodology for assessing the risk to human health from exposure to pathogens via biosolids. MATERIALS: Four models were developed, incorporating direct ingestion, groundwater, and aerosol exposure pathways. Three sources of environmental data were used to estimate risk: pathogen monitoring of sludge, efficacy of sludge treatment, and pathogen monitoring of biosolids. RESULTS: Risk estimates were obtainable even for Class A biosolids, where posttreatsnent monitoring data are below detectable levels, demonstrating that risk assessments for biosolids exposure are practical. Model analyses suggest that: a) a two-digester design decreases the probability of risks > 10-4 compared with one-digester designs, b) risks associated with exposures to groundwater and aerosol pathways were, in general, lower than exposures to the direct ingestion pathway, and c) secondary transmission can be an important factor in risk estimation. CONCLUSIONS: The risk-based approach presented here provides a tool to a) help biosolids producers interpret the results of biosolids monitoring data in terms of its health implications, b) help treatment plant engineers evaluate the risk-based benefits of operational changes to existing or projected treatment processes, and c) help environmental managers evaluate potential capital improvements and/or land application site placement issues. Regulation of pathogens can now be based on human health risk in a manner parallel to other water-related risks. [ABSTRACT FROM AUTHOR]

Rapid, point-of-care human immunodeficiency virus (HIV) testing has the potential to enhance strategies to prevent mother-to-child transmission (MTCT) of HIV infection. Rapid tests need minimal laboratory infrastructure and can be performed by health workers with minimal training. In our systematic review and meta-analysis, we aimed to summarize the overall diagnostic accuracy of rapid HIV tests in pregnancy, and outcomes such as acceptability, patient preference, feasibility and impact of rapid testing. We searched four major databases, identified and screened 1377 citations, and included 17 studies that met our eligibility criteria. Analyses of these studies suggested that the overall sensitivity and specificity of blood-based rapid tests was high compared with oral rapid tests. A two-step testing strategy, particularly parallel testing, was found to be superior to single-test strategy in labour and delivery settings. Acceptability of rapid tests and patient preference was variable across studies. Overall, rapid HIV testing was highly accurate compared with conventional tests and offer a clear advantage of enabling the implementation of timely interventions to reduce MTCT of HIV. To improve diagnostic accuracy and to reduce false-positive results, it may be necessary to use two rapid tests during labour and delivery. [ABSTRACT FROM AUTHOR]

Background: For individuals with AIDS, data exist relatively soon after diagnosis to allow estimation of "early" survival quantiles (e.g., the 0.10, 0.15, 0.20 and 0.30 quantiles, etc.). Many years of additional observation must elapse before median survival, a summary measure of survival, can be estimated accurately. In this study, a new approach to predict AIDS median survival is presented and its accuracy tested using AIDS surveillance data. Methods: The data consisted of 96,373 individuals who were reported to the HIV/AIDS Reporting System of the California Department of Health Services Office of AIDS as of December 31, 1996. We defined cohorts based on quarter year of diagnosis (e.g., the "931" cohort consists of individuals diagnosed with AIDS in the first quarter of 1993). We used early quantiles (estimated using the Inverse Probability of Censoring Weighted estimator) of the survival distribution to estimate median survival by assuming a linear relationship between the earlier quantiles and median survival. From this model, median survival was predicted for cohorts for which a median could not be estimated empirically from the available data. This prediction was compared with the actual medians observed when using updated survival data reported at least five years later. Results: Using the 0.15 quantile as the predictor and the data available as of December 31, 1996, we were able to predict the median survival of four cohorts (933, 934, 941, and 942) to be 34, 34, 31, and 29 months. Without this approach, there were insufficient data with which to make any estimate of median survival. The actual median survival of these four cohorts (using data as of December 31, 2001) was found to be 32, 40, 46, and 80 months, suggesting that the accuracy for this approach requires a minimum of three years to elapse from diagnosis to the time an accurate prediction can be made. Conclusion: The results of this study suggest that early and accurate prediction of median survival time after AIDS diagnosis may be possible using early quantiles of the survival distribution. The methodology did not seem to work well during a period of significant change in survival as observed with highly active antiretroviral treatment, but results suggest that it may work well in a time of more gradual improvement in survival. [ABSTRACT FROM AUTHOR]

Background. Although the clinical severity of cryptosporidiosis is altered by human immunodeficiency virus (HIV)-related immunosuppression, little is known about how risk for Cryptosporidium infection is altered by HIV. Methods. A retrospective cohort study was conducted among 78 participants of the San Francisco Men's Health Study, using stored serological specimens from 8.5 years of follow-up. Cryptosporidium infection was defined as an antibody response to both the recombinant 27-kDa (r27) and native Triton-extracted 17-kDa (TX17) Cryptosporidium antigens. Results. Cryptosporidium infections were detected more frequently by assessment of antibody responses than by routine clinical follow-up (195 [95% confidence interval {CI}, 154–241] vs. 11 [95% CI, 3–30] infections/1000 person-years, respectively). HIV-positive individuals (59%) were more likely than HIV-negative individuals (30%) to have had at least 1 serologically defined infection (P = .028). The estimated infection rate was 230 (95% CI, 175–293) infections/1000 person-years and 140 (95% CI, 86–210) infections/1000 person-years for HIV-positive and HIV-negative individuals, respectively. Median decay time to half-life ranged from 13.8 to 15.1 months. Conclusions. Our study emphasizes that Cryptosporidium infections are common in this population. Although HIV status altered the risk of Cryptosporidium infection, further studies are needed to adequately examine the effect of CD4 cell count. [ABSTRACT FROM AUTHOR]

Risk assessments and intervention trials have been used by the U.S. Environmental Protection Agency to estimate drinking water health risks. Seldom are both methods used concurrently. Between 2001 and 2003, illness data from a trial were collected simultaneously with exposure data, providing a unique opportunity to compare direct risk estimates of waterborne disease from the intervention trial with indirect estimates from a risk assessment. Comparing the group with water treatment (active) with that without water treatment (sham), the estimated annual attributable disease rate (cases per 10,000 persons per year) from the trial provided no evidence of a significantly elevated drinking water risk [attributable risk = -365 cases/year, sham minus active; 95% confidence interval (CI), -2,555 to 1,825]. The predicted mean rate of disease per 10,000 persons per person-year from the risk assessment was 13.9 (2.5, 97.5 percentiles: 1.6, 37.7) assuming 4 log removal due to viral disinfection and 5.5 (2.5, 97.5 percentiles: 1.4, 19.2) assuming 6 log removal. Risk assessments are important under conditions of low risk when estimates are difficult to attain from trials. In particular, this assessment pointed toward the importance of attaining site-specific treatment data and the clear need for a better understanding of viral removal by disinfection. Trials provide direct risk estimates, and the upper confidence limit estimates, even if not statistically significant, are informative about possible upper estimates of likely risk. These differences suggest that conclusions about waterborne disease risk may be strengthened by the joint use of these two approaches. [ABSTRACT FROM AUTHOR]

Many studies have reported the results of interventions to reduce illness through improvements in drinking water, sanitation facilities, and hygiene practices in less developed countries. There has, however, been no formal systematic review and meta-analysis comparing the evidence of the relative effectiveness of these interventions. We developed a comprehensive search strategy designed to identify all peer-reviewed articles, in any language, that presented water, sanitation, or hygiene interventions. We examined only those articles with specific measurement of diarrhoea morbidity as a health outcome in non-outbreak conditions. We screened the titles and, where necessary, the abstracts of 2120 publications. 46 studies were judged to contain relevant evidence and were reviewed in detail. Data were extracted from these studies and pooled by meta-analysis to provide summary estimates of the effectiveness of each type of intervention. All of the interventions studied were found to reduce significantly the risks of diarrhoeal illness. Most of the interventions had a similar degree of impact on diarrhoeal illness, with the relative risk estimates from the overall meta-analyses ranging between 0·63 and 0·75. The results generally agree with those from previous reviews, but water quality interventions (point-of-use water treatment) were found to be more effective than previously thought, and multiple interventions (consisting of combined water, sanitation, and hygiene measures) were not more effective than interventions with a single focus. There is some evidence of publication bias in the findings from the hygiene and water treatment interventions. [Copyright &y& Elsevier]

This systematic review summarises the evidence for treatment efficacy and tolerability of highly active antiretroviral therapies containing two nucleoside reverse transcriptase inhibitors (NRTI) with a protease inhibitor (PI), compared with two NRTIs alone for the treatment of HIV-1 infection in randomised controlled trials. Three electronic databases (Medline, Embase, and the Cochrane Library) were searched up to December 2003. 16 randomised controlled trials met the inclusion criteria and were included in the analysis from 328 articles screened. The pooled analysis indicated that treatment with two NRTIs with a PI is more effective in achieving viral suppression than two NRTIs alone (relative risk [RR] 3·44, 95% confidence interval [CI] 2·43–4·87). However, the RR for discontinuation of treatment due to adverse events of treatment with two NRTIs with a PI compared with two NRTIs alone was 1·81 (95% CI 1·17–2·79). The benefits of treatment with two NRTIs and a PI are substantial among those who can tolerate the regimen in comparison with treatment with two NRTIs alone. [Copyright &y& Elsevier]

Background: Conventional tests for tuberculous pleuritis have several limitations. A variety of new, rapid tests such as nucleic acid amplification tests -- including polymerase chain reaction -- have been evaluated in recent times. We conducted a systematic review to determine the accuracy of nucleic acid amplification (NAA) tests in the diagnosis of tuberculous pleuritis. Methods: A systematic review and meta-analysis of 38 English and Spanish articles (with 40 studies), identified via searches of six electronic databases, hand searching of selected journals, and contact with authors, experts, and test manufacturers. Sensitivity, specificity, and other measures of accuracy were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Heterogeneity in study results was formally explored using subgroup analyses. Results: Of the 40 studies included, 26 used in-house ("home-brew") tests, and 14 used commercial tests. Commercial tests had a low overall sensitivity (0.62; 95% confidence interval [CI] 0.43, 0.77), and high specificity (0.98; 95% CI 0.96, 0.98). The positive and negative likelihood ratios for commercial tests were 25.4 (95% CI 16.2, 40.0) and 0.40 (95% CI 0.24, 0.67), respectively. All commercial tests had consistently high specificity estimates; the sensitivity estimates, however, were heterogeneous across studies. With the in-house tests, both sensitivity and specificity estimates were significantly heterogeneous. Clinically meaningful summary estimates could not be determined for in-house tests. Conclusions: Our results suggest that commercial NAA tests may have a potential role in confirming (ruling in) tuberculous pleuritis. However, these tests have low and variable sensitivity and, therefore, may not be useful in excluding (ruling out) the disease. NAA test results, therefore, cannot replace conventional tests; they need to be interpreted in parallel with clinical findings and results of conventional tests. The accuracy of in-house nucleic acid amplification tests is poorly defined because of heterogeneity in study results. The clinical applicability of inhouse NAA tests remains unclear. [ABSTRACT FROM AUTHOR]

Conventional tests are not always helpful in making a diagnosis of tuberculous meningitis. We did a systematic review and meta-analysis to establish the summary accuracy of nucleic acid amplification (NAA) tests for tuberculous meningitis. We searched six electronic databases and contacted authors, experts, and manufacturers. Measures of diagnostic accuracy were pooled using a random effects model. 49 studies met our inclusion criteria. The summary estimates in 14 studies with commercial NAA tests were: sensitivity 0·56 (95% CI 0·46, 0·66), specificity 0·98 (0·97, 0·99), positive likelihood ratio 35·1 (19·0, 64·6), negative likelihood ratio 0·44 (0·33, 0·60), and diagnostic odds ratio 96·4 (42·8, 217·3). In the 35 studies with in-house (“home-brew”) tests, the summary accuracy could not be established with confidence because of wide variability in test accuracy. On current evidence, commercial NAA tests show a potential role in confirming tuberculous meningitis diagnosis, although their overall low sensitivity precludes the use of these tests to rule out tuberculous meningitis with certainty. [Copyright &y& Elsevier]

Despite numerous studies, uncertainty remains about how water quality indicators can best be used in the regulation of recreational water. We conducted a systematic review of this topic with the goal of quantifying the association between microbial indicators of recreational water quality and gastrointestinal (GI) illness. A secondary goal was to evaluate the potential for Gl illness below current guidelines. We screened 976 potentially relevant studies and from these identified 27 studies. From the latter, we determined summary relative risks for Gl illness in relation to water quality indicator density. Our results support the use of enterococci in marine water at U.S. Environmental Protection Agency guideline levels. In fresh water, Escherichia coli was a more consistent predictor of GI illness than are enterococci and other bacterial indicators. A log (base 10) unit increase in enterococci was associated with a 1.34 [95% confidence intervals (CI), 1.00-1.75] increase in relative risk in marine waters, and a log (base 10) unit increase in E. coli was associated with a 2.12 (95% CI, 0.925-4.85) increase in relative risk in fresh water. Indicators of viral contamination were strong predictors of GI illness in both fresh and marine environments. Significant heterogeneity was noted among the studies. In our analysis of heterogeneity, studies that used a non-swimming control group, studies that focused on children, and studies of athletic or other recreational events found elevated relative risks. Future studies should focus on the ability of new, more rapid and specific microbial methods to predict health effects, and estimating the risks of recreational water exposure among susceptible persons. [ABSTRACT FROM AUTHOR]

Background: Cryptosporidiosis, caused by Cryptosporidium, is an enteric illness that has received much attention as an infection of immunocompromised persons as well as in community outbreaks (frequently waterborne). There are, however, no studies of the risk factors for sporadic community-acquired cryptosporidiosis in the immunocompetent US population. We undertook a case-control study in the San Francisco Bay Area as part of a national study sponsored by the Centers for Disease Control and Prevention to ascertain the major routes of transmission for endemic cryptosporidiosis, with an emphasis on evaluating risk from drinking water. Methods: Cases were recruited from a population-based, active surveillance system and age-matched controls were recruited using sequential random-digit dialing. Cases (n = 26) and controls (n = 62) were interviewed by telephone using a standardized questionnaire that included information about the following exposures: drinking water, recreational water, food items, travel, animal contact, and person-to-person fecal contact, and (for adults) sexual practices. Results: In multivariate conditional logistic regression analyses no significant association with drinking water was detected. The major risk factor for cryptosporidiosis in the San Francisco Bay Area was travel to another country (matched odds ratio [95% confidence interval]: 24.1 [2.6, 220]). Conclusion: The results of this study do not support the hypothesis that drinking water is an independent risk factor for cryptosporidiosis among the immunocompetent population. These findings should be used to design larger studies of endemic cryptosporidiosis to elucidate the precise mechanisms of transmission, whether waterborne or other. [ABSTRACT FROM AUTHOR]

Developing effective policy for environmental health issues requires integrating large collections of information that are diverse, highly variable, and uncertain. Despite these uncertainties in the science, decisions must be made. These decisions often have been based on risk assessment. We argue that two important features of risk assessment are to identify research needs and to provide information for decision making. One type of information that a model can provide is the sensitivity of making one decision over another on factors that drive public health risk. To achieve this goal, a risk assessment framework must be based on a description of the exposure and disease processes. Regarding exposure to waterborne pathogens, the appropriate framework is one that explicitly models the disease transmission pathways of pathogens. This approach provides a crucial link between science and policy. Two studies--a Giardia risk assessment case study and an analysis of the 1993 Milwaukee, Wisconsin, Cryptosporidium outbreak--illustrate the role that models can play in policy making. [ABSTRACT FROM AUTHOR]

The article presents an overview of systematic reviews of diagnostic test evaluations. Systematic reviews are done on a range of clinical questions, such as therapy, diagnosis, prognosis, etiology, harm, and disease prevalence. The core steps of the systematic review process can be broken down further into more discrete steps. Although not as common as systematic reviews on therapeutic questions, an increasing number of diagnostic reviews are being published in the medical literature. The final steps in the systematic review process are interpretation of the results, including discussion of such issues as applicability, and writing the report for publication.