Wayne Enanoria

Water, sanitation, and hygiene interventions to reduce diarrhoea in less developed countries: a systematic review and meta-analysis

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.

Systematic reviews of diagnostic test evaluations: what’s behind the scenes?

As readers of Evidence-Based Medicine, you are aware that systematic reviews are considered the best source of evidence for evidence-based clinical practice. Systematic reviews synthesise data from existing primary research and bring some order and sanity to the otherwise stressful process of sorting out a plethora of studies and staying up to date. However, since not all reviews are created equal, it is important to be able to critically assess their quality. In this editorial, we take you behind the scenes of a systematic review, using diagnostic test accuracy as an illustration. A clear understanding of the process will, hopefully, guide what you look for in a review. Furthermore, if you can’t find an existing diagnostic review and decide to do one yourself, we provide you with a “road map” (figure) for navigation. Se  =  sensitivity; Sp  =  specificity; LR  =  likelihood ratios; DOR  =  diagnostic odds ratios; ROC  =  receiver operating characteristic; SROC  =  summary receiver operating characteristic; TP  =  true positives; FP  =  false positives; TN  =  true negatives; FN  =  false negatives; TPR  =  true positive rate; FPR  =  false positive rate. Superscripts indicate reference numbers. Systematic reviews are done on a range of clinical questions, such as therapy, diagnosis, prognosis, aetiology, harm, and disease prevalence. All systematic reviews follow the same critical steps: 1. Formulation of the review question 2. A comprehensive, systematic search and selection of primary studies 3. Critical appraisal of included studies for quality and data extraction 4. Synthesis and summary of study results 5. Interpretation of the results These steps resemble those of the evidence-based medicine (EBM) process, but are more thorough. In the EBM process, our objective is to quickly hunt down a valid source …

Research findings from nonpharmaceutical intervention studies for pandemic influenza and current gaps in the research.

In June 2006, the Centers for Disease Control and Prevention released a request for applications to identify, improve, and evaluate the effectiveness of nonpharmaceutical interventions (NPIs)-strategies other than vaccines and antiviral medications-to mitigate the spread of pandemic influenza within communities and across international borders (RFA-CI06-010). These studies have provided major contributions to seasonal and pandemic influenza knowledge. Nonetheless, key concerns were identified related to the acceptability and protective efficacy of NPIs. Large-scale intervention studies conducted over multiple influenza epidemics, as well as smaller studies in controlled laboratory settings, are needed to address the gaps in the research on transmission and mitigation of influenza in the community setting. The current novel influenza A (H1N1) pandemic underscores the importance of influenza research.

A Randomized Clinical Trial Comparing Methotrexate and Mycophenolate Mofetil for Noninfectious Uveitis

OBJECTIVE To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN Multicenter, block-randomized, observer-masked clinical trial. PARTICIPANTS Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. INTERVENTION Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. MAIN OUTCOME MEASURES Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. RESULTS Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). CONCLUSIONS There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.

Endemic cryptosporidiosis and exposure to municipal tap water in persons with acquired immunodeficiency syndrome (AIDS): A case-control study

BackgroundIn persons with acquired immunodeficiency syndrome (AIDS), Cryptosporidium parvum causes a prolonged, severe diarrheal illness to which there is no effective treatment, and the risk of developing cryptosporidiosis from drinking tap water in non-outbreak settings remains uncertain. To test the hypothesis that drinking tap water was associated with developing cryptosporidiosis, we conducted a matched case-control study among persons with AIDS in San Francisco.MethodsAmong patients reported to the San Francisco AIDS Registry from May 1996 through September 1998, we compared patients who developed cryptosporidiosis to those who did not. Cases were individually matched to controls based on age, sex, race/ethnicity, CD4+ T lymphocyte count, date of CD4+ count, and date of case diagnosis. Population attributable fractions (PAFs) were calculated.ResultsThe study consisted of 49 cases and 99 matched controls. In the multivariable analysis with adjustments for confounders, tap water consumption inside and outside the home at the highest exposure categories was associated with the occurrence of cryptosporidiosis (inside the home: odds ratio (OR), 6.76; 95% CI 1.37–33.5, and outside the home: OR 3.16; 95% CI 1.23–8.13). The PAF was 85%; that is, the proportion of cases of cryptosporidiosis in San Francisco AIDS patients attributable to tap water consumption could have been as high as 85%.ConclusionsAlthough the results from this observational study cannot be considered definitive, until there is more data, we recommend persons with AIDS, especially those with compromised immune systems, consider avoiding tap water.

When Does Overuse of Antibiotics Become a Tragedy of the Commons

Background Over-prescribing of antibiotics is considered to result in increased morbidity and mortality from drug-resistant organisms. A resulting common wisdom is that it would be better for society if physicians would restrain their prescription of antibiotics. In this view, self-interest and societal interest are at odds, making antibiotic use a classic “tragedy of the commons”. Methods and Findings We developed two mathematical models of transmission of antibiotic resistance, featuring de novo development of resistance and transmission of resistant organisms. We analyzed the decision to prescribe antibiotics as a mathematical game, by analyzing individual incentives and community outcomes. Conclusions A conflict of interest may indeed result, though not in all cases. Increased use of antibiotics by individuals benefits society under certain circumstances, despite the amplification of drug-resistant strains or organisms. In situations where increased use of antibiotics leads to less favorable outcomes for society, antibiotics may be harmful for the individual as well. For other scenarios, where a conflict between self-interest and society exists, restricting antibody use would benefit society. Thus, a case-by-case assessment of appropriate use of antibiotics may be warranted.

Treatment outcomes after highly active antiretroviral therapy: a meta-analysis of randomised controlled trials

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.

Identifying Postelimination Trends for the Introduction and Transmissibility of Measles in the United States

The continued elimination of measles requires accurate assessment of its epidemiology and a critical evaluation of how its incidence is changing with time. National surveillance of measles in the United States between 2001 and 2011 provides data on the number of measles introductions and the size of the resulting transmission chains. These data allow inference of the effective reproduction number, Reff, and the probability of an outbreak occurring. Our estimate of 0.52 (95% confidence interval: 0.44, 0.60) for Reff is smaller than prior results. Our findings are relatively insensitive to the possibility that as few as 75% of cases were detected. Although we confirm that measles remains eliminated, we identify an increasing trend in the number of measles cases with time. We show that this trend is likely attributable to an increase in the number of disease introductions rather than a change in the transmissibility of measles. However, we find that transmissibility may increase substantially if vaccine coverage drops by as little as 1%. Our general approach of characterizing the case burden of measles is applicable to the epidemiologic assessment of other weakly transmitting or vaccine-controlled pathogens that are either at risk of emerging or on the brink of elimination.

Assessing Measles Transmission in the United States Following a Large Outbreak in California.

The recent increase in measles cases in California may raise questions regarding the continuing success of measles control. To determine whether the dynamics of measles is qualitatively different in comparison to previous years, we assess whether the 2014-2015 measles outbreak associated with an Anaheim theme park is consistent with subcriticality by calculating maximum-likelihood estimates for the effective reproduction numbe given this year’s outbreak, using the Galton-Watson branching process model. We find that the dynamics after the initial transmission event are consistent with prior transmission, but does not exclude the possibilty that the effective reproduction number has increased.

Effectiveness of the polysaccharide pneumococcal vaccine among HIV-infected persons in Brazil: a case control study

BackgroundPolysaccharide pneumococcal vaccine is recommended for use in HIV-infected adults in Brazil but there is uncertainty about its effectiveness in this patient population.The main objective of this study was to assess the effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal infection among HIV-infected adult patients in São Paulo, Brazil.MethodsA case-control study of 79 cases and 242 controls matched on CD4+ cell count and health care setting was conducted. Among HIV-infected adults in São Paulo, Brazil, with and without S. pneumoniae recovered from a normally sterile site; prior receipt of 23 valent polysaccharide pneumococcal vaccine was determined by review of medical records and patient interview.ResultsAfter adjustment for confounding factors, the point estimate for the effectiveness of 23 valent polysaccharide vaccine among HIV-infected adults against all invasive pneumococcal infection was 18% (95% CI: <0 to 62%).ConclusionWe were unable to demonstrate a statistically significant protective effect of 23 valent polysaccharide against invasive pneumococcal infection vaccine among HIV-infected adults in Brazil.While the vaccine is relatively inexpensive and safe, its effectiveness among HIV-infected adults in Brazil is uncertain.