John M. Colford

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.

Interferon-γ assays in the immunodiagnosis of tuberculosis: a systematic review

Summary 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.

Burden of disease from inadequate water, sanitation and hygiene in low- and middle-income settings: a retrospective analysis of data from 145 countries

To estimate the burden of diarrhoeal diseases from exposure to inadequate water, sanitation and hand hygiene in low‐ and middle‐income settings and provide an overview of the impact on other diseases.

Water quality indicators and the risk of illness at beaches with nonpoint sources of fecal contamination.

Background: Indicator bacteria are a good predictor of illness at marine beaches that have point sources of pollution with human fecal content. Few studies have addressed the utility of indicator bacteria where nonpoint sources are the dominant fecal input. Extrapolating current water-quality thresholds to such locations is uncertain. Methods: In a cohort of 8797 beachgoers at Mission Bay, California, we measured baseline health at the time of exposure and 2 weeks later. Water samples were analyzed for bacterial indicators (enterococcus, fecal coliforms, total coliforms) using both traditional and nontraditional methods, ie, chromogenic substrate or quantitative polymerase chain reaction. A novel bacterial indicator (Bacteroides) and viruses (coliphage, adenovirus, norovirus) also were measured. Associations of 14 health outcomes with both water exposure and water quality indicators were assessed. Results: Diarrhea and skin rash incidence were the only symptoms that were increased in swimmers compared with nonswimmers. The incidence of illness was not associated with any of the indicators that traditionally are used to monitor beaches. Among nontraditional water quality indicators, associations with illness were observed only for male-specific coliphage, although a low number of participants were exposed to water at times when coliphage was detected. Conclusions: Traditional fecal indicators currently used to monitor these beaches were not associated with health risks. These results suggest a need for alternative indicators of water quality where nonpoint sources are dominant fecal contributors.

Astragalus-Based Chinese Herbs and Platinum-Based Chemotherapy for Advanced Non–Small-Cell Lung Cancer: Meta-Analysis of Randomized Trials

PURPOSE Systemic treatments for advanced non-small-cell lung cancer have low efficacy and high toxicity. Some Chinese herbal medicines have been reported to increase chemotherapy efficacy and reduce toxicity. In particular, Astragalus has been shown to have immunologic benefits by stimulating macrophage and natural killer cell activity and inhibiting T-helper cell type 2 cytokines. Many published studies have assessed the use of Astragalus and other Chinese herbal medicines in combination with chemotherapy. We sought to evaluate evidence from randomized trials that Astragalus-based Chinese herbal medicine combined with platinum-based chemotherapy (versus platinum-based chemotherapy alone) improves survival, increases tumor response, improves performance status, or reduces chemotherapy toxicity. METHODS We searched CBM, MEDLINE, TCMLARS, EMBASE, Cochrane Library, and CCRCT databases for studies in any language. We grouped studies using the same herbal combinations for random-effects meta-analysis. RESULTS Of 1,305 potentially relevant publications, 34 randomized studies representing 2,815 patients met inclusion criteria. Twelve studies (n = 940 patients) reported reduced risk of death at 12 months (risk ratio [RR] = 0.67; 95% CI, 0.52 to 0.87). Thirty studies (n = 2,472) reported improved tumor response data (RR = 1.34; 95% CI, 1.24 to 1.46). In subgroup analyses, Jin Fu Kang in two studies (n = 221 patients) reduced risk of death at 24 months (RR = 0.58; 95% CI, 0.49 to 0.68) and in three studies (n = 411) increased tumor response (RR = 1.76; 95% CI, 1.23 to 2.53). Ai Di injection (four studies; n = 257) stabilized or improved Karnofsky performance status (RR = 1.28; 95% CI, 1.12 to 1.46). CONCLUSION Astragalus-based Chinese herbal medicine may increase effectiveness of platinum-based chemotherapy when combined with chemotherapy. These results require confirmation with rigorously controlled trials.

Household Environmental Conditions Are Associated with Enteropathy and Impaired Growth in Rural Bangladesh

We assessed the relationship of fecal environmental contamination and environmental enteropathy. We compared markers of environmental enteropathy, parasite burden, and growth in 119 Bangladeshi children (≤ 48 months of age) across rural Bangladesh living in different levels of household environmental cleanliness defined by objective indicators of water quality and sanitary and hand-washing infrastructure. Adjusted for potential confounding characteristics, children from clean households had 0.54 SDs (95% confidence interval [CI] = 0.06, 1.01) higher height-for-age z scores (HAZs), 0.32 SDs (95% CI = −0.72, 0.08) lower lactulose:mannitol (L:M) ratios in urine, and 0.24 SDs (95% CI = −0.63, 0.16) lower immunoglobulin G endotoxin core antibody (IgG EndoCAb) titers than children from contaminated households. After adjusting for age and sex, a 1-unit increase in the ln L:M was associated with a 0.33 SDs decrease in HAZ (95% CI = −0.62, −0.05). These results are consistent with the hypothesis that environmental contamination causes growth faltering mediated through environmental enteropathy.

Assessing the impact of drinking water and sanitation on diarrhoeal disease in low- and middle-income settings: Systematic review and meta-regression

To assess the impact of inadequate water and sanitation on diarrhoeal disease in low‐ and middle‐income settings.

Comparison of cemented and uncemented fixation in total hip replacement: a meta-analysis

Background The choice of optimal implant fixation in total hip replacement (THR)—fixation with or without cement—has been the subject of much debate. Methods We performed a systematic review and meta-analysis of the published literature comparing cemented and uncemented fixation in THR. Results No advantage was found for either procedure when failure was defined as either: (A) revision of either or both components, or (B) revision of a specific component. No difference was seen between estimates from registry and single-center studies, or between randomized and non-randomized studies. Subgroup analysis of type A studies showed superior survival with cemented fixation in studies including patients of all ages as compared to those that only studied patients 55 years of age or younger. Among type B studies, cemented titanium stems and threaded cups were associated with poor survival. An association was found between difference in survival and year of publication, with uncemented fixation showing relative superiority over time. Interpretation While the recent literature suggests that the performance of uncemented implants is improving, cemented fixation continues to outperform uncemented fixation in large subsets of study populations. Our findings summarize the best available evidence qualitatively and quantitatively and provide important information for future research.

A sea change ahead for recreational water quality criteria

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.

Delayed Internal Fixation of Femoral Shaft Fracture Reduces Mortality Among Patients with Multisystem Trauma

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, > or =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: t(0) (twelve hours or less), t(1) (more than twelve hours to twenty-four hours), t(2) (more than twenty-four hours to forty-eight hours), t(3) (more than forty-eight hours to 120 hours), and t(4) (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: t(1) (relative risk, 0.45; 95% confidence interval, 0.15 to 0.98; p = 0.03), t(3) (relative risk, 0.58; 95% confidence interval, 0.28 to 0.93; p = 0.03), and t(4) (relative risk, 0.43; 95% confidence interval, 0.10 to 0.94; p = 0.03). Patients with serious abdominal trauma (Abbreviated Injury Score, > or =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 > or =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.