Influence of Zinc Supplementation in Acute Diarrhea Differs by the Isolated Organism

Zinc supplementation is recommended in all acute diarrheas in children from developing countries. We aimed to assess whether zinc supplementation would be equally effective against all the common organisms associated with acute diarrheas. We used data on 801 children with acute diarrhea recruited in a randomized, double blind controlled trial (ISRCTN85071383) of zinc and copper supplementation. Using prespecified subgroup analyses, multidimensionality reduction analyses, tests of heterogeneity, and stepwise logistic regression for tests of interactions, we found that the influence of zinc on the risk of diarrhea for more than 3 days depended on the isolated organism—beneficial in Klebsiella, neutral in Esherichia coli and parasitic infections, and detrimental in rotavirus coinfections. Although we found similar results for the outcome of high stool volume, the results did not reach statistical significance. Our findings suggest that the current strategy of zinc supplementation in all cases of acute diarrheas in children may need appropriate fine tuning to optimize the therapeutic benefit based on the causative organism, but further studies need to confirm and extend our findings

Therapeutic Value of Zinc Supplementation in Acute and Persistent Diarrhea: A Systematic Review

BACKGROUND: For over a decade, the importance of zinc in the treatment of acute and persistent diarrhea has been recognized. In spite of recently published reviews, there remain several unanswered questions about the role of zinc supplementation in childhood diarrhea in the developing countries. Our study aimed to assess the therapeutic benefits of zinc supplementation in the treatment of acute or persistent diarrhea in children, and to examine the causes of any heterogeneity of response to zinc supplementation. METHODS AND FINDINGS: EMBASE, MEDLINE and CINAHL databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention and treatment of childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. The reviews and published RCTs were qualitatively mapped followed by updated random-effects meta-analyses, subgroup meta-analyses and meta-regression to quantify and characterize the role of zinc supplementation with diarrhea-related outcomes. We found that although there was evidence to support the use of zinc to treat diarrhea in children, there was significant unexplained heterogeneity across the studies for the effect of zinc supplementation in reducing important diarrhea outcomes. Zinc supplementation reduced the mean duration of diarrhea by 19.7% but had no effect on stool frequency or stool output, and increased the risk of vomiting. Our subgroup meta-analyses and meta-regression showed that age, stunting, breast-feeding and baseline zinc levels could not explain the heterogeneity associated with differential reduction in the mean diarrheal duration. However, the baseline zinc levels may not be representative of the existing zinc deficiency state. CONCLUSIONS: Understanding the predictors of zinc efficacy including the role of diarrheal disease etiology on the response to zinc would help to identify the populations most likely to benefit from supplementation. To improve the programmatic use of zinc, further evaluations of the zinc salts used, the dose, the frequency and duration of supplementation, and its acceptability are required. The significant heterogeneity of responses to zinc suggests the need to revisit the strategy of universal zinc supplementation in the treatment children with acute diarrhea in developing countries

Clinical Study Influence of Zinc Supplementation in Acute Diarrhea Differs by the Isolated Organism

Zinc supplementation is recommended in all acute diarrheas in children from developing countries. We aimed to assess whether zinc supplementation would be equally effective against all the common organisms associated with acute diarrheas. We used data on 801 children with acute diarrhea recruited in a randomized, double blind controlled trial (ISRCTN85071383) of zinc and copper supplementation. Using prespecified subgroup analyses, multidimensionality reduction analyses, tests of heterogeneity, and stepwise logistic regression for tests of interactions, we found that the influence of zinc on the risk of diarrhea for more than 3 days depended on the isolated organism-beneficial in Klebsiella, neutral in Esherichia coli and parasitic infections, and detrimental in rotavirus coinfections. Although we found similar results for the outcome of high stool volume, the results did not reach statistical significance. Our findings suggest that the current strategy of zinc supplementation in all cases of acute diarrheas in children may need appropriate fine tuning to optimize the therapeutic benefit based on the causative organism, but further studies need to confirm and extend our findings

What zinc supplementation does and does not achieve in diarrhea prevention: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Prevention of diarrhea has presented indomitable challenges. A preventive strategy that has received significant interest is zinc supplementation. Existing literature including quantitative meta-analyses and systematic reviews tend to show that zinc supplementation is beneficial however evidence to the contrary is augmenting. We therefore conducted an updated and comprehensive meta-analytical synthesis of the existing literature on the effect of zinc supplementation in prevention of diarrhea.</p> <p>Methods</p> <p>EMBASE^®, MEDLINE ^®and CINAHL^®databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. Effect of zinc supplementation on the following five outcomes was studied: incidence of diarrhea, prevalence of diarrhea, incidence of persistent diarrhea, incidence of dysentery and incidence of mortality. The published RCTs were combined using random-effects meta-analyses, subgroup meta-analyses, meta-regression, cumulative meta-analyses and restricted meta-analyses to quantify and characterize the role of zinc supplementation with the afore stated outcomes.</p> <p>Results</p> <p>We found that zinc supplementation has a modest beneficial association (9% reduction) with incidence of diarrhea, a stronger beneficial association (19% reduction) with prevalence of diarrhea and occurrence of multiple diarrheal episodes (28% reduction) but there was significant unexplained heterogeneity across the studies for these associations. Age, continent of study origin, zinc salt and risk of bias contributed significantly to between studies heterogeneity. Zinc supplementation did not show statistically significant benefit in reducing the incidence of persistent diarrhea, dysentery or mortality. In most instances, the 95% prediction intervals for summary relative risk estimates straddled unity.</p> <p>Conclusions</p> <p>Demonstrable benefit of preventive zinc supplementation was observed against two of the five diarrhea-related outcomes but the prediction intervals straddled unity. Thus the evidence for a preventive benefit of zinc against diarrhea is inconclusive. Continued efforts are needed to better understand the sources of heterogeneity. The outcomes of zinc supplementation may be improved by identifying subgroups that need zinc supplementation.</p

Skewed Sex Ratios in India: “Physician, Heal Thyself”

Abstract Sex selection, a gender discrimination of the worst kind, is highly prevalent across all strata of Indian society. Physicians have a crucial role in this practice and implementation of the Indian Government’s Pre-Natal Diagnostic Techniques Act in 1996 to prevent the misuse of ultrasound techniques for the purpose of prenatal sex determination. Little is known about family preferences, let alone preferences among families of physicians. We investigated the sex ratios in 946 nuclear families with 1,624 children, for which either one or both parents were physicians. The overall child sex ratio was more skewed than the national average of 914. The conditional sex ratios decreased with increasing number of previous female births, and a previous birth of a daughter in the family was associated with a 38 % reduced likelihood of a subsequent female birth. The heavily skewed sex ratios in the families of physicians are indicative of a deeply rooted social malady that could pose a critical challenge in correcting the sex ratios in India.</jats:p