Adverse events associated with weekly short course isoniazid and rifapentine therapy in pediatric patients with latent tuberculosis: A chart and literature review.

BACKGROUND: Effective yet safe treatment of latent tuberculosis is important for preventing the spread of tuberculosis and the progression to active disease in pediatric patients. As of 2017, the short course combination regimen of weekly isoniazid and rifapentine (3HP) administered by directly observed therapy (DOT) has replaced 9 months of isoniazid as the standard of treatment for latent tuberculosis in pediatric patients. The literature, limited in size, has established the 3HP regimen's superior safety and adherence. METHODS: We completed a retrospective chart review (n = 22) of pediatric patients at our institution receiving the 3HP regimen via DOT between 2017 and 2019. Frequencies of selected outcomes were compared to previously published data collected in a literature review. RESULTS: In this retrospective chart review, pediatric patients ages 2-20 years receiving 3HP with DOT for latent tuberculosis experienced frequent adverse events, more severe adverse events such as anaphylaxis, and higher treatment discontinuation than that which has been previously reported in the literature. Of note, our cohort's race/ethnicity differed from the cohorts described in the literature. CONCLUSIONS: Our data suggests that the short course combination regimen for pediatric latent tuberculosis patients may have a higher adverse event rate than previously established. Although this sample size is small, this study urges further investigation of more diverse cohorts to better establish the 3HP regimen's safety and tolerability.

Are food and drink retailers within NHS venues adhering to NICE Quality standard 94 guidance on childhood obesity? A cross-sectional study of two large secondary care NHS hospitals in England.

OBJECTIVE: To assess whether the food and drink retail outlets in two major National Health Service (NHS) district general hospitals in England adhere to quality statements 1-3 of the UK National Institute for Health and Care Excellence (NICE) quality standard 94. DESIGN: Cross-sectional, descriptive study to assess the food and drink options available in vending machines, restaurants, cafes and shops in two secondary care hospitals. MAIN OUTCOME MEASURES: Adherence to quality statement 1 whereby the food and drink items available in the vending machines were classified as either healthy or less healthy using the Nutrient Profiling Model (NPM). Compliance with quality statements 2 and 3 was assessed through the measurement of how clearly the shops, cafes and restaurants displayed nutrition information on menus, and the availability and prominent display of healthy food and drink options in retail outlets, respectively. RESULTS: Adherence to quality statement 1 was poor. Of the 18 vending machines assessed, only 7 (39%) served both a healthy food and a healthy drink option. Neither hospital was compliant with quality statement 2 wherein nutritional information was not available on menus of food providers in either hospital. There was inconsistent compliance with quality standard 3 whereby healthy food and drink options were prominently displayed in the two main hospital restaurants, but all shops and cafes prioritised the display of unhealthy items. CONCLUSIONS: Neither hospital was consistently compliant with quality statements 1-3 of the NICE quality standard 94. Improving the availability of healthy foods and drinks while reducing the display and accessibility to less healthy options in NHS venues may improve family awareness of healthy alternatives. Making it easier for parents to direct their children to healthier choices is an ostensibly central component of our healthcare system.

Particle size distributions of lead measured in battery manufacturing and secondary smelter facilities and implications in setting workplace lead exposure limits.

Inhalation plays an important role in exposures to lead in airborne particulate matter in occupational settings, and particle size determines where and how much of airborne lead is deposited in the respiratory tract and how much is subsequently absorbed into the body. Although some occupational airborne lead particle size data have been published, limited information is available reflecting current workplace conditions in the U.S. To address this data gap, the Battery Council International (BCI) conducted workplace monitoring studies at nine lead acid battery manufacturing facilities (BMFs) and five secondary smelter facilities (SSFs) across the U.S. This article presents the results of the BCI studies focusing on the particle size distributions calculated from Personal Marple Impactor sampling data and particle deposition estimates in each of the three major respiratory tract regions derived using the Multiple-Path Particle Dosimetry model. The BCI data showed the presence of predominantly larger-sized particles in the work environments evaluated, with average mass median aerodynamic diameters (MMADs) ranging from 21-32 µm for the three BMF job categories and from 15-25 µm for the five SSF job categories tested. The BCI data also indicated that the percentage of lead mass measured at the sampled facilities in the submicron range (i.e., <1 µm, a particle size range associated with enhanced absorption of associated lead) was generally small. The estimated average percentages of lead mass in the submicron range for the tested job categories ranged from 0.8-3.3% at the BMFs and from 0.44-6.1% at the SSFs. Variability was observed in the particle size distributions across job categories and facilities, and sensitivity analyses were conducted to explore this variability. The BCI results were compared with results reported in the scientific literature. Screening-level analyses were also conducted to explore the overall degree of lead absorption potentially associated with the observed particle size distributions and to identify key issues associated with applying such data to set occupational exposure limits for lead.

Preterm human milk composition: a systematic literature review.

There are wide variations in the macronutrient values adopted by neonatal intensive care units and industry to fortify milk in efforts to achieve recommended intakes for preterm infants. Contributing to this is the variation in macronutrient composition of preterm milk between and within mothers and the variable quality of milk analyses used to determine the macronutrient content of milk. We conducted a systematic review of the literature using articles published in English between 1959 and 2013 that reported the concentrations of one or more macronutrients or energy content in human preterm milk, sampled over a representative 24-h period. Searched medical databases included Ovid Medline, Scopus, CINAHL and the Cochrane Library. Results are presented as mean values and ranges for each macronutrient during weeks 1-8 of lactation, and preferred mean values (g/100 ml) for colostrum (week 1) and mature milk (weeks 2-8; protein: 1·27, fat: 3·46, lactose: 6·15 and carbohydrate: 7·34), using data from studies employing the highest-quality analyses. Industry-directed fortification practices using these mean values fail to meet protein targets for infants weighing <1000 g when the fortified milk is fed <170-190 ml/kg per d, and the protein:energy ratio of the fortified milk is inadequate. This study aimed to provide additional information to industry in order to guide their future formulation of breast milk fortifiers. Quality macronutrient analyses of adequately sampled preterm breast milk would improve our understanding of the level of fortification needed to meet recommended protein and energy intakes and growth targets, as well as support standardised reporting of nutritional outcomes.

Rethinking Meta-Analysis: Applications for Air Pollution Data and Beyond.

Meta-analyses offer a rigorous and transparent systematic framework for synthesizing data that can be used for a wide range of research areas, study designs, and data types. Both the outcome of meta-analyses and the meta-analysis process itself can yield useful insights for answering scientific questions and making policy decisions. Development of the National Ambient Air Quality Standards illustrates many potential applications of meta-analysis. These applications demonstrate the strengths and limitations of meta-analysis, issues that arise in various data realms, how meta-analysis design choices can influence interpretation of results, and how meta-analysis can be used to address bias and heterogeneity. Reviewing available data from a meta-analysis perspective can provide a useful framework and impetus for identifying and refining strategies for future research. Moreover, increased pervasiveness of a meta-analysis mindset-focusing on how the pieces of the research puzzle fit together-would benefit scientific research and data syntheses regardless of whether or not a quantitative meta-analysis is undertaken. While an individual meta-analysis can only synthesize studies addressing the same research question, the results of separate meta-analyses can be combined to address a question encompassing multiple data types. This observation applies to any scientific or policy area where information from a variety of disciplines must be considered to address a broader research question.

Providing perspective for interpreting cardiovascular mortality risks associated with ozone exposures.

When identifying standards for air pollutants based on uncertain evidence, both science and policy judgments play critical roles. Consequently, critical contextual factors are important for understanding the strengths, limitations, and appropriate interpretation of available science, and potential benefits of risk mitigation alternatives. These factors include the relative magnitude and certainty of the risks posed by various factors and the impacts of other risk factors on air pollutant epidemiology study findings. This commentary explores ozone's status as a risk factor for cardiovascular mortality in contrast with decades of strong and consistent evidence for other established risk factors. By comparison, the ozone evidence is less conclusive, more heterogeneous, and subject to substantial uncertainty; ozone's potential effects, if any, are small and challenging to discern. Moreover, the absence of a demonstrated causal relationship calls into question efforts to quantify cardiovascular mortality risks attributed to ozone exposures on a population level and highlights the need to explicitly acknowledge this uncertainty if such calculations are performed. These concerns are relevant for other similar policy contexts - where multiple established risk factors contribute to the health impact of interest; exposure-effect associations are relatively small, weak, and uncertain; and a causal relationship has not been clearly established.

Strengthening the foundation of next generation risk assessment.

In a recent draft report, Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology, the US Environmental Protection Agency presents valuable contributions to understanding the roles that evolving toxicity testing methods and associated interpretative techniques can play in assessing the risks associated with chemical exposures. However, the evaluations presented in the NexGen report would benefit from more thorough consideration of several essential components of a critical review of toxicity data, e.g., data quality, data relevance, and the extent to which the test endpoints reflect adverse effects. Such considerations are necessary to ensure that the NexGen report evaluations--and the resulting conclusions and recommendations--are grounded in scientifically sound, representative data reviews. We illustrate these concerns with a critique of the report's prototype ozone evaluation. Although substantial additional research is needed before new toxicity data types can be used reliably in rigorous risk assessment applications, they clearly offer exciting opportunities for advancing toxicological science and risk assessment. By explicitly identifying limitations still to be addressed and providing stronger guideposts for future research needs, the NexGen report could serve an influential role in achieving the promise of these new research approaches.

Weight-of-evidence analysis of human exposures to dioxins and dioxin-like compounds and associations with thyroid hormone levels during early development.

Thyroid hormones play a critical role in the proper development of brain function and cell growth. Several epidemiological studies have been conducted to assess potential associations between pre- and post-natal exposure to dioxins or dioxin-like compounds (DLCs) and the levels of circulating thyroid hormones during early development. Dioxins and DLCs include chlorinated dibenzo-p-dioxins, chlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (PCBs). We identified a total of 23 relevant epidemiological studies (21 cohort studies and 1 case-control study) that measured exposures to various types of dioxins and DLCs as well as markers of thyroid function, such as thyroid stimulating hormone (TSH), total thyroxine (T4), free T4, total triiodothyroxine (T3), free T3, and thyroid-binding globulin concentrations in cord blood or circulation. While some of the studies reported associations between concentrations of dioxins and/or DLCs and some biomarkers of thyroid function, the majority of the observed associations were not statistically significant. Moreover, there were no clear and consistent effects across studies for any of the hormone levels examined, and while a number of studies showed a statistically significant association with exposure for a given marker of thyroid function, other studies showed either no change or changes in the opposite direction for the same thyroid function marker. Similarly, when the results were analyzed considering developmental stage, there generally were no clear and consistent effects at any age from birth through 12 years of age. The absence of a clear correlation between background exposures to dioxins and DLCs and thyroid function biomarkers during development is not consistent with the hypothesis that background exposures to these chemicals cause effects on thyroid function during development.

Developing risk-based target concentrations for carcinogenic polycyclic aromatic hydrocarbon compounds assuming human consumption of aquatic biota.

As part of the remediation process at a former creosote-handling facility in Washington, target groundwater concentrations were developed as goals for the planned cleanup efforts. Considering state regulatory requirements and site-specific conditions, these concentrations were established to protect surface water in the lake adjacent to the site. These risk-based values were calculated assuming that chemicals will (1) be transported in groundwater, (2) discharge into the lake, and (3) be taken up by aquatic organisms that may be consumed by humans. Among the primary chemicals driving remediation decisions at this site are carcinogenic polycyclic aromatic hydrocarbon (cPAH) compounds, which have limited environmental mobility and are metabolized by many types of potentially edible aquatic organisms. This work included assessing the validity for cPAH compounds of the required default regulatory assumptions and deriving alternative risk-based concentrations. These analyses focused on factors that would modify the generic assumption regarding bioconcentration of cPAH compounds in aquatic biota and influence bioavailability of cPAH compounds to humans consuming the biota. Modifications based on these factors and the use of toxicity equivalency factors resulted in alternative risk-based concentrations for individual cPAH compounds that ranged from approximately 7 to 700 times greater than the default value of 0.03 microg/l.