Analysis of FDA's Vuse market authorisation: limitations and opportunities.

This special communication provides a physicians' critique of the US Food and Drug Administration (FDA)'s decision to authorise the Vuse Solo (Vuse) Premarket Tobacco Application (PMTA). The PMTA authorisation represents the first time that FDA has authorised an Electronic Nicotine Delivery System (ENDS) for marketing in the USA. Using the FDA Decision Summary, the special communication identifies significant unanswered public health and scientific questions that prevent the authors from reaching FDA's conclusion that Vuse meets the Appropriate for the Protection of the Public Health (APPH) standard. The authors recommend FDA suspend the market authorisation and use these questions to re-evaluate the PMTA, and to prospectively monitor whether Vuse meets APPH standard. The special communication advances the ENDS harm reduction conversation because it calls for national tobacco regulators to develop an epidemiological prediction of ENDS impact on the population and to expand the scope of their analysis to evaluate the impacts of ENDS on congenital birth defects, abuse liability and non-flavour drivers of youth usage. Through learning from the American experience regulating Vuse, national tobacco regulators around the globe will be better equipped to evaluate the impact of ENDS on the public health.

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children.

BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.

Sepsis and acute respiratory distress syndrome requiring extracorporeal life support in an adolescent with mild cystic fibrosis.

Outcomes for invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO) to treat acute respiratory failure in patients with mild cystic fibrosis (CF) lung disease are not known. We present a case of the successful use of ECMO to treat acute respiratory failure secondary to staphylococcal sepsis in an adolescent CF patient with previously normal lung function. Her post-ECMO course was notable for severe airflow obstruction, hypoxemia, deconditioning, and growth failure. She had significantly improved at six months follow-up, though she continued to have moderate airflow obstruction on pulmonary function testing. This case illustrates that ECMO and prolonged intubation can prolong life in CF patients with mild lung disease who present with potentially reversible acute respiratory failure, though they are associated with significant morbidity.

Patterns of empiric treatment of Chlamydia trachomatis infections in an underserved population.

BACKGROUND AND OBJECTIVES: Appropriate treatment of chlamydia trachomatis (CT) sexually transmitted infections (STIs) is important. Much of this treatment is empiric, and most research on treatment patterns has been conducted in emergency department settings. Few studies have focused on CT treatment in outpatient primary care settings, especially among underserved populations. We aimed to study patterns of empiric CT treatment in an urban safety net clinic. METHODS: We examined electronic health records from all patients in whom a CT lab test was completed between January 1 and December 31, 2007 (n=1,222). We manually reviewed charts to confirm patient demographics, CT testing, STI symptoms, known exposure, empiric treatment, test results, and follow-up. We then conducted univariate and multivariate analyses to study patterns of and characteristics associated with receiving empiric treatment. We also assessed follow-up for non-treated patients with positive tests. RESULTS: Among 488 patients who presented with STI symptoms and who were tested, 181 (37.1%) were empirically treated. In multivariate analyses, women with symptoms had significantly lower odds of receiving empiric treatment, as compared with men. Of the 1,222 patients tested, 75 had a positive CT laboratory test; seven (9.3%) of these patients did not receive empiric treatment and had no documented posttest treatment. CONCLUSIONS: A minority of patients with STI symptoms were empirically treated. Outpatient clinicians should consider whether a patient meets guidelines for empiric STI treatment; this decision should take into account the feasibility of prompt follow-up. This may be especially important in women presenting with STI symptoms.