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Background Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. Methods We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7–10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion. During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. Results Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval,.70–.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P =.22). Conclusions Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285. [ABSTRACT FROM AUTHOR]

Background: The role of nasopharyngeal bacteria in respiratory syncytial virus (RSV) disease has been underestimated. We measured the frequency and burden of respiratory bacteria in the upper respiratory tract of infants with RSV infection over 7 respiratory seasons, and their impact on clinical outcomes.Methods: Children <2 years old with mild (outpatients, n=115) or severe (inpatients, n=566) RSV infection, and matched healthy controls (n=161) were enrolled. Nasopharyngeal samples were obtained for RSV, Streptococcus pneumoniae, Staphylococcus aureus, Moraxella catarrhalis, and Haemophilus influenzae detection and quantitation by PCR. Multivariable models were constructed to identify variables predictive of severe disease.Results: S. pneumoniae, H. influenzae, and M. catarrhalis, but not S. aureus, were detected more frequently in RSV-infected children (84%) than healthy controls (46%; P<.001). Detection of S. pneumoniae and/or H. influenzae was associated with fever, more frequent antibiotic treatment, worse radiologic findings, and higher neutrophil counts (P<.01). In adjusted analyses, S. pneumoniae/H. influenzae codetection was independentlyassociated with greater odds of hospitalization, higher disease severity scores, need for supplemental oxygen, and longer hospitalization.Conclusions: Nasopharyngeal codetection of S. pneumoniae and H. influenzae in infants with RSV infection is associated with increased disease severity. [ABSTRACT FROM AUTHOR]

Background: A greater understanding of the mechanisms of action of weight-management interventions is needed to inform the design of effective interventions.Purpose: To investigate whether dietary restraint, habit strength, or diet self-regulation mediated the impact of a behavioral weight-management intervention on weight loss and weight loss maintenance.Methods: Latent growth curve analysis (LGCA) was conducted on trial data in which adults (N = 1,267) with a body mass index (BMI) ≥28 kg/m2 were randomized to either a brief intervention (booklet on losing weight), a 12 week weight-management program or the same program for 52 weeks. LGCA estimated the trajectory of the variables over four time points (baseline and 3, 12 and 24 months) to assess whether potential mechanisms of action mediated the impact of the weight-management program on BMI.Results: Participants randomized to the 12 and 52 week programs had a significantly greater decrease in BMI than the brief intervention. This direct effect became nonsignificant when dietary restraint, habit strength, and autonomous diet self-regulation were controlled for. The total indirect effect was significant for both the 12 (estimate = -1.33, standard error [SE] = 0.41, p = .001) and 52 week (estimate = -2.13, SE = 0.52, p < .001) program. Only the individual indirect effect for dietary restraint was significant for the 12 week intervention, whereas all three indirect effects were significant for the 52 week intervention.Conclusions: Behavior change techniques that target dietary restraint, habit strength, and autonomous diet self-regulation should be considered when designing weight loss and weight loss maintenance interventions. Longer interventions may need to target both deliberative and automatic control processes to support successful weight management. [ABSTRACT FROM AUTHOR]

Treatment options for Achromobacter xylosoxidans are limited. Eight cystic fibrosis patients with A. xylosoxidans were treated with 12 cefiderocol courses. Pretreatment in vitro resistance was seen in 3 of 8 cases. Clinical response occurred after 11 of 12 treatment courses. However, microbiologic relapse was observed after 11 of 12 treatment courses, notably without emergence of resistance. [ABSTRACT FROM AUTHOR]

Background Given the current opioid crisis, caregivers have mounting fears regarding the use of opioid medication in their children. We aimed to determine caregivers' a) willingness to accept, b) reasons for refusing, and c) past experiences with opioids. Methods A novel electronic survey of caregivers of children aged 4 to 16 years who had an acute musculoskeletal injury and presented to two Canadian paediatric emergency departments (ED) (March to November 2017). Primary outcome was caregiver willingness to accept opioids for moderate pain for their children. Results Five hundred and seventeen caregivers participated; mean age was 40.9 (SD 7.1) years with 70.0% (362/517) mothers. Children included 62.2% (321/516) males with a mean age of 10.0 (SD 3.6) years. 49.6% of caregivers (254/512) reported willingness to accept opioids for ongoing moderate pain in the ED, while 37.1% (190/512) were 'unsure'; 33.2% (170/512) of caregivers would accept opioids for at-home use, but 45.5% (233/512) were 'unsure'. Caregivers' primary concerns were side effects, overdose, addiction, and masking of diagnosis. Caregiver fear of addiction (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.01 to 1.25) and side effects (OR 1.25, 95% CI 1.11 to 1.42) affected willingness to accept opioids in the emergency department ; fears of addiction (OR 1.19, 95% CI 1.07 to 1.32), and overdose (OR 1.15, 95% CI 1.04 to 1.27) affected willingness to accept opioids for at-home use. Conclusions Only half of the caregivers would accept opioids for moderate pain, despite ongoing pain following nonopioid analgesics. Caregivers' fears of addiction, side effects, overdose, and masking diagnosis may have influenced their responses. These findings are a first step in understanding caregiver analgesic decision making. [ABSTRACT FROM AUTHOR]

Background: Uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infection (UTI), one of the most common infectious diseases in humans. UPEC are increasingly associated with resistance to multiple antibiotics. This includes resistance to third-generation cephalosporins, a common class of antibiotics frequently used to treat UTI.Methods: We employed a high-throughput genome-wide screen using saturated transposon mutagenesis and transposon directed insertion-site sequencing (TraDIS) together with phenotypic resistance assessment to identify key genes required for survival of the MDR UPEC ST131 strain EC958 in the presence of the third-generation cephalosporin cefotaxime.Results: We showed that blaCMY-23 is the major ESBL gene in EC958 responsible for mediating resistance to cefotaxime. Our screen also revealed that mutation of genes involved in cell division and the twin-arginine translocation pathway sensitized EC958 to cefotaxime. The role of these cell-division and protein-secretion genes in cefotaxime resistance was confirmed through the construction of mutants and phenotypic testing. Mutation of these genes also sensitized EC958 to other cephalosporins.Conclusions: This work provides an exemplar for the application of TraDIS to define molecular mechanisms of resistance to antibiotics. The identification of mutants that sensitize UPEC to cefotaxime, despite the presence of a cephalosporinase, provides a framework for the development of new approaches to treat infections caused by MDR pathogens. [ABSTRACT FROM AUTHOR]

Background. Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods. Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results. Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged =65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions. Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States. [ABSTRACT FROM AUTHOR]

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There is an urgent need for consistent data sharing policies that promote the advancement of science while respecting the values and interests of those providing their genetic data for research. Responding to the article of Jalayne J. Arias, Genevieve Pham-Kanter, and Eric G. Campbell, 'The Growth and Gaps of Genetic Data Sharing Policies in the United States', this commentary further explores the challenges of human subjects' protection in existing data sharing policies. We will elaborate on the need for data sharing policies to accommodate variation in individual and group preferences around data sharing and privacy concerns by comparing our previously published data on patients' and parents' consent to data sharing and attitudes about privacy to data from focus groups with HIV-positive, underserved individuals who were asked about their willingness to participate in genetic research and share their data broadly. These studies support the observation of Arias, Pham-Kanter, and Campbell that researchers, and funding agencies will need to balance the privacy interests of groups as well as individuals in future genomic data sharing policies. [ABSTRACT FROM AUTHOR]

Purpose. Use of antifungal agents and predictors of total antifungal use among adult inpatients at U.S. academic health centers was characterized. Methods. Claims data obtained from a geographically representative sample of U.S. nonprofit academic health centers were analyzed to characterize use of systemic antifungals during the period 2004-08. Aggregate data were analyzed to identify trends in use of three antifungal classes (azoles, polyenes, echinocandins), as well as individual antifungal agents. Multivariate regression analysis was employed to investigate predictors of total antifungal use and interhospital variability in antifungal use. Results. Aggregate antifungal use at health centers included in the data analysis increased from (mean ± S.D.) 82 ± 36 days of therapy (DOT) per 1000 patient-days in 2004 to 88 ± 39 DOT per 1000 patient-days in 2007 and then declined to 77 ± 36 DOT per 1000 patient-days in 2008. Use of voriconazole increased significantly during the study period (p < 0.0001), while use of caspofungin decreased significantly (p < 0.0001). Higher use of third- or fourth generation cephalosporins was a significant predictor of higher total antifungal use (p = 0.0005); performance of more stem cell or bone marrow transplants was also significantly associated with greater antifungal use. Conclusion. Total antifungal use at a sample of U.S. academic health centers increased from 2004 to 2007 but decreased to below baseline in 2008. Azoles were the most commonly used agents. In 2008, total antifungal use at the centers ranged from 29 to 334 DOT per 1000 patient-days. [ABSTRACT FROM AUTHOR]

Important life history parameters of the mealybug, Maconellicoccus hirsutus (Green), were characterized on hibiscus (Hibiscus rosa-sinensis L.) cuttings at six constant temperatures between 15 and 35°C. The development of M. hirsutus was the fastest at 27°C, where the mealybugs completed development in ≈29 d. The lower (Tmin) and upper (Tmax) developmental thresholds and the optimal developmental temperature (Topt) for the development of female mealybugs were estimated as 14.5, 35, and 29°C, respectively. The thermal constant (K), which is the number of temperature-day or degree-day units required for development, of the females was 347 DD. The original distribution range prediction (based on Tmin = 17.5°C and K = 300 DD) indicated that M. hirsutus could complete at least one generation in all of the continental United States. However, results of this study suggested that the distribution range of M. hirsutus may expand northward because of the lower Tmin, and the predicted number of generations in a year may be lower because of the higher K required to complete each generation. The average cumulative survival rate of M. hirsutus at 25 and 27°C was 72%, which was significantly higher than 51 and 62% at 20 and 30°C, respectively. M. hirsutus reproduced sexually, with each mated female producing 260-300 eggs between 20 and 27°C but only ≈100 eggs at 30°C. Female longevity was reduced from 28 d at 20°C to 19-21 d at 25-30°C. At 27°C, the net reproductive rate (Ro) was estimated at 165 ♀/♀, the intrinsic rate of population increase (rm) was 0.119 (♀/♀/d), the generation time (TG) was 43 d, and the doubling time (DT) was 5.8 d. The life table statistics suggested that the currently released biological control agents, which have higher rm than M. hirsutus, will be able to complete more generations than the mealybug within the tested temperature range; thus, they are effective against M. hirsutus. [ABSTRACT FROM AUTHOR]