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Population-level increases in psychopathology and other negative mental health outcomes, including posttraumatic stress, depression, anxiety, and elevated substance use, are directly linked to large-scale disasters in the United States. Thus, it is unsurprising that the current coronavirus disease 2019 (COVID-19) pandemic is seriously impacting population-level mental health in the United States, especially among socially disadvantanged, young, and racial and ethnic minority persons. The indirect psychological harms of the COVID-19 pandemic for those who belong to minoritized communities are complicated, exacerbated, and compounded by experiences and stressors specific to their marginalized social identities. In this regard, lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) adolescents and young adults have received limited public health attention. This commentary aims to provide a nuanced perspective on the potential indirect mental health effects of the COVID-19 pandemic crisis on LGBTQ young persons. International research suggests that heteronormativity and cisnormativity in practice and policy-level response to large-scale disasters systematically ignores the needs of LGBTQ populations.7 Globally, issues relevant to LGBTQ communities in disaster contexts (eg, discrimination in accessing emergency government services because of LGBTQ status) are largely unreported, and government agencies historically fail to support LGBTQ-affirming interventions during recovery efforts.7 International guidelines and policy frameworks on disaster response and recovery have further failed to consider the needs of LGBTQ populations.7 The dearth of existing research on LGBTQ communities and disaster response in the United States speaks to the invisibility of LGBTQ young persons in the current public health response to the COVID-19 pandemic crisis. Despite limited attention to the mental health needs of LGBTQ young persons during the COVID-19 pandemic, LGBTQ young persons may face unique mental health challenges6,8 driven by the overlapping experience of pandemic-related9-11 and sexual and gender minority–related3,11,12 stressors.

Objective To characterize the prospective controlled clinical studies for all novel drugs that were initially approved by the Food and Drug Administration on the basis of limited evidence.Design Systematic review.Data sources Drugs@FDA database and PubMed.Study inclusion All prospective controlled clinical studies published after approval for all novel drugs initially approved by the FDA between 2005 and 2012 on the basis of a single pivotal trial, pivotal trials that used surrogate markers of disease as primary endpoints, or both. Results Between 2005 and 2012 the FDA approved 117 novel drugs for 123 indications on the basis of a single pivotal trial, pivotal trials that used surrogate markers of disease, or both (single surrogate trials). We identified 758 published controlled studies over a median of 5.5 years (interquartile range 3.4-8.2) after approval, most of which (554 of 758; 73.1%) were studies for indications approved on the basis of surrogate markers of disease. Most postapproval studies used active comparators—67 of 77 (87.0%) indications approved on the basis of single pivotal trials, 365 of 554 (65.9%) approvals based on surrogate marker trials, and 100 of 127 (78.7%) approvals based on single surrogate trials—and examined surrogate markers of efficacy as primary endpoints—51 of 77 (66.2%), 512 of 554 (92.4%), and 110 of 127 (86.6%), respectively. Overall, no postapproval studies were identified for 43 of the 123 (35.0%) approved indications. The median total number of postapproval studies identified was 1 (interquartile range 0-2) for indications approved on the basis of a single pivotal trial, 3 (1-8) for indications approved on the basis of pivotal trials that used surrogate markers of disease as primary endpoints, and 1 (0-2) for single surrogate trial approvals, and the median aggregate number of patients enrolled in postapproval studies was 90 (0-509), 533 (122-3633), and 38 (0-666), respectively. The proportion of approved indications with one or more randomized, controlled, double blind study using a clinical outcome for the primary endpoint that was published after approval and showed superior efficacy was 18.2% (6 of 33), 2.0% (1 of 49), and 4.9% (2 of 41), respectively.Conclusions The quantity and quality of postapproval clinical evidence varied substantially for novel drugs first approved by the FDA on the basis of limited evidence, with few controlled studies published after approval that confirmed efficacy using clinical outcomes for the original FDA approved indication.

ObjectiveDetermine whether management of neonatal hyperbilirubinemia differs if one used end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc) measurements instead of direct antiglobulin test (DAT) results to assess the severity of hemolysis.Study designRetrospective chart review of infants with total bilirubin and ETCOc levels measured from July 2016 to August 2018. The reported treatment is the hypothetical management infants might have received had there been strict adherence to American Academy of Pediatrics guidelines, rather than the actual management they received.ResultOnly 27.2% of 191 DAT(+) infants were hemolyzing based on ETCOc, while 29.1% of DAT (−) infants were hemolyzing based on ETCOc. Management of 18 (9.4%) infants differed depending if ETCOc or DAT were used to determine hemolysis. Eight fewer infants would have received phototherapy if ETCOc was used.ConclusionsETCOc is a more accurate determinant of hemolysis in the newborn, and its use can lead to less phototherapy.

College students situated at the nexus of racial and sexual and gender minority (SGM) identities may experience multiple identity-related oppressions. We assessed whether racist microaggressions and lesbian, gay, bisexual, transgender, queer, or questioning (LGBTQ)-related minority stressors (ie, family rejection, identity concealment, racialized heterosexism and/or cisgenderism, internalized LGBTQ-phobia, and victimization) are associated with greater psychological distress among SGM college students of color (SOC) (students who identified as Hispanic/Latinx and/or any nonwhite race). Participants were a subset of SOC (n = 200) from a larger nonprobability cross-sectional study of SGM college students. Participants were recruited by using online social media platforms and university email listserves from May through August 2020. Participants completed an online Qualtrics survey using previously validated measures of minority stress, racist microaggressions, and psychological distress. Simple and covariate-adjusted multiple linear regression models were used to examine the associations between racist microaggressions and LGBTQ-related minority stressors with psychological distress. In simple linear regression models, racist microaggressions and all LGBTQ-related stressors (ie, family rejection, identity concealment, racialized heterosexism and/or cisgenderism, internalized LGBTQ-phobia, and victimization) were significantly and positively associated with greater psychological distress. In covariate-adjusted multiple linear regression, racist microaggressions, internalized LGBTQ-phobia, and LGBTQ-related family rejection (but not identity concealment, racialized heterosexism and/or cisgenderism, and victimization) were independently and significantly associated with greater psychological distress. Study findings reveal that racist microaggressions, along with LGBTQ-related family rejection and internalized LGBTQ-phobia, have a significant impact on psychological distress among SGM SOC. Public health leaders have an important opportunity for policy and program development and reform to address the identity-related mental health needs of SGM SOC.

Background The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product’s actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. Methods We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Results Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01–2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95% CI -0.15–0.16). Conclusions Many postapproval drug trials are not directly comparable to previously published pivotal trials, particularly with respect to endpoint selection. Although treatment effects from pivotal trials supporting FDA approval of novel therapeutics based on non-continuous surrogate markers of disease are often larger than those observed among postapproval trials using surrogate markers as trial endpoints, there is no evidence of difference between pivotal and postapproval trials using continuous surrogate markers.

Density dependence and, therefore,K(carrying capacity, equilibrium population size) are central to understanding and predicting changes in population size (N). Although resource levels certainly fluctuate,Khas almost always been treated as constant in both theoretical and empirical studies. We quantified temporal variation inKby fitting extensions of standard population dynamic models to 16 annual censuses of a population of the perennial bunchgrassBouteloua rigidiseta. Variable‐Kmodels provided substantially better fits to the data than did models that varied the potential rate of population increase. The distribution of estimated values ofKwas skewed, with a long right tail (i.e., a few “jackpot” years). The population did not trackKclosely. Relatively slow responses to changes inKcombined with large, rapid changes inKsometimes causedNto be far fromK. In 13%–20% of annual intervals,Kwas so much larger thanNthat the population’s dynamics were best described by geometric growth and the population was, in effect, unregulated. Explicitly incorporating temporal variation inKsubstantially improved the realism of models with little increase in model complexity and provided novel information about this population’s dynamics. Similar methods would be applicable to many other data sets.

To investigate density-dependent population regulation in the perennial bunchgrass Bouteloua rigidiseta, we experimentally manipulated density by removing adults or adding seeds to replicate quadrats in a natural population for three annual intervals. We monitored the adjacent control quadrats for 14 annual intervals. We constructed a population projection matrix for each quadrat in each interval, calculated λ, and did a life table response experiment (LTRE) analysis. We tested the effects of density upon λ by comparing experimental and control quadrats, and by an analysis of the 15-year observational data set. As measured by effects on λ and on$N_{t+1}/N_{t}$in the experimental treatments, negative density dependence was strong: the population was being effectively regulated. The relative contributions of different matrix elements to treatment effect on λ differed among years and treatments; overall the pattern was one of small contributions by many different life cycle stages. In contrast, density dependence could not be detected using only the observational (control quadrats) data, even though this data set covered a much longer time span. Nor did experimental effects on separate matrix elements reach statistical significance. These results suggest that ecologists may fail to detect density dependence when it is present if they have only descriptive, not experimental, data, do not have data for the entire life cycle, or analyze life cycle components separately.

The Oncotype DX assay has been validated in predicting response to adjuvant chemotherapy in breast cancer. Its role in neoadjuvant chemotherapy (NCT) has not been established. The National Cancer Database was used to identify all patients with T1-T3, ER-positive, HER2-negative primary invasive breast cancer diagnosed from 2010 to 2015 who had Oncotype DX recurrence scores (RS) and received NCT. RS were classified as low, intermediate, or high. Unadjusted and adjusted regression analyses were performed to determine the association between pathologic complete response (pCR) and RS. A total of 989 patients (mean age, 54.6 years) with available RS who underwent NCT were identified. RS were low in 227 (23.0%) patients, intermediate in 450 (45.5%) patients, and high in 312 (31.5%) patients. Most patients had a T1 (431 [43.6%]) or T2 tumor (451 [45.6%]). Most had N0 disease (757 [76.5%]). Tumor grades were 1 (123 [12.4%]), 2 (517 [52.3%]), or 3 (349 [35.3%]). pCR was achieved by 42 (4.3%) patients. Adjusted multivariable analysis showed a significant association between pCR and high RS (odds ratio 4.87; 95% confidence interval 2.01-11.82). High Oncotype DX RS was associated with pCR after NCT in this national cohort of ER-positive, HER2-negative patients. Oncotype DX testing could help to identify patients most suited for NCT and should be considered for incorporation into the multidisciplinary decision-making process.

Invasive predators can devastate native species and ecosystems. However, native species may be able to coexist with invasive predators through a variety of mechanisms, such as changes in morphology or behavior due to a plastic response or selection on fixed anti-predator traits. We examined whether exposed and naive populations of Pacific tree frog tadpoles ( Pseudacris regilla ) display divergent morphological and behavioral traits in response to the invasive predatory red swamp crayfish ( Procambarus clarkii ). Tadpoles were collected from three study streams with and three without crayfish, in the Santa Monica Mountains of Southern California. We analyzed tadpole morphology and tested anti-predator behavior and survival in the laboratory. Tadpoles from streams with crayfish had shallower, narrower tails than tadpoles from streams without crayfish. Tadpoles from streams with and without crayfish were less active after exposure to crayfish chemical cues. The divergent morphology of naive and exposed tadpoles is consistent with tadpoles exhibiting a plastic response to crayfish or undergoing selection from crayfish predation. In laboratory predation experiments, we found no difference in survival between tadpoles from streams with and without crayfish but tadpoles that survived predation had deeper tail muscles than those that were killed or injured. Our results suggest that deeper tails are advantageous in the presence of crayfish, yet tadpoles from crayfish streams had shallower tails than those from crayfish-free streams. Shallower tails may have an alternative unmeasured advantage or there may be a physiological constraint to developing deeper tails in the wild. These results highlight the ability of a native frog to respond to an invasive predatory crayfish, potentially allowing for coexistence.