First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC.

BACKGROUND: Selpercatinib, a highly selective potent and brain-penetrant RET inhibitor, was shown to have efficacy in patients with advanced RET fusion-positive non-small-cell lung cancer (NSCLC) in a nonrandomized phase 1-2 study. METHODS: In a randomized phase 3 trial, we evaluated the efficacy and safety of first-line selpercatinib as compared with control treatment that consisted of platinum-based chemotherapy with or without pembrolizumab at the investigator's discretion. The primary end point was progression-free survival assessed by blinded independent central review in both the intention-to-treat-pembrolizumab population (i.e., patients whose physicians had planned to treat them with pembrolizumab in the event that they were assigned to the control group) and the overall intention-to-treat population. Crossover from the control group to the selpercatinib group was allowed if disease progression as assessed by blinded independent central review occurred during receipt of control treatment. RESULTS: In total, 212 patients underwent randomization in the intention-to-treat-pembrolizumab population. At the time of the preplanned interim efficacy analysis, median progression-free survival was 24.8 months (95% confidence interval [CI], 16.9 to not estimable) with selpercatinib and 11.2 months (95% CI, 8.8 to 16.8) with control treatment (hazard ratio for progression or death, 0.46; 95% CI, 0.31 to 0.70; P<0.001). The percentage of patients with an objective response was 84% (95% CI, 76 to 90) with selpercatinib and 65% (95% CI, 54 to 75) with control treatment. The cause-specific hazard ratio for the time to progression affecting the central nervous system was 0.28 (95% CI, 0.12 to 0.68). Efficacy results in the overall intention-to-treat population (261 patients) were similar to those in the intention-to-treat-pembrolizumab population. The adverse events that occurred with selpercatinib and control treatment were consistent with those previously reported. CONCLUSIONS: Treatment with selpercatinib led to significantly longer progression-free survival than platinum-based chemotherapy with or without pembrolizumab among patients with advanced RET fusion-positive NSCLC. (Funded by Eli Lilly and others; ClinicalTrials.gov number, NCT04194944.).

HIV Testing and Preexposure Prophylaxis Prescriptions Among U.S. Commercially Insured Transgender Men and Women, 2014 to 2021.

BACKGROUND: Transgender persons are disproportionately affected by HIV, but preexposure prophylaxis (PrEP) use has been low in this population. Clinical encounters for gender-affirming hormone therapy (GAHT) provide opportunities for HIV prevention. OBJECTIVE: To estimate the number of commercially insured transgender women (TGW) and transgender men (TGM) in the United States and their use of HIV prevention services. DESIGN: Retrospective analysis of secondary data. SETTING: Merative MarketScan commercial databases from 2014 to 2021. PARTICIPANTS: TGW and TGM, defined as those with transgender-related diagnoses and prescriptions for feminizing or masculinizing GAHT. MEASUREMENTS: HIV testing and PrEP use. RESULTS: A substantially increasing trend was observed in the prevalence of transgender-related diagnosis codes from 2014 to 2021 and in the proportion of persons who used GAHT. The increases were driven by persons aged 18 to 34 years. In 2021, among 10 613 TGW with a test for or a diagnosis of a sexually transmitted infection (STI) in the previous 12 months, 61.1% had an HIV test; among those, 20.2% were prescribed PrEP. Among 4184 TGM with STI risk, 48.3% had an HIV test; among those, 10.2% were prescribed PrEP. The prevalence of TGW and TGM who had a test for or a diagnosis of an STI, had an HIV test, and were prescribed PrEP increased substantially from 2014 to 2021. LIMITATION: The findings represent only persons with commercial health insurance who sought health care services for GAHT. CONCLUSION: It is important to identify transgender persons to monitor their receipt of HIV prevention services. Encounters for GAHT provide opportunities to offer HIV prevention and other prevention services. Many HIV prevention opportunities were likely missed at clinical encounters for GAHT. PRIMARY FUNDING SOURCE: None.

Accuracy of machine learning in the preoperative identification of ovarian borderline tumors: a meta-analysis.

AIM: The objective of this study is to explore the diagnostic value of machine learning (ML) in borderline ovarian tumors through meta-analysis. METHODS: Pubmed, Embase, Web of Science, and Cochrane Library databases were comprehensively retrieved from database inception untill February 16, 2023. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was adopted to evaluate the risk of bias in the original studies. Sub-group analyses of ML were conducted according to clinical features and radiomics features. We separately discussed the discriminative value of ML for borderline vs benign and borderline vs malignant tumors. RESULTS: Eighteen studies involving 12,778 subjects were included in our analysis. The modeling variables mainly consisted of radiomics features (n=13) and a small number of clinical features (n=5). When distinguishing between borderline and benign tumors, the ML model based on radiomic features achieved a c-index of 0.782 (95% CI: 0.732-0.831), sensitivity of 0.75 (95% CI: 0.67-0.82), and specificity of 0.75 (95% CI: 0.67-0.81) in the validation set. When distinguishing between borderline and malignant tumors, the ML model based on radiomic features achieved a c-index of 0.916 (95% CI: 0.891-0.940), sensitivity of 0.86 (95% CI: 0.78-0.91), and specificity of 0.88 (95% CI: 0.82-0.92) in the validation set. In addition, we analyzed the discriminatory ability of radiologists and found that their sensitivity was 0.26 (95% CI: 0.12-0.46) and specificity was 0.94 (95% CI: 0.90-0.97). CONCLUSIONS: ML has tremendous potential in the preoperative diagnosis and differentiation of borderline ovarian tumors and may be more accurate than radiologists in diagnosing and differentiating borderline ovarian tumors.

Increased Hospitalizations Involving Fungal Infections during COVID-19 Pandemic, United States, January 2020-December 2021.

Hospitalizations involving fungal infections increased 8.5% each year in the United States during 2019-2021. During 2020-2021, patients hospitalized with COVID-19-associated fungal infections had higher (48.5%) in-hospital mortality rates than those with non-COVID-19-associated fungal infections (12.3%). Improved fungal disease surveillance is needed, particularly during respiratory virus pandemics.

Association between thromboembolic events and COVID-19 infection within 30 days: a case-control study among a large sample of adult hospitalized patients in the United States, March 2020-June 2021.

The association between thromboembolic events (TE) and COVID-19 infection is not completely understood at the population level in the United States. We examined their association using a large US healthcare database. We analyzed data from the Premier Healthcare Database Special COVID-19 Release and conducted a case-control study. The study population consisted of men and non-pregnant women aged ≥ 18 years with (cases) or without (controls) an inpatient ICD-10-CM diagnosis of TE between 3/1/2020 and 6/30/2021. Using multivariable logistic regression, we assessed the association between TE occurrence and COVID-19 diagnosis, adjusting for demographic factors and comorbidities. Among 227,343 cases, 15.2% had a concurrent or prior COVID-19 diagnosis within 30 days of their index TE. Multivariable regression analysis showed a statistically significant association between a COVID-19 diagnosis and TE among cases when compared to controls (adjusted odds ratio [aOR] 1.75, 95% CI 1.72-1.78). The association was more substantial if a COVID-19 diagnosis occurred 1-30 days prior to index hospitalization (aOR 3.00, 95% CI 2.88-3.13) compared to the same encounter as the index hospitalization. Our findings suggest an increased risk of TE among persons within 30 days of being diagnosed COVID-19, highlighting the need for careful consideration of the thrombotic risk among COVID-19 patients, particularly during the first month following diagnosis.

Association between mental health workforce supply and clusters of high and low rates of youth suicide: An Australian study using suicide mortality data from 2016 to 2020.

OBJECTIVE: To examine the association between mental health workforce supply and spatial clusters of high versus low incidence of youth suicide. METHODS: A cross-sectional analysis of spatial suicide clusters in young Australians (aged 10-25) from 2016 to 2020 was conducted using the scan statistic and suicide data from the National Coronial Information System. Mental health workforce was extracted from the 2020 National Health Workforce Dataset by local government areas. The Geographic Index of Relative Supply was used to estimate low and moderate-to-high mental health workforce supply for clusters characterised by a high and low incidence of suicide (termed suicide hotspots and coldspots, respectively). Univariate and multivariate logistic regression was used to determine the association between suicide clusters and a range of sociodemographic characteristics including mental health workforce supply. RESULTS: Eight suicide hotspots and two suicide coldspots were identified. The multivariate analysis showed low mental health workforce supply was associated with increased odds of being involved in a suicide hotspot (adjusted odds ratio = 8.29; 95% confidence interval = 5.20-13.60), followed by residential remoteness (adjusted odds ratio = 2.85; 95% confidence interval = 1.68-4.89), and illicit drug consumption (adjusted odds ratio = 1.97; 1.24-3.11). Both coldspot clusters occurred in areas with moderate-to-high mental health workforce supply. CONCLUSION: Findings highlight the potential risk and protective roles that mental health workforce supply may play in the spatial distributions of youth suicide clusters. These findings have important implications for the provision of postvention and the prevention of suicide clusters.

Efficacy of different surgical treatments for management of anal fistula: a network meta-analysis.

PURPOSE: Currently, the anal fistula treatment which optimises healing and preserves bowel continence remains unclear. The aim of our study was to compare the relative efficacy of different surgical treatments for AF through a network meta-analysis. METHODS: Systematic searches of MEDLINE, EMBASE and CENTRAL databases up to October 2022 identified randomised controlled trials (RCTs) comparing surgical treatments for anal fistulae. Fistulae were classified as simple (inter-sphincteric or low trans-sphincteric fistulae crossing less than 30% of the external anal sphincter (EAS)) and complex (high trans-sphincteric fistulae involving more than 30% of the EAS). Treatments evaluated in only one trial were excluded from the primary analyses to minimise bias. The primary outcomes were rates of success in achieving AF healing and bowel incontinence. RESULTS: Fifty-two RCTs were included. Of the 14 treatments considered, there were no significant differences regarding short-term (6 months or less postoperatively) and long-term (more than 6 months postoperatively) success rates between any of the treatments in patients with both simple and complex anal fistula. Ligation of the inter-sphincteric fistula tract (LIFT) ranked best for minimising bowel incontinence in simple (99.1% of comparisons; 3 trials, n = 70 patients) and complex anal fistula (86.2% of comparisons; 3 trials, n = 102 patients). CONCLUSIONS: There is insufficient evidence in existing RCTs to recommend one treatment over another regarding their short and long-term efficacy in successfully facilitating healing of both simple and complex anal fistulae. However, LIFT appears to be associated with the least impairment of bowel continence, irrespective of AF classification.

Abandonment of Human Immunodeficiency Virus Preexposure Prophylaxis Prescriptions at Retail Pharmacies-United States, 2019.

We analyzed a national pharmacy database to estimate the annual number of persons who abandoned preexposure prophylaxis (PrEP) prescriptions and assessed associated factors. About 9% of persons prescribed PrEP abandoned prescriptions in 2019; abandonment was associated with sex, age, insurance type, black race/ethnicity, and drug copayment amount.

Impact of Coronavirus Disease 2019 (COVID-19) on Human Immunodeficiency Virus (HIV) Pre-exposure Prophylaxis Prescriptions in the United States-A Time-Series Analysis.

BACKGROUND: Uptake of HIV pre-exposure prophylaxis (PrEP) has been increasing in the United States since its FDA approval in 2012; however, the COVID-19 pandemic may have affected this trend. Our objective was to assess the impact of COVID-19 on PrEP prescriptions in the United States. METHODS: We analyzed data from a national pharmacy database from January 2017 through March 2021 to fit an interrupted time-series model that predicted PrEP prescriptions and new PrEP users had the pandemic not occurred. Observed PrEP prescriptions and new users were compared with those predicted by the model. Main outcomes were weekly numbers of PrEP prescriptions and new PrEP users based on a previously developed algorithm. The impact of the COVID-19 pandemic was quantified by computing rate ratios and percentage decreases between the observed and predicted counts during 15/3/2020-31/3/2021. RESULTS: In the absence of the pandemic, our model predicted that there would have been 1 058 162 PrEP prescriptions during 15/3/2020-31/3/2021. We observed 825 239 PrEP prescriptions, a 22.0% reduction (95% CI: 19.1-24.8%) after the emergency declaration. The model predicted 167 720 new PrEP users during the same period; we observed 125 793 new PrEP users, a 25.0% reduction (95% CI: 20.9-28.9%). The COVID-19 impact was greater among younger persons and those with commercial insurance. The impact of the pandemic varied markedly across states. CONCLUSIONS: The COVID-19 pandemic disrupted an increasing trend in PrEP prescriptions in the United States, highlighting the need for innovative interventions to maintain access to HIV-prevention services during similar emergencies.

HIV Services and Outcomes During the COVID-19 Pandemic - United States, 2019-2021.

Increasing HIV testing, preexposure prophylaxis (PrEP), and antiretroviral therapy (ART) are pillars of the federal Ending the HIV Epidemic in the U.S. (EHE) initiative, with a goal of decreasing new HIV infections by 90% by 2030.* In response to the COVID-19 pandemic, a national emergency was declared in the United States on March 13, 2020, resulting in the closure of nonessential businesses and most nonemergency health care venues; stay-at-home orders also limited movement within communities (1). As unemployment increased during the pandemic (2), many persons lost employer-sponsored health insurance (3). HIV testing and PrEP prescriptions declined early in the COVID-19 pandemic (4-6); however, the full impact of the pandemic on use of HIV prevention and care services and HIV outcomes is not known. To assess changes in these measures during 2019-2021, quarterly data from two large U.S. commercial laboratories, the IQVIA Real World Data - Longitudinal Prescription Database (IQVIA),† and the National HIV Surveillance System (NHSS)§ were analyzed. During quarter 1 (Q1)¶ 2020, a total of 2,471,614 HIV tests were performed, 190,955 persons were prescribed PrEP, and 8,438 persons received a diagnosis of HIV infection. Decreases were observed during quarter 2 (Q2), with 1,682,578 HIV tests performed (32% decrease), 179,280 persons prescribed PrEP (6% decrease), and 6,228 persons receiving an HIV diagnosis (26% decrease). Partial rebounds were observed during quarter 3 (Q3), with 2,325,554 HIV tests performed, 184,320 persons prescribed PrEP, and 7,905 persons receiving an HIV diagnosis. The proportion of persons linked to HIV care, the number who were prescribed ART, and proportion with a suppressed viral load test (<200 copies of HIV RNA per mL) among those tested were stable during the study period. During public health emergencies, delivery of HIV services outside of traditional clinical settings or that use nonclinical delivery models are needed to facilitate access to HIV testing, ART, and PrEP, as well as to support adherence to ART and PrEP medications.