Designing an App to Support Measurement-Based Peer Supervision of Frontline Health Workers Delivering Brief Psychosocial Interventions in Texas: Multimethod Study.

BACKGROUND: The unmet need for mental health care affects millions of Americans. A growing body of evidence in implementation science supports the effectiveness of task sharing in the delivery of brief psychosocial interventions. The digitization of training and processes supporting supervision can rapidly scale up task-shared interventions and enable frontline health workers (FLWs) to learn, master, and deliver interventions with quality and support. OBJECTIVE: We aimed to assess the perceived feasibility and acceptability of a novel mobile and web app designed and adapted to support the supervision, training, and quality assurance of FLWs delivering brief psychosocial interventions. METHODS: We followed human-centered design principles to adapt a prototype app for FLWs delivering brief psychosocial interventions for depression, drawing from an app previously designed for use in rural India. Using a multimethod approach, we conducted focus group sessions comprising usability testing and group interviews with FLWs recruited from a large health system in Texas to assess the feasibility and acceptability of the app. The positive System Usability Scale was used to determine the app's overall usability. We also calculated the participants' likelihood of recommending the app to others using ratings of 0 to 10 from least to most likely (net promoter score). Focus group transcripts were coded and analyzed thematically, and recommendations were summarized across 4 key domains. RESULTS: A total of 18 FLWs varying in role and experience with client care participated in the study. Participants found the app to be usable, with an average System Usability Scale score of 72.5 (SD 18.1), consistent with the industry benchmark of 68. Participants' likelihood of recommending the app ranged from 5 to 10, yielding a net promoter score of 0, indicating medium acceptability. Overall impressions of the app from participants were positive. Most participants (15/18, 83%) found the app easy to access and navigate. The app was considered important to support FLWs in delivering high-quality mental health care services. Participants felt that the app could provide more structure to FLW training and supervision processes through the systematic collection and facilitation of performance-related feedback. Key concerns included privacy-related and time constraints regarding implementing a separate peer supervision mechanism that may add to FLWs' workloads. CONCLUSIONS: We designed, built, and tested a usable, functional mobile and web app prototype that supports FLW-delivered psychosocial interventions in the United States through a structured supervision mechanism and systematic collection and review of performance measures. The app has the potential to scale the work of FLWs tasked with delivering these interventions to the hardest-to-reach communities they serve. The results of this project will inform future work to evaluate the app's use and efficacy in real-world settings to support task-shared mental health programs across the United States.

Superficial and Bullous Neutrophilic Dermatoses: Sneddon-Wilkinson, IgA Pemphigus, and Bullous Lupus.

Sneddon-Wilkinson disease (SWD), IgA pemphigus, and bullous systemic lupus erythematosus (BSLE) are superficial and bullous neutrophilic dermatoses. They are all characterized by sterile neutrophilic infiltrate but differ in the level of skin affected and presence of autoantibodies. Both SWD and IgA pemphigus present with grouped flaccid pustules and have epidermal involvement; it is unclear whether they are distinct or exist on a spectrum of the same disease. IgA pemphigus is distinguished from SWD by positive direct immunofluorescence showing intercellular IgA deposition. BSLE presents with tense bullae, dermal neutrophilic infiltrate, and direct immunofluorescence showing linear IgG deposition along the dermal-epidermal junction.

Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems.

OBJECTIVE: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. METHODS: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription. RESULTS: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply). CONCLUSIONS: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.

Identification of virulence factors and antibiotic resistance in Salmonella enterica subsp. enterica serovar Javiana (FARPER-220) isolated from broiler chickens.

Genome sequencing of highly virulent Salmonella enterica subsp. enterica serovar Javiana strain FARPER-220 (ST-1674) isolated from broiler chickens in Peru revealed multiple virulence factors, antibiotic resistance genes, and invasion-related subcategories. The results provide insights into the potential importance of this strain in causing infections in various animals.

The Spanish language version of the TAPS tool: protocol for a validation and implementation study in primary care.

BACKGROUND: The TAPS Tool ("Tobacco, Alcohol, Prescription drug, and illicit Substance use") is a screening and brief assessment for detecting unhealthy substance use in healthcare settings that was developed by the National Institute on Drug Abuse Clinical Trials Network and validated in a multisite study. Our team developed a Spanish language version of the TAPS Tool that supports provider- and self-administration screening using a mobile/web-based platform, the TAPS Electronic Spanish Platform (TAPS-ESP). METHODS: This article describes the protocol and rationale for a study to validate the TAPS-ESP in a sample of Spanish-speaking primary care patients recruited from a network of community-based clinics in Texas (target N = 1,000). The TAPS-ESP will be validated against established substance use disorder diagnostic measures, alternative screening tools, and substance use biomarkers. The study will subsequently examine barriers and facilitators to screening with the TAPS-ESP from a provider workflow perspective using qualitative interviews with providers. DISCUSSION: Validating a Spanish language version of the TAPS Tool could expand access to evidence-based, linguistically accurate, and culturally relevant substance use screening and brief assessment for an underserved health disparity population. TRIAL REGISTRATION: The study was registered with www. CLINICALTRIALS: gov : NCT05476588, 07/22/2022.

Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems.

BACKGROUND: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. OBJECTIVE: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). DESIGN: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of  ≥ 50 during six consecutive months. PATIENTS: We identified 60,040 non-cancer patients with  ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). MAIN MEASURES: Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. KEY RESULTS: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality. CONCLUSIONS: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.

An action research partnership in an urban Texas county to explore barriers and opportunities for collaborative community health needs assessments.

Background: The Affordable Care Act mandated triennial community health needs assessments (CHNAs) for greater nonprofit hospital accountability in responding to community health needs. Over 10 years later, hospital spending on community benefits remains largely unchanged. While greater collaboration in CHNA implementation can increase hospital investment in community-based initiatives, nonprofit hospitals in conservative states are subject to policy, political, and economic factors that inhibit public health partnerships and magnify existing disparities in health care access. This participatory action research study explores the decision-making environment of collaborative CHNA implementation within a group of nonprofit hospitals in a north Texas urban county. Methods: In 2017 faculty from an urban anchor institution initiated an academic-community partnership with a coalition of nonprofit hospitals, public health departments, and academic institutions. An interdisciplinary research team engaged in multi-method document review and qualitative data collection to describe historical barriers for local CHNA processes and develop practical strategies for joint CHNA initiatives. Local CHNA documents were first reviewed through team-based content analysis and results applied to develop a qualitative study protocol. Key informants were recruited from county-based nonprofit hospitals, community-based nonprofit organizations, and public health systems. Seventeen senior- and mid-level professionals participated in semi-structured research interviews to describe their perspectives relating to CHNA-related planning and implementation decisions. Through iterative data collection and analysis, the research team explored CHNA-related knowledge, experiences, and processes. A constructivist lens was subsequently applied to examine historical barriers and future opportunities for local collaboration. Results: Findings reveal CHNA implementation is a multi-stage cyclical process in organizational environments with accountability to a wide range of public and private stakeholders. This promotes varied levels of inclusivity and conservatism in data collection and community benefit implementation. Decisions to collaborate are hindered by competing priorities, including compliance with existing guidelines, administrative simplicity, alignment with health care service delivery, and efficient resource use. Efforts to promote greater CHNA collaboration may be facilitated through intentional alignment with organizational priorities and clearly communicated benefits of participation for leaders in both public and private nonprofit health systems. Discussion: We consider implications for policymakers and health systems in restrictive political environments and advance a conceptual framework for greater CHNA collaboration.

Use of Telehealth Early and Late in the COVID-19 Public Health Emergency: Policy Implications for Improving Health Equity.

INTRODUCTION: Early in the COVID-19 pandemic, primary care adopted telehealth rapidly to preserve access. Although policy flexibilities persist, but with in-person access restored, insight regarding long-term policy reform is needed for equitable access, especially for underserved, low income, and rural populations. METHODS: We used electronic health record data to compare primary care telehealth use in practices serving primarily commercially insured patients versus clinics serving low-income uninsured patients, in March-June 2020 ("early COVID") and March-June 2022 ("late COVID"). RESULTS: Primary care visit mode differed significantly (P < .0001) between settings in both periods. In early COVID, video visits were most used in the commercially insured practices (54.50%), followed by office visits (32.76%); in the low-income, uninsured clinics, phone visits were most used (56.67%), followed by office visits (23.55%). In late COVID, 81.05% of visits to commercially insured practices and 92.04% to uninsured clinics were in-office; continuing telehealth use was primarily video. Smaller but significant (P ≤ .0001) differences in telehealth use by race/ethnicity were also observed, with Black and/or Hispanic patients less likely than White patients to use telehealth during both periods, after adjustment for other characteristics. CONCLUSIONS: Findings demonstrate the importance of both phone and video visits in preserving primary care access early in the pandemic. Telehealth use declined in late COVID, but still accounted for ∼20% of primary care visits in the commercially insured setting and less than 10% of visits in the community care clinics. Differences in telehealth use were largely by setting, reflecting income/insurance status, indicating disparities needing to be addressed.

Comorbid Conditions Associated with Alopecia Areata: A Systematic Review and Meta-analysis.

BACKGROUND: Alopecia areata (AA) is a complex autoimmune condition resulting in nonscarring hair loss. In recent years, many studies have provided new evidence on comorbid diseases present in patients with AA. However, some studies have conflicting results, and analyses conducting a comprehensive approach are lacking. OBJECTIVE: The aim of our study was to provide an updated systematic review and meta-analysis of medical comorbidities associated with AA. METHODS: We searched PubMed, Embase, and Web of Science for case-control, cross-sectional, and cohort studies investigating medical comorbidities in AA published from inception through 1 February 2023. RESULTS: We screened 3428 abstracts and titles and reviewed 345 full text articles for eligibility. Ultimately, 102 studies were analyzed, comprising 680,823 patients with AA and 72,011,041 healthy controls. Almost all included studies (100 of 102 studies) were of satisfactory to high quality (Newcastle-Ottawa scale score ≥ 4). Among patients with AA, comorbidities with the highest odds ratios (OR) compared with healthy controls and data available from more than one study included vitamin D deficiency (OR 10.13, 95% CI 4.24-24.20), systemic lupus erythematous (OR 5.53, 95% CI 3.31-9.23), vitiligo (OR 5.30, 95% CI 1.86-15.10), metabolic syndrome (OR 5.03, 95% CI 4.18-6.06), and Hashimoto's thyroiditis (OR 4.31, 95% CI 2.51-7.40). AA may be a protective factor for certain disorders, for which the AA group had lower odds compared with healthy controls, such as irritable bowel syndrome (OR 0.38, 95% CI 0.14-0.99) and colorectal cancer (OR 0.61, 95% CI 0.42-0.89). CONCLUSION: These findings corroborate and contextualize the risks across comorbidities for patients with AA. Further work should be done to identify the underlying pathophysiology and understand appropriate screening criteria.

SecretoMyc, a web-based database on mycobacteria secreted proteins and structure-based homology identification using bio-informatics tools.

To better understand the interaction between the host and the Mycobacterium tuberculosis pathogen, it is critical to identify its potential secreted proteins. While various experimental methods have been successful in identifying proteins under specific culture conditions, they have not provided a comprehensive characterisation of the secreted proteome. We utilized a combination of bioinformatics servers and in-house software to identify all potentially secreted proteins from six mycobacterial genomes through the three secretion systems: SEC, TAT, and T7SS. The results are presented in a database that can be crossed referenced to selected proteomics and transcriptomics studies (https://secretomyc.cbs.cnrs.fr). In addition, thanks to the recent availability of Alphafold models, we developed a tool in order to identify the structural homologues among the mycobacterial genomes.

A phase Ib trial of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer.

Chemoimmunotherapy with anti-programmed cell death 1/ligand 1 and cytotoxic chemotherapy is a promising therapeutic modality for women with triple-negative breast cancer, but questions remain regarding optimal chemotherapy backbone and biomarkers for patient selection. We report final outcomes from a phase Ib trial evaluating pembrolizumab (200 mg IV every 3 weeks) with either weekly paclitaxel (80 mg/m2 weekly) or flat-dose capecitabine (2000 mg orally twice daily for 7 days of every 14-day cycle) in the 1st/2nd line setting. The primary endpoint is safety (receipt of 2 cycles without grade III/IV toxicities requiring discontinuation or ≥21-day delays). The secondary endpoint is efficacy (week 12 objective response). Exploratory aims are to characterize immunologic effects of treatment over time, and to evaluate novel biomarkers. The trial demonstrates that both regimens meet the pre-specified safety endpoint (paclitaxel: 87%; capecitabine: 100%). Objective response rate is 29% for pembrolizumab/paclitaxel (n = 4/13, 95% CI: 10-61%) and 43% for pembrolizumab/capecitabine (n = 6/14, 95% CI: 18-71%). Partial responses are observed in two subjects with chemo-refractory metaplastic carcinoma (both in capecitabine arm). Both regimens are associated with significant peripheral leukocyte contraction over time. Response is associated with clinical PD-L1 score, non-receipt of prior chemotherapy, and the H&E stromal tumor-infiltrating lymphocyte score, but also by a novel 27 gene IO score and spatial biomarkers (lymphocyte spatial skewness). In conclusion, pembrolizumab with paclitaxel or capecitabine is safe and clinically active. Both regimens are lymphodepleting, highlighting the competing immunostimulatory versus lymphotoxic effects of cytotoxic chemotherapy. Further exploration of the IO score and spatial TIL biomarkers is warranted. The clinical trial registration is NCT02734290.

Assessing the differential item functioning of PHQ-9 items for diverse racial and ethnic adults with mental health and/or substance use disorder diagnoses: A retrospective cohort study.

BACKGROUND: Improving health equity in depression care and suicide screening requires that measures like the Patient Health Questionnaire 9 (PHQ-9) function similarly for diverse racial and ethnic groups. We evaluated PHQ-9 differential item functioning (DIF) between racial/ethnic groups in a retrospective cohort study of secondary electronic health record (EHR) data from eight healthcare systems. METHODS: The population (n = 755,156) included patients aged 18-64 with mental health and/or substance use disorder (SUD) diagnoses who had a PHQ-9 with no missing item data in the EHR for primary care or mental health visits between 1/1/2009-9/30/2017. We drew two random samples of 1000 from the following racial/ethnic groups originally recorded in EHRs (n = 14,000): Hispanic, and non-Hispanic White, Black, Asian, American Indian/Alaska Native, Native Hawaiian/Other Pacific Islander, multiracial. We assessed DIF using iterative hybrid ordinal logistic regression and item response theory with p < 0.01 and 1000 Monte Carlo simulations, where change in model R2 > 0.01 represented non-negligible (e.g., clinically meaningful) DIF. RESULTS: All PHQ-9 items displayed statistically significant, but negligible (e.g., clinically unmeaningful) DIF between compared groups. The negligible DIF varied between random samples, although six items showed negligible DIF between the same comparison groups in both random samples. LIMITATIONS: Our findings may not generalize to disaggregated racial/ethnic groups or persons without mental health and/or SUD diagnoses. CONCLUSIONS: We found the PHQ-9 had clinically unmeaningful cross-cultural DIF for adult patients with mental health and/or SUD diagnoses. Future research could disaggregate race/ethnicity to discern if within-group identification impacts PHQ-9 DIF.

A Multiparameter Molecular Classifier to Predict Response to Neoadjuvant Lapatinib plus Trastuzumab without Chemotherapy in HER2+ Breast Cancer.

PURPOSE: Clinical trials reported 25% to 30% pathologic complete response (pCR) rates in HER2+ patients with breast cancer treated with anti-HER2 therapies without chemotherapy. We hypothesize that a multiparameter classifier can identify patients with HER2-"addicted" tumors who may benefit from a chemotherapy-sparing strategy. EXPERIMENTAL DESIGN: Baseline HER2+ breast cancer specimens from the TBCRC023 and PAMELA trials, which included neoadjuvant treatment with lapatinib and trastuzumab, were used. In the case of estrogen receptor-positive (ER+) tumors, endocrine therapy was also administered. HER2 protein and gene amplification (ratio), HER2-enriched (HER2-E), and PIK3CA mutation status were assessed by dual gene protein assay (GPA), research-based PAM50, and targeted DNA-sequencing. GPA cutoffs and classifier of response were constructed in TBCRC023 using a decision tree algorithm, then validated in PAMELA. RESULTS: In TBCRC023, 72 breast cancer specimens had GPA, PAM50, and sequencing data, of which 15 had pCR. Recursive partitioning identified cutoffs of HER2 ratio ≥ 4.6 and %3+ IHC staining ≥ 97.5%. With PAM50 and sequencing data, the model added HER2-E and PIK3CA wild-type (WT). For clinical implementation, the classifier was locked as HER2 ratio ≥ 4.5, %3+ IHC staining ≥ 90%, and PIK3CA-WT and HER2-E, yielding 55% and 94% positive (PPV) and negative (NPV) predictive values, respectively. Independent validation using 44 PAMELA cases with all three biomarkers yielded 47% PPV and 82% NPV. Importantly, our classifier's high NPV signifies its strength in accurately identifying patients who may not be good candidates for treatment deescalation. CONCLUSIONS: Our multiparameter classifier differentially identifies patients who may benefit from HER2-targeted therapy alone from those who need chemotherapy and predicts pCR to anti-HER2 therapy alone comparable with chemotherapy plus dual anti-HER2 therapy in unselected patients.

Clinical Application of Artificial Intelligence for Non-melanoma Skin Cancer.

OPINION STATEMENT: The development and implementation of artificial intelligence is beginning to impact the care of dermatology patients. Although the clinical application of AI in dermatology to date has largely focused on melanoma, the prevalence of non-melanoma skin cancers, including basal cell and squamous cell cancers, is a critical application for this technology. The need for a timely diagnosis and treatment of skin cancers makes finding more time efficient diagnostic methods a top priority, and AI may help improve dermatologists' performance and facilitate care in the absence of dermatology expertise. Beyond diagnosis, for more severe cases, AI may help in predicting therapeutic response and replacing or reinforcing input from multidisciplinary teams. AI may also help in designing novel therapeutics. Despite this potential, enthusiasm in AI must be tempered by realistic expectations regarding performance. AI can only perform as well as the information that is used to train it, and development and implementation of new guidelines to improve transparency around training and performance of algorithms is key for promoting confidence in new systems. Special emphasis should be placed on the role of dermatologists in curating high-quality datasets that reflect a range of skin tones, diagnoses, and clinical scenarios. For ultimate success, dermatologists must not be wary of AI as a potential replacement for their expertise, but as a new tool to complement their diagnostic acumen and extend patient care.

The risks of attrition bias in longitudinal surveys of the impact of COVID-19.

As the COVID-19 pandemic continues, interest in mental health impacts is shifting from short-term to long-term outcomes. As part of a longitudinal online survey study examining mental health impacts of the pandemic, we assessed the risk of attrition bias related to a history of depression-a condition research shows can increase challenges of recruitment and retention. Among 5023 participants who completed the baseline survey, significantly more reporting a history of depression were lost to follow-up: baseline to 3 months: 497/760 (65.4%) vs 2228/4263 (52.3%), P < 0.001; 3 to 6 months: 179/263 (68.1%) vs 1183/2035 (58.1%), P = 0.002. Participants reporting a history of depression also had greater adjusted odds of a Patient Health Questionnaire-8 score ≥10 (odds ratio [OR] = 3.97, 95% confidence interval [CI] 3.27, 4.84), Generalized Anxiety Disorder-7 score ≥10 (OR = 3.77, 95% CI 3.07, 4.62), and Posttraumatic Diagnostic Scale for DSM V score ≥ 28 (OR = 7.17, 95% CI 4.67, 11.00) at baseline, indicating a need to account for attrition bias when examining these outcomes. Similar considerations likely apply to other longitudinal survey studies and are important to address to ensure accurate evidence is available to support policy decisions regarding resource allocation and funding.

Dysregulated Amino Acid Sensing Drives Colorectal Cancer Growth and Metabolic Reprogramming Leading to Chemoresistance.

BACKGROUND & AIMS: Colorectal cancer (CRC) is a devastating disease that is highly modulated by dietary nutrients. Mechanistic target of rapamycin complex 1 (mTORC1) contributes to tumor growth and limits therapy responses. Growth factor signaling is a major mechanism of mTORC1 activation. However, compensatory pathways exist to sustain mTORC1 activity after therapies that target oncogenic growth factor signaling. Amino acids potently activate mTORC1 via amino acid-sensing GTPase activity towards Rags (GATOR). The role of amino acid-sensing pathways in CRC is unclear. METHODS: Human colon cancer cell lines, preclinical intestinal epithelial-specific GATOR1 and GATOR2 knockout mice subjected to colitis-induced or sporadic colon tumor models, small interfering RNA screening targeting regulators of mTORC1, and tissues of patients with CRC were used to assess the role of amino acid sensing in CRC. RESULTS: We identified loss-of-function mutations of the GATOR1 complex in CRC and showed that altered expression of amino acid-sensing pathways predicted poor patient outcomes. We showed that dysregulated amino acid-sensing induced mTORC1 activation drives colon tumorigenesis in multiple mouse models. We found amino acid-sensing pathways to be essential in the cellular reprogramming of chemoresistance, and chemotherapeutic-resistant patients with colon cancer exhibited de-regulated amino acid sensing. Limiting amino acids in in vitro and in vivo models (low-protein diet) reverted drug resistance, revealing a metabolic vulnerability. CONCLUSIONS: Our findings suggest a critical role for amino acid-sensing pathways in driving CRC and highlight the translational implications of dietary protein intervention in CRC.