Importance Integrated models to deliver HIV preexposure prophylaxis (PrEP) and medication for opioid use disorder (MOUD) for people who inject drugs are needed. Objective To determine whether integrated PrEP and MOUD services delivered on a mobile unit with manualized peer navigation improved PrEP and MOUD use compared with peer navigation to existing community-based services. Design, Setting, and Participants This 2-group, open-label, randomized clinical trial was conducted between May 2021 and September 2024 in Houston, Texas; Los Angeles, California; New York, New York; Philadelphia, Pennsylvania; and Washington, DC, among people aged 18 years and older currently injecting drugs, without HIV, with OUD, and not taking MOUD but willing to consider MOUD. Interventions The intervention arm (n = 203) consisted of 26 weeks of manualized peer navigation plus integrated PrEP, MOUD, and limited clinical and supportive services delivered on a mobile unit. The active control arm (n = 206) consisted of 26 weeks of manualized peer navigation to available community-based PrEP, MOUD, harm reduction, and supportive services. Main Outcomes and Measures The co-primary outcomes were PrEP use and MOUD use at 26 weeks. Secondary outcomes included PrEP and MOUD use at 52 weeks, HIV incidence, and all-cause mortality. Results Of 842 people who inject drugs who were screened, 409 were randomized: 134 (32.8%) female; 146 (11.2%) aged 30 years and younger vs older than 30 years. At the 26-week visit, the intervention and active control arms were similar for confirmed PrEP use: 11/203 (5.4%) vs 6/206 (2.9%) and MOUD use: 30/203 (14.8%) vs 22/206 (10.7%), respectively. At the 52-week visit, intervention and active control arms were similar for confirmed PrEP and MOUD: 4/203 (2.0%) vs 4/206 (1.9%) and MOUD use: 27/203 (13.3%) vs 29/206 (14.1%). One HIV acquisition occurred in the intervention and 2 in the active control arms; HIV incidence rate of 0.9 per 100 person-years (95% CI, 0.2-2.6). Four deaths were confirmed in the intervention arm and 13 in the active control arm (hazard ratio, 0.29; 95% CI, 0.1-0.9; P = .03). Conclusions and Relevance In this randomized clinical trial, mobile delivery of integrated HIV prevention, addiction, and navigation services did not improve primary outcomes beyond peer navigation alone. The significantly lower all-cause death rate at 52 weeks in the intervention arm bears replication for delivering integrated PrEP and MOUD services to people who inject drugs. Trial Registration ClinicalTrials.gov Identifier: NCT04804072.
Importance Schizophrenia (SZ) is associated with transcriptome alterations in the dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC), key regions in a distributed network that mediates cognitive functions impaired in the illness. The subcortical dorsal claustrum (dCLA) is structurally densely interconnected with the ACC and dlPFC and functionally coactivated with these regions during certain cognitive tasks. Objective To identify SZ-associated transcriptome alterations in the dCLA. Design, Settings, and Participants This case-control study used RNA sequencing data for dCLA homogenates from postmortem human brain of individuals with SZ and unaffected comparison (UC) individuals. Brain donations were obtained from the Allegheny County Office of the Medical Examiner, Pittsburgh, Pennsylvania. Data analysis was performed from January 12, 2024, through May 22, 2026. Exposure Schizophrenia. Main Outcomes and Measures Gene expression differences in the dCLA between individuals with SZ and UC individuals were the primary outcome. Secondary outcomes included gene set enrichment in the dCLA and comparisons of gene expression differences across the dCLA, ACC, dlPFC, putamen, and caudate between individuals with SZ and UC individuals, including rank-rank hypergeometric overlap (RRHO) analyses. Results In the final dCLA samples from 96 individuals, including 47 individuals with SZ (10 [21.3%] female; mean [SD] age, 49.0 [13.3] years) and 49 UC individuals (10 [20.4%] female; mean [SD] age, 49.9 [14.2] years), there were 1717 differentially expressed genes (DEGs) between individuals with SZ and UC individuals, with 1149 (66.9%) of the DEGs upregulated in SZ. Many upregulated DEGs were associated with immune response or transcription regulation, and many downregulated DEGs were associated with mitochondrial activity or oxidative phosphorylation. In comparisons between individuals with SZ and UC individuals with data from the dCLA, ACC, and dlPFC, the number of DEGs detected was 4 to 12 times greater in the dCLA (1242 DEGs) than in the ACC (289 DEGs) or dlPFC (102 DEGs). However, threshold-free RRHO analyses revealed a conserved pattern of SZ-associated gene expression alterations across all 3 regions. In comparison, concordance of gene expression alterations was lower with the putamen and caudate, subcortical regions with weaker connections to the dCLA. Conclusions and Relevance The results of this case-control study suggest that the dCLA is a prominent site of molecular alterations in SZ. These alterations might reflect the dCLA’s extensive connectivity with affected cortical regions, distinctive intrinsic circuitry, and/or enrichment of vulnerable cell types.
This Viewpoint discusses US regulations about methadone treatment for opioid use disorder in the context of the Modernizing Opioid Treatment Access Act and how it could change the way methadone is dispensed if it is passed.
This article outlines a strategy of pursuing “prediction without hype” and judging AI by whether it is trustworthy, transportable, and useful at the point of care.
