Nevin Manimala

JAMA Netw Open. 2024 Oct 1;7(10):e2437233. doi: 10.1001/jamanetworkopen.2024.37233.

ABSTRACT

IMPORTANCE: Overdose is the leading cause of death among people experiencing homelessness (PEH), but engagement in medication treatment is low in this population. Shelter-based buprenorphine may be a strategy for increasing initiation and retention on lifesaving medications.

OBJECTIVE: To estimate clinical outcomes and conduct an economic analysis of statewide shelter-based opioid treatment in Massachusetts.

DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation study in Massachusetts used a cohort state-transition simulation model. Two cohorts were modeled starting in 2013, including (1) a closed cohort of a fixed population of PEH with history of high-risk opioid use over their lifetimes and (2) an open cohort in which membership could change over time, allowing assessment of population-level trends over a 10-year period. Data analysis occurred from January 2023 to April 2024.

EXPOSURES: Model exposures included (1) no shelter-based buprenorphine (status quo) and (2) offering buprenorphine in shelters statewide.

MAIN OUTCOMES AND MEASURES: Outcomes included overdose deaths, quality-adjusted life-years (QALYs) gained, and health care and modified societal perspective costs. Sensitivity analyses were conducted on key parameters.

RESULTS: In the closed cohort analysis of 13 800 PEH (mean [SD] age, 40.4 [13.1] years; 8749 male [63.4%]), shelter-based buprenorphine was associated with an additional 65.4 person-weeks taking buprenorphine over an individual’s lifetime compared with status quo. Shelter-based buprenorphine was cost saving when compared with the status quo, with a discounted lifetime cost savings from the health sector perspective of $1300 per person, and 0.2 additional discounted QALYs per person and 0.9 additional life-years per person. In the population-level simulation, 254 overdose deaths were averted over the 10-year period with the shelter-based buprenorphine strategy compared with the status quo (a 9.2% reduction of overdose deaths among PEH in Massachusetts). Overdose-related and other health care utilization undiscounted costs decreased by $3.0 million and $66.4 million, respectively. Shelter-based opioid treatment generated $44.7 million in additional medication and clinical costs, but saved $69.4 million in overdose and other health costs.

CONCLUSIONS AND RELEVANCE: In this economic evaluation of clinical and economic outcomes among PEH, shelter-based buprenorphine was associated with fewer overdose deaths and was cost saving. These findings suggest that broad rollout of shelter-based buprenorphine may be an important tool in addressing the overdose crisis.

PMID:39412807 | DOI:10.1001/jamanetworkopen.2024.37233

JAMA Netw Open. 2024 Oct 1;7(10):e2439080. doi: 10.1001/jamanetworkopen.2024.39080.

ABSTRACT

IMPORTANCE: The China National Drug Administration (NMPA) established the breakthrough therapy designation (BTD) in 2020 to encourage the accelerated development of drugs for the prevention and treatment of diseases that are life-threatening. However, the differences between BTD and non-BTD cancer drugs regarding clinical benefit, regulatory approval, and price are unclear.

OBJECTIVES: To compare BTD and non-BTD cancer drugs in clinical benefit (defined as efficacy and safety), novelty, time to approval, and average monthly treatment price.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzes the original indication of BTD and non-BTD novel cancer drugs approved by the NMPA between July 8, 2020, and July 8, 2024. Data on efficacy, safety, regulatory approval, and price of cancer drugs were extracted from pivotal clinical trials based on review reports published by the NMPA, peer-reviewed articles or meeting reports, and winning bid prices for cancer drugs in the Chinese provincial-level centralized procurement process.

MAIN OUTCOMES AND MEASURES: The main outcome was the efficacy and safety associated with BTD vs non-BTD cancer drugs, including progression-free survival (PFS), response rate (RR), duration of response, serious adverse events, grade 3 or higher adverse events, and treatment-related deaths. In addition, the time to approval, novelty, and initial and latest average monthly treatment prices were evaluated, as well as the average annual reduction rate (AARR; the sum of the reduction rates divided by the number of years for the monthly treatment price) for these cancer drugs.

RESULTS: Between July 2020 and July 2024, 18 BTD (36%) and 32 non-BTD (64%) cancer drugs were approved by the NMPA. The median (IQR) clinical development time for BTD drugs was significantly shorter than for non-BTD drugs (5.6 [95% CI, 4.3-7.3] vs 6.6 [95% CI, 6.0-8.5] years; P = .02). No significant differences were observed in PFS (HR, 0.44 [95% CI, 0.38-0.52] vs HR, 0.51 [95% CI, 0.40-0.65]; P = .20), PFS gained (median [IQR], 5.4 [3.9-7.0] vs 2.7 [2.6-5.9] months; P = .77), RR (58% [95% CI, 45%-74%] vs 59% [95% CI, 51%-69%]; P = .85), and duration of response (median [IQR], 18.0 [15.0-21.6] vs 11.1 [7.4-17.4] months; P = .09) between BTD and non-BTD drugs. The rates of serious adverse events (37% [95% CI, 26%-52%] vs 32% [95% CI, 27%-36%]; P = .45), adverse events grade 3 or higher (64% [95% CI, 53%-77%] vs 55% [95% CI, 45%-68%]; P = .31), and treatment-related deaths (2% [95% CI, 1%-4%] vs 1% [95% CI, 1%-2%]; P = .10) were similar between BTD and non-BTD drugs. BTD drugs are more likely to be first-in-class drugs (5 of 18 [28%] vs 1 of 32 [3%]; P = .02). Differences in the median (IQR) initial ($5665 [$3542-$9321] vs $3361 [$2604-$5474]; P = .06) and latest ($5665 [$1553-$9321] vs $2145 [$1318-$4276]; P = .18) average monthly treatment prices for BTD drugs and non-BTD drugs were not significant. The median (IQR) AARRs for BTD drugs and non-BTD drugs were 15.2% (0%-46.9%) and 19.8% (1.0%-42.9%), respectively.

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that BTD has facilitated faster time to market for cancer drugs and improved novelty, but the price of treatment is relatively higher. There was no significant difference on comparative efficacy and safety.

PMID:39412805 | DOI:10.1001/jamanetworkopen.2024.39080

JAMA Netw Open. 2024 Oct 1;7(10):e2439629. doi: 10.1001/jamanetworkopen.2024.39629.

ABSTRACT

IMPORTANCE: In the US, there are more than 1.5 million adults living with congenital heart disease (CHD). The Congenital Heart Initiative (CHI) is a digital, online, patient-empowered registry that was created to advance multicenter research and improve clinical care by gathering patient-reported outcomes (PROs) in adults with CHD.

OBJECTIVE: To report the initial findings of the PROs for adults with CHD from the first 3 years of the CHI.

DESIGN, SETTING, AND PARTICIPANTS: The CHI was launched nationally on December 7, 2020, as an observational cohort (survey) study. Data were collected virtually through December 31, 2023, and stored on Health Insurance Portability and Accountability Act-compliant cloud-based servers with restricted access. Adults with CHD were recruited through email, social media, general advertising through advocacy organizations, and targeted outreach (telephone and in-clinic recruitment) by clinical centers.

MAIN OUTCOMES AND MEASURES: Demographics and validated survey tools on quality of life, mental health, physical activity, and health care utilization were collected at baseline and every 4 months. Descriptive statistics were used to understand the associations between various factors, including the complexity of heart defects, physical activity levels, mental health comorbidities, and socioeconomic and health care access variables. All categorical variables were analyzed using χ2 or Fischer exact test as appropriate.

RESULTS: By December 31, 2023, the CHI had enrolled 4558 participants (2530 female [56%]) with a mean (SD) age of 38.5 (13.9) years, representing all 50 states. Approximately 88% of participants (3998 participants) completed at least 1 electronic visit as of December 31, 2023. The most prevalent CHD anatomy included tetralogy of Fallot (883 participants [22%]), transposition of great arteries (452 participants [11%]), and coarctation of the aorta (429 participants [11%]). Approximately 88% of participants (3998 participants) reported at least 1 comorbidity, with arrhythmia (1300 participants [33%]) as the most common cardiac comorbidity and mood disorder (1326 participants [35%]) as the most common noncardiac comorbidity. Among female participants, 45% (1147 participants) reported having had a pregnancy, with 38% (967 participants) resulting in biological children. Participants with complex CHD were less likely than those with moderate CHD to meet recommended physical activity guidelines (χ22 = 15.9; n = 3320; P < .001), a factor that was more pronounced among female participants. Overall health-related quality of life was rated as good or better by 84% of participants who completed the quality of life PROs (2882 participants), with no difference by CHD complexity.

CONCLUSIONS AND RELEVANCE: In this cohort study of adults living with CHD, many patients reported mood disorders, but most reported good health-related quality of life. The CHI, the largest registry of adults with CHD, is poised to facilitate multicenter research with the goal of improving clinical outcomes for all adults with CHD.

PMID:39412804 | DOI:10.1001/jamanetworkopen.2024.39629

JAMA Netw Open. 2024 Oct 1;7(10):e2439727. doi: 10.1001/jamanetworkopen.2024.39727.

ABSTRACT

IMPORTANCE: Investigating racial and ethnic discrimination in medical education is crucial for addressing disparities and fostering an inclusive environment.

OBJECTIVE: To assess how racial and ethnic discrimination in medical school is associated with personal and professional identity formation (PPIF) by race and ethnicity.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study used deidentified data on 37 610 medical students who matriculated in 2014 or 2015 and took the Association of American Medical Colleges Graduation Questionnaire (GQ) between 2016 and 2020. Statistical analysis was performed from September 1 to November 20, 2023.

EXPOSURES: Experiences of racial and ethnic discrimination were assessed through responses to 3 GQ questions about denial of opportunities, offensive remarks or names, and lower evaluations or grades due to race or ethnicity.

MAIN OUTCOMES AND MEASURES: Personal and professional development were measured as 2 separate outcomes using 2 GQ statements rated on a 5-point Likert scale (where 1 indicated strongly disagree and 5 indicated strongly agree): “My medical school has done a good job fostering and nurturing my development as a person” and “My medical school has done a good job fostering and nurturing my development as a physician.” Variables of personal and professional development were both dichotomized.

RESULTS: Of 37 610 medical students, 18 200 (48.4%) were female, and 19 410 (51.6%) were male; 2458 (6.5%) were African American or Black, 7801 (20.7%) were Asian, 2430 (6.5%) were Hispanic, 21 380 (56.9%) were White, 2404 (6.4%) were multiracial, and 1137 (3%) were other race or ethnicity. Most respondents attested that their medical school fostered their personal (27 272 [72.5%]) and professional (34 560 [91.9%]) development. African American or Black students reported the lowest rates of personal (1603 of 2458 [65.2%]) and professional (2182 of 2458 [88.8%]) development, and experienced lower likelihoods of personal (adjusted risk ratio [ARR], 0.89 [95% CI, 0.86-0.93]) and professional (ARR, 0.95 [95% CI, 0.94-0.97]) development than White students. Racial discrimination was inversely associated with development, with the highest PPIF rates among those never experiencing discrimination (personal, 25 089 of 33 508 [74.9%]; and professional, 31 257 of 33 508 [93.3%]). Those experiencing isolated discrimination (personal: ARR, 0.83 [95% CI, 0.80-0.87]; professional: ARR, 0.92 [95% CI, 0.91-0.95]) and recurrent discrimination (personal: ARR, 0.63 [95% CI, 0.60-0.66]; professional: ARR, 0.82 [95% CI, 0.80-0.84]) had relatively lower likelihoods of PPIF. African American or Black students experienced the highest rate of recurrent discrimination (543 of 2458 [22.1%]). No significant PPIF risk differences were found for other racial and ethnic groups underrepresented in medicine without discrimination compared with White students without discrimination, but all groups with recurrent discrimination had relatively lower PPIF risk.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US medical students, racial and ethnic discrimination was associated with lower PPIF across all racial and ethnic groups compared with White students without such experiences. African American or Black students disproportionately faced this discrimination. Systemic changes in medical education are needed to combat discrimination and ensure equity in holistic student development.

PMID:39412803 | DOI:10.1001/jamanetworkopen.2024.39727

JAMA Netw Open. 2024 Oct 1;7(10):e2439932. doi: 10.1001/jamanetworkopen.2024.39932.

ABSTRACT

IMPORTANCE: Publishing in health professions education (HPE) journals is an integral component of academic discourse and career progression. Research in this field is shifting to an open access (OA) publishing model.

OBJECTIVE: To identify the characteristics and publishing models of HPE journals and explore potential associations between publication costs and journal metrics.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted between September 20, 2023, and February 14, 2024, using the World Bank purchasing power parity (PPP) index to analyze relative costs of article processing charges (APCs). Data on journal characteristics, impact metrics, APCs, and waiver or discount were extracted from the National Library of Medicine, Scimago, Scopus, journal websites, and email correspondence with editorial staff of journals. All HPE journals indexed in PubMed, written in or translated into English, and with HPE as a core component of their mission were included in the analysis.

MAIN OUTCOMES AND MEASURES: Two-year impact factor, H-index, cite score, Scientific Journal Ranking, and APC.

RESULTS: Among the 51 journals included, 27 (53%) adopted OA-only and 24 (47%) adopted hybrid publishing models. The median (IQR) APC for all journals was $2820.00 ($928.00-$3300.00). Associations were observed between impact factor and APC (β coefficient, $386.84; 95% CI, $226.84-$546.84; P < .001) and between cite score and APC (β coefficient, $282.40; 95% CI, $148.12-$416.61; P < .001). Of 20 journal websites with information regarding fee waivers or discounts, 7 journals (35%) confirmed fee waiver or discount. The PPP index analysis of the top 39 countries publishing HPE research showed that the financial burden of meeting the median APC for publication was 1.94 to 10.26 times higher for authors from lower-income countries than for authors from the US.

CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that adoption by HPE journals of an OA publishing model was high but access to APC waivers or discounts was limited. These factors create barriers to equitable OA practices, necessitating concerted efforts, such as increasing transparency of publishing costs, implementing economic impact analysis, expanding waivers to eligible authors, and applying holistic impact factor scoring.

PMID:39412801 | DOI:10.1001/jamanetworkopen.2024.39932

JAMA Netw Open. 2024 Oct 1;7(10):e2439939. doi: 10.1001/jamanetworkopen.2024.39939.

ABSTRACT

IMPORTANCE: Pregnant individuals who repeatedly use emergency care during pregnancy represent a population who could be disproportionately vulnerable to harm, including severe maternal morbidity (SMM).

OBJECTIVE: To explore patterns of unscheduled care visits during pregnancy and ascertain its association with SMM at the time of birth.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from a statewide database that linked hospital records to births and fetal deaths occurring between October 1, 2002, and March 31, 2020, in Massachusetts. Pregnant individuals experiencing births or fetal deaths during the study period were included. Data analysis was conducted from June 2022 to September 2024.

EXPOSURE: The exposure was 4 or more cases of emergency use, defined as either an emergency department visit or observational stay during pregnancy not resulting in hospital admission. Pregnancy episode was ascertained by subtracting the gestational age at birth from the date of birth.

MAIN OUTCOMES AND MEASURES: The outcome of interest was the odds ratio (OR) for SMM at the time of birth. The algorithm includes 20 conditions or procedures (excluding transfusion) identified through International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes across the study period.

RESULTS: A total of 774 092 pregnant individuals (mean [SD] age, 31.2 [5.8] years; 16.8% Hispanic, 9.3% non-Hispanic Asian or Pacific Islander, 9.5% non-Hispanic Black, 63.1% non-Hispanic White) with emergency care visits during the pregnancy were included; 31.3% of these individuals had at least 1 visit. Overall, 18.1% had 1 visit and 3.3% had 4 or more visits. Four or more unscheduled visits were common among those younger than age 25 years (8.7%), with Hispanic (5.7%) or non-Hispanic Black (4.9%) race and ethnicity, with public insurance (6.5%), or with a comorbidity (19.0%) or an opioid use-related hospitalization (26.8%) in the year prior to pregnancy. Of those with 4 or more unscheduled visits, 43.8% visited more than 1 hospital during pregnancy. In a multivariable analysis of the likelihood of SMM, those with 4 or more unscheduled visits had an adjusted OR of 1.46 (95% CI, 1.29-1.66) compared with those with 0 visits.

CONCLUSIONS AND RELEVANCE: This cohort study found that high emergency care use during pregnancy was associated with an increased risk for SMM. With a significant proportion of those with frequent unscheduled visits also using multiple hospitals, solutions that are community-based and integrated across health systems may be most beneficial.

PMID:39412800 | DOI:10.1001/jamanetworkopen.2024.39939

JAMA Cardiol. 2024 Oct 16. doi: 10.1001/jamacardio.2024.3314. Online ahead of print.

ABSTRACT

IMPORTANCE: The differences between the use of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) in the long term are unknown.

OBJECTIVE: To compare long-term outcomes of iFR- and FFR-based strategies to guide revascularization.

DESIGN, SETTING, AND PARTICIPANTS: The DEFINE-FLAIR multicenter study randomized patients with coronary artery disease to use either iFR or FFR as a pressure index to guide revascularization. Patients from 5 continents with coronary artery disease and angiographically intermediate severity stenoses who underwent hemodynamic interrogation with pressure wires were included. These data were analyzed from March, 13, 2014, through April, 27, 2021.

MAIN OUTCOME MEASURES: Five-year major adverse cardiac events (MACE) (a composite of all-cause death, nonfatal myocardial infarction, and unplanned revascularization), as well as the individual components of the combined end point.

RESULTS: At 5 years of follow-up, no significant differences were found between the iFR (mean age [SD], 65.5 [10.8] years; 962 male [77.5%]) and FFR (mean age [SD], 65.2 [10.6] years; 929 male [74.3%]) groups in terms of MACE (21.1% vs 18.4%, respectively; hazard ratio [HR], 1.18; 95% CI, 0.99-1.42; P = .06). While all-cause death was higher among patients randomized to iFR, it was not driven by myocardial infarction (6.3% vs 6.2% in the FFR study arm; HR, 1.01; 95% CI, 0.74-1.38; P = .94) or unplanned revascularization (11.9% vs 12.2% in the FFR group; HR, 0.98; 95% CI, 0.78-1.23; P = .87). Furthermore, patients in whom revascularization was deferred on the basis of iFR or FFR had similar MACE in both study arms (17.9% in the iFR group vs 17.5% in the FFR group; HR, 1.03; 95% CI, 0.79-1.35; P = .80) with similar rates of the components of MACE, including all-cause death. On the contrary, in patients who underwent revascularization after physiologic interrogation, the incidence of MACE was higher in the iFR group (24.6%) compared with the FFR group (19.2%) (HR, 1.36; 95% CI, 1.07-1.72; P = .01).

CONCLUSIONS AND RELEVANCE: At 5-year follow up, an iFR based-strategy was not statistically different than an FFR strategy to guide revascularization in terms of MACE, nonfatal myocardial infarction, and unplanned revascularization.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02053038.

PMID:39412778 | DOI:10.1001/jamacardio.2024.3314

JAMA Psychiatry. 2024 Oct 16. doi: 10.1001/jamapsychiatry.2024.3194. Online ahead of print.

ABSTRACT

IMPORTANCE: In the neurotypical brain, regions develop in coordinated patterns, providing a fundamental scaffold for brain function and behavior. Whether altered patterns contribute to clinical profiles in neurodevelopmental conditions, including autism, remains unclear.

OBJECTIVES: To examine if, in autism, brain regions develop differently in relation to each other and how these differences are associated with molecular/genomic mechanisms and symptomatology.

DESIGN, SETTING, AND PARTICIPANTS: This study was an analysis of one the largest deep-phenotyped, case-control, longitudinal (2 assessments separated by approximately 12-24 months) structural magnetic resonance imaging and cognitive-behavioral autism datasets (EU-AIMS Longitudinal European Autism Project [LEAP]; study dates, February 2014-November 2017) and an out-of-sample validation in the Brain Development Imaging Study (BrainMapASD) independent cohort. Analyses were performed during the 2022 to 2023 period. This multicenter study included autistic and neurotypical children, adolescents, and adults. Autistic participants were included if they had an existing autism diagnosis (DSM-IV/International Statistical Classification of Diseases and Related Health Problems, Tenth Revision or DSM-5 criteria). Autistic participants with co-occurring psychiatric conditions (except psychosis/bipolar disorder) and those taking regular medications were included.

EXPOSURES: Neuroanatomy of neurotypical and autistic participants.

MAIN OUTCOMES AND MEASURES: Intraindividual changes in surface area and cortical thickness over time, analyzed via surface-based morphometrics.

RESULTS: A total of 386 individuals in the LEAP cohort (6-31 years at first visit; 214 autistic individuals, mean [SD] age, 17.3 [5.4] years; 154 male [72.0%] and 172 neurotypical individuals, mean [SD] age, 16.35 [5.7] years; 108 male [62.8%]) and 146 individuals in the BrainMapASD cohort (11-18 years at first visit; 49 autistic individuals, mean [SD] age, 14.31 [2.4] years; 42 male [85.7%] and 97 neurotypical individuals, mean [SD] age, 14.10 [2.5] years; 58 male [59.8%]). Maturational between-group differences in cortical thickness and surface area were established that were mostly driven by sensorimotor regions (eg, across features, absolute loadings for early visual cortex ranged from 0.07 to 0.11, whereas absolute loadings for dorsolateral prefrontal cortex ranged from 0.005 to 0.06). Neurodevelopmental differences were transcriptomically enriched for genes expressed in several cell types and during various neurodevelopmental stages, and autism candidate genes (eg, downregulated genes in autism, including those regulating synaptic transmission; enrichment odds ratio =3.7; P =2.6 × -10). A more neurotypical, less autismlike maturational profile was associated with fewer social difficulties and more typical sensory processing (false discovery rate P <.05; Pearson r ≥0.17). Results were replicated in the independently collected BrainMapASD cohort.

CONCLUSIONS AND RELEVANCE: Results of this case-control study suggest that the coordinated development of brain regions was altered in autism, involved a complex interplay of temporally sensitive molecular mechanisms, and may be associated with both lower-order (eg, sensory) and higher-order (eg, social) clinical features of autism. Thus, examining maturational patterns may provide an analytic framework to study the neurobiological origins of clinical profiles in neurodevelopmental/mental health conditions.

PMID:39412777 | DOI:10.1001/jamapsychiatry.2024.3194

JAMA. 2024 Oct 16. doi: 10.1001/jama.2024.18575. Online ahead of print.

NO ABSTRACT

PMID:39412770 | DOI:10.1001/jama.2024.18575

J Nephrol. 2024 Oct 16. doi: 10.1007/s40620-024-02099-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hormone replacement therapy (HRT) is recommended for alleviating vasomotor symptoms or preventing bone loss in postmenopausal women. This study aimed to investigate the impact of hormone replacement therapy on major adverse cardiovascular events, kidney failure, and mortality in women with chronic kidney disease (CKD).

METHODS: This population-based cohort study analyzed data from the National Cancer Screening Program and the national health examination of South Korea. Data on postmenopausal women were extracted from the 2009 National Cancer Screening Program. Among these postmenopausal women, those with CKD without kidney replacement therapy were selected through a national health examination from 2009 to 2013. The study outcomes were the risks of major adverse cardiovascular events, kidney failure, and all-cause mortality according to hormone replacement therapy.

RESULTS: A total of 768,279 postmenopausal women with CKD were enrolled in this study; of these women, 13.8% (N = 106,052) had a history of hormone replacement therapy. The user and non-user groups differed with respect to baseline characteristics, with the latter being older and having risk factors for cardiovascular disease. After adjustment for confounding factors, the group exposed to hormone replacement therapy showed lower risks of major adverse cardiovascular events, kidney failure, and all-cause mortality.

CONCLUSIONS: This study suggests the potential benefits of hormone replacement therapy in postmenopausal women with CKD and highlighted its potential advantages for cardiovascular and kidney outcomes.

PMID:39412740 | DOI:10.1007/s40620-024-02099-z