JAMA Intern Med. 2025 Mar 10. doi: 10.1001/jamainternmed.2024.8216. Online ahead of print.
NO ABSTRACT
PMID:40063042 | DOI:10.1001/jamainternmed.2024.8216
JAMA Netw Open. 2025 Mar 3;8(3):e250128. doi: 10.1001/jamanetworkopen.2025.0128.
ABSTRACT
IMPORTANCE: While it is well known that data quality underlies evidence validity, the measurement and impacts of data reliability are less well understood. The need has been highlighted in the 21st Century Cures Act of 2016 and US Food and Drug Administration (FDA) Real-World Evidence Program framework in 2018, draft guidance in 2021 and final guidance in 2024. Timely visibility into implementation may be provided by the Transforming Real-World Evidence With Unstructured and Structured Data to Advance Tailored Therapy (TRUST) study, a Verantos Inc-led FDA-funded demonstration project to explore data quality and inform regulatory decision-making.
OBJECTIVE: To report early learnings from the TRUST study on distilling data reliability to practice including developing a practical approach to quantify accuracy, completeness, and traceability of real-world data (routinely collected patient health data) and comparing traditional to advanced data and technologies on these dimensions.
DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study was performed using data from 58 hospitals and more than 1180 associated outpatient clinics from academic and community settings in the US. Participants included patients with asthma treated between January 1, 2014, and December 31, 2022. Data were analyzed from January 1 to June 30, 2024.
EXPOSURES: The traditional approach used medical and pharmacy claims as source documentation. The advanced approach used medical and pharmacy claims, electronic health records with unstructured data extracted using artificial intelligence methods, and mortality registry data.
MAIN OUTCOMES AND MEASURES: Accuracy was assessed using the F1 score. Completeness was estimated as a weighted mean of available data sources during each calendar year under study for each patient. Traceability was estimated as the proportion of data elements identified in clinical source documentation.
RESULTS: In total, 120 616 patients met the minimum data requirements (mean [SD] age, 43.2 [18.5] years; 41 011 male [34.0%]). For accuracy, traditional approaches had F1 scores of 59.5% and advanced approaches had scores of 93.4%. For completeness, traditional approaches yielded mean scores of 46.1% (95% CI, 38.2%-54.0%); advanced approaches, 96.6% (95% CI, 85.8%-1.1%). For traceability, traditional approaches had 11.5% (95% CI, 11.4%-11.5%) and advanced approaches had 77.3% (95% CI, 77.3%-77.3%) of data elements traceable to clinical source data.
CONCLUSIONS AND RELEVANCE: In this study, practical implementation of data reliability measurement is described. Findings suggest the potential of using multiple data sources and applying advanced methods to increase real-world data reliability. The inclusion of data reliability standards when generating evidence from these sources has the potential to strengthen support for the use of real-world evidence in the prescription, reimbursement, and approval of medications.
PMID:40063029 | DOI:10.1001/jamanetworkopen.2025.0128
JAMA Netw Open. 2025 Mar 3;8(3):e250331. doi: 10.1001/jamanetworkopen.2025.0331.
ABSTRACT
IMPORTANCE: The weak link between subjective symptom-based diagnostics for posttraumatic psychopathology and objective neurobiological indices hinders the development of effective personalized treatments.
OBJECTIVE: To identify early neural networks associated with posttraumatic stress disorder (PTSD) development among recent trauma survivors.
DESIGN, SETTING, AND PARTICIPANTS: This prognostic study used data from the Neurobehavioral Moderators of Posttraumatic Disease Trajectories (NMPTDT) large-scale longitudinal neuroimaging dataset of recent trauma survivors. The NMPTDT study was conducted from January 20, 2015, to March 11, 2020, and included adult civilians who were admitted to a general hospital emergency department in Israel and screened for early PTSD symptoms indicative of chronic PTSD risk. Enrolled participants completed comprehensive clinical assessments and functional magnetic resonance imaging (fMRI) scans at 1, 6, and 14 months post trauma. Data were analyzed from September 2023 to March 2024.
EXPOSURE: Traumatic events included motor vehicle incidents, physical assaults, robberies, hostilities, electric shocks, fires, drownings, work accidents, terror attacks, or large-scale disasters.
MAIN OUTCOMES AND MEASURES: Connectome-based predictive modeling (CPM), a whole-brain machine learning approach, was applied to resting-state and task-based fMRI data collected at 1 month post trauma. The primary outcome measure was PTSD symptom severity across the 3 time points, assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes included Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) PTSD symptom clusters (intrusion, avoidance, negative alterations in mood and cognition, hyperarousal).
RESULTS: A total of 162 recent trauma survivors (mean [SD] age, 33.9 [11.5] years; 80 women [49.4%] and 82 men [50.6%]) were included at 1 month post trauma. Follow-up assessments were completed by 136 survivors (84.0%) at 6 months and by 133 survivors (82.1%) at 14 months post trauma. Among the 162 recent trauma survivors, CPM significantly predicted PTSD severity at 1 month (ρ = 0.18, P < .001) and 14 months (ρ = 0.24, P < .001) post trauma, but not at 6 months post trauma (ρ = 0.03, P = .39). The most predictive edges at 1 month included connections within and between the anterior default mode, motor sensory, and salience networks. These networks, with the additional contribution of the central executive and visual networks, were predictive of symptoms at 14 months. CPM predicted avoidance and negative alterations in mood and cognition at 1 month, but it predicted intrusion and hyperarousal symptoms at 14 months.
CONCLUSIONS AND RELEVANCE: In this prognostic study of recent trauma survivors, individual differences in large-scale neural networks shortly after trauma were associated with variability in PTSD symptom trajectories over the first year following trauma exposure. These findings suggest that CPM may identify potential targets for interventions.
PMID:40063028 | DOI:10.1001/jamanetworkopen.2025.0331
JAMA Netw Open. 2025 Mar 3;8(3):e250349. doi: 10.1001/jamanetworkopen.2025.0349.
ABSTRACT
IMPORTANCE: Evidence suggests that trauma-related mortality and morbidities may follow a multiphasic pattern, with outcomes extending beyond hospital discharge.
OBJECTIVES: To determine the incidence of having new mental health conditions after the first (or index) trauma admission and their association with long-term health outcomes.
DESIGN, SETTING, AND PARTICIPANTS: This population-based, linked-data cohort study was conducted between January 1994 and September 2020, with data analyzed in April 2024. Participants were adult patients with trauma admitted to 1 of the 5 adult trauma hospitals in Western Australia. All patients with major trauma with an Injury Severity Score (ISS) greater than 15 were included. For each patient with major trauma, 2 patients with trauma with a lower ISS (<16) were randomly selected.
EXPOSURE: A new mental health condition recorded in either subsequent public or private hospitalizations after trauma admission.
MAIN OUTCOMES AND MEASURES: The primary outcomes were the associations between new mental health conditions after trauma and subsequent risks of trauma readmission, suicide, and all-cause mortality, as determined by Cox proportional hazards regression. Logistic regression was used to determine which factors were associated with developing a new mental health condition after trauma.
RESULTS: Of 29 191 patients (median [IQR] age, 42 [27-65] years; 19 383 male [66.4%]; median [IQR] ISS, 9 [5-16]; 9405 with ISS >15 and 19 786 with ISS <16) considered, 2233 (7.6%) had a mental health condition before their trauma admissions. The median (IQR) follow-up time after the index trauma admission was 99.8 (61.2-148.5) months. Of 26 958 patients without a prior mental health condition, 3299 (11.3%) developed a mental health condition subsequently, including drug dependence (2391 patients [8.2%], with 419 patients [1.4%] experiencing opioid dependence) and neurotic disorders (1574 patients [5.4%]), including posttraumatic stress disorder. Developing a new mental health condition after trauma was associated with subsequent trauma readmissions (adjusted hazard ratio [aHR], 1.30; 95% CI, 1.23-1.37; P < .001), suicides (aHR, 3.14; 95% CI, 2.00-4.91; P < .001), and all-cause mortality (aHR, 1.24; 95% CI, 1.12-1.38; P < .001). Younger age, unemployment, being single or divorced (vs married), Indigenous ethnicity, and a lower socioeconomic status were all associated with developing a new mental health condition after the first trauma admission.
CONCLUSIONS AND RELEVANCE: This cohort study of 29 191 patients with trauma found that mental health conditions after trauma were common and associated with an increased risk of adverse long-term outcomes, indicating that mental health follow-up of patients with trauma, particularly those from vulnerable subgroups, may be warranted.
PMID:40063026 | DOI:10.1001/jamanetworkopen.2025.0349
JAMA Netw Open. 2025 Mar 3;8(3):e250354. doi: 10.1001/jamanetworkopen.2025.0354.
ABSTRACT
IMPORTANCE: Women with idiopathic generalized epilepsy (IGE) face challenges in treatment due to limited options that are both effective and safe.
OBJECTIVE: To evaluate the effectiveness and safety of substitution monotherapy vs add-on therapy as second-line options for women who might become pregnant with IGE after failure of first-line antiseizure medications (ASMs) other than valproic acid.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective comparative effectiveness cohort study at 18 primary, secondary, and tertiary adult and children epilepsy centers across 4 countries, analyzing data from 1995 to 2023. Participants were women aged 10 to 50 years diagnosed with IGE who were prescribed a second line of ASM.
MAIN OUTCOMES AND MEASURES: Treatment failure (TF), defined as the replacement or addition of a second ASM due to ineffectiveness, was compared between patients receiving ASM add-on or substitution monotherapy using inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression. Exploratory analyses were also conducted to assess the effectiveness of individual ASMs and various ASM combinations.
RESULTS: This study included 249 women with a median (IQR) age of 18.0 (15.5-22.0) years. Among them, 146 (58.6%) received an add-on regimen, and 103 (41.4%) received substitution monotherapy. During follow-up, TF occurred in 48 patients (32.9%) receiving add-on therapy and 36 (35.0%) using substitution monotherapy, with no significant differences between groups (IPTW-adjusted hazard ratio [HR], 0.89; 95% CI, 0.53-1.51; P = .69). ASM discontinuation due to ineffectiveness or adverse effects occurred in 36 patients (24.7%) receiving add-on therapy and 29 (28.2%) receiving substitution monotherapy, showing no significant differences (IPTW-adjusted HR, 0.97; 95% CI, 0.57-1.65; P = .92). Rates of ASM discontinuation due to adverse effects only were low in both groups, occurring in 13 patients (9.0%) receiving add-on therapy and 9 (8.7%) receiving a substitution monotherapy. Among add-on regimens other than valproic acid, the combination of levetiracetam and lamotrigine demonstrated a lower risk of TF compared with other combinations with levetiracetam plus other ASM (adjusted HR, 2.41; 95% CI, 1.12-5.17; P = .02) and lamotrigine plus other ASM (adjusted HR, 4.03; 95% CI, 1.73-9.39; P = .001). However, valproic acid remained the most effective second-line ASM when considering individual agents.
CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of second-line treatment strategies for women with IGE, no significant differences were observed between substitution monotherapy and add-on therapy.
PMID:40063025 | DOI:10.1001/jamanetworkopen.2025.0354
JAMA Netw Open. 2025 Mar 3;8(3):e250365. doi: 10.1001/jamanetworkopen.2025.0365.
ABSTRACT
IMPORTANCE: High-quality, person-centered patient-clinician communication is critical in health care and may be less effective for patients with serious illness. Little is understood about differences in patient-clinician communication experiences of adults with and without serious illness.
OBJECTIVES: To determine whether perceptions of patient-clinician communication experiences differ between adults with and without serious illness.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional survey was fielded from April 20 to May 31, 2021, and data were analyzed from January 27, 2023, to December 10, 2024. Participants included a nationally representative sample of US English- or Spanish-speaking adults, including people from historically marginalized groups (eg, Black and Hispanic or Latino individuals, people with low income), responding to an online or telephone survey.
EXPOSURE: Participants were categorized by serious illness status. Participants with serious illness replied yes to (1) having a diagnosis from a list of medical conditions and (2) reporting feeling sicker or having decreased functionality during the last year.
MAIN OUTCOMES AND MEASURES: The survey asked about community partner-derived measures of patient-clinician communication experiences, including trusting clinicians, feeling afraid to speak up, and being unsure about next steps. Multivariable logistic regression models were used to estimate the association of serious illness with these communication experiences, adjusting for sociodemographic characteristics. Percentages were weighted according to the National Opinion Research Center’s statistical weighting methods to account for differences in nonresponse.
RESULTS: Of 6126 individuals invited, 1847 (30.2%) completed the survey and were included in analysis (mean [SD] age, 48.4 [17.5] years); 950 (51.8%) identified as female; 191 (11.9%) identified as Black and 287 (16.7%) as Hispanic; and 434 (17.8%) had an annual income less than $30 000 (here called low income). Among respondents, 363 participants (18.5%) had serious illness (mean [SD] age, 50.2 [18.1] years; 218 [64.5%] female; 34 [12.4%] Black; 54 [16.4%] Hispanic; 131 [27.3%] with low income), and 1484 (81.5%) had no serious illness (mean [SD] age, 48.0 [17.4] years; 732 [48.9%] female; 157 [11.8%] Black; 233 [16.7%] Hispanic; 303 [15.6%] with low income). Compared with adults without serious illness, adults with serious illness were more likely to report leaving a visit unsure about next steps (adjusted odds ratio [AOR], 2.30; 95% CI, 1.62-3.27); being afraid to ask questions or speak up (AOR, 2.18; 95% CI, 1.55-3.08); believing they were talked down to or made to feel inferior (AOR, 1.90; 95% CI, 1.24-2.91); and believing that they were treated unfairly by clinicians (AOR, 3.26; 95% CI, 2.43-4.38).
CONCLUSIONS AND RELEVANCE: In this cross-sectional study, adults with serious illness more often had worse patient-clinician communication experiences. Further research is needed to better understand and develop interventions to improve perceptions of patient-clinician communication experiences for adults with serious illness.
PMID:40063024 | DOI:10.1001/jamanetworkopen.2025.0365
JAMA Netw Open. 2025 Mar 3;8(3):e250371. doi: 10.1001/jamanetworkopen.2025.0371.
ABSTRACT
IMPORTANCE: Flooding is a major environmental hazard, with events increasing in intensity and frequency in the context of climate change. Floods cause significant health and economic impacts, particularly among vulnerable populations, including older adults. However, comprehensive analyses of the health consequences of flooding remain limited.
OBJECTIVE: To evaluate the morbidity and health care costs among Medicare beneficiaries associated with flood exposure in the US.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study analyzed emergency department (ED) use and unplanned hospitalization among Medicare beneficiaries 65 years or older living in zip code tabulation areas (ZCTAs) that were exposed to large-scale flood events from January 1, 2008, to December 31, 2017. This analysis was conducted from April 3 to December 15, 2023.
EXPOSURE: The primary exposure was the presence of a flood as recorded in the Multisourced Flood Inventories, a spatially distributed flood database.
MAIN OUTCOMES AND MEASURES: A conditional fixed-effects regression approach was used to explore the incidence of all-case and cause-specific ED visits and hospitalizations before and after floods. The primary outcomes measured were the incident rate ratios (IRRs) and associated 95% CIs. Attributable risk percentages and estimated attributable excess visits were calculated. Stratified analyses were performed for evaluation of effect modification. Health care costs associated with these events were measured and standardized to 2017 US dollars.
RESULTS: Among 11 801 527 Medicare beneficiaries 65 years or older (mean [SD] age, 74.4 [7.6] years; 56.3% female), the rate of all-cause ED visits and hospital admissions increased by 4.8% (IRR, 1.05; 95% CI, 1.04-1.05) and 7.4% (IRR, 1.07; 95% CI, 1.07-1.08) after flood exposure, respectively. The mean ZCTA-level cost was $3230 (95% CI, $3198-$3261) per ED visit and $11 310 (95% CI, $11 252-$11 367) for hospitalizations. The national costs to the Medicare system were estimated to be $69 275 429 (95% CI, $63 010 840-$76 315 210) for ED visits and $191 409 579 (95% CI, $172 782 870-$206 181 300) for hospitalizations. Stratified analyses highlighted greater impacts for certain demographic groups, including adults older than 85 years, and specific seasonal patterns.
CONCLUSIONS AND RELEVANCE: In this cohort study of Medicare beneficiaries 65 years or older, flood exposure was associated with increased health care use and costs, underscoring the need for targeted public health strategies and improved disaster preparedness, especially for older adults. These findings contribute to a more comprehensive understanding of the health-related costs of flooding and can be used to inform future climate change resilience and health care planning.
PMID:40063023 | DOI:10.1001/jamanetworkopen.2025.0371
JAMA Netw Open. 2025 Mar 3;8(3):e250392. doi: 10.1001/jamanetworkopen.2025.0392.
ABSTRACT
IMPORTANCE: Addressing health disparities in lesbian, gay, bisexual, transgender, and queer (LGBTQ+) communities has been a significant policy focus for more than a decade. Ensuring access to safe, respectful primary health care from knowledgeable clinicians is crucial for reducing health inequalities.
OBJECTIVE: To assess the engagement of primary care practices in LGBTQ+ affirming care activities and identify practice characteristics associated with increased engagement.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the National Survey of Healthcare Organizations and Systems II, which focused on primary care practices in the US and was administered between June 2022 through February 2023. Participants were primary care physicians and practice managers. Percentages were weighted for national representation. Data were analyzed from November 2023 to December 2024.
EXPOSURE: Practice characteristics including practice size, ownership, federally qualified health center (FQHC) designation; percentage of patients enrolled in Medicare; percentage of patients enrolled in Medicaid; having accountable care organization (ACO) contracts for Medicare, Medicaid, or commercial insurance; rurality; census region; and LGBTQ+ Equality Score by state policy.
MAIN OUTCOMES AND MEASURES: Sexual orientation- and gender identity- (SOGI) affirming activities, a composite variable reflecting activity specific to SOGI patients.
RESULTS: Among 1245 practices in the sample (38.4% response rate), 923 (77.40%) collected data on gender identity, 921 (75.62%) on sexual orientation, and 742 (65.83%) on patients’ pronouns. Only 412 practices (34.42%) provided LGBTQ+ training for clinicians and 480 practices (39.20%) provided training for staff. Practices designated as FQHCs had 3.16 (95% CI, 4.60 to 19.73) percentage points higher probability of engaging in all SOGI-affirming activities) compared with non-FQHCs (P = .001). Practices with a Medicaid payer mix at least 50% had 3.28 (95% CI, 1.19 to 5.36) percentage points higher probability than practices with less than 50% Medicaid payer mix (P = .002), and participation in a Medicaid ACO was associated with 4.26 (95% CI, 0.78 to 7.73) percentage points increased probability compared with nonparticipants (P = .02). Each 1-unit increase in the state-level LGBTQ+ Equality Score was associated with 1.07 (95% CI, 0.28 to 1.85) percentage points higher probability of engaging in all SOGI-affirming activities (P = .02). High performance was negatively associated with practice rurality (average marginal effect, -16.00 [95% CI, -29.72 to -2.28]; P = .02), and rural practices were less likely to provide appropriate referrals (average marginal effect, -15.47 [95% CI, -29.22 to -1.72]; P = .03).
CONCLUSIONS AND RELEVANCE: These findings suggest there is a need for federal and state mandates to require LGBTQ+ health care and competency training for health professionals and standardized data collection on SOGI, and these may be particularly important in rural regions. These measures are essential to evaluate practice performance and address health disparities effectively.
PMID:40063021 | DOI:10.1001/jamanetworkopen.2025.0392
JAMA Pediatr. 2025 Mar 10. doi: 10.1001/jamapediatrics.2024.7057. Online ahead of print.
ABSTRACT
IMPORTANCE: Recent studies have associated the COVID-19 pandemic with negative developmental outcomes in children. However, research focused on young children remains limited, with few studies including multiple years of pre- and postpandemic onset data.
OBJECTIVE: To examine the impact of the COVID-19 pandemic on US kindergarteners’ developmental health.
DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional panel study examined developmental health trends, as measured by the Early Development Instrument (EDI), among a convenience sample US kindergarteners from 2010 to 2023. EDI data were obtained from 390 school districts across 19 states. Data were analyzed from June December 2024.
EXPOSURE: Kindergarteners’ developmental health was compared between prepandemic (2018 to 2020) and postpandemic (2021 to 2023) onset cohorts.
MAIN OUTCOMES AND MEASURES: Outcomes were EDI scores across time in 5 domains: (1) physical health and well-being, (2) social competence, (3) emotional maturity, (4) language and cognitive development, and (5) communication and general knowledge. The mean (95% CI) EDI scores were assessed.
RESULTS: In this sample of of 475 740 US kindergarten students, 242 869 were male (51.1%), there were 53 841 African American or Black students (11.4%), 263 037 Hispanic or Latino/a students (55.5%), and 95 258 White students (20.1%), and the mean (SD) age was 6 (0.4) years (range, 4.0-8.0 years). Compared with the immediate prepandemic onset period, the rate of change in EDI scores was significantly lower following the pandemic onset in language and cognitive development (mean change, -0.45; 95% CI, -0.48 to -0.43), social competence (mean change, -0.03; 95% CI, -0.06 to -0.01), and communication and general knowledge (mean change, -0.18; 95% CI, -0.22 to -0.15). EDI scores were significantly higher in emotional maturity (mean change, 0.05; 95% CI, 0.03 to 0.07), and no significant changes were observed in the physical health and well-being domain (mean change, 0; 95% CI, -0.01 to 0.02).
CONCLUSIONS AND RELEVANCE: The COVID-19 pandemic was associated with varying developmental health outcomes in kindergarteners. Negative developmental trends existed immediately before the pandemic, with most persisting or slowing postpandemic onset. These results highlight troubling trends in kindergarteners’ development, both before and during the pandemic, and more information is needed to understand why developmental outcomes are worsening over time.
PMID:40063020 | DOI:10.1001/jamapediatrics.2024.7057
Eur J Psychotraumatol. 2025 Dec;16(1):2469978. doi: 10.1080/20008066.2025.2469978. Epub 2025 Mar 10.
ABSTRACT
Background: Evidence supporting the association between posttraumatic stress disorder (PTSD) and cognitive impairment is accumulating. However, less is known about which factors influence this association.Objective: The aims of this meta-analysis were to (1) elucidate the association between PTSD and a broad spectrum of cognitive impairment, including the risk of developing neurocognitive disorder (NCD) later in life, using a multilevel meta-analytic approach, and (2) identify potential moderating factors of this association by examining the effects of age (20-39, 40-59, 60+), study design (cross-sectional or longitudinal), study population (war-exposed populations/veterans or the general population), neurocognitive outcome assessed (i.e. a diagnosis of NCD or type of cognitive domain as classified according to A Compendium of Neuropsychological tests), gender (≥50% women or <50% women), study quality (high vs low), type of PTSD measure (self-report or clinical diagnosis), as well as the presence of comorbidities such as traumatic brain injury (TBI), depression, and substance use (all coded as either present or absent).Method: Peer-reviewed studies on this topic were extracted from PubMed and Web of Science with predetermined keywords and criteria. In total, 53 articles met the criteria. Hedge’s g effect sizes were calculated for each study and a three-level random effect meta-analysis conducted.Results: After accounting for publication bias, the results suggested a significant association between PTSD and cognitive impairment, g = 0.13 (95% CI: 0.10-0.17), indicating a small effect. This association was consistent across all examined moderators, including various neurocognitive outcomes, age, gender, study design, study population, study quality, type of PTSD measure, and comorbidities such as depression, substance use, and TBI.Conclusions: These findings collectively suggest that PTSD is associated with both cognitive impairment and NCD. This emphasizes the need for early intervention (including prevention strategies) of PTSD, alongside monitoring cognitive function in affected individuals.International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42021219189, date of registration: 02.01.2021.
PMID:40062977 | DOI:10.1080/20008066.2025.2469978