Nevin Manimala

JAMA Netw Open. 2025 Feb 3;8(2):e2460477. doi: 10.1001/jamanetworkopen.2024.60477.

ABSTRACT

IMPORTANCE: Transcranial direct current stimulation (tDCS) has the potential to be a sustainable treatment option in pediatric attention-deficit/hyperactivity disorder (ADHD), but rigorously controlled multicenter clinical trials using state-of-the-art stimulation techniques are lacking.

OBJECTIVES: To determine effect sizes of changes in cognitive and clinical measures and to assess safety and tolerability in the course of optimized multichannel tDCS over prefrontal target regions in pediatric ADHD.

DESIGN, SETTING, AND PARTICIPANTS: In the sham-controlled, double-blind, parallel-group randomized clinical trial E-StimADHD (Improving Neuropsychological Functions and Clinical Course in Children and Adolescents With ADHD With Anodal Transcranial Direct Current Stimulation of the Prefrontal Cortex: A Randomized, Double-Blind, Sham-Controlled, Parallel Group Trial Using an Uncertified Class IIa Device) with 2 independent study arms, participants were enrolled from September 15, 2018, to August 10, 2021, and follow-up was completed October 4, 2021. Data were analyzed January 26, 2022, to November 8, 2023. The trial was conducted at the departments of child and adolescent psychiatry or pediatrics of 5 university hospitals in Portugal and Germany. Youths 10 to 18 years of age with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (all presentations), an IQ of at least 80, and the ability to refrain from stimulant medication during participation in the trial were eligible.

INTERVENTIONS: Optimized multichannel anodal tDCS or sham stimulation (1 mA, 20 minutes) targeting the left dorsolateral prefrontal cortex (lDLPFC; study A) or the right inferior frontal gyrus (rIFG; study B) was applied in 10 sessions, concurrent with performance on a cognitive target task (study A, working memory assessed in the n-back task; study B, interference control assessed in the flanker task).

MAIN OUTCOMES AND MEASURES: Effect sizes for changes in accuracy measures (d-prime or flanker effect) in the target tasks assessed after the intervention. Primary analyses were based on the modified intention-to-treat set.

RESULTS: This study included 69 youths (54 [78%] male) with a median age of 13.3 years (IQR, 11.9-14.9 years). Compared with sham tDCS, verum stimulation of the lDLPFC led to significantly lower working memory accuracy (effect size, -0.43 [95% CI, -0.68 to -0.17]; P = .001). Stimulation of the rIFG significantly improved interference control (effect size, 0.30 [95% CI, 0.04-0.56]; P = .02). Adverse events were mostly mild and transient and did not occur more often in the verum group. For example, the most frequent adverse events were headache (sham, n = 30; verum, n = 20), nasopharyngitis (sham, n = 11; verum, n = 5), and feeling of electric discharge (sham, n = 5; verum, n = 3).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, prefrontal anodal tDCS induced small- to medium-sized effects in youths with ADHD, with only mild and transient adverse events. The optimized multichannel montage chosen to target the lDLPFC, however, decreased working memory performance. This unexpected finding stresses the importance of incorporating insights from basic research on the mechanisms and preconditions of successful tDCS in future study designs to advance application of tDCS in pediatric ADHD.

TRIAL REGISTRATION: German Clinical Trials Register ID: DRKS00012659.

PMID:39982727 | DOI:10.1001/jamanetworkopen.2024.60477

JAMA Netw Open. 2025 Feb 3;8(2):e2461021. doi: 10.1001/jamanetworkopen.2024.61021.

ABSTRACT

IMPORTANCE: Patients often travel for cancer care, yet the extent to which patients cross state lines for cancer care is not well understood. This knowledge can have implications for policies that regulate telehealth access to out-of-state clinicians.

OBJECTIVE: To quantify the extent of cross-state delivery of cancer services to patients with cancer.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed fee-for-service Medicare claims data for beneficiaries (aged ≥66 years) with a diagnosis of breast, colon, lung, or pancreatic cancer between January 1, 2017, and December 31, 2020. Analyses were performed between January 1 and July 30, 2024.

EXPOSURE: Patient rurality.

MAIN OUTCOMES AND MEASURES: The primary outcome of interest was receipt of cancer care across state lines. Frequencies of cancer services (surgery, radiation, and chemotherapy) were summarized by cancer type in relation to in-state vs out-of-state receipt of care based on state of residence for Medicare beneficiaries. Cross-state delivery of cancer services was also quantified by adjacent vs nonadjacent states and overall between-state flows for service utilization.

RESULTS: The study included 1 040 874 Medicare beneficiaries with cancer. The mean (SD) age of the study population was 76.5 (7.4) years. Most patients were female (68.2%) and urban residing (78.5%); one-quarter (25.9%) were aged between 70 and 74 years. In terms of race and ethnicity, 7.0% of patients identified as Black, 3.4% as Hispanic, and 85.5% as White. Overall, approximately 6.9% of cancer care was delivered across state lines, with the highest proportion (8.3%) occurring for surgical care, followed by radiation (6.7%) and chemotherapy (5.6%) services. Out of all cross-state care, 68.4% occurred in adjacent states. Frequency of cross-state cancer care increased with patient rurality. Compared with urban-residing patients, isolated rural-residing patients were 2.5 times more likely to cross state lines for surgical procedures (18.5% vs 7.5%), 3 times more likely to cross state lines for radiation therapy services (16.9% vs 5.7%), and almost 4 times more likely to cross state lines for chemotherapy services (16.3% vs 4.2%).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of Medicare claims data, a notable proportion of cancer services occurred across state lines, particularly for rural-residing patients. These results highlight the need for cross-state telehealth policies that recognize the prevalence of care delivery from geographically distant specialized oncology services.

PMID:39982726 | DOI:10.1001/jamanetworkopen.2024.61021

JAMA Netw Open. 2025 Feb 3;8(2):e2461117. doi: 10.1001/jamanetworkopen.2024.61117.

ABSTRACT

IMPORTANCE: A timely diagnosis is crucial in ensuring high-quality care for individuals with dementia. Comparing age and health status at the time of dementia diagnosis across population subgroups can provide insights into vulnerable groups that may experience delayed diagnosis and/or a poorer prognosis.

OBJECTIVE: To examine how age and health at the time of dementia diagnosis vary across sociodemographic subgroups.

DESIGN, SETTING, AND PARTICIPANTS: A nationwide cross-sectional study of individuals with an incident dementia diagnosis from either specialist care or who were dispensed antidementia drugs, identified from the Swedish National Patient Register and the Prescribed Drug Register between January 2018 and December 2022.

EXPOSURES: Sociodemographic status at the time of dementia diagnosis was assessed through linkage with national registers and included education, place of birth, living arrangement, family status, and family disposable income.

MAIN OUTCOMES AND MEASURES: Health status was assessed by calculating the number of dispensed medications during the year preceding dementia diagnosis, as well as the Charlson Comorbidity Index (CCI) and Hospital Frailty Risk Score (HFRS) using specialist diagnoses during the preceding 5 years.

RESULTS: Of the 107 707 individuals with a dementia diagnosis, 61 127 (56.8%) were women and the mean (SD) age at diagnosis was 82.0 (7.7) years. Individuals with lower education, living alone or in a care home, or without a close relative were a mean (SD) of 3.1 (7.3) years older when diagnosed with dementia compared with their counterparts. At the time of diagnosis, individuals who had lower than high school education had higher CCI (odds ratio [OR], 1.11; 95% CI, 1.07-1.15) and more medications (OR, 1.38; 95% CI, 1.33-1.44) compared with those with university education. Age and health status at dementia diagnosis did not differ significantly by place of birth or income.

CONCLUSIONS AND RELEVANCE: This nationwide register-based study indicated that clinical diagnosis of dementia may be significantly delayed among individuals with low education, those living alone or in a care home, or those without a close relative. These groups also had poorer health at the time of dementia diagnosis, which may impact their prognosis negatively. Future efforts should focus on improving health services to better address the diagnostic and care needs of these vulnerable subgroups.

PMID:39982724 | DOI:10.1001/jamanetworkopen.2024.61117

JAMA Netw Open. 2025 Feb 3;8(2):e2461200. doi: 10.1001/jamanetworkopen.2024.61200.

ABSTRACT

IMPORTANCE: The 2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline concluded that obesity alone should not delay joint replacement. Therefore, a substantially increased utilization of joint replacement among patients with obesity could be expected. However, patients with obesity are at increased risk of revision, posing unique challenges as the surgery is complex and costly, and it remains unknown whether postoperative weight loss could decrease the risk of revision.

OBJECTIVE: To examine the association of the proportion of postoperative weight loss following antiobesity medication use with the risk of revision among patients with obesity undergoing hip or knee replacement.

DESIGN, SETTING, AND PARTICIPANTS: Using a target trial emulation, a causal inference framework, this retrospective cohort study investigated patients with obesity who underwent hip or knee replacement. Data were from the IQVIA Medical Research Database (2000-2023). Statistical analysis was performed from October 2023 to June 2024.

MAIN OUTCOMES AND MEASURES: Emulated analyses of a hypothetical target trial were assessed for the association of small-to-moderate (2%-10%) or large (≥10%) weight loss after initiating antiobesity medications (orlistat, sibutramine, glucagon-like peptide-1 receptor agonists, and rimonabant) within 1 year with the risk of 5-year and 10-year revision after initiation of antiobesity medications.

RESULTS: Among 3691 qualified participants (mean [SD] age, 64.7 [9.3] years; 2322 [62.9%] women), the 5-year risks of revision were 5.6%, 4.4%, and 3.7% for weight gain or stable, small-to-moderate weight loss, and large weight loss groups, respectively. Compared with the weight gain or stable group, the hazard ratios (HRs) were 0.75 (95% CI, 0.55-1.04) for the small-to-moderate weight loss group and 0.57 (95% CI, 0.36-0.91) for the large weight loss group. Similar results were observed when the analyses were performed separately for hip or knee replacement. The HRs for revision were 0.55 (95% CI, 0.32-0.93) for small-to-moderate weight loss and 0.49 (95% CI, 0.25-0.97) for large weight loss groups compared with the weight gain or stable group in patients undergoing knee replacement; the corresponding HRs for revision were 0.82 (95% CI, 0.54-1.25) and 0.53 (95% CI, 0.30-0.93) in patients undergoing hip replacement. Consistent findings were obtained regarding the association of weight loss with the 10-year risks after initiating antiobesity medications.

CONCLUSIONS AND RELEVANCE: In this cohort study using a target trial emulation, a higher proportion of weight loss after initiating antiobesity medications within 1 year was associated with a lower risk of 5-year and 10-year revision among patients with obesity undergoing joint replacement. These results suggest that antiobesity medication use, with relatively safe and sustainable weight loss, may be an effective strategy for improving implant survivorship of hip and knee replacements in the obese population.

PMID:39982723 | DOI:10.1001/jamanetworkopen.2024.61200

JAMA Netw Open. 2025 Feb 3;8(2):e2461208. doi: 10.1001/jamanetworkopen.2024.61208.

ABSTRACT

IMPORTANCE: Socioeconomic status (SES) has an important association with cognitive function and structural brain indices. Identifying the nature of this association will guide strategies for improving health equity.

OBJECTIVE: To test the longitudinal associations of SES with cognitive decline and brain characteristics and to examine whether these associations differ between Black and White individuals.

DESIGN, SETTING, AND PARTICIPANTS: Participants aged 65 years old or older were recruited for this population-based cohort study from 4 communities on the south side of Chicago, Illinois. At-home interviews were conducted between 1993 and 2012. The data were analyzed in April 2024.

MAIN OUTCOMES AND MEASURES: Outcome measures were level and change in global cognition and 4 individual tests. Three magnetic resonance imaging (MRI) measures of the brain included total brain volume, hippocampal volumes, and white matter hyperintensities (WMH). Childhood SES was assessed using parental education levels, father’s occupation, and childhood finance rating. Adulthood SES was assessed using the participants’ education, occupation, and income. Lifetime SES was assessed on the basis of the mother’s education, childhood SES, and participants’ occupation and income.

RESULTS: Of the 7303 participants (mean [SD] age, 72.3 [6.3] years; 4573 female participants [63%]), 4581 (63%) were non-Hispanic Black, and 2722 (37%) were non-Hispanic White. SES was higher for White individuals compared with Black individuals in childhood, adulthood, and across the lifespan. Higher lifetime SES was associated with better global cognitive functioning at baseline (estimate, 0.337; 95% CI, 0.317 to 0.357; P < .001) but not with decline over time (estimate, 0.003; 95% CI, -0.001 to 0.006; P = .10). Higher lifetime SES was associated with a better baseline score on the Mini-Mental State Examination (estimate, 0.281; 95% CI, 0.261 to 0.302; P < .001) and a slower decline for all participants (estimate, 0.012; 95% CI, 0.008 to 0.016; P < .001). In a subset of 933 participants who underwent MRI, there was an association between lifetime SES and healthier brain structures, as measured by total brain volume (estimate, 3.18; 95% CI, 0.20 to 6.17; P = .04) and WMH burden (estimate, -0.11; 95% CI, -0.21 to -0.01; P = .03).

CONCLUSIONS AND RELEVANCE: In this cohort study, SES, mainly in adulthood, was associated with a person’s cognitive status and brain structure, resulting in a discrepancy in cognitive status over time. These findings point to a need for interventions that improve SES throughout the lifespan, particularly for Black individuals, who had lower SES than White individuals.

PMID:39982722 | DOI:10.1001/jamanetworkopen.2024.61208

JAMA Netw Open. 2025 Feb 3;8(2):e2461219. doi: 10.1001/jamanetworkopen.2024.61219.

ABSTRACT

IMPORTANCE: Alzheimer disease and related dementias (ADRD) are especially prevalent among Medicare-Medicaid dual-eligible beneficiaries-the clinical complexity of ADRD amplifies the challenges of managing chronic conditions and accessing care for dual-eligible beneficiaries, and the need to navigate the fragmented Medicare-Medicaid benefits adds to patients’ burdens. Little is known about how enrollment in dual-eligible special needs plans (D-SNPs) that coordinate Medicare and Medicaid coverage is associated with health outcomes for dual-eligible beneficiaries with ADRD.

OBJECTIVE: To examine the associations between Medicare Advantage (MA) plan type and adverse medical events among dual-eligible beneficiaries with ADRD.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used MA encounter data from 2016 to 2019. Participants included dual-eligible, community-dwelling Medicare beneficiaries aged 65 years and older with ADRD who enrolled in MA plans in 50 US states and Washington, DC. Data were analyzed from January to November 2024.

EXPOSURES: Enrollment in non-D-SNP Medicare Advantage plans and D-SNPs. The exposure variable for additional analyses included enrollment in fully integrated special needs plans (FIDE SNPs).

MAIN OUTCOMES AND MEASURES: Preventable hospitalizations, 30-day all-cause readmissions, and avoidable emergency department (ED) visits.

RESULTS: Analysis included a total of 121 145 patients in non-D-SNP plans with an enrollment of 173 662 patient-years (mean [SD] age, 81.8 [7.8] years; 122 565 female [70.6%]; 6078 Asian [3.5%], 34 150 Black [19.7%], 37 580 Hispanic [21.6%], 95 854 White [55.2%]) and 78 166 patients in D-SNP plans with an enrollment of 122 681 patient-years (mean [SD] age, 80.2 [8.0] years; 87 329 female [71.2%]; 10 530 Asian [8.6%], 33 280 Black [27.1%], 43 294 Hispanic [35.3%], 35 577 White [29.0%]). Dual-eligible enrollees with ADRD had a preventable hospitalization rate of 10.8% (95% CI, 10.3%-11.4%), a 30-day readmission rate of 22.3% (95% CI, 21.6%-22.9%), and an avoidable ED visit rate of 21.1% (95% CI, 20.3-21.9) in D-SNPs. These rates were 11.1% (95% CI, 10.7%-11.5%), 23.6% (95% CI, 22.9%-24.3%), and 20.8% (95% CI, 20.1%-21.6%) in non-D-SNP MA plans. There were no statistical differences in rates of preventable hospitalizations or avoidable ED visits between dual-eligible enrollees with ADRD in D-SNPs and those in non-D-SNP MA plans. Compared with non-D-SNPs, enrollees in FIDE SNPs had lower probabilities of preventable hospitalizations by 1.2 percentage points (95% CI, -2.7 to -0.2 percentage points) and 30-day readmissions by 7.2 percentage points (95% CI, -9.3 to -5.1 percentage points).

CONCLUSIONS AND RELEVANCE: Dual-eligible beneficiaries with ADRD enrolled in D-SNPs and non-D-SNP MA plans had similar rates of adverse events. Dual-eligible beneficiaries with ADRD may benefit from enrollment in more coordinated MA plans, such as FIDE SNPs, by lowering unnecessary hospitalizations.

PMID:39982721 | DOI:10.1001/jamanetworkopen.2024.61219

JAMA Netw Open. 2025 Feb 3;8(2):e2461312. doi: 10.1001/jamanetworkopen.2024.61312.

ABSTRACT

IMPORTANCE: When preterm delivery is imminent, it remains unclear whether the timing from administration of antenatal betamethasone to birth may reduce mortality and morbidity among extremely preterm infants.

OBJECTIVE: To evaluate the association of duration from exposure to first dose of antenatal betamethasone with outcomes among extremely preterm infants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study enrolled infants born at 22 0/7 to 27 6/7 weeks’ gestation from January 2016 to February 2021 at National Institute of Child Health and Human Development Neonatal Research Network centers. Infants exposed to multiple doses of antenatal betamethasone, infants who did not receive intensive care, and infants with congenital anomalies were excluded. Data were analyzed from October 2021 to December 2024.

EXPOSURE: Time in hours from anenatal betamethasone administration to birth.

MAIN OUTCOMES AND MEASURES: The primary outcome was survival to discharge. Secondary outcomes included survival without major morbidity and composites of individual morbidities and death. The association of time from antenatal betamethasone administration to birth with neonatal survival and morbidity was assessed using generalized linear models, adjusting for gestational age, infant sex, maternal race, education, small for gestational age, mode of delivery, multiple birth, prolonged rupture of membranes, and center of birth.

RESULTS: Of 7464 infants born during the study period, 1806 infants (928 [51.3%] boys) were included in the cohort: 475 with no betamethasone and 1331 with exposure to a single dose of betamethasone within 24 hours before birth. The median (IQR) administration-to-birth interval for infants born after a single dose of betamethasone was 3.8 (1.4-9.5) hours. The administration-to-birth interval was independently associated with survival (adjusted relative risk [aRR] per 1-hour increase, 1.01 [95% CI, 1.00-1.01]; aRR per 6-hour increase, 1.04 [95% CI, 1.01-1.07]) and survival without severe neonatal morbidity (aRR per 1-hour increase, 1.01 [95% CI, 1.01-1.02]; aRR per 6-hour increase, 1.09 [95% CI, 1.04-1.14].

CONCLUSIONS AND RELEVANCE: In this cohort study, for women at risk of imminent preterm birth, even short duration of exposure to antenatal betamethasone was associated with improved neonatal survival and survival without severe neonatal morbidity.

PMID:39982720 | DOI:10.1001/jamanetworkopen.2024.61312

JAMA Health Forum. 2025 Feb 7;6(2):e245436. doi: 10.1001/jamahealthforum.2024.5436.

ABSTRACT

IMPORTANCE: Considerable efforts have been dedicated to improving the quality of end-of-life care among patients with advanced cancer in the past decade. Whether the quality has shifted in response to these efforts remains unknown.

OBJECTIVE: To examine contemporary patterns of end-of-life care among patients with advanced cancer.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used a recent linkage of Surveillance, Epidemiology, and End Results and Medicare data to characterize patterns of end-of-life care. The cohort included fee-for-service Medicare decedents aged 66 years or older who were originally diagnosed with distant-stage breast, prostate, pancreatic, or lung cancers and died between 2014 and 2019. Analyses were conducted between June 1, 2023, and July 31, 2024.

MAIN OUTCOMES AND MEASURES: Outcomes included monthly use of acute care, systemic therapy, and supportive care (ie, palliative and hospice care and advanced care planning) in the last 6 months of life. Additionally, a claims-based indicator was evaluated of potentially aggressive care in the last 30 days of life, defined as experiencing more than 1 acute care visit, in-hospital mortality, late receipt of systemic therapy, or hospice entry.

RESULTS: The study included 33 744 Medicare decedents with advanced cancer (mean [SD] age, 75.7 [6.9] years; 52.1% male). From 6 months before death to month of death, there was an increase in the mean (SE) number of acute care visits (from 14.0 [0.5] to 46.2 [0.5] per 100 person-months), hospice use (from 6.6 [0.4] to 73.5 [0.5] per 100 person-months), palliative care (from 2.6 [0.2] to 26.1 [0.6] per 100 person-months), and advanced care planning (from 1.7 [0.6] to 12.8 [1.1] per 100 person-months). Overall, 45.0% of decedents experienced any indicator of potentially aggressive care.

CONCLUSIONS AND RELEVANCE: This study found persistent patterns of potentially aggressive care, but low uptake of supportive care, among Medicare decedents with advanced cancer. A multifaceted approach targeting patient-, physician-, and system-level factors associated with potentially aggressive care is imperative for improving quality of care at the end of life.

PMID:39982714 | DOI:10.1001/jamahealthforum.2024.5436

J Med Entomol. 2025 Feb 21:tjaf003. doi: 10.1093/jme/tjaf003. Online ahead of print.

ABSTRACT

Ticks and tick-borne disease (TBD) risks are increasing in Indiana and North America. The successful prevention, diagnosis, and treatment of TBDs requires healthcare professionals be well-informed and prepared. This study reports the findings of a 2020 online survey of 465 Indiana healthcare professionals, designed to assess their knowledge of ticks and TBDs and identify factors influencing total knowledge scores. The survey included 24 discrete/ordinal questions and one open-ended question. Statistical analyses, including ANOVA, t-tests, and the Boruta algorithm, were conducted in R. Indiana healthcare professionals scored 30.8% for tick- and 57.9% for disease-related questions. Professionals scored higher on most disease-related questions, including (i) the importance of prompt tick removal to reduce TBD transmission risk, (ii) that not all Lyme disease cases present with bull’s-eye rash, and (iii) the signs and symptoms of TBDs. They scored lower on tick-related questions, including (i) the tick species capable of transmitting diseases to humans, (ii) TBDs considered endemic, (iii) the distribution of Ixodes scapularis (deer tick), and (iv) regions considered higher risk for Lyme disease transmission in Indiana. Knowledge scores varied across demographic categories, with the use of online resources identified as the most important predictor of total knowledge scores. These findings highlight the importance of increasing awareness of existing resources, expanding online educational materials to cover TBDs beyond Lyme disease, and promoting self-guided learning. Achieving these goals will require collaboration among state and public health agencies, healthcare professionals, research institutions, and community outreach partners.

PMID:39982704 | DOI:10.1093/jme/tjaf003

J Med Entomol. 2025 Feb 21:tjaf017. doi: 10.1093/jme/tjaf017. Online ahead of print.

ABSTRACT

Deer keds (Lipoptena cervi), an introduced European species, are expanding their geographic range in North America. We document their first recorded presence in Québec, Canada, map their distribution, and highlight the detection of pathogens of potential public health relevance. In the Estrie region of southern Québec, 47 deer keds (L. cervi) were collected from 14 (5.5%) of 254 harvested white-tailed deer (Odocoileus virginianus). Borrelia spp. and Anaplasma phagocytophilum were detected in the body of 1/44 and 8/44 L. cervi specimens, respectively. A statistically significant spatial cluster of white-tailed deer infested by L. cervi was found in southern Estrie using the Bernoulli-based spatial scan statistic.

PMID:39982702 | DOI:10.1093/jme/tjaf017