Tag: statistics

JCO Clin Cancer Inform. 2025 Jul;9:e2400234. doi: 10.1200/CCI-24-00234. Epub 2025 Jul 9.

ABSTRACT

PURPOSE: Previous studies have consistently reported disparities in electronic health record portal enrollment. Among patients enrolled in a portal, it is less clear whether there are disparities in usage. We investigated whether disparities existed in portal usage among enrolled oncology patients regarding both sending portal messages to and receiving messages from oncology providers.

METHODS: This retrospective cohort study included patients ≥18 years old with cancer who were seen at an urban academic cancer center between January 2011 and February 2025 and enrolled in the patient portal. We developed Cox proportional hazards models for the outcomes of patients sending portal messages to and receiving messages from oncology providers as the first message in a thread. Time measurement began with the first cancer center visit or portal enrollment, whichever was later. Models were adjusted for demographic, socioeconomic, disease, and administrative visit variables.

RESULTS: Among 101,678 patients, the median age was 62 years (IQR, 51-71), and 68,527 sent and 42,242 received messages. After adjustment, age ≥50 versus 18-29 years, Latinx and Pacific Islander versus White, single and widowed versus partnered, non-English preferred language, and Medicaid and Medicare versus private insurance were associated with reduced likelihood of sending and receiving messages. Black and American Indian/Alaska Native were associated with reduced likelihood of sending messages. Female provider was associated with increased likelihood of sending and receiving messages. Women were more likely to send messages.

CONCLUSION: Among oncology patients enrolled in the patient portal, disparities existed in sending and receiving portal messages. Given the association of messaging with better survival among oncology patients in previous studies, future studies should determine how best to minimize messaging disparities beyond just addressing disparities in portal enrollment.

PMID:40632947 | DOI:10.1200/CCI-24-00234

J Am Acad Orthop Surg Glob Res Rev. 2025 Jul 8;9(7). doi: 10.5435/JAAOSGlobal-D-25-00176. eCollection 2025 Jul 1.

ABSTRACT

INTRODUCTION: Orthopaedic surgery was the fifth most competitive specialty in the 2024 Match cycle as measured by the percentage of positions filled overall (915 of 916 [99.9%]). With the United States Medical Licensing Examination Step 1 examination now pass/fail, research experience and publications have become increasingly important for applicants. This study explores key aspects of orthopaedic surgery research fellowships for medical students including the average number of publications and presentations, additional learning opportunities, and total number of fellows who matched into an orthopaedic surgery residency after their research year.

METHODS: Research year fellowships were identified through an online search using publicly available information and the search terms “Orthopaedic Research Fellowship” and “Orthopaedic Research Gap Year” in May 2024. If available, information from individual program websites was used. Programs were contacted to provide the number of publications, presentations, and clinical opportunities offered by the program and the number of previous research fellows matched.

RESULTS: In total, 130 orthopaedic research year fellowship programs were identified. Information was collected for 80 programs through survey response or publicly available information. The average number of fellowship-related publications was 11.7 (range 2 to 30) and presentations was 11.86 (range 1 to 60). In addition, 68 programs offered additional opportunities including clinical and operating room exposure, educational experiences, and mentorship. The total number of research fellows from each program who matched into orthopaedic surgery ranged from 0 to 30.

CONCLUSION: This study found that orthopaedic research fellowships offer medical students an average of 11.7 publications and 11.86 presentations, along with notable clinical exposure. This study offers insights into key characteristics of research fellowships for students evaluating programs, while also highlighting the need for future research to determine which applicants benefit most and how the role of these fellowships is changing in light of the pass/fail United States Medical Licensing Examination Step 1 examination.

PMID:40632945 | DOI:10.5435/JAAOSGlobal-D-25-00176

Neurol Res. 2025 Jul 9:1-9. doi: 10.1080/01616412.2025.2528974. Online ahead of print.

ABSTRACT

BACKGROUND: The genetic contribution to the development of levodopa-induced motor complications in Parkinson’s disease (PD) remains poorly understood.

OBJECTIVES: We aimed to investigate the association between selected polymorphisms of the catechol-O-methyltransferase (COMT), dopamine receptor D2 (DRD2), ankyrin repeat and kinase domain containing 1 (ANKK1) and dopamine transporter (DAT) genes and the occurrence of motor complications in the group of PD patients.

METHODS: A total of 234 PD patients undergoing levodopa therapy for at least two years were genotyped for the following polymorphisms: rs4680 in COMT; rs6277, rs1076560, and rs2283265 in DRD2; rs1800497 and rs2734849 in ANKK1; and a VNTR (Variable Number of Tandem Repeats) polymorphism in the 3′-UTR (3′-untranslated region) of the DAT gene.

RESULTS: Levodopa-induced dyskinesia (LID) was significantly more frequent in carriers of the AA genotype of rs4680 in COMT compared to AG and GG carriers. Motor fluctuations occurred more frequently in carriers of the ANKK1/DRD2 haplotypes GGAAA and AGGAA than in non-carriers. Independent predictors of motor fluctuations included younger age at disease onset, longer disease duration, daily levodopa dose ≥ 500 mg, and greater disease severity. Independent predictors of LID included female gender, longer disease duration, levodopa equivalent daily dose (LEDD) ≥900 mg, greater disease severity, and the AA genotype of rs4680 in COMT, which conferred a 2.8-fold higher risk of dyskinesia.

CONCLUSION: These findings suggest that genetic variants, particularly in the COMT and ANKK1/DRD2 loci, may contribute to the development of levodopa-induced motor complications in PD. These preliminary results require confirmation in larger, longitudinal studies.

PMID:40632937 | DOI:10.1080/01616412.2025.2528974

JAMA Netw Open. 2025 Jul 1;8(7):e2525559. doi: 10.1001/jamanetworkopen.2025.25559.

NO ABSTRACT

PMID:40632541 | DOI:10.1001/jamanetworkopen.2025.25559

JAMA Netw Open. 2025 Jul 1;8(7):e2519426. doi: 10.1001/jamanetworkopen.2025.19426.

ABSTRACT

IMPORTANCE: Palliative care has been shown to improve important patient outcomes but is rarely available in small or rural hospitals.

OBJECTIVE: To assess whether culturally based palliative care video consultation could improve symptom distress compared with usual inpatient care without palliative care.

DESIGN, SETTING, AND PARTICIPANTS: Recruitment for this multisite, single-blind randomized clinical trial occurred from July 20, 2020, to December 20, 2023; data collection was completed on January 15, 2024. A community-aided approach was used to recruit inpatients from 3 rural hospitals lacking palliative care services in Alabama, Mississippi, and South Carolina. Self-identified non-Hispanic Black or African American and non-Hispanic White adults aged 55 years or older admitted with a serious chronic illness and a willing caregiver were invited to participate. Randomization was stratified by site and race.

INTERVENTIONS: Participants were randomized 1:1 to Community Tele-Pal, culturally based video consultation by a palliative care specialist followed by research coordinator (RC) contacts 3 and 6 days after video consultation (intervention arm), or to routine hospital care (control arm).

MAIN OUTCOMES AND MEASURES: The primary outcome was the between-group difference in the change in patient-reported symptom distress from baseline to day 7, assessed by the Edmonton Symptom Assessment Scale (ESAS; range, 0-90; lower scores indicate lower symptom distress). Secondary outcomes were quality of life (QOL; Patient-Reported Outcomes Measurement Information System global physical and mental health mean T scores), resource use (emergency department visits and hospital readmissions), and an exploratory outcome of feeling heard and understood.

RESULTS: A total of 209 patients were randomized (104 to usual care; 105 to the intervention); mean (SD) age was 73.3 (8.3) years, 120 (57.4%) were female, 58 (27.8%) were Black or African American, 157 (75.1%) were retired, and 75 (35.9%) had a Palliative Performance Scale score less than 70% (indicating need for functional assistance). On day 7, the mean (SE) ESAS score change from baseline was -11.4 (1.5) points in the intervention group and -7.3 (1.5) points in the control group; the between-group difference in change in ESAS scores was not statistically significant (Westfall d, -0.28; 95% CI, -0.56 to 0.01; P = .055). The mean (SE) day 7 between-group difference in ESAS score of -4.0 (1.8) points met the criteria for a minimal clinically important difference of 3 to 4 points. No between-group differences were observed for QOL, resource use, or feeling heard and understood.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the intervention was not associated with reduced symptom distress at day 7 vs baseline or with improved QOL or reduced resource use compared with usual care. However, the between-group difference in the ESAS score met the criteria for a minimal clinically important difference of 3 to 4 points. Palliative video consultation to reduce health care inequities for hospitalized rural-dwelling individuals may warrant further investigation.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03767517.

PMID:40632537 | DOI:10.1001/jamanetworkopen.2025.19426

JAMA Netw Open. 2025 Jul 1;8(7):e2519622. doi: 10.1001/jamanetworkopen.2025.19622.

ABSTRACT

IMPORTANCE: The association between grandchild care and dementia remains unclear, with previous studies yielding mixed results and unclear mechanisms.

OBJECTIVE: To examine the association between grandchild care and dementia odds and to explore the mediating roles of mobile telephone ownership, broadband internet access, and reduced loneliness.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the China Health and Retirement Longitudinal Study from 2013 to 2018. Data analysis was conducted from March 10, 2024, to April 20, 2025. Multistage, stratified, cluster sampling was used to recruit participants from 28 provinces across China. Data were collected through biennial, computer-assisted personal interviews. The analytic sample comprised Chinese adults aged 50 to 79 years who were dementia free at baseline.

EXPOSURE: Grandchild caregiving was classified into 4 groups: noncaregivers (0 hours per week), nonintensive caregivers (1-39 hours per week), intensive caregivers (≥40 hours per week), and those without grandchildren.

MAIN OUTCOMES AND MEASURES: Dementia was assessed using both self-reports and proxy measures, with dementia defined by scores of 0 to 6 on the modified Telephone Interview for Cognitive Status or a score of 4 or higher on the Informant Questionnaire on Cognitive Decline in the Elderly.

RESULTS: From an initial cohort of 18 605 participants, 10 058 were included (5062 men [50.3%]; 4996 women [49.7%]; mean [SD] age, 60.9 [7.2] years). Nonintensive grandchild caregiving was associated with lower odds of dementia (odds ratio [OR], 0.76; 95% CI, 0.60-0.97) than no grandchild care. The mediation analysis revealed that the association of nonintensive grandchild care with dementia odds was partially mediated by mobile telephone ownership (17.68%; 95% CI, 2.05%-37.23%), broadband internet access (17.36%; 95% CI, 5.37%-30.05%), and reduced loneliness (16.83%; 95% CI, 4.52%-30.24%), with a combined mediating proportion of 36.99% (95% CI, 25.01%-51.41%). Neither intensive grandchild caregiving nor having no grandchildren was associated with dementia odds, and no significant indirect effects were observed through the mediators examined.

CONCLUSIONS AND RELEVANCE: In this cohort study of older Chinese adults, nonintensive grandchild caregiving was associated with lower odds of dementia, partly owing to increased digital technology access and reduced loneliness. Promoting digital inclusion and social engagement could be beneficial for cognitive health, particularly among older adults providing moderate levels of grandchild care.

PMID:40632534 | DOI:10.1001/jamanetworkopen.2025.19622

JAMA Netw Open. 2025 Jul 1;8(7):e2519630. doi: 10.1001/jamanetworkopen.2025.19630.

ABSTRACT

IMPORTANCE: An association between interstitial lung disease (ILD) and lung cancer has been hypothesized but never established. To date, whether this potential association persists after controlling for genetic factors has not been addressed.

OBJECTIVE: To evaluate the association between ILD and the subsequent risk of different histological subtypes of lung cancer in the general population and a sibling-controlled cohort.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study incorporated both population-based and sibling-controlled designs and used data from the Swedish Total Population Register and Swedish Multi-generation Register. Participants included individuals born between 1932 and 1987, with follow-up starting January 1, 1987, and continuing until December 31, 2016. Data were analyzed from February 15, 2024, to January 30, 2025.

EXPOSURES: ILD.

MAIN OUTCOMES AND MEASURES: The association between ILD and lung cancer was evaluated using multivariable hazard ratios (HRs) and 95% CIs.

RESULTS: Among the 5 425 976 individuals involved in this study (14 624 with ILD and 5 411 352 from the general population), 2 779 108 (51.2%) were male and most (2 068 062 [38.1%]) were 20 to 40 years of age. Among patients with ILD, most (9630 [65.9%]) were older than 40 years. During a 30-year follow-up period, 40 592 cases of lung cancer were diagnosed among those without ILD (incidence rate, 26.2 per 100 000 person-years) and 227 cases among those with ILD (incidence rate, 355.4 per 100 000 person-years). After adjusting for sex, age, calendar period, educational attainment, and smoking-related diseases, individuals with ILD had a higher risk of lung cancer (HR, 2.16; 95% CI, 1.89-2.46). Sibling-controlled analyses showed a higher risk (HR, 2.91; 95% CI, 1.98-4.27). Elevated risks were observed for adenocarcinoma (HR, 1.60; 95% CI, 1.28-2.01), squamous cell carcinoma (HR, 2.56; 95% CI, 1.99-3.29), small cell carcinoma (HR, 3.29; 95% CI, 2.32-4.68), and other histological types (HR, 2.32; 95% CI, 1.78-3.01). Results from sibling-controlled analyses generally mirrored these findings.

CONCLUSIONS AND RELEVANCE: This large prospective cohort study found that ILD was associated with increased risk of most histological subtypes of lung cancer. Therefore, the presence of ILD should be included in lung cancer risk assessment models.

PMID:40632533 | DOI:10.1001/jamanetworkopen.2025.19630

JAMA Netw Open. 2025 Jul 1;8(7):e2519706. doi: 10.1001/jamanetworkopen.2025.19706.

ABSTRACT

IMPORTANCE: Childhood bereavement increases the risk of common psychiatric disorders later in life. However, the role of stress resilience in this association remains underexplored.

OBJECTIVE: To assess whether stress resilience mediates the association between childhood bereavement and psychiatric disorder risk in adulthood.

DESIGN, SETTING, AND PARTICIPANTS: Three matched cohort studies were performed using data recorded in the Swedish Military Conscription Register. Individuals with childhood loss of either a parent or a sibling (19 162 participants), a parent (16 247 participants), or a sibling (3023 participants) due to death from 1987 to 2020, together with 10 unexposed individuals per exposed individual, were matched on sex, birth year, and county of birth. All participants had available stress resilience measure at conscription. Data were analyzed from February to December 2024.

EXPOSURES: Childhood bereavement was ascertained from the Swedish Multi-Generation and Causes of Death Registers.

MAIN OUTCOMES AND MEASURES: Incident diagnosis of depression, anxiety, substance use disorder, and stress-related disorder was ascertained from the Swedish Patient Register. Cox models were used to estimate the association between childhood bereavement and risk of postconscription psychiatric disorders after multivariable adjustment. Causal mediation analysis was conducted to examine if stress resilience measured at conscription mediated this association.

RESULTS: Among 1 733 085 conscripted individuals (median [IQR] age at conscription 18.2 [18.0-18.5] years; 1 707 960 [98.5%] male), the median (IQR) age of individuals exposed to loss of either a parent or a sibling, parent, or sibling was 13.4 (9.6-15.8), 13.7 (10.4-15.9), and 10.7 (5.5-14.9) years, respectively. The crude incidence rate of any psychiatric disorder was 7.9, 8.1, and 6.6 per 1000 person-years among the 3 groups (5.3, 5.8, and 5.5 per 1000 person-years among the respective unexposed groups). A positive association was noted for loss of either a parent or a sibling (HRs ranged from 1.13; 95% CI, 1.06-1.20 for anxiety to 1.31; 95% CI, 1.23-1.40 for substance abuse disorder) and loss of a parent (HRs ranged from 1.10; 95% CI, 1.01-1.20 for stress-related disorders to 1.19; 95% CI, 1.12-1.27 for depression). For loss of a sibling, the statistically significant associations were for any common psychiatric disorder (HR, 1.12; 95% CI, 1.00-1.25) and stress-related disorders (1.27; 95% CI, 1.04-1.55). Stress resilience partially mediated the associations (proportions for loss of either a parent or a sibling ranged from 10.6%-19.4%, for a parent ranged from 15.6%-21.7%, and for a sibling ranged from 6.2% for stress-related disorders to 18.4% for any common psychiatric disorder).

CONCLUSIONS AND RELEVANCE: In this cohort study of a nationwide Swedish sample, altered stress resilience was found to be one mechanism through which childhood bereavement is associated with risk of psychiatric disorders later in life.

PMID:40632532 | DOI:10.1001/jamanetworkopen.2025.19706

JAMA Dermatol. 2025 Jul 9. doi: 10.1001/jamadermatol.2025.2004. Online ahead of print.

ABSTRACT

IMPORTANCE: No prospective epidemiologic studies have investigated genetic vs environmental factors on the risks of nevus-associated melanoma (NAM) and de novo melanoma.

OBJECTIVE: To determine whether the risk factor profile differs for nevus-associated and de novo invasive melanoma, and whether the associations differ according to sex.

DESIGN, SETTING, AND PARTICIPANTS: This population-based prospective cohort study (the QSkin Study) conducted in Queensland, Australia, included participants aged 40 to 69 years at baseline. Participants were recruited in 2011 and followed up until December 2022. All analyses were conducted between October 2024 and January 2025.

EXPOSURES: Self-reported information from the baseline survey on phenotypic factors (hair color, tanning ability, nevus density, family history), sun exposure-related factors (sunburns, history of skin cancers and actinic lesions), and polygenic risk scores for melanoma and nevus development was collected.

MAIN OUTCOME AND MEASURES: The primary outcome was incident invasive melanoma (nevus-associated and de novo).

RESULTS: A total of 17 752 males and 21 049 females were included and 859 were analyzed. During a median (IQR) follow-up of 11.4 (11.2-11.7) years, 209 participants developed an invasive nevus-associated melanoma (129 in males and 80 in females) and 650 developed an invasive de novo melanoma (362 in males and 288 in females). Many of the known phenotypic and sun exposure-related risk factors for melanoma were similarly associated with nevus-associated and de novo melanoma, but high nevus density and high genetic propensity for melanoma development had significantly higher hazard ratios (HRs) for NAM than de novo melanoma (HR for many moles vs no moles, 6.86 [95% CI, 3.82-12.33] vs 3.21 [95% CI, 2.23-4.63]; P = .001; HR for melanoma polygenic risk score tertile 3 vs tertile 1, 6.46 [95% CI, 3.42-12.20) vs 2.98 [95% CI, 2.21-4.02]; P = .006). No significant differences in the risk factor profile for NAM were found for sex, but the HR for older age was significantly higher among males with de novo melanoma than in females. The site distribution of NAM differed for males and females, occurring mostly commonly on the trunk in males and on the limbs in females.

CONCLUSIONS AND RELEVANCE: Results of this study identified distinct risk factor profiles for NAM and de novo melanomas, particularly polygenic risk and nevus propensity. Males and females tended to develop NAM on different body sites, which may have implications for early detection strategies.

PMID:40632528 | DOI:10.1001/jamadermatol.2025.2004

Epilepsia. 2025 Jul 9. doi: 10.1111/epi.18539. Online ahead of print.

ABSTRACT

OBJECTIVE: The CSMD genes, including CSMD1, CSMD2, and CSMD3, encoding synaptic transmembrane proteins, play important roles in neuronal maturation, growth of dendrites, and processes of synapses. Our recent study showed that CSMD1 was associated with developmental epileptic encephalopathy (DEE) and generalized epilepsy. The significance of CSMD2 and CSMD3 in human disease is unknown.

METHODS: Trio-based whole-exome sequencing was performed in patients with focal epilepsy without acquired etiologies. The gene-disease association was validated by excess and damaging effect of variants, genotype-phenotype correlation, and studies on spatial-temporal and single-cell expression.

RESULTS: CSMD2 variants were identified in six and CSMD3 variants were identified in four cases with focal epilepsy. Additional CSMD3 variants were identified in three cases with febrile seizures plus and one case with infantile spasms. The variants included 1 de novo, 1 homozygous, and 12 pairs of compound heterozygous variants. All variants were missense except one and presented no or extremely low minor allele frequencies, which were significantly lower than that of benign variants and higher in excess by multiple statistical analyses. The gene-disease association was further supported by correlation between damage scoring of variants and phenotype severity. The three CSMD genes are expressed predominantly at early development stages, correlated with the neurodevelopment abnormalities/DEE. CSMD1 expression increases significantly starting with later childhood, consistent with the poor prognosis of DEE. CSMD2 presented the highest expression in the developing brain, with predominance in inhibitory neurons, explaining the focal epilepsy and focal cortical dysplasia (FCD). CSMD3 expressed in relatively low levels with less neuron-specificity explained the heterogeneous phenotypes.

SIGNIFICANCE: The CSMD genes are associated with epilepsies, CSMD2 with focal epilepsy/FCD, and CSMD3 with a phenotype spectrum that includes focal epilepsy, febrile seizures, and DEE. The distinct phenotypes of CSMD genes are explained by their features of genetic dependent stage and the development-dependent expression pattern of neuron specificity.

PMID:40632521 | DOI:10.1111/epi.18539