Tag: statistics

Early Interv Psychiatry. 2026 Jul;20(7):e70215. doi: 10.1111/eip.70215.

ABSTRACT

AIM: To evaluate the effectiveness of digital interventions in supporting young caregivers’ mental health, well-being, and caregiving experiences, and to assess implementation factors including adherence and acceptability.

METHOD: We systematically searched six databases (MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Central, and Scopus) and grey literature sources from inception to March 2025, identifying studies evaluating digital interventions for caregivers aged 25 years or younger. Study selection, data extraction, and risk of bias assessment were conducted independently by two reviewers. Due to substantial heterogeneity, narrative synthesis was performed following the Synthesis Without Meta-analysis (SWiM) reporting guidelines.

RESULTS: From 752 records, six studies met inclusion criteria, comprising three randomized controlled trials, one feasibility study, and two development/adaptation studies. Interventions included web-based platforms, mobile applications, audio-conferencing systems, and e-learning platforms. Digital tools showed limited effectiveness for mental health outcomes but demonstrated promise for quality-of-life improvements, with one trial showing statistically significant results (Wilks’ λ = 0.95, F(4, 418) = 2.74, p = 0.03). Adherence varied dramatically between self-guided platforms (26%) and structured programs (93%). All RCTs demonstrated a high risk of bias.

DISCUSSION: These findings reveal a ‘digital paradox’ whereby the theoretical advantages of accessibility failed to translate into engagement without human facilitation. Digital interventions for young caregivers require hybrid models combining technological convenience with relational support, structured flexibility, and continuous co-design with young caregivers to optimize engagement and effectiveness. The limited number of included studies and uniformly high risk of bias across RCTs underscore the need for pragmatic trials with robust implementation evaluations.

PROSPERO REGISTRATION: CRD42024604175.

PMID:42385212 | DOI:10.1111/eip.70215

Int J Nurs Pract. 2026;32(4):e70162. doi: 10.1111/ijn.70162.

ABSTRACT

BACKGROUND: Health literacy and fear of disease progression can predict quality of life, yet the underlying mechanisms among these three factors remain poorly understood.

AIM: This study aimed to investigate the hypothesis that health literacy among patients with ischemic stroke is associated with fear of disease progression and both directly and indirectly influence quality of life through the mediating role of fear of disease progression.

METHODS: Between December 2023 and June 2024, questionnaires were distributed to 300 in-patients with ischemic stroke selected by convenience sampling from the neurology departments of three tertiary general hospitals in the Xiangxi region of Hunan Province. Assessments were conducted using the General Information Questionnaire, the Medical Outcomes Study Short Form 36 (SF-36), Health Literacy Management Scale (HeLMS) and Fear of Progression Questionnaire-Short Form (FoP-Q-SF). Pearson correlation analysis was employed to examine the correlations between variables; AMOS 24.0 statistical analysis software was used to explore the pathways and effect sizes of fear of disease progression and health literacy on quality of life.

RESULTS: Health literacy was positively correlated with quality of life (r = 0.412, p < 0.01), while fear of disease progression was negatively correlated with quality of life (r = -0.445, p < 0.01). Fear of disease progression partially mediated the relationship between health literacy and quality of life, accounting for 41.3% of the total effect.

CONCLUSIONS: Findings support the development of targeted psychosocial intervention strategies aimed at enhancing patients’ health literacy to effectively alleviate disease-related fear, ultimately improving quality of life and optimizing care outcomes for stroke patients.

PMID:42385192 | DOI:10.1111/ijn.70162

Stat Med. 2026 Jul;45(15-17):e70659. doi: 10.1002/sim.70659.

ABSTRACT

The current bedrock of precision prevention is selecting high-risk individuals for screening or other prevention services under the assumption that those at highest risk would have the highest benefit from prevention services. However, this may not hold when disease risk and competing mortality are highly correlated. In such cases, risk-based prevention may preferentially select older individuals with multiple comorbidities who would have substantially reduced life-years gainable from the service and increased risks of harm from any resulting surgical procedures. For such prevention services, we propose a benefit-based selection strategy in which individuals are selected according to their expected gain in life-years (i.e., difference in mean survival time with and without the prevention service). We estimate the expected gain in life-years for individuals in a target screening population by combining data from a randomized trial, which may not be population-representative, and data from a population-representative survey that has larger sample size, more covariates, and longer follow-up time to evaluate mortality than the trial. We derive the Taylor-linearized variances for the estimated expected gain in life-years that take into account the randomness due to both trial and survey sample. We show that benefit-based selection of ever-smokers for lung-cancer screening can identify individuals with more favorable benefit-harm trade-offs compared to risk-based selection. Using simulation studies, we examine the conditions in which one strategy may be preferable over the other.

PMID:42385157 | DOI:10.1002/sim.70659

Int J Inj Contr Saf Promot. 2026 Jul 1:1-16. doi: 10.1080/17457300.2026.2689077. Online ahead of print.

ABSTRACT

This paper explores historical and contemporary intersections between mass-mortality epidemics and violent crime in South Africa, focusing on four major epidemics – Spanish Flu, tuberculosis, HIV, and Covid-19. The study integrates epidemiological data and contextual historical information such as crime statistics, archival records, and secondary scholarship to explore whether epidemic-driven mortality crises are associated with subsequent changes in violence and injury profiles. With the possible exception of gendered violence, the study finds little evidence that earlier epidemics directly contributed to rapid or sustained increases in violent crime, despite causing substantial adult mortality and long-term social and economic disruption. A comparison between epidemic and socio-economic profiles strongly suggests that the significant increases in violent crime recorded after the Covid-19 pandemic are highly localised, and may be more strongly related to lockdown responses, including alcohol restrictions, rather than the effects of disease itself.

PMID:42385127 | DOI:10.1080/17457300.2026.2689077

J Clin Oncol. 2026 Jul 1:JCO2600550. doi: 10.1200/JCO-26-00550. Online ahead of print.

ABSTRACT

PURPOSE: Mantle cell lymphoma (MCL) is a rare and typically aggressive B-cell non-Hodgkin lymphoma characterized by recurrent relapse after short remissions. Sonrotoclax (BGB-11417) is a next-generation B-cell lymphoma 2 inhibitor with greater selectivity and potency than venetoclax, a shorter half-life, and no drug accumulation. Sonrotoclax monotherapy was evaluated in Bruton tyrosine kinase inhibitor-pretreated patients with relapsed/refractory (R/R) MCL.

METHODS: BGB-11417-201 (ClinicalTrials.gov identifier: NCT05471843) is an ongoing global, open-label, phase I/II trial. Sonrotoclax was orally administered once daily with gradual, 4-week ramp-up to 160 mg or 320 mg to mitigate tumor lysis syndrome (TLS). The primary end point was overall response rate by the independent review committee (ORR-IRC) per Lugano classification; secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Overall, 125 patients were enrolled and assigned to receive sonrotoclax 160 mg (n = 10) or 320 mg (n = 115) target doses once daily. Most patients had advanced disease (stage IV, 78.3%) and were heavily pretreated (median prior therapies, 3). In efficacy-evaluable patients (n = 103), the ORR-IRC was 52.4% (95% CI, 42.4 to 62.4), a statistically significant increase versus the historic control ORR (30%; P < .0001); the complete response rate was 15.5%. Responses were seen across high-risk subgroups, including patients with TP53 mutation (59.1%). With a median study follow-up of 14.2 months, the median DOR-IRC was 15.8 months, and the median PFS-IRC was 6.5 months. Median OS was not reached. The most common all-grade/grade ≥3 treatment-emergent adverse events were neutropenia (35.7%/19.1%), thrombocytopenia (24.3%/9.6%), and anemia (24.3%/7.8%). TLS occurred in 7.0% of patients; all cases resolved without sequelae.

CONCLUSION: Sonrotoclax demonstrated rapid, durable responses and manageable safety in heavily pretreated patients with R/R MCL, including high-risk subgroups, supporting its further clinical evaluation as an oral therapy for R/R MCL.

PMID:42385124 | DOI:10.1200/JCO-26-00550

Neurology. 2026 Jul 28;107(2):e218280. doi: 10.1212/WNL.0000000000218280. Epub 2026 Jul 1.

ABSTRACT

BACKGROUND AND OBJECTIVES: Genetics represent a nonmodifiable risk factor for Alzheimer disease (AD), with 60%-80% heritability. Midlife hypertension is a modifiable risk factor for both dementia and death. Our primary objective was to determine how genetic risk for AD modifies the association between hypertension and dementia.

METHODS: The Atherosclerosis Risk in Communities Study is an ongoing community-based prospective cohort study of 4 US centers. We analyzed White and Black participants free of dementia at age 55 years with genotypes and blood pressure measured at visit 1 (1987-1989). Three genetic risk groups (low, medium, high) were defined based on tertiles of a race-specific AD polygenic risk score. Dementia was ascertained through cognitive testing, informant interviews, hospitalization, codes and death records. Death was ascertained through the National Death Index. We examined the association of midlife hypertension with incident dementia within 3 genetic risk groups using Cox proportional-hazards and cumulative incidence function estimations. We used age 55 years as the time origin, with left truncation to allow entry at ages older than 55 years; age on December 31, 2022, was the administrative censoring date.

RESULTS: Among 8,931 White and 2,666 Black participants, the median follow up time was 26.6 and 23.8 years, the mean age was 54.0/53.5 years, and 53.0%/62.5% were female, respectively. After adjusting for demographics, midlife hypertension was significantly associated with dementia incidence across all genetic risk groups among White participants (low risk hazard ratio [HR] 1.29; 95% CI 1.07-1.55, medium risk HR 1.34; 95% CI 1.13-1.58, high risk HR 1.19; 95% CI 1.03-1.38) and among Black participants at high genetic risk (HR 1.31; 95% CI 1.04-1.66). Associations for low and medium genetic risk Black participants were consistent but not statistically significant. There were no significant differences in association of hypertension with dementia by AD genetic risk group. Individuals with hypertension had a 0%-2% higher probability of developing dementia by age 80 and a 6%-13% lower probability of dementia-free survival to age 80 years vs those without hypertension, across race and genetic risk groups.

DISCUSSION: Genetic risk for AD does not modify the association between hypertension and dementia. These data support the fact that all individuals with hypertension are likely to benefit from antihypertensive treatment.

PMID:42385118 | DOI:10.1212/WNL.0000000000218280

Neurology. 2026 Jul 28;107(2):e218226. doi: 10.1212/WNL.0000000000218226. Epub 2026 Jul 1.

ABSTRACT

BACKGROUND AND OBJECTIVES: Putamen dopamine depletion characterizes Parkinson disease (PD). Intraneuronal processes determining dopamine stores have not been systematically examined. This study explored relative contributions of dopamine synthesis, storage, and metabolism to control-PD differences.

METHODS: We updated an intramural tabulation from 2002 to 2024 of postmortem putamen tissue contents of reactants, including the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), from patients with PD and controls. Based on computational models applying first-order kinetics and equilibrium equations, we then compared estimated rates of dopamine synthesis through tyrosine hydroxylase (TH), L-aromatic-amino-acid decarboxylase, vesicular active uptake and passive leakage, exocytotic release and reuptake, and other intraneuronal processes. Results from the modeling were compared with those from in vivo ¹⁸F-DOPA PET.

RESULTS: Postmortem data were analyzed from 13 patients with PD (median age 77 years, range 73-85 years) and 20 controls (median age 77 years, range 35-91 years). There was approximately a 98% decrease in putamen tissue dopamine in PD, and the concentration ratio of DOPAL/dopamine (DA) was approximately 9 times that of control. Applying the simplest kinetic model, vesicular sequestration was estimated to be decreased by 98.5% (0.073 vs 4.91 nmol/minute). Approximately 3-fold greater in vivo “washout” of putamen ¹⁸F-DOPA-derived radioactivity compared with controls also indicated attenuated vesicular storage in PD. According to the complete model, control-PD differences in intraneuronal reaction rates were in descending order of vesicular uptake ≈ vesicular leakage > exocytotic release ≈ neuronal reuptake > L-aromatic-amino-acid decarboxylase activity ≈ TH activity > other reactions.

DISCUSSION: Convergent quantitative evidence points to a substantial vesicular storage defect in residual dopaminergic terminals in PD. This finding challenges the sufficiency of nigrostriatal dopaminergic denervation alone to account for the biochemical phenotype of PD and highlights vesicular dopamine handling as a critical determinant of putamen dopamine deficiency. The reaction rate estimates were drawn from published point values rather than fitted to an experimental data set, and so conventional goodness-of-fit regression statistics were not conducted. Because of the assumption of steady-state conditions for calculating reaction rates based on equilibrium equations, the model does not address the dynamics of disease pathogenesis over years but does provide a platform for further extension to disease progression.

BRIEF SUMMARY: We estimated rates of reactions involved with the synthesis, storage, release, reuptake, and metabolism of dopamine in the putamen in PD and found that the main intraneuronal functional abnormality separating PD from controls was attenuated vesicular sequestration, implicating decreased vesicular uptake through the vesicular monoamine transporter and increased vesicular leakiness as key determinants of putamen dopamine deficiency in PD.

PMID:42385115 | DOI:10.1212/WNL.0000000000218226

JCO Precis Oncol. 2026 Jul;10(7):e2600045. doi: 10.1200/PO-26-00045. Epub 2026 Jul 1.

ABSTRACT

PURPOSE: Intermediate-risk neuroblastoma patients older than 18 months, with non-MYCN amplified, International Neuroblastoma Risk Group Staging System localized, unresectable or International Neuroblastoma Staging System stage 3 tumors, and unfavorable histology have inferior outcomes compared with other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup.

METHODS: We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms and gene expression in a subset, and correlated results with patient survival.

RESULTS: Among 98 tumors, 9/98 (9.2%) had oncogene amplifications (CDK4/MDM2/TERT coamplification (n = 1), CDK4/MDM2 coamplification (n = 4), CDK4 (n = 2), TERT (n = 1), and MYC (n = 1)), while 63/98 (64.3%) had typical segmental chromosomal aberrations (tSCAs). Patients with tumors with oncogene amplification had the worst 5-year event-free survival (EFS; 0%; P < .0001 log-rank test) and 5-year overall survival (OS; 44.4% [95% CI, 21.4 to 92.3]; P < .01 log-rank test). Patients with tumors harboring tSCAs had inferior EFS compared with those with numerical chromosomal aberrations only (51.7% [95% CI, 40.6 to 65.8] v 93.3% [95% CI, 81.5 to 100]; P < .01). Patients with p53 pathway tumor alterations (n = 10) had worse EFS than those without (0% v 61.1% [95% CI, 50.3 to 74.3]; P < .0001, log-rank test) and worse OS (26.7% [95% CI, 8.9 to 80.3] v 80.9% [95% CI, 71.8 to 91.3]; P < .001 log-rank test). Multivariable analysis identified tSCAs as an independent prognostic variable for EFS and oncogene amplification or p53 pathway abnormalities as independent prognostic variables for EFS and OS.

CONCLUSION: Oncogene amplification and/or p53 pathway abnormalities and/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.

PMID:42385103 | DOI:10.1200/PO-26-00045

JCO Clin Cancer Inform. 2026 Jul;10(3):e2500208. doi: 10.1200/CCI-25-00208. Epub 2026 Jul 1.

ABSTRACT

PURPOSE: Recurrent cancers are not captured in a standardized way by US tumor registries, making it difficult to conduct research on risk factors for cancer recurrence. We developed rule-based algorithms to be used with electronic health data to identify recurrent cases of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

METHODS: Incident DLBCL and FL cases (2000-2018) were identified in tumor registry data at two health plan study sites. We captured pharmacy and procedure codes to indicate first-line treatment initiation. Recurrent cases were defined as those who completed first-line treatment followed by ≥6 months with no treatment-related codes, but who later restarted treatment. The baseline algorithm was built using a claims-based database from Fallon Health (FH; Massachusetts) and tested using electronic health records and claims data at Henry Ford Health (Michigan). Results were validated by chart review at Henry Ford, and measures of validity calculated overall and by subtype. The algorithm was subsequently revised to reduce the false-positive rate.

RESULTS: FH identified 137 DLBCL and 88 FL eligible cases; 42 patients met the baseline algorithm-defined criteria for recurrent disease. Henry Ford identified 246 DLBCL and 146 FL cases. The baseline algorithm identified 115 recurrent cases with a 54% false-positive rate; the revised algorithm (R2D-non-Hodgkin lymphoma [NHL]) identified 60 recurrent cases, with a 10% false-positive rate. Following chart review, the R2D-NHL algorithm had a sensitivity of 74%, specificity of 90%, negative predictive value of 83%, and positive predictive value of 83%. Measures varied slightly between subtypes.

CONCLUSION: We developed a rule-based algorithm that can be applied to electronic health data for population-based research requiring the identification of recurrence for two common but dissimilar NHL subtypes.

PMID:42385099 | DOI:10.1200/CCI-25-00208

JCO Glob Oncol. 2026 Jul;12(7):e2500352. doi: 10.1200/GO-25-00352. Epub 2026 Jul 1.

ABSTRACT

PURPOSE: The number of cancer survivors from low- and middle-income countries is rising, but most research has been conducted in high-income countries. Although studies have characterized the detection and treatment of cervical cancer in Botswana, survivorship care is a severely understudied area. We assessed short- and long-term survivorship visit adherence and factors associated with adherence in patients treated for cervical cancer in Botswana.

METHODS: Between 2015 and 2022, females with cervical cancer were prospectively enrolled in an observational cohort study. Based on recommendations in the Botswana National Cervical Cancer Guidelines, adherence was defined as completion of a clinical visit biannually (every 6 months) during short-term survivorship care (0-2 years after treatment) and annually for long-term survivorship care (3-5 years after treatment). Generalized estimating equations (adjusted odds ratio [aOR]) were used to evaluate factors associated with short- and long-term adherence.

RESULTS: This cohort included 857 females treated with definitive- or curative-intent surgery- or radiation-based treatment, with a median age of 47.7 years (IQR, 41.6-58.2 years) and 68.6% living with HIV. On multivariable analysis of short-term care (n = 772), patients who traveled ≥100 km to the treatment facility (aOR, 0.35; P < .001), had advanced-stage (III and IV) cervical cancer (aOR, 0.69; P = .007), and were undergoing care during the COVID-19 pandemic (aOR, 0.72; P = .005) were less likely to be adherent. Results were similar for long-term care.

CONCLUSION: Adherence to recommended survivorship visits in Botswana is suboptimal. Strategies to help survivors, particularly those living farther away from treatment facilities and with advanced disease, are needed to improve adherence and reduce cervical cancer mortality.

PMID:42385095 | DOI:10.1200/GO-25-00352