Tag: nevin manimala

Stat Med. 2025 Aug;44(18-19):e70109. doi: 10.1002/sim.70109.

ABSTRACT

The benefits of vaccination to protect against the different variants of the SARS-CoV-2 Virus are well-known in the literature. In the United States, public health policy has led to a wide availability of COVID-19 vaccines that are usually freely available to everyone 6 months and older. However, several factors including misinformation create vaccine hesitancy and threaten to undercut the advances of the COVID-19 vaccination program. In this article, we take a network-based approach to investigate community acceptance of vaccines at the county level in the United States, using data from the Centers for Disease Control and Prevention (CDC). We use an exponential random graph model to discover important sociodemographic factors that influence the patterns of vaccination between counties and communities. In addition, we undertake an advanced topological data analysis (TDA) based network clustering method to discover more macrolevel communities that show common trends for COVID-19 vaccine acceptance in the United States. Our study uncovers that sociodemographic features, for example, higher education, household income, and US census regions have significant effects on COVID-19 vaccine acceptance. The cluster analysis demonstrates that different census regions as well as rural and urban areas have distinct preferences in COVID-19 vaccine acceptance.

PMID:40844841 | DOI:10.1002/sim.70109

Nephrol Dial Transplant. 2025 Aug 22:gfaf169. doi: 10.1093/ndt/gfaf169. Online ahead of print.

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a serious complication during pediatric cancer treatment. Nephrotoxic medication may increase the risk of developing AKI, which may necessitate modifications to standard treatment and may also increase the risk of chronic kidney disease (CKD). This study investigates the incidence of AKI, the impact of nephrotoxic medications and the association between AKI and the development of CKD.

METHODS: In this retrospective national cohort study, we analyzed 1 525 pediatric cancer patients treated at the Princess Máxima Center between 2015 and 2021. AKI was classified using KDIGO criteria based on serum creatinine. The effect of nephrotoxic medications and other risk factors on AKI incidence and progression was assessed by using a cause specific hazard regression model. The cumulative incidence of AKI was estimated with a competing risk model with death as competing event. The effect of risk factors on CKD, defined as an eGFR < 90 ml/min/1.73m² one year after cancer treatment, was evaluated with a logistic reression.

RESULTS: We included 1525 patients, 37% experienced AKI. A competing risk model identified treatment with ifosfamide, amphotericin B, acyclovir and busulfan as strong, independent risk factors for a first episode of AKI. Older age was also associated with an increased risk of AKI.At one-year follow-up (n = 1 159), 13.6% had CKD (eGFR < 90 mL/min/1.73 m²), and 2.8% had an eGFR < 60. AKI (occurred during treatment) was the strongest predictor of CKD: a single AKI episode increased the risk 2.6-fold, while more episodes increased it nearly 16-fold. Nephrectomy was also identified as independent risk factors for CKD.

CONCLUSION: Acute kidney injury (AKI) is common in children with cancer and is strongly associated with an increased risk of chronic kidney disease (CKD). Awareness is crucial for high-risk patients, particularly those receiving nephrotoxic medications, with a history of multiple AKI episodes or a prior nephrectomy. Comprehensive monitoring strategies should be implemented at diagnosis, during therapy, and during the post-treatment period to enable early detection and timely intervention, ultimately reducing the risk of AKI and its progression to CKD.

PMID:40844823 | DOI:10.1093/ndt/gfaf169

Biostatistics. 2024 Dec 31;26(1):kxaf022. doi: 10.1093/biostatistics/kxaf022.

ABSTRACT

Brain functional connectivity (FC), the temporal synchrony between brain networks, is essential to understand the functional organization of the brain and to identify changes due to neurological disorders, development, treatment, and other phenomena. Independent component analysis (ICA) is a matrix decomposition method used extensively for simultaneous estimation of functional brain topography and connectivity. However, estimation of FC via ICA is often sub-optimal due to the use of ad hoc estimation methods or temporal dimension reduction prior to ICA. Bayesian ICA can avoid dimension reduction, estimate latent variables and model parameters more accurately, and facilitate posterior inference. In this article, we develop a novel, computationally feasible Bayesian ICA method with population-derived priors on both the spatial ICs and their temporal correlation (that is, their FC). For the latter, we consider two priors: the inverse-Wishart, which is conjugate but is not ideally suited for modeling correlation matrices; and a novel informative prior for correlation matrices. For each prior, we derive a variational Bayes algorithm to estimate the model variables and facilitate posterior inference. Through extensive simulation studies, we evaluate the performance of the proposed methods and benchmark against existing approaches. We also analyze fMRI data from over 400 healthy adults in the Human Connectome Project. We find that our Bayesian ICA model and algorithms result in more accurate measures of functional connectivity and spatial brain features. Our novel prior for correlation matrices is more computationally intensive than the inverse-Wishart but provides improved accuracy and inference. The proposed framework is applicable to single-subject analysis, making it potentially clinically viable.

PMID:40844820 | DOI:10.1093/biostatistics/kxaf022

Neurol Ther. 2025 Aug 22. doi: 10.1007/s40120-025-00813-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Perimesencephalic subarachnoid hemorrhage (pmSAH) is a rare, typically benign subtype of non-aneurysmal subarachnoid hemorrhage (SAH). While the majority of patients demonstrate a positive recovery trajectory, a subset of patients experiences complications, including vasospasm, hydrocephalus, or delayed cerebral ischemia (DCI). Reliable imaging markers for risk stratification are lacking. This study evaluates whether volumetric CT-based biomarkers-validated in aneurysmal SAH (aSAH)-are also predictive for pmSAH.

METHODS: In this retrospective single-center study, 72 patients with confirmed pmSAH between 2011 and 2024 were analyzed. The automated volumetric segmentation was performed using 3D Slicer and TotalSegmentator to quantify intracranial volume (ICV), brain volume (BV), cerebrospinal fluid (CSF), and selective sulcal volume (SSV). The associations between volumetric parameters and clinical presentation, complications, and functional outcome (Glasgow Outcome Scale, GOS) were assessed using non-parametric statistics and Spearman correlation.

RESULTS: The median intracranial volume was 1352.7 mL, brain volume 1247.3 mL, cerebrospinal fluid volume 95.9 mL, and selective sulcal volume 19.4 mL. Vomiting at presentation was associated with higher CSF and SSV values (p = 0.04 and p = 0.005, respectively), but no significant volumetric differences were found regarding other symptoms or complications (vasospasm, hydrocephalus, DCI). GOS scores were uniformly high (median = 5), and none of the volumetric markers significantly correlated with outcome or complication rate (all p > 0.05).

CONCLUSION: In contrast to aSAH, volumetric CT biomarkers such as ICV, BV, CSF, and SSV do not offer predictive value in patients with pmSAH. Risk stratification should continue to rely on initial hemorrhage pattern and volume, clinical monitoring, and individualized assessment rather than other volumetric parameters.

PMID:40844796 | DOI:10.1007/s40120-025-00813-y

Parasitol Res. 2025 Aug 22;124(8):96. doi: 10.1007/s00436-025-08508-x.

ABSTRACT

Ehrlichia ruminantium, the causative agent of heartwater, is a tick-borne pathogen affecting livestock in Africa and the Caribbean. This disease is transmitted primarily by Amblyomma variegatum ticks and poses a significant threat to animal health. In Madagascar, the prevalence of E. ruminantium remains poorly documented. During a Rift Valley fever (RVF) outbreak in Mananjary, Madagascar (April-May 2021), we conducted a field study to assess the circulation of vector-borne pathogens in ticks collected from ruminants. Ticks were morphologically identified, and DNA was extracted for quantitative PCR targeting the pCS20 gene of E. ruminantium. Statistical analyses were performed to explore associations between tick infection status, ruminant health, and infestation levels. A total of 332 ticks were collected from 25 ruminants. The tick species identified included Rhipicephalus microplus (51.5%) and Amblyomma variegatum (48.2%). E. ruminantium DNA was detected in 5.1% (17/332) of ticks, consisting of 16 A. variegatum and one R. microplus, with the majority being male. No association was observed between ruminant clinical signs and the presence of infected ticks. This study provides the first molecular evidence of E. ruminantium circulation in ticks from Madagascar during an RVF outbreak. Our findings emphasize the need for improved disease surveillance and integrated tick control strategies to mitigate the impact of heartwater on livestock.

PMID:40844790 | DOI:10.1007/s00436-025-08508-x

Eur J Trauma Emerg Surg. 2025 Aug 22;51(1):279. doi: 10.1007/s00068-025-02950-3.

ABSTRACT

BACKGROUND: Severe trauma continues to pose a substantial burden on survivors, particularly in terms of long-term physical, psychological, and social functioning. While survival rates have improved, data on long-term outcomes remain limited. This study evaluates ten-year post-injury outcomes in patients with major trauma, focusing on return to work and social participation.

METHODS: In this single-center, retrospective cohort study, adult patients (≥ 18 years) with an Injury Severity Score (ISS) ≥ 9 treated between 2010 and 2013 were surveyed and distributed minimally 10 years later. Patients completed standardized questionnaires assessing sociodemographic and occupational data, functional status, and psychological well-being using the Trauma Outcome Profile (TOP).

RESULTS: Ninety-one patients completed the follow-up. The mean age at injury was 43.0 years, with a mean ISS of 20.8. Ten years post-trauma, 82.4% of patients had returned to work; 10.6% required vocational retraining, and 25.3% changed occupations. Failure to return to work was significantly associated with higher ISS (p = 0.027), increased anxiety (p = 0.005), post-traumatic stress disorder (PTSD, p = 0.039), and reduced mental functioning (p = 0.009), but not with physical functioning ten years after the trauma. Patients with mental health impairments were more likely to experience reduced independence, impaired social participation, and difficulties in activities of daily living.

CONCLUSION: A majority of patients successfully reintegrated into the workforce ten years after trauma. Mental health, rather than physical disability, emerged as the primary determinant of long-term occupational reintegration. These findings underscore the necessity for comprehensive, long-term rehabilitation programs that prioritize psychosocial support.

PMID:40844786 | DOI:10.1007/s00068-025-02950-3

JAMA Netw Open. 2025 Aug 1;8(8):e2527284. doi: 10.1001/jamanetworkopen.2025.27284.

ABSTRACT

IMPORTANCE: Long-term back problems impact an individual’s ability to participate in the workforce productively, potentially resulting in financial stress and furthering inequities. Estimates of future productivity losses could inform advocacy and policy making.

OBJECTIVE: To estimate the productivity losses of long-term back problems in working-age Australians (aged 15-64 years) over the next 10 years (2024-2033).

DESIGN, SETTING, AND PARTICIPANTS: This modeling study used a dynamic population-level model to simulate the population of working Australians with long-term back problems. Age- and sex-specific prevalence and workforce participation data were obtained from the 2022 National Health Survey. Excess all-cause mortality, absenteeism, and presenteeism data due to long-term back problems were derived from published sources.

MAIN OUTCOMES AND MEASURES: Primary outcomes were years of life lost, full-time equivalent workers lost, and productivity losses due to long-term back problems. Productivity losses were estimated as productivity-adjusted life-years and associated costs to Australia’s gross domestic product (GDP).

RESULTS: In 2024, 2 950 538 Australians had long-term back problems, which was projected to increase to 3 258 612 million by 2033. Long-term back problems resulted in an estimated loss of 3 394 255 productivity-adjusted life-years over the 10-year period, equating to a loss of more than 638 billion Australian dollars in Australia’s GDP. Reducing the relative prevalence and incidence of long-term back problems by 10% was estimated to result in a gain of 41.4 billion Australian dollars in GDP over the 10-year period.

CONCLUSIONS AND RELEVANCE: In this modeling study estimating future productivity losses from long-term back problems, substantial economic gains could be achieved from reducing the prevalence and impact of the condition. This model highlights the need to assess the effectiveness of interventions on work-related outcomes.

PMID:40844779 | DOI:10.1001/jamanetworkopen.2025.27284

JAMA Netw Open. 2025 Aug 1;8(8):e2527769. doi: 10.1001/jamanetworkopen.2025.27769.

ABSTRACT

IMPORTANCE: Immune checkpoint inhibitors (ICIs) show efficacy in treatment of several solid tumors, but microsatellite-stable rectal cancer is largely resistant. Radiotherapy may enhance tumor immunogenicity and thus may make the combination of radiotherapy and ICIs a promising strategy to treat rectal cancer. While anti-programmed cell death protein 1 antibodies in neoadjuvant regimens have been linked to higher complete response rates, the added benefit of including a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor remains unclear.

OBJECTIVE: To evaluate the safety and feasibility of combining ipilimumab and nivolumab with neoadjuvant chemoradiotherapy (CRT) for rectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: The CHINOREC trial was a prospective, randomized, open-label, multicenter phase 2 clinical trial conducted from June 2, 2020, to March 15, 2024, across multiple academic and tertiary medical centers in Austria. Analysis was based on intention to treat.

INTERVENTION: Neoadjuvant CRT consisted of 50 Gy in 2-Gy fractions with concurrent capecitabine (1650 mg/m2/d). The experimental arm received additional intravenous ipilimumab (1 mg/kg on day 7) and nivolumab (3 mg/kg every 2 weeks starting on day 14) (CRT plus ipilimumab and nivolumab group). Surgical resection was performed 10 to 12 weeks after CRT.

MAIN OUTCOME AND MEASURES: The primary outcome was the safety and feasibility of combining CRT with sequential ipilimumab and nivolumab, assessed by surgical complications and reoperation rates. Secondary outcomes included clinical and pathological response rates.

RESULTS: Of the 145 patients assessed, 80 were randomized to receive either CRT alone (CRT group) (n = 30) or to the CRT plus ipilimumab and nivolumab group (n = 50) (49 male [61%]; median age, 60 [range, 36-83] years). Differences in surgical complication rates were not statistically significant between the CRT and CRT plus ipilimumab and nivolumab groups (any grade, 20 of 26 patients [77%] vs 33 of 43 [77%]; P > .99), as were reoperation rates (2 of 26 [8%] vs 3 of 43 [7%]; P > .99). Major pathological response (10 of 26 [38%] vs 16 of 43 [37%]; P > .99) and complete response (9 of 30 [30%] vs 11 of 50 [22%]; P = .44) rates were overall high in both groups.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of patients with rectal cancer, integrating ipilimumab and nivolumab into neoadjuvant CRT was safe and feasible, with no increase in surgical complications. Although complete response rates did not significantly improve, the dual ICI regimen demonstrated promising clinical activity. These findings support further translational research to optimize timing, dosing, and fractionation of radiotherapy and ICI therapy and to guide patient selection.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04124601.

PMID:40844778 | DOI:10.1001/jamanetworkopen.2025.27769

JAMA Health Forum. 2025 Aug 1;6(8):e252273. doi: 10.1001/jamahealthforum.2025.2273.

ABSTRACT

IMPORTANCE: Persons from marginalized racial and ethnic groups and of low socioeconomic status are at high risk of dementia but are underrepresented in clinical trials. Financial incentives may improve representation.

OBJECTIVE: To evaluate the effect of financial incentives on enrollment of county health system patients into a memory concerns registry.

DESIGN, SETTING, AND PARTICIPANTS: Between March 1, 2024, and April 24, 2024, patients 50 years and older without a dementia diagnosis within a single integrated county health system that includes a hospital and 9 outpatient health centers were invited to enroll in the Alzheimer Prevention Trials (APT) Webstudy, an online observational study aimed at accelerating enrollment into Alzheimer disease clinical trials.

INTERVENTIONS: Patients were randomized 1:1:1 to an invitation message (arm 1), a message with a small ($25) enrollment incentive (arm 2), or a message with an enrollment incentive of entry into a $2500 lottery with 1 in 100 odds of award (arm 3).

MAIN OUTCOMES AND MEASURES: The primary outcome was enrollment, defined as APT Webstudy registration and completion of at least 1 of 2 remote cognitive assessments. Outcomes were measured through April 30, 2024.

RESULTS: Of 44 844 patients invited to the APT Webstudy, the mean (SD) age was 64.7 (10.1) years, 25 447 (56.8%) were women, 25 044 (55.8%) had Medicaid insurance, 11 347 (25.3%) were Hispanic/Latino, 9526 (21.2%) were non-Hispanic Asian, 6044 (13.5%) were non-Hispanic Black, and 12 109 (27%) were non-Hispanic White. A total of 401 participants (0.9%) enrolled in the APT Webstudy. Relative to the message-only arm, participants randomized to the small incentive arm were more likely to enroll (adjusted odds ratio [OR], 1.39; 95% CI, 1.09-1.76; P = .008) in the APT Webstudy while those in the prize incentive arm were not more likely to enroll (adjusted OR, 1.08; 95% CI, 0.84-1.39; P > .99). Enrollment in the prize incentive arm was lower relative to the small incentive arm (adjusted OR, 0.78; 95% CI, 0.61-0.98; P = .04). Secondary heterogeneity analyses indicated that patients of White race (adjusted OR, 1.61; 95% CI, 1.15-2.25; P = .006) and male sex (adjusted OR, 2.40; 95% CI, 1.55-3.75; P < .001) were most responsive to the small $25 incentive relative to the message-only arm.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, relative to message invitations, invitations with guaranteed, small financial incentives but not lottery incentives increased enrollment of economically but not necessarily racially or ethnically diverse participants to a study that aimed to increase enrollment in clinical studies.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06033066.

PMID:40844772 | DOI:10.1001/jamahealthforum.2025.2273

JAMA Health Forum. 2025 Aug 1;6(8):e252631. doi: 10.1001/jamahealthforum.2025.2631.

ABSTRACT

IMPORTANCE: Brand-name drugs in the US are sold at high prices during market exclusivity periods defined by their patents, before prices are lowered by generic competition. Drug manufacturers use several strategies to extend these market exclusivity periods and delay generic competition, including obtaining overlapping thickets of patents.

OBJECTIVE: To estimate excess US spending associated with delays in generic competition due to extended market exclusivity for 4 top-selling drugs.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective serial cross-sectional study focused on 4 top-selling drugs that experienced new generic competition between 2014 and 2018 to allow enough time for determining postexclusivity price trajectories: imatinib (Gleevec, cancer), glatiramer (Copaxone, multiple sclerosis), celecoxib (Celebrex, arthritis), and bimatoprost (Lumigan, glaucoma). Drug monthly spending data from 2011 to 2021 were retrieved from a large commercial claims database (Merative MarketScan) and a random sample of Medicare beneficiaries with at least 1 month of Medicare Parts A, B, and D coverage and adjusted for estimated rebates obtained from SSR Health, LLC. The analysis was performed between March 2023 and January 2024.

EXPOSURES: Extended market exclusivity was calculated as the time between expiration of the key patent and first generic marketing.

MAIN OUTCOMES AND MEASURES: The primary outcome was net monthly national drug spending in commercial insurance and Medicare Part D. Spending was estimated under 2 scenarios: (1) the status quo, reflecting observed spending trends, and (2) a counterfactual scenario, modeling spending in the absence of extended market exclusivity. Segmented linear regression analyses were used to assess level and slope changes in monthly spending following generic entry. Weights were applied to extrapolate sample-based estimates to the full US commercially insured and Medicare Part D populations.

RESULTS: Market exclusivity extensions beyond expiration of the key patent ranged from 7 (celecoxib) to 13 (glatiramer) months. In the absence of extended market exclusivity, and over a 2-year period following generic competition, net spending would have decreased by $3.5 billion, including $1.9 (95% CI, $1.3-$2.5) billion in commercial plans and $1.6 (95% CI, $1.1-$2.1) billion in Medicare-including $67 (95% CI, $22-$115) million for bimatoprost, $726 (95% CI, $516-$938) million for celecoxib, $1.7 (95% CI, $1.0-$2.4) billion for glatiramer, and $1.0 (95% CI, $0.8-$1.2) billion for imatinib.

CONCLUSIONS AND RELEVANCE: This study found that promoting timely generic availability and avoiding extending market exclusivity for top-selling drugs may result in substantial savings for US patients and payers, including both public and private health insurance programs.

PMID:40844771 | DOI:10.1001/jamahealthforum.2025.2631