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Nevin Manimala Statistics

Meta-analysis models with group structure for pleiotropy detection at gene and variant level using summary statistics from multiple datasets

Biostatistics. 2024 Dec 31;26(1):kxaf037. doi: 10.1093/biostatistics/kxaf037.

ABSTRACT

Genome-wide association studies (GWASs) have highlighted the importance of pleiotropy in human diseases, where one gene can impact 2 or more unrelated traits. Examining shared genetic risk factors across multiple diseases can enhance our understanding of these conditions by pinpointing new genes and biological pathways involved. Furthermore, with an increasing wealth of GWAS summary statistics available to the scientific community, leveraging these findings across multiple phenotypes could unveil novel pleiotropic associations. Existing selection methods examine pleiotropic associations one by one at a scale of either the genetic variant or the gene, and thus cannot consider all the genetic information at the same time. To address this limitation, we propose a new approach called MPSG (Meta-analysis model adapted for Pleiotropy Selection with Group structure). This method performs a penalized multivariate meta-analysis method adapted for pleiotropy and takes into account the group structure information nested in the data to select relevant variants and genes (or pathways) from all the genetic information. To do so, we implemented an alternating direction method of multipliers algorithm. We compared the performance of the method with other benchmark meta-analysis approaches such as GCPBayes, PLACO, and ASSET by considering as inputs different kinds of summary statistics. We provide an application of our method to the identification of potential pleiotropic genes between breast and thyroid cancers.

PMID:41241933 | DOI:10.1093/biostatistics/kxaf037

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Nevin Manimala Statistics

Long-Term Follow-Up of Neoadjuvant Enzalutamide Plus Androgen Deprivation Therapy in Localized Prostate Cancer: A Secondary Analysis of a Neoadjuvant Feasibility Trial

Prostate. 2025 Nov 16. doi: 10.1002/pros.70093. Online ahead of print.

ABSTRACT

INTRODUCTION: Neoadjuvant intense androgen deprivation therapy (ADT) with androgen receptor signaling inhibitors (ARSIs) has shown pathologic complete responses (pCR) in prostate cancer (PCa), but long-term survival outcomes remain unclear. This study evaluates the durability of response following neoadjuvant ADT plus enzalutamide before robot-assisted radical prostatectomy (RARP) and lymph node dissection.

METHODS: We conducted a secondary analysis of an open-label feasibility trial enrolling men with NCCN intermediate-, high-, very high-risk localized and regional PCa treated with 6 months of neoadjuvant ADT and enzalutamide. Factors associated with biochemical recurrence (BCR) and metastases were evaluated using appropriate univariable statistical tests, and BCR-, metastasis-free survival (MFS), and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method.

RESULTS: Of 39 patients enrolled, 36 patients completed all study interventions. Eighteen (66.7%) patients had NCCN very high-risk disease or clinical regional lymph nodes on imaging. Four patients (11.1%) achieved pCR, although two (5.6%) developed BCR. One patient (2.8%) had M1 and three (8.3%) had N1 disease on final pathology, and all four developed metastases. Eleven (30.6%) patients received salvage therapy, with all but one receiving ADT with radiation. Factors associated with BCR included biopsy ISUP grade and positive surgical margins, while NCCN risk group, biopsy ISUP grade, perineural invasion, and pathological stage were associated with metastases (p < 0.05). Median follow-up was 7.3 (95% CI 6.3-8.3) years, and the 5-year BCR-free survival, MFS, and CSS were 64.1%, 84.6%, and 94.3%, respectively.

CONCLUSIONS: Neoadjuvant enzalutamide and ADT was associated with favorable long-term oncologic outcomes, supporting continued investigation in localized PCa.

PMID:41241930 | DOI:10.1002/pros.70093

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Nevin Manimala Statistics

Spinal Muscular Atrophy Carrier Screening: Assessment of Provider Knowledge and Clinical Practice

Prenat Diagn. 2025 Nov 16. doi: 10.1002/pd.70023. Online ahead of print.

ABSTRACT

OBJECTIVE: The American College of Obstetricians and Gynecologists (ACOG) recommends offering spinal muscular atrophy (SMA) carrier screening (CS) preconception or prenatally. This study aimed to determine provider knowledge of SMA and SMA CS practice patterns and to describe the relationship between knowledge and comfort while discussing screening and results.

METHOD: Prenatal providers completed an anonymous web-based survey on SMA knowledge, CS practice patterns, and comfort in interpretation of results. Data were summarized with descriptive statistics. The relationship between provider training and SMA knowledge with provider comfort was analyzed.

RESULTS: 75% (112/150) of providers responded and 64.6% completed the survey. Participants varied in roles and years of experience. The mean score on knowledge was 3.8/8 (47.5%) with 20.6% of respondents scoring ≥ 75% and 51.6% scoring ≥ 50%. Knowledge did not vary with years of experience. Although 91.3% of providers offer SMA screening, less than 25% reported complete comfort discussing screening and results. Comfort correlated with role and experience. Providers who felt completely comfortable discussing SMA screening had higher knowledge scores.

CONCLUSION: Although the majority of providers offer SMA CS, provider knowledge regarding SMA is low, and most are not comfortable discussing screening and results.

PMID:41241929 | DOI:10.1002/pd.70023

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Nevin Manimala Statistics

The final year for community-dwelling older adults with dementia in an Asian setting: admissions, interventions, and caregiver burden

J Gerontol A Biol Sci Med Sci. 2025 Nov 6;80(12):glaf227. doi: 10.1093/gerona/glaf227.

ABSTRACT

BACKGROUND: Current understanding of the last year of life with dementia is disproportionately informed by studies conducted in western contexts, primarily within long-term care settings. This study examines the last year of life experience for community-dwelling older adults and their caregivers in an Asian setting.

METHODS: Using prospective longitudinal cohort data from 125 family caregivers to older adults who have died during the study, we estimate separate random effects regression models to identify factors associated with hospital admissions, medical interventions, care experience, and informal caregiving hours. We also estimate costs associated with informal caregiving hours.

RESULTS: Nearly half (48%) of older adults experienced an inpatient admission, and nearly all (92%) experienced a potentially burdensome intervention. Urinary tract infections were the strongest predictor of hospital admissions (adjusted odds ratio [AOR] = 10.42, p = .00) and medical interventions (AOR = 9.61, p = .02). Pneumonia (AOR = 8.40, p = .05) and febrile episodes (AOR = 3.94, p = .03) were associated with increased odds of intervention, whereas caregivers who prioritized comfort care only were associated with reduced interventions (AOR = 0.28, p = .04) and increased admissions (AOR = 3.20, p = .04). Family caregivers provided 42 hours of care per week on average, and 30% gave up their employment to care for the older adult during the older adult’s final year.

CONCLUSIONS: Community-dwelling older adults in Singapore experienced similar clinical problems and potentially more burdensome interventions, including feeding tubes and physical restraints, than described previously in other contexts, highlighting the need for a palliative approach not apparent in the frequent acute care utilization, interventions, and caregiving burden observed.

PMID:41241927 | DOI:10.1093/gerona/glaf227

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Nevin Manimala Statistics

Hierarchy of nanoparticles toxicity factors significance as extracted from NanoCommons knowledge base: influence of compound, cell line and particle size on cell viability

Nanotoxicology. 2025 Sep;19(6):553-574. doi: 10.1080/17435390.2025.2555307. Epub 2025 Nov 16.

ABSTRACT

The objective of the paper was to conduct a thorough statistical meta-analysis of a publicly available database by examining cell membrane damage (CMD), mitochondrial membrane potential (MMP), nuclear size (NS), nuclear intensity (NI), and cell viability (CVV) responses toward nanoparticles. The set of individual 880 and the subset of 630 measurements contained exposure dose, particle diameter, nanoparticle identity (TiO2, Ag, SiO2, CeO2, ZnO, Cu), and cell type (A549, HCT116, HepaRG, HEPG2, RAW264.7) correlated to toxicity markers. The exposure dose was revealed as the most consistent predictor of toxicity across all endpoints, with higher doses significantly influencing toxicity. The compound-specific response was another important factor, where Ag, ZnO, and Cu, were consistently more cytotoxic, while ZnO and Cu correlated to loss of CVV and MMP. Contrary, TiO2, CeO2 and SiO2 displayed partial protective effects, depending on cell context. The effect of particle size was compound- and endpoint-specific, e.g. smaller particles of CeO2 displayed greater disruption to nuclear architecture (NS, NI) and MMP, while size had minimal effect on CVV for other compounds. HepaRG cells were the most sensitive, specifically from Cu and ZnO, while epithelial lines (e.g. HCT116, HEPG2) showed more complex patterns. Generally, the dose was confirmed as the most impactful predictor, due to consistent and statistically significant effects. Compounds and cell lines were determined as factors of next-highest importance, displaying mixed but significant effects, and the particle size showed lowest effects. These findings highlight the importance of multi-endpoint, multi-cell-type frameworks in nanotoxicology for compound- and cell-specific risk assessments.

PMID:41241926 | DOI:10.1080/17435390.2025.2555307

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Personal and work-related factors that impact the decision to have the first and recurrent abortion among women in Serbia

Libyan J Med. 2025 Dec 31;20(1):2575709. doi: 10.1080/19932820.2025.2575709. Epub 2025 Nov 16.

ABSTRACT

Despite the wide availability of contraception, the abortion rate in Serbia remains high. Being in a steady relationship and perceiving low risk to catch sexually transmitted infections have been identified as the most common reason to not use condom, while around 11% of females used oral contraceptive pill. The study aim was to investigate the reasons of Serbian women to seek induced abortion as well as the factors that might impact the decision to terminate pregnancy. A cross-sectional study was conducted at the Clinic for Ob/Gyn, University Clinical Centre of Serbia in Belgrade, which is a referral public tertiary health care institution. Women who underwent induced abortions from 2022 to 2024 filled in a questionnaire on socio-demographic characteristics, life-style and habits, medical history and motives for an induced abortion. Multivariate regression models were used to identify factors associated with each reported abortion motive. The study analyzed 433 women aged 16 to 49 years (mean 32.0 years). The most common motives for abortion were already having enough children (44.3%) and financial difficulties for child upbringing (42.0%). In contrast, gaining weight and concerns about physical changes due to pregnancy was the least endorsed reason for seeking an abortion. The majority of women (52.9%) reported multiple motives for abortion. Motives were generally the same for women who the first and recurrent abortion. Most common factors influencing the decision to terminate pregnancy were not being in a relationship or marriage and vigorous physical activity at workplace. One-half of women had multiple motives for abortion and more than 50% of women sought abortion multiple times. The most important factors associated with voluntary abortion seeking is not having a steady partner and working in a physically demanding job. These findings should be considered in the public health policy agenda.

PMID:41241916 | DOI:10.1080/19932820.2025.2575709

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Nevin Manimala Statistics

Comparison of single-incision and traditional laparoscopic surgery for the risk of incisional hernia: a systematic review and meta-analysis of randomized controlled trials

Updates Surg. 2025 Nov 16. doi: 10.1007/s13304-025-02434-4. Online ahead of print.

ABSTRACT

Despite the growing popularity of single-incision laparoscopic surgery (SILS), no large-scale meta-analysis has compared the incidence of incisional hernia (IH) between SILS and traditional laparoscopic surgery (TLS).We make a meta-analysis of randomized controlled trials (RCTs) to compare the risk of IH between SILS and TLS. We searched studies in PubMed, Web of Science, and EMBASE databases for RCTs that compared SILS to TLS and reported IHs with a minimum follow-up period of 6 months. The risk of bias was assessed using the ROBINS-II tool. We used the R software to summarize and compare the incidence of IH between SILS and TLS. Additionally, we conducted subgroup analyses to explore the impact of surgical (including procedure type, incision length, incision approach, incision direction, fascia closure, and operation time) and patient factors (including BMI, age, and race) on the incidence of IH. 37 RCT studies were included in this meta-analysis. In the single-arm analysis, the incidence of IH in the SILS group was 0.7% (95% CI 0.2-1.5%), and 0.3% (95% CI 0.1-0.8%) in the TLS group. SILS does not confer an increased risk of IH, with an OR of 1.52 (95% CI 0.98-2.36) and P = 0. 57. Only variations in surgical procedures significantly influenced the incidence of IH when comparing SILS and TLS. Our study did not demonstrate a statistically significant difference in the incidence of IH between the SILS and TLS groups. Therefore, SILS is a viable alternative for patients who require minimally invasive surgical interventions. However, future RCTs with larger sample sizes and extended follow-up periods are warranted to further validate the safety profile.

PMID:41241886 | DOI:10.1007/s13304-025-02434-4

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Nevin Manimala Statistics

Prevalence and correlates of indoor smoking bans on traditional tobacco use in Hungary in 2009 and 2022

Orv Hetil. 2025 Nov 16;166(46):1818-1826. doi: 10.1556/650.2025.33410. Print 2025 Nov 16.

ABSTRACT

Bevezetés: A dohányzás lakáson belüli tiltása csökkenti a másodlagos dohányfüstnek való kitettséget, megelőzi a rászokást, és elősegíti a leszokást. Magyarországon kevés adat áll rendelkezésre a dohányfüstmentes háztartási szabályok időbeli változásáról és korrelátumairól. Célkitűzés: A hagyományos dohányzás lakáson belüli önkéntes tiltásának prevalenciáját, időbeli trendjét és szociodemográfiai korrelátumait feltáró vizsgálat. Módszer: Két 2009-ben és egy 2022-ben felvett kérdőíves kutatás adatainak másodelemzését végeztük el. Az elemzési egység a háztartás volt. Z-próbát, Cochran–Armitage-trendtesztet és binomiális logisztikus regressziót alkalmaztunk átlagos marginális hatásérték (AME) számításával. Eredmények: A dohányzás lakáson belüli teljes tiltásának aránya 2009 és 2022 között 60,6%-ról 75,1%-ra emelkedett (h = 0,3; p<0,01) Magyarországon. Ennek ellenére 2022-ben a 18 év alatti gyermekek 25,2%-a (95% CI 22,5–28,0%) továbbra is olyan háztartásban élt, ahol megengedett volt a beltéri dohányzás. A pénzügyi nehézségek (AME ≈ –0,09 – –0,01) és a legalább egy dohányzó háztartástag (AME ≈ –0,42 – –0,30) minden modellben negatív hatást mutatott. 18 éven aluli gyermek jelenléte a háztartásban enyhén növelte a teljes tiltás valószínűségét (AME ≈ 0,02–0,10). Megbeszélés: Bár a lakáson belüli tiltás terén javulás tapasztalható, a 18 éven aluliakat továbbra sem védi megfelelően a beltéri dohányfüsttől minden magyar háztartás. Következtetés: Eredményeink célzott egészségkommunikációs és intervenciós beavatkozások szükségességére hívják fel a figyelmet, különösen a hátrányos helyzetű és dohányzó taggal rendelkező gyermekes háztartások körében. Orv Hetil. 2025; 166(46): 1818–1826.

PMID:41241884 | DOI:10.1556/650.2025.33410

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Nevin Manimala Statistics

Reproducibility and Consistency of Methods to Define Hospital-Level Procedural Volume Thresholds for Pancreatectomy

J Surg Oncol. 2025 Nov 16. doi: 10.1002/jso.70134. Online ahead of print.

ABSTRACT

INTRODUCTION: Procedural volume thresholds (VTs) for hospital quality reporting rely on expert consensus or analytic methods that may produce inconsistent VTs (e.g. restricted cubic splines (RCS), optimal cutpoints, classification and regression trees (CART), stratum specific likelihood ratios (SSLR)). The objective of this study was to compare variation in hospital-level VTs for pancreatectomy across multiple methodologies.

METHODS: Patients undergoing pancreatectomy from 2004 to 2021 were identified using the National Cancer Database. RCS, optimal cutpoints, CART, and SSLR were used to compute VTs based on 90-day mortality. From a single clinical data set, VTs were derived multiple times for each method by varying statistical parameters within each model.

RESULTS: Overall, 61,920 patients underwent pancreatectomy at 982 hospitals. VTs associated with reductions in 90-day mortality ranged from 9.2 to 26.1 cases/year (RCS), 15.7-33.8 cases/year (optimal cutpoints), and 11-18 cases/year (CART), all based on modifiable statistical parameters. SSLR analysis yielded a singular VT of 21 cases/year without variability due to lack of statistical input.

CONCLUSION: Among 4 common strategies for identifying VT that we studied, SSLR required the fewest assumptions. This may make it ideal for enhancing transparency and standardization in outcomes reporting.

PMID:41241876 | DOI:10.1002/jso.70134

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Effect of Including Cervical Stability Training with Treatment Modalities for Patients with Forward Head Posture and Chronic Neck Pain: a Randomized Trial

J Manipulative Physiol Ther. 2025 Nov 15:S0161-4754(25)00055-7. doi: 10.1016/j.jmpt.2025.10.025. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to examine the effect of adding cervical stability training (CST) to a battery of treatment modalities on somatosensory evoked potential (SSEP) in patients with forward head (FHP) and chronic mechanical neck pain (CMNP).

METHODS: Sixty patients with FHP and CMNP were randomized into 2 groups: Group A (study group) was subjected to CST and a battery of treatment modalities, whereas Group B (traditional group) underwent a battery of treatment modalities alone. Treatment was applied 3 sessions per week for 8 successive weeks. The primary outcomes were SSEP and craniovertebral angle (CVA). The secondary outcomes were visual analog scale for pain intensity, Neck Disability Index Arabic version for functional disability, an endurance test for neck flexor and extensor muscles, craniocervical flexion test for deep cervical flexor muscles activation, lateral radiographs using the posterior tangent method for cervical lordotic curvatures, and a phone application clinometer for cervical range of motion.

RESULTS: The findings demonstrated short-term statistically significant differences (P < .05) at posttreatment between the study and traditional treatment groups in favor of the study group. The mean difference and 95% CI between both groups in SSEP and CVA = 1.83 (1.63, 2.03) and 7.37 (6.49, 8.25), respectively.

CONCLUSION: For patients with chronic neck pain, CST exercises plus a battery of treatment modalities exhibited a greater effect on primary and secondary outcomes than the battery of treatment modalities alone.

PMID:41241867 | DOI:10.1016/j.jmpt.2025.10.025