Tag: statistics

HGG Adv. 2026 Mar 26:100595. doi: 10.1016/j.xhgg.2026.100595. Online ahead of print.

ABSTRACT

The genetic liability to a complex phenotype can be assessed via polygenic risk scores (PRS) and is calculated as the sum of genotypes, weighted by effect size estimates derived from summary statistics of genome-wide association study (GWAS) data. Due to different allele frequencies (AF) and linkage disequilibrium (LD) patterns across populations, PRS that were developed on one population drop drastically in predictive performance when transferred to another. One of the major factors contributing to AF and LD heterogeneity is genetic drift, which acts strongly during population bottlenecks and is influenced by the dominance of certain alleles. In particular, since the causal variants on empirical data are typically not known, the presence of population specific LD-patterns will strongly affect transferability of PRS models. In this work, we therefore conducted demographic simulations to investigate the influence of the dominance coefficient on the transferability of PRS among European, African and Asian populations. By modifying the length and size of the bottleneck leading to the split of Eurasian and African populations, we gain a deeper understanding of the underlying dynamics. Finally, we illustrate that in our simulations PRS models that are adapted to the underlying dominance coefficient can substantially increase the prediction performance in out-of-target populations.

PMID:41902401 | DOI:10.1016/j.xhgg.2026.100595

Pharmacoepidemiol Drug Saf. 2026 Apr;35(4):e70362. doi: 10.1002/pds.70362.

ABSTRACT

Immunocompromised individuals experience an impaired immune function due to conditions that might be either congenital or acquired over the course of their lives. Epidemiological studies often rely on clinical definitions which, in some cases, benefit from being translated into machine-readable algorithms for application to electronic health records (EHRs) databases. The transient nature of certain immunocompromised states and the variability of phenotypes, definitions, coding practices, and data availability entangle this operation. To address these challenges, we conducted a scoping review of existing immunocompromised status definitions in MEDLINE, focusing on epidemiologic and pharmacoepidemiologic studies involving immunocompromised populations. Data extraction was guided by clinical experts, categorizing conditions and medications into seven categories: genetic/hereditary conditions, infectious diseases, malignancies and chemotherapy, organ and stem-cell transplantations, severe systemic conditions, immunosuppressive drugs, and autoimmune conditions associated with immunosuppressant use. Out of 137 citations, 56 studies were included. Most of the studies focused on a particular disease or therapeutic area. Frequently cited diagnoses included HIV/AIDS (17.9%) and organ transplantation (14.2%). Methotrexate, corticosteroids, TNF-alpha inhibitors, and calcineurin inhibitors were the most common drugs used to define immunocompromised status. Building on this review and expert opinion, we developed a phenotype algorithm that combines diagnostic, therapeutic, and procedural data in a modular way to identify immunocompromised populations in EHR data sources. The proposed phenotype algorithm can be applied across diverse data sources, settings and research questions. Future research should test its applicability across heterogeneous EHR data sources.

PMID:41902365 | DOI:10.1002/pds.70362

Trauma Violence Abuse. 2026 Mar 27:15248380261429956. doi: 10.1177/15248380261429956. Online ahead of print.

ABSTRACT

Experiences of instability and unpredictability within the family context have been demonstrated to augment risk for child abuse and neglect. This scoping review aimed to synthesize and evaluate current evidence of the association between childhood instability and risk for maltreatment. Studies were identified using predetermined search terms and parameters across three electronic databases. Inclusion criteria for this review were peer-reviewed empirical articles, written in English, that conducted statistical analysis of the relationship between instability and child maltreatment. A total of 64 articles were included in the review, the majority of which focused on residential instability (n = 23), followed by economic instability (n = 11) and relational instability (n = 11), housing instability (n = 10), school instability (n = 6), and psychological instability (n = 4). Across over 4 decades of research, our review suggests that childhood instability is a multifaceted construct that is often associated with elevated exposure to abuse and neglect. In addition, the association between childhood instability and risk for maltreatment was pronounced among younger children. This review underscores the importance of examining childhood instability as a dynamic factor implicated in the etiology of child maltreatment. Integrating the multiple dimensions of childhood instability into a unified conceptual framework may facilitate the development of more precise maltreatment risk models that are both informed by and responsive to the complex and evolving needs of vulnerable families.

PMID:41902360 | DOI:10.1177/15248380261429956

Pharmacoepidemiol Drug Saf. 2026 Apr;35(4):e70361. doi: 10.1002/pds.70361.

ABSTRACT

PURPOSE: Pregnant women in Norway are offered routine ultrasound examinations in the first and second trimester during gestational weeks 11-13 and 17-19, but attendance rates are unknown. With the introduction of maternal pertussis vaccination, we sought to investigate whether ultrasound attendance during pregnancy could identify the target population for maternal vaccination. Our study aims to investigate if pregnancy-related ultrasound codes alone can provide reliable estimates of ongoing pregnancies before data is available in birth records.

METHODS: In this nationwide population-based register study, we linked individual-level data from women with births in the Medical Birth Registry of Norway (MBRN) and first or second trimester ultrasound codes in the Norwegian Patient Registry (NPR) during 2018-2023. We calculated the proportion of pregnancies with pregnancy-related ultrasound examination codes, with trimester-specific codes from 2022, and median gestational age at ultrasound stratified by code.

RESULTS: For the entire study period (2018-2023), we retrieved data on 323 549 pregnancies for 249 915 women. Of the 59 739 pregnancies identified through MBRN in 2022-2023, 57 416 (96.1%) had at least one recorded routine trimester-specific ultrasound. The second trimester ultrasound was recorded in 92.9% (55 503/59 739) of pregnancies, with 87.7% (48 672/55 503) at the recommended time. The first trimester ultrasound code was recorded in 61.6% (36 799/59 739) of pregnancies, and 58.4% (34 886/59 739) had both codes.

CONCLUSIONS: The high attendance rate of at least one routine ultrasound examination during pregnancy (96.1%) in 2022-2023 confirms the reliability of trimester-specific ultrasound codes as an indicator for ongoing pregnancies. This provides valuable data for timely assessment of interventions targeting pregnant women, before information is available in birth registries.

PMID:41902358 | DOI:10.1002/pds.70361

Pharmacoepidemiol Drug Saf. 2026 Apr;35(4):e70355. doi: 10.1002/pds.70355.

ABSTRACT

OBJECTIVE: To assess the safety of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in pregnant women in the United States using data from the Vaccine Adverse Event Reporting System (VAERS).

DESIGN, SETTING: We searched VAERS for reports of Tdap in pregnant women vaccinated during July 2015 through September 2023. We reviewed reports and available medical records for pregnancy and non-pregnancy specific adverse events (AEs) in Tdap recipients. Reporting rates were estimated for reports of preterm birth, hypertensive disorders of pregnancy (HDP), and stillbirths and compared to published background rates for these conditions.

RESULTS: VAERS received a total of 654 reports after Tdap vaccine in pregnancy and 137 (20.9%) were serious; no maternal or infant deaths were reported. The most common pregnancy specific conditions reported were preterm birth (45, 6.9%), hypertensive disorders of pregnancy (40, 6.1%), and stillbirth (18, 2.8%). Two reports of verified Guillain-Barré Syndrome (GBS) were reported. The most common non-pregnancy specific conditions reported were pain (120, 18.3%), nausea (93, 14.2%), and fever (87, 13.3%). Reporting rates for preterm birth, HDP, and stillbirths were below background rates for these conditions.

CONCLUSION: Most reports were non-serious and the most common AEs were similar to those observed in pre- and post-licensure studies. No new or unexpected AE was identified.

PMID:41902357 | DOI:10.1002/pds.70355

Personal Ment Health. 2026 May;20(2):e70072. doi: 10.1002/pmh.70072.

ABSTRACT

The alternative model for personality disorders (AMPD) is approaching readiness for inclusion in the main section of the DSM, yet research informing its development has largely overlooked the perspectives of those who receive personality disorder diagnoses. This commentary argues that centering lived experience is essential for evaluating the AMPD’s diagnostic language, given evidence that certain trait terminology (notably “manipulativeness”) is perceived as highly stigmatizing. The AMPD’s Criterion A, which emphasizes personality functioning rather than dispositional traits, may offer a less stigmatizing framework-a possibility supported by emerging lived experience accounts. Building on recent work by Sharp, Cano, Masland, Navarré, and colleagues, this commentary proposes research priorities for integrating lived experience perspectives into AMPD evaluation and considers whether the ICD-11‧s sub-diagnostic “personality difficulty” category could serve both clinical and destigmatizing functions if adopted within the AMPD.

PMID:41902346 | DOI:10.1002/pmh.70072

Orthop Surg. 2026 Mar 27. doi: 10.1111/os.70290. Online ahead of print.

ABSTRACT

OBJECTIVE: This study introduces a modified minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) technique to address the limitations of conventional MIS-TLIF, including soft tissue injury, excessive reliance on intraoperative fluoroscopy, and a steep learning curve. We evaluated the clinical efficacy of this modified approach in the treatment of single-level degenerative lumbar spine disease, with the aim of elucidating its advantages over the traditional technique and summarizing key technical considerations.

METHODS: This retrospective study analyzed 286 patients who underwent surgery between January 2018 and July 2021 for single-level degenerative lumbar disease. Patients were divided into modified MIS-TLIF (n = 131) and traditional MIS-TLIF (n = 155) groups. Clinical outcomes were evaluated using the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association (JOA) scores. Surgical parameters included operation time, intraoperative blood loss, fluoroscopy time, hospital stay, and complication rates. Radiographic assessments used CT and dynamic lateral X-rays to evaluate interbody fusion, while MRI was used to measure the fatty infiltration ratio of the multifidus (MF-FI Ratio). Continuous variables were compared between groups using independent-samples t tests, whereas categorical variables were analyzed using the chi-square test or Fisher’s exact test when expected cell counts were < 5. Paired t tests were employed to compare preoperative and postoperative measurements within each group. A two-tailed p < 0.05 was considered statistically significant.

RESULTS: Baseline characteristics showed no significant differences between groups (p > 0.05). Postoperative VAS, ODI, and JOA scores improved significantly in both groups (p < 0.05). All cases achieved successful fusion at the final follow-up. Compared to the traditional group, the modified MIS-TLIF group had shorter operation time (101.83 ± 26.23 vs. 117.81 ± 27.87 min), less blood loss (111.83 ± 26.22 vs. 147.68 ± 28.19 mL), shorter fluoroscopy time (12.35 ± 1.72 vs. 50.33 ± 6.36 s), fewer complications (5/131 vs. 16/155), and a lower MF-FI ratio (36.67% ± 4.52% vs. 39.61% ± 4.58%).

CONCLUSION: The modified MIS-TLIF technique better preserves paravertebral muscles, reduces radiation exposure, shortens operative time, and lowers complication rates, offering a more optimized treatment option for managing single-segment lumbar degeneration.

PMID:41902343 | DOI:10.1111/os.70290

Clin Transl Allergy. 2026 Apr;16(4):e70166. doi: 10.1002/clt2.70166.

ABSTRACT

BACKGROUND: In the United States, beta-lactam allergy labels (BLAL) are documented in 9%-16% of hospitalized patients and associated with worse clinical outcomes such as increased mortality, length of hospital stay (LOS), intensive care unit (ICU) admission, and use of alternative antibiotics, providing an incentive for broad delabeling protocols. In Europe, BLAL prevalences are lower (0.6%-5%) and the association with clinical outcomes insufficiently explored. Therefore, we assessed the association between BLAL and penicillin allergy label (PenAL) and clinical outcomes and antibiotic use in hospitalized patients in Belgium.

METHODS: Retrospective population-based cohort study of all patients admitted to the University Hospitals Leuven between 2010 and 2018 for pneumonia, pyelonephritis (therapeutic indications), or appendectomy, coronary artery bypass grafting, total knee or hip replacement (prophylactic indications) or heart, kidney, liver, or lung transplantation (mixed indications). Multivariable regression analysis was performed, using BLAL or PenAL as independent variable, and age, gender, Charlson Comorbidity Index, and diagnosis as a priori hypothesized confounders.

RESULTS: We included 21,999 patients accounting for 23,842 admissions. A BLAL was recorded in 1394 (6.3%) patients, with 1113 (5.1%) having an unspecified PenAL. An increased use of next-line antibiotics was observed among patients with BLAL or PenAL. However, BLAL or PenAL were not associated with altered in-hospital or 3-month post-hospitalization mortality, LOS or ICU admission.

CONCLUSION: Despite altered antibiotic use, we observed no association of BLAL or PenAL with clinical outcome parameters, highlighting regional differences and limiting transferability of non-EU findings to guide EU delabeling protocols.

PMID:41896181 | DOI:10.1002/clt2.70166

Mil Med. 2026 Mar 27:usag138. doi: 10.1093/milmed/usag138. Online ahead of print.

ABSTRACT

INTRODUCTION: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA) is a rare, self-resolving, under-recognized autoinflammatory condition impacting young children. There is limited management and outcome data on PFAPA. Our study aims to describe the diagnostic and treatment approach, family impact, and outcomes of children with PFAPA from the perspective of their parents.

MATERIALS AND METHODS: We performed a survey-based case series study targeted toward parents of children diagnosed with PFAPA. Department of Defense beneficiaries diagnosed with PFAPA between ages 0 and 18 years and cared for by a Military Pediatric Infectious Disease physician at Naval Medical Center Portsmouth or Walter Reed National Capital Consortium between 2012 and 2023 were included. Parents of these patients were contacted via telephone and invited to participate in the online anonymous survey covering PFAPA diagnostic timeline, management strategies, clinical outcomes, and the impact on the patient’s family. Quantitative data from the survey was analyzed using descriptive statistics, and qualitative data from free text responses underwent manual thematic analysis.

RESULTS: Twenty-two children were identified with PFAPA, and 17 parents were successfully contacted and invited to participate. Of these, 10 parents completed the survey. For eight (80%) patients, a PFAPA diagnosis required more than four healthcare visits and took greater than a year from symptom onset. Seven parents reported use of abortive corticosteroids for PFAPA treatment, and four (40%) underwent tonsillectomy, resulting in immediate cessation of fever episodes for three of the four patients. At the time of the survey, 70% of children with PFAPA had experienced resolution of their fever episodes. Nearly every parent stated that PFAPA led to missed school and workdays. Half of respondents stated that PFAPA negatively impacted their child’s mental health and/or family well-being. More than half (60%) of respondents expressed feeling dismissed in their concerns and wished more providers were knowledgeable about PFAPA.

CONCLUSIONS: For most children with PFAPA, diagnosis requires more than four healthcare visits and over a year of time. PFAPA is a self-limited condition but poorly impacts families through missed school, missed workdays, and other family life disruptions. Parents of children with PFAPA want to be heard when they express concerns about frequent fever episodes and want providers to be better informed about PFAPA and available treatment options.

PMID:41896172 | DOI:10.1093/milmed/usag138

Pediatr Neonatol. 2026 Mar 7:S1875-9572(26)00036-7. doi: 10.1016/j.pedneo.2025.11.013. Online ahead of print.

ABSTRACT

BACKGROUND: Torsades de Pointes (TdP) is a life-threatening polymorphic ventricular tachycardia often associated with corrected QT prolongation (QTc). In infants, the risk factors and drug associations remain poorly characterized, despite their vulnerability to adverse drug reactions. This study aimed to identify drugs associated with TdP and QT prolongation in infants using data from the USFDA Adverse Event Reporting System (AERS).

METHODS: We conducted a disproportionality analysis utilizing data from the USFDA AERS database, applying the Standardized MedDRA Narrow Query (SMQ) for TdP/QT prolongation. Reports were filtered for infants aged ≤1 year, and duplicate cases were excluded. We employed both frequentist and Bayesian statistical methods for signal detection, focusing on the reporting odds ratio and proportional reporting ratio for frequentist analysis, and the Information Component for Bayesian analysis.

RESULTS: A total of 224 unique reports were identified. Significant signals for drugs associated with TdP and QT prolongation were detected, including anesthetics (fentanyl, propofol), systemic antibacterials (erythromycin, azithromycin), and various cardiac medications (propranolol, amiodarone, flecainide). Notably, midazolam was strongly associated with long QT syndrome, while a range of drugs showed links to ventricular tachycardia. Overall, 19 (8.5%) reports resulted in death, 117 (52.2%) involved hospitalization, and 51 (22.8%) were life-threatening events.

CONCLUSION: This study highlights critical drug safety signals for TdP and QT prolongation in infants, emphasizing the need for vigilant monitoring and cautious drug use in this vulnerable population. Further research is essential to elucidate risk factors and improve pharmacovigilance strategies in pediatric care.

PMID:41896159 | DOI:10.1016/j.pedneo.2025.11.013