Category: Statistics

Otol Neurotol. 2025 Jul 10. doi: 10.1097/MAO.0000000000004597. Online ahead of print.

ABSTRACT

BACKGROUND: Bell’s palsy (BP), a sudden onset of facial paralysis, has been reported in patients with COVID-19. The relationship between COVID-19 infection and BP remains unclear, as does the impact of COVID-19 vaccination on its incidence. This study aims to assess the occurrence of BP before and after the COVID-19 pandemic and to explore any potential effects of COVID-19 vaccination on BP cases.

METHODS: This study utilized data from the TriNetX global health research network, specifically the US Collaborative Network of 68 healthcare organizations, encompassing 99,852,106 patients with ICD codes from 2016 to 2024. BP cases were identified using ICD-10 code G51.0, while COVID-19 vaccinations and infections were identified using CPT codes and TNX Curated 9088, respectively. We conducted an incidence and prevalence analysis of BP cases annually over the 8-year period to detect trends and compared BP rates between prepandemic (2016-2020) and postpandemic (2020-2024) periods using odds ratios. Additionally, we assessed BP incidence among COVID-19 patients and performed a subgroup analysis on vaccinated individuals to evaluate the impact of vaccination on BP incidence. To reduce potential confounding, we employed propensity score matching using the greedy nearest neighbor method available in the TriNetX platform, matching patients on age, sex, race, type 2 diabetes mellitus, and vascular commodities. Statistical analyses were executed within the TriNetX platform and supplemented by online AI tools using Python.

RESULTS: The analysis of BP cases from 2016 to 2024 revealed an upward trend in both incidence and prevalence. The incidence proportion rose from 48 cases per 100,000 people in 2016-2017 to 69 cases per 100,000 by 2023-2024, with a significant increase noted from 2021 onwards. Similarly, the incidence rate increased from 0.00000155 to 0.00000333 over the same period. Prevalence also showed a steady rise, from 228 to 434 cases per 100,000 people. Trend analyses confirmed these increases as statistically significant, with p-values indicating upward trends in incidence and prevalence. Comparing prepandemic (2016-2020) to postpandemic (2020-2024) periods, there was a significant rise in incidence proportions (p-value ≈ 0.0074) and prevalence rates (p-value = 0.0180). Among COVID-positive patients, the incidence proportion remained stable, while prevalence increased, indicating a higher burden compared to the general population. After propensity score matching, vaccinated individuals exhibited a significantly lower risk of BP compared to unvaccinated individuals (hazard ratio: 0.723, 95% CI: 0.618-0.84, p < 0.001).

CONCLUSION: This highlights a significant increase in the incidence and prevalence of BP during the COVID-19 pandemic years compared to prepandemic levels. While the incidence of BP among vaccinated individuals showed a gradual increase, when mitigating for confounding influences using propensity score-matched analyses, it is revealed that these rates remained significantly lower than in unvaccinated populations, indicating a potentially protective association with vaccination. Changes in lifestyle, stress, and distribution of environmental viral loads and potentials during the pandemic may have contributed to a higher susceptibility to BP in the general population.

PMID:40690195 | DOI:10.1097/MAO.0000000000004597

Stat Med. 2025 Jul;44(15-17):e70177. doi: 10.1002/sim.70177.

ABSTRACT

For many diseases and disorders, such as Alzheimer’s disease, patients demonstrate considerable heterogeneity in their responses to treatment interventions. One treatment may be most effective for some patients, while another may be most effective for others, and neither may be effective for another subset of patients. This potentially renders the conventional parallel group design highly inefficient. An attractive alternative is the N-of-1 design, also called the multi-crossover randomized controlled trial. In this design, each participant serves as their own control in a series of randomized blocks of treatment assignments. We propose novel designs for both the single-person and multi-person N-of-1 trials that employ sequential monitoring. In particular, we allow for early stopping for a single participant as soon as there is sufficient evidence of a preferred treatment for them, and early stopping for the group of participants as soon as there is sufficient evidence of a preferred treatment for the population of patients. We provide sample size calculations and decision rules for terminating the trial early and illustrate their properties in simulation studies. We apply our proposed methods to N-of-1 studies of brain tumor excisions and of methylphenidate in mild cognitive impairment.

PMID:40690192 | DOI:10.1002/sim.70177

J Neurooncol. 2025 Jul 21. doi: 10.1007/s11060-025-05107-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer globally with rising incidence in the young population. While rare, brain metastasis (BM) in CRC patients leads to significant morbidity and mortality. The incidence of BM is expected to rise due to improved screening and treatments extending patient survival. However, limited screening guidelines exist to detect BM in patients with CRC.

METHODS: Adult patients with colon and rectum tumors, with and without brain metastases, diagnosed between January 1, 2013, and December 31, 2023, were identified using ICD-10 codes from the TrinetX Oncology database. Statistical analyses were performed on TrinetX. The “incidence and prevalence” function assessed BM prevalence, while the “explore cohorts” function evaluated BM diagnoses over time. The “compare cohorts” function compared patient demographics and oncological characteristics, and the “compare outcomes” function generated Kaplan-Meier survival curves.

RESULTS: There were 8,621 patients with CRC diagnosed at Stage IV and 279 (3.4%) developed BM. Patients who develop BM were younger (58.5 ± 12.6 years vs. 62.3 ± 14 years, p < 0.001) and a greater proportion had a KRAS mutation (37.0% vs. 16.0%, p < 0.001) and HER2 amplification (23.0% vs. 12.0%). BM were more common in primary CRC located on the left, specifically in the rectum (41.0%, vs. 36.0%, p < 0.001) or rectosigmoid junction (48.0% vs. 24.0%, p < 0.001). Patients with lung metastasis (OR [95%CI]: 1.67 [1.11-2.57]) or bone (OR [95%CI]: 4.30 [3.05-5.85]) had increased odds of developing BM. Patients with bone metastases developed BM at a median time of less than six months. Stage IV CRC patients who developed BM had decreased overall survival compared to those without BM (liver HR [95%CI]: 1.35 [1.11-1.64]; lung: 1.98 [1.62-2.43]; bone: 1.69 [1.42-2.07]).

CONCLUSION: Brain metastasis significantly reduces overall survival in Stage IV CRC patients. Stage IV CRC with pulmonary or osseous metastases have increased risk of BM development. These patients merit increased surveillance to identify BM early and improve survival. Other risk factors include a younger age at diagnosis, left sided primary tumor, KRAS mutation, or HER2 amplification.

PMID:40690187 | DOI:10.1007/s11060-025-05107-9

Int Urol Nephrol. 2025 Jul 21. doi: 10.1007/s11255-025-04671-3. Online ahead of print.

ABSTRACT

BACKGROUND: Overactive bladder (OAB) is a common condition in children, affecting 5-12% of children between the ages of 5 and 10 years. It is characterized by urinary urgency, frequency, and nocturia, often leading to incontinence. OAB significantly impacts a child’s emotional and social development, causing anxiety, low self-esteem, and social withdrawal. Oxybutynin is the standard treatment for overactive bladder in children, but side effects like dry mouth, constipation, and cognitive issues can make it difficult for patients to stick with the therapy.

METHODS: This study systematically reviewed and analyzed existing research to evaluate and compare the effectiveness and safety of transcutaneous electrical nerve stimulation (TENS) versus oxybutynin for treating overactive bladder in children. We performed an electronic search of PubMed, Cochrane, and other databases up to April 2023 to identify randomized controlled trials (RCTs) that reported outcomes related to symptom improvement and adverse effects in children with OAB. We included studies based on the PICO criteria: pediatric patients (under 18 years), OAB treatment (TENS or Oxybutynin), and outcomes such as urinary urgency and incontinence. The risk ratios were calculated to compare the two treatments, and heterogeneity was assessed using the I² statistics.

RESULTS: The search found six relevant studies and three of these were suitable for the meta-analysis. The results showed that TENS was much more effective than oxybutynin in improving symptoms, with a risk ratio of 1.93 (95% CI 1.35-2.74). TENS also caused fewer side effects compared to oxybutynin, with a risk ratio of 0.09 (95% CI 0.03-0.30). There was no variation between the studies (I² = 0), indicating that the results were consistent across all trials.

CONCLUSION: TENS has been shown to be both more effective and safer than oxybutynin for treating overactive bladder in children. It leads to greater improvement in symptoms and is linked to fewer side effects. These results indicate that TENS may be a better option, especially for children who have difficulty tolerating medication due to adverse reactions.

PMID:40690105 | DOI:10.1007/s11255-025-04671-3

Forensic Sci Med Pathol. 2025 Jul 21. doi: 10.1007/s12024-025-01045-0. Online ahead of print.

ABSTRACT

A diagnosis of atherosclerotic cardiovascular disease is critical importance in forensic medicine, particularly because severe atherosclerosis is known to be associated with a high risk of sudden death. In South Korea, the assessment of coronary atherosclerosis during autopsy largely depends on the forensic pathologist’s visual measurements, which may limit diagnostic accuracy. The objective of this study was to develop a deep learning algorithm for rapid and precise assessment of coronary atherosclerosis and to identify factors influencing the model’s prediction of atherosclerosis severity. A total of 3,717 digital photographs were retrospectively extracted from a database of 1,920 forensic autopsies, with one image each selected for the left anterior descending coronary artery and the right coronary artery. The deep learning algorithm developed in this study demonstrated a high level of agreement (0.988, 95% CI: 0.985-0.990) and absolute agreement (0.986, 95% CI: 0.978-0.991) between predicted and ground truth atherosclerosis values on the test set. The model demonstrated strong overall performance on the test set, achieving a weighted F1-score of 0.904. However, the class-wise F1-scores were 0.957 for mild, 0.785 for moderate, and 0.876 for severe grades, indicating that performance was lowest for the moderate grade. Additionally, decomposition, stent implantation, and thrombi did not have a statistically significant impact on coronary atherosclerosis assessment except for calcification. Although enhancing model performance for moderate grades remains a challenge, this study’s findings demonstrate the potential of artificial intelligence as a practical tool for assessing coronary atherosclerosis in autopsy photographs.

PMID:40690102 | DOI:10.1007/s12024-025-01045-0

Invest New Drugs. 2025 Jul 21. doi: 10.1007/s10637-025-01565-0. Online ahead of print.

ABSTRACT

INTRODUCTION: No correlation between the dose, adverse events, and efficacy was detected in clinical trials of anti-PD-1 antibodies across a range of solid and hematological malignancies. Given that dose reduction with potentially comparable clinical efficacy may improve access to treatment, particularly in low-income regions, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose PD-1 inhibitor monotherapy in relapsed/refractory (r/r) classic Hodgkin lymphoma (cHL).

MATERIALS AND METHODS: Relevant reports were identified through PUBMED, MEDLINE, Cochrane, ScienceDirect databases, and major international conference proceedings, from inception till December 1, 2024. The risk of bias was assessed independently by two authors using the Joanna Briggs’s critical appraisal checklist for studies reporting prevalence data. Heterogeneity was assessed using Cochran’s Q test, with statistical significance defined as p < 0.05; I² statistic was used to quantify heterogeneity. Random effects models (Der-Simonian method) was used to pool results from primary studies in the presence of significant heterogeneity.

RESULTS: After screening, 13 reports including 148 patients were included in the systematic review. After exclusion of duplicated reports, studies with less than 5 patients, and studies with unextractable data, five studies with a total of 84 patients were included in the meta-analysis. The pooled objective response rate (ORR) with low-dose PD-1 inhibition in r/r cHL, as determined by meta-analysis, was 87% (95% CI, 71.9%-100%), with a corresponding complete response (CR) rate of 53.9% (95% CI, 34.7%-73.1%). The ORR with low-dose nivolumab was 83.8% (95% CI, 64.2%-100%), with a CR rate of 43.3% (95% CI, 29.7%-56.9%). The pooled rate of any-grade adverse events after low-dose PD-1 inhibition was 55.7% (95% CI, 36.1%-75.3%), with a grade 3-4 adverse event rate of 7.5% (95% CI, 1.7%-13.3%).

CONCLUSIONS: This systematic review and meta-analysis demonstrated the high efficacy and acceptable toxicity of low-dose PD-1 inhibition in r/r cHL.

PMID:40690099 | DOI:10.1007/s10637-025-01565-0

Acta Parasitol. 2025 Jul 21;70(4):163. doi: 10.1007/s11686-025-01099-8.

ABSTRACT

BACKGROUND: Cyclospora cayetanensis is a coccidian protozoan parasite belonging to the phylum Apicomplexa. This systematic review and meta-analysis aimed to assess the prevalence and risk factors of C. cayetanensis in patients with Human Immunodeficiency Virus (HIV)/ Acquired Immunodeficiency Syndrome (AIDS).

METHODS: A literature search was performed in international databases for studies published until October 18, 2024, focusing on cross-sectional and case-control studies. Data from eligible studies were analyzed using Comprehensive Meta-Analysis (CMA) software, employing random-effects models for pooled estimates and weighted odds ratios (ORs), along with heterogeneity assessment via I² statistic.

RESULTS: This systematic review analyzed 73 studies, including 48 cross-sectional and 25 case-control involving 13,986 HIV/AIDS patients and 3,559 non-HIV/AIDS controls across 22 countries, mainly in Asia and Africa. The global prevalence of C. cayetanensis infection was 4% in HIV/AIDS patients (95% CI: 2.9-5.4%) versus 1.8% in controls (95% CI: 1.1-3.2%), resulting in an OR of 3.5 (95% CI: 2.04-6.06), indicating HIV/AIDS patients were significantly more likely to be infected. Sensitivity analysis indicated that none of the studies significantly affected the pooled estimates and weighted ORs. The prevalence of infection showed no significant association with quantitative variables such as publication year, sample size, and Human Development Index (HDI). Moreover, the pooled prevalence of C. cayetanensis infection was estimated across various subgroups, including publication year, World Health Organization (WHO) region, country, continent, country income level, HDI value, and sample size.

CONCLUSION: The findings confirm the opportunistic nature of C. cayetanensis infection and highlight the need for increased awareness and diagnosis of this infection in HIV/AIDS patients. Monitoring this opportunistic infection is vital for patient management, particularly in resource-limited areas.

PMID:40690092 | DOI:10.1007/s11686-025-01099-8

Eat Weight Disord. 2025 Jul 21;30(1):56. doi: 10.1007/s40519-025-01767-8.

ABSTRACT

PURPOSE: The present study reports on the psychometric properties of the Dutch translation of the clinical impairment assessment (CIA) questionnaire in female patients with eating disorders. The aim of this study was to determine the factor structure of the CIA as there are conflicting studies supporting a three-factor, bifactor, and single-factor model with a general factor and three specific factors.

METHODS: The CIA was translated and administered to 321 female patients with various eating disorders receiving treatment in a specialized eating disorder center. Its factor structure, internal consistency, convergent validity, and sensitivity to change were investigated.

RESULTS: Confirmatory factor analyses showed the best fit was a bifactor model with one strong general factor and three less strong specific factors for personal, social, and cognitive impairment. Furthermore, good internal consistency (Cronbach’s α = 0.91), good convergent validity between CIA global score and eating disorder examination questionnaire global score (r = 0.58; p < 0.001) and good sensitivity to change (t (115) = 13.76, p < 0.001) were found.

CONCLUSIONS: The Dutch CIA is a reliable and valid instrument to measure impairment secondary to eating disorder symptoms, but interpretations made from subscales scores should be used with caution.

LEVEL OF EVIDENCE: Level III, validation study.

PMID:40690077 | DOI:10.1007/s40519-025-01767-8

Arch Orthop Trauma Surg. 2025 Jul 21;145(1):382. doi: 10.1007/s00402-025-05993-8.

ABSTRACT

BACKGROUND: Hip fractures have a significant impact on morbidity and mortality in older adults, often leading to loss of function and an increased healthcare burden. The role of geriatric co-management in improving postoperative outcomes remains controversial. This meta-analysis evaluates the impact of geriatric care on functional recovery, complications, length of hospital stay, and one-year mortality in older patients with hip fractures.

METHODS: A meta-analysis was conducted according to PRISMA guidelines. Randomized controlled trials (RCTs) and prospective cohort studies comparing standard orthopedic care with geriatric co-management were included. The primary outcomes examined were one-year mortality, functional independence (Barthel ADL scores, independent walking), length of hospital stay and postoperative complications (delirium, infections, falls).

RESULTS: Six RCTs with 1,780 patients (894 geriatric care, 886 standard care) were analyzed. Geriatric care was associated with improved ADL scores (Cohen’s d = 0.066, 95% CI 0.027-0.105) and a 19% higher rate of independent walking (RR = 1.19, 95% CI 1.092-1.288). The length of hospital stay was reduced by 1.39 days (95% CI – 1.98 to – 0.80). Complication rates decreased slightly (- 3.60%), but no significant reduction in one-year mortality was observed (- 2.26%). Heterogeneity was high for functional outcomes (I² = 99.91%) and LOS (I² = 99.99%).

CONCLUSIONS: Geriatric care improves short-term functional outcomes, reduces complications and shortens hospital stay in elderly patients with hip fractures. However, its impact on one-year mortality is limited. Standardized geriatric care models and further research on long-term recovery strategies are needed to optimize outcomes.

PMID:40690069 | DOI:10.1007/s00402-025-05993-8

Int Ophthalmol. 2025 Jul 21;45(1):301. doi: 10.1007/s10792-025-03669-1.

ABSTRACT

PURPOSE: To investigate the effect of posterior corneal surface abnormalities following deep anterior lamellar keratoplasty (DALK) on visual outcomes and high order aberrations (HOA).

METHODS: A retrospective cohort study was conducted on DALK cases. Patients were divided into two groups: Group A with posterior corneal surface abnormalities (interface haze, pre-Descemet’s scarring, central Descemet’s membrane (DM) perforation, and central DM folds) and Group B (control group) with regular posterior surface. Visual acuity, refractive outcomes, contrast sensitivity, and HOA were assessed in both groups.

RESULTS: This study included 84 eyes of 78 patients. Group A included 42 eyes of 38 patients and an equal number of control eyes were randomly included in group B. Group A exhibited significantly lower corrected distance visual acuity (CDVA) compared to Group B (Mean LogMAR 0.45 ± 0.25 in group A vs 0.31 ± 0.21 in group B, P = 0.012). Subgroup analysis revealed the lowest visual acuity in eyes with multiple posterior surface abnormalities, although the difference was not statistically significant. The mean topographic astigmatism was significantly higher in group A than in group B (4.47 ± 2.36 diopters vs 3.11 ± 2.16 diopters, respectively, P = 0.001). No significant differences were found between the 2 groups regarding total eye or corneal HOA. Contrast sensitivity was significantly lower in Group A at lower spatial frequencies (P = 0.013 and P = 0.004 at 3 and 6 cycles per degree, respectively), particularly in eyes with large DM perforations.

CONCLUSION: Posterior corneal surface abnormalities after DALK can negatively impact visual outcomes, especially contrast sensitivity.

PMID:40690055 | DOI:10.1007/s10792-025-03669-1