Tag: statistics

Syst Rev. 2025 Dec 10. doi: 10.1186/s13643-025-03011-x. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH), a progressive subtype of steatotic liver disease, imposes a substantial global health burden due to its association with obesity and metabolic syndrome. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrate therapeutic potential through pleiotropic mechanisms, including appetite regulation, metabolic enhancement, and anti-inflammatory activity. However, clinical evidence remains limited by methodological heterogeneity and insufficient long-term efficacy data, necessitating a rigorous systematic evaluation.

METHODS: This protocol for a systematic review and meta-analysis will include randomized controlled trials (RCTs) evaluating GLP-1 RAs versus placebo in adults with biopsy-confirmed MASH. Comprehensive searches of PubMed, Web of Science, Embase, and the Cochrane Library will be conducted using predefined strategies. Two independent reviewers will perform study screening, data extraction, and risk-of-bias assessment with the Cochrane ROB 2 tool. Primary outcomes are histological: (1) MASH resolution without fibrosis worsening, and (2) fibrosis improvement without MASH deterioration. Secondary outcomes encompass physiological and biochemical parameters. Data synthesis will utilize random-effects meta-analysis, complemented by meta-regression to explore heterogeneity sources. Trial sequential analysis (TSA) will be used to control random errors (α = 0.05, power = 80%) and validate evidence sufficiency, strengthening result reliability. Sensitivity analyses will assess robustness. Statistical analyses will employ RevMan 5.4 and R 4.3.1. Evidence certainty will be evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework.

ETHICS AND DISSEMINATION: Ethical approval is not required as this study synthesizes published data. Findings will be disseminated through peer-reviewed publication and conference presentations.

SYSTEMIC REVIEW REGISTRATION: PROSPERO CRD420251090801.

PMID:41373001 | DOI:10.1186/s13643-025-03011-x

Trials. 2025 Dec 10. doi: 10.1186/s13063-025-09315-6. Online ahead of print.

ABSTRACT

BACKGROUND: In clinical trials, evaluating de-intensified oncologic treatment strategies can help reduce treatment-related toxicities while preserving patients’ quality of life. However, de-intensification is typically evaluated in cancers with a low relapse rate, and if the cancer type is uncommon, a randomized trial may require an impractically extended period to accumulate sufficient events for reliable inferential conclusions.

METHOD: This paper introduces a Bayesian adaptive method for the single-arm trial design that provides efficient analysis of survival data under these constraints. By incorporating data from previous studies to establish prior knowledge and a historical control arm, this approach enables robust and accurate estimations and predictions for trial design, sample size determination, and inferential decision-making. To support the implementation of this method, we developed an R package called “BayesAT,” which offers significant flexibility in modelling and supports multi-stage interim analyses, particularly for evaluating de-intensified oncologic treatments.

RESULT: Our approach is validated through comprehensive simulation studies and sensitivity analyses. Additionally, this algorithm has been applied to a pediatric Hodgkin lymphoma trial, showcasing its capability to effectively leverage information from previous studies and conduct interim analyses that expedite conclusions regarding treatment efficacy.

PMID:41372997 | DOI:10.1186/s13063-025-09315-6

Parasit Vectors. 2025 Dec 10. doi: 10.1186/s13071-025-07142-x. Online ahead of print.

ABSTRACT

BACKGROUND: Members of the genus Trichinella are muscle-dwelling zoonotic parasites of global importance for public health, animal husbandry, and trade. Trichinella chanchalensis (T13) is the newest species in the genus, first described in the Yukon and the Northwest Territories, for which the geographical distribution remains unknown due to limitations of the gold standard test for genotyping (multiplex polymerase chain reaction [PCR]). Our primary objective was to determine whether T. chanchalensis was present in Alaska, using a new molecular method that enables the description of the prevalence, co-infection, host associations, and risk factors for Trichinella spp. infection in wild carnivores.

METHODS: Trichinella spp. larvae were recovered through artificial digestion of muscle and genotyped using next-generation sequencing (NGS).

RESULTS: Trichinella spp. larvae were detected in 53/157 (34%) animals, namely wolverines (Gulo gulo), arctic foxes (Vulpes lagopus), red foxes (Vulpes vulpes), coyotes (Canis latrans), wolves (Canis lupus), brown bears (Ursus arctos), and polar bears (Ursus maritimus), but not in black bears (Ursus americanus) or lynx (Lynx canadensis). Prevalence was highest in polar bears and wolverines, while intensity (larvae per gram, LPG) was highest in red foxes, arctic foxes, and wolves. Most animals (65%) harbored single infections with Trichinella nativa, followed by mixed infections of T. nativa and Trichinella T6 (33%). A single wolverine was infected with T. nativa, T6, and T. chanchalensis. Combining NGS with statistical methods, we found no evidence of competition between T. nativa and T6 in host muscles. Trichinella spp. infection (primarily T. nativa) was the highest in the Northwestern region, whereas T6 infection probability was higher in the Interior and Southern regions, suggesting differences in environmental resistance even among these three taxa. In a single, highly infected brown bear, we detected a rare case of Trichinella spiralis of foreign origin based on whole-genome sequencing, suggesting illegal importation and disposal of meat.

CONCLUSIONS: We report a new geographical record for T. chanchalensis and a rare finding of T. spiralis in North American wildlife, and demonstrate the utility of new NGS methods for describing the ecology of parasites maintained in wildlife hosts commonly presenting as co-infections.

PMID:41372994 | DOI:10.1186/s13071-025-07142-x

Genome Med. 2025 Dec 10. doi: 10.1186/s13073-025-01582-x. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) diagnosis relies on identifying disease episodes disseminated in space and time, and excluding other disease explanations. MS is a genetically complex autoimmune and neurodegenerative disorder that shares features with some monogenic progressive neurological conditions. The extent to which people diagnosed with MS have an alternate diagnosis (MS mimic), or genetic multimorbidity is unknown. Additionally, the burden of rare variation associated with MS risk and severity in monogenic neurological disease genes has not been evaluated. We investigated the prevalence of disease-causing variants in progressive neurological disease genes, and their contribution to MS risk and severity, in 4,340 MS cases diagnosed in sub-speciality clinics in Australia and New Zealand, and in 2,861 local controls.

METHODS: Exome sequencing and array-based genotyping data were analysed for 1,680 genes with pathogenic or likely pathogenic variants reported in ClinVar. Clinical history reviews of MS cases with putative disease-causing variants were conducted. We specifically examined the contribution of rare, likely deleterious variants in a subset of 30 hereditary spastic paraplegia (HSP) genes in 421 individuals with progressive onset MS (POMS). Gene-based association tests with MS risk and severity were performed for all genes in the cohort.

RESULTS: We identified 166 MS cases (3.82%) with variants prompting clinical history reviews, and of 75 cases reviewed, four (0.13% of all cases) had either genetic multimorbidity in addition to MS or a potential misdiagnosis. In contrast to previous findings we observed no enrichment of likely deleterious variants in HSP genes in POMS, nor did we find significant associations between neurological disease genes and MS risk or severity.

CONCLUSIONS: Our findings suggest that rare deleterious genetic variation in progressive neurological disease genes does not play a substantive role in MS risk or severity, and that misdiagnosis is exceedingly rare in this cohort. Consequently, among individuals diagnosed with MS by a specialist, a very small proportion may benefit from clinical genomic testing to inform MS diagnosis or an alternate diagnosis, which could have implications for healthcare management.

PMID:41372986 | DOI:10.1186/s13073-025-01582-x

BMC Med Educ. 2025 Dec 11. doi: 10.1186/s12909-025-08443-6. Online ahead of print.

ABSTRACT

BACKGROUND: Adolescence is a crucial stage for forming long-term health and nutritional habits. Many healthcare providers lack formal training in adolescent nutrition. This study assessed the effectiveness of a training course grounded in Merrill’s First Principles of Instruction in enhancing healthcare providers’ knowledge and satisfaction.

METHODS: This quasi-experimental study employed a pretest-posttest control group design with three measurement points and was; conducted in the Damghan Health Network (August 2024). A total of 100 health care providers were selected through convenience sampling and assigned to two groups: an intervention group (n = 40) and a control group (n = 50). The data collection tools included a 12-item nutrition knowledge test and 10-item satisfaction questionnaire. The training for the intervention group was designed usingaccording to Merrill’s five principles, whileereas the control group received standard training. Data were analyzed using ANCOVA.

RESULTS: The average knowledge score in the intervention group increased from 7.52 ± 1.92 to 10.71 ± 1.70 (42% increase), while the control group improved from 7.31 ± 1.47 to 9.17 ± 1.70 (25% increase). After adjusting for the pretest, the difference between groups was statistically significant (F = = 35.64, p < 0.001, η²= = 0.28, d = = 0.9). At the two-week follow-up, the intervention group maintained a higher mean score (8.27 ± 2.41) compared to baseline (p = 0.02). Participant satisfaction was also significantly higher in the intervention group (42.3 ± 4.1 vs. 36.8 ± 5.2; p < 0.001).

CONCLUSIONS: Training based on Merrill’s principles significantly improved providers’ knowledge and satisfaction regarding adolescent nutrition, supporting its use in health education programs.

PMID:41372975 | DOI:10.1186/s12909-025-08443-6

Res Involv Engagem. 2025 Dec 10. doi: 10.1186/s40900-025-00815-y. Online ahead of print.

ABSTRACT

BACKGROUND: The Family Engagement in Research (FER) Course launched in 2018 for researchers and family members to co-learn the principles and practice of engagement in neurodevelopmental disability and child health research. The first six cohorts of the FER Course (2018-2021) were part of a pre-post evaluation to assess learners’ perceptions and satisfaction of the FER Course, and the impact on their perceived knowledge, abilities, attitudes, and self-confidence in FER. This paper reports on the findings from this pre-post study.

METHODS: Sixty-nine self-selected researchers and family members enrolled in the course completed pre-and post-evaluations; satisfaction was evaluated after the course only (n = 96). Data collection involved surveys with 10-point Likert Scale questions about experiences of the course, perceived knowledge, abilities, attitudes towards, and self-confidence in family engagement in research, and overall satisfaction. We conducted Wilcoxon rank sum to compare differences between researchers and family members’ responses about self-confidence to engage, with the Wilcoxon signed rank tests used to evaluate change in outcomes from before to after the course. Open-ended survey responses were analyzed descriptively.

RESULTS: There were statistically significant increases in survey respondents’ perceived knowledge, abilities, and self-confidence to engage in research. Positive attitudes towards FER were rated highly at baseline and post-test, with no significant change. Respondents reported high levels of satisfaction with the FER Course.

CONCLUSIONS: The FER Course meets the need for training both family members and researchers, so that they are equipped with the perceived knowledge, abilities, and confidence to collaborate in neurodevelopmental disability and child health research.

PMID:41372969 | DOI:10.1186/s40900-025-00815-y

BMC Womens Health. 2025 Dec 10. doi: 10.1186/s12905-025-04171-7. Online ahead of print.

ABSTRACT

BACKGROUND: Cervical cancer (CC) causes significant morbidity and mortality in low-and middle-income settings, ranking second commonest female cancer in Ghana, affecting 26.4/100,000 with mortality rate 22.9/100,000 women. Previous studies focused on adults, females and involved smaller sample sizes. This study assessed CC knowledge among secondary school students in Ghana to generate evidence for implementing school-based educational interventions.

METHODS: It was a multi-site, cross-sectional study across 14 secondary schools in Greater Accra (GAR) and Central regions(C/R) of Ghana. Self-administered pre-tested questionnaires focused on students’ knowledge on causes, risk factors, symptoms, and prevention of CC. Four main domains were covered: general knowledge; cervical cancer features; risk factors; and screening and prevention. Domain scores were categorised into adequate knowledge (>50%) and inadequate knowledge (< 50%). Chi-square was used to test association between knowledge in various domains with participants’ gender, school type, and region. P-value below 0.05 was considered statistically significant.

RESULTS: A total of 9,767 students from 14 schools, 25.6% (n=2,280) males and 74.4% (n=6,630) females with mean age 16.9+1.2years participated. Overall, 58.4% of students had adequate general knowledge about CC; 61.1% demonstrated adequate knowledge of risk factors; 21.5% adequate knowledge of features, and 51.8% also had adequate knowledge of screening and prevention. Across all domains tested, 60.6%% of students had inadequate knowledge. More female students(60.9%) had adequate general knowledge than males(50.1%) (p< 0.001).

CONCLUSION: Significant knowledge gaps exist on risk factors, features, screening and prevention of cervical cancer among senior high school students in Ghana, necessitating targeted educational interventions based on identified gaps.

PMID:41372939 | DOI:10.1186/s12905-025-04171-7

BMC Nurs. 2025 Dec 10. doi: 10.1186/s12912-025-04189-0. Online ahead of print.

ABSTRACT

BACKGROUND: Venous ulcers negatively affect quality of life and generate high health care costs. Physical activity may improve their evolution; however, the evidence is limited and heterogeneous.

OBJECTIVE: To evaluate the effectiveness of a structured physical activity intervention as an adjunct treatment for the complete healing of venous ulcers in primary care at 3 and 6 months of follow-up.

DESIGN: This was a randomized, pragmatic clinical trial with 6 months of follow-up.

METHODS: Between February 2021 and June 2023, 44 people with a diagnosis of venous ulcers and an ankle-brachial index between 0.8 and 1.3 were recruited from 13 health centres in Madrid. Both groups received standard treatment. The intervention group also received a structured educational intervention of physical exercise and daily walking guidelines. The main outcomes were complete healing (RESVECH 2.0 scale) and time to healing (days). The secondary variables included degree of healing, ulcer area, pain, adherence, and variables related to healing and prognosis. Data were collected at the beginning and at 3 and 6 months of follow-up. Survival analysis (Kaplan‒Meier and Cox) was performed to measure the effectiveness of the treatments, as was intention-to-treat analysis.

RESULTS: At 3 months, 77.3% [95% CI 54-91] of the patients in the intervention group and 68.2% [95% CI 45-85] of those in the control group achieved complete healing, without statistically significant differences between groups. Overall adherence to the intervention was low; only 20% and 46% of the participants reached the level of compliance established in the first two visits, which progressively decreased.

CONCLUSIONS: The Active Legs programme showed a positive effect on the healing of venous ulcers in primary care.

TRIAL REGISTRATION: http://NCT04039789. [https://ClinicalTrials.gov]. 11/07/2019.

PMID:41372918 | DOI:10.1186/s12912-025-04189-0

Eur J Med Res. 2025 Dec 10. doi: 10.1186/s40001-025-03614-z. Online ahead of print.

ABSTRACT

OBJECTIVES: Several prior studies have shown that in metastasized colorectal cancer, the primary cancer’s location influences patients’ survival rates, with left-sided colorectal cancer being associated with longer survival than right-sided colorectal cancer. This study aimed to explore the influence of the primary location of colorectal cancer on survival following brain metastasis.

METHODS: To address this clinical question, we conducted a systematic review and meta-analysis. We included studies focused on patients diagnosed with brain metastasis from colorectal cancer. These studies reported survival outcomes based on different primary tumor sites (right versus left and colon versus rectum). The primary outcome was to aggregate the hazard ratio (HR) of left-sided colorectal cancer when metastasized to the brain compared with right-sided colorectal cancer. The secondary outcome was to aggregate the HR of rectal cancer when it metastasized to the brain compared with colon cancer.

RESULTS: Ten studies with a total of 1792 patients were included in the meta-analysis, and combined HR was calculated. Left-sided colon cancer showed higher overall survival compared with right-sided colon cancer when metastasized to the brain (HR: 0.71, 95% CI: 0.54-0.94, I² = 0%). Rectal cancer did not show a statistically significant difference in overall survival compared with colon cancer (HR: 0.75, 95% CI: 0.40-1.41, I² = 81%).

CONCLUSIONS: Concordant with lung and liver metastases, the primary location of colorectal cancer influenced overall survival when metastasized to the brain. Left-sided colon cancer demonstrated higher overall survival than right-sided colon cancer.

PMID:41372917 | DOI:10.1186/s40001-025-03614-z

BMC Complement Med Ther. 2025 Dec 10. doi: 10.1186/s12906-025-05213-1. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular disease (CVD) is a pressing public health issue worldwide. Accordingly, primary and secondary CVD prevention are essential. Many clinical trials have investigated the effects of sumac (Rhus Coriaria) supplementation on CVD risk factors (CVDRFs). However, these studies have yielded contradictory findings. This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to comprehensively assess the impact of sumac supplementation on CVDRFs in human subjects.

METHODS AND MATERIALS: We searched the MEDLINE/PubMed, EMBASE, CENTRAL, and Web of Science to identify the relevant studies in any language until March 2025. RCTs that investigated the impact of sumac supplementation compared no sumac consumption or placebo capsule interventions or consumed substitutions containing no sumac on CVD outcomes in adults at least 2 weeks were included for data synthesis. The primary outcomes were the mean difference in lipid profiles, blood pressure, glycemic control, and anthropometric indices. Secondary outcomes were the mean difference in inflammatory and oxidative stress markers. The quality of the included trials was assessed using the Cochrane Risk-of-Bias tool. Effect sizes were calculated using a random effect model and presented as weighted mean differences and 95% confidence intervals (CIs), while the I² index was utilized to assess between-study heterogeneity. To explore the potential sources of heterogeneity, subgroup and meta regression analyses were evaluated. Additionally, publication bias and sensitivity analyses were conducted. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to evaluate the quality of evidence.

RESULTS: A total of 17 trials (comprising 18 treatment arms) with 1170 participants were included in our analysis. The findings revealed statistically significant effects of sumac consumption on various CVDRFs, including low-density lipoprotein cholesterol (-9.62 mg/dL; 95% CI= -14.59 to -4.65), total cholesterol (-9.47 mg/dL; 95% CI= -15.92 to -3.02), triglycerides (-8.96 mg/dL; 95% CI= -16.19 to -1.73), high-density lipoprotein cholesterol (2.95 mg/dL; 95% CI = 0.66 to 5.25), diastolic blood pressure ( -2.87 mmHg; 95% CI= -4.23 to -1.51), insulin (-1.68 µU/mL; 95% CI: -3.26 to -0.09), homeostatic model assessment of insulin resistance ( -0.87; 95% CI: -1.61 to -0.14), body weight ( -1.03 kg; 95% CI= -1.89 to -0.17), body mass index (WMD = -0.31 kg/m; 95% CI= -0.55 to -0.07), waist circumference (-0.59 cm; 95% CI= -1.06 to -0.12), malondialdehyde (0.84 µmol/L; 95% CI = 0.38 to 1.30), and total antioxidant capacity ( -0.83 µU/L; 95% CI = -1.10 to -0.56). However, no significant effects were observed for other analyzed CVDRFs, such as systolic blood pressure, fasting blood glucose, quantitative insulin sensitivity check index, hip circumference, waist-to-hip ratio and hypersensitive C-reactive protein. These results were stable in sensitivity analysis, and no significant publication bias was detected. The GRADE profile for sumac supplementation evaluated the certainty of the outcomes and indicated that the quality of evidence was was rated as very low to high across all outcomes.

CONCLUSION: The findings of our present study suggest that sumac supplementation may have potential benefits in improving various CVDRFs, such as blood lipid levels, blood glucose control, weight management, and oxidative stress markers. Therefore, integrating sumac could be explored as a complementary dietary approach to improve the overall cardiometabolic health. However, these results warrant cautious interpretation, as the findings were derived predominantly from Iranian populations, and significant heterogeneity was observed across trials for different outcomes. Moreover, our pooled results were based on unadjusted estimates, the precise effect of sumac on CVDRFs could be impacted by various confounders. Further large-scale and high-quality RCTs with longer duration are required to confirm these results.

PMID:41372916 | DOI:10.1186/s12906-025-05213-1