Category: Statistics

Stat Med. 2026 Jun;45(13-14):e70611. doi: 10.1002/sim.70611.

ABSTRACT

Trials with recurrent event responses are frequently encountered during clinical trials. Benefits have been demonstrated in previous studies when trials were conducted with a doubly biased coin design (DBCD). However, there is a lack of discussion about sample size determination. In this paper, we provide the methods to compute the required sample size with a given test power when DBCD is used. More importantly, our proposed sample size determination procedure also allows unequal follow-up time due mainly to possible patient dropout. Without considering patient dropout, it is shown that the required sample size to reach the prespecified test power is underestimated. Theoretical results are derived to measure the impact of dropouts on the required sample size and treatment allocation proportions. A simulation study is conducted to illustrate the usefulness of our proposed procedure. Finally, a clinical example is used to illustrate the advantages of our proposed procedure in practice.

PMID:42219516 | DOI:10.1002/sim.70611

Res Integr Peer Rev. 2026 Jun 1;11(1):14. doi: 10.1186/s41073-026-00198-y.

ABSTRACT

BACKGROUND: The Patient-Centered Outcomes Research Institute (PCORI) reviews research applications using a process that includes preliminary review by primary reviewers, followed by panel discussion where primary reviewers and other reviewers on the panel (panelists) discuss and score the most competitive applications. PCORI switched from in-person to virtual panel discussions during the COVID-19 pandemic. This study compared reviewers’ scores and perceptions of panel interactions for virtual and in-person review panels and assessed reviewers’ perspectives about virtual panels. PCORI uniquely includes patients and other stakeholders as reviewers alongside scientists; thus, differences between reviewer types were also explored.

METHODS: This observational study utilized repeated cross-sectional data from PCORI funding cycles before and after switching to virtual review, including reviewer score data and closed- and open-ended responses from reviewer surveys. The study team used linear and logistic regression to examine reviewer scores and quantitative survey responses and conducted thematic analysis of open-ended survey responses.

RESULTS: There were no statistically significant differences between in-person and virtual panels in primary reviewers’ post-discussion scores or the magnitude of score change from pre- to post-discussion. In contrast, panelists gave stronger post-discussion scores in virtual panels, and this difference between formats was greater for stakeholder reviewers compared to scientists. Reviewers’ ratings of panel interactions appeared to be similar between formats. While reviewers noted challenges of virtual panels, including challenges related to discussion quality and social interactions, they also noted benefits, such as lack of travel.

CONCLUSIONS: Overall, this study suggests that virtual and in-person review panels were largely comparable on reviewer scores and some key aspects of reviewer experiences in a multi-stakeholder review process. Despite having some challenges, virtual review processes may be a viable approach for funders during times of necessity and beyond. Practical considerations and recommendations for virtual panels are discussed.

PMID:42219512 | DOI:10.1186/s41073-026-00198-y

BMC Public Health. 2026 Jun 1;26(1):1758. doi: 10.1186/s12889-026-27997-8.

ABSTRACT

BACKGROUND: People with functional limitations may be lonelier than those without functional limitations, as health-related constraints can restrict social participation. However, this relationship might also vary depending on the type of loneliness considered and the age of the individual. Consequently, this study examines differences in emotional and social loneliness according to functional limitation status and across age groups.

METHODS: Population-based data from 3,984 participants aged 40 and older from the 2023 German Aging Survey were analyzed. Emotional and social loneliness were measured using the De Jong Gierveld Loneliness Scale, and functional limitations were assessed using the Global Activity Limitation Indicator (GALI). Analysis of variance examined differences across age groups and functional limitation severity.

RESULTS: Results showed that participants with functional limitations generally reported progressively higher levels of both types of loneliness compared to those without functional limitations. Emotional loneliness showed consistent patterns across age groups, with progressive increases from no functional limitations to moderate functional limitations to severe functional limitations. In contrast, social loneliness displayed a significant interaction with age group, where middle-aged adults (40-65 years) showed much stronger progressions in social loneliness according to functional limitation severity as compared to older adults (66+).

CONCLUSIONS: These findings suggest that functional limitations are generally associated with increased loneliness, but that the extent varies by both type of loneliness and age group. The stronger differences in social loneliness among middle-aged adults indicate that functional limitations may have particularly pronounced social implications earlier in the life course. Middle-aged adults with functional limitations thus represent a particularly psychosocially vulnerable group.

PMID:42219485 | DOI:10.1186/s12889-026-27997-8

Respir Res. 2026 Jun 1. doi: 10.1186/s12931-026-03747-7. Online ahead of print.

ABSTRACT

BACKGROUND: Genetic variation in CYP2A6, an enzyme which inactivates nicotine and activates nitrosamines, alters smoking behaviours and was associated with chronic obstructive pulmonary disease (COPD) and lung cancer (LC) in a phenome-wide association study.

RESEARCH QUESTIONS: Does smoking quantity mediate the association between CYP2A6 and the risk for COPD and LC? Does the extent of mediation differ between the diseases?

METHODS: We implemented two-step two-sample mediated Mendelian Randomization (MR) and observational mediation analyses. CYP2A6 activity was instrumented using a CYP2A6 genetic score. We tested pack-years (chronic smoking exposure), cigarettes per day (CPD; self-reported), and the summation of nicotine’s main metabolites, cotinine, and trans-3′-hydroxycotinine (COT+3HC; nicotine intake biomarker) as quantity measures among current smokers. We sourced smoking quantity genetic instruments for MR from genome-wide significant summary statistics. This research was conducted using the UK Biobank Resource.

RESULTS: All three smoking quantity measures significantly mediated the effects of CYP2A6 activity on COPD and LC risk in forward mediated MR (p values < 0.05). Given the many assumptions of MR, this provides only a potential direction of effect. Smoking quantity measures mediated a large proportion of the COPD risk but less for LC. In reverse mediated MR (i.e., negative control), CYP2A6 activity did not mediate smoking quantity effects on COPD and LC.

INTERPRETATION: Mediated MR and observational mediation analyses together supported a mechanistic role of faster CYP2A6 influencing smoking quantity increase, which increases COPD and LC risk. The observational mediation analyses suggest additional mechanisms may be involved in CYP2A6’s impact on LC.

PMID:42219484 | DOI:10.1186/s12931-026-03747-7

BMC Med Educ. 2026 Jun 1. doi: 10.1186/s12909-026-09569-x. Online ahead of print.

ABSTRACT

BACKGROUND: Gross anatomy is foundational in medical education and is traditionally taught through cadaveric dissection. However, post-COVID-19 technological advancements have introduced digital tools, such as the anatomage table (AT), which offers interactive 3D virtual dissection to enhance learning outcomes and overcome logistical challenges.

OBJECTIVE: This study assessed the perceived educational benefits of AT and associated factors among medical students at the University of Global Health Equity (UGHE), Rwanda.

METHODS: A cross-sectional analytical study using a structured, validated questionnaire was conducted among 148 first- to third-year Bachelor of Medicine and Bachelor of Surgery students. Data were collected using the KoboToolbox and analyzed using SPSS. Chi-square tests and logistic regression were used to identify factors associated with perceived educational benefits of AT. A p-value < 0.05 with a 95% confidence interval was considered statistically significant.

RESULTS: Of the 135 participating medical students (response rate of 91.2%), 83.0% perceived AT as beneficial, while 83.7% demonstrated good practice and a favorable attitude toward its use. Additionally, 65.9% of the participants reported improved learning due to the use of AT. Logistic regression identified female sex (AOR = 3.51, CI: 1.26-9.76), good practice (AOR = 3.05, CI: 1.26-7.36), and perceived learning improvement (AOR = 4.45, CI: 2.26-9.13) as significant predictors of perceived benefits.

CONCLUSION: This study shows that students perceived AT as a beneficial educational tool for learning gross anatomy and associated it with a positive attitude and improved learning experience.

PMID:42219483 | DOI:10.1186/s12909-026-09569-x

BMC Oral Health. 2026 Jun 1. doi: 10.1186/s12903-026-08754-0. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluated the color adjustment potential (CAP) and translucency adjustment potential (TAP) of monoshade and polyshade composites, and the influence of opaquer/blocker use, before and after aging in anterior Class IV restorations.

METHODS: A total of 105 acrylic teeth in A1, A2, and A3 shades (Vita Classic) were restored across seven groups based on composite type: monoshade (Omnichroma, Omnichroma with Blocker, Zenchroma) and polyshade (Estelite Sigma Quick, Estelite Sigma Quick with Opaquer, Palfique, Palfique with Opaquer) (n = 5 per group). Specimens underwent 10,000 thermal cycles and coffee staining. Color measurements were performed using a spectrophotometer, and color differences were calculated using the CIEDE2000 formula.CAP and TAP were calculated at baseline (T0) and after aging (T1). Data were analyzed statistically (α = 0.05).

RESULTS: Aging produced material-specific significant changes in CAP, while TAP was not significantly affected by aging. Opaquer/blocker use did not significantly affect CAP values, while a significant effect on TAP was observed only at baseline (T0) in the Estelite comparison. Polyshade composites generally exhibited higher CAP and TAP values than monoshade materials, although these differences were not statistically significant at all evaluation time points.

CONCLUSIONS: Polyshade composites may be preferred in anterior restorations requiring improved color and translucency matching. Clinicians should carefully consider opaquer/blocker use, as it may influence optical outcomes depending on the composite type.

CLINICAL RELEVANCE: This study provides guidance to clinics on achieving the correct color and translucency in anterior fracture cases; it also presents information on the long-term color and translucency compatibility of the composite parts used.

PMID:42219478 | DOI:10.1186/s12903-026-08754-0

BMC Surg. 2026 Jun 1. doi: 10.1186/s12893-026-03903-2. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the clinical efficacy of oblique lumbar interbody fusion (OLIF) combined with unilateral pedicle screw fixation (OLIF-UPS) performed in a single lateral position for degenerative lumbar diseases.

METHODS: Clinical data of patients who underwent OLIF-UPS in a single lateral position were collected retrospectively. During the same period, patients who received OLIF combined with bilateral pedicle screw fixation (OLIF-BPS) requiring intraoperative position change were enrolled as the control group. Perioperative parameters, Visual Analogue Scale (VAS) scores, Oswestry Disability Index (ODI) scores, and the modified MacNab criteria were recorded to assess clinical outcomes. Radiographic parameters, including disc height (DH), lumbar lordosis (LL), cage subsidence rate, and interbody fusion rate, were compared between the two groups.

RESULTS: The operative time in the OLIF-UPS group was significantly shorter than that in the OLIF-BPS group (p <0.001), whereas no significant differences were observed in intraoperative blood loss or postoperative hospital stay between the two groups (p >0.05). Postoperatively, VAS scores for back and leg pain and ODI scores were significantly improved in both groups compared with preoperative values (p <0.001), with a further improvement noted at 1 year postoperatively compared with 1 month postoperatively. Postoperative DH and LL were significantly increased in both groups relative to preoperative measurements (p <0.001). A slight reduction in DH and LL was observed at 1 year postoperatively compared with the immediate postoperative period, but this difference was not statistically significant (p >0.05). The interbody fusion rate was 92.2% in the OLIF-UPS group and 93.5% in the OLIF-BPS group. Both groups achieved favorable functional recovery and high patient satisfaction.

CONCLUSION: In patients with normal to near-normal bone density (T-score > -2.5), Grade I or no spondylolisthesis, no segmental instability, and BMI <30 kg/m2, single-position OLIF-UPS achieves short-term outcomes comparable to OLIF-BPS while significantly reducing operative time. Given the relatively short follow-up period, further long-term observation is warranted to verify its long-term clinical efficacy.

PMID:42219477 | DOI:10.1186/s12893-026-03903-2

BMC Musculoskelet Disord. 2026 Jun 1. doi: 10.1186/s12891-026-09999-0. Online ahead of print.

ABSTRACT

BACKGROUND: Osteoporotic vertebral fractures affect many elderly patients, and complications after common treatments such as vertebroplasty (VP) may reduce treatment satisfaction and radiographic stability. This study investigated whether the addition of posterior instrumentation with cement-augmented fenestrated pedicle screws (VP + PI) was associated with improved short-term radiographic outcomes compared with VP alone.

METHODS: We retrospectively analyzed 153 patients with osteoporotic vertebral fractures treated between 2017 and 2022. Patients underwent either VP alone or VP + PI. To reduce treatment-selection bias, propensity score matching was performed. Vertebral collapse was assessed on serial radiographs at 1, 3, and 6 months postoperatively, and statistical analyses were performed using SAS software.

RESULTS: After propensity score matching, the VP + PI group had significantly lower anterior column collapse rates at 3 and 6 months postoperatively. Multivariable logistic regression confirmed that VP + PI was independently associated with a reduced risk of anterior column collapse at 6 months (adjusted OR: 0.147, 95% CI: 0.043-0.502, p = 0.0022). At 6 months, screw loosening was observed in 6 of 75 patients in the VP + PI group, and none required revision surgery during the follow-up period.

CONCLUSIONS: VP + PI may provide better short-term radiographic stability than VP alone in selected patients with osteoporotic vertebral fractures. However, given the longer operation time and hospital stay, lack of functional outcome assessment, and limited follow-up duration, the clinical benefit and long-term safety of VP + PI require further investigation.

TRIAL REGISTRATION: Not applicable.

PMID:42219476 | DOI:10.1186/s12891-026-09999-0

BMC Oral Health. 2026 Jun 1. doi: 10.1186/s12903-026-08755-z. Online ahead of print.

ABSTRACT

BACKGROUND: Polymethyl methacrylate (PMMA) denture base materials are routinely exposed to chemical cleansers during daily use, yet the material effects of unconventional agents, such as oral probiotics, remain unclear.

OBJECTIVES: This study investigated the effects of experimental exposure to a BLIS M18 oral probiotic solution and conventional denture cleansers on the color stability and surface properties of conventionally processed, milled, and 3D-printed PMMA during simulated denture care for up to 90 days.

METHODS: One hundred and twenty PMMA discs were fabricated using conventional processing, CAD/CAM milling, and 3D-printing, and were then immersed in distilled water, an effervescent tablet cleanser, 1% sodium hypochlorite, or BLIS M18 oral probiotic solution (experimental). Color change (ΔE₀₀), surface roughness, and Vickers hardness were measured at baseline (T0) and after 90 days (T3), with additional color and hardness measurements at 30 (T1) and 60 (T2) days. Surface morphology was examined using scanning electron microscopy. Data were analyzed using mixed repeated-measures ANOVA with Bonferroni post hoc tests (α = 0.05).

RESULTS: Manufacturing techniques significantly influenced baseline and post-exposure material properties, with 3D-printed PMMA exhibiting higher roughness and lower hardness than milled and conventionally processed materials (p < 0.001). Simulated denture cleansing increased surface roughness Ra, with post-exposure values ranging from 0.31 to 0.46 μm and reduced hardness (5.8-30.7%) over time, whereas cleanser-related effects were statistically significant but small. Color changes remained limited for all groups (0.50-1.73). Experimental exposure to BLIS M18 resulted in minimal changes in color, roughness and hardness compared with conventional cleansers.

CONCLUSIONS: PMMA surface integrity is primarily determined by the manufacturing technique rather than the cleanser chemistry. Under simulated denture care conditions, experimental exposure to BLIS M18 demonstrated compatibility with PMMA denture base materials without compromising surface properties or color stability.

PMID:42219474 | DOI:10.1186/s12903-026-08755-z

BMC Prim Care. 2026 Jun 1. doi: 10.1186/s12875-026-03394-3. Online ahead of print.

ABSTRACT

BACKGROUND: Early diagnosis and prompt referral are critical for improving outcomes in systemic sclerosis (SSc), yet disparities in diagnostic capabilities between healthcare levels may delay treatment and impact survival. This study aimed to compare mortality risk among SSc patients based on their diagnostic pathway: initial diagnosis at a secondary care hospital before referral versus prompt referral and diagnosis at a tertiary center.

METHODS: Using National Health Security Office cohort data (fiscal years 2016-2023), we identified 17,036 patients aged ≥ 18 years with SSc (ICD-10 M34) diagnosed at tertiary or university hospitals. The primary outcome was mortality risk through December 31, 2024. Mortality rates (95% CI) were stratified by the initial diagnostic facility. Cox regression analysis with a time-dependent interaction term for age was used to evaluate factors associated with mortality.

RESULTS: A total of 4,404 patients with SSc from 102 tertiary care hospitals were referred from secondary care hospitals. Patients first diagnosed at secondary care hospitals exhibited a significantly higher mortality rate (0.89 per 100 person-months; 95% CI 0.85-0.93) compared to those first diagnosed at tertiary care hospitals (0.67 per 100 person-months; 95% CI 0.65-0.69; p < 0.001). Increased mortality risk was associated with older age (HR 1.055), referral duration > 180 days vs. ≤ 7 days (HR 1.300), acute myocardial infarction (HR 1.895), and primary pulmonary hypertension (HR 1.654). An interaction between age and log(time) demonstrated that the effect of age on mortality decreased by approximately 0.5% per month of follow-up.

CONCLUSION: The initial diagnosis of SSc at tertiary care hospitals was associated with a better prognosis than that at secondary care hospitals. A longer referral duration was associated with poorer survival. Advanced age and coexisting cardiopulmonary diseases were significantly associated with mortality in patients with SSc. These findings highlight the need for standardized referral criteria and “red flag” checklists to facilitate earlier specialized care.

PMID:42219459 | DOI:10.1186/s12875-026-03394-3