Category: Statistics

J Clin Lab Anal. 2026 Jul 30:e70324. doi: 10.1002/jcla.70324. Online ahead of print.

ABSTRACT

BACKGROUND: In Hiroshima, thyroid cancer tissue samples from A-bomb survivors have been preserved since 1958. However, the feasibility of using these old formalin-fixed paraffin-embedded (FFPE) specimens for genetic analysis has not been fully evaluated. Here, we aimed to assess the quality of DNA extracted from long-term stored FFPE specimens obtained from patients with papillary thyroid carcinoma (PTC) in Hiroshima and to evaluate their applicability to whole exome sequencing (WES).

METHODS: We extracted DNA from tumor and adjacent normal regions of FFPE thyroid tumor specimens from 57 cases stored for up to 55 years at three hospitals in Hiroshima and confirmed the quality of the extracted DNA. From this cohort, tumor and paired normal samples from 24 patients with PTC were selected for WES, and sequencing metrics were evaluated.

RESULTS: Both DNA yield and DNA integrity number were negatively correlated with storage duration. WES analysis showed that storage duration was also negatively correlated with mean insert size and normalized read depth. In contrast, the uniformity score, which reflects the evenness of sequence coverage across targeted regions, did not show a significant correlation with storage duration. Among the 22 BRAF V600E-positive cases identified by droplet digital PCR, 18 cases (82%) had at least one sequencing read supporting the mutation.

CONCLUSIONS: These findings suggest that FFPE samples preserved for up to 55 years may be amenable to sequencing with increased read depth. However, the progressive decline in DNA quality with longer storage periods indicates that careful interpretation of sequencing results is warranted.

PMID:42533294 | DOI:10.1002/jcla.70324

Diabetes Obes Metab. 2026 Jul 30. doi: 10.1111/dom.71170. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence on psychological, cognitive and functional outcomes of advanced diabetes technologies in older adults with long-standing type 1 diabetes (T1D) remains limited. We evaluated whether initiation of advanced hybrid closed-loop (AHCL) therapy was associated with changes in fear of hypoglycaemia, diabetes distress, psychological well-being, cognition, frailty-related measures and mobility-related function in adults aged ≥ 65 years with T1D.

METHODS: This prespecified, exploratory secondary analysis was conducted within a single-centre, open-label, randomised, controlled, parallel-group trial including adults aged ≥ 65 years with long-standing T1D. Participants were randomly assigned (1:1) to initiate AHCL therapy using the MiniMed 780G system or to continue standard diabetes treatment. The secondary outcomes included WHO-5, the 17-item Diabetes Distress Scale (DDS), Hypoglycemia Fear Survey-II (HFS-II), Montreal Cognitive Assessment, Digit Symbol Substitution Test, Fried frailty phenotype and performance-based functional measures. No formal sample-size calculation was performed for these secondary outcomes.

RESULTS: Thirty-one participants were randomised and 29 completed 12 months of follow-up and were included in the treatment-effect analyses. In the baseline-adjusted primary analysis, AHCL therapy was associated with a lower HFS-II score than standard treatment (adjusted mean difference -18.9; 95% CI: -32.4 to -5.4; nominal p = 0.008), although this finding did not remain statistically significant after Holm correction (adjusted p = 0.104) or in an exploratory model additionally adjusted for sex (difference -13.6; 95% CI: -32.2 to 5.0; p = 0.145). Diabetes distress, psychological well-being, global cognition and processing speed did not differ between groups. In sex-adjusted sensitivity analyses, the between-group differences remained statistically significant for 6-min walk distance (92.6 m; 95% CI: 36.8 to 148.3; p = 0.002) and Timed Up and Go performance (-2.27 s; 95% CI: -4.28 to -0.27; p = 0.028), but not for gait speed (0.27 m/s; 95% CI: -0.05 to 0.59; p = 0.099). At 12 months, 12 of 14 AHCL participants were robust and 2 were pre-frail; in the control group, 11 of 15 were robust and 4 were pre-frail. No participant was classified as frail at follow-up.

CONCLUSIONS: In this small, selected cohort, AHCL therapy was associated with a nominally lower fear-of-hypoglycaemia score and better performance on selected mobility-related tests over 12 months. The fear-of-hypoglycaemia finding did not remain statistically significant after correction for multiple comparisons or additional adjustment for sex. Six-minute walk distance and Timed Up and Go remained statistically significant in the exploratory sex-adjusted sensitivity analyses, whereas the gait-speed difference did not. No measurable between-group deterioration in global cognition or processing speed was observed. These exploratory findings require confirmation in larger studies with balanced representation by sex and direct measurement of physical activity. These findings also support a person-centred clinical message: older age alone should not be regarded as a barrier to AHCL when treatment is introduced with individualised education and appropriate ongoing support.

PMID:42533279 | DOI:10.1111/dom.71170

Diabetes Obes Metab. 2026 Jul 30. doi: 10.1111/dom.71103. Online ahead of print.

ABSTRACT

AIM: To estimate the societal costs of Type 1 diabetes (T1D) in France, including direct and indirect costs.

MATERIALS AND METHODS: We conducted a descriptive retrospective cross-sectional study on all adult patients (aged 18 and over) with T1D identified in the SFDT1 cohort and compared them to a matched cohort of patients without diabetes considering age, gender, deprivation status and geographical area. An Insurance claim data analysis was conducted for the year 2023 individually and then extrapolated to all of France. Costs were broken down by expense categories and insulin delivery devices.

RESULTS: The average individual societal cost of T1D in France in 2023 compared with the absence of diabetes was estimated at €9940 (€9340 when considering direct costs only). Nearly half of the identified costs were attributable to the use of medical devices. An analysis stratifying patients by treatment modality (closed-loop, pump or multiple daily injections) highlighted the significant costs associated with the use of the most advanced technologies for delivering insulin (average costs were respectively €13 557, €11 062, and €7004, respectively). The total cost of T1D in France was estimated at between €1.59 and €1.79 billion in 2023 excluding undiagnosed cases and premature mortality associated with the disease.

CONCLUSIONS: Our results suggest that the most advanced insulin delivery devices have a significant short-term economic impact. Although this paper does not cover the research, model-based studies do suggest that there are some advantages to using such devices, including potential future savings due to lower complication rates.

PMID:42533268 | DOI:10.1111/dom.71103

Ann Surg Oncol. 2026 Jul 30. doi: 10.1245/s10434-026-20315-x. Online ahead of print.

ABSTRACT

PURPOSE: Incidence of appendiceal cancer is increasing, with one-third of patients diagnosed before age 50 years. Fertility preservation (FP) is important for patients who have not completed childbearing; however, the safety of oocyte and embryo banking remains unclear due to concerns for ovarian metastases. This study evaluates incidence of ovarian metastases at cytoreductive surgery (CRS) and describes FP practices and outcomes among reproductive-aged women with appendiceal cancer.

METHODS: A retrospective review was conducted of female patients aged 18-45 years treated for appendiceal cancer at MD Anderson Cancer Center from January 2020 to January 2025. Clinical, surgical, pathologic, and fertility-related variables were collected. Descriptive statistics assessed rates and laterality of ovarian metastases, FP practices, and reproductive outcomes.

RESULTS: A total of 100 reproductive-aged women (median age 35.9 years, range 19-44 years) with histology-confirmed appendiceal cancer were identified, of whom 47 underwent CRS. Ovarian metastases were documented in 89.4% (42/47), with bilateral involvement in 71.4% (30/42) and unilateral involvement in 28.6% (12/42). Fertility-sparing surgery included retention of one ovary in 25.5% (12/47) and uterine preservation in 19.1% (9/47). Among patients retaining an ovary, 60% developed amenorrhea after adjuvant therapy. Desire for FP was documented in 23.4% (11/47), all were referred for oncofertility consultation. Five patients underwent oocyte or embryo cryopreservation before CRS, including three with confirmed ovarian involvement.

CONCLUSION: Reproductive-aged women with appendiceal cancer have a high and often bilateral incidence of ovarian metastases, with important implications for FP safety. Individualized fertility counseling prior to CRS is essential to optimize reproductive outcomes while maintaining oncologic safety.

PMID:42533253 | DOI:10.1245/s10434-026-20315-x

Pharmacoecon Open. 2026 Jul 30. doi: 10.1007/s41669-026-00662-x. Online ahead of print.

ABSTRACT

BACKGROUND: Pembrolizumab has become a cornerstone in the treatment of multiple tumor types. In Portugal, it is currently reimbursed across 25 indications. However, a comprehensive holistic assessment of its cumulative clinical and humanistic impact is lacking.

OBJECTIVE: The aim was to estimate the population-level clinical and humanistic outcomes associated with pembrolizumab use in Portugal from 2017 to 2024, and to project its potential future impact until 2030.

METHODS: We developed a Microsoft Excel-based tool to aggregate outputs from validated, Portugal-adapted, cost-effectiveness models across all reimbursed indications for pembrolizumab. Using a real-world number of treated patients, clinical outcomes such as incremental life years (LYs), incremental quality-adjusted life years (QALYs), and avoided deaths were estimated. Forecasts through 2030 were developed using market and epidemiological projections. Alternative scenarios evaluated the additional benefits of accelerated reimbursement decisions and expanded patient access.

RESULTS: Between 2017 and 2024, among 13,530 treated patients, pembrolizumab was associated with estimated lifetime outcomes of 14,042 incremental QALYs, 17,914 incremental LYs, and 2021 deaths avoided. Scenario analyses showed that with accelerated reimbursement, within 180 days of market approval, and full uptake, cumulative gains could have increased by up to 14,705 QALYs (total 28,746 QALYs) and an additional 1250 deaths could have been avoided (total 3271 avoided deaths). Forecasts project continued substantial benefits for patients treated between 2025 and 2030, with lifetime outcomes estimated at approximately 31,306 QALYs, 38,274 LYs, and 4841 deaths avoided for the currently reimbursed indications.

CONCLUSION: Pembrolizumab has delivered significant clinical benefits in Portugal. Our results suggest that more timely reimbursement decisions and broader access could have yielded measurable additional health gains. These findings highlight the potential impact of access timelines on health outcomes, while acknowledging that broader assessments of value require consideration of cost-effectiveness, budget impact, and opportunity costs. Pembrolizumab’s benefits to the Portuguese health system is expected to grow through 2030.

PMID:42533247 | DOI:10.1007/s41669-026-00662-x

Ophthalmic Physiol Opt. 2026 Jul 30. doi: 10.1007/s44402-026-00158-5. Online ahead of print.

ABSTRACT

PURPOSE: To investigate 3-year dynamic changes in relative peripheral refraction (RPR) and their association with axial elongation and myopia progression stages in children.

METHODS: A total of 564 children (mean age 9.22 ± 0.59 years; 51.1% female) completed three annual visits in a longitudinal observational cohort study (2020-2023) in Guangzhou, China. Annual assessments included cycloplegic spherical equivalent refraction (SER), axial length (AL) and multispectral refractive topography. RPR was calculated across annular diameters up to 53° and quadrants; the total RPR (TRPR) was the mean across all regions. Analysis was stratified by baseline refractive status (myopia: SER ≤ -0.50 D, non-myopic: SER > -0.50 D) and 3-year outcomes (remained non-myopic, myopia onset or established myopia). Right eye data were included in the analysis.

RESULTS: In non-myopic children, differences in baseline RPR were observed 1 year before myopia onset. Baseline temporal RPR showed a modest association with myopia onset (odds ratio = 2.24, 95% CI: 1.08-4.66, p = 0.03). Longitudinal hyperopic RPR shifts were more pronounced in the peripheral retina >30°. The 3-year ΔTRPR was higher in the myopia-onset group (0.21 D) and the remaining non-myopic group (0.16 D) than in established myopia (0.06 D). Additionally, significant differences in ΔAL were observed: myopia-onset (+0.91 mm), established myopia (+0.81 mm) and remained non-myopic (+0.45 mm) (p < 0.001). ΔTRPR was correlated with ΔAL in the myopia-onset group (r = 0.32, p < 0.001), but not in established myopia. Baseline SER alone showed strong predictive accuracy for 1-year onset with an area under the curve (AUC) of 0.87, while RPR alone yielded moderate accuracy (AUC = 0.71), outperforming AL alone (AUC = 0.64). Adding RPR to SER did not improve discrimination (AUC = 0.88).

CONCLUSIONS: Baseline central refractive error remains the dominant predictor of myopia onset. Changes in RPR may be associated with myopia development. Dynamic RPR changes may provide complementary information regarding ocular shape remodelling, with limited added predictive value beyond baseline SER.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:42533234 | DOI:10.1007/s44402-026-00158-5

Neurol Sci. 2026 Jul 31;47(8):671. doi: 10.1007/s10072-026-09262-3.

ABSTRACT

INTRODUCTION: Lacunar strokes are caused by occlusion of small penetrating arteries. Although CT perfusion (CTP) is widely used in the acute settings, automated core/penumbra software often fails to detect lacunar perfusion abnormalities, so its diagnostic and prognostic roles remain unclear. This study aimed to assess the ability of CTP to detect perfusion asymmetries in patients with lacunar stroke and to determine whether such asymmetries are associated with clinical characteristics and functional outcomes.

MATERIAL AND METHODS: We retrospectively analyzed 68 patients with lacunar stroke who underwent whole-brain CTP within 4.5 h from stroke onset or recognition. CTP maps (MTT, CBF, CBV, and summary) were visually assessed. Demographic, clinical and imaging data along with stroke metrics and outcomes measurements were collected. Statistical analyses explored CTP detection rate, the association between admission variables and the presence of CTP asymmetries and between these asymmetries and 3-month mRS (dichotomized as either mRS 0-1 or ≥ 2).

RESULTS: 41.18% of patients exhibited CTP-detected asymmetries, with the MTT map showing the highest detection rate (39.71%). No demographic or clinical factors predicted CTP positivity. The presence of CTP asymmetries was associated with larger infarct volumes and was independently associated with lower odds of excellent functional recovery (3-month mRS 0-1) (OR 0.232; p = 0.012).

CONCLUSIONS: Qualitative assessment of individual CTP maps, and especially of MTT map, improves detection of lacunar strokes, particularly with whole-brain coverage. Asymmetries may reflect impaired microvascular perfusion and predict worse outcomes. Therefore, CTP is a valuable diagnostic and prognostic tool in lacunar stroke.

PMID:42533228 | DOI:10.1007/s10072-026-09262-3

CNS Drugs. 2026 Jul 31. doi: 10.1007/s40263-026-01317-5. Online ahead of print.

ABSTRACT

BACKGROUND: Drugs that inhibit phosphodiesterase 10A (PDE10A) activity have shown efficacy in animal models. However, clinical trials of PDE10A inhibitors in patients with schizophrenia have failed to provide clinically significant results up to this point. Our study investigated whether alofropodect (previously referred to as CPL’36 or CPL500036), a PDE10A inhibitor with an improved pharmacological profile compared with other PDE10A inhibitors, including a fast dissociation rate and high activity, could improve symptoms of acute schizophrenia.

METHODS: In this phase 2, randomised, double-blind, placebo-controlled, parallel-group trial (11 centres, three countries), investigators randomly assigned hospitalised patients with acute schizophrenia to treatment or placebo groups. The main inclusion criteria were age 18-65 years, a documented diagnosis of schizophrenia for at least 2 years before screening and a positive and negative syndrome scale (PANSS) total score ≥ 80. Participants were randomly assigned (1:1:1) to receive oral alofropodect (20 mg or 40 mg) or placebo administered once daily in the morning for 4 weeks. The primary endpoint of the study was an improvement in the PANSS positive subscale at week 4. The secondary endpoints included improvements in PANSS total and negative subscale scores, along with other efficacy and safety assessments. Clinical responders were defined as those with a ≥ 30% reduction in PANSS total score from baseline at week 4.

RESULTS: Between 24 May 2021 and 8 May 2024, investigators randomised 189 patients into three groups: 58 into the alofropodect 20 mg group, 66 into the alofropodect 40 mg group and 65 into the placebo group. The mean age was 41.7 years (standard deviation (SD) 10.1), and 119 (63%) participants were men, 70 (37%) were women. All participants were White. We measured the difference in PANSS positive subscale before and after treatment, and the change met the primary endpoints at week 4 with the group where alofropodect 20 mg was compared with placebo (- 3.70 [90% CI – 5.51 to – 1.89]; p < 0.001) and alofropodect 40 mg versus placebo (- 6.35 [90% CI – 8.12 to – 4.57]; p = 0.001). Both the 20-mg and 40-mg doses of alofropodect were effective in improving the total PANSS score compared with placebo and met most secondary efficacy endpoints. A clinical response was observed in 2 of 53 patients (3.8%) in the placebo group, 8 of 52 patients (15.4%) in the 20 mg group and 22 of 52 patients (42.3%) in the 40 mg group at week 4. The compound was well tolerated, with only a few serious adverse events. The discontinuation rates were similar in the placebo and treatment arms. Extrapyramidal symptoms (EPS) occurred only in the active treatment groups, but rates were low overall. Somnolence was also reported only in alofropodect groups. Vital signs and biochemical parameters remained unaffected by either dose at any time point. Specifically, blood glucose, total cholesterol and triglycerides did not increase at any dose compared with placebo within our study window.

CONCLUSIONS: Alofropodect was effective in the treatment of acute schizophrenia symptoms and was well-tolerated, warranting further investigation in larger clinical studies.

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05278156; registration date: 2022-02-09.

PMID:42533223 | DOI:10.1007/s40263-026-01317-5

Int J Implant Dent. 2026 Jul 31;12(1):39. doi: 10.1186/s40729-026-00705-2.

ABSTRACT

OBJECTIVES: The Pink Esthetic Score (PES) is widely used to assess peri-implant soft-tissue esthetics around single-tooth implant restorations; however, frontal-view assessment may incompletely capture three-dimensional peri-implant features such as buccolingual contour, emergence profile, and mucosal scarring. This study introduced the Extended Pink Esthetic Score (E-PES), a multidirectional assessment framework incorporating frontal, profile, and occlusal views.

MATERIALS AND METHODS: Thirty single-tooth implant restorations in the maxillary esthetic zone were evaluated using standardized photographs. Twenty blinded evaluators (five periodontists, five prosthodontists, five orthodontists, and five general practitioners) scored each case using two assessment systems. The traditional frontal-view assessment using the seven-variable PES, then the multidirectional E-PES assessment using frontal, profile, and occlusal views with nine variables. The E-PES retained the seven core PES variables, with emergence profile and mucosal scarring added to the variables to give a multidirectional view. Assessments were repeated after a three-week washout period with randomized image order. Reliability, agreement, and score-distribution analyses were performed.

RESULTS: A total of 600 first-round assessments were completed for each scoring system and included in the paired frontal-view versus multidirectional score analysis. Original PES and multidirectional E-PES-compatible total scores averaged 9.98 ± 3.96 and 9.76 ± 3.52, respectively, yielding a small but statistically significant mean paired difference of 0.22 points (P < 0.001). Scores differed in 442 of 600 paired assessments (73.67%). Agreement between frontal-view and multidirectional total scores remained excellent (ICC = 0.919; ICC = 0.958). The alveolar process/buccal contour parameter showed the greatest mean shift, decreasing from 1.31 ± 0.69 to 1.10 ± 0.74 (P < 0.001). Inter-examiner reliability for multidirectional total scores was moderate at the individual-rater level (single-measure ICC = 0.633) and high at the group level (average-measure ICC = 0.972).

CONCLUSIONS: E-PES preserved the reliability of the original PES while identifying clinically relevant esthetic differences not fully captured by frontal-view assessment alone. Multidirectional evaluation particularly enhanced assessment of alveolar-process/buccal-contour morphology, supporting E-PES as a practical refinement of PES for more comprehensive peri-implant esthetic evaluation.

PMID:42533208 | DOI:10.1186/s40729-026-00705-2

Support Care Cancer. 2026 Jul 30;34(8):818. doi: 10.1007/s00520-026-11041-x.

ABSTRACT

PURPOSE: Most women with breast cancer undergo radiation therapy (RT) as part of treatment, but the impact of prior sexual trauma on their RT experience remains unclear. We sought to understand the patient experience and comfort during breast RT with a focus on how sexual trauma may negatively affect the RT experience of patients.

METHODS: Between May and October 2022, IRB-approved surveys were distributed to female breast cancer patients treated with radiation at Sidney Kimmel Cancer Center. The 35-question survey assessed demographics, treatment details, body image satisfaction, comfort during various times throughout the RT process, and trauma history. Statistical analysis was performed using chi-square.

RESULTS: Of the 505 surveys collected, 420 met the inclusion criteria. At the time of their radiation treatment, most patients surveyed were over 60 (70%), postmenopausal (75%), and had at least a college degree (63%). Most patients had localized breast cancer (69%), had undergone a lumpectomy prior to radiation (79%), were treated by a female physician (53%), and had completed radiation therapy less than five years prior (61%) at the time of the survey. Although most patients reported general comfort during RT, notable discomfort was associated with gender dynamics. Fewer patients felt uncomfortable changing for treatment (9.8%), waiting in the general area (20%), or being set up for RT (22%), but many more expressed discomfort in waiting rooms with men (43%) or when treated by male radiation therapists (38%). A history of trauma exposure was prevalent: 38% had experienced verbal harassment, 39% an unwanted sexual advance, 33% unwanted sexual touching, and 19% an unwanted sexual encounter. Trends towards greater discomfort were associated with body exposure during treatment (p = 0.29), setup (p = 0.18) and being left alone in the treatment room (p = 0.29), though none of these differences reached statistical significance.

CONCLUSIONS: This study underscores the potential negative influence of prior sexual trauma on the RT experience for breast cancer patients. Although most patients reported overall comfort, those with a trauma history experienced trends toward greater distress related to exposure during treatment.

IMPLICATIONS FOR CANCER SURVIVORS: Adopting trauma-informed practices to increase provider training, gender considerations, and patient-centered modifications could enhance patient comfort, adherence, and satisfaction for breast cancer treatment.

PMID:42533207 | DOI:10.1007/s00520-026-11041-x