Tag: statistics

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

Biol Trace Elem Res. 2026 Jul 31. doi: 10.1007/s12011-026-05271-7. Online ahead of print.

ABSTRACT

Tea consumption represents a primary dietary pathway for human exposure to heavy metals. In many countries, “tea rinsing”-the traditional practice of discarding the first infusion-is widely practiced, with some believing that this habit may reduce heavy metal intake. However, robust scientific evidence quantifying whether tea rinsing can effectively reduce heavy metal leaching and thereby mitigate associated health risks remains lacking. The study quantified the concentrations of ten elements (Pb, As, Cr, Co, Cd, Mn, Cu, Fe, Al, and Zn) in tea infusions before and after rinsing, and evaluated the mitigating effect of this practice on health risks using a probabilistic assessment. The results indicate that concentrations of Cr, Mn, Cu, Fe, and Zn decrease significantly (P < 0.05) following the first rinse. The rinsing procedure lowers the mean adult total carcinogenic risk by 36.2%, though all risk values remain within the acceptable regulatory range. Sensitivity analyses identify exposure duration and frequency as the primary drivers of these probabilistic risks. As emerges as the dominant contributor to carcinogenic risk. The findings suggest that discarding the initial tea infusion serves as a simple method to statistically reduce the intake of toxic elements from the evaluated teas.

PMID:42533199 | DOI:10.1007/s12011-026-05271-7

Oecologia. 2026 Jul 30;208(8):103. doi: 10.1007/s00442-026-05944-z.

ABSTRACT

Ecological data are often dependent on sampling effort, such as counts measured per unit area. Such data come from monitoring programs across ecology and fisheries (e.g. point counts, camera and trap surveys, fishery sampling), and underpin abundance indices, species distribution models, and often management decisions. A common tool to account for effort differences is the ‘offset term’ in generalized linear models, enforcing fixed proportionality between effort and the response. However, detailed guidance is limited on applying offsets and transformations, or when an effort covariate is preferable. This article reviews approaches for modelling sampling effort in regression analyses, provides best-practice recommendations, and uses simulation to examine performance of alternative parameterisations across scenarios. Offsets of log-transformed effort are preferable when proportionality is strongly supported, guaranteeing proportionality and avoiding misspecification bias. When deviation from proportionality is possible (which may be common), effort should be included as a log-transformed covariate, ideally a constrained smoother, to allow estimation of non-linear or saturated relationships. The choice between offset and covariate also depends on modelling aims: offsets support standardisation, whereas covariates enable inference on effort effects. In delta or hurdle models, effort covariates are useful because offsets have different interpretations across model components. Additional considerations include multiple effort variables, collinearity, endogeneity (when effort responds to abundance), and species-specific responses in multi-species models. Rather than modelling effort routinely, researchers should explore the effort-response relationship (proportional, otherwise linear on the link or original scales, or non-linear), drawing on prior knowledge, practical experience, data exploration, and statistical tests.

PMID:42533195 | DOI:10.1007/s00442-026-05944-z

Cardiol Ther. 2026 Jul 31. doi: 10.1007/s40119-026-00461-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Acoramidis, an oral transthyretin stabilizer that achieves near-complete stabilization, is approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) based on the phase 3 study, ATTRibute-CM (NCT03860935). To complement trial data, ACO-REAL (NCT07235462) was designed to generate real-world evidence on acoramidis use in ATTR-CM. This article describes the rationale and design of ACO-REAL.

METHODS: ACO-REAL is an ongoing, prospective, non-interventional, multicenter study planned in approximately 2000 adults with ATTR-CM (wild-type or variant) initiating treatment with acoramidis in real-world settings across 21 European countries. The primary objective of ACO-REAL is to assess the characteristics and treatment patterns of participants with ATTR-CM receiving acoramidis during an observational period of around 12 months.

PLANNED OUTCOMES: The primary objective is to assess demographics (including age and sex), disease characteristics, and treatment patterns of participants treated with acoramidis. Disease characteristics include type, diagnosis, and manifestations of ATTR-CM, and ATTR-CM-relevant comorbidities. Treatment patterns include adherence, persistence, and reasons for treatment modifications, including switching from a different ATTR-CM medication to acoramidis. The secondary objective is to describe the safety profile of acoramidis. The clinical course of ATTR-CM in participants initiating acoramidis is also being evaluated through measuring cardiac function, functional capacity and health status (New York Heart Association classification and 6-min walk distance), and health-related quality of life (Kansas City Cardiomyopathy Questionnaire and EuroQol 5-Dimension 5-Level questionnaire). Healthcare resource utilization is also being evaluated. Statistical analyses will be exploratory and descriptive. Categorical variables will be presented as frequencies and continuous variables as sample statistics.

CONCLUSIONS: ACO-REAL is the first multinational observational study to collect regular, prospective, real-world data in participants with ATTR-CM treated with acoramidis. This study aims to provide insights into ATTR-CM treatment using real-world evidence from European healthcare systems and may help to guide decision-making in clinical practice. Graphical abstract available for this article.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT07235462.

PMID:42533192 | DOI:10.1007/s40119-026-00461-9

Arch Virol. 2026 Jul 30;171(8):240. doi: 10.1007/s00705-026-06697-z.

ABSTRACT

HDV has a high genetic diversity among isolates and a high capacity to accumulate mutations over time. The mechanisms involved in the clinical progression of HDV are not fully elucidated. Few studies relate mutations to clinical implications, which makes this variable extremely relevant for research into HDV-3, a genotype associated with worse clinical progression. The aim of this study was to analyze mutations in complete genome sequences of HDV-3 isolated in the Brazilian Western Amazon. During 2010 to 2023, 35 hepatitis Delta patients with mild or advanced fibrosis gave serum samples that were submitted to conventional PCR and sequencing. Synonymous and non-synonymous mutations were analyzed along the delta antigen sequence based on the reference strain NC_076103.1. N-terminal and C-terminal regions of Large HDAg, molecular modeling and docking analyses were performed. 114 non-synonymous substitutions were identified in 76 positions along the HDAg-L. To synonymous mutations, 46 substitutions were found in 44 nucleotide sites. S/L8P/Q/M was the most frequent mutation among the advanced fibrosis group. The D46E and A70T mutation was more observed among patients with increased AST. These associations showed statistically significant p-values. Mutations in the N-terminal region of Large HDAg led to minor conformational changes. The C-terminal region indicates moderate structural differences caused by the mutations. The binding conformation of Large HDAg with Mutant2C exhibiting the most stable interaction, as suggested by its docking score. This study shows some evidence of the influence of HDAg mutations in relation to clinical significance, providing insights for further, longitudinal research.

PMID:42533182 | DOI:10.1007/s00705-026-06697-z

J Artif Organs. 2026 Jul 30;29(3):49. doi: 10.1007/s10047-026-01577-4.

ABSTRACT

The novel lab-scale hollow fiber membrane module was fabricated to determine the apparent sieving coefficient ([Formula: see text]) of commercial hemodiafiltration membranes, MFX-SW eco (polyethersulfone, Sample A) and NVF-P (polysulfone, Sample B), using the aqueous solution of dextran with a broader molecular weight distribution. All the molecular weight cut-off curves plotted as [Formula: see text] versus filtration flow rate (Q_F) exhibited smooth profiles without intersecting each other, showing distinct variations depending on Q_F across a wide range of molecular weights. Field emission scanning electron microscopy (FE-SEM) observations revealed that the equivalent pore diameters of samples A and B were nearly identical at 23.0 ± 15.5 nm and 23.3 ± 15.5 nm, respectively. Although the surface porosity of sample A (14.5 ± 3.9%) was higher than that of sample B (10.2 ± 3.2%), the difference was not statistically significant. These numerical data were in excellent agreement with the qualitative morphological findings obtained from the FE-SEM images. Furthermore, it is suggested that the subtle structural differences between the two membranes are also reflected in the relationship between the real sieving coefficients ([Formula: see text]) calculated by using [Formula: see text] and the equivalent pore diameters. Since the lab-scale modules are fabricated relatively easily by hand, this methodology is extremely valuable to rigorously define membrane performance.

PMID:42533176 | DOI:10.1007/s10047-026-01577-4

Surg Endosc. 2026 Jul 30. doi: 10.1007/s00464-026-13215-4. Online ahead of print.

ABSTRACT

BACKGROUND: Barrett’s esophagus (BE) is associated with longstanding gastroesophageal reflux disease and can progress to esophageal adenocarcinoma. BE is primarily managed with proton pump inhibitors (PPIs), which are metabolized by cytochrome P450 2C19 (CYP2C19). CYP2C19 polymorphisms affect PPI plasma levels, which are categorized as poor (PM), intermediate (IM), normal (NM), rapid (RM), and ultra-rapid (UM) metabolizers. This study assessed the prevalence of CYP2C19 phenotypes in patients with BE and concomitant hiatal hernias (HH).

METHODS: This was a single-institution retrospective review of medically-managed adult BE patients with CYP2C19 genotyping. Patients were grouped by HH size (small, medium, or large). CYP2C19 phenotypes were stratified by genotype as: PM/IM, NM, and RM/UM based on anticipated need for PPI dose adjustment. Descriptive statistics and a multivariable analysis to determine factors associated with RM/UM were used.

RESULTS: A total of 97 patients (58% female, median age 61, mean BMI 27.5) were included, and CYP2C19 phenotypes were PM/IM (32%, 95% CI 0.27-0.41), NM (37%, 95% CI 0.27-0.47), and RM/UM (31%, 95% CI 0.22-0.40). HHs were present in 59 patients. Notably, 17% of RM/UM patients had concomitant severe erosive esophagitis, LA grade C/D. On sub-analysis, there was a trend toward higher prevalence of RM/UMs(53%) compared with PM/IM/NM (33%, p = 0.06) in patients who did not have a HH. The presence of HHs tended to be more frequent in the PM/IM/NMs (67%) compared with RM/UMs (47%, p = 0.06). On multivariable analysis, this trend persisted with HHs being less present with RM/UMs (OR 0.43, 95% CI 0.18-1.03).

CONCLUSION: There is a trend toward high prevalence of the RM/UM phenotype in patients with BE. Patients with RM/UM phenotype could benefit from PPI dose optimization. Given the poor survival associated with esophageal adenocarcinoma and its association with BE, assessing CYP2C19 phenotype to optimize PPI dosage and effectiveness could have significant public health implications, and additional prospective studies are needed.

PMID:42533164 | DOI:10.1007/s00464-026-13215-4

Nature. 2026 Jul 30. doi: 10.1038/d41586-026-02079-2. Online ahead of print.

NO ABSTRACT

PMID:42533145 | DOI:10.1038/d41586-026-02079-2