Nevin Manimala

J Biopharm Stat. 2025 Sep 9:1-16. doi: 10.1080/10543406.2025.2547590. Online ahead of print.

ABSTRACT

A randomized clinical trial with multiple experimental groups and one common control group is often used to speed up development to select the best experimental regimen or to increase the chance of success of clinical trials. Most of the time, multiple dose levels of an experimental drug or multiple combinations of one experimental drug with other drugs comprise multiple experimental groups. Because the experimental drug appears in multiple comparisons with a shared control group, multiple testing adjustments to control the family-wise type I error rate are needed. We extend the stepwise over-correction (SOC) method that is applied to a multi-arm trial with a response rate as its endpoint to a multi-arm trial where time to event is the primary endpoint and confidence interval of the hazard ratio determines the statistical significance. We provide the formula of the bias of the maximum treatment effect estimate toward the true treatment effect between the selected experimental group and the shared control group. We aim to use the bias-corrected estimate for the inference of treatment effects in multi-arm trials on the full alpha level and demonstrate a completely new type of reject region. This approach does not require us to split alpha level among the multiple comparisons or to specify the test order ahead of time. The type I error control and the power enhancement of the proposed approach are both held.

PMID:40923261 | DOI:10.1080/10543406.2025.2547590

J Anim Sci. 2025 Sep 5:skaf252. doi: 10.1093/jas/skaf252. Online ahead of print.

ABSTRACT

Fish oil is a source of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) that confer several health benefits. To ensure continuity in the supply of n-3 fatty acids, alternative sources are being sought. Algal oil may serve as a promising alternative to fish oil for supplementing DHA in cat foods. The purpose of this study was to determine if inclusion of algal oil in place of fish oil in feline foods would result in similar serum DHA and EPA concentrations. Cats were first fed a control food for 5 weeks and then randomized into two groups and fed test foods containing either fish oil or algal oil in sequential increasing concentrations of DHA (0.2%, 0.4%, and 0.6%). Serum was analyzed at the beginning and end of each of these 5-week feeding periods. Oil type had no effect on body weight of cats consuming foods containing either algal oil or fish oil; only cats that consumed the algal oil food with 0.6% DHA had a significant decrease from baseline in food intake (P = 0.0011). Analysis of serum fatty acid concentrations showed that serum DHA increased at similar rates when fish oil and algal oil levels were increased in the food. Although increasing levels of fish and algal oil both increased serum EPA concentrations, the higher concentrations of EPA in the fish oil foods resulted in higher circulating concentrations of EPA in those cats. Algal oil was included at levels 3.7-fold lower than fish oil due to the high DHA content of algal oil. Overall, these data indicate that algal oil may serve as a good alternative dietary source of DHA. Fatty acid profiles of algal oil should be considered when selecting a replacement for fish oil in feline foods.

PMID:40923230 | DOI:10.1093/jas/skaf252

Clin Neuropsychol. 2025 Sep 9:1-16. doi: 10.1080/13854046.2025.2554745. Online ahead of print.

ABSTRACT

Objective: This study compared symptom reporting and cognitive test performance within 72 h of a suspected concussion between high school student-athletes with and without pre-injury self-reported mental health treatment. Methods: Eight hundred seventy-nine high school athletes with (n = 75) and without (n = 804) a self-reported history of treatment for anxiety or depression underwent preseason baseline testing, and post-injury testing within 72 h of suspected concussion. Results: At baseline, adolescents with a self-reported history of treatment for anxiety or depression (n = 75, 8.5%) endorsed significantly greater affective (Cohen’s d = 0.70), cognitive (d = 0.52), physical (d = 0.53), and sleep-arousal (d = 0.50) symptoms compared to those with no mental health treatment history (n = 804). There was not a statistically significant group-by-time interaction for the total symptom severity score (F(4, 874)=2.27; p=.06), indicating that the magnitude of acute symptom worsening following concussion did not appear to differ in association with pre-injury mental health status. There were no significant group differences in neurocognitive composite scores at baseline or following concussion. Similarly, adolescents with self-reported history of treatment for anxiety or depression not more likely to exceed the reliable change cutoffs for worsening symptoms or cognitive functioning as compared to those without a self-reported history of treatment for anxiety or depression. Conclusions: Although there was no difference in the magnitude of change from baseline to post-injury symptom scores between the two groups, adolescents with pre-injury mental health difficulties reported more symptoms at baseline and acutely following a concussion. Adolescents with a self-reported history of treatment for anxiety or depression did not differ from those without on cognitive scores at baseline or following concussion.

PMID:40923224 | DOI:10.1080/13854046.2025.2554745

Cancer Med. 2025 Sep;14(17):e71219. doi: 10.1002/cam4.71219.

ABSTRACT

INTRODUCTION: In the past decade, the management of advanced prostate cancer has shifted to novel hormonal therapies. As a result, urologists have increased their involvement in the management of advanced prostate cancer. These therapies require close monitoring due to the possibility of adverse cardiometabolic events. We assessed outcomes among men diagnosed with advanced prostate cancer started on novel hormonal therapy by a urologist compared to those by a medical oncologist.

METHODS: We performed a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer treated with a novel hormonal therapy between 2012 and 2019. The primary outcome was an adverse event comprised of a hospital visit for a cardiometabolic event within 6 months of starting a novel hormonal therapy. Secondary outcomes included monthly out-of-pocket costs and treatment adherence.

RESULTS: There were 1212 (23%) and 4124 (77%) patients who were prescribed a novel hormonal therapy for the first time by a urologist and medical oncologist, respectively. No difference in the composite adverse event measure was observed in those managed by urologists or medical oncologists (4.2% vs. 4.7%, respectively, p = 0.49). Out-of-pocket costs, in men without low-income subsidies, did not vary by specialty ($772 vs. $790, p = 0.58). Adherence to treatment did not vary in men managed by urologists or medical oncologists (75% vs. 74%, respectively, p = 0.64).

CONCLUSIONS: The specialty of the physician prescribing a novel hormonal therapy was not associated with the risk of a cardiometabolic adverse event. Further, management by a urologist did not adversely affect costs to patients or adherence.

PMID:40923220 | DOI:10.1002/cam4.71219

Orthod Craniofac Res. 2025 Sep 9. doi: 10.1111/ocr.70024. Online ahead of print.

ABSTRACT

OBJECTIVE(S): In this pilot study, exosomes from saliva were isolated and tested for the presence of metabolomic biomarkers for physiological external root resorption and/or pathological alveolar bone resorption.

SETTINGS AND SAMPLE POPULATION: Saliva samples of 20 individuals in the mixed dentition stage of dental development.

MATERIALS AND METHODS: Saliva was obtained from healthy control children with resorbing primary teeth or children with localised aggressive periodontitis (LAP) showing alveolar bone loss but little root resorption. Exosomes were isolated by differential centrifugation and analysed by electron microscopy, nanoparticle tracking analysis (NTA) and enzyme-linked immunosorbent assay (ELISA). Subsequently, exosomes were subjected to mass spectrometry to identify and quantitate metabolites. Differences between groups were statistically determined.

RESULTS: Over 2000 metabolites were detected in salivary exosomes. Metabolites that differed significantly between exosomes from the saliva of LAP patients and controls included L-pipecolic acid, acetylcholine, creatinine, N-acetylneuraminate and numerous unidentified molecules.

CONCLUSION: This pilot study provided a proof-in-principle for using metabolites from salivary exosomes as biomarkers.

PMID:40923219 | DOI:10.1111/ocr.70024

Eur J Neurol. 2025 Sep;32(9):e70273. doi: 10.1111/ene.70273.

ABSTRACT

BACKGROUND: Changes in handgrip strength have recently been adapted as clinical biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) under the assumption of a disease-specific peripheral neuromuscular dysfunction. However, some have proposed that strength impairments in ME/CFS are better explained by alterations in higher-order motor control. In serial measurements, exertion can been assessed through analysis of variation, since maximal voluntary contractions exhibit lower coefficients of variation (CV) than submaximal contractions.

METHODS: Serial handgrip strength measurements of 105 ME/CFS patients and 66 healthy controls from a previously published biomarker validation study are analyzed post hoc regarding their CV. CV is separately compared in a subsample of participant with normal indexes of fatigability.

RESULTS: Compared to healthy controls, patients had significantly higher CV, largely over the conservative 15% cutoff associated with submaximal exertion. In the subsample of study participants, whose within-session fatigability was within normal bounds, CV was still significantly higher in female patients; the difference in male patients was not statistically significant (p = 0.06).

CONCLUSIONS: This analysis suggests that loss of grip strength is likely compounded by alterations in higher-order motor control, challenging its utility as a biomarker of peripheral dysfunction. Functional weakness is discussed within a framework that sees motor fatigue as a result of reduced implicit self-efficacy acquired in the context of chronic dyshomoeostasis and disability.

PMID:40923211 | DOI:10.1111/ene.70273

Rhinology. 2025 Sep 9. doi: 10.4193/Rhin23.271. Online ahead of print.

ABSTRACT

BACKGROUND: Smell tests in children need to be standardized and validated, include odors familiar to children, and be defined by age-dependent standards. This study aimed to adapt the Sniffin Kids Test (SKT) for Polish children and conduct validation and evaluation of the Sniffin Kids Poland Test (SKPOL).

METHODOLOGY: The study included 382 children (4-14 years old) recruited in Poland, who were allocated into healthy (n=343) and sick (with subjective olfactory disorders, n=39), divided into 3 age subgroups, but also 13 anosmic children with Kallmann syndrome (KS) and olfactory bulb aplasia. Firstly, the smell testing was performed in 382 children using SKT, and subsequently, SKPOL was created using odors identified by at least 75% of healthy individuals. The 10th percentile of SKPOL results in healthy children was adopted as a cutoff point between norm and pathology. SKPOL validation and reliability were assessed using the KS group results.

RESULTS: Odor identification score in SKT of Polish children in healthy 6-14-year-olds did not meet the criteria for a test adapted for population studies. An odor identification rate was obtained for 5 odors in 4-7 years old, 7 odors in 8-10 years old, and 9 odors in 11-14 years old. SKPOL was created using these odors. Age-dependent norms for SKPOL were ≥4, ≥5, and ≥7, respectively. All KS children had SKPOL results below the 10th percentile.

CONCLUSIONS: Validation and evaluation of SKPOL confirmed good adaptation and high reproducibility of the test for Polish children aged 4-14 years.

PMID:40923196 | DOI:10.4193/Rhin23.271

Int Endod J. 2025 Sep 9. doi: 10.1111/iej.70030. Online ahead of print.

ABSTRACT

INTRODUCTION: Accurate diagnosis of pulpal health is crucial to identify the most effective therapeutic approach. However, differentiating pulpal conditions, which may require different treatment approaches, remains a challenge. This study aimed to address this gap by investigating the protein levels of 17 inflammatory biomarkers simultaneously in the dental pulp with different clinical diagnoses.

METHODS: This study employed a cross-sectional exploratory design, enrolling 64 adult patients. After obtaining ethical approval, researchers conducted clinical and radiographic examinations to categorise teeth into four diagnostic groups: normal pulp, reversible pulpitis, symptomatic irreversible pulpitis and asymptomatic irreversible pulpitis. Pulpal blood samples were then collected and analysed using Luminex technology to measure the levels of inflammatory proteins and matrix metalloproteinases (MMPs). Statistical analyses, including the Mann-Whitney U test and Spearman’s rank correlation, were used to compare the levels of these markers across the different diagnoses and to assess their correlation with patient symptoms.

RESULTS: The study revealed significant increases in several inflammatory proteins, including IL-4, IL-8, MCP-1, MIP-1α, RANTES and MMP-9, in both types of irreversible pulpitis cases compared with other diagnostic categories p < 0.05. These elevated levels exhibited positive correlations with patient-reported pain scores, instances of spontaneous pain and bleeding times. Notably, only IL-4 and IL-7 exhibited correlations with prolonged bleeding times (over 10 min) p < 0.05, while IL-1α and MMP-2 were associated with shorter bleeding times (under 10 min) p < 0.05. Additionally, IL-8 and MCP-1 levels were significantly associated with positive palpation findings p < 0.05, whereas MIP-1α and MMP-1 were correlated with positive percussion results p < 0.05.

CONCLUSION: Differential specific inflammatory potential biomarker levels may differentiate pulpal disease states. Integrating molecular diagnostics into longitudinal clinical trials and eventually into routine endodontic practice, could revolutionise treatment decisions.

PMID:40923157 | DOI:10.1111/iej.70030

Emerg Med Australas. 2025 Oct;37(5):e70135. doi: 10.1111/1742-6723.70135.

ABSTRACT

OBJECTIVE: This study aimed to identify presentations to the Alice Springs Emergency Department that could be managed in an Urgent Care Centre (UCC).

METHODS: We reviewed 1 year of ED presentation data at Alice Springs Hospital (ASH) from August 2022 to August 2023 and used a sequence of exclusion criteria to identify patients most likely to be eligible for UCC management.

RESULTS: Our model indicated that 35.0% of ED presentations at ASH during this period could have been managed in a UCC. Only 41.5% of these presentations (14.5% of total presentations) occurred during UCC operating hours.

CONCLUSIONS: According to this model, a significant proportion of ED presentations could potentially be managed in a UCC, although a large proportion of these occurred outside of UCC opening hours. The impact of the introduction of a UCC into a remote community on ED presentations, patient experience, patient outcomes and the broader system requires further study.

PMID:40923149 | DOI:10.1111/1742-6723.70135

Cancer Rep (Hoboken). 2025 Sep;8(9):e70341. doi: 10.1002/cnr2.70341.

ABSTRACT

BACKGROUND AND AIMS: Breast cancer is the most commonly diagnosed cancer in women worldwide. Several studies have investigated the relationship between breast cancer and specific foods or nutrients, rather than examining an overall dietary pattern. This study aims to investigate the association between breast cancer and the predominant dietary pattern in Ahvaz city.

METHODS: This hospital-based case-control study was conducted on 106 women with breast cancer and 107 controls. Dietary intake data were collected using a 147-item food frequency questionnaire. We merged the data on the 147 foods into 20 food groups to identify major dietary patterns. Factor analysis with varimax rotation was then employed to determine the primary dietary patterns. Binary logistic regression was used to assess the association between dietary patterns and breast cancer, with adjustment for potential confounders.

RESULTS: Three dietary patterns were identified: healthy, western, and traditional. The Western dietary pattern was robustly associated with a higher risk of breast cancer in premenopausal women (OR = 4.22; 95% CI: 1.09, 16.31; p = 0.03) in the adjusted model. However, no association was found between a healthy and traditional pattern and breast cancer.

CONCLUSION: These findings suggest that the Western dietary pattern is positively associated with breast cancer risk in premenopausal Iranian women.

PMID:40923112 | DOI:10.1002/cnr2.70341