Category: Statistics

Mov Disord Clin Pract. 2026 Jun 19. doi: 10.1002/mdc3.70712. Online ahead of print.

ABSTRACT

BACKGROUND: Orthostatic myoclonus is characterized by irregular, lower limb myoclonic bursts during stance and is a major cause of postural instability and falls. However, studies are limited, and little is known about its pathophysiology.

OBJECTIVES: We sought to define the clinical and electrophysiological features of orthostatic myoclonus in a large, single-center cohort.

METHODS: We included 42 participants (24 males, 18 females) with a mean age of 74 years (range, 46-93) from Westmead Hospital presenting with orthostatic myoclonus from 2007 to 2023. Medical records were retrospectively reviewed for demographic details, symptoms, co-morbidities, and treatment. Lower limb surface electromyography (EMG) was analyzed using a custom-designed algorithm to automatically identify myoclonic bursts and measure their duration, synchronicity, and rhythmicity. Differences in burst parameters between muscles and associations between burst parameters and clinical characteristics were statistically evaluated.

RESULTS: Mean burst durations during standing were 77 to 90 ms across lower limb muscles. Maximum burst activity and bilateral synchronicity occurred in tibialis anterior. Only 12% of participants exhibited any rhythmicity. A total of 79% of participants had a coexistent neurological disorder including 26% with parkinsonism. There was no significant association between parkinsonism and burst parameters. However, there was a significant, inverse correlation between the presence of neuropathy or radiculopathy and synchronous activity (P = 0.02).

CONCLUSIONS: We provide a computationally robust clinical and electrophysiological analysis of orthostatic myoclonus in a large cohort. Our findings support the theory of a subcortical generator arising from protean secondary causes and subject to peripheral modulation. Further work is needed to clarify treatment outcomes.

PMID:42322040 | DOI:10.1002/mdc3.70712

Int J Cancer. 2026 Jun 19. doi: 10.1002/ijc.70613. Online ahead of print.

ABSTRACT

Cancer-related fatigue (CRF) is a prevalent symptom among colorectal cancer (CRC) survivors. While inflammation is a proposed underlying mechanism, longitudinal evidence including pre-treatment assessments remains scarce. Within the population-based PROCORE study, newly diagnosed CRC patients provided blood samples and completed questionnaires at diagnosis (n = 411; 60.6% male; age = 67.0 years), 12- (n = 304), and 24-month follow-up (n = 252). Eleven inflammatory biomarkers (CRP, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, sTNFRI, and sTNFRII) were assayed; CRF was measured with the Multidimensional Fatigue Inventory. Hybrid linear mixed models disentangled between- and within-subject associations, controlling for sociodemographic (e.g., age), clinical (e.g., cancer treatment), and lifestyle covariates (e.g., BMI), sleep quality, and pain. A normative age- and sex matched sample (n = 204; 52.5% male; age = 64.3 years) was included for comparison. Soluble TNF receptors (sTNFRI/II) were most robustly and positively associated with nearly all fatigue dimensions. CRP was positively associated with mental and physical fatigue; IL-8 positively associated with multiple domains including reduced motivation; and IFN-γ positively associated with general fatigue and reduced activity. Lower IL-1α was associated with more mental fatigue. Between-subject effects mirrored overall results; within-subject effects were more selective. Associations were most consistently observed for mental fatigue. In controls, less associations were significant; CRP was the most robust marker and positively associated with general fatigue, reduced activity, and reduced motivation. CRC survivors exhibited a broader, mostly TNF-α driven inflammatory signature of fatigue than controls. Findings highlight inflammation as a potential target underlying CRF, informing survivorship care strategies.

PMID:42322026 | DOI:10.1002/ijc.70613

Cancer Med. 2026 Jun;15(6):e71973. doi: 10.1002/cam4.71973.

ABSTRACT

INTRODUCTION: Cervical cancer is the fourth leading cause of cancer deaths in women, and mortality varies significantly by region, with the highest rate in southeastern US. This study evaluated the association between comorbidity burden and cervical cancer survival and compared the prognostic performance of the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI).

METHODS: A retrospective cohort study was conducted using electronic medical records of women diagnosed with cervical cancer between 2011 and 2021 at a large academic hospital in southeastern US. CCI and ECI were estimated to assess 5-year overall survival using the Kaplan-Meier methods and multivariable Cox proportional hazard models, stratified by age at diagnosis (young < 50 vs. old ≥ 50 years) and adjusting for baseline demographics. Two-year survival analyses were also conducted. Predictive discrimination of CCI and ECI models was compared using Harrell’s C-statistic.

RESULTS: Higher comorbidity burden was associated with increased mortality across age groups. Compared with patients with no comorbidities (CCI = 0), CCI scores of 1-4 and ≥ 5 were associated with higher 5-year mortality among younger women (adjusted hazard ratio [aHR] = 2.35 (1.03-5.35); 2.80 (1.38-5.69), respectively) and older women (aHR = 2.38 (1.26-4.50); 1.43 (0.63-3.27), respectively). ECI scores ≥ 3 were also strongly associated with increased 5-year mortality in both age groups. Both indices demonstrated acceptable and comparable predictive discrimination for 5-year survival in both age groups (C-statistics ranging from 0.74-0.70). Findings were consistent in 2-year survival analyses.

CONCLUSION: Greater comorbidity burden is independently associated with worse survival among cervical cancer patients; highlighting the importance of comorbidity management in cervical cancer care.

PMID:42322013 | DOI:10.1002/cam4.71973

Cancer Rep (Hoboken). 2026 Jun;9(6):e70611. doi: 10.1002/cnr2.70611.

ABSTRACT

BACKGROUND: Post-treatment weight gain and gut dysbiosis are important concerns in breast cancer patients. However, evidence on the gut microbiota in this population, particularly in relation to physical activity, is limited.

AIM: Therefore, we compared gut microbiota in breast cancer patients with obesity with healthy controls and non-cancer controls with obesity and subsequently examined the effects of a combined dance and dietary intervention on gut microbiota, metabolic health, physical fitness, and quality of life.

METHODS AND RESULTS: The observational part compared gut microbiota in breast cancer patients with obesity (BCO, BMI 32.43 ± 4.90 kg/m²) with non-cancer controls with obesity (OC, BMI 37.78 ± 6.68 kg/m²) and healthy controls (HC, BMI 21.26 ± 1.26 kg/m²). A controlled trial was conducted in breast cancer patients with obesity, with an intervention group (INT, n = 13) receiving a 12-week combined dance and dietary intervention and non-intervention controls (CTRL, n = 10). Gut microbiota was assessed using 16S rRNA sequencing, physical fitness was evaluated by an incremental bicycle ergometer test and motor tests, and quality of life was measured using the EORTC QLQ-C30 and BR23 questionnaires. In the observational study, breast cancer patients showed significant differences in beta diversity and a lower relative abundance of health-associated bacteria (e.g., Faecalibacterium prausnitzii) compared with both controls. In the controlled trial, the intervention led to a significant improvement in body composition, physical fitness (e.g., Vo2max, handgrip strength), and several validated quality-of-life domains (e.g., fatigue, body image). A statistically significant difference in beta diversity at the post-intervention phylum level was observed (p = 0.046, R² = 0.11). Microbiota composition within INT shifted toward, increased health-associated taxa (Bifidobacterium spp.) and reduced opportunistic pathogens (Klebsiella oxytoca). However, a decrease in butyrate-producing taxa (Ruminococcus bromii, Ruminiclostridium hungatei) was also observed.

CONCLUSION: Breast cancer patients showed more negative shifts in gut microbiota compared with both controls. In addition, a 12-week combined dance and dietary intervention improved body composition, physical fitness, quality of life, and was associated with mixed but potentially beneficial changes in select gut microbiota taxa among breast cancer patients with obesity.

TRIAL REGISTRATION: Clinical trial registration number: NCT07213271.

PMID:42321999 | DOI:10.1002/cnr2.70611

BMC Nutr. 2026 Jun 20. doi: 10.1186/s40795-026-01270-y. Online ahead of print.

ABSTRACT

BACKGROUND: Poor sleep and malnutrition are prevalent issues among older adults, contributing to negative outcomes such as depression, sarcopenia, and reduced quality of life. A bidirectional relationship has been proposed between diet and sleep. This study aimed to examine the association between the Healthy Eating Index (HEI) and both sleep quality and duration in older adults.

METHODS: This cross-sectional analysis was conducted using baseline data from the Neyshabur Elderly Longitudinal Study (NeLSA, 2016-2022), including 2,026 adults aged ≥ 60. Dietary data were collected via a validated food frequency questionnaire, and HEI-2015 scores were calculated. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), with a score > 5 indicating poor sleep quality. Sleep duration was self-reported and categorized as adequate (≥ 7 h) or insufficient (< 7 h). Multivariable logistic regression was used to assess associations between HEI quartiles and sleep outcomes, adjusting for demographics, BMI, smoking, education, and chronic diseases.

RESULTS: Participants had a mean age of 69.1 ± 7.6 years; 55.5% were women. Women reported poorer sleep quality and shorter sleep duration than men (P < 0.001). There was no statistically significant association between HEI and sleep quality or duration in the overall population or by gender (P > 0.05). However, a borderline non-significant inverse association was observed between HEI and insufficient sleep duration in older women. (Q4 vs. Q1, OR: 0.709; 95% CI: 0.502-1.003; P = 0.052).

CONCLUSION: Higher HEI scores were not independently associated with sleep quality or duration among older adults. Although higher diet quality showed a non-significant inverse association between better sleep in women, the relationship may be influenced by other health-related factors. Further longitudinal and interventional studies are recommended.

PMID:42321951 | DOI:10.1186/s40795-026-01270-y

Genes Environ. 2026 Jun 19. doi: 10.1186/s41021-026-00362-2. Online ahead of print.

ABSTRACT

BACKGROUND: The in vivo micronucleus (MN) assay is used for evaluation of chromosomal aberration induced by chemicals, and the liver MN assay can detect genotoxic compounds which require metabolic activation to induce micronucleus formation. However, species differences in liver metabolism are known, and therefore results obtained from mouse and rat liver MN assays may not always be directly extrapolated to humans. Chimeric mouse with human hepatocytes (the PXB-mouse®) is expected to be used in genotoxicity studies as an animal model of metabolic reactions in humans. To date, the use of the liver MN assay with PXB-mice has been reported, but its application has been limited to compounds that do not require metabolic activation to induce chromosomal aberrations.

RESULTS: In this study, we used the liver MN assay in PXB-mice to evaluate diethylnitrosamine (DEN) and N-nitrosodimethylamine (NDMA), both of which require metabolic activation to induce chromosomal aberrations. After repeated administration of DEN for 14 days or NDMA for 28 days, statistically significant increases in micronucleus frequency were observed.

CONCLUSION: From the results of this examination, it was demonstrated that the liver MN assay using PXB-mice can detect the genotoxicity of compounds that require metabolic activation to exert genotoxicity. Although some issues remain, such as the presence of residual mouse hepatocytes, the liver MN assay using PXB-mice is expected to provide supportive information for more accurate evaluation of chemical genotoxicity in humans.

PMID:42321939 | DOI:10.1186/s41021-026-00362-2

BMC Psychol. 2026 Jun 19. doi: 10.1186/s40359-026-05044-w. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased risk of depressive symptoms across the life course. Medical students are exposed to sustained academic and psychosocial stress, which may interact with earlier adversity to influence mental health outcomes. However, evidence from non-Western contexts remains limited. This study examined the prevalence of ACEs and their association with depressive symptoms among Thai medical students.

METHODS: A cross-sectional study was conducted between April and July 2025 among medical students at one faculty of medicine and two affiliated medical education centers in Southern Thailand. All participants completed an anonymous online survey that included the Thai version of the Adverse Childhood Experiences questionnaire and the validated Thai version of the Patient Health Questionnaire-9 (PHQ-9). ACE exposure was categorized as low (0-1), moderate (2-3), and high (≥ 4). Depressive symptoms were defined as PHQ-9 scores ≥ 9. Multivariable logistic regression analyses were performed to examine associations between ACE exposure and depressive symptoms, adjusting for demographic variables, physical illness, and recent life stress.

RESULTS: Among 540 participants (median age 21 years; 60.4% female), 54.6% reported at least one ACE. Moderate and high ACE exposure were observed in 20.2% and 6.7% of students, respectively. The most commonly reported ACE domains were physical neglect (31.9%), parental divorce or separation (28.8%), and household mental illness (26.8%). Depressive symptoms were present in 17.6% of participants. In multivariable analyses, moderate ACE exposure was independently associated with depressive symptoms (adjusted odds ratio [aOR] = 2.26; 95% CI: 1.29-3.93; p = 0.004). High ACE exposure showed a similar magnitude of association but did not reach statistical significance. Current life stress (aOR = 5.83; 95% CI: 2.77-14.31; p < 0.001) and physical illness (aOR = 2.30; 95% CI: 1.19-4.36; p = 0.012) were also independently associated with depressive symptoms.

CONCLUSION: ACEs were common among Thai medical students and were associated with higher odds of depressive symptoms after adjustment for current stressors. These findings highlight the role of early-life adversity as a potential vulnerability factor for psychological distress in medical training. Longitudinal research is warranted to clarify temporal pathways and inform culturally appropriate mental health support strategies in medical education settings.

PMID:42321925 | DOI:10.1186/s40359-026-05044-w

Pilot Feasibility Stud. 2026 Jun 20. doi: 10.1186/s40814-026-01862-2. Online ahead of print.

ABSTRACT

BACKGROUND: Cognitive difficulties are common in people with multiple sclerosis (MS) and predict poorer quality of life, yet effective treatment is lacking. Cognitive remediation therapy (CRT) improves functioning in individuals with severe mental health conditions and could benefit people with MS if adequately adapted. Recognising patient and public involvement (PPI) benefits in developing acceptable interventions, this study engaged people with MS to develop a protocol to assess the feasibility of delivering a computerised, therapist-assisted CRT programme (CIRCuiTS™) to people with MS. This paper describes this process and presents the trial protocol, highlighting how PPI informed the study design and treatment implementation.

METHODS: Protocol co-development involved three phases of consultation with people with MS. First, the PPI lead, who has MS, contributed along with mental health professionals to the design draft. Second, co-development using an observational qualitative design was conducted with people with MS in a structured 2-day workshop. Workshop discussions were recorded, transcribed, and analysed thematically to arrive at 24 specific, actionable recommendations. These recommendations, alongside statistical input, guided the trial design. Finally, a separate PPI group provided feedback on the trial documents. The proposed trial will recruit 24 people with MS experiencing cognitive difficulties from a UK NHS service, randomly assigning them to receive a 12-week CIRCuiTS™ MS programme immediately or after a 13-week wait. This relatively short waiting period was recommended as likely to maintain engagement. Standard CIRCuiTS™ delivery will be adapted to MS needs by offering remote sessions, dexterity tailoring and MS-specific therapist training. Primary outcomes are feasibility and acceptability. Guided by PPI-anticipated benefits, the secondary outcomes will be goal attainment, cognition, fatigue, mood, and daily functioning. Two people with MS continue to guide the study in the oversight group and a PPI Advisory group will provide ongoing advice on trial management.

DISCUSSION: PPI, as recommended in the new CONSORT 2025 statement, strengthened the feasibility and acceptability of the trial by addressing challenges and shaping the protocol. This collaboration enhances the evaluation of CRT for people with MS and provides a model for transparent PPI reporting in trial development.

TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06877273, 14th March 2025.

PMID:42321924 | DOI:10.1186/s40814-026-01862-2

J Cannabis Res. 2026 Jun 19. doi: 10.1186/s42238-026-00463-3. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertension is a leading risk factor for cardiovascular disease, particularly in ageing populations. While pharmacological interventions are common, issues with long-term adherence and side effects have prompted interest in alternative treatments. Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa, has been proposed as a potential agent for blood pressure regulation due to its anxiolytic, anti-inflammatory, and vasodilatory properties. This systematic review aimed to evaluate the effects of oral CBD supplementation on blood pressure in adults with normotension and hypertension.

METHODS: A systematic search of PubMed, Web of Science, Scopus, and Medline was conducted in September 2024. Eligible studies were randomised controlled trials (RCTs) involving oral CBD administration in normotensive or hypertensive adults, with blood pressure as an outcome. Studies involving animals, inhaled CBD, or non-English texts were excluded. Risk of bias was assessed using the Cochrane Risk of Bias tool. Clinical heterogeneity was assessed by comparing study populations, CBD dosing regimens, outcome measures, and assessment conditions. Substantial variability in dosing and blood pressure outcome reporting precluded quantitative pooling; therefore, results were synthesised narratively due to clinical heterogeneity.

RESULTS: Four RCTs involving 120 participants met the inclusion criteria. Studies varied in CBD dose (225-600 mg/day), duration (two hours to 5 weeks), and participant health status. An association was observed between CBD dosage (mg/day) and reductions in blood pressure indicators, with greater reductions occurring at higher doses. All four studies reported statistically significant reductions in systolic blood pressure compared to placebo, particularly under stress or during sleep. Two studies reported lower diastolic pressure. The strongest effects were observed with acute administration of the highest-dose studies of 600 mg/day. Side effect severity was generally mild to moderate, including nausea, diarrhoea, and fatigue. No serious cardiovascular events were reported.

CONCLUSION: Oral CBD may reduce blood pressure amongst healthy and hypertensive individuals, particularly under stressful conditions and during sleep. Limitations included small sample sizes, short trial durations, variability in CBD matrices and dosages, lack of pharmacokinetic data, and uncertainty surrounding hepatic safety. Larger, longer-term trials with homogeneous supplementation strategies and bioavailability measures are needed to determine CBD’s therapeutic role in blood pressure management.

PMID:42321899 | DOI:10.1186/s42238-026-00463-3

Confl Health. 2026 Jun 19. doi: 10.1186/s13031-026-00815-z. Online ahead of print.

ABSTRACT

BACKGROUND: Access to essential medicines is a fundamental human right and a critical pillar of effective healthcare. In Africa, armed conflicts severely weaken health systems, disrupting the availability of essential medicine, leading to gaps in patients’ treatment and, in turn, posing a serious risk to overall public health. Therefore, this study aimed to identify the impact of armed conflicts on the availability of essential medicines as a cornerstone of healthcare across African regions, and quantify the extent of this disruption over time and by country.

METHODS: In this systematic review and meta-analysis, data were retrieved from published articles accessible in PubMed, Semantic Scholar, and grey literature covering the period from 1985 to 2025 and 2001 to 2024 for system impact and medicines availability studies, respectively. The literature search was conducted from January to May 2025. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, studies were independently screened by two reviewers and included if they contained information on medicine availability or its relation to health systems in conflict zones and were published in English. The quality of studies was evaluated using the Joanna Briggs Institute criteria. Pooled estimates of medicine availability and their 95% CIs were obtained using a random-effects analysis. Heterogeneity was assessed using the I² statistic. The risk of bias and small study effects were assessed with funnel plots and Egger’s test. Additionally, the leave-one-out sensitivity test and influence diagnostics test were considered to evaluate study-level impact.

RESULTS: The review included data from 1,581 health facilities and 989 essential medicines across eight conflict-affected African countries. The pooled availability of essential medicines calculated from the data obtained from 41 studies conducted in African countries shouldering frequent armed conflict was estimated at 55% (95% CI, 47-63), with substantial heterogeneity across studies (I² = 93%, p < 0.001). Country-level analysis showed the highest availability in the Central African Republic (79%; 95% CI, 49-95) and the lowest in Nigeria (40%; 95% CI, 1-78). A temporal decline in medicine availability was observed, from 76% (2001-2010) to 46% post-2020. No significant publication bias was detected (funnel plot asymmetry p = 0.9560; Egger’s test p = 0.494). Additionally, the influence diagnostic test and the leave-one-out sensitivity analysis indicated that observed heterogeneity likely reflects methodological differences and the sample size across the studies rather than bias or outliers. The systematic review revealed that armed conflicts have profoundly compromised health system functionality through the destruction of healthcare infrastructure, closure of medical facilities, displacement of the health workforce, pervasive insecurity and psychological distress among healthcare providers, and disruptions in supply chains and transportation networks, all of which have adversely affected the accessibility of essential medicines.

CONCLUSION: On average, only 55% of essential medicines were available in conflict-affected regions of Africa, which was below the WHO benchmark of 80%. This finding underscores the severe threat that armed conflict poses to medicine availability and, consequently, to increased indirect morbidity and mortality. Additionally, the conflict undermines medicine availability through multiple, often interconnected mechanisms, indicating the need for a coordinated, multisectoral approach to ensure continuous access to essential medicines. Therefore, strengthening healthcare infrastructure in conflict settings is critical. Furthermore, the international community should enforce accountability mechanisms for violations affecting healthcare services, while donors and regional humanitarian assistance and emergency response mechanisms should increase investment and medicine supply in resilient medicine supply systems capable of maintaining availability during periods of armed conflict.

STUDY PROTOCOL REGISTRATION: The study protocol was registered in PROSPERO (CRD420251154811), the International Prospective Register of Systematic Reviews, maintained by the National Institute for Health and Care Research (NIHR).

PMID:42321895 | DOI:10.1186/s13031-026-00815-z