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Nevin Manimala Statistics

What is the optimal approach to analyse ventilator-free days? A simulation study

Crit Care. 2025 Jun 19;29(1):251. doi: 10.1186/s13054-025-05474-9.

ABSTRACT

BACKGROUND: Ventilator-free days (VFDs) are a composite outcome in critical care research, reflecting both survival and mechanical ventilation duration. However, analysis methods for VFDs are inconsistent, with some focusing on counts and others on time-to-event outcomes, while other approaches such as the multistate model and the win ratio have emerged. We aimed to evaluate various statistical models through simulations to identify the optimal approach for analysing VFDs.

METHODS: First, 16 datasets of 300 individuals were simulated, comparing a control group to an intervention with varying survival rates and ventilation durations. Various statistical models were evaluated for statistical power and Type I error rate. Four clinical trial datasets (LIVE study, NCT02149589; ARMA study, NCT00000579; ACURASYS study, NCT00299650; COVIDICUS study, NCT04344730) were then used to apply the same statistical models to analyse VFDs. Twelve statistical methods were evaluated, including count-based, time-to-event approaches, and the win-ratio. Additionally, sensitivity analyses were conducted.

RESULTS: Most statistical methods effectively controlled Type I error rate, except for the zero-inflated and hurdle Poisson/negative binomial count submodels, as well as the cause-specific Cox regression model for death. The power to detect survival benefit and ventilation duration effects varied, with time-to-event approaches, the Mann-Whitney test, the proportional odds model and the win ratio generally performing best. Similar results were observed in sensitivity analyses. In the real datasets, the multistate model, the Mann-Whitney test, the proportional odds model and the win ratio generally showed a significant association between VFDs and randomisation groups.

CONCLUSIONS: The multistate model could be recommended as the optimal approach for analysing VFDs, as it outperformed the other methods and offers a more interpretable effect size than the proportional odds model and the win ratio.

PMID:40537834 | DOI:10.1186/s13054-025-05474-9

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Nevin Manimala Statistics

Changes in influenza-associated excess mortality in China between 2012-2019 and 2020-2021: a population-based statistical modelling study

Infect Dis Poverty. 2025 Jun 20;14(1):52. doi: 10.1186/s40249-025-01323-7.

ABSTRACT

BACKGROUND: The seasonal cycle of the influenza virus causes substantial morbidity and mortality globally. The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the circulation of influenza viruses can influence influenza-associated excess mortality. Given the few studies that have explored this topic, the objective of this study was to evaluate influenza-associated excess mortality in the Chinese mainland from 2012 to 2021 and quantify the changes from 2020 to 2021 compared with 2012-2019.

METHODS: Using data from national influenza surveillance report and disease surveillance points, we fitted a generalized additive model on all-cause (AC), pneumonia & influenza (P&I), and respiratory (R) mortality rates. In this model, we included data of influenza activity (A/H1N1, A/H3N2 and B), temperature, absolute humidity, the COVID-19 pandemic, and time trends. The excess mortality was estimated by subtracting the fitted baseline mortality from the predicted mortality, which set influenza activity to zero.

RESULTS: The respiratory mortality model explained more than 90% of the variance, indicating the good performance. We found that the influenza-associated mortality was generally decreasing from 2020 to 2021, for instance, influenza A/H1N1-associated excess respiratory mortality (ERM) decreased from 2.62 per 100,000 persons (95% confidence interval: 0.16-5.21) to 0.31 (0.02-0.60) in the northern region and from 3.79 (0.09-7.05) to 0.24 (0.02-0.46) in the southern region between 2012-2019 and 2020-2021. A similar pattern was observed for A/H3N2-associated ERM. While the influenza B remained similar scale, for instance, the ERM was 2.90 (0.72-4.3) and 2.26 (1.76-2.76) in the southern region between 2012-2019 and 2020-2021, respectively. Distinct pattern was observed for the AC and P&I outcomes.

CONCLUSIONS: The COVID-19 pandemic has reduced influenza-associated excess mortality, which may be a result of the reduced activity of the influenza virus caused by nonpharmaceutical interventions. Different patterns of regional differences differed for influenza-associated AC, P&I and R mortality. It should be noticed that the contribution of influenza B was generally similar when comparing 2012-2019 and 2020-2021, which highlighted the attention on the influenza B activity. Additional studies are needed to explore the changes in influenza-associated excess mortality afterwards.

PMID:40537833 | DOI:10.1186/s40249-025-01323-7

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Identifying pathways to cardiovascular mortality by causal graphical models and mediation analysis among hypertensive patients: insights from a prospective study

J Transl Med. 2025 Jun 19;23(1):690. doi: 10.1186/s12967-025-06755-1.

ABSTRACT

BACKGROUND: Many biochemical markers are involved in cardiovascular (CV) prognosis in the hypertensive population, but most findings are derived from a single-exposure setting, and their interaction and potential pathways remain scarce. The aim of this study was to determine the direct cause-effect relationship and the mediating effect of CV mortality to suggest potential pathways.

METHODS: This prospective study analysed a data from 3559 hypertensive individuals from the National Health and Nutrition Examination Survey (1999-2018), with their CV mortality ascertained through linkage to the National Death Index on December 31, 2019. Baseline sociodemographic characteristics, habits, medical history data and serum biochemical markers, including cardiometabolic markers, inflammatory markers, liver enzyme markers, blood-cell based inflammatory and immune markers and kidney and renal markers were recorded. The Mixed Graphical Model-Fast-Causal Inference-Maximum algorithm (MGM-FCI-MAX) was applied to build a causal graphical model (CGM) depicting direct and indirect causes of CV mortality, then pathways were further identified from CGM where mediation analyses were performed.

RESULTS: Of the total participants, 562 (15.79%, 302 men and 260 women) CV deaths occurred after a median follow-up of 154 months. Survival analysis revealed significant sex- and ethnicity-specific differences in CV mortality rates (log-rank P < 0.01 and P < 0.01, respectively). Based on the resulting CGM, we identified three direct causes, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and monocytes, of CV mortality, representing direct pathways underlying kidney and renal function and blood-cell based inflammatory function, respectively. BUN significantly mediated 30.29% of the effect of the eGFR on CV mortality, whereas neither the liver enzyme markers nor insulin pathway with the eGFR as a mediator showed a significant tendency towards a mediated effect after adjusting for covariates. Sex and race were significantly (21.73% and 20.96%, respectively) mediated by monocytes and the eGFR for CV mortality.

CONCLUSION: By using prospective survey data and background clinical knowledge, CGM retrieved direct and indirect causes of CV prognosis and identified pathways and the associated mediated effects. These insights will be useful in designing clinical protocols and targeting improvements in hypertensive patient management.

PMID:40537785 | DOI:10.1186/s12967-025-06755-1

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Diagnostic performance of anthropometric measurements for identifying obesity in high-altitude pediatric populations: evidence from tibet via bioelectrical impedance analysis

Lipids Health Dis. 2025 Jun 19;24(1):216. doi: 10.1186/s12944-025-02623-5.

ABSTRACT

BACKGROUND: The diagnostic accuracy of anthropometric measurements for obesity screening in high-altitude pediatric populations remains understudied, particularly since existing measurements have been validated predominantly in lowland populations. This study evaluated the effectiveness of 19 anthropometric measurements for obesity screening among youth residing in the Tibetan Plateau region, aiming to identify the most reliable measurement approach for this distinct demographic.

METHODS: This study included 1,650 Tibetan and Han Chinese students aged 8-18 years from six schools in Lhasa’s Chengguan District (altitude 3,650 m). Anthropometric measurements comprised both basic anthropometric parameters and computed indices. The basic anthropometric parameters included height, weight, waist circumference, mid-upper arm circumference as well as skinfold thickness measured at three sites, such as abdominal skinfold thickness (AST). The computed indices consisted of Body Mass Index (BMI), the tri-ponderal mass index (TMI), the sum of skinfold thickness from two or three (SuST3) sites, the waist-to-height ratio, the mid-upper arm-to-height ratio, the conicity index (C-index), the relative fat mass, the body roundness index, two variants of a body shape index (ABSIOR and ABSICN), and two percentage body fat values derived from two skinfold thickness equations (such as Y-PBF). Bioelectrical impedance analysis-derived percentage of body fat (PBFBIA) was used as the reference method to construct Receiver Operating Characteristic (ROC) curves for the 19 anthropometric measurements, and the Area Under the Curve (AUC) was calculated to evaluate the performance of each measurement in obesity screening.

RESULTS: Statistical analysis revealed that TMI, SuST3, AST, and BMI consistently demonstrated robust correlations with PBFBIA across all demographic subgroups (p < 0.001, r > 0.7) and exhibited strong diagnostic capabilities (AUC > 0.800). Among all anthropometric measurements, the TMI, SuST3, AST, Y-PBF, and BMI had the highest subgroup mean rankings according to the AUC (top 5), and the ABSIOR, C-index, and ABSICN were the worst (bottom 3). DeLong’s test confirmed these measurements as optimal measures in the majority of population subgroups (> 10 out of 19 subgroups), with the TMI showing the most comprehensive applicability (valid for the total sample and 17 subgroups). Notably, the TMI also demonstrated the highest stability in cutoff values (SD = 0.49, range = 1.89) and superior diagnostic performance (accuracy = 0.84, precision = 0.70, recall = 0.83, F score = 0.75).

CONCLUSIONS: Our findings indicate that the TMI is the best anthropometric indices for screening for obesity in children and adolescents on the Tibetan Plateau, with a wide range of applicability to population subgroups and a stable optimal cutoff value.

PMID:40537784 | DOI:10.1186/s12944-025-02623-5

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Medical students’ attitudes toward providing patients with audio recordings of their medical encounters: a cross-sectional online survey

BMC Med Educ. 2025 Jun 19;25(1):853. doi: 10.1186/s12909-025-07460-9.

ABSTRACT

BACKGROUND: Medical encounters often involve complex information that can be challenging to process, especially in emotionally charged situations. Providing patients with audio recordings of their medical encounters, termed consultation recordings, has shown promising benefits such as improved information recall and understanding. In prior research, patients largely reported favorable attitudes toward consultation recordings; physicians were more skeptical, particularly regarding legal risks. To date, consultation recordings are rare in Germany. This study aimed at understanding medical students’ attitudes toward consultation recordings, as they are the healthcare professionals of the future and could therewith play a crucial role in further implementation efforts.

METHODS: We conducted a nationwide cross-sectional quantitative online survey with medical students in Germany, assessing attitudes toward and desire for future consultation recordings. Data was analyzed using descriptive statistics.

RESULTS: Two hundred twenty-two participants were included. 56% of participants expressed positive attitudes toward consultation recordings, acknowledging benefits such as information recall and preparation for follow-up consultations. However, they also expressed significant concerns about potential misuse, legal implications, and physicians feeling pressured. About 16% of participants expressed a clear willingness to offer consultation recordings in the future, while 44% were hesitant.

CONCLUSIONS: Our findings that medical students recognize potential benefits of consultation recordings, while simultaneously expressing concerns about this intervention, are comparable to results from studies conducted in physician samples. Medical students’ limited clinical experience and the low prevalence of consultation recordings in Germany likely contribute to these apprehensions. These mixed attitudes could be addressed by providing opportunities for positive experiences with consultation recordings during medical and postgraduate education as well as in clinical practice. Providing role models who support patient-centered care could also foster greater acceptance. Future research should focus on the integration of patient-centered interventions such as consultation recordings in the medical curricula. Overall, consultation recordings have the potential to become a valuable tool in routine healthcare if current barriers are effectively addressed.

PMID:40537780 | DOI:10.1186/s12909-025-07460-9

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Reinforced locking screws with enhanced head and neck junction: improving biomechanical stability in opening-wedge high tibial osteotomy applications

J Orthop Surg Res. 2025 Jun 19;20(1):603. doi: 10.1186/s13018-025-06015-4.

ABSTRACT

BACKGROUND: Locking plates and screws are essential in orthopedic surgeries, including opening-wedge high tibial osteotomy (OWHTO), owing to their ability to provide angular stability and support under mechanical stress. However, screw breakage at the head and neck junction remains a significant issue, compromising fixation and requiring revision surgery. This study aimed to determine whether increasing the diameter of the locking screws at the head and neck junctions enhances biomechanical stability.

METHODS: Sixty screws, divided into two groups (n = 30 per group) -a non-reinforced group with a standard design and a reinforced group with an increased head and neck diameter- were tested. Both groups consisted of 5.0 mm locking screws, each with a length of 80 mm. Biomechanical testing, which included compression, fatigue, and torsional strength tests, was conducted to reflect clinically relevant conditions.

RESULTS: The reinforced screws demonstrated significantly superior biomechanical performance. In the compression test, they exhibited a higher load to failure (909.0 ± 30.4 N vs. 757.5 ± 46.2 N, p < 0.001). In the fatigue test, the reinforced screws endured more cycles before failure (70788.6 ± 6310.6 cycles vs. 23016.2 ± 5,157.9 cycles, p < 0.001) and had a greater displacement distance (3.0 ± 0.4 mm vs. 2.3 ± 0.3 mm, p = 0.001). The torsional test showed higher torque at failure for the reinforced screws (17.3 ± 0.3 Nm vs. 16.5 ± 0.4 Nm, p < 0.001), although the angular displacement differences were not statistically significant (202.0° ± 63.9° vs. 247.2° ± 64.9°, p = 0.105).

CONCLUSIONS: Reinforcing the head and neck junction of locking screws significantly improves their biomechanical performance. These findings suggest that structural modifications can reduce hardware failure risks in high-stress procedures such as OWHTO, enhancing implant durability and clinical outcomes.

PMID:40537777 | DOI:10.1186/s13018-025-06015-4

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Developmental milestones and cognitive trajectories in school-aged children with 16p11.2 deletion

J Neurodev Disord. 2025 Jun 19;17(1):33. doi: 10.1186/s11689-025-09615-7.

ABSTRACT

BACKGROUND: 16p11.2 deletion syndrome (16p11.2DS) is a recurrent CNV that occurs de novo in approximately 70% of cases and confers risk for neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorders (ASD). The current study focusses on developmental milestones, cognitive profiles and longitudinal cognitive trajectories.

METHODS: In-person assessments, digital medical records and parental interviews on developmental history of 24 children (5-16 years) with a confirmed BP4-BP5 16p11.2DS were reviewed and analysed for developmental milestones (motor, language, continence). Standardised intelligence tests were administered in all children, and longitudinal IQ-data were available for a subgroup (79%, 19/24).

RESULTS: Motor, language, and continence milestones were delayed. Average IQ was in the borderline range (IQ 71) with 46% (11/24) having borderline IQ (IQ 70-84). Both intra- and interindividual variability were found across the five cognitive domains with significant discrepancies between verbal and non-verbal skills in 55% (11/20). Longitudinal IQ-data indicate that school-aged children with 16p11.2DS perform statistically significantly lower at the second time point (p < 0.001) with 58% showing a growing into deficit trajectory.

CONCLUSION: Delayed motor, language and continence milestones are common in 16p11.2DS carriers. School-aged children with 16p11.2DS show increasing cognitive impairments over time, pointing to the need for early diagnosis, regular cognitive follow-up and individualised intervention. The high prevalence of disharmonic IQ-profiles highlights the importance of expanding the focus beyond full-scale IQ (FSIQ) outcomes. Future studies in larger cohorts including carrier relatives are needed to gain more insight into the penetrance and phenotypic variability of 16p11.2DS.

PMID:40537766 | DOI:10.1186/s11689-025-09615-7

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Sex-stratified patterns in geriatric patients with mild traumatic brain injury and intracranial bleeding: a retrospective cohort study

Int J Emerg Med. 2025 Jun 19;18(1):107. doi: 10.1186/s12245-025-00915-2.

ABSTRACT

BACKGROUND: Mild traumatic brain injury (mTBI) is a common diagnosis among elderly patients treated in emergency departments. It is often complicated by age-related physiological changes such as brain atrophy, cognitive impairment, and frailty. While sex differences are increasingly recognized in TBI pathophysiology and clinical management, limited research has explored their impact on geriatric mTBI complicated by intracranial bleeding. This study aimed to investigate sex-stratified patterns in injury mechanisms, clinical presentation, and associated injuries among older adults with mTBI.

METHODS: We conducted a retrospective, single-center cohort study of geriatric patients (≥ 65 years) hospitalized at the Louis Pasteur University Hospital in Košice, Slovakia with mTBI complicated by intracranial bleeding over a 30-month period (July 2022- December 2024). Patient data were extracted from electronic health records, including demographic characteristics, injury mechanisms, symptomatology, radiological findings, and clinical outcomes. Statistical analysis was performed using descriptive and comparative methods.

RESULTS: A total of 117 patients (55 females, 62 males) met the inclusion criteria. The median age was 77.0 years (IQR: 12.0), with females presenting at a higher median age than males (80 vs. 75.5 years). Causes of injury differed significantly between sexes (p < 0.001); while mechanical falls were predominant in both groups, alcohol-related injuries were significantly more common in males (37.1% vs. 7.3%). Symptom presentation also varied, with females exhibiting a higher prevalence of multiple symptoms, while males more frequently reported amnesia or loss of consciousness (p = 0.029). Additional injuries showed sex-related differences, with skull fractures more prevalent in males (41.9% vs. 21.8%) and pelvic (0 vs. 7.3%) or upper limb fractures (0 vs. 12.7%) more common in females (p = 0.005).

CONCLUSION: Sex-based differences in the presentation and symptomatology of geriatric patients with mTBI and intracranial bleeding highlight the need for tailored diagnostic and management approaches. Recognizing these differences could improve clinical assessment and individualized care. Further research is needed to refine sex-specific diagnostic and therapeutic strategies in this vulnerable population.

PMID:40537750 | DOI:10.1186/s12245-025-00915-2

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How many children have parents with gambling disorder – a Germany-based estimate

BMC Public Health. 2025 Jun 19;25(1):2166. doi: 10.1186/s12889-025-23520-7.

ABSTRACT

BACKGROUND: Parental gambling disorder has detrimental financial, psychological, physiological, familial, and behavioral implications for the offspring, making these children highly vulnerable. In Germany, population-based estimates on how many minor children have parents with gambling disorder are lacking; thus, the immediacy of need for corresponding (public) health care policies remains unknown.

METHODS: Based on the population-representative German Gambling Survey 2023, we estimated the number of children having parents with gambling disorder, including estimates for rates at each parental gambling disorder severity level (mild, moderate, severe). Both cohabiting children and separate living children were considered. To extrapolate lower and upper bounds of estimates, data on number of parents in the household and average number of children was combined with official population statistics.

RESULTS: Of 282 participants with gambling disorder, 46.8% (n = 132) cohabit with 1.55 children on average; 16.7% (n = 47) are parents of 1.51 separate living children on average. Therefore, in Germany 574,079 to 604,966 children have a parent with gambling disorder, with about 84.0% of them (482,076 to 508,712) cohabiting with the gambling parent. The likelihood of cohabiting decreases with increasing gambling disorder severity (mild: 97.7%; moderate: 85.0%; severe: 72.2%).

DISCUSSION: In Germany about 1 in 25 children has a parent with gambling disorder. Given that parental gambling disorder is an established risk factor for developing own gambling problems, more comprehensive addiction care and health policy are needed to address this issue. Integrated care and counselling offers targeting both gambling parents and their children may be a promising starting point. Special attention should be paid to separate living children in these approaches.

PMID:40537747 | DOI:10.1186/s12889-025-23520-7

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Prospective randomized, placebo-controlled study: role of branched-chain amino acids infusion as adjunct therapy post-liver surgery for patients in the intensive care unit

BMC Gastroenterol. 2025 Jun 19;25(1):439. doi: 10.1186/s12876-025-03696-3.

ABSTRACT

BACKGROUND AND AIM: Several animal studies have shown that Branched-chain amino acids (BCAAs) may prevent acute liver injury, although its effects in humans are as yet undetermined. Thus the purpose of this study is to evaluate the impact of intravenous BCAAs infusion on liver profile post-liver surgery in the intensive care unit (ICU).

METHODS: A randomized study that was applied for post liver surgery patients who were randomly allocated to receive either intravenous BCAA immediately post-operative or placebo.

MEASUREMENTS: Follow-up liver profile, Child-Pugh, and SOFA scores during the first week post-surgery.

MAIN RESULTS: A significant decline of bilirubin and ALT on day three and five in the BCAA group compared to the control group respectively. There was a significant improvement of PT on day seven 12.5 in the BCAA group versus 12.9 in the control group, p-value 0.01. Total bilirubin levels decreased by 75% in the BCAA group, whereas in the control group saw an increase of 6.25% from the baseline which was statistically significant, p-value 0.0376. SOFA score was markedly improved in the BCAA group (p-value 0.013). In addition to a significantly shorter ICU stay in the BCAA group than in the control group (p-value 0.018).

CONCLUSION: There are beneficial effects of BCAAs infusion post-liver surgery; including improved metabolic profile (liver function tests), and shorter ICU stay.

TRIAL REGISTRATION: (Clinicaltrials.gov registration number:NCT03448848), 28/02/2018.

PMID:40537743 | DOI:10.1186/s12876-025-03696-3