Category: Statistics

Euro Surveill. 2024 Apr;29(15). doi: 10.2807/1560-7917.ES.2024.29.15.2400178.

ABSTRACT

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI: 91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

PMID:38606570 | DOI:10.2807/1560-7917.ES.2024.29.15.2400178

Br J Nutr. 2024 Apr 12:1-23. doi: 10.1017/S0007114524000709. Online ahead of print.

ABSTRACT

The ability to provide adequate nutrition is considered a key factor in evaluating the sustainability of foods and diets. Nutrient indices are used as functional units (FUs) in life cycle assessment of foods to include nutritional performance in the environmental assessment of a product. Several general and food group-specific nutrient indices exist but many lack validation, particularly when used as FU. In addition, the nutrient selection strategies and reference units for nutrient intake can vary considerably among studies. To validate intake-based product-group-specific nutrient indices previously developed for protein (NR-FI_prot) and carbohydrate (NR-FI_carb) foods and for fruits and vegetables (NR-FI_veg), we applied principal component analysis to investigate correlations between nutrients in foods and dishes representing a typical Finnish diet. The reference amounts for meal components were based on a plate model that reflected Finnish dietary recommendations. The portion sizes for the different food groups were anchored at 100 g, 135 g and 350 g for proteins, carbohydrates and fruits/vegetables, respectively. Statistical modelling largely validated the NR-FI indices, highlighting protein foods as sources of niacin, vitamin B12 and selenium, carbohydrate foods as sources of magnesium, iron and phosphorous, and fruits/vegetables as sources of potassium, vitamin K, vitamin C, fibre and thiamine. However, in contrast to the intake-based approach applied in NR-FI_prot, the dietary recommendation-based validation process suggested that fruits and vegetables should be favoured as sources of riboflavin and vitamin B6.

PMID:38606563 | DOI:10.1017/S0007114524000709

Eur J Heart Fail. 2024 Apr 12. doi: 10.1002/ejhf.3232. Online ahead of print.

ABSTRACT

AIMS: Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long-term safety and sustainable symptomatic improvement.

METHODS AND RESULTS: BeAT-HF was a prospective, multicentre, randomized, two-arm, parallel-group, open-label, non-implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT-proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre-specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6-min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all-cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow-up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57-1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system- and procedure-related major adverse neurological and cardiovascular event-free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02-1.58) and freedom from all-cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43-1.01) favoured the BAT group but did not reach statistical significance.

CONCLUSION: The BeAT-HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient’s functional status, 6MHWD and QOL.

PMID:38606555 | DOI:10.1002/ejhf.3232

ESC Heart Fail. 2024 Apr 12. doi: 10.1002/ehf2.14783. Online ahead of print.

ABSTRACT

AIMS: Chronic systolic heart failure (CHF) is a major health burden. A relevant number of patients shows asymptomatic left ventricular dysfunction (ALVSD) before symptomatic CHF or becomes asymptomatic after initiating heart failure therapy. Clinical course, prognosis, and response to pharmacological and device-based treatment are largely unknown in these two distinct groups of patients. Current pharmacological and interventional therapies do neither properly address the underlying pathophysiology nor prevent malignant loss of function. New therapeutic paradigms are needed to stop the progression from asymptomatic to symptomatic heart failure. Key questions are what causes progression of clinically asymptomatic New York Heart Association (NYHA) I heart failure to overt heart failure (>NYHA I) in some but not all patients and the underlying reasons for this transition. This requires the identification of disease mechanisms and biomarkers that predict outcome in well-defined cohorts for innovative preclinical and clinical trials.

METHODS AND RESULTS: TransitionCHF is a prospective, multicentre, longitudinal pathophysiological evaluation cohort study in patients with asymptomatic systolic dysfunction NYHA I and left ventricular ejection fraction ≤40%. The cohort comprises both incidental findings and patients who had become asymptomatic after a previous symptomatic event. TransitionCHF has recruited 1000 patients with ALVSD caused by various aetiologies in 20 university heart failure clinics across Germany. Both patients with and without comorbidities at study entry will be recruited. Patients will be systematically investigated and followed up annually over the course of the study. The primary composite endpoint is time to hospitalization for heart failure and cardiovascular death. The secondary endpoints assess time to all-cause mortality, to cardiovascular mortality, to heart failure mortality, to all-cause hospitalization, to heart failure hospitalization, and to recurrent heart failure hospitalizations, as well as time to assist device implantation/transplantation. Additional investigations focusing on biomarkers, comorbidities, gender aspects, nutrition, and functional parameters including quality of life will be performed.

CONCLUSIONS: TransitionCHF will provide a more thorough pathophysiological understanding of the progression of asymptomatic systolic dysfunction into symptomatic heart failure that will help develop therapies tailored to prevent progressive heart failure.

PMID:38606543 | DOI:10.1002/ehf2.14783

Eur J Heart Fail. 2024 Apr 12. doi: 10.1002/ejhf.3222. Online ahead of print.

ABSTRACT

AIMS: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients.

METHODS AND RESULTS: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.09), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group.

CONCLUSIONS: Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

PMID:38606524 | DOI:10.1002/ejhf.3222

Hosp Pediatr. 2024 Apr 12:e2023007714. doi: 10.1542/hpeds.2023-007714. Online ahead of print.

ABSTRACT

BACKGROUND: Health care workers in the United States are facing increasing rates of exposure to aggressive behavior, resulting in an increase in employee injuries related specifically to patient behavioral events. By leveraging interprofessional collaboration and system-level innovation, we aimed to reduce the rate of employee injuries related to patient behavioral events at a children’s hospital by 50% over a 3-year period.

METHODS: An interdisciplinary quality improvement team comprising physicians, behavior analysts, nursing, and other key stakeholders developed a comprehensive behavior program in our children’s hospital. The team developed 5 key pillars: aggression mitigation tools, clinical resources, advanced training, screening and management, and behavior emergency response. The outcome measure was rate of reported employee safety events related to patient behavioral events. This was tracked via prospective time series analysis statistical process control chart using established rules to detect special cause variation.

RESULTS: The average rate of employee injuries resulting from patient behavioral events decreased from 0.96 to 0.39 per 1000 adjusted patient-days, with special cause variation observed on a statistical process control U-chart. This improvement has been sustained for 16 months. Staff members who experienced injuries included nurses and patient technicians, with common antecedents to injuries including medical interventions or patient requests that could not be safely met.

CONCLUSIONS: A unified and multimodal system aimed to address pediatric patient behavioral events can reduce employee injuries and foster a culture of employee safety in the pediatric inpatient setting.

PMID:38606483 | DOI:10.1542/hpeds.2023-007714

Expert Opin Pharmacother. 2024 Apr 12. doi: 10.1080/14656566.2024.2342413. Online ahead of print.

ABSTRACT

INTRODUCTION: Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone for refractory epilepsy.

METHODS: A thorough search of electronic databases was conducted to identify relevant randomized controlled trials involving patients with drug-resistant focal epilepsy and CDKL5 deficiency disorder. Efficacy and safety outcomes were extracted from the selected studies. Cochrane Review Manager was utilized for data synthesis and analysis, with risk ratios and mean differences calculated to evaluate the efficacy and safety profile of Ganaxolone.

RESULTS: The meta-analysis included a total of five randomized controlled trials. Ganaxolone exhibited significant efficacy in reducing seizure frequency by at least 50% from baseline [RR 0.90 (95% CI: 0.83, 0.98), p = 0.02]. However, the results did not reach significance for reducing 28-day seizure frequency [Mean Difference -1.45 (95% CI: -3.39, 0.49), p = 0.14]. Ganaxolone exhibited a positive safety profile, with no statistically significant occurrence of adverse events [RR 1.30 (95% CI: 0.93, 1.83), p = 0.12] and adverse events leading to discontinuation of the study drug [RR 1.01 (95% CI: 0.42, 2.39), p = 0.99] compared to placebo.

CONCLUSION: Ganaxolone presents itself as a viable therapeutic option for refractory epilepsy, showing efficacy in reducing seizure frequency and exhibited a favorable safety profile.

PROSPERO REGISTRATION NUMBER: CRD42023434883.

PMID:38606458 | DOI:10.1080/14656566.2024.2342413

JOR Spine. 2024 Apr 10;7(2):e1331. doi: 10.1002/jsp2.1331. eCollection 2024 Jun.

ABSTRACT

OBJECTIVES: The objective of this study is to evaluate the value of S100-A8 protein as a diagnostic marker for spinal tuberculosis and to explore its role in the potential pathogenesis of spinal tuberculosis (STB).

METHODS: The peripheral blood of 100 spinal tuberculosis patients admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were collected as the observation group, and the peripheral blood of 30 healthy medical examiners were collected as the control group. Three samples from the observation group and three samples from the control group were selected for proteomics detection and screening of differential proteins. Kyoto Encyclopedia of Genes (KEGG) was used to enrich and analyze related signaling pathways to confirm the target protein. The serum expression levels of the target proteins were determined and compared between the two groups using enzyme-linked immunosorbent assay (ELISA). Statistical methods were used to evaluate the value of target protein as a diagnostic marker for STB. A macrophage model of Mycobacterium tuberculosis infection was constructed and S100-A8 small interfering RNA was used to investigate the molecular mechanism of the target protein.

RESULTS: S100-A8 protein has the value of diagnosing spinal tuberculosis (AUC = 0.931, p < 0.001), and the expression level in the peripheral blood of the observation group (59.04 ± 19.37 ng/mL) was significantly higher than that of the control group (43.16 ± 10.07 ng/mL) (p < 0.05). S100-A8 protein expression showed a significant positive correlation with both CRP and ESR values (p < 0.01). Its AUCs for combined bacteriological detection, T-SPOT results, diagnostic imaging, antacid staining results, and pathological results were 0.705 (p < 0.05), 0.754 (p < 0.01), 0.716 (p < 0.01), 0.656 (p < 0.05), and 0.681 (p < 0.01), respectively. Lack of S100-A8 leads to a significant decrease in the expression levels of TLR4 and IL-17A in infected macrophages.

CONCLUSION: S100-A8 protein is differentially expressed in the peripheral blood of patients with spinal tuberculosis and healthy individuals and may be a novel candidate biomarker for the diagnosis of spinal tuberculosis. The feedback loop on the S100-A8-TLR4-IL-17A axis may play an important role in the inflammatory mechanism of spinal tuberculosis.

PMID:38606423 | PMC:PMC11007257 | DOI:10.1002/jsp2.1331

IEEE Winter Conf Appl Comput Vis. 2024 Jan;2024:7867-7876. doi: 10.1109/wacv57701.2024.00770. Epub 2024 Apr 9.

ABSTRACT

Age is one of the major known risk factors for Alzheimer’s Disease (AD). Detecting AD early is crucial for effective treatment and preventing irreversible brain damage. Brain age, a measure derived from brain imaging reflecting structural changes due to aging, may have the potential to identify AD onset, assess disease risk, and plan targeted interventions. Deep learning-based regression techniques to predict brain age from magnetic resonance imaging (MRI) scans have shown great accuracy recently. However, these methods are subject to an inherent regression to the mean effect, which causes a systematic bias resulting in an overestimation of brain age in young subjects and underestimation in old subjects. This weakens the reliability of predicted brain age as a valid biomarker for downstream clinical applications. Here, we reformulate the brain age prediction task from regression to classification to address the issue of systematic bias. Recognizing the importance of preserving ordinal information from ages to understand aging trajectory and monitor aging longitudinally, we propose a novel ORdinal Distance Encoded Regularization (ORDER) loss that incorporates the order of age labels, enhancing the model’s ability to capture age-related patterns. Extensive experiments and ablation studies demonstrate that this framework reduces systematic bias, outperforms state-of-art methods by statistically significant margins, and can better capture subtle differences between clinical groups in an independent AD dataset. Our implementation is publicly available at https://github.com/jaygshah/Robust-Brain-Age-Prediction.

PMID:38606366 | PMC:PMC11008505 | DOI:10.1109/wacv57701.2024.00770

Front Genet. 2024 Mar 28;15:1364993. doi: 10.3389/fgene.2024.1364993. eCollection 2024.

ABSTRACT

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, caused by a complex interplay of genetic and environmental factors. This study aimed to evaluate the combined efficacy of multi-polygenic risk scores and pooled cohort equations (PCE) for predicting future CVD risks in the Korean population. In this longitudinal study, 7,612 individuals from the Ansan and Ansung cohorts were analyzed over a 17-year follow-up period. The participants were genotyped using the Korea Biobank Array, and quality-controlled genetic data were subjected to imputation analysis. The weighted sum of the PRSs (wPRSsum) was calculated using PRS-CS with summary statistics from myocardial infarction, ischemic stroke, coronary artery disease, and hypertension genome-wide association studies. The recalibrated PCE was used to assess clinical risk, and the participants were stratified into risk groups based on the wPRSsum and PCE. Associations between these risk scores and incident CVD were evaluated using Cox proportional hazards models and Kaplan-Meier analysis. The wPRSsum approach showed a significant association with incident CVD (HR = 1.15, p = 7.49 × 10^-5), and the top 20% high-risk genetic group had an HR of 1.50 (p = 5.04 × 10^-4). The recalibrated PCE effectively differentiated between the low and high 10-year CVD risk groups, with a marked difference in survival rates. The predictive models constructed using the wPRSsum and PCE demonstrated a slight improvement in prediction accuracy, particularly among males aged <55 years (C-index = 0.640). We demonstrated that while the integration of wPRSsum with PCE did not significantly outperform the PCE-only model (C-index: 0.703 for combined and 0.704 for PCE-only), it provided enhanced stratification of CVD risk. The highest risk group, identified through the combination of high wPRSsum and PCE scores, exhibited an HR of 4.99 for incident CVD (p = 1.45 × 10^-15). These findings highlight the potential of integrating genetic risk assessments with traditional clinical tools for effective CVD risk stratification. Although the addition of wPRSsum to the PCE provided a marginal predictive improvement, it proved valuable in identifying high-risk individuals and supporting personalized treatment strategies. This study reinforces the utility of multi-PRS in conjunction with clinical risk assessment tools, paving the way for more tailored approaches for CVD prevention and management in diverse populations.

PMID:38606355 | PMC:PMC11007088 | DOI:10.3389/fgene.2024.1364993