Search

We introduce the parity-odd power (POP) spectra, a novel set of observables for probing parity violation in cosmological N -point statistics. POP spectra are derived from composite fields obtained by applying non-linear transformations, involving also gradients, curls, and filtering functions, to a scalar field. This compresses the parity-odd trispectrum into a power spectrum. These new statistics offer several advantages: they are computationally fast to construct, estimating their covariance is less demanding compared to estimating that of the full parity-odd trispectrum, and they are simple to model theoretically. We measure the POP spectra on simulations of a scalar field with a specific parity-odd trispectrum shape. We compare these measurements to semi-analytic theoretical calculations and find agreement. We also explore extensions and generalizations of these parity-odd observables. [ABSTRACT FROM AUTHOR]

Background Given that obesity and insulin resistance play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the connection between leptin and these metabolic diseases, the association between NAFLD and a leptin receptor gene (LEPR) polymorphism was examined. Methods In this genetic case-control association study, 144 biopsy-proven NAFLD patients and 144 controls were genotyped for the LEPR gene Gln223Arg (rs1137101) polymorphism using the polymerase chain reaction–restriction fragment length polymorphism method. Results The distributions of genotypes and alleles of Gln223Arg variant were in accordance with the Hardy-Weinberg equilibrium in the study groups (P >.05). Multivariate logistic regression analysis showed that the LEPR Gln223Arg Arg/Arg genotype was an independent risk factor for NAFLD; the Arg/Arg genotype, compared with the Gln/Gln genotype, was associated with a 2.09-fold increased risk for NAFLD (P =.036, odds ratio = 2.09 [95% CI = 1.31-5.95]). Conclusions We found that the LEPR Gln223Arg Arg/Arg genotype was independently associated with a more than 2-fold rise in biopsy-proven NAFLD risk. Our findings, however, need to be corroborated by further studies. [ABSTRACT FROM AUTHOR]

Objective This study was designed to compare thiol/disulfide and ischemia-modified albumin (IMA) levels between psoriatic arthritis (PsA) and healthy controls and evaluate the correlation between these molecules and the disease activity scores used in PsA. Methods A total of 63 PsA patients and 49 healthy volunteers were included in the study. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), modified disease activity score 28 (DAS28), and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were used as disease activity indices for PsA patients. Calculations of native thiol (-SH), disulfide (-SS), and total thiol (-SH+-SS) molecules were made by the automatic spectrophotometric method, and the albumin cobalt binding test was used to measure IMA levels. Results In the PsA group, -SS/-SH and -SS/(-SH+-SS) levels were higher and -SH/(-SH+-SS) levels were lower than in controls. In the linear regression analysis, a significant correlation relationship was detected between DAS28-erythrocyte sedimentation rate (ESR) and -SS/(-SH+-SS) (β = 0.795, CI 95%, 0.196-1.395; P =.010), -SH/(-SH+-SS) (β = -0.475, CI 95%, 0.114-0.836; P =.010) and IMA (β = 3.932, CI 95%, 0.859-7.005; P =.013). Additionally, a significant correlation was detected between IMA and BASDAI and BASFI. Conclusion In PsA, thiol/disulfide homeostasis has shifted in favor of disulfide as an oxidative indicator. Serum thiol/disulfide levels are correlated with PsA disease activity indices. [ABSTRACT FROM AUTHOR]

Background Pancreatic cancer (PC) is usually detected in the advanced stages. Liquid biopsy has become a revolutionary strategy for cancer diagnosis and prognosis prediction. This study aims to investigate the diagnostic and prognostic value of circulating exosomal glypican-1 (GPC-1) in PC. Methods We systematically searched relevant studies. For diagnostic accuracy, pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated. Regarding prognostic value, hazard ratios (HRs) and 95% CIs for overall survival (OS) were summarized by using a random-effects model. Results We found 8 studies that examined the diagnostic value of circulating exosomal GPC-1 in PC, and 3 studies that investigated its prognostic value. Pooled sensitivity and specificity were 0.88 (95% CI, 0.65-0.97) and 0.86 (95% CI, 0.72-0.94). The AUC was 0.93 (95% CI, 0.90-0.95). Prognostic analysis showed that higher levels of circulating exosomal GPC-1 were associated with poorer OS in PC patients, and the combined HR for OS was 4.59 (random-effects model, 95% CI = 1.17-18.03, P =.022). The results of both studies were robust and neither had publication bias. Conclusion Circulating exosomal GPC-1 may be used as a diagnostic and prognostic biomarker for PC. However, this result needs to be validated by further research using a larger sample size. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness. Study Design In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined. Study Results Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P  < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P  < .05, false discovery rate correction). Conclusions Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients. [ABSTRACT FROM AUTHOR]

Background Malnutrition is a public health problem that affects physical and psychosocial well-being. It manifests as a rapid deterioration in nutritional status and bilateral edema due to inadequate food intake or illness. Methods This study is a retrospective cohort of 1208 children with severe acute malnutrition (SAM) in Sofala Province from 2018 to 2022. It includes hospitalized children aged 6–59 months with SAM and related complications. The dependent variable is recovery, and the independent variables include age, sex of the child, vomiting, dehydration, hypoglycemia, nutritional edema and anthropometry. Survival curves were plotted using the Kaplan–Meier method, and bivariable and multivariable Cox regression analyses were performed. Results The crude analysis revealed significant factors for nutritional recovery in children with SAM, including age, weight, height, malaria, diarrhea and dehydration. Children under 24 months had a 28% lower likelihood of recovery. Weight below 6.16 kg decreased the likelihood by 2%, and height above 71.1 cm decreased it by 20%. Conversely, malaria, diarrhea and dehydration increased the likelihood of recovery. However, after adjustment, only diarrhea remained a significant predictor of nutritional recovery. Conclusion This study found that diarrhea is a predictor of nutritional recovery in children with SAM. [ABSTRACT FROM AUTHOR]

This paper presents analytical results on the anatomy of nested sampling, from which a technique is developed to estimate the run-time of the algorithm that works for any nested sampling implementation. We test these methods on both toy models and true cosmological nested sampling runs. The method gives an order-of-magnitude prediction of the endpoint at all times, forecasting the true endpoint within standard error around the halfway point. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with coronavirus disease 2019 (COVID-19) who received remdesivir plus standard of care (SoC) compared with SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. Methods This post hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19. Any first AE that occurred between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves, and Kaplan-Meier estimates were calculated for event rates. Results Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (hazard ratio [HR], 1.0; 95% confidence interval [CI],.7–1.5; P =.98), even when serious and nonserious cardiac AEs were evaluated separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between the two groups in the occurrence of cardiac AE subclasses, including arrhythmic events (HR, 1.1; 95% CI,.7–1.7; P =.68). Conclusions Remdesivir treatment was not associated with an increased risk of cardiac AEs compared with control in patients hospitalized with moderate or severe COVID-19. These results are consistent with other randomized, controlled trials and meta-analyses. Clinical Trials Registration. NCT 04315948; EudraCT 2020-000936-23. [ABSTRACT FROM AUTHOR]

Aims To compare patient-reported outcomes (PROs) in patients newly (<6 months) diagnosed with atrial fibrillation (AF) with those who have had a longer diagnosis (≥6 months) and to investigate whether or not these outcomes change over a 6-month period. Methods and results In this longitudinal survey study, 129 patients with AF completed the Revised Illness Perception Questionnaire, the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia, and the Hospital Anxiety and Depression Scale at baseline and after 6 months. At baseline, patients newly diagnosed with AF (n = 53), compared with patients with a previous diagnosis (n = 76), reported AF as more temporary (P = 0.003) and had a higher belief in personal and treatment control (P = 0.004 and P = 0.041, respectively). At a 6-month follow-up, patients newly diagnosed reported a lower symptom burden (P = 0.004), better health-related quality of life (HRQoL); (P = 0.015), and a higher personal control (P < 0.001) than patients previously diagnosed. Over time, in patients newly diagnosed, symptom burden and the anxiety symptom score decreased (P = 0.001 and P = 0.014, respectively) and HRQoL improved (P = 0.002). Conclusion Patients newly diagnosed with AF reported more positive PROs both at baseline and at a 6-month follow-up than patients with a previous diagnosis of AF. Therefore, it is important to quickly capture patients newly diagnosed to support their belief in their own abilities. Such support may, alongside medical treatments, help patients manage the disease, which may lead to reduced symptom burden and better HRQoL over time. [ABSTRACT FROM AUTHOR]

Objective Total knee replacement (TKR) is a common solution for patients with advanced knee osteoarthritis (OA). Still, fall rates remain relatively high after surgery. TKR may alter pain and knee function, balance control, and proprioception. However, given the role of complex (dual-task) walking in fall prediction for older adults, it is unknown how TKR alters the attentional demand of walking in older adults. The goal of this study was to examine the effect of TKR on dual-task walking among older adults. Methods Participants were evaluated 1 month before surgery and 4.5 months after surgery. Participants walked along an instrumented 7-meter path for 1 minute with and without a cognitive task (serial-3 subtraction). Pain and knee function, knee proprioception, dynamic balance, and balance confidence, as well as dual-task costs (DTC) were compared before and after the surgery and factors associated with change in gait DTCs were assessed. Results Thirty-eight participants completed the study (age 72.6 years, SD = 4.9; 11 men). A significant decrease in pain was found following TKR, with no change in balance, balance confidence, or proprioception. There were no differences in gait DTCs before and after the surgery. However, change in dynamic balance, specifically reactive postural control and dynamic gait, predicted changes in gait speed and stride time DTCs. Conclusion The absence of an effect of TKR on gait DTCs can potentially underlie increased fall risk after TKR. Results from this study emphasize the significance of balance as a measure and focal point for rehabilitation after TKR. Impact This study contributes to our understanding of the attentional cost of walking in people before and after TKR, as well as to factors associated with it. Results from this work can assist formulation of rehabilitation programs for people with knee OA. [ABSTRACT FROM AUTHOR]

The European Health Literacy Survey Questionnaire (HLS-EU-Q47) is available in multiple languages, and shortened versions have also been developed. This study aimed to examine the reliability and validity of the short version of the questionnaire (HLS-Q12) developed for community-dwelling older adults in Japan. The HLS-Q12 was developed using 12 of the 47 items of the Japanese version of the HLS-EU-Q47. In this study, the survey was conducted by distributing self-administered questionnaires to community-dwelling individuals aged 65 years and older who consented to participate; their responses were collected by mail. The correlation between the HLS-Q12 and the HLS-EU-Q47 was tested to assess criterion validity. To test construct validity, nine novel hypotheses were proposed. We also conducted a confirmatory factor analysis of the HLS-Q12. Based on a resurvey after 5–7 days, test–retest reliability was examined using interclass correlation coefficients (ICCs) and Bland–Altman analysis. In total, 118 individuals provided valid responses to the questionnaire. The Spearman rank correlation coefficient between the HLS-Q12 and the HLS-EU-Q47 was r  = 0.98 (p  < 0.001), and eight of the nine hypotheses were supported. The ICC was 0.96 (p  < 0.001), and the 95% limit of agreement was −0.26 ± 5.9, suggesting no systematic error. Thus, the Japanese version of the HLS-Q12 was found to be reliable with high criterion validity and reproducibility. Hence, the HLS-Q12 is a useful scale for measuring health literacy among older adults in Japan. [ABSTRACT FROM AUTHOR]

Considering that a sizable segment of the population spends significant amount of time at work, workplaces have been identified as practical platforms for health educational programs. Although employee wellness programs in high-income countries have shown measurable benefits in productivity and physical and mental health, evidence-based programs in low- and middle-income countries, such as Lebanon, are unavailable. The aim is to develop and implement a pilot workplace wellness program focusing on health-related areas to improve health knowledge and behavior among working men and women of reproductive age. In collaboration with March of Dimes, the National Collaborative Perinatal Neonatal Network developed a culturally sensitive health education program focusing on lifestyle, infection, nutrition and family planning. Sessions were delivered by a multidisciplinary team of specialists at a local bank in Lebanon. To assess the impact of the program, participants completed Knowledge and Behavior Assessment Questionnaire (KBAQ) before and after implementation. KBAQ was conducted 6 months after implementation to measure retention and continuing impact. Forty-seven participants completed the program, of whom 44.7% are male, 98% have university degree and 56.5% are married. Total knowledge score improved significantly from 64.2 to 74.3 and remained significant at 6 months post-implementation with a score of 71.7 (p  < 0.001). At 6-month follow-up, emotional score improved (p  = 0.028), while smoking decreased (p  = 0.008). Also, employees' health knowledge and behavior showed sustained and significant improvement. We plan to implement our program at other sites and among employees from different backgrounds to understand the impact of the wellness program on employees' knowledge and behaviors at a larger scale. [ABSTRACT FROM AUTHOR]

The number of genome assemblies has rapidly increased in recent history, with NCBI databases reaching over 41,000 eukaryotic genome assemblies across about 2,300 species. Increases in read length and improvements in assembly algorithms have led to increased contiguity and larger genome assemblies. While this number of assemblies is impressive, only about a third of these assemblies have corresponding genome size estimations for their respective species on publicly available databases. In this paper, genome assemblies are assessed regarding their total size compared to their respective publicly available genome size estimations. These deviations in size are assessed related to genome size, kingdom, sequencing platform, and standard assembly metrics, such as N50 and BUSCO values. A large proportion of assemblies deviate from their estimated genome size by more than 10%, with increasing deviations in size with increased genome size, suggesting nonprotein coding and structural DNA may be to blame. Modest differences in performance of sequencing platforms are noted as well. While standard metrics of genome assessment are more likely to indicate an assembly approaching the estimated genome size, much of the variation in this deviation in size is not explained with these raw metrics. A new, proportional N50 metric is proposed, in which N50 values are made relative to the average chromosome size of each species. This new metric has a stronger relationship with complete genome assemblies and, due to its proportional nature, allows for a more direct comparison across assemblies for genomes with variation in sizes and architectures. [ABSTRACT FROM AUTHOR]

The main objective of mapping quantitative trait loci (QTL) and genome-wide association studies (GWAS) is to identify and locate QTLs on the genome. Estimating the sizes of QTL is equally important as identifying the QTLs. The size of a QTL is often measured by the QTL variance, or the proportion of phenotypic variance explained by the QTL, known as the QTL heritability. The reported QTL heritability is biased upward for small-sized QTLs estimated from small samples, especially in GWAS with a very small P -value threshold accommodating to Bonferroni correction for multiple tests. The phenomenon is called the Beavis effect. Methods of correcting the Beavis effect have been developed for additive effect models. Corresponding methods are not available for QTLs with more than one effect, such as QTLs including dominance and other genetic effects. In this study, we developed explicit formulas for estimating the variances and heritability for QTL with multiple effects. We also developed a method to remove nuisance parameters via an annihilator matrix. Finally, biases in estimated QTL variances caused by the Beavis effect are investigated and corrected. The new method is demonstrated by analyzing the 1000 grain weight (KGW) trait in a hybrid rice population. [ABSTRACT FROM AUTHOR]

How do we construct our causal directed acyclic graphs (DAGs)—for example, for life-course modeling and analysis? In this commentary, I review how the data-driven construction of causal DAGs (causal discovery) has evolved, what promises it holds, and what limitations or caveats must be considered. I find that expert- or theory-driven model-building might benefit from some more checking against the data and that causal discovery could bring new ideas to old theories. [ABSTRACT FROM AUTHOR]

Introduction Recurrent falls are observed frequently among older people, and they are responsible for significant morbidity and mortality. The aim of the present study was to verify sensitivity, specificity and accuracy of World Guidelines for Falls Prevention and Management (WGFPM) falls risk stratification algorithm using data from the Osteoarthritis Initiative (OAI). Methods Participants aged between 40 and 80 years were stratified as 'low risk', 'intermediate risk' or 'high risk' as per WGFPM stratification. Data from the OAI cohort study were used, a multi-centre, longitudinal, observational study focusing primarily on knee osteoarthritis. The assessment of the outcome was carried out at baseline and during the follow-up visit at 24 months. Data about sensitivity, specificity and accuracy were reported. Results Totally, 4796 participants were initially included. Participants were aged a mean of 61.4 years (SD = 9.1) and were predominantly women (58.0%). The population was divided into three groups: low risk (n  = 3266; 82%), intermediate risk (n  = 25; 0.6%) and high risk (n  = 690; 17.3%). WGFPM algorithm applied to OAI, excluding the intermediate-risk group, produced a sensitivity score of 33.7% and specificity of 89.9% for predicting one or more falls, with an accuracy of 72.4%. Conclusion In our study, WGFPM risk assessment algorithm successfully distinguished older people at greater risk of falling using the opportunistic case finding method with a good specificity, but limited sensitivity, of WGFPM falls risk stratification algorithm. [ABSTRACT FROM AUTHOR]

Mobile mammography units (MMUs) can enhance access to breast cancer screening by providing convenient, cost-effective service, particularly for uninsured and underinsured women. However, prior studies indicate that acceptability concerns about quality and privacy, among other issues, may prevent women from utilizing MMUs. The current study employs a within-participant experimental design exposing participants to messages about different MMU characteristics to determine which characteristics are most effective in persuading them to use an MMU. The study also examined how messaging interacts with participants' ethnic identity to influence outcomes. Data were collected from a diverse sample of uninsured and underinsured women as part of a formative study to promote the utilization of a mobile mammography facility in Central Texas. Results of mixed-effect linear models show that messages about equity, appointment convenience, privacy and comfort, and quality of equipment and staff were rated as more persuasive than messages about convenience of location and language accessibility. However, Hispanic women rated language accessibility higher than other participants did. The results can guide MMU organizers and promotion managers as they determine the best approach to promote mobile mammography services in different communities. [ABSTRACT FROM AUTHOR]

Aims Mitral regurgitation (MR) causes left atrial (LA) enlargement and impaired reservoir function. We assessed whether changes in LA size, strain, and stiffness in significant (moderate or greater) primary MR are sex-specific. Methods and results In the 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation study, 111 patients with primary MR were prospectively investigated with 2D and 3D echocardiography. MR was severe if the 3D regurgitant fraction was ≥50%. LA size was assessed by maximum, minimum, and pre-A 3D volume (LAV), mechanics by peak reservoir (LASr) and contractile strain, and stiffness by the ratio: mitral peak E-wave divided by the annular e′ velocity (E/e′)/LASr. Women were older, had higher heart rate, and lower body mass index and MR regurgitant volumes (P < 0.05). 3D LAV indexed for body surface area and LA contractile strain did not differ by sex, while LASr was lower (22.2 vs. 25.0%) and LA stiffness higher in women (0.56 vs. 0.44) (P < 0.05). In linear regression analysis, female sex was associated with higher LA stiffness independent of age, minimum LAV, left ventricular global longitudinal strain, diabetes, and coronary artery disease (R 2 = 0.56, all P < 0.05). In logistic regression analysis, women had a four-fold (95% CI 1.2–13.1, P = 0.02) higher adjusted risk of increased LA stiffness than men. Conclusion Women with significant primary MR have more impaired LA reservoir mechanics and increased LA stiffness compared with men despite lower MR regurgitant volumes and similar indexed LA size. The findings reveal sex-specific features of LA remodeling in MR. Trial Registration ClinicalTrials.gov Identifier: NCT04442828 [ABSTRACT FROM AUTHOR]

Aims To date, no studies have investigated the association between lipid species and coronary plaque changes over time, quantitatively assessed by serial imaging. We aimed to prospectively determine the association between lipid species quantified by a plasma lipidomic analysis and coronary plaque changes according to composition assessed by a quantitative serial analysis of coronary computed tomography angiography (CTA). Methods and results Patients with suspected coronary artery disease (CAD) undergoing baseline coronary CTA were prospectively enrolled by seven EU centres in the SMARTool study and submitted to clinical, molecular, and coronary CTA re-evaluation at follow-up (an inter-scan period of 6.39 ± 1.17 years). Out of 202 patients who were analysed in the SMARTool main clinical study, a lipidomic analysis was performed in 154 patients before the baseline coronary CTA, and this group was included in the present study. A quantitative CTA analysis was performed by using a separate core laboratory blinded from clinical data. In the univariable analysis, it was found that no lipid species were significantly associated with annual total and calcified plaque changes. After adjusting for clinical variables at baseline and statin use, it was found that three lipid species were significantly associated with non-calcified plaque progression. In detail, cholesteryl ester(20:3), sphingomyelin (SM)(40:3), and SM(41:1) were found to be positively related to non-calcified plaque progression (Bonferroni-adjusted P -values = 0.005, 0.016, and 0.004, respectively). Conclusion The current study showed an independent relationship between specific lipid species determined by a plasma lipidomic analysis and non-calcified coronary plaque progression assessed by a serial, quantitative coronary CTA analysis. [ABSTRACT FROM AUTHOR]

Background Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection. Methods Time to deterioration in QoL was analyzed for the primary study population. Subsequently, a post hoc analysis was undertaken to identify subgroups for which time to deterioration in QoL was improved with TARE/Chemo vs Chemo. Progression-free survival (PFS), hepatic (h)PFS, time to subsequent therapy, and safety outcomes were compared between treatments. Results The primary population showed no significant difference in time to deterioration in QoL between treatment arms; however, significance was seen in 2 identified subgroups, namely: Subgroup A (N  = 303) which excluded patients with both Eastern Cooperative Oncology Group (ECOG) 1 and baseline CEA ≥ 35 ng/mL from both treatment arms; subgroup B (N  = 168) additionally excluded patients with KRAS (Kirsten rat sarcoma) mutation. In subgroup A, TARE/Chemo patients (N  = 143) demonstrated superior outcomes vs Chemo (N  = 160): PFS (9.4 vs. 7.6 months, hazard ratio (HR): 0.64; 1-sided P  = .0020), hPFS (10.8 vs. 7.6 months, HR: 0.53; 1-sided P  < .0001), time to deterioration in QoL (5.7 vs. 3.9 months, HR: 0.65; 1-sided P  = .0063), and time to subsequent therapy (21.2 vs. 10.5 months, HR: 0.52; 1-sided P  < .0001). Subgroup B patients showed similar but larger significant differences between treatment arms. Median PFS, hPFS, and time to deterioration in QoL were numerically greater for TARE/Chemo in both subgroups vs the primary population, with the greatest magnitude of difference in subgroup B. Both subgroups exhibited higher percentage of CEA responders and improved ORR with TARE/Chemo vs chemo alone. Safety (reported as event rate/100 patient-years) was higher with Chemo in all populations. Additional efficacy analyses in the primary population are also reported. Conclusions Careful patient selection, including consideration of the prognostic factors ECOG, baseline CEA, and KRAS status, sets outcome expectations in patients with colorectal liver metastases suitable for TARE/Chemo as second-line treatment (Trial Registry Number: NCT01483027). [ABSTRACT FROM AUTHOR]

Background This prospective observational study evaluated the real-world effectiveness of nivolumab monotherapy in previously treated advanced gastric cancer (GC). A preplanned 2-year final analysis was performed to confirm survival and tumor behavior with nivolumab monotherapy. Patients and Methods The primary endpoint was overall survival (OS). The data regarding tumor size were prospectively collected and evaluated using the RECIST criteria. Exploratory analyses were performed for survival according to the tumor response and depth of response (DpR) in patients with measurable lesions who were receiving nivolumab monotherapy as third- or later-line therapy. Results In 487 patients, the median OS and progression-free survival (PFS) were 5.8 (95% CI 5.3-6.9) months and 1.8 (95% CI 1.7-2.0) months, respectively. The response rate (RR) was 14.5% in 282 patients with measurable lesions. In 234 patients treated with third- or later-line, the DpR was found to be associated with PFS and OS in the Spearman analysis (r  = 0.55 and 0.44, respectively) as well as using a discrete variable. When the DpR was divided into 5 groups (−20%≥DpR; −20%

Objectives Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) dermatomyositis patients exhibit a variety of clinical features. We therefore investigated whether patterns of B-cell epitope recognition are linked to the clinical course of MDA5+ dermatomyositis. Methods Our cross-sectional study used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 24 MDA5+ myositis patients. Correlations between clinical features and standardized anti-MDA5 subfragment antibody titres were assessed via Spearman's rank correlation coefficients. Results Twenty-four MDA5+ patients submitted serum samples within a median of 0 (interquartile range, 0–74) days from the initial clinic visit. In addition to typical dermatomyositis rashes, these patients exhibited muscle symptoms (n  = 11), vascular dysfunction (n  = 9) and interstitial lung disease (ILD) (n  = 16). Female patients exhibited higher titres of antibodies recognizing fragment H (aa 905–1026) compared with male patients. Muscle involvement was associated with higher levels of anti-fragment F (aa 646–801) antibody. Conversely, patients with vascular abnormalities had higher anti-fragment B (aa 130–284) and E (aa 517–671) antibody titres than those without vascular dysfunction. Four patients died due to ILD progression and showed higher anti-fragment A (aa 1–155) antibody titres than the other 20 patients. Differences in the ratio of anti-fragment to anti-full-length MDA5 antibody titres were found for sex (H: anti-MDA5) and vascular dysfunction (anti-fragment B, E: anti-MDA5). Conclusions Various clinical features of MDA5+ dermatomyositis correlated with levels of antibodies targeting selected subfragments of this autoantigen, providing a link between fragment-specific immune responses and disease course. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to evaluate if and how the incidence of serious infection (SI) and active tuberculosis (TB) differ among seven biologic DMARDs (bDMARDs) in patients with RA considering the line of therapy. Methods Patients with RA from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) cohort who initiated etanercept, certolizumab, infliximab, adalimumab, abatacept, rituximab or tocilizumab from the first to fifth line of therapy were included. Follow-up extended up to 3 years. The primary outcome was SI and the secondary outcome was TB. Event rates were calculated and compared using Cox proportional hazards models, controlling for confounding with inverse probability of treatment weights. Comparisons were made overall and stratified by line of therapy. Sensitivity analysis was restricted to all treatment courses from 2009 (tocilizumab availability) until the end of the study (2018). Results Among 33 897 treatment courses (62 513 patient-years) the incidence of SI was 4.4/100 patient-years (95% CI 4.2, 4.5). After adjustment, hazards ratios (HRs) of SI were slightly higher with adalimumab and infliximab compared with etanercept. However, no clear pattern was observed when stratifying by line of therapy in terms of incidence rate or HR. Sensitivity analyses showed similar HRs among these treatments. Regarding TB, all 49 cases occurred during the first three lines of treatment and rarely since 2009. Conclusion The risk of serious infections does not appear to be influenced by the line of therapy in patients with RA. However, the risk of TB seems to be more frequent during the initial lines of treatment or prior to 2009. [ABSTRACT FROM AUTHOR]

Objective Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder. The understanding of the changes in adaptive immune cells and the crosstalk between innate and adaptive immune systems in AOSD is limited. This study aimed to examine the peripheral immune cell composition and inflammatory protein levels in AOSD patients. Methods Twenty-nine active AOSD patients were enrolled. Flow cytometry was used to analyse the cell populations in peripheral blood. Antibody chips were utilized to detect the protein expression profile in serum. Results In active AOSD patients, there was an increase in the percentage of classical and non-classical monocytes among peripheral blood mononuclear cells. The proportion of natural killer (NK) cells decreased, with an increase in CD56dim NK1 cells and a decrease in CD56bright NK2 cells compared with healthy controls (HCs). The percentage of naïve central memory T cells was decreased, while the percentage of effector and effector memory T cells was increased among adaptive lymphocytes. The proportion of naïve B and memory B cells was decreased, while plasma cells were increased in AOSD patients, indicating activation of the adaptive immune system. Additionally, the serum levels of 40 proteins were elevated in AOSD patients, primarily involved in cytokine–cytokine receptor interaction, inflammatory response and regulation of mitogen-activated protein kinase cascade. Conclusion Our findings showed the activation of the innate and adaptive immune system in AOSD. The protein–protein interaction analysis suggested potential communication between innate and adaptive cell subsets. These findings provide new insights into the pathogenesis of the disease and the development of targeted therapies. [ABSTRACT FROM AUTHOR]

Aims Motivational interviewing (MI) has been recognized as highly effective for treating chronic diseases and various conditions, with encouraging results demonstrating its effectiveness in promoting health behaviour change. The current study was proposed to evaluate the feasibility of MI on adherence to care practices, emotional intelligence (EI), and dispositional optimism among patients with permanent pacemakers. Methods and results This study was a parallel arm randomized controlled trial. Seventy clients with permanent pacemakers were randomly allocated to a six-session MI intervention (n = 35) or a waiting list control group (n = 35). A statistically significant improvement in the mean scores of adherence to care practices, EI, and dispositional optimism, along with a significant reduction in pessimism, was registered among the study group compared with the control group. Conclusion Following the intervention for 1- and 2-month follow-up measurements, there were statistically significant improvements in self-care practice adherence. After 1 month of intervention, there were statistically significant gains in EI and dispositional optimism, but at the 2-month follow-up measurement, this improvement had somewhat lessened. The findings suggest that MI may be a feasible and practical approach for improving adherence to care practices, EI, and dispositional optimism in patients with permanent pacemakers. Registration ClinicalTrials.gov: NCT05883514 [ABSTRACT FROM AUTHOR]

Background Subjective cognitive decline (SCD), i.e. self/other-reported concerns on one's cognitive functioning without objective evidence of significant decline, is an indicator of dementia risk. There is little consensus on reliability and validity of the available SCD measures. Therefore, introducing a novel and psychometrically sound measure of SCD is timely. Objective The psychometric properties of a new SCD measure, the McCusker Subjective Cognitive Impairment Inventory–Self-Report (McSCI-S), are reported. Methods Through review of previously published measures as well as our clinical and research data on people with SCD, we developed a 46-item self-report questionnaire to assess concerns on six cognitive domains, namely, memory, language, orientation, attention and concentration, visuoconstruction abilities and executive function. The McSCI-S was examined in a cohort of 526 participants using factor analysis, item response theory analysis and receiver operating characteristic (ROC) curve. Results A unidimensional model provided acceptable fit (CFI = 0.94, TLI = 0.94, RMSEA [90% CI] = 0.052 [.049, 0.055], WRMR = 1.45). The McSCI-S internal consistency was excellent (.96). A cut-off score of ≥24 is proposed to identify participants with SCDs. Higher McSCI-S scores were associated with poorer general cognition, episodic verbal memory, executive function and greater memory complaints and depressive scores (P  < .001), controlling for age, sex and education. Conclusions Excellent reliability and construct validity suggest the McSCI-S estimates SCDs with acceptable accuracy while capturing self-reported concerns for various cognitive domains. The psychometric analysis indicated that this measure can be used in cohort studies as well as on individual, clinical settings to assess SCDs. [ABSTRACT FROM AUTHOR]

Background Medical laboratory science (MLS) professionals play a crucial role in health care teams. However, research culture in the profession has not been well developed or studied. It is necessary to characterize attitudes toward research and scholarly activities among MLS professionals and identify ways to promote research in the profession. Methods A cross-sectional survey was administered through American Society for Clinical Laboratory Science channels. Survey responses were summarized using descriptive statistics, and linear regression models were constructed to identify characteristics that predicted 2 research attitudes: "valuing the role of research" and "perceived research environment" in the profession. Results Of the 116 MLS professionals in this study, 53% reported currently participating in research activities. Opinions toward research were generally positive, although many respondents were not currently conducting research. Individuals with education and research practice focuses tended to place greater value on research, and education level was a significant predictor of perceived research environment. Dedicated research time and mentorship were cited as effective ways for employers to promote research in MLS. Conclusion Overall, respondents had favorable attitudes toward research in MLS, but approximately half of participants noted a lack of incentives to conduct research. This study highlights several initiatives that may be effective for promoting increased research activity among MLS professionals. [ABSTRACT FROM AUTHOR]

Background Diagnostic accuracy of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) in identification of intracranial abnormalities detected by computed tomography (CT) in mild traumatic brain injury (mTBI), and in patients with mild neurological symptoms not caused by head trauma but suspected with a neurological disorder, was examined. Methods GFAP and UCH-L1 were determined using the chemiluminescence immunoassays on the Alinity i analyzer (Abbott Laboratories). Results Significantly higher GFAP (median 53.8 vs 25.7 ng/L, P <.001) and UCH-L1 (median 350.9 vs 153.9 ng/L, P <.001) were found in mTBI compared to non-head trauma patients. In mTBI diagnostic sensitivity (Se) and specificity (Sp) for the combination of GFAP and UCH-L1 were 100% and 30.9%, respectively, with area under the curve (AUC) 0.655. GFAP alone yielded Se 85.7%, Sp 41.8%, and AUC 0.638, while UCH-L1 yielded Se 57.1%, Sp 56.4%, and AUC 0.568. In non-head trauma patients, the combination of GFAP and UCH-L1 showed Se 100%, Sp 87.9%, and AUC 0.939, while GFAP alone demonstrated Se 100%, Sp 90.9%, and AUC 0.955. Conclusions If these results are reproduced on a larger sample, GFAP and UCH-L1 may reduce CT use in patients with mild neurological symptoms after systemic causes exclusion and neurologist's evaluation. [ABSTRACT FROM AUTHOR]

Background A1C ≥6.0% is associated with increased risk of adverse outcomes in pregnant diabetic patients. A1C testing is recommended by the American Diabetes Association as a secondary measure of glycemic control in pregnant patients. Objective To determine the utility of A1C point-of-care testing (POCT) during pregnancy to facilitate rapid counseling and diabetes care, particularly in relatively low-income transient patient populations. Methods We performed a single-center, retrospective analysis of patients presenting to an outpatient obstetrics office with routine, in-laboratory A1C testing, before and after the implementation of POCT for A1C (n = 70 and n = 75, respectively). Demographics, results, physician referral to a nutritionist, counseling, and outcomes were retrieved from patient electronic medical records. Results In total, 9% and 23% of the in-laboratory and POCT groups, respectively, were referred for nutrition services (P =.02). Of these, 22% of the in-laboratory group and 42% of the POCT group received immediate counseling (P <.01). An inverse correlation was observed between A1C level at study entry and gestational weeks at delivery, with a Pearson r value of −0.39 (−0.58 to −0.16) for the in-laboratory group and −0.38 (−0.57 to −0.14) for the POCT group. No statistically significant difference in pregnancy outcomes was observed. Conclusion Implementation of A1C POCT was associated with immediate counseling and management of the health of pregnant patients, but was not associated with improved outcomes, in a low-resource patient population. [ABSTRACT FROM AUTHOR]

The aim of this article is to establish a causal link between the policies implemented by technology companies and the outcomes they yield within intricate temporal and/or spatial dependent experiments. We propose a novel temporal/spatio-temporal Varying Coefficient Decision Process model, capable of effectively capturing the evolving treatment effects in situations characterized by temporal and/or spatial dependence. Our methodology encompasses the decomposition of the average treatment effect into the direct effect (DE) and the indirect effect (IE). We subsequently devise comprehensive procedures for estimating and making inferences about both DE and IE. Additionally, we provide a rigorous analysis of the statistical properties of these procedures, such as asymptotic power. To substantiate the effectiveness of our approach, we carry out extensive simulations and real data analyses. [ABSTRACT FROM AUTHOR]

Aims Hypertensive patients of African ancestry (Afr-a) have higher incidences of heart failure and worse clinical outcomes than hypertensive patients of European ancestry (Eu-a), yet the underlying mechanisms remain misunderstood. This study investigated right (RV) and left (LV) ventricular remodelling alongside myocardial tissue derangements between Afr-a and Eu-a hypertensives. Methods and results 63 Afr-a and 47 Eu-a hypertensives underwent multi-parametric cardiovascular magnetic resonance. Biventricular volumes, mass, function, mass/end-diastolic volume (M / V) ratios, T2 and pre-/post-contrast T1 relaxation times, synthetic extracellular volume, and myocardial fibrosis (MF) were measured. 3D shape modelling was implemented to delineate ventricular geometry. LV and RV mass (indexed to body-surface-area) and M/V ratio were significantly greater in Afr-a than Eu-a hypertensives (67.1 ± 21.7 vs. 58.3 ± 16.7 g/m2, 12.6 ± 3.48 vs. 10.7 ± 2.71 g/m2, 0.79 ± 0.21 vs. 0.70 ± 0.14 g/mL, and 0.16 ± 0.04 vs. 0.13 ± 0.03 g/mL, respectively; P < 0.03). Afr-a patients showed greater basal interventricular septum thickness than Eu-a patients, influencing LV hypertrophy and RV cavity changes. This biventricular remodelling was associated with prolonged T2 relaxation time (47.0 ± 2.2 vs. 45.7 ± 2.2 ms, P = 0.005) and higher prevalence (23% vs. 4%, P = 0.001) and extent of MF [2.3 (0.6–14.3) vs. 1.6 (0.9–2.5) % LV mass, P = 0.008] in Afr-a patients. Multivariable linear regression showed that modifiable cardiovascular risk factors and greater end-diastolic volume, but not ethnicity, were independently associated with greater LV mass. Conclusion Afr-a hypertensives had distinctive biventricular remodelling, including increased RV mass, septal thickening and myocardial tissue abnormalities compared with Eu-a hypertensives. From this study, modifiable cardiovascular risk factors and ventricular geometry, but not ethnicity, were independently associated with greater LV myocardial mass. [ABSTRACT FROM AUTHOR]

Background Clinical trials of treatments for serious infections commonly use the primary endpoint of all-cause mortality. However, many trial participants survive their infection and this endpoint may not truly reflect important benefits and risks of therapy. The win ratio uses a hierarchical composite endpoint that can incorporate and prioritize outcome measures by relative clinical importance. Methods The win ratio methodology was applied post hoc to outcomes observed in the MERINO trial, which compared piperacillin-tazobactam with meropenem. We quantified the win ratio with a primary hierarchical composite endpoint, including all-cause mortality, microbiological relapse, and secondary infection. A win ratio of 1 would correspond to no difference between the 2 antibiotics, while a ratio <1 favors meropenem. Further analyses were performed to calculate the win odds and to introduce a continuous outcome variable in order to reduce ties. Results With the hierarchy of all-cause mortality, microbiological relapse, and secondary infection, the win ratio estimate was 0.40 (95% confidence interval [CI],.22–.71]; P =.002), favoring meropenem over piperacillin-tazobactam. However, 73.4% of the pairs were tied due to the small proportion of events. The win odds, a modification of the win ratio accounting for ties, was 0.79 (95% CI,.68–.92). The addition of length of stay to the primary composite greatly minimized the number of ties (4.6%) with a win ratio estimate of 0.77 (95% CI,.60–.99; P =.04). Conclusions The application of the win ratio methodology to the MERINO trial data illustrates its utility and feasibility for use in antimicrobial trials. [ABSTRACT FROM AUTHOR]

Objectives Complement activation has been advocated as one mechanism by which aPLs can induce thrombosis. In patients with catastrophic APS or re-thrombosis, enhanced complement activation has been shown, even in the quiescent phase of the disease. We aimed to assess complement activation and to investigate its association with clinical variables in aPL-positive patients with a favourable disease course. Methods Subjects with at least two consecutive positive aPL results obtained ≥12 weeks apart were enrolled. They were subjects without a history of thrombosis or pregnancy morbidity (aPL carriers), patients with pregnancy morbidity alone, i.e. obstetric APS patients (OAPS patients), and/or patients with arterial, venous, or small-vessel thrombotic APS (TAPS patients); for enrolment, all patients were required to have been free of symptoms for ≥2 years. Patients affected with systemic autoimmune diseases were excluded. Healthy age- and sex-matched subjects were included as controls. Plasma C5a and C5b-9 levels were assessed by commercially available ELISA assays. The non-parametric Mann–Whitney test and Spearman's correlation were applied. Results Thirty-seven OAPS patients, 38 TAPS patients, 42 aPL carriers and 30 healthy subjects were enrolled. The median C5a and C5b-9 levels were significantly higher in quiescent aPL-positive patients (OAPS, TAPS, aPL carriers) compared with controls: C5a ng/ml 10.61 [interquartile range (IQR) 6.87–15.46] vs 4.06 (2.66–7.35), P  < 0.001; C5b-9 ng/ml 283.95 (175.8–439.40) vs 165.90 (124.23–236.8), P  < 0.001. Similar C5a and C5b-9 levels were observed in OAPS and TAPS patients and aPL carriers. A positive correlation between the median C5b-9 levels and the number of aPL-positive tests was found (P  = 0.002). Conclusion The persistence of aPL antibodies is associated with a persistent subclinical activation of the complement cascade. [ABSTRACT FROM AUTHOR]

Forecasting of seasonal mortality patterns can provide useful information for planning health-care demand and capacity. Timely mortality forecasts are needed during severe winter spikes and/or pandemic waves to guide policy-making and public health decisions. In this article, we propose a flexible method for forecasting all-cause mortality in real time considering short-term changes in seasonal patterns within an epidemiologic year. All-cause mortality data have the advantage of being available with less delay than cause-specific mortality data. In this study, we use all-cause monthly death counts obtained from the national statistical offices of Denmark, France, Spain, and Sweden from epidemic seasons 2012-2013 through 2021-2022 to demonstrate the performance of the proposed approach. The method forecasts deaths 1 month ahead, based on their expected ratio to the next month. Prediction intervals are obtained via bootstrapping. The forecasts accurately predict the winter mortality peaks before the COVID-19 pandemic. Although the method predicts mortality less accurately during the first wave of the COVID-19 pandemic, it captures the aspects of later waves better than other traditional methods. The method is attractive for health researchers and governmental offices for aiding public health responses because it uses minimal input data, makes simple and intuitive assumptions, and provides accurate forecasts both during seasonal influenza epidemics and during novel virus pandemics. [ABSTRACT FROM AUTHOR]

Assessing heterogeneous treatment effects (HTEs) is an essential task in epidemiology. The recent integration of machine learning into causal inference has provided a new, flexible tool for evaluating complex HTEs: causal forest. In a recent paper, Jawadekar et al (Am J Epidemiol. 2023;192(7):1155-1165) introduced this innovative approach and offered practical guidelines for applied users. Building on their work, this commentary provides additional insights and guidance to promote the understanding and application of causal forest in epidemiologic research. We start with conceptual clarifications, differentiating between honesty and cross-fitting, and exploring the interpretation of estimated conditional average treatment effects. We then delve into practical considerations not addressed by Jawadekar et al, including motivations for estimating HTEs, calibration approaches, and ways to leverage causal forest output with examples from simulated data. We conclude by outlining challenges to consider for future advancements and applications of causal forest in epidemiologic research. [ABSTRACT FROM AUTHOR]

Background Alternative data sources for surveillance have gained importance in maintaining coronavirus disease 2019 (COVID-19) situational awareness as nationwide testing has drastically decreased. Therefore, we explored whether rates of sick-leave from work are associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) notification trends and at which lag, to indicate the usefulness of sick-leave data for COVID-19 surveillance. Methods We explored trends during the COVID-19 epidemic of weekly sick-leave rates and SARS-CoV-2 notification rates from 1 June 2020 to 10 April 2022. Separate time series were inspected visually. Then, Spearman correlation coefficients were calculated at different lag and lead times of zero to four weeks between sick-leave and SARS-CoV-2 notification rates. We distinguished between four SARS-CoV-2 variant periods, two labour sectors and overall, and all-cause sick-leave versus COVID-19-specific sick-leave. Results The correlation coefficients between weekly all-cause sick-leave and SARS-CoV-2 notification rate at optimal lags were between 0.58 and 0.93, varying by the variant period and sector (overall: 0.83, lag −1; 95% CI [0.76, 0.88]). COVID-19-specific sick-leave correlations were higher than all-cause sick-leave correlations. Correlations were slightly lower in healthcare and education than overall. The highest correlations were mostly at lag −2 and −1 for all-cause sick-leave, meaning that sick-leave preceded SARS-CoV-2 notifications. Correlations were highest mostly at lag zero for COVID-19-specific sick-leave (coinciding with SARS-CoV-2 notifications). Conclusion All-cause sick-leave might offer an earlier indication and evolution of trends in SARS-CoV-2 rates, especially when testing is less available. Sick-leave data may complement COVID-19 and other infectious disease surveillance systems as a syndromic data source. [ABSTRACT FROM AUTHOR]

Objective. Clinical practice guidelines recommend the radial nerve mechanosensitivity evaluation in patients with lateral epicondylalgia. Despite different positions and sequences having been described, no research analyzed how each variation triggers symptoms associated with lateral epicondylalgia. The aim of this study was to explore the effects of different positions and sequences in the upper limb neural tension test 2b (ULNT2b) in symptom responses in patients with lateral epicondylalgia. Methods. In this observational study, 66 patients underwent 4 test conditions: standard ULNT2b, ULNT2b proximal to distal, ULNT2B with resisted supination, and resisted supination isolated. Paresthesia sensations, symptom reproduction, pain intensity (measured using a visual analog scale), and distribution of painful symptoms data were collected. Results. Significant differences in paresthesia sensations were observed between groups, with significant differences between the standard ULNT2B and other ULNT variations or resisted supination maneuvers. Symptom reproduction also differed significantly across groups, with significant differences between the standard ULNT2B and other ULNT or resisted supination tests. The positive/negative test and percentage of distribution of painful symptoms scores varied significantly across 4 conditions in both lateral and frontal views. Although pain intensity scores during tests were comparable among the tests, distribution of painful symptoms differed significantly. Conclusion. Variations in the ULNT2b test can affect symptom responses in patients with lateral epicondylalgia. The standard ULNT2b test appears more effective at reproducing symptoms, intensity of paresthesia, and distribution of painful symptoms compared to other ULNT variations and the resisted supination test. Impact. ULNT2b sequences have been shown to elicit varying responses concerning paresthesia, replication of familiar symptoms, positive/negative test results, and distribution of painful symptoms. Clinicians should consider specific test variations during the patients' radial nerve mechanosensitivity assessment to identify aggravating factors reproducing recognizable symptoms. A control group of asymptomatic participants and the role of presence of other comorbidities, psychological factors, or the duration of symptoms were not considered in this study and might play an important role influencing the results of the tests. [ABSTRACT FROM AUTHOR]

Formation of proper handwashing techniques and habits from childhood is important for disease prevention. However, there are few studies that comprehensively and longitudinally evaluate the effectiveness of handwashing education for kindergarteners. This study aims to evaluate the effectiveness of continuous handwashing education using multiple activities to improve handwashing practices and skills among first- to third-grade students at a kindergarten in central Japan. A quasi-experimental one group pre- and post-test design was used. The education program consisted of three activities: (i) a 1-day teaching session by a researcher in January 2021, (ii) a 1-month follow-up activity led by kindergarten teachers and (iii) a 1-month follow-up activity led by parents at home, both occurring from late January to late February 2021. The study used questionnaires and handwashing skill experiments to investigate the kindergarteners' handwashing practices and comprehensive handwashing skills (handwashing steps, handwashing time, rinsing time and areas of the hands left unwashed) before and after Activities 1, 2 and 3. Data were obtained from 56 kindergarteners (64.4%). Second and third graders showed a significant improvement in their handwashing practices after coughing or sneezing. With the exception of rinsing time, handwashing skills significantly improved in all grades after the 1-day teaching session. After 1-month follow-up activities, the number of areas left unwashed by first graders significantly decreased, and the score for handwashing steps significantly improved. This study indicated that continuous handwashing education is partially effective at improving and maintaining handwashing practices and skills, except for rinsing time, among kindergarteners of all grades. [ABSTRACT FROM AUTHOR]

The role of religiosity in shaping family functioning, in general, and parental discipline, in particular, have received wide research attention, especially in studies conducted amongst Christian parents from Western cultures. Little is known about the relationship between religiosity and parenting in non-Western cultures. The current study explored the role religion and religiosity play in predicting maternal use of psychological control and punitive discipline of mothers from Israel who belong to two ethnonational groups: Jews and Arabs, and who represent four religions: Jewish, Muslims, Christian and Druze. The study was based on a survey of 502 Israeli mothers of children aged three to five years (31.6 per cent Jewish, 36.0 per cent Muslims, 16.8 per cent Christians and 15.6 per cent Druze). Mothers were asked to fill out an online structured, anonymous self-report questionnaire survey distributed through social networks. We used multivariate hierarchal regression to explore the role of religion and religiosity in predicting mother's use of punitive discipline and psychological control, after controlling for child and family factors. The results showed that religiosity was significantly and positively associated with mothers' use of both psychological control and punitive discipline. Furthermore, it was found that Arab mothers reported using psychological control more than did Jewish mothers. [ABSTRACT FROM AUTHOR]

Background The COVID-19 pandemic has significantly impacted the lifestyle and health of children and adolescents. This study aimed to assess the lifestyle changes brought about by COVID-19-related school closures and their impact on the Body Mass Index for Age Z (BAZ) scores of governmental school students in Qatar. Methods An analytical cross-sectional study was conducted between June and August 2022 targeting students aged 8–15 years. Data on lifestyle behaviors were gathered through telephone interviews with parents of selected students. The BAZ scores before and after school closures that were automatically calculated by the electronic health records system were extracted. Results We completed 1546 interviews. We found a significant increase in unhealthy food categories, a reduction in physical activity and an increase in the screen time over the period of schools' closure. The BAZ increased significantly by 0.30 (95% CI 0.26–0.35). The increase in BAZ scores was significantly higher among male students and the younger age group compared to females and older counterparts, respectively. The student's age group, sex, nationality and change in physical activity were significant predictors of the change in BAZ scores. Conclusions School closures during the COVID-19 pandemic negatively impacted the lifestyle of students in Qatar and resulted in a significant increase in the BAZ scores. [ABSTRACT FROM AUTHOR]

Background E-cigarettes have emerged as popular products, especially for younger populations. However, concerns regarding health effects exist and there is a notable gap in understanding the prevalence and nature of adverse events. This study aims to examine the rate of adverse events in individuals who use e-cigarettes in a large sample. Methods A cross-sectional survey was conducted with a sample of 4695 current and former e-cigarette users with a median age of 34 years. The survey collected data on e-cigarette use, adverse events experienced, product characteristics, related behaviors, sociodemographic factors and presence of medical comorbidities. Statistical analyses were conducted using Pearson's chi-squared tests and logistic regression. Results A total of 78.9% of respondents reported experiencing an adverse event within 6 h of using a vaping device, with the most common events being headache, anxiety and coughing. Product characteristics and related behaviors significantly influenced the risk of adverse events. There were also sociodemographic disparities, with Hispanic respondents and those with at least college-level education reporting higher rates of adverse events. Conclusions Our study found a high rate of adverse events among e-cigarette users. We identified that certain e-cigarette product characteristics, behaviors and medical comorbidities significantly increased the risk of these events. [ABSTRACT FROM AUTHOR]

Aims Although systolic expansion of the annulus has been recognized in Barlow's disease, the mechanisms of the unique pathological movement of the annulus and its relation to the leaflet augmentation have not yet been clarified. We aimed to investigate the detailed mechanisms of the characteristic mitral apparatus dynamics in Barlow's disease by frame-by-frame sequential geometric analysis using real-time 3D transoesophageal echocardiography. Methods and results Fifty-three patients with Barlow's disease and severe mitral regurgitation without torn chordae, as well as 10 controls, were included. We evaluated geometric changes in the mitral complex using 3D transoesophageal echocardiography at five points during systole. To identify early systolic billowing of leaflets, the annulo-leaflet angle was measured. We also performed a more detailed analysis in four consecutive frames just before and after leaflet free-edge prolapse above the annulus plane. The median annulo-leaflet angle of both leaflets in early systole was >0° (above annulus plane) in patients with Barlow's disease, and billowing of the leaflet body was observed from early systole. The prolapse volume of both leaflets increased markedly from early to mid-systole [1.60 (0.85–2.80) to 4.00 (2.10–6.45) mL; analysis of variance (ANOVA), P < 0.001; post hoc , P < 0.05]. With frame-by-frame analysis, dynamic augmentation of the annulus and leaflets developed between frames just before and just after leaflet free-edge prolapse (ANOVA, P < 0.01; post hoc , P < 0.05). Conclusion In Barlow's disease, early systolic billowing of the mitral leaflet induces systolic annulus expansion followed by leaflet augmentation and leaflet free-edge prolapse. [ABSTRACT FROM AUTHOR]

Background Control of schistosomiasis (SCH) relies on the regular distribution of preventive chemotherapy (PC) over many years. For the sake of sustainable SCH control, a decision must be made at some stage to scale down or stop PC. These "stopping decisions" are based on population surveys that assess whether infection levels are sufficiently low. However, the limited sensitivity of the currently used diagnostic (Kato-Katz [KK]) to detect low-intensity infections is a concern. Therefore, the use of new, more sensitive, molecular diagnostics has been proposed. Methods Through statistical analysis of Schistosoma mansoni egg counts collected from Burundi and a simulation study using an established transmission model for schistosomiasis, we investigated the extent to which more sensitive diagnostics can improve decision making regarding stopping or continuing PC for the control of S. mansoni. Results We found that KK-based strategies perform reasonably well for determining when to stop PC at a local scale. Use of more sensitive diagnostics leads to a marginally improved health impact (person-years lived with heavy infection) and comes at a cost of continuing PC for longer (up to around 3 years), unless the decision threshold for stopping PC is adapted upward. However, if this threshold is set too high, PC may be stopped prematurely, resulting in a rebound of infection levels and disease burden (+45% person-years of heavy infection). Conclusions We conclude that the potential value of more sensitive diagnostics lies more in the reduction of survey-related costs than in the direct health impact of improved parasite control. [ABSTRACT FROM AUTHOR]

Background Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults. Methods The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up. Results Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI},.86–1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI,.28–1.30]). Statistical power to assess effect modification in other subgroups was limited. Conclusions In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study. Clinical Trials Registration. NCT01169259. [ABSTRACT FROM AUTHOR]

Background Widespread antibiotic resistance has sparked interest in the identification of nonantibiotic strategies, particularly probiotics for the prevention of recurrent urinary tract infections (UTIs). We evaluated the effectiveness of prophylactic probiotic supplementation through oral and intravaginal routes in the prevention of recurrent UTIs. Methods This double-blind, placebo-controlled study enrolled 174 premenopausal women with a history of recurrent UTIs and randomized them to 1 of the 4 treatment groups: placebo (G1, oral placebo + vaginal placebo), oral probiotic (G2, oral lactic acid bacteria and bifidobacteria + vaginal placebo), vaginal probiotic (G3, oral placebo + vaginal lactobacilli), and probiotic combination (oral lactic acid bacteria and bifidobacteria + vaginal lactobacilli), for 4 months. Participants were followed up for symptomatic UTIs for 1 year. The primary end points were the number of symptomatic UTIs at 4 months, the proportion of participants with at least 1 symptomatic UTI, and the time to the first symptomatic UTI. Results The incidence of UTI at 4 months in G1, G2, G3, and G4 was 70.4%, 61.3%, 40.9%, and 31.8%, respectively. The mean number of symptomatic UTI recurrences at 4 months was significantly lower (P <.05) in G3 (1.06) and G4 (1.07) compared with G1 (2.1) and G2 (1.63). Further, the time to first symptomatic UTI (days) was significantly longer (P <.05) in G3 (123.8) and G4 (141.8) compared with G1 (69.3) and G2 (71.9). Probiotic supplementations were well tolerated with no serious adverse events. Conclusions Prophylactic supplementation with either vaginal probiotics or in combination with oral probiotics demonstrated effectiveness in preventing recurrent symptomatic UTI episodes. Clinical Trials Registration Registered at Clinical Trials Registry India (CTRI): CTRI/2014/02/004425 (https://ctri.nic.in). [ABSTRACT FROM AUTHOR]

Objective We investigated the incidence of and risk factors for myelodysplastic syndrome (MDS) in patients with rheumatologic disease. Methods We conducted a retrospective cohort study of patients who were diagnosed with rheumatologic diseases at a tertiary care hospital between May 2009 and July 2022 and identified the patients who were subsequently diagnosed with MDS. Each patient with MDS was matched with five age- and sex-matched controls chosen from the cohort of patients with each specific rheumatologic disease. Results During a total follow-up of 55 841 person-years (PY), MDS occurred in 64 patients, yielding an incidence rate of 1.15/1000 PY {median age 57.0 years [interquartile range (IQR) 41.0–69.0], median duration to MDS diagnosis 6.5 years (IQR 3.0–9.0)]. In an age-matched analysis, SLE was a significant risk factor for MDS [adjusted hazard ratio 2.61 (CI 1.19, 36.06), P  = 0.01]. Refractory cytopenia with multilineage dysplasia was the most common phenotype of MDS (35.9%), and more than half of the patients had karyotypes with a favourable prognosis (54.7%). Compared with matched controls, RA, SLE and AS patients with MDS had lower levels of haemoglobin at the time of diagnosis of rheumatologic disease. Furthermore, the MDS patients with SLE and Behçet's disease had higher levels of glucocorticoid use in terms of frequency of use and mean dose than control patients. Conclusion SLE is a significant risk factor for MDS among patients with rheumatologic diseases. A lower haemoglobin level at the time of diagnosis of rheumatologic disease was associated with the future development of MDS. [ABSTRACT FROM AUTHOR]

In this paper, we present a practical approach for computing the sandwich variance estimator in 2-stage regression model settings. As a motivating example for 2-stage regression, we consider regression calibration, a popular approach for addressing covariate measurement error. The sandwich variance approach has rarely been applied in regression calibration, despite its requiring less computation time than popular resampling approaches for variance estimation, specifically the bootstrap. This is probably because it requires specialized statistical coding. Here we first outline the steps needed to compute the sandwich variance estimator. We then develop a convenient method of computation in R for sandwich variance estimation, which leverages standard regression model outputs and existing R functions and can be applied in the case of a simple random sample or complex survey design. We use a simulation study to compare the sandwich estimator to a resampling variance approach for both settings. Finally, we further compare these 2 variance estimation approaches in data examples from the Women's Health Initiative (1993–2005) and the Hispanic Community Health Study/Study of Latinos (2008–2011). In our simulations, the sandwich variance estimator typically had good numerical performance, but simple Wald bootstrap confidence intervals were unstable or overcovered in certain settings, particularly when there was high correlation between covariates or large measurement error. [ABSTRACT FROM AUTHOR]

Epidemiologists are attempting to address research questions of increasing complexity by developing novel methods for combining information from diverse sources. Cole et al. (Am J Epidemiol. 2023;192(3)467–474) provide 2 examples of the process of combining information to draw inferences about a population proportion. In this commentary, we consider combining information to learn about a target population as an epidemiologic activity and distinguish it from more conventional meta-analyses. We examine possible rationales for combining information and discuss broad methodological considerations, with an emphasis on study design, assumptions, and sources of uncertainty. [ABSTRACT FROM AUTHOR]

Objective The serum squamous cell carcinoma antigen (SCCA) level is a well-known tumor marker for squamous cell carcinoma. In this study, we examined the impact of immunoglobulin (Ig)-bound macromolecular SCCA on serum SCCA levels measured by 2 different methods. Methods Seventy-five serum samples with an SCCA level >5.0 ng/mL as determined by a chemiluminescent immunoassay (CLIA) were also analyzed using a chemiluminescent enzyme immunoassay (CLEIA). The levels of IgG- and IgA-type anti-SCCA antibodies, which form immunoglobulins and macromolecules, respectively, were determined using an enzyme-linked immunosorbent assay. An absorption test was performed to confirm the presence of anti-SCCA antibodies. Results The correlation coefficient between the values measured by CLEIA and CLIA was 0.768. The ratio of SCCA levels measured by CLEIA to those measured by CLIA in 14 samples with IgG-type anti-SCCA antibodies was significantly lower than that in samples without these antibodies (P <.031). Absorption tests showed that SCCA levels measured by CLIA might be falsely high in samples with IgG-type anti-SCCA antibodies, probably due to reactions with SCCA1. Conclusion The level of SCCA as measured by CLIA and CLEIA methods correlate well, but the presence of SCCA antibodies can affect the results of the CLIA method. [ABSTRACT FROM AUTHOR]

Objective To evaluate the associations between analytical methods, such as microarray and enzyme-linked immunosorbent assay (ELISA); expedient cutoffs; and the lowest possible number of microarrays in analysis for target biomarker estimation in case-control studies. Methods This study included 321 serum specimens, gathered in different case-control studies to test for atherosclerosis and atrial fibrillation. Among them, 48 serum specimens were analyzed using microarray technology. We used ELISA and commercial kits for confirmation of the results. Results Three proteins—cadherin-P, neuronal nitric oxide synthase, and adenovirus fiber—were shown to have distinctly different values in the case group vs the control group. As a result, we used those proteins as the target for confirmation using our alternative analytical method. Also, these protein values represented the limiting range between the highest and lowest differences in case-control groups. The results of microarray assay were confirmed using ELISA and commercial kits in the same specimens, in which microarray profiling was performed, and also in separate large case-control groups. Conclusions A 1.5-fold difference in the protein content, as measured using microarray technology, was shown to be sufficient for further investigation of the candidate proteins. As few as 3 microarrays were considered sufficient for perspective evaluation of the target proteins. Microarray serum profiling, therefore, provides semiquantitative determination of protein in serum. [ABSTRACT FROM AUTHOR]