Exposure Variables Research Articles

Associations of Accelerometer-Measured Physical Activity With Dementia, Anxiety, and Depression Among Older Adults.

Higher physical activity (PA) is associated with better neuropsychiatric health, but prior studies have been limited by cross-sectional designs, self-reported PA measures, and small numbers of older individuals. We examined associations between baseline and changes in accelerometer-measured moderate-vigorous PA (MVPA) with neuropsychiatric health among individuals aged ≥ 70 years in the National Health and Aging Trends Study. We used the average daily minutes of accelerometer-measured MVPA above a validated threshold of 2184 counts per minute as a continuous measure at baseline for the exposure variable. For longitudinal analyses, we categorized change in MVPA as follows: an increase of > 20 min/day over 1 year, a decrease of > 20 min/day over 1 year, and staying within 20 min/day over 1 year. Our outcomes were possible/probable dementia and anxiety or depression. Associations were estimated using confounder-adjusted logistic regressions. In our survey-weighted analytic sample of 639 individuals aged ≥ 70 years, 56% were ≥ 75 years, and 53% were female. After adjusting for confounders, a 20-min/day higher baseline MVPA was significantly associated with lower odds of possible/probable dementia 1 year later (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.83-0.96) but not with depression and anxiety symptoms. Compared to no change in PA over 1 year, an increase in MVPA by > 20 min/day was associated with decreased odds of depression and anxiety symptoms (OR = 0.06, 95% CI = 0.03-0.14) but not with possible/probable dementia. Compared to no change in MVPA over 1 year, a decrease in MVPA by > 20 min/day was associated with higher odds of possible/probable dementia (OR = 3.82, 95% CI = 1.34-10.87) but not with depression and anxiety symptoms. Higher and increasing MVPA over time is associated with better neuropsychiatric health in individuals aged ≥ 70 years. Future studies should prioritize evaluating detailed PA trajectories to better understand how different doses, intensities, and modalities of PA impact neuropsychiatric decline in older adults.

Continuing exposure to disadvantageous material and perceived economic factors on self-rated health in different life stages: fixed effects analyses with data from the German Socioeconomic Panel

BackgroundLife course epidemiology explores health disparities over time. The accumulation thesis thereby suggests an add-up of disadvantages, while the adaptation model assumes an adjustment to disadvantageous conditions. Examining the relevance of these accumulation and adaptation processes, the present study analyses continuing exposure to various material and perceived economic factors on self-rated health (SRH) across different life stages.MethodsAll analyses are based on longitudinal data from the German Socio-Economic Panel (SOEP) from 1994 to 2017. Exposure variables, including loan burdens, housing status and quality (material factors) as well as financial and occupational worries, housing and income satisfaction (perceived economic factors), were analyzed dichotomously. Exposure duration was calculated as observed years in exposure for each of the factors, taking only continuous exposure years into account. The analyses were carried out separately for sex and life stages (emerging, early middle & later middle, late adulthood) using fixed effects models to adjust for time-varying covariates.ResultsThe analyses showed accumulation processes associated with housing status, financial worries and income satisfaction impacting SRH across most life stages. The effects of continuing exposure to occupational worries, housing satisfaction, housing quality, and loan burdens were more variable, indicating accumulation processes in certain life stages and sex-specific variations.ConclusionsWhile predominantly accumulation effects were found for certain factors, others showed more varied patterns. Future research should explore the mechanisms underlying these effects to develop well-timed measures that mitigate the negative health implications of continuing exposures to disadvantageous factors, emphasizing the importance of multiple exposures and later life health effects that may impede healthy ageing.

Effects of maternal healthcare service utilization on modern postpartum family planning access in Bangladesh: insights from a National representative survey.

Access to modern family planning is critical for improving maternal and child health outcomes, yet it remains severely lacking in low- and middle-income countries, including Bangladesh. Maternal healthcare utilization during and after pregnancy is vital for promoting postpartum family planning. This study examined the effects of maternal healthcare service utilization on postpartum family planning uptake in Bangladesh. Reproductive calendar data from 4,081 women with recent live births were extracted from the cross-sectional 2017/18 Bangladesh Demographic and Health Survey and analyzed. The outcome variable was uptake of modern postpartum family planning methods and the exposure variables were different types of maternal healthcare services. Kaplan-Meier methods were used to calculate cumulative probabilities of modern postpartum family planning method uptake within 12 months post-delivery, and modified Poisson regression models were used to estimate the effects of utilizing maternal healthcare services on modern postpartum family planning method uptake. Modern family planning methods in the 12 month postpartum period were used by 72% of women, with over 60% starting after day 40. Less than 4% used long-acting family planning methods, while almost 40% relied on the oral contraceptive pill. Utilizing maternal healthcare services was associated with up to a 7% higher uptake of modern postpartum family planning methods compared to non-users. Three-quarters of Bangladeshi women use modern family planning within the 12 months postpartum, but often rely on less effective methods. Additionally, 25% of these women resort to traditional or no use of contraceptive methods, increasing the risks of unintended pregnancy, short birth intervals, and adverse maternal and infant health outcomes. Maternal healthcare services, including private facilities, should prioritize modern postpartum family planning provision, along with education and counseling on the benefits of long-acting contraception.

The Mediation Effects of Self-Efficacy on the Relationship Between Diabetes-Related Content Exposure and Self-Management Among Older Diabetics: A Cross-Sectional Study.

To map the diabetes-related content exposure of older adults with Type 2 diabetes mellitus, and explore the association between the exposure and self-management and the mediation effects of self-efficacy. Cross-sectional study. This study was conducted among 257 eligible older adults with Type 2 diabetes mellitus from five communities in China. Diabetes self-management and self-efficacy were measured with standardised assessment tools. The variable of diabetes-related content exposure was generated by the collection of all content exposure and the transformation of Q-methodology. Descriptive statistics and the relative mediation effect model were used to do the analyses. Among the participants, 61.1% had hyperbeneficial content exposure, 13.6% had hypobeneficial content exposure, 24.9% had irrelevant content exposure, and 0.4% had harmful content exposure. Compared with those with irrelevant content exposure, older adults with hyperbeneficial content exposure exhibited higher self-management scores (β = 0.448, 95% CI = 0.174-0.721); in the mediation model, the relative direct effect of hyperbeneficial content exposure on self-management remained significant (β = 0.377, 95% CI = 0.104-0.650), and self-efficacy significantly mediated this relationship (β = 0.071, 95% CI = 0.011-0.154). The relative mediation effect accounted for 15.8% of the relative total effect. Conversely, no significant effect of hypobeneficial content exposure on self-management was observed. Social media can empower the self-management of older adults with Type 2 diabetes mellitus exposed to hyperbeneficial contents, with self-efficacy serving as a significant mediator. In contrast, exposure to hypobeneficial contents on social media did not lead to significant improvement in the self-management. This suggests that not all diabetes-related contents on social media are equally beneficial, and the relevance of information matters. Healthcare providers should consider leveraging social media platforms in conjunction with traditional education programmes to enhance the self-management of older adults with Type 2 diabetes mellitus. Older adults with Type 2 diabetes mellitus may search positively diabetes-related hyperbeneficial contents on social media. The report of this study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement guidelines. No patient or public contribution.

Impact of smoking habits on cardiovascular and neoplastic events and all-cause death in people with HIV from the STOPSHIV cohort.

The study aimed to assess the impact of smoking exposure on major clinical events (MCEs) in a real-life setting of people with HIV (PWH). An observational, longitudinal, multicenter cohort study from Italy. Consecutive 983 PWH were enrolled in "STOP Smoking in HIV people" (STOPSHIV) projects and followed from July 2014 until September 2023. The observed MCE defined as cardiovascular events, neoplastic diseases, or death for any reason was assessed according to smoking status and related variables (number of cigarettes smoked daily, pack-years, Fagerström test) in participants. The association between exposure variables and the event was evaluated using the Cox proportional hazard model [hazard ratios, and 95% confidence interval (95% CI)]. Over 6997.6 person-years of follow-up (PYFU), we found a total of 49 cardiovascular events, 61 neoplastic events, and 47 deaths. The overall incidence rate of MCE was 17.6 /1000 PYFU (95% CI 14.7-21.0). All-cause death rate was 6.7 (95% CI 5.0-8.9)/1000 PYFU. In a multivariate analysis, older age (hazard ratio 1.07, CI 1.05-1.09), high Fagerström Test for Nicotine Dependence (hazard ratio 1.09, CI 1.03-1.15), a low nadir CD4 + cell count less than 200 cells/μl (hazard ratio 1.63, CI 1.10-1.41), history of previous neoplasm (hazard ratio 2.41; CI 1.34-4.43), and IDU as a risk factor for HIV infection (hazard ratio 2.36; CI 1.52-3.68) were independent predictors of any MCE. Non-AIDS clinical conditions are the most observed clinical events in PWH from Italy. Smoking exposure significantly increases the risk of MCE in PWH, and a high Fagerström Test for Nicotine Dependence is a predictor of MCE.

Abstract TMP97: Association Between Race/Ethnicity and New Onset Atrial Fibrillation and Stroke Following Noncardiac Surgery

Background: Racial differences in postoperative atrial fibrillation (POAF) and stroke rates following noncardiac surgery are not well understood and may be influenced by varying betablocker prescription patterns. 1 Methods: This multicentric retrospective observational study included 205,886 adult patients without pre-existing atrial fibrillation who underwent non-cardiac surgery between 2005 and 2021 at two tertiary care academic healthcare networks in the Bronx, New York, and Boston, Massachusetts. The study population consisted of 133,500 (65%) Non-Hispanic White (NHW), 38,237 (19%) Non-Hispanic Black (NHB), and 34,149 (17%) Hispanic individuals. The exposure variable was self-identified race and ethnicity with NHW patients serving as the reference group. The incidence of POAF within 30 days of surgery and postoperative stroke within the first year after the procedure were assessed. Modified Poisson regression with robust error variances was used to evaluate the association between race/ethnicity and POAF and postoperative stroke, adjusting for pre-defined confounders. Mediation analysis was used to determine whether beta-blocker use modified the association between race/ethnicity and stroke. Results: NHB and Hispanic patients were less likely to develop POAF than NHW patients (NHB: RRadj = 0.59; 95%CI: 0.52-0.68; P < .001; Hispanic: RRadj = 0.65; 95%CI: 0.56-0.76; P < .001) but more likely to experience postoperative stroke (NHB: RRadj = 1.39; 95%CI, 1.30-1.49; P < .001; Hispanic: RRadj = 1.34; 95%CI, 1.24-1.46; P < .001). NHB and Hispanic patients were also more likely to be on preexisting beta-blocker therapy than NHW patients (NHB: RRadj = 1.10; 95%CI: 1.07-1.14; P < .001; Hispanic: RRadj = 1.07; 95%CI: 1.03-1.12; P < .001). Beta-blocker use was significantly associated with an increased risk of postoperative stroke (RRadj = 1.17; 95%CI: 1.11-1.24; P < .001) and explained 16% (95%CI: 14%-20%) and 20% (95%CI: 16%-26%) of the variability in postoperative stroke rates among NHB and Hispanic patients, respectively. Conclusion: NHB and Hispanic patients are at higher risk of developing postoperative stroke following noncardiac surgery compared to NHW patients, despite having a lower risk of POAF. This increased stroke risk may be partially attributable to the higher likelihood of preoperative beta-blocker prescriptions in these populations. Reference 1 - POISE Study Group. The Lancet. 2008 May 31;371(9627):1839-47.

Association of active commuting with incidence of depression and anxiety: prospective cohort study.

Evidence is limited on the incidence of depression and anxiety in relation to active commuting. Our study aimed to explore their association and examine the mediating role of inflammatory. This study included 240,547 workers in the UK Biobank. The exposure variable was the mode of transport used to get to and from work including active (walking, cycling, mixed mode) and non-active commuting (car or public transport). The incidence of depression and anxiety was defined using ICD-10 codes. Cox proportional hazard regression models were used to explore the hazard ratios (HRs) of active commuting with depression and anxiety, and mediation analyses were used to test the mediating role of inflammatory in this association. There were 10,862 depression and 9407 anxiety events. Active commuting was associated with lower risk of depression [cycling: HR 0.775, 95% confidence interval (0.674-0.890); mixed mode walking: 0.858 (0.800-0.919); mixed mode cycling: 0.821 (0.744-0.907)] and anxiety [cycling: 0.781 (0.675-0.904); mixed mode walking: 0.867 (0.805-0.934); mixed mode cycling 0.810 (0.728-0.902)], and there were distinct dose-response trends between commuting distance and incidence of depression or anxiety. Inflammatory explained 19.75% of the association between cycling with depression, and 18.05% with anxiety. There were interactions between commuting and occupation type. Cycle and mix mode commuting were associated with lower risk of depression and anxiety, and inflammation partially mediated these association. Implementing initiatives that facilitate active commuting may help alleviate the poor mental health.

Exploring air temperature variability and socio-demographic inequalities in heat exposure through machine learning: A case study of Maricopa County, Arizona

Exploring air temperature variability and socio-demographic inequalities in heat exposure through machine learning: A case study of Maricopa County, Arizona

The association between personality traits and myocardial infarction- A European cross-sectional study.

Myocardial infarction (MI) is a serious condition that increases with age. It is valuable to identify the reasons why some are affected, and possibly, why different personality traits can be associated with an increased or decreased risk for myocardial infarction. This is a cross-sectional study based on wave 7 data from the Survey of Health, Ageing and Retirement in Europe (SHARE). A total of 52,231 individuals aged 50years or older were included in the study. The Big Five personality traits constituted the main exposure variables and were analyzed separately. The value of each personality trait variable was standardized. The association between each personality trait and MI was examined by logistic regression models which were used to estimate the Odds Ratios (ORs) and 95% Confidence Intervals (CIs). A total of 6336 participants reported having a MI in this study. The odds of MI were higher in individuals with greater Neuroticism (OR: 1.15, 95% CI: 1.12-1.18). Higher Conscientiousness was associated with decreased odds of MI (OR: 0.96, 95% CI: 0.94-0.99). Higher Agreeableness was associated with lower odds of MI (OR: 0.96, 95% CI: 0.94-0.99). There were no significant associations between Openness or Extraversion and the odds of MI, respectively. Higher Neuroticism was associated with increased odds of MI. Higher Agreeableness and Conscientiousness were associated with decreased odds of MI, respectively. Our study is of interest for the prevention of MI.

The influence of depression on esophageal cancer outcomes: Using the National Inpatient Sample (NIS) 2021.

338 Background: Esophageal cancer (EC) remains a challenging malignancy with high morbidity and mortality rates. Depression is prevalent among cancer patients and has been shown to affect various clinical outcomes. This study aims to evaluate the impact of depression on mortality, length of stay (LOS), and hospitalization charges in patients with esophageal cancer using data from the NIS. Methods: We conducted a retrospective, population-based study using the NIS data to analyze patients diagnosed with esophageal cancer. Depression was the primary exposure variable using the appropriate ICD-10 code. We applied survey-weighted descriptive statistics, logistic regression, and linear regression models to assess outcomes, adjusting for demographic and clinical factors, including age, sex, race, comorbidities (Charlson Comorbidity Index), hospital teaching status, and regional characteristics. Results: A total of 40,855 patients with esophageal cancer were included, with 11.4% (n = 4,855) having a concurrent diagnosis of depression. The unadjusted mortality rate for the cohort was 9.18%, with depressed patients showing a lower mortality rate (6.45% vs. 9.53%, p = 0.0018). After adjusting for covariates, depression was associated with significantly lower in-hospital mortality (adjusted OR 0.63, 95% CI 0.48–0.83, p = 0.001). While the unadjusted mean length of stay (LOS) was slightly higher in depressed patients (7.66 vs. 7.25 days, p = 0.132), adjusted models showed no significant difference (β = 0.42 days, p = 0.132). Depression was associated with lower unadjusted total hospitalization charges ($92,321 vs. $104,156, p = 0.023), and in adjusted analyses, depressed patients incurred significantly lower costs (β = -$10,327, 95% CI -$19,233 to -$1,421, p = 0.023). Significant predictors of increased hospitalization charges included teaching hospital status (β = $34,029, p < 0.0001) and large hospital size (β = $38,481, p < 0.0001). Conclusions: Depression, while common among patients with esophageal cancer, was unexpectedly associated with lower in-hospital mortality, despite a longer length of stay and higher comorbidity burden. This suggests that depressed patients may receive more comprehensive or prolonged care, which could contribute to their reduced mortality risk. Additionally, despite extended hospital stays, these patients incurred significantly lower hospitalization costs, indicating possible differences in resource utilization or treatment intensity. These findings highlight the complex relationship between mental health and cancer outcomes, emphasizing the need for further research to explore the mechanisms behind these associations and to better tailor care for esophageal cancer patients with depression.

Association between the triglyceride glucose body mass index and asthma: evidence from NHANES 2011–2018

BackgroundAsthma is a common chronic respiratory disease whose increasing prevalence poses a significant burden to human health and the economy. Several studies indicate that insulin resistance (IR) is associated with asthma development. The triglyceride-glucose body mass index (TyG-BMI) is a novel biomarker used to evaluate insulin resistance; however, limited research exists on the relationship between TyG-BMI and asthma. This study aimed to investigate the relationship between TyG-BMI and asthma in U.S. adults.MethodThis cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) database for the 2011–2018 cycles. The exposure variable was the TyG-BMI of participants at baseline, which was calculated based on triglycerides (TG), fasting blood glucose (FBG), and body mass index (BMI). The primary outcome variable was asthma status, determined via questionnaire. We analyzed participants’ baseline characteristics and employed weighted multivariate logistic regression models to assess the correlation between TyG-BMI and asthma. A subgroup analysis was conducted to assess whether the relationship between TyG-BMI and asthma was influenced by other factors.ResultsIn total, 8,553 participants were analyzed, revealing a positive association between TyG-BMI and asthma. In the analysis of TyG-BMI as a continuous variable, after adjusting for confounding variables, the Odds ratio (OR)(95% CI) for the association between TyG-BMI and asthma was 1.003. After further dividing TyG-BMI into quartiles and adjusting for potential confounders in Model 3, the prevalence of asthma was 0.561 times higher in those with the highest TyG-BMI than in those in the lowest quartile (OR: 1.561, 95% CI: 1.181, 2.065). There was a significant interaction between asthma and TyG-BMI among subgroups defined by gender, coronary heart disease, and stroke (interaction P < 0.05).ConclusionsThis cross-sectional study found a positive association between TyG-BMI and asthma. These results suggest that TyG-BMI has the potential to be used as an indicator to monitor the prevalence of asthma, but further longitudinal studies are needed to confirm causality and to assess its utility in the management of long-term comorbidities.Clinical trial numberNot applicable.

Methyltrimethoxysilane (MTMS).

Methyltrimethoxysilane (MTMS) has been used as a coupling agent in thermoplastics and thermosetting resins, a cross-linker in silicone sealants, a water repellent component, and in silicone hard-coats for plastics. Acute studies in experimental animals showed a low order of toxicity for MTMS via oral, dermal, and inhalation routes. MTMS was slightly irritating to both eyes and skin in rabbits. A weight of evidence assessment supports that MTMS is not a dermal sensitizer. Available in vitro and in vivo assays indicated MTMS has a low potential for genotoxicity. MTMS did not produce any changes in either reproductive or developmental parameters. Short-term, repeated inhalation in rats produced treatment-related observations in the urinary bladder and kidney. In a 90-day inhalation study in rats, MTMS was associated with production of urinary bladder epithelial hyperplasia, calculi formation, and moderate kidney dilation with hyperplasia of the pelvic epithelium and granulomatous inflammation. However, an expert panel review concluded that changes in the bladder and kidney were adaptive responses to physical or chemical irritation. The NOAEL of 100 ppm (557mg/m3) from the 90-day inhalation study was considered the point of departure for the health-based WEEL derivation. After adjusting to account for duration of exposure and interindividual variability, the resulting 8-h TWA WEEL value of 10 ppm (55mg/m3) is fully expected to provide a significant margin of safety against potential adverse health effects in workers.

Prediction of long-term drug-free outcomes in ACPA-positive and ACPA-negative rheumatoid arthritis by combined clinical and ultrasound assessment of residual disease: a 5-year prospective study

ObjectiveTo delineate, within the framework of current clinical practice and criteria, the sustainability of first-line immuno-suppressive treatment discontinuation in rheumatoid arthritis (RA) and the impact of residual disease in remission...

210. Implementation of a Pharmacist Driven Beta-lactam Therapeutic Drug Monitoring Program with Daily Result Reporting: Initial Experiences and Challenges Faced

Abstract Background Beta-lactam (BL) antibiotics are a cornerstone of treatment for patients with serious infections. Individualized BL dosing using therapeutic drug monitoring (TDM) is an emerging approach to address variability in BL exposure that adversely impacts PK/PD; however, challenges can emerge when implementing TDM programs in the real-world. We sought to characterize the implementation of a BL TDM program by describing initial successes and challenges. Methods In September 2023, we implemented a front-line pharmacist driven BL TDM clinical protocol (Figure 1) with daily result reporting for the following BLs: cefepime (FEP), meropenem (MEM), and piperacillin-tazobactam (TZP). Patients with FEP, MEM, and TZP plasma TDM data analyzed between September 26th, 2023 and March 31st, 2024 were included. TDM results were interpreted using Bayesian analysis (InsightRX). For each TDM event, we characterized ordering provider specialty, whether or not TDM was performed per protocol, whether or not changes were made in response to TDM results, Bayesian model fitness, treatment indication, culture information, and PK/PD target attainment [including predicted steady state trough concentration (Ctrss) and fT&amp;gt; 1xMIC and fT&amp;gt; 4xMIC]. Results Eighty-two BL TDM levels were obtained in 47 patients. FEP was most frequently monitored (70.7%). Model fit was good or intermediate in &amp;gt; 95% of cases (Table 1). The most common treatment indications were HAP/VAP (n=12, 25.5%), surgical prophylaxis (n=6, 12.8%), bone/joint (n=6, 12.8%), and CNS infection (n=6, 12.8%) (Table 2). Dose adjustments were made in 34% (n=16) of patients. In 57.4% of patients the level order or dose-adjustment deviated from recommended protocols. Targets of 100% fT&amp;gt; MIC and 100% fT&amp;gt; 4xMIC were achieved in 91.5% and 61.7% of patients, respectively (Table 3). Ctrss was above goal in 21% of patients. Conclusion We found that &amp;gt; 90% of patients undergoing BL TDM achieved 100% fT&amp;gt; MIC, whereas nearly 40% failed to achieve 100% fT&amp;gt; 4xMIC at baseline, and &amp;gt; 20% had a Ctrss exceeding safety goals. BL TDM resulted in dose or agent change over 60% of the time, but protocol deviations in dose adjustment were common. The frequency of interventions observed underscores the potential clinical impact of BL TDM on a broader scale when daily reporting is available. Disclosures Nathaniel J. Rhodes, PharmD MS, Apothecademy, LLC: Advisor/Consultant

P-1778. Factors Underlying Infection-Related Mortality: Learnings from an Academic Institution with Antimicrobial Stewardship Practices

Abstract Background Limited research has explored the efficacy of Antimicrobial Stewardship (AMS) interventions in reducing Infection-Related Mortality (IRM). This study aims to evaluate the impact of AMS practices on IRM and its associated factors. Methods A retrospective case-cohort study was conducted on inpatients who expired during hospitalization between May 1, 2022, and April 30, 2023, in a tertiary hospital. The case group comprised patients with infection-related mortalities, defined as deaths caused by any potential life-threatening infection, such as sepsis, pneumonia, infective endocarditis, peritonitis, encephalitis, abscesses, meningitis, empyema, pyelonephritis, and cholecystitis. Patients who expired without such infections constituted the control group. The primary exposure variable was adherence to AMS practices during the hospital stay. A Binomial Logistic Regression model was employed to identify risk factors (e.g., age, sex, recent multi-drug-resistant organism culture positivity) for infection-related mortality in both AMS-adherent and non-adherent groups. Results Among the 1225 total mortalities, 41.3% (=506) represents the case group. It was found that only recent multi-drug resistant organism culture positivity has a significant association with AMS adherence (odds ratio =0.328 &amp; p =0.003). The statistical modeling of both groups depicted in figure 1&amp;2. Conclusion Despite adherence to AMS practices, the presence of multi-drug-resistant organism culture positivity predisposes individuals to infection-related mortality. Disclosures All Authors: No reported disclosures

Ceftaroline versus vancomycin for methicillin-resistant Staphylococcus aureus bacteraemia, a matched cohort study.

Vancomycin remains the treatment-of-choice in MRSA bacteraemia (MRSAB) despite significant limitations. To compare the effectiveness of ceftaroline and vancomycin monotherapy as the initial targeted therapy for MRSAB. We conducted a retrospective matched cohort study. Consecutive adult patients treated with ceftaroline in the years 2019-2021 were matched in a 1:2 ratio with patients who received vancomycin. Controls were matched for performance of trans-oesophageal echocardiography, Charlson comorbidity index and age. The primary outcome was a composite of treatment failure, defined as 90-day mortality or microbiological failure. Descriptive statistics were used to compare the ceftaroline and vancomycin-treated groups. Univariate and multivariable binary logistic regression models were created using ceftaroline treatment as the exposure variable. Forty-five patients treated with ceftaroline for MRSAB were matched with 83 patients who received vancomycin. The groups were well balanced with regards to demographics and clinical characteristics. The primary outcome of treatment failure occurred at a similar rate in patients treated with ceftaroline or vancomycin (51.1%, 23/45% versus 57.8%, 48/83, respectively, P = 0.47). In the multivariable analysis, only age (aOR 1.06, 95% CI 1.01-1.1, P = 0.02) was associated with treatment failure. Acute kidney injury was more common among patients treated with ceftaroline (51.1%, 23/45% versus 18.1%, 15/83, P < 0.001). Ceftaroline was not associated with improved outcomes compared to vancomycin when given as initial treatment for MRSAB, however, it appears to be a viable alternative to vancomycin. Larger studies are needed to provide definitive results and to elucidate the risk of nephrotoxicity.

Evaluation of the Effect of Loperamide on the Cardiac Repolarization Interval Using Exposure-Response Analysis.

This analysis assessed the relationship between the plasma concentrations of loperamide and its N-desmethyl loperamide meta- bolite (M1) and the potential QT interval prolongation at therapeutic and supratherapeutic doses. The exposure-response analysis was performed using the data from healthy adults participating in a randomized, double-blind, single-dose, four-way (placebo; loperamide 8 mg [therapeutic]; loperamide 48 mg [supratherapeutic]; moxifloxacin 400 mg [positive control]) crossover study. The electrocardiographic measurements extracted from 12-lead digital Holter recordings were time-matched to pharmacokinetic sampling of loperamide/M1. The primary response variable was placebo-adjusted change from baseline in Fridericia-corrected QT interval (ΔΔQTcF); the exposure variable was loperamide and/or M1 concentration. A total of 53 participants with 1408 time-matched pharmacokinetic and ΔΔQTcF measurements was analyzed. Hysteresis between both loperamide and M1 concentrations and ΔΔQTcF was observed with supratherapeutic dose. The pre-specified linear concentration-ΔΔQTcF relationship was driven by M1 concentrations in the effect compartment. The model-predicted mean ΔΔQTcF at the geometric mean of the maximum concentration in the effect compartment was -0.526 msec (90% CI, -1.51 to 0.462) following 8-mg dose (2.1 ng/mL) and 6.06 msec (90% CI, 3.86-8.27) following 48-mg dose (14.2 ng/mL). The upper bound of two-sided 90% CI was < 10 msec for both doses. The sensitivity analysis considering loperamide concentrations in the effect compartment instead of M1 as input for the concentration-ΔΔQTcF analysis confirmed these findings. The data showed that loperamide or M1 does not have an effect on cardiac repolarization that exceeds the threshold of regulatory concern in healthy participants at doses of 8 and 48 mg.

Binge eating behaviours are associated with recurrent weight gain after metabolic and bariatric surgery.

Recurrent weight gain (RWG) is a major post-operative challenge among metabolic and bariatric surgery (MBS) patients. Binge eating behaviours (BEB) and food addiction (FA) have been identified as significant predictors of post-MBS RWG. However, limited research has investigated their independent associations with post-MBS RWG. This cross-sectional study collected data via a self-reported questionnaire of post-MBS patient demographics and eating behaviours from a single-site academic obesity medicine program. The Binge Eating Scale and Yale Food Addiction Scale 2.0 collected data on BEB and FA exposure variables, respectively. ANOVA/chi-square tests determined bivariate associations with BEB and FA, while multivariable logistic regression models examined independent adjusted associations of BEB and FA with RWG% cut-offs. Of the 294 MBS patients (90.48% female, and 51.71% non-Hispanic white), 42.3% had BEB, 12.55% had severe FA, 7.36% moderate FA, and 7.36% mild FA. After adjustment, BEB was significantly associated with all magnitudes of post-MBS RWG, with the highest odds observed at 50% RWG [OR = 3.07; 95% CI: 1.45, 6.49; p = 0.003]. FA was not significantly associated with post-MBS RWG. Results showed that BEB, but not FA, was associated with post-MBS RWG. MBS patient support teams should consider screening for BEB at post-MBS visits.

Prolonged screen time is associated with increased severity of tic symptoms in children with tic disorders

BackgroundRecent studies have emphasized the association between prolonged screen exposure and neurodevelopmental disorders, though its correlation with tic disorders (TDs) remains ambiguous. We thus conducted this study to investigate the association between screen time (ST) and the severity of tic symptoms in children diagnosed with TDs.MethodsWe conducted a retrospective case-control study with 342 cases of TDs and 270 controls, collecting data from March 2021 to December 2023. The main exposure variable was daily ST for each child, and tic severity, evaluated using the Yale Global Tic Severity Scale (YGTSS), was the outcome variable. Statistical analysis included descriptive statistics, Pearson’s correlation analysis to examine the relationship between screen time and tic severity, and multivariate regression analysis to evaluate the predictive power of screen time for tic symptoms.ResultsOur findings revealed that children with TDs had significantly longer ST compared to the control group, averaging 116.06 ± 147.9 min/day versus 43.23 ± 37.5 min/day, p < 0.001. We also noted a positive correlation between ST and TDs( r = 0.461, p < 0.01). Daily ST was a significant predictor of overall YGTSS scores (t = 9.58, p < 0.001), suggesting that increased ST is associated with heightened tic symptoms. However, age of first exposure to screens was not significantly correlated with tic severity (p > 0.05). Though we observed a negative correlation between ST and vitamin D levels, the results were not statistically significant (p > 0.05).ConclusionChildren with TDs had longer ST compared to their control’s counterparts, and prolonged ST was significantly associated with heightened tic severity, which highlights the critical need for careful monitoring and regulation of screen time in children with TDs.

Factoring fu Variability Into Estimates of Unbound Drug Concentrations Negatively Biases the MIC Versus% Probability of Target Attainment Relationship of Antimicrobial Agents.

The clinical breakpoint for a drug-pathogen combination reflects the drug susceptibility of the pathogen wild-type population, the location of the infection, the integrity of the host immune response, and the drug-pathogen pharmacokinetic (PK)/pharmacodynamic (PD) relationship. That PK/PD relationship, along with the population variability in drug exposure, is used to determine the probability of target attainment (PTA) of the PK/PD index at a specified minimum inhibitory concentration (MIC) for a selected target value. The PTA is used to identify the pharmacodynamic cutoff value (COPD), which is one of the three components used to establish the clinical breakpoint. A challenge encountered when defining the COPD is that the available PK information typically reflects total (free plus protein-bound) plasma concentrations. However, it is the unbound drug concentrations that exert the therapeutic effects and how the population fraction unbound (fu) incorporated into the COPD assessments can markedly influence the COPD. Factors examined included the estimated population fu mean (risk of bias) and the incorporation of estimated fu population variability into the Monte Carlo simulations when converting total to unbound plasma concentrations (risk of inflating variability). In this in silico study, the drug fu, systemic clearance, and the variability of both were altered so that the relative impact of each could be explored. We demonstrate that incorporating fu variability into the estimation of fAUCback can bias the COPD assessment and that the magnitude of bias reflects the relative variability in systemic clearance and fu.