JAMA Netw Open. 2024 Aug 1;7(8):e2430989. doi: 10.1001/jamanetworkopen.2024.30989.
NO ABSTRACT
PMID:39196561 | DOI:10.1001/jamanetworkopen.2024.30989
JAMA Netw Open. 2024 Aug 1;7(8):e2429654. doi: 10.1001/jamanetworkopen.2024.29654.
ABSTRACT
IMPORTANCE: The widespread use of antihistamines in children for treatment of common cold symptoms and their central nervous system effects, like drowsiness, underscore the importance of being aware of the associated risks.
OBJECTIVE: To assess associations between prescriptions of first-generation antihistamines and seizures in children using a comprehensive and nationwide dataset.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a self-controlled case-crossover design. Data were obtained from the National Health Insurance Service database in Korea. Children born between January 1, 2002, and December 31, 2005, who visited the emergency department for seizure events (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes R56.8, G40, and G41) during the follow-up period were included. Follow-up was completed on December 31, 2019, and data were analyzed from June 3, 2023, to January 30, 2024.
EXPOSURE: First-generation antihistamine prescription.
MAIN OUTCOMES AND MEASURES: Primary outcome consisted of an index seizure event. Odds ratios (ORs) for seizure events were estimated using a conditional logistic regression model, comparing first-generation antihistamine prescription 1 to 15 days before seizure (hazard period) against control period 1 (31-45 days before the event) and control period 2 (61-75 days before the event) using the same period windows. Stratified analyses were conducted to examine the association with individual participant characteristics.
RESULTS: Of 11 729 children who had a seizure event, 3178 (1776 [55.9%] boys) were identified as having been prescribed antihistamines during the hazard or the control period, but not both. Seizure events were predominantly observed in children aged 6 to 24 months (985 [31.0%]) and 25 months to 6 years (1445 [45.5%]). During the hazard period, 1476 first-generation antihistamine prescriptions were recorded, in contrast to 1239 and 1278 prescriptions during control periods 1 and 2, respectively. After multiple confounder adjustments, first-generation antihistamine prescription was associated with an increased seizure event risk during the hazard period (adjusted OR [AOR], 1.22 [95% CI, 1.13-1.31]). Stratified subgroup analyses showed consistent results, particularly in children aged 6 to 24 months who were prescribed first-generation antihistamines having a higher risk (AOR, 1.49 [95% CI, 1.31-1.70]) than children aged 25 months to 6 years (AOR, 1.11 [95% CI, 1.00-1.24]; P = .04 for interaction). Furthermore, sensitivity analyses, including adjustment for exposure window periods, evaluation of new first-generation antihistamine prescriptions, comparison of control points from the same period 1 year prior, and exclusion of individuals using combination drugs, confirmed a similarly high risk.
CONCLUSIONS AND RELEVANCE: In this cohort study, prescriptions for first-generation antihistamines were associated with a 22.0% higher seizure risk in children, especially in those aged 6 to 24 months. These findings emphasize the need for careful and judicious prescription of first-generation antihistamines in young children and underline the need for further research to elucidate associations between antihistamine prescriptions and seizure risk.
PMID:39196558 | DOI:10.1001/jamanetworkopen.2024.29654
JAMA Netw Open. 2024 Aug 1;7(8):e2430700. doi: 10.1001/jamanetworkopen.2024.30700.
ABSTRACT
IMPORTANCE: Previous studies on alcohol consumption and incident gout have mostly included men or combined both sexes, and the sex-specific associations between alcohol consumption and gout are poorly understood.
OBJECTIVE: To evaluate the consumption of total and specific alcoholic beverages in association with incident gout in men and women.
DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 401 128 participants in the UK Biobank aged 37 to 73 years who were free of gout at baseline (2006-2010). Participants were followed up through December 31, 2021, and data were analyzed between August 2023 and June 2024.
EXPOSURE: Questionnaire-based consumption of total alcohol and specific alcoholic beverages.
MAIN OUTCOMES AND MEASURES: The outcome was incident gout, identified using hospital records. Multivariable Cox proportional hazards regression models were used to estimate sex-specific hazard ratios (HRs) and 95% CIs of incident gout associated with alcohol consumption, with a particular consideration of reverse causation bias.
RESULTS: The main analysis included 179 828 men (mean [SD] age, 56.0 [8.2] years) and 221 300 women (mean [SD] age, 56.0 [8.0] years). Current drinkers showed a higher risk of gout than never drinkers among men (HR, 1.69; 95% CI, 1.30-2.18) but not among women (HR, 0.83; 95% CI, 0.67-1.03). Among current drinkers, higher total alcohol consumption was associated with a higher risk of gout among both sexes and more strongly among men than women (men: HR, 2.05 [95% CI, 1.84-2.30]; women: HR, 1.34 [95% CI, 1.12-1.61]). The most evident sex difference in the consumption of specific alcoholic beverages was observed for beer or cider (men: mean [SD], 4.2 [4.8] pints per week; women: mean [SD], 0.4 [1.1] pints per week). Consumption of champagne or white wine, beer or cider, and spirits each was associated with a higher risk of gout among both sexes, with beer or cider showing the strongest association per 1 pint per day (men: HR, 1.60 [95% CI, 1.53-1.67]; women: HR, 1.62 [95% CI, 1.02-2.57]). Some inverse associations between light to moderate consumption of specific alcoholic beverages and gout were eliminated after adjusting for other alcoholic beverages and excluding individuals who had reduced alcohol consumption for health reasons, self-reported poor health, or had cardiovascular disease, cancer, or kidney failure at baseline, or developed gout within the first 2 years of follow-up.
CONCLUSIONS AND RELEVANCE: In this cohort study, higher consumption of several specific alcoholic beverages was associated with a higher risk of gout among both sexes. The sex-specific associations for total alcohol consumption may be associated with differences between men and women in the types of alcohol consumed.
PMID:39196557 | DOI:10.1001/jamanetworkopen.2024.30700
JAMA Netw Open. 2024 Aug 1;7(8):e2430711. doi: 10.1001/jamanetworkopen.2024.30711.
ABSTRACT
IMPORTANCE: Adverse childhood experiences are pervasive and heterogeneous, with potential lifelong consequences for psychiatric morbidity and brain health. Existing research does not capture the complex interplay of multiple adversities, resulting in a lack of precision in understanding their associations with neural function and mental health.
OBJECTIVES: To identify distinct childhood adversity profiles and examine their associations with adolescent mental health and brain connectivity.
DESIGN, SETTING, AND PARTICIPANTS: This population-based birth cohort used data for children who were born in 20 large US cities between 1998 and 2000 and participated in the Future Families and Child Well-Being Study. Families were interviewed when children were born and at ages 1, 3, 5, 9, and 15 years. At age 15 years, neuroimaging data were collected from a subset of these youths. Data were collected from February 1998 to April 2017. Analyses were conducted from March to December 2023.
EXPOSURES: Latent profiles of childhood adversity, defined by family and neighborhood risks across ages 0 to 9 years.
MAIN OUTCOMES AND MEASURES: Internalizing and externalizing symptoms at age 15 years using parent- and youth-reported measures. Profile-specific functional magnetic resonance imaging connectivity across the default mode network (DMN), salience network (SN), and frontoparietal network (FPN).
RESULTS: Data from 4210 individuals (2211 [52.5%] male; 1959 [46.5%] Black, 1169 [27.7%] Hispanic, and 786 [18.7%] White) revealed 4 childhood adversity profiles: low-adversity (1230 individuals [29.2%]), medium-adversity (1973 [46.9%]), high-adversity (457 [10.9%]), and high maternal depression (MD; 550 [13.1%]). High-adversity, followed by MD, profiles had the highest symptoms. Notably, internalizing symptoms did not differ between these 2 profiles (mean difference, 0.11; 95% CI, -0.03 to 0.26), despite the MD profile showing adversity levels most similar to the medium-adversity profile. In the neuroimaging subsample of 167 individuals (91 [54.5%] female; 128 [76.6%] Black, 11 [6.6%] Hispanic, and 20 [12.0%] White; mean [SD] age, 15.9 [0.5] years), high-adversity and MD profiles had the highest DMN density relative to other profiles (F(3,163) = 11.14; P < .001). The high-adversity profile had lower SN density relative to the low-adversity profile (mean difference, -0.02; 95% CI, -0.04 to -0.003) and the highest FPN density among all profiles (F(3,163) = 18.96; P < .001). These differences were specific to brain connectivity during an emotion task, but not at rest.
CONCLUSIONS AND RELEVANCE: In this cohort study, children who experienced multiple adversities, or only elevated MD, had worse mental health and different neural connectivity in adolescence. Interventions targeting multiple risk factors, with a focus on maternal mental health, could produce the greatest benefits.
PMID:39196556 | DOI:10.1001/jamanetworkopen.2024.30711
Dokl Biochem Biophys. 2024 Aug 28. doi: 10.1134/S1607672924701084. Online ahead of print.
ABSTRACT
Netakimab has shown high efficacy in controlled clinical trials in the treatment of AS patients. This article presents results of an observational study of netakimab using in routine clinical practice.
OBJECTIVE: : To evaluate retention rates and safety of netakimab in patients with AS in real-world clinical practice. Additionally, the efficacy of netakimab was evaluated at 1-year follow-up.
MATERIALS AND METHODS: : Patients were recruited for the study from August 2020 to December 2021 at 23 centers in the Russian Federation. The study included patients who were prescribed netakimab therapy before enrollment, so clinical and medical history data for the first visit were entered retrospectively, and following visits at 12, 24, and 52 weeks of therapy were collected within the study. Drug survival rate was calculated according to Kaplan-Meier analysis.
RESULTS: : The study included 137 (93 men and 44 women) patients with AS. The average age of patients was 42.3 (11.9) years, 34.3% of patients had previously received therapy with bDMARD, mainly TNF inhibitors. At the end of the analyzed period (52 weeks of therapy), 90.4% (95% CI, 85.4-95.7) of patients continued treatment with netakimab. The BASDAI and ASDAS-CRP showed statistically significant decreases in scores from baseline at all time points. Netakimab was well tolerated by patients; AEs, related to therapy according to the investigator’s opinion, were reported in 7 (5.1%) patients. Two patients stopped taking netakimab due to AEs (terminal ileitis and chronic colitis).
CONCLUSIONS: : In real-world clinical practice, netakimab demonstrated high retention rates, a favorable safety profile, and sustained efficacy throughout the first year of therapy.
PMID:39196530 | DOI:10.1134/S1607672924701084
Curr Med Sci. 2024 Aug 28. doi: 10.1007/s11596-024-2916-9. Online ahead of print.
ABSTRACT
OBJECTIVE: Qiliqiangxin (QLQX) capsule- a traditional Chinese medicine used for treating heart failure (HF), can modulate inflammatory cytokines in rats with myocardial infarction. However, its immune-regulating effect on dilated cardiomyopathy (DCM) remains unknown. The aim of this study was to investigate whether QLQX has a unique regulatory role in the imbalance of pro- and anti-inflammatory cytokines in patients with DCM.
METHODS: The QLQX-DCM is a randomized- double-blind trial conducted at 24 tertiary hospitals in China. A total of 345 patients with newly diagnosed virus-induced DCM were randomly assigned to receive QLQX capsules or placebo while receiving optimal medical therapy for HF. The primary endpoints were changes in plasma inflammatory cytokines and improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) over the 12-month treatment.
RESULTS: At the 12-month follow-up, the levels of IFN-γ, IL-17, TNF-α, and IL-4 decreased significantly, while the level of IL-10 increased in both groups compared with baselines (all P<0.0001). Furthermore-these changes, coupled with improvements in LVEF, NT-proBNP and New York Heart Association (NYHA) functional classification, excluding the LVEDd in the QLQX group, were greater than those in the placebo group (all P<0.001). Additionally, compared with placebo, QLQX treatment also reduced all-cause mortality and rehospitalization rates by 2.17% and 2.28%, respectively, but the difference was not statistically significant.
CONCLUSION: QLQX has the potential to alleviate the imbalance of inflammatory cytokines in patients with DCM, potentially leading to further improvements in cardiac function when combined with anti-HF standard medications.
PMID:39196518 | DOI:10.1007/s11596-024-2916-9
Blood Res. 2024 Aug 28;59(1):29. doi: 10.1007/s44313-024-00023-9.
ABSTRACT
PURPOSE: This study aimed to investigate the pharmacokinetics (PK) of factor VIII (FVIII) in Korean patients, as limited information is available on the PK of FVIII in this population.
METHODS: We collected the FVIII PK results from patients with moderate-to-severe hemophilia A using myPKFiT. PK variations were assessed according to age, blood type, inhibitor history, von Willebrand factor antigen (vWF:Ag) level, and body mass index. Additionally, the correlation between the PK profile and prophylaxis regimen was specifically analyzed for each product in severe cases.
RESULTS: The PK data of 48 and 81 patients treated with octocog alfa and rurioctocog alfa pegol, respectively, were obtained. The median half-lives of octocog alfa and rurioctocog alfa pegol were 9.9 (range: 6.3-15.2) h and 15.3 (range: 10.4-23.9) h, respectively. The PK profiles for each product did not differ according to age group; however, blood type-O patients had shorter half-lives and time to 1% compared to non-blood type-O patients. In regression analysis, the PK of octocog alfa showed a statistically significant difference according to age, whereas the PK of rurioctocog alfa pegol correlated with vWF:Ag. Only the frequency of rurioctocog alfa pegol use showed a statistically significant difference in relation to time to 1%, although the coefficient of determination was small.
CONCLUSION: This study confirmed significant interpatient variation in the PK of FVIII among Korean patients with hemophilia A. To achieve optimized prophylaxis, personalizing the regimen based on the PK profile of each individual patient is essential.
PMID:39196490 | DOI:10.1007/s44313-024-00023-9
Eur J Clin Microbiol Infect Dis. 2024 Aug 28. doi: 10.1007/s10096-024-04921-9. Online ahead of print.
ABSTRACT
PURPOSE: Bacterial isolation is associated with worse outcomes after lung transplantation (LTx), and successful bacterial eradication is shown to improve long-term survival and pulmonary function. Outpatient Parenteral Antibiotic Therapy (OPAT) may be an effective therapeutic modality for bacterial eradication post-LTx.
METHODS: A single-center, retrospective analysis of OPAT characteristics, efficacy, safety, and costs in non-cystic fibrosis LTx recipients.
RESULTS: A total of 156 OPAT courses (from June 2019 to December 2022) were evaluated in 108 distinct LTx recipients. OPAT mainly consisted of dual antibiotic therapy (69%) for pulmonary bacterial isolation (97%), mostly Pseudomonas aeruginosa (66%). Successful eradication at 3 months post-OPAT was achieved in 71%. Eradication rate was significantly higher in patients treated after the first post-operative year (79%), compared to patients within the first year (61%) (p = 0.017). Eradication rate was similar for multidrug resistance (eradication rate 61%) versus no multidrug resistance (74%) (p = 0.116). Spirometry remained stable at 90 days post-OPAT. A statistically significant, but clinically negligible, increase in serum creatinine at 90 days post-OPAT was observed (1.33 mg/dL vs. 1.39 mg/dL, p < 0.001), yet unrelated to the antibiotic regimen used. OPAT-related hospital admissions occurred in 13% and line-related adverse events in 6%. Median number of hospitalization days saved per OPAT-course was 10 days (range 2-92), accounting for a total of 1841 avoided admission days and an estimated net cost reduction of 47% per treatment course.
CONCLUSION: OPAT is an effective and safe therapeutic modality for bacterial eradication post-LTx, associated with a significant reduction in hospitalization days and treatment costs.
PMID:39196488 | DOI:10.1007/s10096-024-04921-9
J Clin Monit Comput. 2024 Aug 28. doi: 10.1007/s10877-024-01211-9. Online ahead of print.
ABSTRACT
Pulse oximetry (SpO2) is a critical monitor for assessing oxygenation status and guiding therapy in critically ill patients. Race has been identified as a potential source of SpO2 error, with consequent bias and inequities in healthcare. This study was designed to evaluate the incidence of occult hypoxemia and accuracy of pulse oximetry associated with the Massey-Martin scale and characterize the relationship between Massey scores and self-identified race. This retrospective single institute study utilized the Massey-Martin scale as a quantitative assessment of skin pigmentation. These values were recorded peri-operatively in patients enrolled in unrelated clinical trials. The electronic medical record was utilized to obtain demographics, arterial blood gas values, and time matched SpO2 values for each PaO2 ≤ 125 mmHg recorded throughout their hospitalizations. Differences between SaO2 and SpO2 were compared as a function of both Massey score and self-reported race. 4030 paired SaO2-SpO2 values were available from 579 patients. The average error (SaO2-SpO2) ± SD was 0.23 ± 2.6%. Statistically significant differences were observed within Massey scores and among races, with average errors that ranged from – 0.39 ± 2.3 to 0.53 ± 2.5 and – 0.55 ± 2.1 to 0.37 ± 2.7, respectively. Skin color varied widely within each self-identified race category. There was no clinically significant association between error rates and Massey-Martin scale grades and no clinically significant difference in accuracy observed between self-reported Black and White patients. In addition, self-reported race is not an appropriate surrogate for skin color.
PMID:39196478 | DOI:10.1007/s10877-024-01211-9
Adv Health Sci Educ Theory Pract. 2024 Aug 28. doi: 10.1007/s10459-024-10365-9. Online ahead of print.
ABSTRACT
To design effective instruction, educators need to know what design strategies are generally effective and why these strategies work, based on the mechanisms through which they operate. Experimental comparison studies, which compare one instructional design against another, can generate much needed evidence in support of effective design strategies. However, experimental comparison studies are often not equipped to generate evidence regarding the mechanisms through which strategies operate. Therefore, simply conducting experimental comparison studies may not provide educators with all the information they need to design more effective instruction. To generate evidence for the what and the why of design strategies, we advocate for researchers to conduct experimental comparison studies that include mediation or moderation analyses, which can illuminate the mechanisms through which design strategies operate. The purpose of this article is to provide a conceptual overview of mediation and moderation analyses for researchers who conduct experimental comparison studies in instructional design. While these statistical techniques add complexity to study design and analysis, they hold great promise for providing educators with more powerful information upon which to base their instructional design decisions. Using two real-world examples from our own work, we describe the structure of mediation and moderation analyses, emphasizing the need to control for confounding even in the context of experimental studies. We also discuss the importance of using learning theories to help identify mediating or moderating variables to test.
PMID:39196469 | DOI:10.1007/s10459-024-10365-9