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Antithrombin during veno-venous extracorporeal membrane oxygenation with heparin anticoagulation:A single-center cohort study
No full textIntroduction: Antithrombin (AT) is a natural anticoagulant essential to enhancing the unfractionated heparin (UFH) anticoagulant effect. Its supplementation in the management of UFH-based anticoagulation during veno-venous extracorporeal membrane oxygenation (VV ECMO) has a strong pathophysiological rationale. Methods: This is a single-center, retrospective cohort study of adult VV ECMO patients with anticoagulation maintained by UFH targeting an activated partial thromboplastin time (aPTT) of 40–50 s and AT activity >80%. We compare anticoagulation management and survival outcomes between AT subpopulations, defined by a threshold AT activity ≥80%. Linear and logistic regression analyses were used to evaluate the variation in AT activity and its association with ICU survival. Results: In 244 patients enrolled from 2009 to 2022, anticoagulation was maintained by a median heparin dose of 11.4 IU/kg/h [IQR: 8.2–14.7] with a mean aPTT of 46.1 s (±7.3) and AT activity of 88.9% (±17.0). A lower mean aPTT, higher dose of UFH and shorter fraction of time without UFH were associated with higher AT activity (p <.01). Higher AT activity showed a consistent association with ICU survival (for 10% increase of AT, odds ratio for ICU mortality: 0.95; 95% CI 0.93–0.97; p value <.01). Conclusions: There is a positive association between AT activity and UFH requirements but no significant difference in the rate of bleeding events. A higher mean AT during VV ECMO was associated with ICU survival. Future studies are needed to differentiate between exogenously supplemented versus endogenous AT effect.</p
Suicidal Ideation and Suicide Attempts After Direct or Indirect Psychotherapy A Systematic Review and Meta-Analysis
Get PDFImportance Suicidal ideation and suicide attempts are debilitating mental health problems that are often treated with indirect psychotherapy (ie, psychotherapy that focuses on other mental health problems, such as depression or personality disorders). The effects of direct and indirect psychotherapy on suicidal ideation have not yet been examined in a meta-analysis, and several trials have been published since a previous meta-analysis examined the effect size of direct and indirect psychotherapy on suicide attempts. Objective To investigate the effect sizes of direct and indirect psychotherapy on suicidal ideation and the incidence of suicide attempts. Data Sources PubMed, Embase, PsycInfo, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials were searched for articles published up until April 1, 2023. Study Selection Randomized clinical trials of psychotherapy for any mental health problem, delivered in any setting, compared with any control group, and reporting suicidal ideation or suicide attempts were included. Studies measuring suicidal ideation with 1 item were excluded. Data Extraction and Synthesis PRISMA guidelines were followed. Summary data were extracted by 2 independent researchers and pooled using 3-level meta-analyses. Main Outcomes and Measures Hedges g was pooled for suicidal ideation and relative risk (RR) was pooled for suicide attempts. Results Of 15 006 studies identified, 147 comprising 193 comparisons and 11 001 participants were included. Direct and indirect psychotherapy conditions were associated with reduced suicidal ideation (direct: g, -0.39; 95% CI, -0.53 to -0.24; I-2, 83.2; indirect: g, -0.30; 95% CI, -0.42 to -0.18; I-2, 52.2). Direct and indirect psychotherapy conditions were also associated with reduced suicide attempts (direct: RR, 0.72; 95% CI, 0.62 to 0.84; I-2, 40.5; indirect: RR, 0.68; 95% CI, 0.48 to 0.95; I-2, 0). Sensitivity analyses largely confirmed these results. Conclusions and Relevance Direct and indirect interventions had similar effect sizes for reducing suicidal ideation and suicide attempts. Suicide prevention strategies could make greater use of indirect treatments to provide effective interventions for people who would not likely seek treatment for suicidal ideation or self-harm
Large language models to facilitate pregnancy prediction after in vitro fertilization
No full textWe evaluated the efficacy of large language models (LLMs), specifically, generative pre-trained transformer-4 (GPT-4), in predicting pregnancy following in vitro fertilization (IVF) treatment and compared its accuracy with results from an original published study. Our findings revealed that GPT-4 can autonomously develop and refine advanced machine learning models for pregnancy prediction with minimal human intervention. The prediction accuracy was 0.79, and the area under the receiver operating characteristic curve (AUROC) was 0.89, exceeding or being at least equivalent to the metrics reported in the original study, that is, 0.78 for accuracy and 0.87 for AUROC. The results suggest that LLMs can facilitate data processing, optimize machine learning models in predicting IVF success rates, and provide data interpretation methods. This capacity can help bridge the knowledge gap between data scientists and medical personnel to solve the most pressing clinical challenges. However, more experiments on diverse and larger datasets are needed to validate and promote broader applications of LLMs in assisted reproduction.</p
Failure to Rescue After Resection of Perhilar Cholangiocarcinoma in an International Multicenter Cohort
No full textBackground: Failure to rescue (FTR) is defined as the inability to prevent death after the development of a complication. FTR is a parameter in evaluating multidisciplinary postoperative complication management. The aim of this study was to evaluate FTR rates after major liver resection for perihilar cholangiocarcinoma (pCCA) and analyze factors associated with FTR. Patients and Method: Patients who underwent major liver resection for pCCA at 27 centers were included. FTR was defined as the presence of a Dindo grade III or higher complication followed by death within 90 days after surgery. Liver failure ISGLS grade B/C were scored. Multivariable logistic analysis was performed to identify predictors of FTR and reported using odds ratio and 95% confidence intervals. Results: In the 2186 included patients, major morbidity rate was 49%, 90-day mortality rate 13%, and FTR occurred in 24% of patients with a grade III or higher complication. Across centers, major complication rate varied from 19 to 87%, 90-day mortality rate from 5 to 33%, and FTR ranged from 11 to 50% across hospitals. Age [1.04 (1.02–1.05) years], ASA 3 or 4 [1.40 (1.01–1.95)], jaundice at presentation [1.79 (1.16–2.76)], right-sided resection [1.45 (1.06–1.98)], and annual hospital volume < 6 [1.44 (1.07–1.94)] were positively associated with FTR. When liver failure is included, the odds ratio for FTR is 9.58 (6.76–13.68). Conclusion: FTR occurred in 24% of patients after resection for pCCA. Liver failure was associated with a nine-fold increase of FTR and hospital volume below six was also associated with an increased risk of FTR.</p
Exploring the Interactions Between Psychotic Symptoms, Cognition, and Environmental Risk Factors:A Bayesian Analysis of Networks
No full textBackground and Hypothesis Psychotic disorders (PDs) have huge personal and societal impact, and efforts to improve outcomes in patients are continuously needed. Environmental risk factors (ERFs), especially modifiable risk factors, are important to study because they pose a target for intervention and prevention. No studies have investigated ERFs, cognition, and psychotic symptoms together in a network approach.Study Design We explored interactions between 3 important ERFs (tobacco smoking, cannabis use, and childhood trauma), 6 cognitive domains, and 3 dimensions of symptoms in psychosis. From the Genetic Risk and Outcome of Psychosis (GROUP) cohort, we used data from patients, siblings, and healthy controls to construct networks using Bayesian analyses of all 12 variables. We constructed networks of the combined sample and of patients and siblings separately.Study Results We found that tobacco smoking was directly associated with cognition and psychotic symptoms. The cognitive variable processing speed was the most central node, connecting clusters of psychotic symptoms and substance use through the variables of positive symptoms and tobacco smoking. Comparing the networks of patients and siblings, we found that networks were relatively similar between patients and siblings.Conclusions Our results support a potential central role of processing speed deficits in PDs. Findings highlight the importance of integrating tobacco smoking as potential ERFs in the context of PDs and to broaden the perspective from cannabis discontinuation to smoking cessation programs in patients or people at risk of PDs
A novel lineage-tracing tool reveals that hypoxic tumor cells drive tumor relapse after radiotherapy
No full textPurpose: Tumor hypoxia imposes a main obstacle to the efficacy of anti-cancer therapy. Understanding the cellular dynamics of individual hypoxic cells before, during and post-treatment has been hampered by the technical inability to identify and trace these cells over time. Methods and materials: Here, we present a novel lineage-tracing reporter for hypoxic cells based on the conditional expression of a HIF1a-CreER T2-UnaG biosensor that can visualize hypoxic cells in a time-dependent manner and trace the fate of hypoxic cells over time. We combine this system with multiphoton microscopy, flow cytometry, and immunofluorescence to characterize the role of hypoxic cells in tumor relapse after irradiation in H1299 tumor spheroids and in vivo xenografts. Results: We validate the reporter in monolayer cultures and we show that tagged cells colocalize in spheroids and human tumor xenografts with the hypoxic marker pimonidazole. We found that irradiation of H1299-HIFcreUnaG spheroids leads to preferential outgrowth of cells from the hypoxic core. Similarly, in xenografts tumors, although initially UnaG-positive-cells coincide with pimonidazole-positive tumor areas and they are merely quiescent, upon irradiation UnaG-positive cells enrich in regrowing tumors and are mainly proliferative. Conclusions: Collectively, our data provide clear evidence that the hypoxic cells drive tumor relapse after irradiation.</p
Genetic Landscape of Patients With Dilated Cardiomyopathy and a Systemic Immune-Mediated Disease
No full textBackground: Systemic immune-mediated diseases (SIDs) are a well-known cause of dilated cardiomyopathy (DCM), a cardiac phenotype influenced by genetic predispositions and environmental factors. Objectives: This study sought to examine if an underlying genetic predisposition is present in patients with DCM and SID. Methods: Genotyped DCM-SID patients (n = 183) were enrolled at 3 European centers. Genetic variants were compared with healthy control subjects (n = 20,917), DCM patients without SID (n = 560), and individuals with a suspicion of an SID (n = 1,333). Clinical outcomes included all-cause mortality, heart failure hospitalization, and life-threatening arrhythmias. Results: The SID diagnosis preceded the DCM diagnosis by 4.8 months (Q1-Q3: −68.4 to +2.4 months). The prevalence of pathogenic/likely pathogenic (P/LP) variants in DCM patients with an SID from the Maastricht cohort was 17.1%, compared with 1.9% in healthy control subjects (P < 0.001). In the Madrid/Trieste cohort, the prevalence was 20.5% (P < 0.001). Truncating variants showed the strongest enrichment (10.7% [OR: 24.5] (Maastricht) and 16% [OR: 116.6 (Madrid/Trieste); both P < 0.001), with truncating TTN (titin) variant (TTNtv) being the most prevalent. Left ventricular ejection fraction at presentation was reduced in TTNtv-SID patients compared with DCM patients with SID without a P/LP (P = 0.016). The presence of a P/LP variant in DCM-SID had no impact on clinical outcomes over a median follow-up of 8.4 years (Q1-Q3: 4.9-12.1 years). Conclusions: One in 6 DCM patients with an SID has an underlying P/LP variant in a DCM-associated gene. This highlights the role of genetic testing in those patients with immune-mediated DCM, and supports the concept that autoimmunity may play a role in unveiling a DCM phenotype in genotype-positive individuals.</p
The impact of nutrition claims on purchase behavior for food products
No full textFaced by increasing emphasis on health, manufacturers try to persuade consumers by using nutrition claims on their packaging. Although experimental research suggests that such claims influence consumer behavior in different ways, it remains unknown whether and to what extent they have an effect in actual grocery situations with large amounts of information to process. In this study, the authors investigate the effect of presence (stressing the presence of a healthy ingredient) and absence nutrition claims (stressing the absence of an unhealthy ingredient) on consumer purchase behavior using UK household scanner purchase data from 17 product categories during the years 2009–2012. They find that presence nutrition claims increase choice while absence nutrition claims decrease choice. Both types of nutrition claims do not influence the quantity purchased. Importantly, a nutrition claim’s effectiveness depends on SKU and category characteristics. Presence nutrition claims are more effective in healthy categories, and absence nutrition claims for SKUs with fewer promotions. At the same time, both nutrition claims are less effective for higher priced SKUs and more effective for brands with higher advertising spending. Absence nutrition claims are more effective when fewer SKUs in the category have the same type of nutrition claim, but presence nutrition claims benefit when more SKUs have the same type of nutrition claim
Parental Gender Stereotypes and Student Well-Being in China
No full textA prominent gender stereotype claims that "boys are better at learning mathematics than girls." Confronted with such a parental attitude, how does this affect the well-being of 11- to 18-year-old students in Chinese middle schools? Although well-being has often been shown to be not much gender-diverse, the intergenerational consequences of such stereotypes are not well studied. Expecting too much from boys and too little from girls might damage self-esteem among school kids. Using large survey data covering districts all over China reveals that one-quarter of the parents agree with the math stereotype. It is shown that this has strong detrimental consequences for the offspring's well-being. Students are strongly more depressed, feeling blue, unhappy, not enjoying life, and sad with no male-female differences, whereas parental education does not matter for this transfer. Various robustness tests including other than math stereotypes and an IV analysis confirm the findings. Moderating such effects, which is in line with societal objectives in many countries, not only supports gender equality but also strengthens the mental health of children
The association of overweight, obesity, and long-term obesity with SARS-CoV-2 infection:a meta-analysis of 9 population-based cohorts from the Netherlands Cohorts Consortium
No full textBackground: Obesity may affect an individual’s immune response and subsequent risk of infection, such as a SARS-CoV-2 infection. It is less clear whether overweight and long-term obesity also constitute risk factors. We investigated the association between the degree and duration of overweight and obesity and SARS-CoV-2 infection. Methods: We analyzed data from nine prospective population-based cohorts of the Netherlands Cohorts Consortium, with a total of 99,570 participants, following a standardized procedure. Body mass index (BMI) and waist circumference (WC) were assessed two times before the pandemic, with approximately 5 years between measurements. SARS-CoV-2 infection was defined by self-report as a positive PCR or rapid-antigen test or as COVID-19 ascertained by a physician between March 2020 and January 2023. For three cohorts, information on SARS-CoV-2 infection by serology was available. Results were pooled using random-effects meta-analyses and adjusted for age, sex, educational level, and number of SARS-CoV-2 infection measurements. Results: Individuals with overweight (25 ≤ BMI < 30 kg/m 2) (odds ratio (OR) = 1.08, 95%-confidence interval (CI) 1.04-1.13) or obesity (BMI ≥ 30 kg/m 2) (OR = 1.43, 95%-CI 1.18–1.75) were more likely to report SARS-CoV-2 infection than individuals with a healthy body weight. We observed comparable ORs for abdominal overweight (men: 94 cm≤WC < 102 cm, women: 80 cm≤WC < 88 cm) (OR = 1.09, 95%-CI 1.04–1.14, I 2 = 0%) and abdominal obesity (men: WC ≥ 102 cm, women: WC ≥ 88 cm) (OR = 1.24, 95%-CI 0.999–1.55, I 2 = 57%). Individuals with obesity long before the pandemic, but with a healthy body weight or overweight just before the pandemic, were not at increased risk. Conclusion: Overweight and obesity were associated with increased risk of SARS-CoV-2 infection with stronger associations for obesity. Individuals with a healthier weight prior to the pandemic but previous obesity did not have an increased risk of SARS-CoV-2, suggesting that weight loss in those with obesity reduces infection risk. These results underline the importance of obesity prevention and weight management for public health.</p