Sex, Gender, and Stroke Recovery: Functional Limitations and Inpatient Care Needs in Canadian and European Survivors.

BACKGROUND: Stroke is a leading cause of long-term disability among survivors. Past literature already investigated the biological sex differences in stroke outcome, still limited work on gender differences is published. Therefore, the study aimed at investigating whether biological sex and sociocultural gender of survivors play a role as determinants of disability and quality of life among stroke survivors across Europe and Canada. METHODS: Data were gathered from the European Health Information Survey (EHIS, n=316,333) and Canadian Community Health Survey (CCHS, n=127,462) datasets. Main outcomes of interest were disability, assessed through evaluating the impairment of Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (iADL), and inpatient care needs, such as hospitalization or institutionalization. Multivariate logistic regression models were utilized to identify factors independently associated with outcomes. Federated analysis was conducted for cross-country comparisons. Data were adjusted for the country-specific Gender Inequality Index (GII), with higher score corresponding to more gender inequality towards femalesResults: Female survivors showed greater impairments in iADL (OR=1.73, 95% CI 1.53 - 1.96) and ADL (OR=1.25, 95% CI 1.09-1.44), without a corresponding increase in inpatient care needs. Socioeconomic factors such as marital status and income level were significant predictors of disability, with low income and being single/divorced associated with higher risks. The impact of sex was more pronounced in countries with higher GII, indicating the influence of gender inequality on stroke outcomes. INTERPRETATION: The findings highlight the significant impact of biological sex and gender-related social determinants on post-stroke disability, with female sex and unfavorable socioeconomic conditions being associated with worse outcomes.

Investigating a New Way to Assess Metabolic Risk in Pregnant Females with Prior RYGB Surgery.

BACKGROUND: Obesity in pregnancy is linked to adverse clinical outcomes such as gestational diabetes. Recently, a risk score calculated by different ceramide concentrations was recognized as a new way to investigate cardiovascular risk. The aim was to analyze if the ceramide risk score and cardiometabolic risk vary between normal-weight, obese, and females with prior Roux-en-Y bypass surgery (RYGB) during pregnancy. METHODS: Three cohorts were investigated: first, 25 pregnant females with a history of RYGB; second, 19 with preconception BMI ≥ 35 kg/m2; and third, 19 normal-weight (preconception BMI < 25 kg/m2). Around the 24th to 28th weeks of gestation routine laboratory assessments, 3 h 75 g oral and intravenous glucose tolerance tests were carried out. The correlation of ceramide risk scores and ceramide ratios (Cer(d18:1/18:0)/Cer(d18:1/16:0)) with metabolic parameters was analyzed via Pearson correlation. The cohorts were compared via ANOVA and unpaired t-tests. RESULTS: The RYGB cohort had lower ceramide risk scores and ratios compared to obese pregnant females (7.42 vs. 9.34, p = 0.025; 0.33 vs. 0.47, p < 0.001). Ceramide risk score and ratio were found to correlate negatively with insulin sensitivity (measured with the Matsuda (r = -0.376, p = 0.031; r = -0.455, p = 0.008) and calculated sensitivity index (r = -0.358, p = 0.044; r = -0.621, p < 0.001) in females without RYGB. The ceramide risk score correlated positively with body fat in RYGB females (r = 0.650, p = 0.012). CONCLUSIONS: We found that females after RYGB have lower ceramide risk scores and ceramide ratios compared to obese pregnant females, possibly indicating lower metabolic risk.

Socioeconomic Gender Variables Impact the Association between Hypertension and Chronic Health Issues: Cross-Sectional Study.

Our aim is to investigate if sex and gender influence the association of hypertension and their comorbidities. We investigated how gender differences in five socioeconomic factors impact the relation between hypertension and ten comorbidities including diabetes mellitus, renal disease, and chronic pulmonary disease in European countries grouped by their gender inequality index using representative survey data from the European Health Interview Survey. Using logistic regressions, we compute the ratio of odds ratios in females versus males. Therefore, an ORR > 1 is associated with a higher odds ratio for females than for males while an ORR < 1 means the opposite. To account for multiple hypothesis testing, we applied the Bonferroni correction. Hypertension in both sexes was associated with lower educational level, being unemployed, and lower income. In males, being divorced/widowed (OR1.12, p < 0.001) had an association to hypertension, whereas in females, being common-law/married (OR1.30, p < 0.001) and being divorced/widowed (OR1.17, p < 0.001) was associated with a higher risk for hypertension. Moreover, in hypertension, females who worked had an association with myocardial infarction (OR1.39, p < 0.001) and having post-secondary education had an association with arthrosis (OR 1.35, p < 0.001) compared to males. Our findings show that gender variables influence the association of hypertension and comorbidities, especially in females. These results can be used to inform targeted prevention measures taking gender-specific contextual factors into account.

The Effects of Caloric Restriction and Clinical Psychological Intervention on the Interplay of Gut Microbial Composition and Stress in Women.

Both mental and metabolic disorders are steadily becoming more prevalent, increasing interest in non-pharmacological lifestyle interventions targeting both types of disorders. However, the combined effect of diet and psychological interventions on the gut microbiome and mental health outcomes remains underexplored. Thus, in this study, we randomized 41 women into two caloric restriction (CR) dietary groups, namely very-low-calorie diet (VLCD) and F.X. Mayr diet (FXM). The patients were then further randomized to either receive clinical psychological intervention (CPI) or no CPI. Blood and fecal samples were collected before and after two weeks of CR. Psychometric outcomes were assessed using the Perceived Stress Scale (PSS), Brief Symptom Index (BSI), and Burnout Dimension Inventory (BODI). Stool samples underwent 16S-rRNA sequencing. Upon two weeks of CR, α-diversity decreased overall and longitudinal PERMANOVA models revealed significant shifts in ß-diversity according to diet, CPI, age, and body-mass-index. Furthermore, Agathobacter, Fusicatenibacter, and Subdoligranulum decreased in abundance. However, the Oscillibacter genus was enriched solely in FXM. CPI had a negligible effect on the microbiome. Dimension reduction models revealed clusters of taxa which distinctly associated with psychometric outcomes. Members of the Oscillospiraceae family were linked to favorable psychometric outcomes after two weeks of CR. Despite α-diversity reductions after CR, enrichment of Oscillospiraceae spp., solely seen in FXM, correlated with improved psychometric outcomes. This study suggests a promising direction for future interventions targeting mental health through gut microbial modulation.

Sex differences in the diagnostic algorithm of screening for heart failure by symptoms and NT-proBNP in patients with type 2 diabetes.

OBJECTIVES: This study aimed to assess the guideline recommended diagnostic tools NT-proBNP and NYHA classification, with a focus on sex-specific differences. BACKGROUND: Patients with Type 2 Diabetes (T2D) face a heart failure (HF) risk up to four times higher than those without T2D, particularly affecting women more than twice as much as men. Despite distinct pathophysiological differences between men and women, there are currently no sex-specific recommendations for the diagnostic algorithm of HF in diabetic patients. METHODS: A total of 2083 patients with T2D were enrolled, and the primary endpoint was heart failure during hospitalization within a 5-year timeframe. The secondary endpoint was all-cause death. RESULTS: In female patients, frequency of HF diagnosis prior to or during hospitalization and mortality did not differ significantly between NYHA II and III, in contrast to male patients. Additionally, there was no notable difference in mean NT-proBNP levels between NYHA stage II and III only in female patients. The multivariable regression analysis highlighted NYHA classification not to be a predictor of NT-proBNP levels in female but solely in male patients. On multivariable Cox regression NYHA score was also no significant risk factor for occurence of HF in female patients. Furthermore, there was no significant disparity in mortality between men with NT-proBNP levels between 125 and 400 pg/ml and those below 125 pg/ml, whereas in women mortality was significantly higher in the group with NT-proBNP levels between 125 and 400 pg/ml than below 125 pg/ml. CONCLUSION: These findings suggest that NYHA classification may not be the most suitable tool for assessing the diagnosis of HF in female patients with T2D. Moreover, the need for consideration of a more symptom-independent screening for HF in female patients with T2D and re-evaluation of current guidelines especially regarding sex-specific aspects is highlighted.

Effect of treatment for early gestational diabetes mellitus on neonatal respiratory distress: A secondary analysis of the TOBOGM study.

OBJECTIVE: To identify factors associated with neonatal respiratory distress (NRD) in early Gestational diabetes mellitus (eGDM). DESIGN: Nested case-control analysis of the TOBOGM trial. SETTING: Seventeen hospitals: Australia, Sweden, Austria and India. POPULATION: Pregnant women, <20 weeks' gestation, singleton, GDM risk factors. METHODS: Women with GDM risk factors completed an oral glucose tolerance test (OGTT) before 20 weeks: those with eGDM (WHO-2013 criteria) were randomised to immediate or deferred GDM treatment. Logistic regression compared pregnancies with/without NRD, and in pregnancies with NRD, those with/without high-dependency nursery admission for ≤24 h with those admitted for >24 h. Comparisons were adjusted for age, pre-pregnancy body mass index, ethnicity, smoking, primigravity, education and site. Adjusted odds ratios (95% CI) are reported. MAIN OUTCOME MEASURES: NRD definition: ≥4 h of respiratory support (supplemental oxygen or supported ventilation) postpartum. Respiratory distress syndrome (RDS): Supported ventilation and ≥24 h nursery stay. RESULTS: Ninety-nine (12.5%) of 793 infants had NRD; incidence halved (0.50, 0.31-0.79) if GDM treatment was started early. NRD was associated with Caesarean section (2.31, 1.42-3.76), large for gestational age (LGA) (1.83, 1.09-3.08) and shorter gestation (0.95, 0.93-0.97 per day longer). Among NRD infants, >24 h nursery-stay was associated with higher OGTT 1-h glucose (1.38, 1.08-1.76 per mmol/L). Fifteen (2.0%) infants had RDS. CONCLUSIONS: Identifying and treating eGDM reduces NRD risk. NRD is more likely with Caesarean section, LGA and shorter gestation. Further studies are needed to understand the mechanisms behind this eGDM complication and any long-term effects.

Putting person-centred psychosocial diabetes care into practice: two psychosocial care pathways based on outcome preferences of people with diabetes and healthcare professionals.

BACKGROUND: Diabetes increases the risk of psychosocial health problems. Person-centred psychosocial care is therefore advocated. However, several barriers to implementation exist, including uncertainty about how to approach psychosocial problems in consultations. OBJECTIVE: We aimed to explore which psychosocial outcomes patients and healthcare professionals consider important and whether certain characteristics are associated with this. We propose strategies for facilitating psychosocial diabetes care on this basis. METHODS: The results of an international Delphi study aimed at achieving multi-stakeholder consensus on a diabetes outcome set were analysed. We compared the importance ratings of the two stakeholder groups for each psychosocial outcome. A multivariable linear regression analysis tested whether certain characteristics would predict the importance attributed to outcomes that were not generally considered important. FINDINGS: Patients and healthcare professionals agreed on the importance of regularly assessing psychological well-being, diabetes distress and diabetes-specific quality of life, while they regarded it as less important to monitor depression, anxiety, eating problems, social support and sexual health. Being a woman, younger and living with type 1 diabetes were associated with considering it important to assess eating problems. CONCLUSIONS: We propose two psychosocial care pathways that reflect the outcome preferences of patients and healthcare providers. They follow a stepped approach, starting with the assessment of psychological well-being and quality of life and proceeding from there. CLINICAL IMPLICATIONS: Adopting this approach can facilitate the implementation of person-centred psychosocial diabetes care by reducing the burden and making psychosocial issues more accessible. This approach should be tested for feasibility, safety and effectiveness.

Monitoring what matters to people with diabetes: Do we underestimate the importance of behaviour, attitude, and well-being?

OBJECTIVE: Despite improvements in diabetes monitoring and treatment many patients do not achieve treatment goals. Person-centred approaches have been proposed. However, their practical implementation lags. One barrier is uncertainty about which person-reported outcomes (PROs) should be considered to add the most value. We sought to identify PROs that may be prioritised. METHODS: We used data from a multi-stakeholder Delphi study aimed at developing a person-centred diabetes outcome set and analysed which PROs patients considered important for regular monitoring but healthcare providers less so. Linear regression analyses tested whether belonging to either stakeholder group would predict the importance attributed to an outcome. RESULTS: We found disagreement between patients and healthcare providers on eleven PROs. Stakeholder group predicted perceived importance for ten: self-management behaviours (including performance, perceived importance, motivation, and capacity), sleep quality, diabetes symptoms, screening visit attendance, health status, lifestyle behaviours, and side effects. CONCLUSION: Our findings suggest that, according to patients' preferences, self-management behaviours, health status and sleep are currently not adequately considered in diabetes management, compromising person-centred care. PRACTICAL IMPLICATIONS: This study suggests that prioritising these PROs can facilitate the implementation of more person-centred diabetes monitoring which may support better-informed treatment decisions to achieve treatment goals.

Relationship Between Early-Pregnancy Glycemia and Adverse Outcomes: Findings From the TOBOGM Study.

OBJECTIVE: We evaluated associations between early-pregnancy oral glucose tolerance test (OGTT) glucose and complications in the Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) cohort to inform prognostic OGTT thresholds. RESEARCH DESIGN AND METHODS: Individuals with risk factors for hyperglycemia were recruited for an international, multicenter, randomized controlled gestational diabetes mellitus (GDM) (World Health Organization 2013 criteria) treatment trial. A 2-h 75-g OGTT was performed at <20 weeks' gestation. Individuals with early treated hyperglycemia in pregnancy were excluded from the primary analysis. Early OGTT glucose concentrations were analyzed continuously and in glycemic categories (normal, low band, and high band). RESULTS: Overall, 3,645 individuals had an OGTT at (mean ± SD) 15.6 ± 2.5 weeks. For each 1-SD increase in fasting, 1-h, and 2-h glucose values, there were continuous positive associations with late GDM: adjusted odds ratio (aOR) 2.04 (95% CI 1.82-2.27), 3.05 (2.72-3.43), and 2.21 (1.99-2.45), respectively. There were continuous positive associations between 1-h and 2-h glucose and the perinatal composite (birth <37 + 0 weeks, birth trauma, birth weight ≥4,500 g, respiratory distress, phototherapy requirement, stillbirth/neonatal death, and shoulder dystocia), with aOR 1.15 (95% CI 1.04-1.26) and 1.14 (1.04-1.25), respectively, and with large-for-gestational-age offspring, with aOR 1.18 (1.06-1.31) and 1.26 (1.01-1.25), respectively. Significant associations were also observed between 1-h glucose and cesarean section and between fasting and 2-h glucose and neonatal hypoglycemia. In categorical analysis, only the high-band 1-h glucose (≥10.6 mmol/L [191 mg/dL]) predicted the perinatal composite. CONCLUSIONS: There is a continuous positive association between early-pregnancy OGTT glucose and complications. In individuals with hyperglycemia risk factors, only the high-glycemic-band 1-h glucose corresponded to increased risk of major perinatal complications.

Cost-effectiveness of diagnosis and treatment of early gestational diabetes mellitus: economic evaluation of the TOBOGM study, an international multicenter randomized controlled trial.

Background: A recently undertaken multicenter randomized controlled trial (RCT) "Treatment Of BOoking Gestational diabetes Mellitus" (TOBOGM: 2017-2022) found that the diagnosis and treatment of pregnant women with early gestational diabetes mellitus (GDM) improved pregnancy outcomes. Based on data from the trial, this study aimed to assess the cost-effectiveness of diagnosis and treatment of early GDM (from <20 weeks') among women with risk factors for hyperglycemia in pregnancy compared with usual care (no treatment until 24-28 weeks') from a healthcare perspective. Methods: Participants' healthcare resource utilization data were collected from their self-reported questionnaires and hospital records, and valued using the unit costs obtained from standard Australian national sources. Costs were reported in US dollars ($) using the purchasing power parity (PPP) estimates to facilitate comparison of costs across countries. Intention-to-treat (ITT) principle was followed. Missing cost data were replaced using multiple imputations. Bootstrapping method was used to estimate the uncertainty around mean cost difference and cost-effectiveness results. Bootstrapped cost-effect pairs were used to plot the cost-effectiveness (CE) plane and cost-effectiveness acceptability curve (CEAC). Findings: Diagnosis and treatment of early GDM was more effective and tended to be less costly, i.e., dominant (cost-saving) [-5.6% composite adverse pregnancy outcome (95% CI: -10.1%, -1.2%), -$1373 (95% CI: -$3,749, $642)] compared with usual care. Our findings were confirmed by both the CE plane (88% of the bootstrapped cost-effect pairs fall in the south-west quadrant), and CEAC (the probability of the intervention being cost-effective ranged from 84% at a willingness-to-pay (WTP) threshold value of $10,000-99% at a WTP threshold value of $100,000 per composite adverse pregnancy outcome prevented). Sub-group analyses demonstrated that diagnosis and treatment of early GDM among women in the higher glycemic range (fasting blood glucose 95-109 mg/dl [5.3-6.0 mmol/L], 1-h blood glucose ≥191 mg/dl [10.6 mmol/L] and/or 2-h blood glucose 162-199 mg/dl [9.0-11.0 mmol/L]) was more effective and less costly (dominant) [-7.8% composite adverse pregnancy outcome (95% CI: -14.6%, -0.9%), -$2795 (95% CI: -$6,638, -$533)]; the intervention was more effective and tended to be less costly [-8.9% composite adverse pregnancy outcome (95% CI: -15.1%, -2.6%), -$5548 (95% CI: -$16,740, $1547)] among women diagnosed before 14 weeks' gestation as well. Interpretation: Our findings highlight the potential health and economic benefits from the diagnosis and treatment of early GDM among women with risk factors for hyperglycemia in pregnancy and supports its implementation. Long-term follow-up studies are recommended as a key future area of research to assess the potential long-term health benefits and economic consequences of the intervention. Funding: National Health and Medical Research Council (grants 1104231 and 2009326), Region O¨rebro Research Committee (grants Dnr OLL-970566 and OLL-942177), Medical Scientific Fund of the Mayor of Vienna (project 15,205 and project 23,026), South Western Sydney Local Health District Academic Unit (grant 2016), and Western Sydney University Ainsworth Trust Grant (2019).

Association of prediabetes with clinical outcomes in patients with chronic coronary syndrome: a post hoc analysis of the ISCHEMIA and ISCHEMIA-CKD trials.

BACKGROUND: There is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect of prediabetes in patients with chronic coronary syndrome on clinical outcomes. METHODS: This is a secondary analysis of data from the ISCHEMIA and ISCHEMIA-CKD trials, including patients with chronic coronary syndrome determined by coronary computed tomography angiography or exercise-stress testing. Participants were assigned to the normoglycemia group (HbA1c < 5.7% [< 39 mmol/mol]), prediabetes group (HbA1c 5.7-6.4% [40-47 mmol/mol]), or diabetes group (HbA1c ≥ 6.5% [≥ 48 mmol/mol]). The primary end point of this study was all-cause mortality. Secondary endpoints included major adverse cardiovascular events and composites thereof. RESULTS: Overall, the primary endpoint all-cause mortality occurred in 330 (8.4%) of 3910 patients over a median follow-up time of 3.1 years (IQR 2.1-4.1). The primary endpoint all-cause mortality occurred in 37 (5.2%) of 716 patients in the normoglycemia group, in 63 (6.9%) of 911 in the prediabetes group, and in 230 (10.1%) of 2283 in the diabetes group. In the covariate-adjusted Cox model analysis, the estimated adjusted HR (aHR) in the prediabetes group as compared with the normoglycemia group was 1.45 (95%CI, 0.95-2.20). The aHR in the diabetes group as compared with the normoglycemia group was 1.84 (95%CI, 1.29-2.65). Prediabetes, compared with normoglycemia, was associated with an increased risk of stroke (aHR, 3.44, 95%CI, 1.15-10.25). Subgroup analyses suggested an increased risk of all-cause death associated with prediabetes in males and patients under 65 years. CONCLUSIONS: In patients with chronic coronary syndrome, diabetes but not prediabetes was associated with significantly increased risk of all-cause death within a median follow-up period of 3.1 years. Trial Registration NCT01471522, BioLINCC ID 13936.

Poor adherence during adolescence is a risk factor for becoming lost-to-follow-up in patients with phenylketonuria.

Purpose: A high rate of lost to follow-up (LTFU) in patients with phenylketonuria (PKU) represents a main challenge. In this study, we investigated potential risk factors for becoming LTFU related to adolescence as a critical period of life. Methods: We retrospectively analyzed longitudinal data collected from 1993 to 2019 of patients diagnosed with classic PKU that were followed at our center during adolescence (14-18 y) and at least once in adulthood (>18 y). Patients who interrupted their contact with our center after the 18th birthday for at least 2 years were classified as LTFU. We performed a multivariate regression analysis to investigate following potential risk factors for becoming LTFU in adult life: sex, dietary compliance during adolescence assessed through the mean of the annual medians of phenylalanine plasma values, average number of contacts with the center during adolescence and age at first visit after the 18th birthday. Results: 93 patients (52 males, 41 females) were included in the study. 58% became LTFU during adulthood. The mean age at the last visit before becoming LTFU was 26.2 ± 5.1 years. In the multivariate Cox regression analysis we found that poor dietary compliance during adolescence was significantly associated with a higher risk of becoming LTFU during adulthood (p-value = 0.028). Discussion: Adult patients who displayed poor treatment adherence during adolescence should be identified and carefully monitored to prevent loss of contact.

The impact of the SARS-CoV2 pandemic on the prescription of thyroid medication in Austria - A nationwide population-based registry analysis.

BACKGROUND: Case reports indicate a clinical connection between SARS-CoV-2 and thyroid dysfunctions. However, evidence from large population-based registry analyses is sparse, especially in Europe, where iodine deficiency is common. This study aimed to analyze the impact of the COVID-19 pandemic on healthcare provision for thyroid diseases in Austria. METHODS: We performed a retrospective, population-based registry analysis of the Austrian health insurance fund database, covering more than 9 million inhabitants. Data from all patients with prescriptions of thyroid-specific drugs and/or inpatient thyroid-related diagnoses from 2017 to 2019 (pre-pandemic years) were compared to 2020 and 2021 (pandemic years; characterized by high numbers of SARS-CoV2 infections and population-wide vaccination strategy). The incidence rates of thyroid medication prescriptions for hypothyroidism and hyperthyroidism were calculated for every year to evaluate the impact of the pandemic. RESULTS: The incidence rate for total thyroid medication prescription was 539.07/100,000 individuals (534.23-543.93 95%CI) in 2018 and declined during the pandemic (2020: 387.19/100,000 (383.12-391.29 95%CI); 2021: 336.90/100,000 (333.11-340.73 95%CI)). Similarly, the incidence rate for levothyroxine prescription was higher pre-pandemic (2018: 465.46/100,000 (460.97-469.98 95%CI) and declined during the pandemic (2020: 348.14/100,000 (344.28-352.03 95%CI); 2021: 300.30/100,000 (296.7-303.91 95%CI). The incidence rates of thiamazole prescriptions (2018: 10.24/100,000 (9.58-10.93 95%CI); 2020: 8.62/100,000 (8.03-9.26 95%CI); 2021: 11.17/100,000 (10.49-11.89 95%CI) were stable. CONCLUSIONS: These findings suggest no clinically significant impact of SARS-CoV2 and/or vaccination on thyroid function at a population level.

Female Patients Show a Larger Reduction in Suicidal Ideation in Inpatient Addiction Treatment Than Male Patients: Results of a Single-Center Observational Study.

Background: Substance use disorders (SUD) are prevalent disorders worldwide. Among other associated health problems, patients with SUD are at an increased risk of dying of suicide, with females displaying an even higher risk than males. Therefore, the aim of this study was to conduct a gender-sensitive evaluation of changes in suicidal ideation during multimodal inpatient treatment at a hospital facility specialized in treating addiction. Methods: A total of 694 patients (68.2% male) completed routine assessment including suicidal ideation, abstinence confidence, impulsivity, emotion regulation, self-efficacy and autonomy and joy both before (T1) and at the end (T2) of treatment. Mean changes were evaluated with repeated measures MANOVAs. Results: Before treatment, a total of n=127 (18.3%) of the respondents reported suicidal ideation, which was reduced to n=72 (10.4%) by the end of treatment. Among female patients, the change in reported suicidal ideation compared from T1 to T2 (21.7% vs 7.7%) was significantly higher than among male patients (T1: 16.7%%, T2: 11.6%; p=0.040). Generally, females reported worse symptoms scores and slightly higher numbers of suicidal thoughts at baseline (effect sizes ranging from η²=.008 - 0.044). While both genders significantly profited from the treatment, female patients generally showed larger improvements than male. Discussion: Our study underscores the beneficial effect of addiction-specialized inpatient treatment on suicidal ideation. Additionally, we found a substantial gender effect: while female patients generally were more distressed before treatment, they also reported higher symptom reduction during the treatment. This result highlights the need to perform more gender-sensitive research and develop more gender-sensitive treatment programs.

Sex differences of post-Covid patients undergoing outpatient pulmonary rehabilitation.

BACKGROUND: Following years of pandemic severe acute respiratory syndrome coronavirus 2 infections labelled Covid-19, long lasting impairment summarized as post-Covid syndrome (PCS) challenges worldwide healthcare. Patients benefit from rehabilitation programs, but sex specific aspects of improvement remain little understood. The aim of the study was to assess whether women and men differ in response to outpatient pulmonary rehabilitation for PCS. METHODS: 263 (54.4% female) patients partaking in outpatient pulmonary rehabilitation (OPR) due to PCS between March 2020 and July 2022 were included in a prospective observational cohort study. Outcomes were assessed at baseline and before discharge from OPR and included six-minute walking distance (6MWD), 1-second forced expiratory volume (FEV1), diffusion capacity for carbon monoxide, maximal inspiratory pressure (MIP), dyspnea (medical research council scale), and post-Covid functional status scale (PCFS). Sexspecific changes in outcomes following OPR were assessed by linear mixed model and presented as mean differences (MD) with 95% confidence intervals. Linear regression was applied to test whether 6MWD correlates with PCFS and the minimal clinically important difference (MCID) in 6MWD regarding an improvement of at least one point in PCFS was computed with logistic regression. RESULTS: Significant improvement throughout OPR was observed for all outcomes (all p < 0.0001). Despite less severe Covid-19 infections, PCFS scores remained higher in females after OPR (p = 0.004) and only 19.4% of women compared to 38.5% of men achieved remission of functional impairment. At baseline as well as after OPR, females showed higher symptom load compared to men in dyspnea (p = 0.0027) and scored lower in FEV1 (p = 0.009) and MIP (p = 0.0006) assessment. Performance in 6MWD was comparable between men and women. An increase of 35 m in 6MWD was computed as minimal clinically important difference to improve functional impairment. CONCLUSION: Both subjective symptoms such as fatigue and dyspnea and objective impairment in performance in pulmonary function were more frequently observed among women. Despite improvement throughout OPR in both women and men, the sex-gap in symptom load could not be closed as women less often achieved remission from functional impairment due to PCS. Intensified treatment of these symptoms should be considered in women undergoing rehabilitation for PCS.

While female sex is protective during the acute infection of Covid-19, women are at increased risk of developing post-Covid syndrome (PCS) even after only mild Covid-19 infections. Severity and frequency of symptoms such as fatigue and shortness of breath are known to be higher in women compared to men. Many different rehabilitation protocols are used for PCS, but a knowledge gap regarding sex related differences in rehabilitation success remains.Both female and male patients with PCS undergoing outpatient pulmonary rehabilitation improved in the maximum walking distance achieved within 6 min and selfrated impairment in everyday living. Although women less frequently required inpatient treatment for acute Covid-19 infection, female patients with PCS showed higher impairment in everyday living, lower capacity of physical exercise and more frequent shortness of breath, fatigue and breathing muscle weakness. Only 19.4% of women compared to 38.5% of men achieved complete remission of impairment in everyday living. Our results show that women treated for PCS retain greater symptom burden and are at risk of unsuccessful rehabilitation, calling for more targeted treatment in female patients after Covid-19 infection.

Regression From Early GDM to Normal Glucose Tolerance and Adverse Pregnancy Outcomes in the Treatment of Booking Gestational Diabetes Mellitus Study.

OBJECTIVE: To compare pregnancy outcomes among women with a normal oral glucose tolerance test (OGTT) before 20 weeks' gestation (early) and at 24-28 weeks' gestation (late) (no gestational diabetes mellitus, or No-GDM), those with early GDM randomized to observation with a subsequent normal OGTT (GDM-Regression), and those with GDM on both occasions (GDM-Maintained). RESEARCH DESIGN AND METHODS: Women at <20 weeks' gestation with GDM risk factors who were recruited for a randomized controlled early GDM treatment trial were included. Women with treated early GDM and late GDM (according to the World Health Organization's 2013 criteria) were excluded from this analysis. Logistic regression compared pregnancy outcomes. RESULTS: GDM-Regression (n = 121) group risk factor profiles and OGTT results generally fell between the No-GDM (n = 2,218) and GDM-Maintained (n = 254) groups, with adjusted incidences of pregnancy complications similar between the GDM-Regression and No-GDM groups. CONCLUSIONS: Women with early GDM but normal OGTT at 24-28 weeks' gestation had pregnancy outcomes that were similar to those of individuals without GDM. Identifying early GDM likely to regress would allow treatment to be avoided.

Unraveling cradle-to-grave disease trajectories from multilayer comorbidity networks.

We aim to comprehensively identify typical life-spanning trajectories and critical events that impact patients' hospital utilization and mortality. We use a unique dataset containing 44 million records of almost all inpatient stays from 2003 to 2014 in Austria to investigate disease trajectories. We develop a new, multilayer disease network approach to quantitatively analyze how cooccurrences of two or more diagnoses form and evolve over the life course of patients. Nodes represent diagnoses in age groups of ten years; each age group makes up a layer of the comorbidity multilayer network. Inter-layer links encode a significant correlation between diagnoses (p < 0.001, relative risk > 1.5), while intra-layers links encode correlations between diagnoses across different age groups. We use an unsupervised clustering algorithm for detecting typical disease trajectories as overlapping clusters in the multilayer comorbidity network. We identify critical events in a patient's career as points where initially overlapping trajectories start to diverge towards different states. We identified 1260 distinct disease trajectories (618 for females, 642 for males) that on average contain 9 (IQR 2-6) different diagnoses that cover over up to 70 years (mean 23 years). We found 70 pairs of diverging trajectories that share some diagnoses at younger ages but develop into markedly different groups of diagnoses at older ages. The disease trajectory framework can help us to identify critical events as specific combinations of risk factors that put patients at high risk for different diagnoses decades later. Our findings enable a data-driven integration of personalized life-course perspectives into clinical decision-making.