Laura Werlen

Prolactin (PRL) is involved in the modulation of sexual function. Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) have been proposed to modulate reward‐related processes beyond their effects on appetite, including sexual desire. In our previously published randomized parent trial of dulaglutide and sexual desire, we hypothesized that any potential effect on sexual desire could involve changes in PRL concentrations. Predefined secondary analysis of a single‐center randomized, double blind, placebo‐controlled, crossover trial involving 24 healthy eugonad men of normal weight (BMI 18.5–25 kg/m ² or BMI 25.1–30 kg/m ² and waist circumference 2 (IQR [22.2, 25.0]). PRL levels changed by −31.1 mU/L (SD 87.0 mU/L) on dulaglutide and +44.6 mU/L (SD 113.1 mU/L) on placebo over 4 weeks (estimated difference: −149.3 mU/L; 95% CI: [−298.5, −0.1]). On dulaglutide treatment, reductions in PRL correlated weakly with weight loss ( r = 0.25), and more than half of participants (13/24) showed parallel decreases in PRL and appetite scores. Regarding sexuality, we found no association of PRL levels and sexual desire. Four weeks of dulaglutide treatment reduced PRL concentrations compared with placebo in healthy men. These findings may point to broader neuroendocrine effects of GLP‐1 receptor activation and warrant further investigation. Trial registration: ClinicalTrials.gov NCT04687514.

BACKGROUND: Biomarkers may increase the understanding of the pathophysiology of brain lesions in newly evaluated atrial fibrillation. BTG (β-thromboglobulin) is released from platelet alpha granules upon activation, reflecting platelet activation or destruction, or both. We assessed the association of plasma BTG with cerebral microbleeds (CMBs) and ischemic brain lesions using brain magnetic resonance imaging (bMRI) in patients with atrial fibrillation. METHODS: BTG was analyzed using the Luminex assay. CMBs and ischemic brain lesions were detected by standardized bMRI of 1724 patients from the Swiss-Atrial Fibrillation cohort, a prospective, national, multicenter cohort study that enrolled patients between 2014 and 2017. For this cross-sectional analysis, associations of BTG with bMRI lesions were evaluated by logistic and linear regression analyses using 2 models. The first model was adjusted for age and sex, and the second model was additionally multivariable-adjusted for a large number of clinical characteristics, including coronary artery disease, hypertension, diabetes, chronic kidney disease, history of heart failure, major bleeding, as well as concomitant platelet inhibitor, and anticoagulation therapy. RESULTS: Mean age at baseline was 72.5 years (SD, 8.4), and 27.3% were female. On bMRI, CMBs were found in 369 patients (21.4%) and cerebral infarcts in 635 (36.8%). After multivariable adjustment, a 1-unit increase of log-transformed plasma BTG was associated with 25% lower odds of having CMBs (odds ratio, 0.75 [95% CI, 0.59–0.96]). However, BTG was not associated with the presence of large noncortical or cortical infarcts (odds ratio, 0.85 [95% CI, 0.66–1.09]) or small noncortical infarcts (odds ratio, 1.06 [95% CI, 0.83–1.35]). CONCLUSIONS: In patients with atrial fibrillation, the platelet-specific biomarker BTG was inversely and independently associated with CMBs on bMRI. Low-grade platelet activation may improve vascular integrity. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02105844.

BACKGROUND: Medication-related readmissions are significant burdens on patients and healthcare systems and are particularly prevalent among older adults. We aimed to identify potentially preventable medication-related readmissions and to describe their causes. METHODS: We conducted a retrospective cohort study of 500 randomly selected patients, aged 65 or older, discharged from the general internal medicine department of a university hospital in Switzerland between January 2022 and October 2023 and readmitted within 30 days. Two pharmacists independently screened their electronic health records and analysed whether their readmission was medication-related using the AT-HARM10 tool. We assessed preventability using judgements similar to the Schumock statements. In cases of disagreement between the two pharmacists, readmissions were also screened by a senior physician. We analysed the causes of potentially preventable medication-related readmissions. RESULTS: We identified 116 (23.2%) potentially preventable medication-related readmissions among the 500 readmissions analysed. The most common diagnoses associated with readmission were heart failure (21.6%), worsening pain (12.1%) and infection (12.1%). The most common causes of readmission were underprescribing (29.3%), Other prescribing problems such as suboptimal medication selection or dosage issues (28.4%), and non-adherence (12.9%). Diuretics, analgesics and antibiotics were the most frequently involved medications. CONCLUSIONS: Nearly one-quarter of 30-day readmissions involving older adults were medication-related and potentially preventable. The primary contributing factors were prescribing and non-adherence issues. The study highlighted common causes of such readmissions and underlines the need for further research to determine which interventions – such as medication reviews or improved care transitions – are most effective in addressing them. Identifying high-risk patients will also be essential to optimise the use of healthcare resources.

Background: Preventable medication‐related readmissions (pMRRs) are a significant contributor to older adult morbidity, mortality, and health care costs. There are currently no specific screening tools for identifying patients at a high risk of pMRRs. This study aimed to develop and internally validate a screening tool to identify general internal medicine patients aged 65 or older at risk of 30‐day pMRRs.Methods: Data on 500 patients discharged between January 1, 2022 and October 18, 2023, and readmitted within 30 days were reviewed, and 116 pMRRs were identified. An additional 500 control patients without pMRRs were selected. A multivariable logistic regression model was developed using the four pre‐specified predictors of each patient's number of medications, hospitalizations in the past year, high‐risk medications at discharge (anticoagulants, opioids, and sedatives), and the number of the following diagnoses: heart failure, diabetes, chronic kidney disease, and chronic obstructive pulmonary disease.Results: The screening tool's performance was evaluated and internally validated using bootstrapping. The screening tool demonstrated moderate discriminatory power, with a C‐statistic of 0.714 (95% confidence interval [CI]: 0.663–0.764). Overall performance was assessed as acceptable, with a Brier score of 0.177. Bootstrapping yielded an optimism‐corrected C‐statistic of 0.704 (95% CI: 0.654–0.755), indicating the tool's robustness.Conclusions: The screening tool's discriminatory power suggested its potential utility for flagging patients at risk of pMRRs. External validation and a search for additional predictors will be necessary to enhance the tool's performance and generalizability. If validated, a cost‐effectiveness analysis would be needed to ensure its feasibility for clinical implementation.

Introduction: Standardisation has the potential to serve as a measure to mitigate complication rates. The objective was to assess the impact of standardisation by implementing a colorectal bundle (CB), which comprises nine elements, on the complication rates in left-sided colorectal resections. Patients and Methods: This prospective, multicentre, observational, cohort trial was conducted in Switzerland at nine participating hospitals. During the control period, each patient was treated in accordance with the local standard protocol at their respective hospital. In the CB period, all patients were treated in accordance with the CB. The primary endpoint was the Comprehensive Complication Index (CCI) at 30 days. Results: A total of 1141 patients were included (723 in the No CB group and 418 in the CB group). Median age was 66 years and 50.6% were female. Median CCI before and after CB implementation was 0.0 (Interquartile Range [IQR]: 0.0-20.9). A hurdle model approach was used for the analysis. The CB was not associated with the presence or severity of complications. Older age (Odds Ratio [OR] 1.02, 95% Confidence Intervall [CI]: 1.00-1.03), surgery for malignancy (OR 1.34, 95% CI: 1.01-1.92), emergency surgery (OR 2.19, 95% CI: 1.31-3.41), elevated nutritional risk score (OR 1.13, 95% CI: 1.01-1.24) and Body-Mass Index (OR 1.04, 95% CI: 1.00-1.06) were associated with higher odds of postoperative complications. In a supplementary per-protocol analysis, for each additional item of the CB fulfilled, the odds of anastomotic leakage (AL) were 24% lower (OR 0.76, 95% CI: 0.64-0.93). Conclusions: Dedicated teams can establish high quality colorectal services in a network of hospitals with a joint standard. The study can serve as a model for other healthcare settings to conduct and implement quality improvement programs. The consistent implementation of the CB items can reduce the occurrence of AL.

Omega-3 fatty acids (n-3 FAs) are associated with a lower risk of ischemic stroke in patients with atrial fibrillation (AF). Antithrombotic mechanisms may in part explain this observation. Therefore, we examined the association of n-3 FAs with D-dimer and beta-thromboglobulin (BTG), markers for activated coagulation and platelets, respectively. The n-3 FAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA) were determined via gas chromatography in the whole blood of 2373 patients with AF from the Swiss Atrial Fibrillation cohort study (ClinicalTrials.gov Identifier: NCT02105844). In a cross-sectional analysis, we examined the association of total n-3 FAs (EPA + DHA + DPA + ALA) and the association of individual fatty acids with D-dimer in patients with detectable D-dimer values (n = 1096) as well as with BTG (n = 2371) using multiple linear regression models adjusted for confounders. Median D-dimer and BTG levels were 0.340 ug/mL and 448 ng/mL, respectively. Higher total n-3 FAs correlated with lower D-dimer levels (coefficient 0.94, 95% confidence interval (Cl) 0.90–0.98, p = 0.004) and lower BTG levels (coefficient 0.97, Cl 0.95–0.99, p = 0.003). Likewise, the individual n-3 FAs EPA, DHA, DPA and ALA showed an inverse association with D-dimer. Higher levels of DHA, DPA and ALA correlated with lower BTG levels, whereas EPA showed a positive association with BTG. In patients with AF, higher levels of n-3 FAs were associated with lower levels of D-dimer and BTG, markers for activated coagulation and platelets, respectively. These findings suggest that n-3 FAs may exert antithrombotic properties in patients with AF.

BACKGROUND: Atrial fibrillation is a major risk factor for stroke and silent brain infarcts. We studied whether a multimodal approach offers additional insights to the CHA ₂ DS ₂ -VASc score in predicting stroke or new brain infarcts on magnetic resonance imaging (MRI) over a 2-year follow-up. METHODS: Swiss-AF is a prospective, multicenter cohort study of patients with known atrial fibrillation. We included patients with available brain MRI both at enrollment and 2 years later. The dates of the baseline and follow-up visits ranged from March 2014 to November 2020. The primary outcome was assessed 2 years after baseline and was defined as a composite of clinically identified stroke or any new brain infarct on the 2-year MRI. We compared a multivariable logistic regression model including prespecified clinical, biomarker, and baseline MRI variables to the CHA ₂ DS ₂ -VASc score. RESULTS: We included 1232 patients, 89.8% of them taking oral anticoagulants. The primary outcome occurred in 78 patients (6.3%). The following baseline variables were included in the final multivariate model and were significantly associated with the primary outcome: white matter lesion volume in milliliters (adjusted odds ratio [aOR], 1.91 [95% CI, 1.45–2.56]), NT-proBNP (N-terminal pro-B-type natriuretic peptide; aOR, 1.75 [95% CI, 1.20–2.63]), GDF-15 (growth differentiation factor-15; aOR, 1.68 [95% CI, 1.11–2.53]), serum creatinine (aOR, 1.50 [95% CI, 1.02–2.22]), IL (interleukin)-6 (aOR, 1.37 [95% CI, 1.00–1.86]), and hFABP (heart-type fatty acid–binding protein; aOR, 0.48 [95% CI, 0.31–0.73]). Overall performance and discrimination of the new model was superior to that of the CHA ₂ DS ₂ -VASc score (C statistic, 0.82 [95% CI, 0.77–0.87] versus 0.64 [95% CI, 0.58–0.70]). CONCLUSIONS: In patients with atrial fibrillation, a model incorporating white matter lesion volume on baseline MRI and selected blood markers yielded new insights on residual stroke risk despite a high proportion of patients on oral anticoagulants. This may be relevant to develop further preventive measures.

The present study aimed to assess various stressful situations and the psychological impact of the first COVID-19 pandemic lockdown among youths in Switzerland. We included samples of 1627 young adults aged 19–24 from the Swiss Youth Epidemiological Study on Mental Health and 1146 children and adolescents aged 12–17 years and their parents. We assessed symptoms of various mental health problems, internet use, and perceived stress during the first COVID-19 lockdown. In the analyses, data were weighted to be representative of the Swiss population. During the first lockdown in Switzerland, the most common sources of perceived stress were the disruption of social life and important activities, uncertainty about how long the state of affairs would last, and the pandemic itself. In addition, around one-fifth of the young adults met the criteria for at least one of the mental health problems (attention deficit hyperactivity disorder, depression, generalized anxiety disorder), while one-third of children/adolescents screened positive for at least one of the mental health problems (attention deficit hyperactivity disorder, oppositional defiant disorder, depression, anxiety). Moreover, 30.1% of children and 21.3% of young adults met the criteria for problematic internet use. The study showed considerable stress perceived by young adults and symptoms of mental health problems, especially among females, during the first COVID-19 lockdown in Switzerland.

Aims: Mental disorders in children are a significant and growing cause of morbidity worldwide. Although interventions to help overcome barriers along the pathway to accessing health care for children with mental disorders exist, there is no overview of randomised controlled trials (RCTs) on these interventions as yet. This study aimed to systematically identify RCTs of interventions to improve access to mental health care for children and synthesise them using a conceptual framework of access to health care.Methods: This systematic review was performed following a predefined protocol registered with PROSPERO (ID: CRD42018081714). We searched the databases MEDLINE, EMBASE, PsycINFO and CENTRAL for RCTs up to 15 May 2019 using terms related to the concepts ‘young people,’ ‘mental disorders’ and ‘help-seeking interventions’ and scanned reference lists from relevant studies. Two reviewers independently screened all identified articles in a two-stage process, extracted results on outcomes of interest (knowledge, attitudes, intentions, help-seeking, accessing care, mental health outcomes and satisfaction), assessed the risk of bias and conducted meta-analyses where deemed appropriate.Results: After screening 5641 identified articles, 34 RCTs were eligible for inclusion. Eighty per cent of universal school-based interventions measuring knowledge (n= 5) and 67% measuring attitudes (n= 6) reported significantly better results compared with controls on those outcomes, whereas 20% measuring access to care (n= 5) and none measuring mental health outcomes (n= 7) did. In contrast, 71% of interventions targeting at-risk individuals (n= 21) reported better access to care compared with controls, while just 33% (n= 6) did for mental health outcomes. For satisfaction with care, this proportion was 80% (n= 5). Meta-analyses of interventions measuring initial appointment attendance yielded combined odds ratios of 3.11 (2.07–4.67) for appointment reminder interventions and 3.51 (2.02–6.11) for treatment engagement interventions. The outcomes for universal school-based interventions were heterogeneous and could not be summarised quantitatively through meta-analysis.Conclusions: To have a population-level effect on improving children's access to mental health care, two-stage interventions that identify those in need and then engage them in the health-care system may be necessary. We need more evidence on interventions to target contextual factors such as affordability and infrastructural barriers.