Background: We performed a random-effects network meta-analysis to study the efficacy and safety of newly developed drugs for the acute treatment of migraine attacks. Methods: MEDLINE via PubMed, Embase and The Cochrane Register of Controlled Trials were searched from inception to 11 February 2022. Phase 3 randomized controlled trials examining all formulations of lasmiditan, rimegepant and ubrogepant for the acute treatment of adults with migraine, were included. Data were extracted following the PRISMA guidelines. Results: Seven studies (SAMURAI, SPARTAN, CENTURION, Study 302, Study 303, ACHIEVE I and II) involving n = 12,859 patients were included. All treatments were superior in efficacy to placebo. Lasmiditan 200 mg showed the highest two-hour pain freedom, while two-hour freedom from most bothersome symptom was equally achieved by the higher doses of lasmiditan (100 and 200 mg), rimegepant and the higher doses of ubrogepant (50 and 100 mg). The odds of treatment-emergent adverse events were greatest with all doses of lasmiditan. Conclusion: Lasmiditan 200 mg was the most effective intervention in the treatment of migraine attacks, although it was associated with high degrees of dizziness, nausea and somnolence. Rimegepant showed slightly lower, but similar efficacy rates to lasmiditan. Ubrogepant had overall the best tolerability profile. These conclusions are limited by the absence of head-to-head comparisons, limitations of individual trials and of the meta-analysis methodology itself. PROSPERO trial registration: CRD42022308224

Anaemia is frequently observed in patients with cirrhosis and was identified as a predictor of adverse outcomes, such as increased mortality and occurrence of acute-on-chronic liver failure. To date, the possible effects of iron supplementation on these adverse outcomes are not well described. We therefore aimed to assess the role of iron supplementation in patients with cirrhosis and its capability to improve prognosis. Laboratory diagnostics were performed in consecutive outpatients with cirrhosis admitted between July 2018 and December 2019 to the University Hospital Essen. Associations with transplant-free survival were assessed in regression models. A total of 317 outpatients with cirrhosis were included, of whom 61 received a liver transplant (n = 19) or died (n = 42). In multivariate Cox regression analysis, male sex (hazard ratio [HR] = 3.33, 95% CI [1.59, 6.99], p = 0.001), model for end-stage liver disease score (HR = 1.19, 95% CI [1.11, 1.27], p <0.001) and the increase of haemoglobin levels within 6 months (ΔHb6) (HR = 0.72, 95% CI [0.63, 0.83], p <0.001) were associated with transplant-free survival. Regarding the prediction of haemoglobin increase, intake of rifaximin (beta = 0.50, SD beta = 0.19, p = 0.007) and iron supplementation (beta = 0.79, SD beta = 0.26, p = 0.003) were significant predictors in multivariate analysis. An increase of haemoglobin levels is associated with improvement of transplant-free survival in patients with cirrhosis. Because the prediction of haemoglobin increase significantly depends on rifaximin and iron supplementation, application of these two medications can have an important impact on the outcome of these patients. Anaemia is very common in patients with cirrhosis and is known to be a predictor of negative outcomes, but little is known about the effect of iron substitution in these individuals. In our cohort, increase of haemoglobin levels improved transplant-free survival of patients with cirrhosis. The increase of haemoglobin levels was mainly induced by iron supplementation and was even stronger in the case of concomitant use of iron and rifaximin. UME-ID-10042.

Background and Objective: The melanocortin-4 receptor agonist setmelanotide compensates for upstream gene defects in the brain leptin-melanocortin pathway and reduces hyperphagia and obesity in selected monogenic obesity forms and Bardet-Biedl syndrome (BBS). We aimed to evaluate the short-term impact of setmelanotide treatment in BBS presenting original real-world data focusing on metabolic dysfunction-associated steatotic liver disease (MASLD) and kidney function. Methods: This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy. Ultrasound examination of the liver including shear wave elastography, dispersion and attenuation imaging (ATI), a bioimpedance analysis, and a hyperphagia questionnaire survey were applied in addition to clinical data collection. Results: Twenty-six patients with BBS (mean age 19.2 years, range [6.2; 51.8]; mean body mass index (BMI) z-score 2.95, range [1.32; 4.84]) were included. All were classified with MASLD (54% S3, 23% each S1 and S2). After 6 months of setmelanotide treatment, estimated glomerular filtration rate increased up to 10.1 mL/min/1.73 m² (95% confidence interval (CI) [4.3; 15.9]). The following parameters also improved: BMI z-score −0.5 (95% CI [−0.6; −0.3]); hyperphagia score −12.3 (95% CI [−15.5; −9.0]); total body fat −3.1% (95% CI [−5.7; −0.5]); ATI −0.14 dB/cm/MHZ (95% CI [−0.17; −0.11]). A total of 85% of patients exhibited either resolution of MASLD or stabilization at grade S1. MASLD improvement correlated only with liver size, not BMI reduction. Conclusion: Setmelanotide treatment is associated with improvement of MASLD independent of BMI reduction as well as increased glomerular filtration rate in BBS.

Chronic low back disorders are the leading cause of direct and indirect healthcare burden globally. Exercise training improves pain intensity, mental health and physical function. However, the optimal prescription variables are unknown. We aim to compare the efficacy of various exercise dosages for chronic low back disorders to identify the optimal prescription variables. Six databases (Medline, SPORTDiscus, CINAHL, PsycINFO, EMBASE and CENTRAL), trial registries (ClinicalTrials.gov and WHO International Clinical Trials Registry Platform) and reference lists of prior systematic reviews will be searched, and we will conduct forward and backward citation tracking. We will include peer-reviewed randomised controlled trials (individual, cluster or cross-over trials) published in English or German language comparing exercise training to other exercise training or non-exercise training interventions (conservative, non-surgical, non-pharmacological, non-invasive treatments, placebo, sham, usual/standard care, no-treatment control, waitlist control) in adults with chronic low back disorders. Outcomes will include pain intensity, disability, mental health, adverse events, adherence rate, dropout rate and work capacity. Version 2 of the Cochrane risk-of-bias tool will be employed. The dose will be categorised as cumulative dose (total and weekly minutes of exercise training) and individual dose prescription variables (intervention duration, session duration, frequency and intensity). Dose-response model-based network meta-analysis will be used to assess the comparative efficacy of different exercise doses to determine a dose–response relationship. The certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation. Information about optimal exercise training dosage will help in enhancing treatment outcomes.

Background/Objectives: The “Palliative Care and Rapid Emergency Screening Tool” (P-CaRES) is used to identify patients with palliative needs in the emergency department. This study aims to translate, adapt, and validate the P-CaRES tool for the German healthcare context. Methods: This is a monocentric, non-interventional, retrospective study conducted in the emergency department of the University Hospital Essen, Germany. After a structured translation process, the tool’s face and content validity were evaluated using questionnaires completed by healthcare workers. Construct validity was established by comparing the results with the German-validated Supportive and Palliative Care Indicators Tool (SPICT). A palliative care physician blinded to the tool, independently assessed the screened patients, and made recommendations on the appropriateness of palliative care referrals. Results: Two hundred eighty-nine emergency department visits were examined. In addition, a total of 26 healthcare professionals were surveyed. 258 screenings were conducted, with P-CaRES identifying 50 positive cases (19.4%). Agreement between SPICT and P-CaRES was 88.4% (kappa: 0.67, 95% confidence interval (CI): [0.56, 0.78]), showing 64.7% sensitivity and 96.8% specificity. Expert comparison yielded 85.5% agreement (kappa: 0.54, 95% CI: [0.41, 0.68]), with 64.0% sensitivity and 90.8% specificity. Face and content validity showed strong agreement regarding the tool’s design, including its comprehensibility, applicability, ease of use, and precision, as well as its usefulness in referring patients to a specialized palliative care team. Conclusions: The study successfully validated a cultural and linguistic equivalent German version of the P-CaRES tool. Further research is necessary to assess the tool’s effectiveness in clinical practice.