In the failing human myocardium, both impaired calcium homoeostasis and alterations in the levels of contractile proteins have been observed, which may be responsible for reduced contractility as well as diastolic dysfunction. In addition, levels of a key protein in calcium cycling, i.e. the sarcoplasmic reticulum Ca(2+)-ATPase, and of the alpha-myosin heavy chain have been shown to be enhanced by treatment with etomoxir, a carnitine palmitoyltransferase inhibitor, in normal and pressure-overloaded rat myocardium. We therefore studied, for the first time, the influence of long-term oral application of etomoxir on cardiac function in patients with chronic heart failure. A dose of 80 mg of etomoxir was given once daily to 10 patients suffering from heart failure (NYHA functional class II-III; mean age 55+/-4 years; one patient with ischaemic heart disease and nine patients with dilated idiopathic cardiomyopathy; all male), in addition to standard therapy. The left ventricular ejection fraction was measured echocardiographically before and after a 3-month period of treatment. Central haemodynamics at rest and exercise (supine position bicycle) were defined by means of a pulmonary artery catheter and thermodilution. All 10 patients improved clinically; no patient had to stop taking the study medication because of side effects; and no patient died during the 3-month period. Maximum cardiac output during exercise increased from 9.72+/-1.25 l/min before to 13.44+/-1.50 l/min after treatment (P<0.01); this increase was mainly due to an increased stroke volume [84+/-7 ml before and 109+/-9 ml after treatment (P<0.01)]. Resting heart rate was slightly reduced (not statistically significant). During exercise, for any given heart rate, stroke volume was significantly enhanced (P<0.05). The left ventricular ejection fraction increased significantly from 21.5+/-2.6% to 27.0+/-2.3% (P<0.01). In acute studies, etomoxir showed neither a positive inotropic effect nor vasodilatory properties. Thus, although the results of this small pilot study are not placebo-controlled, all patients seem to have benefitted from etomoxir treatment. Etomoxir, which has no acute inotropic or vasodilatory properties and is thought to increase gene expression of the sarcoplasmic reticulum Ca(2+)-ATPase and the alpha-myosin heavy chain, improved clinical status, central haemodynamics at rest and during exercise, and left ventricular ejection fraction.

Physical exercise has been shown to be effective in the treatment of non-communicable chronic diseases. However, patients with multiple chronic diseases (multimorbidity) have received little attention in health policy. This pilot trial served as a proof of concept of a 6-months person-oriented exercise intervention for people at risk of or with diagnosed cardiovascular diseases, diabetes mellitus type 2, overweight and/or hip/knee osteoarthritis, regarding effects on health outcomes as well as adherence and safety. The intervention (‘MultiPill-Exercise’) was designed to promote physical exercise participation, considering an individual perspective by addressing personal and environmental factors. Outcomes were assessed at baseline (t0) and after three- (t3) and six-months (t6). The primary outcome was self-reported physical exercise participation in minutes/week comparing t3 and t6 vs. t0. Secondary outcomes included cardio-respiratory fitness (maximum oxygen uptake VO2peak during incremental cycling ergometry), isometric peak torque of knee extensors and flexors, health-related quality of life (Veterans Rand 12 with its subscales of perceived general health (GH), mental health (MCS), and physical health (PCS)) and blood levels. Adherence to exercise (% of attended sessions during the first 12-weeks of the intervention) and adverse events were monitored as well. Data were analyzed using a non-parametric procedure for longitudinal data, estimating rank means (MRank) and relative treatment effects (RTE) as well as linear-mixed effect models for parametric data. The primary endpoint of physical exercise participation was significantly higher at t3 and t6 compared to baseline (t3 vs. t0: MRank = 77.1, p < 0.001, RTE: 0.66; t6 vs. t0: MRank = 70.6, p < 0.001, RTE = 0.60). Improvements at both follow-up time points compared to t0 were also found for relative VO2peak (t3 vs. t0 = 2.6 mL/kg/min, p < 0.001; t6 vs. t0 = 2.0 mL/kg/min, p = 0.001), strength of knee extensors (t3 vs. t0 = 11.7 Nm, p = 0.007; t6 vs. t0= 18.1 Nm, p < 0.001) and GH (t3 vs. t0 = 16.2, p = 0.003; t6 vs. t0 = 13.4, p = 0.008). No changes were found for MCS, PCS and for blood levels. Overall exercise adherence was 77%. No serious adverse events were recorded. Results of this pilot trial represent a first proof of concept for the intervention ‘MultiPill-Exercise’ that will now be implemented and evaluated in a real-world health care setting.

Background Multimorbidity is a major problem in Europe, increasing the need for prevention and rehabilitation programs. In Germany no guidelines have been developed that focus on patients with multiple chronic non-communicable diseases (NCDs). Benefits of physical activity (PA) and exercise in NCDs have been proven, but most interventions focus on single conditions. The evaluation of the effectiveness, efficiency and safety of PA programs in patients suffering from multiple NCDs and the feasibility of the implementation within the health care service remain open research questions. Methods The multi-site randomized controlled pragmatic trial includes 320 sedentary subjects with at least two of the following NCDs, either manifested or in a pre-stage with evident risk factors: Cardio-vascular disease, Diabetes mellitus type 2, knee/ hip osteoarthritis and obesity. Participants will be recruited from general practitioners and medical specialists and randomized to standard care of a statutory health insurance or MultiPill-Exercise. Standard care includes a choice of one or a maximum of two 8- to 12-week health programs, including nutrition, exercise, relaxation or special disease management programs. MultiPill-Exercise is based on the bio-psycho-social health model, considering a person-oriented perspective in light of given individual characteristics and context factors. The 24-weeks intervention focuses on aerobic and strengthening exercises in line with the WHO PA recommendations. Psychological and pedagogical elements along with behavior change techniques are implemented to ease the initiation and maintenance of exercise participation and lifestyle change, including nutrition. Primary outcome will be short- and long-term PA measured with the European Health Interview Survey-Physical Activity Questionnaire (EHIS-PAQ). Secondly, the effectiveness of the program on generic, disease specific, economic, and exercise behavioral parameters, as well as program adherence and safety will be evaluated. Discussion Results of this trial evaluate the PA intervention program in people with multiple NCDs in a real-life scenario. It will serve as a proof of concept with the opportunity of translation into routine practice. This approach, as a multi-site RCT with its rigorous methods and standardized operating procedures for the conduction of the intervention, will allow valid conclusions for the implementation of PA interventions in people with multimorbidity. Trial registration The trial was registered at www.drks.de (ID: DRKS00025033) on 30th September 2021.

Background: To date multimorbidity has not received much attention in health policies, even though multiple chronic diseases put high demands on the health care system in industrial nations. Enormous costs of care and a physically, mentally, and socially reduced quality of life are common consequences of multimorbidity. Physical activity (PA) has a positive preventive and therapeutic effect on common non-communicable diseases. The objective of this study will be to evaluate the health benefits and harms of PA interventions for sedentary adults with multimorbidity in primary care settings. Methods: This is the study protocol for a systematic review. We will search PubMed, MEDLINE (Ovid), Web of Science, CINHAL, and the Cochrane Library (from inception onwards). In addition, clinical trial registers and reference lists of included studies will be searched. We will include randomized controlled trials, quasi-experimental, and non-randomized trials examining the health benefits and harms of PA interventions with or without additional lifestyle interventions for sedentary adult patients with multimorbidity (e.g., two or more chronic non-communicable diseases) in primary care. Eligible control groups will be standard care, placebo, or medications. Two reviewers will independently screen all citations, abstracts data, and full-text articles. The primary outcomes will be health-related quality of life and mortality. Secondary outcomes will include cardiovascular fitness, muscular strength and disease-specific outcomes (e.g., depression score), biomarkers as well as control of metabolic risk factors (e.g., blood pressure, HBA1c, body weight) and any adverse event. The methodological quality of the studies will be appraised using appropriate tools. If feasible, we will conduct random effects meta-analysis. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., study design, geographical location, or type of intervention). Strength of the body of evidence will be assessed according to the Grading of Recommendations Assessment (GRADE).

Background Several studies have evaluated the applicability of the Functional Movement Screen (FMS) as a screening tool for injury prediction. However, only few studies investigate gender differences for FMS as a screening tool for female and male college students. Objective To evaluate gender differences in FMS single items and the overall score. In addition, the applicability of FMS as a diagnostic tool for injury prevention of German exercise students will be investigated. Method N = 99 college students performed an FMS at the beginning of the semester. Injuries were recorded for the entire term. Gender differences of FMS single items were assessed using the Mann-Whitney-U-Test. Differences in injury prediction were calculated using logistic regression. If the model was statistically significant, diagnostic accuracy was calculated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). The Youden index was used to identify a cut-off score. 2 × 2 contingency tables, sensitivity and specifity, positive/negative predictive values, and likelihood ratios were assessed. Results There were significant gender differences for Deep Squat, Shoulder Mobility, Trunk Stability Push Up, and Active Straight Leg Raise. The logistic regression showed that the composite score was statistically significant in clarifying the model for females (p = 0.005, RN 2 = 0.14), but not for males (p = 0.18, RN 2 = 0.04). The ROC curve indicated acceptable injury prediction in females (AUC: 0.66, p = 0.02) and poor injury prediction in males (AUC: 0.40, p = 0.19). The cut-off score of ≤ 16 for females resulted in a sensitivity of 63 % and specificity of 54 %. No cut-off score was calculated for males. Conclusion Females performed better on flexibility items, while males scored higher on strength exercises. Results of the study indicate low predictive accuracy. Therefore, no solid recommendation can be made for the use of the FMS as an injury screening tool for either female or male German exercise science students.