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Responsiveness of exercise parameters in children with inflammatory myositis

OBJECTIVE: Juvenile dermatomyositis (DM) is an inflammatory myopathy in which the immune system targets the microvasculature of the skeletal muscle and skin, leading to significant muscle weakness and exercise intolerance, although the precise etiology is unknown. The goal of this study was to investigate the changes in exercise capacity in children with myositis during active and inactive disease periods and to study the responsiveness of exercise parameters.METHODS: Thirteen children with juvenile DM (mean+/-SD age 11.2+/-2.6 years) participated in this study. Patients performed a maximal exercise test using an electronically braked cycle ergometer and respiratory gas analysis system. Exercise parameters were analyzed, including peak oxygen uptake (VO2peak), peak work rate (Wpeak), and ventilatory anaerobic threshold (VAT). All children were tested during an active period of the disease and during a remission period. From these data, 4 different response statistics were calculated.RESULTS: The children performed significantly better during a remission period compared with a period of active disease. Most exercise parameters showed a very large response. The 5 most responsive parameters were Wpeak, Wpeak (percent predicted), oxygen pulse, VO2peak, and power at the VAT.CONCLUSION: We found in our longitudinal study that children with active juvenile DM had significantly reduced exercise parameters compared with a remission period. Moreover, we found that several parameters had very good responsiveness. With previously established validity and reliability, exercise testing has been demonstrated to be an excellent noninvasive instrument for the longitudinal followup of children with myositis.

Protein intake, nutritional status and outcomes in ICU survivors

The impact of bed rest on human skeletal muscle metabolism

Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.

Oxygenation threshold derived from near-infrared Spectroscopy

BACKGROUND: Near-infrared spectroscopy (NIRS) measurements of oxygenation reflect O2 delivery and utilization in exercising muscle and may improve detection of a critical exercise threshold.PURPOSE: First, to detect an oxygenation breakpoint (Δ[O2HbMb-HHbMb]-BP) and compare this breakpoint to ventilatory thresholds during a maximal incremental test across sexes and training status. Second, to assess reproducibility of NIRS signals and exercise thresholds and investigate confounding effects of adipose tissue thickness on NIRS measurements.METHODS: Forty subjects (10 trained male cyclists, 10 trained female cyclists, 11 endurance trained males and 9 recreationally trained males) performed maximal incremental cycling exercise to determine Δ[O2HbMb-HHbMb]-BP and ventilatory thresholds (VT1 and VT2). Muscle haemoglobin and myoglobin O2 oxygenation ([HHbMb], [O2HbMb], SmO2) was determined in m. vastus lateralis. Δ[O2HbMb-HHbMb]-BP was determined by double linear regression. Trained cyclists performed the maximal incremental test twice to assess reproducibility. Adipose tissue thickness (ATT) was determined by skinfold measurements.RESULTS: Δ[O2HbMb-HHbMb]-BP was not different from VT1, but only moderately related (r = 0.58-0.63, p<0.001). VT1 was different across sexes and training status, whereas Δ[O2HbMb-HHbMb]-BP differed only across sexes. Reproducibility was high for SmO2 (ICC = 0.69-0.97), Δ[O2HbMb-HHbMb]-BP (ICC = 0.80-0.88) and ventilatory thresholds (ICC = 0.96-0.99). SmO2 at peak exercise and at occlusion were strongly related to adipose tissue thickness (r2 = 0.81, p<0.001; r2 = 0.79, p<0.001). Moreover, ATT was related to asymmetric changes in Δ[HHbMb] and Δ[O2HbMb] during incremental exercise (r = -0.64, p<0.001) and during occlusion (r = -0.50, p<0.05).CONCLUSION: Although the oxygenation threshold is reproducible and potentially a suitable exercise threshold, VT1 discriminates better across sexes and training status during maximal stepwise incremental exercise. Continuous-wave NIRS measurements are reproducible, but strongly affected by adipose tissue thickness.

Study protocol of a randomized, doubleblind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain

Abstract Background: Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. Methods: In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m2) of at least 16years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 allocation to placebo or metformin, and will be treated for a total of 26 weeks. Metformin will be started at 500 mg b.i.d. and escalated to 1000 mg b.i.d. 2 weeks thereafter (up to a maximum of 2000mg daily). In addition, all participants will undergo a lifestyle intervention as part of the usual treatment consisting of a combination of an exercise program and dietary consultations. The primary outcome measure is difference in body weight as a continuous trait between the two arms from treatment inception until 26 weeks of treatment, compared to baseline. Secondary outcome measures include: 1) Any element of metabolic syndrome (MetS); 2) Response, defined as ≥5% body weight loss at 26 weeks relative to treatment inception; 3) Quality of life; 4) General mental and physical health; and 5) Cost-effectiveness. Finally, we aim to assess whether genetic liability to BMI and MetS may help estimate the amount of weight reduction following initiation of metformin treatment. Discussion: The pragmatic design of the current trial allows for a comparison of the efficacy and safety of metformin in combination with a lifestyle intervention in the treatment of AiWG, facilitating the development of guidelines on the interventions for this major health problem.

Effects of closed loop ventilation on ventilator settings, patient outcomes and ICU staff workloads - A systematic review

BACKGROUNDLung protective ventilation is considered standard of care in the intensive care unit. However, modifying the ventilator settings can be challenging and is time consuming. Closed loop modes of ventilation are increasingly attractive for use in critically ill patients. With closed loop ventilation, settings that are typically managed by the ICU professionals are under control of the ventilator's algorithms.OBJECTIVESTo describe the effectiveness, safety, efficacy and workload with currently available closed loop ventilation modes.DESIGNSystematic review of randomised clinical trials.DATA SOURCESA comprehensive systematic search in PubMed, Embase and the Cochrane Central register of Controlled Trials search was performed in January 2023.ELIGIBILITY CRITERIARandomised clinical trials that compared closed loop ventilation with conventional ventilation modes and reported on effectiveness, safety, efficacy or workload.RESULTSThe search identified 51 studies that met the inclusion criteria. Closed loop ventilation, when compared with conventional ventilation, demonstrates enhanced management of crucial ventilator variables and parameters essential for lung protection across diverse patient cohorts. Adverse events were seldom reported. Several studies indicate potential improvements in patient outcomes with closed loop ventilation; however, it is worth noting that these studies might have been underpowered to conclusively demonstrate such benefits. Closed loop ventilation resulted in a reduction of various aspects associated with the workload of ICU professionals but there have been no studies that studied workload in sufficient detail.CONCLUSIONSClosed loop ventilation modes are at least as effective in choosing correct ventilator settings as ventilation performed by ICU professionals and have the potential to reduce the workload related to ventilation. Nevertheless, there is a lack of sufficient research to comprehensively assess the overall impact of these modes on patient outcomes, and on the workload of ICU staff.