BACKGROUND: Critical illness polyneuropathy and myopathy (CIP/CIM) are frequent complications in the intensive care unit (ICU) with major consequences for the progress and outcome of subjects. CIP/CIM delays the weaning process, prolongs the hospital stay and increases the mortality rate. Additionally, it may have long-term consequences beyond the hospitalisation phase with prolonged disability. Even though there is growing interest in CIP/CIM, research about the clinical and post-clinical course as well as the middle-term and long-term outcomes of subjects with CIP/CIM is scarce. A large prospective study of critically ill subjects is needed with accurate diagnosis during the acute stage and comprehensive assessment during long-term follow-up.
METHODS: This prospective observational cohort study aims to compare the clinical and post-clinical course of chronically critically ill subjects with and without the diagnosis of CIP/CIM and to determine predictors for the middle-term and long-term outcomes of subjects with CIP/CIM. In addition, the influence of the preclinical health status and the preclinical frailty on the long-term outcome of subjects with CIP/CIM will be investigated.This single-centre study will include 250 critically ill patients who were invasively ventilated for at least 5 days at the ICU and show reduced motor strength. At five study visits at admission and discharge to neurological rehabilitation, and 12, 18 and 24 months after disease onset, a comprehensive test battery will be applied including assessments of functioning and impairment, independence, health-related quality of life, activity and participation, cognition, gait and balance, fatigue, mental health and frailty.Secondary objectives are the documentation of therapy goals, therapy content and achieved milestones during the rehabilitation, to evaluate the clinimetric properties of the Mini-BESTest in critically ill patients, and to evaluate the time course and outcome of subjects with CIP/CIM after SARS-CoV-2 infection.
BACKGROUND: The study was approved by the ethical committee of the Ludwig-Maximilians University Munich. Participants will be included in the study after having signed informed consent.Results will be published in scientific, peer-reviewed journals and at national and international conferences.
BACKGROUND: German Clinical Trial Register (DRKS00021753).

OBJECTIVE: To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use.
METHODS: We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses.
RESULTS: Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs.
CONCLUSIONS: Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients\' quality of life.

Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

Fatty acid oxidation (FAO) disorders are autosomal recessive genetic disorders affecting either the transport or the oxidation of fatty acids. Acute symptoms arise during prolonged fasting, intercurrent infections, or intense physical activity. Metabolic crises are characterized by alteration of consciousness, hypoglycemic coma, hepatomegaly, cardiomegaly, arrhythmias, rhabdomyolysis, and can lead to death. In this retrospective and multicentric study, the data of 54 patients with FAO disorders were collected. Overall, 35 patients (64.8%) were diagnosed after newborn screening (NBS), 17 patients on clinical presentation (31.5%), and two patients after family screening (3.7%). Deficiencies identified included medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (75.9%), very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (11.1%), long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency (3.7%), mitochondrial trifunctional protein (MTP) deficiency (1.8%), and carnitine palmitoyltransferase 2 (CPT 2) deficiency (7.4%). The NBS results of 25 patients were reviewed and the neurological outcome of this population was compared with that of the patients who were diagnosed on clinical presentation. This article sought to provide a comprehensive overview of how NBS implementation in Southern Belgium has dramatically improved the neurological outcome of patients with FAO disorders by preventing metabolic crises and death. Further investigations are needed to better understand the physiopathology of long-term complications in order to improve the quality of life of patients and to ensure optimal management.

UNASSIGNED: Proximal hamstring complex injury (PHCI) is a common injury among professional athletes, particularly those participating in pivot contact sports. Previous studies have suggested that surgery can be effective in restoring function and allowing athletes to return to sport (RTS), but the factors influencing successful RTS have been less clear.
UNASSIGNED: To assess RTS capabilities after surgical treatment of PHCI in professional athletes and to identify favorable predictors of RTS.
UNASSIGNED: Case series; Level of evidence, 4.
UNASSIGNED: This study (2002-2022) was conducted on professional athletes who underwent surgical treatment for PHCI at a sports surgery center. The primary outcome of the study was the RTS capability, evaluated based on the rate of athletes\' return to their preinjury level of competition, time delay to RTS, and quality of RTS as measured using their level of performance and progression of scores on activity scales such as the Tegner Activity Scale (TAS) and University of California, Los Angeles (UCLA), scale. \"Maintained performance\" was defined as athletes returning to the same preinjury activity level (per the TAS and UCLA scale) and perceiving themselves to have maintained their performance. Secondary outcomes covered the potential RTS predictors and complication rate. The study distinguished 2 types of PHCI: proximal hamstring tendon avulsion injury (proximal rupture with empty footprint, or having a \"positive dropped ice cream sign\") and complete proximal hamstring free tendon rupture (PHTR; proximal rupture without empty footprint, or having a \"negative dropped ice cream sign\").
UNASSIGNED: The study examined 64 professional athletes (mean age, 27.3 years; 82.8% male) undergoing surgery for PHCI. The RTS rate was 98.4%, with 78.1% of the athletes returning to their preinjury level of competition at 6.2 months (SD, 2.5 months). Twelve (19%) patients had returned to sport at an inferior level of competition, and 2 (3.1%) were unable to continue in their preinjury sport. Subgroup analysis revealed variation in RTS based on sport type, with the highest rate of return to preinjury performance found in athletes in handball and sports with splits (fencing, squash, and escalade; 100%) and soccer (95.2%). In the univariate analysis, male sex (hazard ratio [HR], 4.05; 95% CI, 1.45-11.3; P = .008), higher preinjury TAS score (HR, 1.27; 95% CI, 1.06-1.52; P = .011), injury involving the semimembranosus (HR, 4.84; 95% CI, 2.31-10.2; P < .001) or conjoint tendon (HR, 3.12; 95% CI, 1.55-6.25; P = .001), and PHTR (HR, 7.77; 95% CI, 3.54-17.0; P < .001) were significantly associated with a better postoperative level of competition. Multivariate analysis identified 3 favorable predictors of RTS with HRs of 2.91 (95% CI, 1.01-8.35; P = .047) for male sex, 3.86 (95% CI, 1.78-8.37; P < .001) for isolated semimembranosus injury, and 5.18 (95% CI, 2.24-12.0; P < .001) for PHTR. The complication rate was 4.7%.
UNASSIGNED: Favorable predictors of early RTS were male sex, isolated semimembranosus injury, and PHTR injuries.
UNASSIGNED: NCT02906865 (ClinicalTrials.gov identifier).

BACKGROUND: Drug-drug interactions (DDIs) can harm patients admitted to the intensive care unit (ICU). Yet, clinical decision support systems (CDSSs) aimed at helping physicians prevent DDIs are plagued by low-yield alerts, causing alert fatigue and compromising patient safety. The aim of this multicentre study was to evaluate the effect of tailoring potential DDI alerts to the ICU setting on the frequency of administered high-risk drug combinations.
METHODS: We implemented a cluster randomised stepped-wedge trial in nine ICUs in the Netherlands. Five ICUs already used potential DDI alerts. Patients aged 18 years or older admitted to the ICU with at least two drugs administered were included. Our intervention was an adapted CDSS, only providing alerts for potential DDIs considered as high risk. The intervention was delivered at the ICU level and targeted physicians. We hypothesised that showing only relevant alerts would improve CDSS effectiveness and lead to a decreased number of administered high-risk drug combinations. The order in which the intervention was implemented in the ICUs was randomised by an independent researcher. The primary outcome was the number of administered high-risk drug combinations per 1000 drug administrations per patient and was assessed in all included patients. This trial was registered in the Netherlands Trial Register (identifier NL6762) on Nov 26, 2018, and is now closed.
RESULTS: In total, 10 423 patients admitted to the ICU between Sept 1, 2018, and Sept 1, 2019, were assessed and 9887 patients were included. The mean number of administered high-risk drug combinations per 1000 drug administrations per patient was 26·2 (SD 53·4) in the intervention group (n=5534), compared with 35·6 (65·0) in the control group (n=4353). Tailoring potential DDI alerts to the ICU led to a 12% decrease (95% CI 5-18%; p=0·0008) in the number of administered high-risk drug combinations per 1000 drug administrations per patient, after adjusting for clustering and prognostic factors.
CONCLUSIONS: This cluster randomised stepped-wedge trial showed that tailoring potential DDI alerts to the ICU setting significantly reduced the number of administered high-risk drug combinations. Our list of high-risk drug combinations can be used in other ICUs, and our strategy of tailoring alerts based on clinical relevance could be applied to other clinical settings.
BACKGROUND: ZonMw.

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. Our aim was to describe the clinical, radiological, and functional characteristics of a cohort with SLS and its evolution over time.
A retrospective study was conducted between 2009 and 2018. Demographic, clinical, functional, radiological, and treatment data were collected.
Out of a total of 225 patients, 11 presented with SLS (prevalence of 4.8%). Two patients were excluded. The mean age was 39.33±16 years, and 6 were female. The main symptoms were dyspnea and pleuritic pain. The mean forced vital capacity was 49%, total lung capacity was 60%, carbon monoxide diffusing capacity was 66%, carbon monoxide transference factor was 128%, maximal inspiratory pressure was 66%, and maximal expiratory pressure was 82%. All patients received corticosteroids. After a median follow-up of 19 months, 4 cases showed improvement, and 4 cases remained stable.
SLS should be considered in every lupus patient with unexplained dyspnea. Although it often shows improvement, many cases experience persistent deterioration despite treatment.

BACKGROUND: Statins are the leading lipid-lowering drugs, reducing blood cholesterol by controlling its synthesis. Side effects are linked to the use of statins, in particular statin-associated muscle symptoms (SAMS). Some data suggest that vitamin D supplementation could reduce SAMS.
OBJECTIVE: The purpose of this study was to evaluate the potential benefits of vitamin D supplementation in a randomized controlled trial.
METHODS: Men (n = 23) and women (n = 15) (50.5 ± 7.7 years [mean ± SD]) in primary cardiovascular prevention, self-reporting or not SAMS, were recruited. Following 2 months of statin withdrawal, patients were randomized to supplementation (vitamin D or placebo). After 1 month of supplementation, statins were reintroduced. Before and 2 months after drug reintroduction, muscle damage (creatine kinase and myoglobin) was measured. Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (FHG) were also measured with isokinetic and handheld dynamometers, respectively. The Short Form 36 Health Survey (SF-36) questionnaire and a visual analog scale (VAS) were administrated to assess participants\' self-reported health-related quality of life and SAMS intensity, respectively. Repeated-measures analysis was used to investigate the effects of time, supplementation, and their interaction, according to the presence of SAMS.
RESULTS: Despite no change for objective measures, subjective measures worsened after reintroduction of statins, independent of supplementation (VAS, SF-36 mental component score, all p < 0.05). However, no interaction between time and supplementation according to the presence of SAMS was observed for any variables.
CONCLUSIONS: Vitamin D supplementation does not appear to mitigate SAMS.

Fragility fractures are frequently reported in neuromuscular diseases and negatively influence functional prognosis, quality of life and survival. In LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON(SEPN1)-related congenital myopathy (SELENON-RM) cross-sectional and prospective natural history studies on bone quality and fragility long bone fractures (LBFs) are lacking. We therefore aim to systematically assess bone quality and provide recommendations for clinical care. We performed a one-year prospective natural history study in 21 LAMA2-MD and 10 SELENON-RM patients including a standardized fracture history and bone quality assessment through dual energy Xray absorptiometry scan (DEXA-scan) and/or bone health index (BHI). Ninety percent of the LAMA2-MD and SELENON-RM patients showed low bone quality. Eight (38%) LAMA2-MD and five (50%) SELENON-RM patients had a history of fragility LBFs. During the one-year follow-up period, one LAMA2-MD patient (female, 3 years) experienced a fragility LBF of the right humerus. We found no difference in bone mineral density between baseline and one-year follow-up. Based on general international guidelines for osteoporosis, we advise adequate vitamin D and calcium intake, and standardized clinical follow-up through a DEXA-scan or BHI in all LAMA2-MD and SELENON-RM patients. On indication, patients should be referred to the pediatrics or internal medicine for consideration of additional treatments.

OBJECTIVE: This study aimed to determine the usefulness of electrophysiological exercise tests. The significance of slightly abnormal exercise tests was also examined.
METHODS: We identified all the patients who had undergone exercise testing between February 2007 to June 2022 in Tampere University Hospital, Finland. Their medical records after diagnostic workup and exercise test reports were reviewed. A binary logistic regression was performed to evaluate the association between positive test result in short exercise test, long exercise test, or short exercise test with cooling and genetically confirmed skeletal muscle channelopathy or myotonic disorder.
RESULTS: We identified 256 patients. 27 patients were diagnosed with nondystrophic myotonia, periodic paralysis, myotonic dystrophy type 1, myotonic dystrophy type 2, or other specified myopathy. 14 patients were suspected to have a skeletal muscle channelopathy, but pathogenic variants could not be identified. The remaining 215 patients were diagnosed with other conditions than skeletal muscle channelopathy or myotonic disorder. The combined sensitivity of exercise tests was 59.3% and specificity 99.1%. Abnormal exercise test result was associated with increased risk of skeletal muscle channelopathy or myotonic disorder (OR 164.3, 95% CI 28.3-954.6, p < 0.001).
CONCLUSIONS: Electrophysiological exercise test is not optimal to exclude skeletal muscle channelopathy. It may be useful if a skeletal muscle channelopathy is suspected and genetic testing is negative or indeterminate and further evidence is required. Slightly abnormal exercise test results are possible in various conditions and result from different aetiologies. There is a demand for neurophysiological studies with higher sensitivity to detect skeletal muscle channelopathies.