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Latent transition analysis (LTA) is a useful statistical modelling approach for describe transitions between latent classes over time. LTA may be characterized in terms of prevalence at each time point and through transition probabilities over time. Investigating predictors of these transitions is often of key interest. Currently, LTA can mostly be carried out using commercial and specialized software and only to some limited extent by means of open source statistical software. This tutorial demonstrates a flexible and modular approach for LTA, providing a powerful alternative using R through a combination latent class analysis and multiple logistic regression models. This approach has several advantages from a modelling perspective, as demonstrated through revisiting a previously conducted LTA, published in PLoS ONE recently. In short, results were very similar to the original analysis using commercial software although some additional novel results were also obtained. The proposed alternative approach offers more options in terms of choice of effect measures, model assumptions such as hierarchical structures and covariate adjustment, and differential handling of missing data. R code snippets are provided in the tutorial. A detailed accompanying script is also provided for full reproducibility.

Background Sleep is essential for child and adolescent health and well-being. There is an increasing interest in whether electronic media use affects children and young adolescents’ sleep. Prior reviews have focused on a school-aged population. Moreover, it is crucial that research continuously addresses the processes of technology and media use and the implication on sleep. This systematic review examines the evidence of electronic media use related to sleep among 0–15-year-olds. Methods Searches were carried out in four databases (CINAHL, Web of Science, EMBASE, and Medline). Inclusion criteria included age ≤ 15 years, and intervention, cohort, or cross-sectional studies from western countries. Methodological quality was rated using the Quality Assessment Tool for Quantitative Studies by two independent reviewers. Data was extracted using a standardized data extraction form. Synthesis was done by summarizing results across studies by age groups of 0–5, 6–12, and 13–15 years within four sleep domains: Bedtime and sleep onset; Sleep quality; Sleep duration; Daytime tiredness. Results The search identified 10,719 unique studies, of which 109 fulfilled inclusion and exclusion criteria and were assessed for methodological quality. In total, 49 studies were included in the review. The study designs were randomized controlled trials ( n  = 3), quasi-experimental studies ( n  = 2), prospective cohort studies ( n  = 15), and cross-sectional studies ( n  = 29). Evidence for an association between electronic media use and sleep duration was identified, with stronger evidence for 6–15-years-olds than 0–5-year-olds. The evidence for a relationship between electronic media use and other sleep outcomes was more inconclusive. However, for 6–12-year-old children, there was evidence for associations of electronic media use with delayed bedtime and poor sleep quality. For 13–15-year-olds, there was evidence for associations between screen time and problems falling asleep, and between social media use and poor sleep quality. Conclusions Overall, electronic media use was generally associated with shorter sleep duration in children and adolescents. Studies with stronger research design and of higher quality are needed to draw solid conclusions about electronic media’s impact on other sleep outcomes. Public awareness and interventions could be promoted about the potential negative impact on children’s sleep of electronic media devices that are used excessively and close to bedtime.

This statement paper summarises and appraises the evidence on diagnosis, prevention, and treatment of common shoulder injuries in sports. We systematically searched Medline and Embase. The Grading of Recommendations Assessment, Development and Evaluation tool was applied to evaluate the overall quality of evidence.For diagnosis, we included 19 clinical tests from mixed populations. Tests for anterior instability, biceps-labrum complex injuries and full subscapularis rupture had high diagnostic accuracy (low to moderate quality of evidence).For prevention, the Oslo Sports Trauma Research Center, the Shoulder Control, the FIFA 11+ shoulder injury prevention programmes, and a baseball-specific programme (range of motion, stretching, dynamic stability and strengthening exercises) showed moderate to large effect size in reducing the risk of shoulder injury compared with no intervention (very low to moderate quality of evidence).For treatment, a rehabilitation programme including stretching, ice packs, electrotherapy and compression, and strengthening exercises showed a large effect size in reducing pain and disability compared with no intervention in athletes with subacromial impingement syndrome (very low to moderate quality of evidence). For the treatment of supraspinatus tendinopathy, hyperthermia treatment (heating the skin to 38°C–40°C) resulted in large effect size in reducing pain and disability compared with ultrasound or pendular swinging and stretching exercises (moderate quality of evidence). Strengthening exercise alone or in combination with stretching exercises promoted a large effect in reducing shoulder pain (cohort studies, no comparators) (very low quality of evidence). The quality of evidence for most estimates was low to moderate, indicating that future high-quality research may alter our recommendations for clinical practice.

ObjectiveTo determine concussion incidence in youth handball.DesignProspective cohort study nested in a randomised controlled trialSettingCommunity handball clubsParticipants758 players aged 11–17 yearsInterventions (or Assessment of Risk Factors)Handball playing hours and head traumas were monitored weekly by the Oslo Sport Trauma Research Center Health questionnaire (OSTRC-H2) and a concussion specific question over 21 weeks using the app Athlete Monitoring. Players reporting a head injury via the OSTRC-H2 questionnaire or answered yes to the concussion specific question underwent a standardized 5–10-Minute telephone interview within 1 week.Outcome MeasuresCases of concussion was defined according to the Consensus in Sport Group. Handball playing hours was defined as time spend in handball training and match. Incidence is reported as cases per 1000 playing hours.Main Results44 cases of concussion were identified. Overall incidence of concussion was 0,94 per 1000 hours [95% CI; 0,68- 1,26]. Female athletes sustained twice as many concussions than male athletes (incidence rate ratio (IRR) 2,20 [95% CI; 1,09–4,84]). Concussion happened 9 times more often during match compared to training (9,09 [95% CI; 4,72–18,25]). No statistically significant difference in IRR between age groups (U13/U15 vs. U17) was found.ConclusionsThis is the first study reporting concussion incidence in youth handball. Incidence was higher amongst female handball players compared to males and in match versus training. No difference in concussion incidence was found between age groups.

The present first‐in‐human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose‐derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease and ischemic heart failure (IHF). Batches of CSCC_ASC were isolated from three healthy donors by liposuction from abdominal adipose tissue. Adipose mesenchymal stromal cells were culture expanded in bioreactors without the use of animal constituents, cryopreserved, and stored in vials in nitrogen dry‐storage containers until use. Direct injection of CSCC_ASC into the myocardium did not cause any complications or serious adverse events related to either treatment or cell administration in a 6‐month follow‐up period. Four out of ten heart failure patients developed donor‐specific de novo human leukocyte antigen (HLA) class I antibodies, and two out of ten patients had donor‐specific HLA antibodies already at baseline. There were no clinical symptoms or changes in inflammatory parameters in the follow‐up period that indicated an ongoing immune response. There was a tendency toward improvement in cardiac function after CSCC_ASC treatment at 6‐month follow‐up: left ventricular end systolic volume decreased and left ventricular ejection fraction increased. In addition, exercise capacity increased. These changes were independent of the presence or absence of HLA antibodies. It is concluded that the newly developed cryopreserved product CSCC_ASC from healthy donors was a safe and feasible treatment. We observed a tendency toward efficacy in patients with IHF. These findings have to be confirmed in larger placebo controlled clinical trials. Stem Cells Translational Medicine 2017;6:1963–1971 Production circle of allogeneic mesenchymal stromal cells from healthy donors to treatment of heart failure patients.

This statement summarises and appraises the evidence on diagnostic tests and clinical information, and non-operative treatment of femoroacetabular impingement (FAI) syndrome and labral injuries. We included studies based on the highest available level of evidence as judged by study design. We evaluated the certainty of evidence using the Grading of Recommendations Assessment Development and Evaluation framework. We found 29 studies reporting 23 clinical tests and 14 different forms of clinical information, respectively. Restricted internal hip rotation in 0° hip flexion with or without pain was best to rule in FAI syndrome (low diagnostic effectiveness; low quality of evidence; interpretation of evidence: may increase post-test probability slightly), whereas no pain in Flexion Adduction Internal Rotation test or no restricted range of motion in Flexion Abduction External Rotation test compared with the unaffected side were best to rule out (very low to high diagnostic effectiveness; very low to moderate quality of evidence; interpretation of evidence: very uncertain, but may reduce post-test probability slightly). No forms of clinical information were found useful for diagnosis. For treatment of FAI syndrome, 14 randomised controlled trials were found. Prescribed physiotherapy, consisting of hip strengthening, hip joint manual therapy techniques, functional activity-specific retraining and education showed a small to medium effect size compared with a combination of passive modalities, stretching and advice (very low to low quality of evidence; interpretation of evidence: very uncertain, but may slightly improve outcomes). Prescribed physiotherapy was, however, inferior to hip arthroscopy (small effect size; moderate quality of evidence; interpretation of evidence: hip arthroscopy probably increases outcome slightly). For both domains, the overall quality of evidence ranged from very low to moderate indicating that future research on diagnosis and treatment may alter the conclusions from this review.

Staphylococcus aureus is a major human pathogen that has evolved very efficient immune evading strategies leading to persistent colonization. During different stages of growth, S. aureus express various surface molecules, which may affect the immune stimulating properties, but very little is known about their role in immune stimulation and evasion. Depending on the growth phase, S. aureus may affect antigen presenting cells differently. Here, the impact of growth phases and the surface molecules lipoteichoic acid, peptidoglycan and poly-N-acetyl glucosamine on the induction of IL-12 imperative for an efficient clearance of S. aureus was studied in dendritic cells (DCs). Exponential phase (EP) S. aureus was superior to stationary phase (SP) bacteria in induction of IL-12, which required actin-mediated endocytosis and endosomal acidification. Moreover, addition of staphylococcal cell wall derived peptidoglycan to EP S. aureus stimulated cells increased bacterial uptake but abrogated IL-12 induction, while addition of lipoteichoic acid increased IL-12 production but had no effect on the bacterial uptake. Depletion of the capability to produce poly-N-acetyl glucosamine increased the IL-12 inducing activity of EP bacteria. Furthermore, the mutant dltA unable to produce D-alanylated teichoic acids failed to induce IL-12 but like peptidoglycan and the toll-like receptor (TLR) ligands LPS and Pam3CSK4 the mutant stimulated increased macropinocytosis. In conclusion, the IL-12 response by DCs against S. aureus is highly growth phase dependent, relies on cell wall D-alanylation, endocytosis and subsequent endosomal degradation, and is abrogated by receptor induced macropinocytosis.

Persistent (>4 weeks) postconcussion symptoms (PPCS) are challenging for both patients and clinicians. There is uncertainty about the effect of commonly applied nonpharmacological treatments for the management of PPCS. To systematically assess and summarize evidence for outcomes related to 7 nonpharmacological interventions for PPCS in adults (aged >18 years) and provide recommendations for clinical practice. Systematic literature searches were performed via Embase, MEDLINE, PsycINFO, CINAHL, PEDro, OTseeker, and Cochrane Reviews (via MEDLINE and Embase) from earliest possible publication year to March 3, 2020. The literature was searched for prior systematic reviews and primary studies. To be included, studies had to be intervention studies with a control group and focus on PPCS. A multidisciplinary guideline panel selected interventions based on frequency of use and need for decision support among clinicians, including early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of neck and back, oculomotor vision treatment, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. To be included, studies had to be intervention studies within the areas of the predefined clinical questions, include a control group, and focus on symptoms after concussion or mild traumatic brain injury. Extraction was performed independently by multiple observers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data abstraction and data quality assessment. Included studies were assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Cochrane Risk of Bias (randomized clinical trials) tool. Meta-analysis was performed for all interventions where possible. Random-effects models were used to calculate pooled estimates of effects. The level and certainty of evidence was rated and recommendations formulated according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. All outcomes were planned before data collection began according to a specified protocol. The primary outcomes were the collective burden of PPCS and another outcome reflecting the focus of a particular intervention (eg, physical functioning after graded exercise intervention). Eleven systematic reviews were identified but did not contribute any primary studies; 19 randomized clinical trials comprising 2007 participants (1064 women [53.0%]) were separately identified and included. Evidence for the 7 interventions ranged from no evidence meeting the inclusion criteria to very low and low levels of evidence. Recommendations were weak for early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of the neck and back, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. No relevant evidence was identified for oculomotor vision treatment, so the panel provided a good clinical practice recommendation based on consensus. Based on very low to low certainty of evidence or based on consensus, the guideline panel found weak scientific support for commonly applied nonpharmacological interventions to treat PPCS. Results align with recommendations in international guidelines. Intensified research into all types of intervention for PPCS is needed.

Correspondence to Lars Damsbo, Danish Society for Sports Physical Therapy, Odense C, Denmark; ld@sportsfysioterapi.dk It is finally time to meet again in person. The extensive congress programme leaves room for active reflection and networking in a 2-hour lunch and activity break, where we invite participants to take part in different activities. Physical activity as medicine In this BJSM issue, authors of an original paper conclude that the proportion of time spent in moderate to vigorous physical activity is significantly associated with lower risk of all-cause mortality (see page 1277) .

Background Social inequality in smoking remains an important public health issue. Upper secondary schools offering vocational education and training (VET) comprise more students from lower socioeconomic backgrounds and have higher smoking prevalence than general high schools. This study examined the effects of a school-based multi-component intervention on students’ smoking. Methods A cluster randomized controlled trial. Eligible participants were schools offering VET basic courses or preparatory basic education in Denmark, and their students. Schools were stratified by subject area and eight schools were randomly allocated to intervention (1,160 invited students; 844 analyzed) and six schools to control (1,093 invited students; 815 analyzed). The intervention program comprised smoke-free school hours, class-based activities, and access to smoking cessation support. The control group was encouraged to continue with normal practice. Primary outcomes were daily cigarette consumption and daily smoking status at student level. Secondary outcomes were determinants expected to impact smoking behavior. Outcomes were assessed in students at five-month follow-up. Analyses were by intention-to-treat and per protocol (i.e., whether the intervention was delivered as intended), adjusted for covariates measured at baseline. Moreover, subgroup analyses defined by school type, gender, age, and smoking status at baseline were performed. Multilevel regression models were used to account for the cluster design. Missing data were imputed using multiple imputations. Participants and the research team were not blinded to allocation. Results Intention-to-treat analyses showed no intervention effect on daily cigarette consumption and daily smoking. Pre-planned subgroup analyses showed statistically significant reduction in daily smoking among girls compared with their counterparts in the control group (OR = 0.39, 95% CI: 0.16, 0.98). Per-protocol analysis suggested that schools with full intervention had higher benefits compared with the control group (daily smoking: OR = 0.44, 95% CI: 0.19, 1.02), while no marked differences were seen among schools with partial intervention. Conclusion This study was among the first to test whether a complex, multicomponent intervention could reduce smoking in schools with high smoking risk. Results showed no overall effects. There is a great need to develop programs for this target group and it is important that they are fully implemented if an effect is to be achieved. Trial registration https://www.isrctn.com/ISRCTN16455577 , date of registration 14/06/2018.