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Abstract Background Musculoskeletal injuries are a common occurrence in sport. The goal of sport injury epidemiology is to study these injuries at a population level to inform their prevention and treatment. Main body This review provides an overview of musculoskeletal sport injuries and the musculoskeletal system from a biological and epidemiologic perspective, including injury mechanism, categorizations and types of sport injuries, healing, and subsequent injuries. It is meant to provide a concise introductory substantive background of musculoskeletal sport injuries for epidemiologists who may not have formal training in the underlying anatomy and pathophysiology. Conclusion An understanding of sport injuries is important for researchers in sport injury epidemiology when determining how to best define and assess their research questions and measures.

In recent years, a large focus has been placed on managing training load for injury prevention. To minimise injuries, training recommendations should be based on research that examines causal relationships between load and injury risk. While observational studies can be used to estimate causal effects, conventional methods to study the relationship between load and injury are prone to bias. The target trial framework is a valuable tool that requires researchers to emulate a hypothetical randomised trial using observational data. This framework helps to explicitly define research questions and design studies in a way that estimates causal effects. This article provides an overview of the components of the target trial framework as applied to studies on load and injury and describes various considerations that should be made in study design and analyses to minimise bias.

Background and objectives: Despite the importance of the Objective Structured Clinical Examination (OSCE) in Sport and Exercise Medicine, the literature on the topic is fragmented and has been poorly developed. The goal of this review was to map current knowledge about how the OSCE is used in Sport and Exercise Medicine, and to identify knowledge gaps for future research. Method: The authors conducted a scoping review. They searched PubMed and Scopus for articles using key terms related to 'OSCE' and 'sport medicine' with no limit on search start date and up to July 2022. Retrieved records were imported, abstracts were screened, and full-text articles were reviewed. A forward and backward citation tracking was conducted. Data was extracted and a qualitative meta-summary of the studies was conducted. Results: A total of 469 records were screened, and 22 studies were included. The objectives of the studies included using OSCEs to assess knowledge/skills after a training program (n = 11), to assess an intervention (n = 8), and to assess and improve the OSCE itself (n = 3). Thirteen studies reported validity and/or reliability of the OSCE. Conclusion: Despite the widespread use of OSCEs in the examination of Sport and Exercise Medicine trainees, only a handful of scholarly works have been published. More research is needed to support the use of OSCE in Sport and Exercise Medicine for its initial purpose. We highlight avenues for future research such as assessing the need for a deeper exploration of the relationship between candidate characteristics and OSCE scores.

Objective: Cannabis is frequently co-used with tobacco/nicotine products, especially among young adults. Little is known about the effects of this co-use on cannabis cessation outcomes. Within a sample of young adults using cannabis frequently (current use of ≥5 days/week in the past 3 months), this study aimed to (a) document sources of exposure to tobacco/nicotine products, whether used simultaneously with cannabis or on different occasions, (b) examine if the level of cumulated exposure to tobacco/nicotine (self-reported or from biochemical testing) could predict time to cannabis lapse during a cannabis abstinence period, and (c) explore the relationship between nicotine/tobacco exposure and time to cannabis lapse according to tobacco cigarette smoking status. Method: Urine cotinine measures and self-reported data on use of different tobacco/nicotine products, collected from 32 participants (aged 19 to 23), were analyzed to predict time to lapse during a 2-week period of attempted abstinence from cannabis, controlling for cannabis dependence and sex. Results: Half of participants (56.3%) used at least one tobacco/nicotine product. Higher urine cotinine, representing higher cumulated tobacco/nicotine exposure, was related to a higher risk of lapsing (Hazard Ratio [HR] = 1.64; 95%CI [1.04, 2.58]). The risk of lapsing was even higher ([HR] = 3.46; 95%CI [1.17, 10.25]) among heavily tobacco/nicotine exposed (>600 ng/mL, urine cotinine) participants than among unexposed (

BackgroundScreening, brief intervention, and referral to treatment for adolescents (SBIRT-A) is widely recommended to promote detection and early intervention for alcohol and other drug (AOD) use in pediatric primary care. Existing SBIRT-A procedures rely almost exclusively on adolescents alone, despite the recognition of caregivers as critical protective factors in adolescent development and AOD use. Moreover, controlled SBIRT-A studies conducted in primary care have yielded inconsistent findings about implementation feasibility and effects on AOD outcomes and overall developmental functioning. There is urgent need to investigate the value of systematically incorporating caregivers in SBIRT-A procedures. ObjectiveThis randomized effectiveness trial will advance research and scope on SBIRT-A in primary care by conducting a head-to-head test of 2 conceptually grounded, evidence-informed approaches: a standard adolescent-only approach (SBIRT-A-Standard) versus a more expansive family-based approach (SBIRT-A-Family). The SBIRT-A-Family approach enhances the procedures of the SBIRT-A-Standard approach by screening for AOD risk with both adolescents and caregivers; leveraging multidomain, multireporter AOD risk and protection data to inform case identification and risk categorization; and directly involving caregivers in brief intervention and referral to treatment activities. MethodsThe study will include 2300 adolescents (aged 12-17 y) and their caregivers attending 1 of 3 hospital-affiliated pediatric settings serving diverse patient populations in major urban areas. Study recruitment, screening, randomization, and all SBIRT-A activities will occur during a single pediatric visit. SBIRT-A procedures will be delivered digitally on handheld tablets using patient-facing and provider-facing programming. Primary outcomes (AOD use, co-occurring behavior problems, and parent-adolescent communication about AOD use) and secondary outcomes (adolescent quality of life, adolescent risk factors, and therapy attendance) will be assessed at screening and initial assessment and 3-, 6-, 9-, and 12-month follow-ups. The study is well powered to conduct all planned main and moderator (age, sex, race, ethnicity, and youth AOD risk status) analyses. ResultsThis study will be conducted over a 5-year period. Provider training was initiated in year 1 (December 2023). Participant recruitment and follow-up data collection began in year 2 (March 2024). We expect the results from this study to be published in early 2027. ConclusionsSBIRT-A is widely endorsed but currently underused in pediatric primary care settings, and questions remain about optimal approaches and overall effectiveness. In particular, referral to treatment procedures in primary care remains virtually untested among youth. In addition, whereas research strongly supports involving families in interventions for adolescent AOD, SBIRT-A effectiveness trial testing approaches that actively engage family members in primary care are absent. This trial is designed to help fill these research gaps to inform the critical health decision of whether and how to include caregivers in SBIRT-A activities conducted in pediatric primary care. Trial RegistrationClinicalTrials.gov NCT05964010; https://www.clinicaltrials.gov/study/NCT05964010 International Registered Report Identifier (IRRID)PRR1-10.2196/54486

BackgroundAlcohol and other substance use disorders usually begin with substance use in adolescence. Pediatric primary care offices, where most adolescents receive health care, are a promising venue for early identification of substance use and for brief intervention to prevent associated problems and the development of substance use disorder. ObjectiveThis study tests the effects of a computer-facilitated screening and brief intervention (cSBI) system (the CRAFFT [Car, Relax, Alone, Forget, Family/Friends, Trouble] Interactive System [CRAFFT-IS]) on heavy episodic drinking, riding with a driver who is substance impaired, or driving while substance impaired among adolescents aged 14 to 17 years presenting for a well visit at pediatric primary care practices. MethodsWe are conducting a cluster randomized controlled trial of the CRAFFT-IS versus usual care and recruiting up to 40 primary care clinicians at up to 20 pediatric primary care practices within the American Academy of Pediatrics (AAP) Pediatric Research in Office Settings network. Clinicians are randomized 1:1 within each practice to implement the CRAFFT-IS or usual care with a target sample size of 1300 adolescent patients aged 14 to 17 years. At study start, intervention clinicians complete web-based modules, trainer-led live sessions, and mock sessions to establish baseline competency with intervention counseling. Adolescents receive mailed recruitment materials that invite adolescents to complete an eligibility survey. Eligible and interested adolescents provide informed assent (parental permission requirement has been waived). Before their visit, enrolled adolescents seeing intervention clinicians complete a self-administered web-based CRAFFT screening questionnaire and view brief psychoeducational content illustrating substance use–associated health risks. During the visit, intervention clinicians access a computerized summary of the patient’s screening results and a tailored counseling script to deliver a motivational interviewing–based brief intervention. All participants complete previsit, postvisit, and 12-month follow-up study assessments. Primary outcomes include past 90-day heavy episodic drinking and riding with a driver who is substance impaired at 3-, 6-, 9-, and 12-month follow-ups. Multiple logistic regression modeling with generalized estimating equations and mixed effects modeling will be used in outcomes analyses. Exploratory aims include examining other substance use outcomes (eg, cannabis and nicotine vaping), potential mediators of intervention effect (eg, self-efficacy not to drink), and effect moderation by baseline risk level and sociodemographic characteristics. ResultsThe AAP Institutional Review Board approved this study. The first practice and clinicians were enrolled in August 2022; as of July 2023, a total of 6 practices (23 clinicians) had enrolled. Recruitment is expected to continue until late 2024 or early 2025. Data collection will be completed in 2025 or 2026. ConclusionsFindings from this study will inform the promotion of high-quality screening and brief intervention efforts in pediatric primary care with the aim of reducing alcohol-related morbidity and mortality during adolescence and beyond. Trial RegistrationClinicalTrials.gov NCT04450966; https://www.clinicaltrials.gov/study/NCT04450966 International Registered Report Identifier (IRRID)DERR1-10.2196/55039

Abstract Many natural and man-made systems are prone to critical transitions—abrupt and potentially devastating changes in dynamics. Deep learning classifiers can provide an early warning signal for critical transitions by learning generic features of bifurcations from large simulated training data sets. So far, classifiers have only been trained to predict continuous-time bifurcations, ignoring rich dynamics unique to discrete-time bifurcations. Here, we train a deep learning classifier to provide an early warning signal for the five local discrete-time bifurcations of codimension-one. We test the classifier on simulation data from discrete-time models used in physiology, economics and ecology, as well as experimental data of spontaneously beating chick-heart aggregates that undergo a period-doubling bifurcation. The classifier shows higher sensitivity and specificity than commonly used early warning signals under a wide range of noise intensities and rates of approach to the bifurcation. It also predicts the correct bifurcation in most cases, with particularly high accuracy for the period-doubling, Neimark-Sacker and fold bifurcations. Deep learning as a tool for bifurcation prediction is still in its nascence and has the potential to transform the way we monitor systems for critical transitions.

BackgroundScreening, Brief Intervention, and Referral to Treatment (SBIRT) for substance use is increasingly used in clinical care. Despite its endorsement by several professional societies, the U.S. Preventive Services Task Force has found the evidence base for adolescent SBIRT to be insufficient. A measure of substance use that is brief enough to embed in the electronic medical record could be used in pragmatic trials that enroll large numbers of primary care patients, facilitating research in this area.MethodsParticipants aged 14-18 years (N = 492) completed an electronic survey that included a 90-day Timeline Follow Back (TLFB) Calendar, considered the criterion standard, along with three survey questions about the frequency of their alcohol use: days of use in the past three months, average days of use per week in the past three months, and average days of use per month in the past year. We calculated the correlation between the number of days reported on each of the three questions and the total number of days of use reported on the TLFB.ResultsThe question on number of days of use in the past three months was highly correlated with alcohol consumption frequency on the 90-day TLFB assessment (rho = 0.903). Other items displayed lower but satisfactory correlation with the TLFB (rho = 0.719-0.830).ConclusionsA single question about past 3-month frequency of alcohol use was highly correlated with alcohol use frequency on the criterion standard TLFB among adolescents presenting for routine primary care.

Targeted therapies have increased cancer therapy-related diarrhea (CTD) burden, with high incidence and/or severity of diarrhea for some agents that inhibit epidermal growth factor receptor and receptor tyrosine kinases. Neratinib is a pan-HER tyrosine kinase inhibitor approved for breast cancer treatment and causes severe diarrhea in >95% of patients. Crofelemer, a novel intestinal chloride ion channel modulator, is an approved antidiarrheal drug for symptomatic relief of noninfectious diarrhea in patients with HIV/AIDS receiving antiretroviral therapy. The objective of this study was to evaluate the effectiveness of crofelemer prophylaxis in reducing the incidence /severity of neratinib-induced diarrhea without concomitant administration of loperamide in female beagle dogs. A pilot study using 3 dogs determined a maximum daily tolerated dose of neratinib was between 40 and 80 mg; this dose would induce a consistent incidence/severity of diarrhea without risking severe dehydration. In the definitive study, 24 female beagle dogs (8/group) received neratinib once daily and placebo capsules (CTR) four times/day, or neratinib once daily and crofelemer 125 mg delayed-release tablets given two times (BID), or neratinib once daily and crofelemer 125 mg delayed-release tablets given four times per day (QID). Fecal scores were collected twice daily using an established canine stool scoring scale called the Purina Fecal Scoring (PFS) System. After 28 days, using analysis of covariance (ANCOVA), dogs in the CTR group had a significantly higher average number of weekly loose/watery stools (PFS of 6 or 7) when compared to either crofelemer BID (8.71±2.2 vs. 5.96±2.2, p = 0.028) or crofelemer QID (8.70±2.2 vs. 5.74±2.2, p = 0.022) treatment groups. The average number of weekly loose/watery stools were not different between the crofelemer BID and QID treatment groups (p = 0.84). This study showed that crofelemer prophylaxis reduced the incidence/severity of neratinib-associated diarrhea in female beagle dogs without the need for any loperamide administration.

Abstract Background Many genetic diseases are due to defects in protein trafficking where the mutant protein is recognized by the quality control systems, retained in the endoplasmic reticulum (ER), and degraded by the proteasome. In many cases, the mutant protein retains function if it can be trafficked to its proper cellular location. We have identified structurally diverse correctors that restore the trafficking and function of the most common mutation causing cystic fibrosis, F508del-CFTR. Most of these correctors do not act directly as ligands of CFTR, but indirectly on other pathways to promote folding and correction. We hypothesize that these proteostasis regulators may also correct other protein trafficking diseases. Methods To test our hypothesis, we used stable cell lines or transient transfection to express 2 well-studied trafficking disease mutations in each of 3 different proteins: the arginine-vasopressin receptor 2 (AVPR2, also known as V2R), the human ether-a-go-go-related gene (KCNH2, also known as hERG), and finally the sulfonylurea receptor 1 (ABCC8, also known as SUR1). We treated cells expressing these mutant proteins with 9 structurally diverse F508del-CFTR correctors that function through different cellular mechanisms and assessed whether correction occurred via immunoblotting and functional assays. Results were deemed significantly different from controls by a one-way ANOVA (p Results Here we show that F508del-CFTR correctors RDR1, KM60 and KM57 also correct some mutant alleles of other protein trafficking diseases. We also show that one corrector, the cardiac glycoside ouabain, was found to alter the glycosylation of all mutant alleles tested. Conclusions Correctors of F508del-CFTR trafficking might have broader applications to other protein trafficking diseases.

Objective: This study aims to investigate the effectiveness of Ecological Momentary Motivational Enhancement Therapy (EM-MET) in reducing craving and severity of Cannabis Use Disorder (CUD) among young adults. Methods: This multicenter, single-blinded randomized controlled trial (RCT) will be conducted over a period of 11 weeks. Eighty patients with CUD will be randomly assigned to two equal-sized parallel groups, either the Motivational Enhancement Therapy (MET) group or the EM-MET group. All participants will receive four individual face-to-face sessions of MET (twice a week). The MET group will not receive any other treatments after these sessions; however, in the EM-MET group, the top triggers of patients will be assessed using mobile-based Ecological Momentary Assessment (EMA) five times a day within three weeks (after face-to-face sessions) and they will receive a call from the therapist who provides them with EM-MET (in the form of an emergency telephone helpline) as soon as they report experiencing triggers of cannabis use that are assessed using EMA in their everyday lives. Primary outcomes including CUD severity and the severity of craving will be evaluated using the Leeds Dependence Questionnaire and the Self-efficacy and Temptation Scale, respectively. These assessments will be conducted at pre-treatment, post-treatment, and a six-week follow-up. Discussion: If proven feasible and effective, the results of this study will offer clinicians an evidence-based treatment approach to address craving and dependency in patients with CUD. Moreover, these patients will receive effective treatment in real time and in real life, when and where it is most needed. However, it is important to consider the limitations of this study, such as the specific population studied in Tehran, Iran, which may affect the generalizability of the results. Nevertheless, the implementation of Ecological Momentary Interventions (EMIs) in real-life settings holds promise for timely and effective treatment.Trial registration: This trial was registered in the Iranian Registry of Clinical Trials on 21 February 2023. Registry No. IRCT20221224056908N1.

Although increasing numbers of youth are seeking help to reduce or abstain from marijuana use, little research has investigated the contextual facilitators and barriers to doing so among urban youth utilizing primary care. We qualitatively investigated contextual facilitators and barriers to marijuana reduction/abstinence in an ethnically diverse primary care sample of youth who frequently use marijuana. We interviewed thirteen (Black/African American (69%), Hispanic (8%), White (8%) unknown (15%)) youth (eight females) aged 15-23 years (mean = 19.46). Data were analyzed using Interpretative Phenomenological Analysis. Participants' motivations for marijuana reduction/abstinence included physical health, cognitive functioning, future goals, and money. Barriers to reduction/abstinence were psychological (e.g. stress and boredom), and sociocontextual (e.g. family, friends, and the neighborhood). Our findings suggest using a two-pronged approach to support marijuana reduction/abstinence in youth: individual-level interventions to address psychological factors that impede behavior change, and broader community-based interventions to address sociocontextual factors.

Abstract Preliminary evidence points to a link between C-reactive protein (CRP) and spinal pain in adults. However, there is a paucity of research in younger populations. Therefore, we aimed to determine associations between CRP and spinal pain in childhood and adolescence. We identified trajectories of spinal pain from childhood to adolescence and investigated the associations between CRP and trajectory subgroups. Six- to 11-year-old children from 13 primary schools, were followed from October 2008 and until 2014. High-sensitivity CRP collected at baseline (2008) was measured using serum samples. The outcome was the number of weeks with non-traumatic spinal pain between November 2008 and June 2014. We constructed a trajectory model to identify different spinal pain trajectory subgroups. The associations between CRP and spinal pain trajectory subgroups were modelled using mixed-effects multinominal logistic regression. Data from 1556 participants (52% female), with a mean age of 8.4 years at baseline, identified five spinal pain trajectory subgroups: “no pain” (55.3%), “rare” (23.7%), “rare, increasing” (13.6%), “moderate, increasing” (6.1%), and “early onset, decreasing” (1.3%). There were no differences in baseline high-sensitivity CRP levels between spinal pain trajectory subgroups. Thus, the heterogeneous courses of spinal pain experienced were not defined by differences in CRP at baseline.

Chinchin Wang,1,2 Tyrel Stokes,3 Russell J Steele,3 Niels Wedderkopp,4 Ian Shrier1 1Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, H3T 1E2, Canada; 2Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, H3A 1A2, Canada; 3Department of Mathematics and Statistics, McGill University, Montreal, Quebec, H3A 0B9, Canada; 4Orthopedic Department University Hospital of South West Denmark, Department of Regional Health Research, University of Southern Denmark, Odense, DenmarkCorrespondence: Ian Shrier, Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, McGill University, 3755 Côte Ste-Catherine Road, Montreal, Quebec, H3T 1E2, Canada, Tel +1-514-229-0114, Email ian.shrier@mcgill.caPurpose: Researchers often use model-based multiple imputation to handle missing at random data to minimize bias. However, constraints within the data may sometimes result in implausible values, making model-based imputation infeasible. In these contexts, we illustrate how random hot deck imputation can allow for plausible multiple imputation in longitudinal studies.Patients and Methods: Our motivating example is the Childhood Health, Activity, and Motor Performance School Study Denmark (CHAMPS-DK), a prospective cohort study that measured weekly sports participation for 1700 Danish schoolchildren. Using observed data on 4 variables (pain, activity frequency, sport, sport counts), we created a gold-standard data set without missing data. We then created a synthetic data set by setting some variable values to missing based on a prediction model that mimicked real-data missingness patterns. To create 5 imputed data sets, we matched each record with missing data to several fully observed records, generated probabilities from matched records, and sampled from these records based on the probability of each occurring. We assessed variability and agreement (kappa) between the imputed data sets and the gold-standard data set. We compare results to common model-based imputation methods.Results: Variability across data sets appeared reasonable. The range of kappa for the random hot deck approach was moderate for activity frequency (0.65 to 0.71) and sport (0.59 to 0.85), and poor for common model-based approaches (range 0.00 to 0.11). The range of kappas for sport count was strong (0.87 to 0.97) for random hot deck imputation and weak to moderate (0.55 to 0.71) for common model-based imputation. Agreement was higher when more information was present, and when prevalence was higher for our binary variable sport.Conclusion: Random hot deck imputation should be considered as an alternative method when model-based approaches are infeasible, specifically where there are constraints within and between covariates.Keywords: multiple imputation, missing data, missing at random, hot deck imputation, random hot deck imputation, longitudinal studies

Abstract We introduce a multi-institutional data harvesting (MIDH) method for longitudinal observation of medical imaging utilization and reporting. By tracking both large-scale utilization and clinical imaging results data, the MIDH approach is targeted at measuring surrogates for important disease-related observational quantities over time. To quantitatively investigate its clinical applicability, we performed a retrospective multi-institutional study encompassing 13 healthcare systems throughout the United States before and after the 2020 COVID-19 pandemic. Using repurposed software infrastructure of a commercial AI-based image analysis service, we harvested data on medical imaging service requests and radiology reports for 40,037 computed tomography pulmonary angiograms (CTPA) to evaluate for pulmonary embolism (PE). Specifically, we compared two 70-day observational periods, namely (i) a pre-pandemic control period from 11/25/2019 through 2/2/2020, and (ii) a period during the early COVID-19 pandemic from 3/8/2020 through 5/16/2020. Natural language processing (NLP) on final radiology reports served as the ground truth for identifying positive PE cases, where we found an NLP accuracy of 98% for classifying radiology reports as positive or negative for PE based on a manual review of 2,400 radiology reports. Fewer CTPA exams were performed during the early COVID-19 pandemic than during the pre-pandemic period (9806 vs. 12,106). However, the PE positivity rate was significantly higher (11.6 vs. 9.9%, p

Plain English summary Research shows that the COVID-19 pandemic continues to have far-reaching adverse effects on mental health. For adolescents and young adults, the COVID-19 pandemic has altered critical aspects of their daily lives. The objective of this study is to investigate binge-eating behaviors in adolescents and young adults during the COVID-19 pandemic and to examine if individuals in households that experienced pandemic-related challenges such as food availability and food affordability had greater increases in bingeing behaviors and negative emotions such as feelings of anxiety, worry, mood, and loneliness. Thirty-nine adolescents and young adults previously assessed in an outpatient weight and lifestyle management program at an urban pediatric hospital were surveyed between November 2020 and January 2021. Almost half (48.7%) of these participants reported moderate to severe bingeing behaviors during the pandemic. Participants who reported higher impact of COVID-related stress on the CEFIS-AYA scale reported the highest level of binge-eating behaviors. There were no associations between food availability and affordability and binge eating or between food availability and affordability and negative feelings. This study highlights the importance of assessing patients’ perception of how they experience the myriad impacts of COVID-19 on their daily lives, and the critical need for increases in accessible mental health services and continued support during the on-going pandemic.