High-throughput allele-specific expression across 250 environmental conditions.

Gene-by-environment (GxE) interactions determine common disease risk factors and biomedically relevant complex traits. However, quantifying how the environment modulates genetic effects on human quantitative phenotypes presents unique challenges. Environmental covariates are complex and difficult to measure and control at the organismal level, as found in GWAS and epidemiological studies. An alternative approach focuses on the cellular environment using in vitro treatments as a proxy for the organismal environment. These cellular environments simplify the organism-level environmental exposures to provide a tractable influence on subcellular phenotypes, such as gene expression. Expression quantitative trait loci (eQTL) mapping studies identified GxE interactions in response to drug treatment and pathogen exposure. However, eQTL mapping approaches are infeasible for large-scale analysis of multiple cellular environments. Recently, allele-specific expression (ASE) analysis emerged as a powerful tool to identify GxE interactions in gene expression patterns by exploiting naturally occurring environmental exposures. Here we characterized genetic effects on the transcriptional response to 50 treatments in five cell types. We discovered 1455 genes with ASE (FDR < 10%) and 215 genes with GxE interactions. We demonstrated a major role for GxE interactions in complex traits. Genes with a transcriptional response to environmental perturbations showed sevenfold higher odds of being found in GWAS. Additionally, 105 genes that indicated GxE interactions (49%) were identified by GWAS as associated with complex traits. Examples include GIPR-caffeine interaction and obesity and include LAMP3-selenium interaction and Parkinson disease. Our results demonstrate that comprehensive catalogs of GxE interactions are indispensable to thoroughly annotate genes and bridge epidemiological and genome-wide association studies.

QuASAR: quantitative allele-specific analysis of reads.

MOTIVATION: Expression quantitative trait loci (eQTL) studies have discovered thousands of genetic variants that regulate gene expression, enabling a better understanding of the functional role of non-coding sequences. However, eQTL studies are costly, requiring large sample sizes and genome-wide genotyping of each sample. In contrast, analysis of allele-specific expression (ASE) is becoming a popular approach to detect the effect of genetic variation on gene expression, even within a single individual. This is typically achieved by counting the number of RNA-seq reads matching each allele at heterozygous sites and testing the null hypothesis of a 1:1 allelic ratio. In principle, when genotype information is not readily available, it could be inferred from the RNA-seq reads directly. However, there are currently no existing methods that jointly infer genotypes and conduct ASE inference, while considering uncertainty in the genotype calls. RESULTS: We present QuASAR, quantitative allele-specific analysis of reads, a novel statistical learning method for jointly detecting heterozygous genotypes and inferring ASE. The proposed ASE inference step takes into consideration the uncertainty in the genotype calls, while including parameters that model base-call errors in sequencing and allelic over-dispersion. We validated our method with experimental data for which high-quality genotypes are available. Results for an additional dataset with multiple replicates at different sequencing depths demonstrate that QuASAR is a powerful tool for ASE analysis when genotypes are not available. AVAILABILITY AND IMPLEMENTATION: http://github.com/piquelab/QuASAR. CONTACT: fluca@wayne.edu or rpique@wayne.edu SUPPLEMENTARY INFORMATION: Supplementary Material is available at Bioinformatics online.

Risk factors for tibial stress injuries: a case-control study.

OBJECTIVE: To identify physical and behavioral characteristics related to the incidence of tibial stress injuries (TSIs). DESIGN: Case-control study. No clinical care was conducted. SETTING: Research laboratories in the San Francisco (the United States) and Gold Coast (Australia) areas. PARTICIPANTS: Forty-eight patients (21 men and 27 women) with acute TSI, and 36 (16 men and 20 women) age-matched, sex-matched, height-matched, weight-matched, and activity-matched controls with no history of TSI. INDEPENDENT VARIABLES: Height, weight, body mass index, bone, lean and fat mass, lower limb alignment anomalies, foot type, orthotics, calcium, recent weight change, menstrual history, oral contraceptive use, medications, smoking, alcohol, sleep, training type, and intensity. Differences in continuous variables were tested using 1-way analysis of variance. Categorical variable comparisons were performed with Fisher exact test. MAIN OUTCOME MEASURE: Tibial stress injury. RESULTS: Tibial stress injury cases had 2.7% more fat (P < 0.001) and 2.6% less muscle (P < 0.001) as well as lower trochanteric bone mineral content (BMC) (P < 0.001), lumbar spine (LS) area (P < 0.001), femoral neck BMC (P < 0.001), length (P < 0.05), area (P < 0.001), cortical width (P < 0.01), cross-sectional moment of inertia (P < 0.001), and index of bending strength (P < 0.001) than controls. Controls had lower LS BMC (P < 0.01), length (P < 0.001), and broadband ultrasound attenuation (P < 0.001). The use of orthotic insoles was more prevalent in TSI cases than controls (25% vs 5.6%, respectively; P < 0.02), as were foot anomalies (56.3% vs 27.8%, respectively; P = 0.01). CONCLUSIONS: Tibial stress injury cases had lower lean and higher fat mass, a tendency for smaller bones, and for foot anomalies compared with uninjured matched controls. bone mineral density was normal for both groups. CLINICAL RELEVANCE: Enhancing lean mass and limiting gains in fat may provide some protection against TSI. Individuals with small skeletal frames are advised to increase training loads particularly gradually and to reduce training intensity at the first sign of pain in the shins.

Advancing the preparticipation physical evaluation: an ACSM and FIMS joint consensus statement.

: While the preparticipation physical evaluation (PPE) is widely accepted, its usage and content are not standardized. Implementation is affected by cost, access, level of participation, participant age/sex, and local/regional/national mandate. Preparticipation physical evaluation screening costs are generally borne by the athlete, family, or club. Screening involves generally agreed-upon questions based on expert opinion and tested over decades of use. No large-scale prospective controlled tracking programs have examined PPE outcomes. While the panel did not reach consensus on electrocardiogram (ECG) screening as a routine part of PPE, all agreed that a history and physical exam focusing on cardiac risk is essential, and an ECG should be used where risk is increased. The many areas of consensus should help the American College of Sports Medicine and Fédération Internationale du Médicine du Sport in developing a universally accepted PPE. An electronic PPE, using human-centered design, would be comprehensive, would provide a database given that PPE is mandatory in many locations, would simplify PPE administration, would allow remote access to clinical data, and would provide the much-needed data for prospective studies in this area.

Advancing the preparticipation physical evaluation (PPE): an ACSM and FIMS joint consensus statement.

While the preparticipation physical evaluation (PPE) is widely accepted, its usage and content are not standardized. Implementation is affected by cost, access, level of participation, participant age/sex, and local/regional/national mandate. PPE screening costs are generally borne by the athlete, family, or club. Screening involves generally agreed-upon questions based on expert opinion and tested over decades of use. No large-scale prospective controlled tracking programs have examined PPE outcomes. While the panel did not reach consensus on electrocardiogram screening as a routine part of PPE, all agreed that a history and physical exam focusing on cardiac risk is essential, and an ECG should be used where risk is increased. The many areas of consensus should help the American College of Sports Medicine and the Fédération Internationale du Médicine du Sport in developing a universally accepted PPE. An electronic PPE, using human-centered design, would be comprehensive, would provide a database given that PPE is mandatory in many locations, would simplify PPE administration, would allow remote access to clinical data, and would provide the much-needed data for prospective studies in this area.

Analytical validation of HER2DX genomic test for early-stage HER2-positive breast cancer.

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

Prevention and management of non-communicable disease: the IOC consensus statement, Lausanne 2013.

Morbidity and mortality from preventable, non-communicable chronic disease (NCD) threatens the health of our populations and our economies. The accumulation of vast amounts of scientific knowledge has done little to change this. New and innovative thinking is essential to foster new creative approaches that leverage and integrate evidence through the support of big data, technology and design thinking. The purpose of this paper is to summarise the results of a consensus meeting on NCD prevention sponsored by the IOC in April 2013. Within the context of advocacy for multifaceted systems change, the IOC's focus is to create solutions that gain traction within healthcare systems. The group of participants attending the meeting achieved consensus on a strategy for the prevention and management of chronic disease that includes the following: (1) Focus on behavioural change as the core component of all clinical programmes for the prevention and management of chronic disease. (2) Establish actual centres to design, implement, study and improve preventive programmes for chronic disease. (3) Use human-centred design in the creation of prevention programmes with an inclination to action, rapid prototyping and multiple iterations. (4) Extend the knowledge and skills of Sports and Exercise Medicine (SEM) professionals to build new programmes for the prevention and treatment of chronic disease focused on physical activity, diet and lifestyle. (5) Mobilise resources and leverage networks to scale and distribute programmes of prevention. True innovation lies in the ability to align thinking around these core strategies to ensure successful implementation of NCD prevention and management programmes within healthcare. The IOC and SEM community are in an ideal position to lead this disruptive change. The outcome of the consensus meeting was the creation of the IOC Non-Communicable Diseases ad hoc Working Group charged with the responsibility of moving this agenda forward.

Team clinician variability in return-to-play decisions.

OBJECTIVE: To describe the variability in the return-to-play (RTP) decisions of experienced team clinicians and to assess their clinical opinion as to the relevance of 19 factors described in a RTP decision-making model. DESIGN: Survey questionnaire. SETTING: Advanced Team Physician Course. PARTICIPANTS: Sixty-seven of 101 sports medicine clinicians completed the questionnaire. MAIN OUTCOME MEASURES: Results were analyzed using descriptive statistics. For categorical variables, we report percentage and frequency. For continuous variables, we report mean (SD) if data were approximately normally distributed and frequencies for clinically relevant categories for skewed data. RESULTS: The average number of years of clinical sports medicine experience was 13.6 (9.8). Of the 62 clinicians who responded fully, 35% (n = 22) would "clear" (vs "not clear") an athlete to participate in sport even if the risk of an acute reinjury or long-term sequelae is increased. When respondents were given 6 different RTP options rather than binary choices, there were increased discrepancies across some injury risk scenarios. For example, 8.1% to 16.1% of respondents who chose to clear an athlete when presented with binary choices, later chose to "not clear" an athlete when given 6 graded RTP options. The respondents often considered factors of potential importance to athletes as nonimportant to the RTP decision process if risk of reinjury was unaffected (range, n = 4 [10%] to n = 19 [45%]). CONCLUSIONS: There is a high degree of variability in how different clinicians weight the different factors related to RTP decision making. More precise definitions decrease but do not eliminate this variability.

Prevention and management of noncommunicable disease: the IOC Consensus Statement, Lausanne 2013.

Morbidity and mortality from preventable, noncommunicable chronic disease (NCD) threatens the health of our populations and our economies. The accumulation of vast amounts of scientific knowledge has done little to change this. New and innovative thinking is essential to foster new creative approaches that leverage and integrate evidence through the support of big data, technology, and design thinking. The purpose of this paper is to summarize the results of a consensus meeting on NCD prevention sponsored by the International Olympic Committee (IOC) in April 2013. Within the context of advocacy for multifaceted systems change, the IOC's focus is to create solutions that gain traction within health care systems. The group of participants attending the meeting achieved consensus on a strategy for the prevention and management of chronic disease that includes the following: 1. Focus on behavioral change as the core component of all clinical programs for the prevention and management of chronic disease. 2. Establish actual centers to design, implement, study, and improve preventive programs for chronic disease. 3. Use human-centered design (HCD) in the creation of prevention programs with an inclination to action, rapid prototyping and multiple iterations. 4. Extend the knowledge and skills of Sports and Exercise Medicine (SEM) professionals to build new programs for the prevention and treatment of chronic disease focused on physical activity, diet, and lifestyle. 5. Mobilize resources and leverage networks to scale and distribute programs of prevention. True innovation lies in the ability to align thinking around these core strategies to ensure successful implementation of NCD prevention and management programs within health care. The IOC and SEM community are in an ideal position to lead this disruptive change. The outcome of the consensus meeting was the creation of the IOC Non-Communicable Diseases ad hoc Working Group charged with the responsibility of moving this agenda forward.

Can Acupuncture be a Part of the Treatment for Breast Cancer-Related Lymphedema? A Systematic Review of the Safety and Proposed Model for Care.

Acupuncture is a potential therapy for breast cancer-related lymphedema (BCRL). Despite a recent meta-analysis on efficacy, data on acupuncture safety in BCRL are lacking. Current clinical guidelines recommend avoiding needling in the upper extremity affected by lymph node dissection. We undertook a systematic review focusing on acupuncture safety and treatment protocols in clinical trials for BCRL. Literature searches were conducted in PubMed, Ovid, CINAHL, and Cochrane library. Eight clinical trials on acupuncture for BCRL were analyzed. The Standards of Acupuncture intervention (STRICTA 2010) and Cochrane risk of bias (RoB2 2019) were applied to assess methods for acupuncture interventions within Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Quantity and severity of adverse events (AE) were reviewed. A total of 189 subjects participated in 8 clinical trials with 2965 acupuncture treatments. No serious adverse events (SAE) were reported regardless of treatment laterality or protocol, with only a single grade 2 skin infection in 2,965 total treatments (0.034%), including 1,165 bilateral and 225 ipsilateral treatments. Our comprehensive review of clinical trials of acupuncture for BCRL demonstrated no significant adverse events in 2,965 treatments, including 1,390 in the affected limb. An approach for routine integration of acupuncture into BCRL maintenance therapy is proposed.

Tibial stress injury: relationship of radiographic, nuclear medicine bone scanning, MR imaging, and CT Severity grades to clinical severity and time to healing.

PURPOSE: To examine the relationship between severity grade for radiography, triple-phase technetium 99m nuclear medicine bone scanning, magnetic resonance (MR) imaging, and computed tomography (CT); clinical severity; and recovery time from a tibial stress injury (TSI), as well as to evaluate interassessor grading reliability. MATERIALS AND METHODS: This protocol was approved by the Griffith University Human Research Ethics Committee, the Stanford University Panel on Human Subjects in Medical Research, the U.S. Army Human Subjects Research Review Board, and the Australian Defense Human Research Ethics Committee. Informed consent was obtained from all subjects. Forty subjects (17 men, 23 women; mean age, 26.2 years ± 6.9 [standard deviation]) with TSI were enrolled. Subjects were examined acutely with standard anteroposterior and lateral radiography, nuclear medicine scanning, MR imaging, and CT. Each modality was graded by four blinded clinicians. Mixed-effects models were used to examine associations between image severity, clinical severity, and time to healing, with adjustments for image modality and assessor. Grading reliability was evaluated with the Cronbach α coefficient. RESULTS: Image assessment reliability was high for all grading systems except radiography, which was moderate (α = 0.565-0.895). Clinical severity was negatively associated with MR imaging severity (P ≤ .001). There was no significant relationship between time to healing and severity score for any imaging modality, although a positive trend existed for MR imaging (P = .07). CONCLUSION: TSI clinical severity was negatively related to MR imaging severity. Radiographic, bone scan, and CT severity were not related to time to healing, but there was a positive trend for MR imaging.

Prevention of sport injury II: a systematic review of clinical science research.

OBJECTIVE: To characterise the nature of the sport injury prevention literature by reviewing published articles that evaluate specific clinical interventions designed to reduce sport injury risks. DATA SOURCES: PubMed, Cinahl, Web of Science and Embase. MAIN RESULTS: Only 139 of 2525 articles retrieved met the inclusion criteria. Almost 40% were randomised controlled trials and 30.2% were cohort studies. The focus of the study was protective equipment in 41%, training in 32.4%, education in 7.9%, rules and regulations in 4.3%, and 13.3% involved a combination of the above. Equipment research studied stability devices (42.1%), head and face protectors (33.3%), attenuating devices (17.5%) as well as other devices (7%). Training studies often used a combination of interventions (eg, balance and stretching); most included balance and coordination (63.3%), with strength and power (36.7%) and stretching (22.5%) being less common. Almost 70% of the studies examined lower extremity injuries, and a majority of these were joint (non-bone)-ligament injuries. Contact sports were most frequently studied (41.5%), followed by collision (39.8%) and non-contact (20.3%). CONCLUSION: The authors found only 139 publications in the existing literature that examined interventions designed to prevent sports injury. Of these, the majority investigated equipment or training interventions whereas only 4% focused on changes to the rules and regulations that govern sport. The focus of intervention research is on acute injuries in collision and contact sports whereas only 20% of the studies focused on non-contact sports.

Prevention of sports injury I: a systematic review of applied biomechanics and physiology outcomes research.

OBJECTIVE: To analyse published articles that used interventions aimed at investigating biomechanical/physiological outcomes (ie, intermediate risk factors) for sport injury prevention in order to characterise the state of the field and identify important areas not covered in the literature. DATA SOURCES: PubMed, Cinahl, Web of Science and Embase were searched using a broad search strategy. MAIN RESULTS: Only 144 of 2525 articles retrieved by the search strategy met the inclusion criteria. Crossover study designs increased by 175% in the late 1980s until 2005 but have declined 32% since then. Randomised controlled trial (RCT) study designs increased by 650% since the early 1980s. Protective equipment studies (61.8% of all studies) declined by 35% since 2000, and training studies (35.4% of all studies) increased by 213%. Equipment research studied stability devices (83.1%) and attenuating devices (13.5%) whereas training research studied balance and coordination (54.9%), strength and power (43.1%) and stretching (15.7%). Almost all (92.1%) studies investigated the lower extremity and 78.1% were of the joint (non-bone)-ligament type. Finally, 57.5% of the reports studied contact sports, 24.2% collision and 25.8% non-contact sports. CONCLUSION: The decrease in crossover study design and increase in RCTs over time suggest a shift in study design for injury prevention articles. Another notable finding was the change in research focus from equipment interventions, which have been decreasing since 2000 (35% decline), to training interventions, which have been increasing (213% increase). Finally, there is very little research on overuse or upper extremity injuries.

A quality process study of lymph node evaluation in endometrial cancer.

Our objective was to analyze the reported lymph node counts between surgeons, histology prosectors, and pathologists using a cohort of patients enrolled on a national protocol that standardized surgical intent.This is a retrospective review of patients with uterine cancer who underwent a standardized formal staging procedure as dictated by a National Cancer Institute sponsored protocol. Patients were staged using the International Federation of Gynecology and Obstetrics 1988 guidelines. All patients required a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. Lymphadenectomy specimens were separated by the following regions: external iliac, obturator, common iliac, and periaortic. Lymph node counts were analyzed by region, surgeon, histology prosector, and pathologist.There were 78 patients enrolled in the protocol during the study period. Of them, 72 (92%) patients met the inclusion criteria. A total of 2397 lymph nodes were counted, with an average total number of 33 (SD=9) lymph nodes dissected per patient. Surgeons A, B, and C had an average lymph node count of 32, 33, and 35, respectively, with no significant difference in mean node count (P=0.66). Prosectors 1 to 4 dissected an average of 34, 33, 28, and 35 lymph nodes, respectively (P=0.091). There were 2 pathologists with ≥ 10 cases. Their mean lymph node counts were 35 and 30, respectively, with no significant difference in mean node count (P=0.079).This systematic review did not identify a discrepancy in nodal count among surgeons, prosectors, or pathologists at our institution. The methods used may be helpful in structuring interdepartmental reviews for completeness of nodal dissections in cases where surgical intent has been standardized.

Responsibility of sport and exercise medicine in preventing and managing chronic disease: applying our knowledge and skill is overdue.

BACKGROUND: The rapidly increasing burden of chronic disease is difficult to reconcile with the large, compelling body of literature that demonstrates the substantial preventive and therapeutic benefits of comprehensive lifestyle intervention, including physical activity, smoking cessation and healthy diet. Physical inactivity is now the fourth leading independent risk factor for death caused by non-communicable chronic disease. Although there have been efforts directed towards research, education and legislation, preventive efforts have been meager relative to the magnitude of the problem. The disparity between our scientific knowledge about chronic disease and practical implementation of preventive approaches now is one of the most urgent concerns in healthcare worldwide and threatens the collapse of our health systems unless extraordinary change takes place. FINDINGS: The authors believe that there are several key factors contributing to the disparity. Reductionism has become the default approach for healthcare delivery, resulting in fragmentation rather than integration of services. This, in turn, has fostered a disease-based rather than a health-based model of care and has produced medical school curricula that no longer accurately reflect the actual burden of disease. Trying to 'fit' prevention into a disease-based approach has been largely unsuccessful because the fundamental tenets of preventive medicine are diametrically opposed to those of disease-based healthcare. RECOMMENDATION: A clinical discipline within medicine is needed to adopt disease prevention as its own reason for existence. Sport and exercise medicine is well positioned to champion the cause of prevention by promoting physical activity. CONCLUSION: This article puts forward a strong case for the immediate, increased involvement of clinical sport and exercise medicine in the prevention and treatment of chronic disease and offers specific recommendations for how this may begin.

Return-to-play decisions: are they the team physician's responsibility?

OBJECTIVE: Return-to-play (RTP) decisions are a central component of the Team Physician's clinical work, yet there is little more than anecdotal reference to these in the literature. We recently published a 3-step model for return-to-play medical decision making and, in the current paper, undertook a systematic review of the literature to determine the level of evidence in support of this model. DATA SOURCES: PubMed, Web of Science, and CINAHL electronic databases. Any article specifically related to concussion, head injuries, neck injuries, illness, medical conditions (including cardiovascular and renal), and preparticipation in sport or that reported RTP as a clinical outcome was excluded. Any article that contained a discussion on one of the components of the 3-step decision-based RTP model was included. RESULTS: We reviewed 148 articles that met the criteria for inclusion and found 98 review articles, 39 original articles, 6 case reports, and 5 editorials. Of these, 141 articles mentioned Step 1 of the medical decision-making process for RTP (Medical Factors), 26 mentioned Step 2 (Sport Risk Modifiers), and 20 mentioned Step 3 (Decision Modifiers). Of the 148 articles in total, only 13 focused on RTP as the main subject and the remaining 135 mentioned RTP anecdotally. Of these 13 articles, 5 were reviews, 4 were editorials, and 4 were original research. CONCLUSIONS: Although 148 articles we retrieved mention RTP in relation to a specific injury, medical condition, or specific topic, only 13 articles focused specifically on the RTP decision-making process, and 6 of 13 were restricted to Step 1 of the 3-step model (Medical Factors). Return-to-play is a fertile field for research and thought leadership beginning with a focus on the Team Physician's appropriate role in RTP decision making, particularly considering the factors identified in Step 3 (Decision Modification).

Effectiveness of cervical spine stabilization techniques.

OBJECTIVE: To compare head motions that occur when trained professionals perform the head squeeze (HS) and trap squeeze (TS) C-spine stabilization techniques. DESIGN: Cross-over design. PARTICIPANTS: Twelve experienced lead rescuers. MAIN OUTCOME MEASURES: Peak head motion with respect to initial conditions using inertial measurement units attached to the forehead and trunk of the simulated patient. We compared both HS and TS during lift-and-slide (L&S) and log-roll (LR) placement on spinal board, and agitated patient trying to sit up (AGIT-Sit) or rotate his head (AGIT-Rot). The a priori minimal important difference (MID) was 5 degrees for flexion or extension and 3 degrees for rotation or lateral flexion. RESULTS: The L&S technique was statistically superior to the LR technique. The only differences to exceed the MID were extension and rotation during LR (HS > TS). In the AGIT-Sit test scenario, differences in motion exceeded MID (HS > TS) for flexion, rotation, and lateral flexion. In the AGIT-Rot scenario, differences in motion exceeded MID for rotation only (HS >TS). There was similar intertrial variability of motion for HS and TS during L&S and LR but significantly more variability with HS compared with TS in the agitated patient. CONCLUSIONS: The L&S is preferable to the LR when possible for minimizing unwanted C-spine motion. There is little overall difference between HS and TS in a cooperative patient. When a patient is confused, the HS is much worse than the TS at minimizing C-spine motion.

Return-to-play in sport: a decision-based model.

OBJECTIVE: Return-to-play (RTP) decisions are fundamental to the practice of sports medicine but vary greatly for the same medical condition and circumstance. Although there are published articles that identify individual components that go into these decisions, there exists neither quantitative criteria nor a model for the sequence or weighting of these components within the medical decision-making process. Our objective was to develop a decision-based model for clinical use by sports medicine practitioners. DATA SOURCES: English literature related to RTP decision making. MAIN RESULTS: We developed a 3-step decision-based RTP model for an injury or illness that is specific to the individual practitioner making the RTP decision: health status, participation risk, and decision modification. In Step 1, the Health Status of the athlete is assessed through the evaluation of Medical Factors related to how much healing has occurred. In Step 2, the clinician evaluates the Participation Risk associated with participation, which is informed by not only the current health status but also by the Sport Risk Modifiers (eg, ability to protect the injury with padding, athlete position). Different individuals are expected to have different thresholds for "acceptable level of risk," and these thresholds will change based on context. In Step 3, Decision Modifiers are considered and the decision to RTP or not is made. CONCLUSIONS: Our model helps clarify the processes that clinicians use consciously and subconsciously when making RTP decisions. Providing such a structure should decrease controversy, assist physicians, and identify important gaps in practice areas where research evidence is lacking.