Higher Triad Risk Scores Are Associated With Increased Risk for Trabecular-Rich Bone Stress Injuries in Female Runners.

OBJECTIVE: Bone stress injuries (BSIs) in trabecular-rich bone are associated with greater biological risk factors compared with cortical-rich bone. We hypothesized that female runners with high Female Athlete Triad (Triad)-related risk would be at greater risk for trabecular-rich BSIs than runners with low Triad-related risk. DESIGN: Prospective cohort study. SETTING: Two NCAA institutions. PARTICIPANTS: Female runners were followed prospectively for up to 5 years. INTERVENTION: The intervention consisted of team nutrition presentations focused on optimizing energy availability plus individualized nutrition sessions. Triad Cumulative Risk Assessment (CRA) categories were assigned yearly based on low-energy availability, menstrual status, age of menarche, low body mass index, low bone mineral density, and prior BSI. MAIN OUTCOME MEASURES: The outcome was the annual incidence of trabecular- and cortical-rich BSI. Generalized Estimating Equations (GEE, to account for the correlated nature of the observations) with a Poisson distribution and log link were used for statistical modeling. RESULTS: Cortical-rich BSI rates were higher than trabecular-rich BSI rates (0.32 vs 0.13 events per person-year). Female runners with high Triad-related risk had a significantly higher incidence rate ratio of trabecular-rich BSI (RR: 4.40, P = 0.025) and cortical-rich BSI (RR: 2.87, P = 0.025) than women with low Triad-related risk. Each 1-point increase in Triad CRA score was associated with a significant 26% increased risk of trabecular-rich BSI ( P = 0.0007) and a nonsignificant 14% increased risk of cortical-rich BSI ( P = 0.054). CONCLUSIONS: Increased Triad CRA scores were strongly associated with increased risk for trabecular-rich BSI. Incorporating Triad CRA scores in clinical care could guide BSI prevention.

Healthy Runner Project: a 7-year, multisite nutrition education intervention to reduce bone stress injury incidence in collegiate distance runners.

Objectives: We evaluated the effect of a nutrition education intervention on bone stress injury (BSI) incidence among female distance runners at two NCAA Division I institutions. Methods: Historical BSI rates were measured retrospectively (2010-2013); runners were then followed prospectively in pilot (2013-2016) and intervention (2016-2020) phases. The primary aim was to compare BSI rates in the historical and intervention phases. Pilot phase data are included only for descriptive purposes. The intervention comprised team nutrition presentations focused on optimising energy availability plus individualised nutrition sessions for runners with elevated Female Athlete Triad risk. Annual BSI rates were calculated using a generalised estimating equation Poisson regression model adjusted for age and institution. Post hoc analyses were stratified by institution and BSI type (trabecular-rich or cortical-rich). Results: The historical phase included 56 runners and 90.2 person-years; the intervention phase included 78 runners and 137.3 person-years. Overall BSI rates were not reduced from the historical (0.52 events per person-year) to the intervention (0.43 events per person-year) phase. Post hoc analyses demonstrated trabecular-rich BSI rates dropped significantly from 0.18 to 0.10 events per person-year from the historical to intervention phase (p=0.047). There was a significant interaction between phase and institution (p=0.009). At Institution 1, the overall BSI rate dropped from 0.63 to 0.27 events per person-year from the historical to intervention phase (p=0.041), whereas no decline was observed at Institution 2. Conclusion: Our findings suggest that a nutrition intervention emphasising energy availability may preferentially impact trabecular-rich BSI and depend on team environment, culture and resources.

Homeopathy can offer empirical insights on treatment effects in a null field.

OBJECTIVES: A "null field" is a scientific field where there is nothing to discover and where observed associations are thus expected to simply reflect the magnitude of bias. We aimed to characterize a null field using a known example, homeopathy (a pseudoscientific medical approach based on using highly diluted substances), as a prototype. STUDY DESIGN AND SETTING: We identified 50 randomized placebo-controlled trials of homeopathy interventions from highly cited meta-analyses. The primary outcome variable was the observed effect size in the studies. Variables related to study quality or impact were also extracted. RESULTS: The mean effect size for homeopathy was 0.36 standard deviations (Hedges' g; 95% confidence interval: 0.21, 0.51) better than placebo, which corresponds to an odds ratio of 1.94 (95% CI: 1.69, 2.23) in favor of homeopathy. 80% of studies had positive effect sizes (favoring homeopathy). Effect size was significantly correlated with citation counts from journals in the directory of open-access journals and CiteWatch. We identified common statistical errors in 25 studies. CONCLUSION: A null field like homeopathy can exhibit large effect sizes, high rates of favorable results, and high citation impact in the published scientific literature. Null fields may represent a useful negative control for the scientific process.

With Great Power Comes Great Responsibility: Common Errors in Meta-Analyses and Meta-Regressions in Strength & Conditioning Research.

BACKGROUND AND OBJECTIVE: Meta-analysis and meta-regression are often highly cited and may influence practice. Unfortunately, statistical errors in meta-analyses are widespread and can lead to flawed conclusions. The purpose of this article was to review common statistical errors in meta-analyses and to document their frequency in highly cited meta-analyses from strength and conditioning research. METHODS: We identified five errors in one highly cited meta-regression from strength and conditioning research: implausible outliers; overestimated effect sizes that arise from confusing standard deviation with standard error; failure to account for correlated observations; failure to account for within-study variance; and a focus on within-group rather than between-group results. We then quantified the frequency of these errors in 20 of the most highly cited meta-analyses in the field of strength and conditioning research from the past 20 years. RESULTS: We found that 85% of the 20 most highly cited meta-analyses in strength and conditioning research contained statistical errors. Almost half (45%) contained at least one effect size that was mistakenly calculated using standard error rather than standard deviation. In several cases, this resulted in obviously wrong effect sizes, for example, effect sizes of 11 or 14 standard deviations. Additionally, 45% failed to account for correlated observations despite including numerous effect sizes from the same study and often from the same group within the same study. CONCLUSIONS: Statistical errors in meta-analysis and meta-regression are common in strength and conditioning research. We highlight five errors that authors, editors, and readers should check for when preparing or critically reviewing meta-analyses.

Female Athlete Triad Risk Factors Are More Strongly Associated With Trabecular-Rich Versus Cortical-Rich Bone Stress Injuries in Collegiate Athletes.

Background: Bone stress injuries (BSIs) are common in athletes. Risk factors for BSI may differ by skeletal anatomy and relative contribution of trabecular-rich and cortical-rich bone. Hypothesis: We hypothesized that Female Athlete Triad (Triad) risk factors would be more strongly associated with BSIs sustained at trabecular-rich versus cortical-rich skeletal sites. Study Design: Cohort study; Level of evidence, 2. Methods: The study population comprised 321 female National Collegiate Athletic Association Division I athletes participating in 16 sports from 2008 to 2014. Triad risk factors and a Triad cumulative risk score were assessed using responses to preparticipation examination and dual energy x-ray absorptiometry to measure lumbar spine and whole-body bone mineral density (BMD). Sports-related BSIs were diagnosed by a physician and confirmed radiologically. Athletes were grouped into those sustaining a subsequent trabecular-rich BSI, a subsequent cortical-rich BSI, and those without a BSI. Data were analyzed with multinomial logistic regression adjusted for participation in cross-country running versus other sports. Results: A total of 19 participants sustained a cortical-rich BSI (6%) and 10 sustained a trabecular-rich BSI (3%) over the course of collegiate sports participation. The Triad cumulative risk score was significantly related to both trabecular-rich and cortical-rich BSI. However, lower BMD and weight were associated with significantly greater risk for trabecular-rich than cortical-rich BSIs. For every value lower than 1 SD, the odds ratios (95% CIs) for trabecular-rich versus cortical-rich BSI were 3.08 (1.25-7.56) for spine BMD; 2.38 (1.22-4.64) for whole-body BMD; and 5.26 (1.48-18.70) for weight. Taller height was a significantly better predictor of cortical-rich than trabecular-rich BSI. Conclusion: The Triad cumulative risk score was significantly associated with both trabecular-rich and cortical-rich BSI, but Triad-related risk factors appeared more strongly related to trabecular-rich BSI. In particular, low BMD and low weight were associated with significantly higher increases in the risk of trabecular-rich BSI than cortical-rich BSI. These findings suggest Triad risk factors are more common in athletes sustaining BSI in trabecular-rich than cortical-rich locations.

Adherence to contemporary antiretroviral treatment regimens and impact on immunological and virologic outcomes in a US healthcare system.

BACKGROUND: Only a few recent reports have examined longitudinal adherence patterns in US clinics and its impact on immunological and virological outcomes among large cohorts initiating contemporary antiretroviral therapy (ART) in US clinics. METHODS: We followed all persons with HIV (PLWH) in a California clinic population initiating ART between 2010 and 2017. We estimated longitudinal adherence for each PLWH by calculating the medication possession ratio within multiple 6-month intervals using pharmacy refill records. RESULTS: During the study, 2315 PWLH were followed for a median time of 210.8 weeks and only 179 (7.7%) were lost-to-follow-up. The mean adherence was 84.9%. Age (Hazard Ratio (HR): (95% confidence interval): 1.25 (1.20-1.31) per 10-year increase) and Black race (HR: 0.62 (0.53-0.73) vs. White) were associated with adherence in the cohort. A 10% percent increase in adherence increased the odds of being virally suppressed by 37% (OR and 95% CI: 1.37 [1.33-1.41]) and was associated with an increase in mean CD4 count by 8.54 cells/ul in the next 6-month interval (p-value <0.0001). CONCLUSIONS: Our study shows that despite large improvements in retention in care, demographic disparities in adherence to ART persist. Adherence was lower among younger patients and black patients. Our study confirmed the strong association between adherence to ART and viral suppression but could only establish a weak association between adherence and CD4 count. These findings reaffirm the importance of adherence and retention in care and further highlight the need for tailored patient-centered HIV Care Models as a strategy to improve PLWH's outcomes.

The Impacts of COVID-19 on Mental Health and Training in US Professional Endurance Athletes.

OBJECTIVE: We examined how professional athletes are affected by COVID-19. Our primary aim was to assess changes in mental health that occurred after COVID-19 restrictions, and our secondary aim was to assess changes in exercise volume and intensity. DESIGN: Cross-sectional study. SETTING: United States. PARTICIPANTS: Strava professional endurance athletes. ASSESSMENT OF RISK FACTORS: Participants completed a survey, and a subset of participants consented to have their activity data analyzed. The survey included questions on COVID-19 symptoms, exercise, and mental health, as measured by a modified Patient Health Questionnaire. MAIN OUTCOME MEASURES: Participants were asked about 2 periods in 2020: before COVID-19 (January 1-March 14) and during COVID-19 (March 15-August 25), and activity data from both periods were downloaded. Activity data consisted of Global Positioning System and self-reported uploads. RESULTS: One hundred thirty-one male and female Strava athletes were enrolled, and a subset of athletes (n = 114) consented to have their activity data analyzed. During COVID-19 restrictions, 22.2% of participants reported feeling down or depressed and 27.4% of participants reported feeling nervous or anxious at least half the days in a week compared with 3.8% and 4.6% before COVID-19 restrictions, respectively (P < 0.0001). Activity data revealed a significant increase (P < 0.0001) in exercise minutes per day during COVID-19 (mean = 103.00, SD = 42.1) compared with before COVID-19 restrictions (mean = 92.4, SD = 41.3), with no significant changes in intensity. CONCLUSIONS: Athletes reported significant increases in feeling down or depressed and nervous or anxious despite an increase in exercise duration during COVID-19. Future research should assess how to support athletes with mental health resources.

Prevalence of Female and Male Athlete Triad Risk Factors in Ultramarathon Runners.

OBJECTIVE: To identify the prevalence of male and female athlete triad risk factors in ultramarathon runners and explore associations between sex hormones and bone mineral density (BMD). DESIGN: Multiyear cross-sectional study. SETTING: One hundred-mile ultramarathon. PARTICIPANTS: Competing runners were recruited in 2018 and 2019. ASSESSMENT OF RISK FACTORS: Participants completed a survey assessing eating behaviors, menstrual history, and injury history; dual-energy x-ray absorptiometry for BMD; and laboratory evaluation of sex hormones, vitamin D, and ferritin (2019 cohort only). MAIN OUTCOME MEASURE: A Triad Cumulative Risk Assessment Score was calculated for each participant. RESULTS: One hundred twenty-three runners participated (83 males and 40 females, mean age 46.2 and 41.8 years, respectively). 44.5% of men and 62.5% of women had elevated risk for disordered eating. 37.5% of women reported a history of bone stress injury (BSI) and 16.7% had BMD Z scores <-1.0. 20.5% of men had a history of BSI and 30.1% had Z-scores <-1.0. Low body mass index (BMI) (<18.5 kg/m 2 ) was seen in 15% of women and no men. The Triad Cumulative Risk Assessment classified 61.1% of women and 29.2% of men as moderate risk and 5.6% of both men and women as high risk. CONCLUSIONS: Our study is the first to measure BMD in both male and female ultramarathon runners. Our male population had a higher prevalence of low BMD than the general population; females were more likely to report history of BSI. Risk of disordered eating was elevated among our participants but was not associated with either low BMD or low BMI.

Ordinal Prediction Model of 90-Day Modified Rankin Scale in Ischemic Stroke.

Background and Purpose: Prediction models for functional outcomes after ischemic stroke are useful for statistical analyses in clinical trials and guiding patient expectations. While there are models predicting dichotomous functional outcomes after ischemic stroke, there are no models that predict ordinal mRS outcomes. We aimed to create a model that predicts, at the time of hospital discharge, a patient's modified Rankin Scale (mRS) score on day 90 after ischemic stroke. Methods: We used data from three multi-center prospective studies: CRISP, DEFUSE 2, and DEFUSE 3 to derive and validate an ordinal logistic regression model that predicts the 90-day mRS score based on variables available during the stroke hospitalization. Forward selection was used to retain independent significant variables in the multivariable model. Results: The prediction model was derived using data on 297 stroke patients from the CRISP and DEFUSE 2 studies. National Institutes of Health Stroke Scale (NIHSS) at discharge and age were retained as significant (p < 0.001) independent predictors of the 90-day mRS score. When applied to the external validation set (DEFUSE 3, n = 160), the model accurately predicted the 90-day mRS score within one point for 78% of the patients in the validation cohort. Conclusions: A simple model using age and NIHSS score at time of discharge can predict 90-day mRS scores in patients with ischemic stroke. This model can be useful for prognostication in routine clinical care and to impute missing data in clinical trials.

Sun Protective Behaviors and Attitudes of Runners.

Sun exposure is a risk factor for skin cancer. Knowledge and behaviors around sun exposure protective measures are poorly described in athletes including runners. Our primary objective was to describe sun exposure behaviors and knowledge in a population of runners. A cross-sectional online survey was administered to 697 runners to measure the frequency of seven sun protective behaviors: sunscreen use on the face or body; wearing a hat, sunglasses, or long sleeves; running in shade; and avoidance of midday running. Between 54% and 84% of runners reported that they engaged in these behaviors at least sometimes, but only 7% to 45% reported frequent use. Of 525 runners who gave a primary reason for not using sunscreen regularly, 49.0% cited forgetfulness; 17.3% cited discomfort; and only a small percentage cited maintaining a tan (6.1%) or optimizing vitamin D (5.1%). Of 689 runners who responded to a question about what factor most influences their overall sun exposure habits, 39.2% cited fear of skin cancer, 28.7% cited comfort level, and 15.8% cited fear of skin aging. In addition to the seven individual behaviors, we also asked runners how frequently they took precautions to protect against the sun overall. We explored associations between participant characteristics and the overall use of sun protection using ordinal logistic regression. Overall, sun protection was used more frequently in runners who were female, older, or had a history of skin cancer. Runners appear to recognize the importance of sun protection and the potential consequences of not using it, but report forgetfulness and discomfort as the biggest barriers to consistent use. Interventions using habit-formation strategies and self-regulation training may prove to be most useful in closing this gap between knowledge and practice.

Lower Trabecular Bone Score and Spine Bone Mineral Density Are Associated With Bone Stress Injuries and Triad Risk Factors in Collegiate Athletes.

INTRODUCTION: Determinants of bone health and injury are important to identify in athletes. Bone mineral density (BMD) is commonly measured in athletes with Female Athlete Triad (Triad) risk factors; the trabecular bone score (TBS) has been proposed to predict fracture risk independent of BMD. Evaluation of TBS and spine BMD in relation bone stress injury (BSI) risk has not been studied in female collegiate athletes. OBJECTIVE: We hypothesized that spine BMD and TBS would each independently predict BSI and that the combined measures would improve injury prediction in female collegiate athletes. We also hypothesized that each measure would be correlated with Triad risk factors. DESIGN: Retrospective cohort. SETTING: Academic Institution. METHODS: Dual energy x-ray absorptiometry (DXA) of the lumbar spine was used to calculate BMD and TBS values. Chart review was used to identify BSI that occurred after the DXA measurement and to obtain Triad risk factors. We used logistic regression to examine the ability of TBS and BMD alone or in combination to predict prospective BSI. RESULTS: Within 321 athletes, 29 (9.0%) sustained a BSI after DXA. BMD and TBS were highly correlated (Pearson correlation r = 0.62, P < .0001). Spine BMD and TBS had similar ability to predict BSI; the C-statistic and 95% confidence intervals were 0.69 (0.58 to 0.81) for spine BMD versus 0.68 (0.57 to 0.79) for TBS. No improvement in discrimination was observed with combined BMD + TBS (C-statistic 0.70, 0.59 to 0.81). Both TBS and BMD predicted trabecular-rich BSI (defined as pelvis, femoral neck, and calcaneus) better than cortical-rich BSI. Both measures had similar correlations with Triad risk factors. CONCLUSION: Lower BMD and TBS values are associated with elevated risk for BSI and similar correlation to Triad risk factors. TBS does not improve prediction of BSI. Collectively, our findings suggest that BMD may be a sufficient measure of skeletal integrity from DXA in female collegiate athletes.

Assessing Diagnostic and Severity Grading Accuracy of Ultrasound Measurements for Carpal Tunnel Syndrome Compared to Electrodiagnostics.

BACKGROUND: The combined sensory index (CSI) is the most sensitive electrodiagnostic criteria for carpal tunnel syndrome (CTS), and the CSI and Bland criteria have been shown to predict surgical treatment outcomes. The proposed ultrasound measurements have not been assessed against the CSI for diagnostic accuracy and grading of CTS severity. OBJECTIVE: To investigate the use of ultrasound evaluations for both diagnosis and assessment of severity grading of CTS in comparison to electrodiagnostic assessment. DESIGN: All patients underwent an electrodiagnostic evaluation using the CSI and Bland severity grading. Each patient underwent an ultrasound evaluation including cross-sectional area (CSA), the change in CSA from the forearm to the tunnel (∆CSA), and the wrist-forearm ratio (WFR). These measurements were assessed for diagnostic and severity grading accuracy using the CSI as the gold standard. SETTING: Tertiary academic center. PARTICIPANTS: All patients referred for electrodiagnostic evaluation for CTS were eligible for the study. Only those with idiopathic CTS were included and those with prior CTS treatment were also excluded. Ninety-five patients were included in the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary study outcome measure was concordance between CSI diagnosis and severity categories and the ultrasound measurements. Both outcomes were also assessed using Bland criteria. RESULTS: Optimal cut-points for diagnosis of CTS were found to be CSA ≥12 mm2 , ∆CSA ≥4 mm2 , WFR ≥1.4. Using these cut-points, C-statistics comparing diagnosis of CTS using ultrasound measurements versus using the CSI ranged from 0.893-0.966. When looking at CSI severity grading compared to ∆CSA, however, the C-statistics were 0.640-0.661 with substantial overlap between severity groups. CONCLUSIONS: Although ultrasound measurements had high diagnostic accuracy for CTS based on the CSI criteria, ultrasound measurements were unable to adequately distinguish between CSI severity groups among patients with CTS.

Virological Failure and Acquired Genotypic Resistance Associated With Contemporary Antiretroviral Treatment Regimens.

BACKGROUND: There are few descriptions of virologic failure (VF) and acquired drug resistance (HIVDR) in large cohorts initiating contemporary antiretroviral therapy (ART). METHODS: We studied all persons with HIV (PWH) in a California clinic population initiating ART between 2010 and 2017. VF was defined as not attaining virologic suppression, discontinuing ART, or virologic rebound prompting change in ART. RESULTS: During the study, 2315 PWH began ART. Six companion drugs were used in 93.3% of regimens: efavirenz, elvitegravir/c, dolutegravir, b-darunavir, rilpivirine, and raltegravir. During a median follow-up of 36 months, 214 (9.2%) PWH experienced VF (2.8 per 100 person-years) and 62 (2.7%) experienced HIVDR (0.8 per 100 person-years). In multivariable analyses, younger age, lower CD4 count, higher virus load, and b-atazanavir were associated with increased VF risk; lower CD4 count, higher virus load, and nevirapine were associated with increased HIVDR risk. Compared with efavirenz, dolutegravir, raltegravir, and b-darunavir were associated with reduced HIVDR risk. Risks of VF and HIVDR were not significantly associated with ART initiation year. Of the 62 PWH with HIVDR, 42 received an non-nucleoside RT inhibitor (NNRTI), 15 an integrase-strand transfer inhibitor (INSTI), and 5 a protease inhibitor (PI). Among those with HIVDR on an NNRTI or first-generation INSTI, 59% acquired dual class resistance and 29% developed tenofovir resistance; those receiving a PI or dolutegravir developed just M184V. CONCLUSIONS: Despite the frequent use of contemporary ART regimens, VF and HIVDR continue to occur. Further efforts are required to improve long-term ART virological responses to prevent the consequences of ongoing HIV-1 replication including virus transmission and HIVDR.

Systematic review of the use of "magnitude-based inference" in sports science and medicine.

Magnitude-based inference (MBI) is a controversial statistical method that has been used in hundreds of papers in sports science despite criticism from statisticians. To better understand how this method has been applied in practice, we systematically reviewed 232 papers that used MBI. We extracted data on study design, sample size, and choice of MBI settings and parameters. Median sample size was 10 per group (interquartile range, IQR: 8-15) for multi-group studies and 14 (IQR: 10-24) for single-group studies; few studies reported a priori sample size calculations (15%). Authors predominantly applied MBI's default settings and chose "mechanistic/non-clinical" rather than "clinical" MBI even when testing clinical interventions (only 16 studies out of 232 used clinical MBI). Using these data, we can estimate the Type I error rates for the typical MBI study. Authors frequently made dichotomous claims about effects based on the MBI criterion of a "likely" effect and sometimes based on the MBI criterion of a "possible" effect. When the sample size is n = 8 to 15 per group, these inferences have Type I error rates of 12%-22% and 22%-45%, respectively. High Type I error rates were compounded by multiple testing: Authors reported results from a median of 30 tests related to outcomes; and few studies specified a primary outcome (14%). We conclude that MBI has promoted small studies, promulgated a "black box" approach to statistics, and led to numerous papers where the conclusions are not supported by the data. Amidst debates over the role of p-values and significance testing in science, MBI also provides an important natural experiment: we find no evidence that moving researchers away from p-values or null hypothesis significance testing makes them less prone to dichotomization or over-interpretation of findings.