A Machine Learning Approach for Predicting Real-time Risk of Intraoperative Hypotension in Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. Episodes of hypotension are associated with worse TBI outcomes. Our aim was to model the real-time risk of intraoperative hypotension in TBI patients, compare machine learning and traditional modeling techniques, and identify key contributory features from the patient monitor and medical record for the prediction of intraoperative hypotension. METHODS: The data included neurosurgical procedures in 1005 TBI patients at an academic level 1 trauma center. The clinical event was intraoperative hypotension, defined as mean arterial pressure <65 mm Hg for 5 or more consecutive minutes. Two types of models were developed: one based on preoperative patient-level predictors and one based on intraoperative predictors measured per minute. For each of these models, we took 2 approaches to predict the occurrence of a hypotensive event: a logistic regression model and a gradient boosting tree model. RESULTS: The area under the receiver operating characteristic curve for the intraoperative logistic regression model was 0.80 (95% confidence interval [CI]: 0.78-0.83), and for the gradient boosting model was 0.83 (95% CI: 0.81-0.85). The area under the precision-recall curve for the intraoperative logistic regression model was 0.16 (95% CI: 0.12-0.20), and for the gradient boosting model was 0.19 (95% CI: 0.14-0.24). Model performance based on preoperative predictors was poor. Features derived from the recent trend of mean arterial pressure emerged as dominantly predictive in both intraoperative models. CONCLUSIONS: This study developed a model for real-time prediction of intraoperative hypotension in TBI patients, which can use computationally efficient machine learning techniques and a streamlined feature-set derived from patient monitor data.

Cytotoxic Effects of Common Irrigation Solutions on Chondrosarcoma and Giant Cell Tumors of Bone.

BACKGROUND: Irrigation is commonly used as an adjuvant treatment during the intralesional curettage of bone tumors. The goal of the present study was to analyze the in vitro cytotoxicity of commonly used irrigation solutions on chondrosarcoma and giant cell tumor (GCT) cells as there is no consensus on which solution leads to the greatest amount of cell death. METHODS: An in vitro evaluation was performed by exposing human GCT and human chondrosarcoma cell lines to 0.9% saline solution, sterile water, 70% ethanol, 3% hydrogen peroxide, 0.05% chlorhexidine gluconate (CHG), and 0.3% povidone iodine solutions independently for 2 and 5 minutes. A low-cytotoxicity control (LCC) and a high-cytotoxicity control (HCC) were established to determine the mean cytotoxicity of each solution and each solution's superiority to LCC and non-inferiority to HCC. RESULTS: The present study demonstrated that 0.05% CHG was non-inferior to the HCC when chondrosarcoma was exposed for 5 minutes and when GCT was exposed for 2 and 5 minutes (mean cytotoxicity, 99% to 102%) (p < 0.003 for all). Sterile water was superior to the LCC when chondrosarcoma was exposed for 5 minutes and when GCT was exposed for 2 minutes (mean, 28% to 37%) (p < 0.05). Sterile water (mean, 18% to 38%) (p < 0.012) and 3% hydrogen peroxide (mean, 7% to 16%) (p < 0.001) were both inferior to the HCC. The 3 other solutions were non-superior to the LCC (mean, -24% to -5%) (p < 0.023). CONCLUSIONS: In vitro irrigation in 0.05% CHG provided high cytotoxicity, comparable with the HCC. Therefore, the use of a 0.05% CHG solution clinically could serve as a potential chemical adjuvant during intralesional curettage of chondrosarcoma and GCT. CLINICAL RELEVANCE: In an effort to reduce the burden of residual tumor cells, irrigation solutions are often utilized as adjuvant local therapy. Use of a 0.05% CHG solution clinically could serve as a potential chemical adjuvant to intralesional curettage of chondrosarcoma and GCT. Further in vivo studies may be indicated to assess clinical outcomes and safety associated with the use of 0.05% CHG in the treatment of chondrosarcoma and GCT.

Use of a modified Burow's solution to treat canine otitis externa: A randomised comparative clinical study.

BACKGROUND: Given the increase in antimicrobial drug resistance of several pathogens that affect the ear, there is a need for alternative therapy for canine otitis externa (OE). We hypothesised that the efficacy of modified Burow's solution would be non-inferior to that of standard treatment with Surolan. METHODS: The treatment success rate of a topical aluminum acetate 2% and betamethasone 0.1% (modified Burow's) otic solution was compared with that of a standard topical otic treatment of polymyxin B sulfate, prednisolone acetate and miconazole (Surolan) suspension in a prospective, open-label clinical trial. For 10 days, 142 dogs (232 ears) with OE were treated with modified Burow's solution or Surolan. The primary study endpoint was the cure rate at 10 days. Clinical efficacy was analysed as a secondary endpoint but without assessment for non-inferiority. RESULTS: The 10-day OE cure rate was 65% and 59% in the Burow's and Surolan groups, respectively. The modified Burow's solution was non-inferior to Surolan at a non-inferiority margin of -11.5% and was more clinically effective than Surolan in dogs with OE caused by yeast or bacteria. CONCLUSION: The results of this study demonstrate that modified Burow's solution is an effective treatment for OE in dogs.

Implementing Primary Palliative Care in Post-acute nursing home care: Protocol for an embedded pilot pragmatic trial.

INTRODUCTION: Older adults with serious illness frequently receive post-acute rehabilitative care in nursing homes (NH) under the Part A Medicare Skilled Nursing Facility (SNF) Benefit. Treatment is commonly focused on disease-modifying therapies with minimal consideration for goals of care, symptom relief, and other elements of palliative care. INTERVENTION: The evidence-based Primary Palliative Care in Post-Acute Care (PPC-PAC) intervention for older adults is delivered by nurse practitioners (NP). PPC-PAC NPs assess and manage symptoms, conduct goals of care discussions and assist with decision making; they communicate findings with NH staff and providers. Implementation of PPC-PAC includes online and face-to-face training of NPs, ongoing facilitation, and a template embedded in the NH electronic health record to document PPC-PAC. OBJECTIVES: The objectives of this pilot pragmatic clinical trial are to assess the feasibility, acceptability, and preliminary effectiveness of the PPC-PAC intervention and its implementation for 80 seriously ill older adults newly admitted to a NH for post-acute care. METHODS: Design is a two-arm nonequivalent group multi-site pilot pragmatic clinical trial. The unit of assignment is at the NP and unit of analysis is NH patients. Recruitment occurs at NHs in Pennsylvania, New Jersey, Delaware, and Maryland. Effectiveness (patient quality of life) data are collected at two times points-baseline and 14-21 days. CONCLUSION: This will be the first study to evaluate the implementation of an evidence-based primary palliative care intervention specifically designed for older adults with serious illness who are receiving post-acute NH care.

Echocardiographic and hemodynamic indices of myocardial contractility simultaneously evaluated in telemetered beagle dogs: A HESI-sponsored cross-company evaluation.

INTRODUCTION: Alterations in cardiac contractility can have significant clinical implications, highlighting the need for early detection of potential liabilities. Pre-clinical methods to assess contractility are typically invasive and their translation to human measures of cardiac function are not well defined. Clinically, cardiac function is most often measured non-invasively using echocardiography. The objective of these studies was to introduce echocardiography into standard large animal cardiovascular safety pharmacology studies and determine the feasibility of this combination. METHODS: A consortia of laboratories combined their data sets for evaluation. At each site, telemetered beagle dogs, in a 4 × 4 Latin square crossover study design (n = 4), were administered either pimobendan (positive inotrope) or atenolol (negative inotrope) orally at clinically relevant dose levels. Standard telemetry parameters were collected (heart rate, mean arterial blood pressure, etc.) continuously over 24 h, as well as derived contractility endpoints: QA interval and LV +dP/dtmax. At Tmax, echocardiography was performed in conscious dogs with minimal restraint to collect contractility parameters: ejection fraction (EF) and fractional shortening (FS). RESULTS: Correlations between telemetry and echo contractility endpoints showed that, in general, a change in LV +dP/dtmax of 1000 mmHg/s translates to a 5.2% change in EF and a 4.2% change in FS. Poor correlations were shown between QA interval derived simultaneously, to both EF and FS. DISCUSSION: Comparing data from telemetry-only groups to those that included echocardiography collections showed no effect in the ability to interpret test article-related effects, providing the foundation for the inclusion of echocardiography without compromising standard telemetry data quality.

The validation of a new scoring method for assessing ego development based on three dimensions of language.

We describe research on the validity of a new theoretical framework and scoring methodology, called STAGES, for sentence completion tests of meaning-making maturity or complexity (also called ego development or perspective-taking capacity). STAGES builds upon research on the substantially validated Washington University Sentence Completion Test of Jane Loevinger as updated by Susanne Cook-Greuter. STAGES proposes an underlying structural explanation for the Cook-Greuter system based on three dimensions. Two of these are polar factors: individual/collective, and passive/active; and the third is a categorization of the sophistication of the types of objects referred to (i.e. as concrete, subtle/abstract, or "metaware"). We describe two validation studies for the STAGES scoring method and model. The first is a replication study of concurrent validity, using 73 inventories to test the hypothesis that the STAGES scoring method replicates the Cook-Greuter scoring method. Using the weighted Kappa statistic, we demonstrate a very strong match between the two methods, confirming the first hypothesis. This study includes levels up to and including Strategist (i.e. a substantial percentage of test-takers from most populations). Levels above Strategist were validated using another method because (1) there is less Cook-Greuter data available at these levels, and (2) the two scoring methods diverge sufficiently, making comparison difficult. The second study, of 71 inventories, attempts to validate the STAGES scoring method at levels above Strategist by testing the inter-rater reliability among four scorers. The inter-rater reliability above Strategist, using the weighted Kappa statistic, was found to be moderate to substantial, indicating that the instrument and scoring method has internal validity for these four, rare higher levels. Additionally, the inter-rater reliability over all STAGES levels were found to be very strong.

Psychometric Evaluation of a Pain Intensity Measure for Persons with Dementia.

OBJECTIVE: The goal of this study was to conduct initial psychometric analyses of a seven-item pain intensity measure for persons with dementia (PIMD) that was developed using items from existing pain observational measures. DESIGN AND METHODS: We evaluated validity by examining associations with an expert clinician's pain intensity rating (ECPIR) and an established pain observation tool (Mobilization Observation Behaviour Intensity Dementia [MOBID]). We also examined correlations between the PIMD and known correlates of pain: depression, sleep disturbances, agitation, painful diagnoses, and caregiver pain reports. We examined the differences between PIMD scores for "at rest" and "during movement" observations. We assessed reliability by calculating Cronbach's alpha and estimating inter-rater reliability using intraclass correlations (ICCs). Finally, we examined whether six additional "recent changes in behavior" items improved the PIMD's ability to predict expert clinicians' pain ratings. SETTING: Sixteen nursing homes located in Alabama, Georgia, Pennsylvania, and New Jersey. PARTICIPANTS: One hundred ninety residents with moderate to severe cognitive impairment, mean age of 84 years, 49.5% female, and 70% white. RESULTS: PIMD during movement scores were highly correlated with the ECPIR and overall MOBID scores. As expected, there were large differences between at rest and during movement PIMD scores. Associations of PIMD with known correlates of pain were generally low and statistically nonsignificant. Internal consistency was supported with a Cronbach alpha of 0.72 and an inter-rater ICC of 0.82 for during movement PIMD scores. CONCLUSIONS: Initial evaluation of the PIMD supports its validity and reliability. Additional testing is needed to evaluate the tool's sensitivity to changes in pain intensity.

Developing a Pain Intensity Measure for Persons with Dementia: Initial Construction and Testing.

OBJECTIVE: The goal of this study was to identify a limited set of pain indicators that were most predicive of physical pain. We began with 140 items culled from existing pain observation tools and used a modified Delphi approach followed by statistical analyses to reduce the item pool. METHODS: Through the Delphi Method, we created a candidate item set of behavioral indicators. Next, trained staff observed nursing home residents and rated the items on scales of behavior intensity and frequency. We evaluated associations among the items and expert clinicians' assessment of pain intensity. SETTING: Four government-owned nursing homes and 12 community nursing homes in Alabama and Southeastern Pennsylvania. PARTICIPANTS: Ninety-five residents (mean age = 84.9 years) with moderate to severe cognitive impairment. RESULTS: Using the least absolute shrinkage and selection operator model, we identified seven items that best predicted clinicians' evaluations of pain intensity. These items were rigid/stiff body or body parts, bracing, complaining, expressive eyes, grimacing, frowning, and sighing. We also found that a model based on ratings of frequency of behaviors did not have better predictive ability than a model based on ratings of intensity of behaviors. CONCLUSIONS: We used two complementary approaches-expert opinion and statistical analysis-to reduce a large pool of behavioral indicators to a parsimonious set of items to predict pain intensity in persons with dementia. Future studies are needed to examine the psychometric properties of this scale, which is called the Pain Intensity Measure for Persons with Dementia.

Risk Factors for Lower Extremity Overuse Injuries in Female Youth Soccer Players.

BACKGROUND: Youth soccer injuries are common and of increasing concern, with sport specialization occurring at younger ages. Limited research is available regarding overuse injuries and risk factors in young female athletes. PURPOSE: To identify the number and rate of overuse injuries in female soccer players (ages 12-15 years), describe the anatomic location and type of injury, and evaluate contributing risk factors. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 351 female youth soccer players, ages 12 to 15 years, from Washington State were evaluated from 2008 to 2012. Players with lower extremity overuse injuries were identified through weekly emails and were interviewed by telephone to obtain data on injury type and body region. We evaluated the association between overuse injuries and preseason risk factors, including joint hypermobility, hip and knee muscle strength, and jump biomechanics, using Poisson regression to estimate relative risk (RR) and 95% CIs. RESULTS: The incidence rate for first-time lower extremity overuse injuries was 1.7 per 1000 athlete-exposure hours (AEH; 95% CI, 1.4-2.2), and that for repeat injuries was 3.4 per 1000 AEH (95% CI, 2.1-5.6). Knee injuries accounted for 47% of overuse injuries. Increased valgus was associated with a 3.2-fold increased risk (95% CI, 1.52-6.71) for knee injury. A 1-standard deviation (SD) increase in hamstring strength was associated with a 35% decreased risk (RR, 0.65; 95% CI, 0.46-0.91) for overuse knee injuries, and a 1-SD increase in quadriceps strength was associated with a 30% decreased risk (RR, 0.70; 95% CI, 0.50-0.98). A 1-SD increase in hip flexor strength was associated with a 28% decreased risk (RR, 0.72; 95% CI, 0.51-1.00) for overuse knee injuries, and a 1-SD increase in external rotation strength was associated with a 35% decreased risk (RR, 0.65; 95% CI, 0.46-0.91). Playing on more than 1 soccer team was associated with a 2.5-fold increased risk (95% CI, 1.08-5.35) for overuse knee injuries, and participating in other physical activities was associated with a 61% decreased risk (odds ratio, 0.39; 95% CI, 0.15-0.81). CONCLUSION: In this study, lower extremity overuse injuries in female youth soccer players affected primarily the knee. Lower knee separation distance, decreased lower extremity strength, and playing on more than 1 soccer team increased injury risk.

Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes: The MRI Substudy in AIM-HIGH.

OBJECTIVES: The aim of this study was to investigate whether and what carotid plaque characteristics predict systemic cardiovascular outcomes in patients with clinically established atherosclerotic disease. BACKGROUND: Advancements in atherosclerosis imaging have allowed assessment of various plaque characteristics, some of which are more directly linked to the pathogenesis of acute cardiovascular events compared to plaque burden. METHODS: As part of the event-driven clinical trial AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes), subjects with clinically established atherosclerotic disease underwent multicontrast carotid magnetic resonance imaging (MRI) to detect plaque tissue composition and high-risk features. Prospective associations between MRI measurements and the AIM-HIGH primary endpoint (fatal and nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, and symptom-driven revascularization) were analyzed using Cox proportional hazards survival models. RESULTS: Of the 232 subjects recruited, 214 (92.2%) with diagnostic image quality constituted the study population (82% male, mean age 61 ± 9 years, 94% statin use). During median follow-up of 35.1 months, 18 subjects (8.4%) reached the AIM-HIGH endpoint. High lipid content (hazard ratio [HR] per 1 SD increase in percent lipid core volume: 1.57; p = 0.002) and thin/ruptured fibrous cap (HR: 4.31; p = 0.003) in carotid plaques were strongly associated with the AIM-HIGH endpoint. Intraplaque hemorrhage had a low prevalence (8%) and was marginally associated with the AIM-HIGH endpoint (HR: 3.00; p = 0.053). High calcification content (HR per 1 SD increase in percent calcification volume: 0.66; p = 0.20), plaque burden metrics, and clinical risk factors were not significantly associated with the AIM-HIGH endpoint. The associations between carotid plaque characteristics and the AIM-HIGH endpoint changed little after adjusting for clinical risk factors, plaque burden, or AIM-HIGH randomized treatment assignment. CONCLUSIONS: Among patients with clinically established atherosclerotic disease, carotid plaque lipid content and fibrous cap status were strongly associated with systemic cardiovascular outcomes. Markers of carotid plaque vulnerability may serve as novel surrogate markers for systemic atherothrombotic risk.

Does Early Surgical Decompression in Cauda Equina Syndrome Improve Bladder Outcome?: Comments on a Recent Study by Srikandarajah et al.

STUDY DESIGN AND OBJECTIVES: This study by Srikandarajah et al is a retrospective cohort study of 200 CES patients. Although parts of the study appear to be well done we identified serious problems that impacted their conclusions. SUMMARY OF BACKGROUND DATA: There is strong consensus that patients with incomplete cauda equina syndrome (CESI) should be operated upon expeditiously to prevent progression to CES with urinary retention (CESR). There is controversy concerning optimal timing of surgery in patients who have entered CESR. Some studies conclude urgent surgery for CESR does nothing to improve chance of recovery; others conclude surgery should be done within a 48 or 24-hours window after onset of bladder paralysis. Srikandarajah et al concluded that in CESI patients, decompressive surgery within 24 hours of onset of autonomic symptoms reduces bladder dysfunction at follow-up. In CESR patients, "no statistically significant difference in outcome was observed" regarding timing of surgery. METHODS: We analyzed the methods used by Srikandarajah et al to collect and analyze their data. RESULTS: The primary problem with their study is that it does not consider deterioration to CESR that occurs in CESI patients over time. We also found serious problems with the methods, implementation (including numeric errors), and interpretation of the statistical analysis. CONCLUSION: The authors' conclusion that in CESR patients, "no statistically significant difference in outcome was observed" regarding timing of surgery is not justified as a representation of their findings, because absence of statistical significance does not mean acceptance of the null hypothesis of "no effect". Their numeric results do show elevated risk of delay. We do not want to detract from the basic importance of this study, because it emphasizes the importance of operating expeditiously on patients with CESI. However, the authors' conclusions are compromised by the methodological problems. LEVEL OF EVIDENCE: N/A.

Summary of clinical and laboratory data of study subjects with and without DCE-MRI plaque measurements in the AIM-HIGH clinical trial.

This brief data article summarizes the clinical risk factors and laboratory data of a group of subjects recruited for the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) and an associated magnetic resonance imaging (MRI) substudy. The sample is restricted to those on statin therapy at the time of enrollment and data are presented stratified by whether dynamic contrast enhanced MRI (DCE-MRI) markers of carotid plaque vascularity and inflammation were available or not. The data provided herein are directly related to the article "Longer Duration of Statin Therapy is Associated with Decreased Carotid Plaque Vascularity by Magnetic Resonance Imaging" [2].

Pain Management Algorithms for Implementing Best Practices in Nursing Homes: Results of a Randomized Controlled Trial.

OBJECTIVE: To enhance pain practices in nursing homes (NHs) using pain assessment and management algorithms and intense diffusion strategies. DESIGN: A cluster, randomized controlled trial. The intervention consisted of intensive training and support for the use of recommended pain assessment and management practices using algorithms (ALGs). Control facilities received pain education (EDU) only. SETTING: Twenty-seven NHs in the greater Puget Sound area participated. Facilities were diverse in terms of size, quality, and ownership. PARTICIPANTS: Data were collected from 485 NH residents; 259 for the intervention and 226 for the control group. MEASUREMENTS: Resident outcomes were nursing assistant (proxy) report and self-reported resident pain intensity. Process outcomes were adherence to recommended pain practices. Outcomes were measured at baseline, completion of the intervention (ALG) or training (EDU), and again 6 months later. RESULTS: Among 8 comparisons of outcome measures between ALG and EDU (changes in 4 primary pain measures compared at 2 postintervention time points) there was only 1 statistically significant but small treatment difference in proxy- or self-reported pain intensity. Resident-reported worst pain decreased by an average of 0.8 points from baseline to 6 months among the EDU group and increased by 0.2 points among the ALG (P = .005), a clinically nonsignificant difference. There were no statistically significant differences in adherence to clinical guideline practice recommendations between ALG and EDU following the intervention. CONCLUSIONS: Future research needs to identify and test effective implementation methods for changing complex clinical practices in NHs, including those to reduce pain.

Shoe and Field Surface Risk Factors for Acute Lower Extremity Injuries Among Female Youth Soccer Players.

OBJECTIVE: To describe acute lower extremity injuries and evaluate extrinsic risk factors in female youth soccer. DESIGN: Nested case-control study. SETTING: Youth soccer clubs in Seattle, WA. PARTICIPANTS: Female soccer players (n = 351) ages 11 to 15 years randomly selected from 4 soccer clubs from which 83% of their players were enrolled with complete follow-up for 92% of players. INTERVENTIONS: Injured players were interviewed regarding injury, field surface, shoe type, and position. Uninjured controls, matched on game or practice session, were also interviewed. MAIN OUTCOME MEASURES: The association between risk factors and acute lower extremity injury using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: One hundred seventy-three acute lower extremity injuries occurred involving primarily the ankle (39.3%), knee (24.9%), and thigh (11.0%). Over half (52.9%) recovered within 1 week, whereas 30.2% lasted beyond 2 weeks. During practices, those injured were approximately 3-fold (OR, 2.83; 95% CI, 1.49-5.31) more likely to play on grass than artificial turf and 2.4-fold (95% CI, 1.03-5.96) more likely to wear cleats on grass than other shoe and surface combinations. During games, injured players were 89% (95% CI, 1.03-4.17) more likely to play defender compared with forward. CONCLUSIONS: Half of the acute lower extremity injuries affected the ankle or knee. Grass surface and wearing cleats on grass increased training injuries. CLINICAL RELEVANCE: The majority, 64%, of female youth soccer players' acute injuries involve the ankle and knee and injury prevention strategies in this age group should target these areas. When considering playing surfaces for training, communities and soccer organizations should consider the third-generation artificial turf a safe alternative to grass.

Is Knee Separation During a Drop Jump Associated With Lower Extremity Injury in Adolescent Female Soccer Players?

BACKGROUND: Knee injuries are common in older adolescent and adult female soccer players, and abnormal valgus knee appearance characterized by low normalized knee separation (NKS) is a proposed injury risk factor. What constitutes normal NKS in younger adolescents and whether low NKS is an injury risk factor are unknown. PURPOSE: To determine the normal range of NKS using a drop-jump test in female perimenarchal youth soccer players and whether low NKS contributes to lower extremity injuries or knee injuries. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: From 2008 to 2012, a total of 351 female elite youth soccer players (age range, 11-14 years) were followed for 1 season, with complete follow-up on 92.3% of players. Baseline drop-jump testing was performed preseason. Lower extremity injuries during the season were identified using a validated, Internet-based injury surveillance system with weekly email reporting. Normalized knee separation at prelanding, landing, and takeoff was categorized 2 ways: as ≤10th percentile (most extreme valgus appearance) compared with >10th percentile and as a continuous measure of 1 SD. Poisson regression modeling with adjustment for clustering by team estimated the relative risk (RR) and 95% confidence interval (CI) of the association between the NKS and the risk of lower extremity and knee injury, stratified by menarche. RESULTS: Of the study participants, 134 players experienced 173 lower extremity injuries, with 43 (24.9%) knee injuries. For postmenarchal players (n = 210), those with NKS ≤10th percentile were at 92% increased risk of lower extremity injury (RR, 1.92; 95% CI, 1.17-3.15) and a 3.62-fold increased risk of knee injury (RR, 3.62; 95% CI, 1.18-11.09) compared with NKS >10th percentile at prelanding and landing, respectively. Among postmenarchal players, there was an 80% increased risk of knee injury (RR, 1.80; 95% CI, 1.01-3.23) with a decrease of 1 SD in landing NKS and a 66% increased risk of knee injury (RR, 1.66; 95% CI, 1.04-2.64) with a decrease of 1 SD in takeoff NKS. Among premenarchal players (n = 141), there was no statistically significant association between the NKS at prelanding, landing, and takeoff and the risk of lower extremity or knee injury. CONCLUSION: Low NKS was associated with increased risk of lower extremity and knee injury only among postmenarchal players.

Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging.

OBJECTIVE: Plaque neovasculature is a major route for lipoprotein and leukocyte ingress into plaques, and has been identified as a risk factor for carotid plaque disruption. Vp, a variable derived from pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), correlates with plaque neovasculature density. Because lipid-lowering therapy has been associated with regression of neovasculature in animal models, we sought to determine clinical correlates of carotid plaque neovasculature (as assessed by Vp) in participants on statin therapy for established cardiovascular disease. METHODS: 98 participants from an AIM-HIGH sub-study underwent DCE-MRI of their carotid arteries. Expert readers who were blinded to all clinical variables analyzed the MR images to measure carotid plaque Vp in all participants. Associations between Vp and duration of statin therapy and other clinical risk factors were analyzed. RESULTS: Prior duration of statin treatment at enrollment ranged from <1 year (21%) 1-5 years (40%) and >5 years (39%). In univariate analyses, shorter duration of statin therapy (P = 0.01), the presence of metabolic syndrome (P = 0.02), and higher body mass index (P = 0.01) and lipoprotein(a) (P = 0.01) were all significantly associated with higher baseline Vp values. In multivariate analyses, significant associations remained between shorter duration of statin therapy (P = 0.004) and lipoprotein(a) (P = 0.04). CONCLUSIONS: These are the first human, in vivo findings suggesting a relationship between duration of statin therapy and regression of carotid plaque neovasculature. Future longitudinal studies are warranted both to confirm this finding and to address whether changes in neovasculature may translate into change in risk for plaque disruption. CLINICALTRIALS. GOV IDENTIFIERS: NCT00880178, NCT01178320 and NCT00120289.

Prediction of pain outcomes in a randomized controlled trial of dose-response of spinal manipulation for the care of chronic low back pain.

BACKGROUND: No previous studies have created and validated prediction models for outcomes in patients receiving spinal manipulation for care of chronic low back pain (cLBP). We therefore conducted a secondary analysis alongside a dose-response, randomized controlled trial of spinal manipulation. METHODS: We investigated dose, pain and disability, sociodemographics, general health, psychosocial measures, and objective exam findings as potential predictors of pain outcomes utilizing 400 participants from a randomized controlled trial. Participants received 18 sessions of treatment over 6-weeks and were followed for a year. Spinal manipulation was performed by a chiropractor at 0, 6, 12, or 18 visits (dose), with a light-massage control at all remaining visits. Pain intensity was evaluated with the modified von Korff pain scale (0-100). Predictor variables evaluated came from several domains: condition-specific pain and disability, sociodemographics, general health status, psychosocial, and objective physical measures. Three-quarters of cases (training-set) were used to develop 4 longitudinal models with forward selection to predict individual "responders" (≥50% improvement from baseline) and future pain intensity using either pretreatment characteristics or post-treatment variables collected shortly after completion of care. The internal validity of the predictor models were then evaluated on the remaining 25% of cases (test-set) using area under the receiver operating curve (AUC), R(2), and root mean squared error (RMSE). RESULTS: The pretreatment responder model performed no better than chance in identifying participants who became responders (AUC = 0.479). Similarly, the pretreatment pain intensity model predicted future pain intensity poorly with low proportion of variance explained (R(2) = .065). The post-treatment predictor models performed better with AUC = 0.665 for the responder model and R(2) = 0.261 for the future pain model. Post-treatment pain alone actually predicted future pain better than the full post-treatment predictor model (R(2) = 0.350). The prediction errors (RMSE) were large (19.4 and 17.5 for the pre- and post-treatment predictor models, respectively). CONCLUSIONS: Internal validation of prediction models showed that participant characteristics preceding the start of care were poor predictors of at least 50% improvement and the individual's future pain intensity. Pain collected shortly after completion of 6 weeks of study intervention predicted future pain the best.