Steve Marshall

Incidence of allergy and allergy symptoms among workers exposed to laboratory animals

Background and Aims: Few studies have described relations between exposure to laboratory animals and the incidence of laboratory animal allergy (LAA). Studies that have found exposure-response relations have been cross sectional in design or have focused on exposure to rats and mice. This study used longitudinal data collected over a 12 year period to describe the relations between indices of exposure to laboratory animals and the development of LAA and LAA symptoms. Methods: Data were obtained from questionnaires and serological laboratory results from a dynamic cohort of workers exposed to a variety of laboratory animals in a pharmaceutical manufacturing company. Poisson regression was used to model the incidence rate ratios of species specific and general LAA and LAA symptoms at different levels of exposure. Results: The 12 year incidence rates of LAA symptoms and LAA for all workers were 2.26 (95% CI 1.61 to 2.91) and 1.32 (95% CI 0.76 to 1.87) per 100 person-years, respectively. Higher rate ratios were seen with increasing reported hours of exposure to tasks that required working with animal cages or with many animals at one time. The most common symptoms were related to rhinitis rather than to asthma. Conclusions: This study suggests that the risk of LAA increases with duration of exposure to animals and work in animal related tasks. Incidence might be reduced by limiting hours per week of exposure to laboratory animals.

124 SERUM CARTILAGE OLIGOMERIC MATRIX PROTEIN HYALURONAN HIGH-SENSITIVITY C-REACTIVE PROTEIN AND KERATAN SULFATE AS PREDICTORS OF INCIDENT RADIOGRAPHIC KNEE OSTEOARTHRITIS: DIFFERENCES BY CHRONIC KNEE SYMPTOMS

124 – Table 1. Adjusted Hazard Ratios (HR) of Knee Outcomes, by Biomarker, Stratified by Chronic Knee Symptoms Biomarker Knee Outcome Chronic Knee Symptoms No Chronic Knee Symptoms P-value of interaction between between ln(biomarker) and knee symptoms # Knees # Knees Adjusted HR 95% CI # Knees # Knees Adjusted HR 95% CI at Risk with Outcome at Risk with Outcome ln(COMP) KL Score 166 46 1.49 0.80-2.78 374 64 1.43 0.80-2.54 0.83 OST 97 33 4.19 1.85-9.48 250 61 1.83 1.02-3.30 0.11 JSN 129 35 2.47 1.08-5.65 308 64 1.98 1.07-3.66 0.46 ln(HA) KL Score 166 46 1.30 0.91-1.87 374 64 1.02 0.77-1.35 0.81 OST 97 33 1.13 0.67-1.89 250 61 0.86 0.63-1.17 0.29 JSN 129 35 2.12 1.37-3.28 308 64 1.47 1.08-2.00 0.22 ln(hsCRP) KL Score 166 46 0.98 0.76-1.27 374 64 1.00 0.80-1.24 0.67 OST 97 33 1.03 0.75-1.41 250 61 0.88 0.71-1.10 0.23 JSN 129 35 1.08 0.78-1.49 308 64 1.10 0.90-1.36 0.13 ln(KS) KL Score 166 46 1.79 0.74-4.32 374 64 0.91 0.43-1.95 0.12 OST 97 33 3.85 1.25-11.87 250 61 1.19 0.52-2.71 0.42 JSN 129 35 2.78 0.98-7.90 308 64 0.86 0.41-1.83 0.24 OST and JSN outcomes among knees with chronic symptoms at baseline compared to knees without symptoms. Conclusions: Higher baseline lnCOMP and lnHA levels were associated with incident knee OA, OST, and JSN over an average follow-up period of 6.3 years. These results did not vary by history of lower extremity injury, but this interpretation is incomplete due to power limitations and the potential misclassification that comes with self-report and long duration since reported injury. The presence of chronic knee symptoms, in combination with higher levels of serum COMP, HA, or KS, may provide clues to the early detection of OA.

Defining Controlled Substances Overdose: Should Deaths from Substance Use Disorders and Pharmaceutical Adverse Events be included?

Background: The rate of mortality attributable to drug poisoning has risen consistently since the 1990s. State-based vital statistics registries estimate the incidence of drug overdose deaths using International Classification of Disease 10th revision (ICD-10) codes. Composite ICD-10-based definitions of “overdose” may include deaths that do not involve controlled substances while missing deaths that do. This has implications for incidence estimates, funding priorities, and intervention evaluation. Methods: We evaluated the impact of including substance use disorders and pharmaceutical adverse events codes in definitions of overdose. Seven proposed ICD-10-based definitions, including ones from the Injury Surveillance Workgroup (ISW) and the Centers for Disease Control and Prevention (CDC), were applied to North Carolina mortality data from 2008 through 2011. We examined whether overdose deaths varied among definitions. Results: Approximately 1.5% of all deaths among NC residents were due to overdose. Prescription opioids were involved in 63.4% of drug overdose deaths. The estimated number of overdose deaths ranged from 734 to 1,202 per year depending on which definition was used. Of deaths identified using the CDC definition, between 6.4% and 16.1% were pharmaceutical adverse events that showed no evidence of controlled substance involvement. However, there were 12 additional deaths per year that appeared to be overdoses involving controlled substances that were not identified. We propose a definition that includes 28 deaths from substance use disorders, but removes 88 deaths from adverse events, resulting in 1,149 deaths per year on average from overdoses involving controlled substances. Conclusions: Quantifying mortality from drug overdose depends on close cooperation of diverse health professionals. State health department injury control officials should carefully choose which ICD-10 codes are most relevant for their data. Researchers evaluating interventions to prevent overdoses from controlled substances may obtain a more accurate measure of effect by separating pharmaceutical adverse events from non-controlled medicines.

Utilization of Emergency Department Data for Drug Overdose Surveillance in North Carolina

The United States is in the midst of a drug overdose epidemic, primarily due to opioid analgesics. Emergency department data are an important source of morbidity data for public health surveillance. This population-based study will describe visits to North Carolina emergency departments for drug, and more specifically, opioid overdoses.

Associations between cartilage proteoglycan density and patient outcomes 12 months following anterior cruciate ligament reconstruction

BACKGROUND Lower proteoglycan density (PGD) of the articular cartilage may be an early marker of osteoarthritis following anterior cruciate ligament (ACL) reconstruction (ACL-R). The purpose this study was to determine associations between the Knee Injury and Osteoarthritis Outcomes Score (KOOS) and PGD of the articular cartilage in the femur and tibia 12-months following ACL-R. METHODS We evaluated KOOS pain, symptoms, function in activities of daily living (ADL), function in sport and recreation (Sport), and quality of life (QOL), as well as PGD using T1rho magnetic resonance imaging in 18 individuals 12.50±0.70months (these are all mean±standard deviation) following unilateral ACL-R (10 females, eight males; 22.39±4.19years; Marx Score=10.93±3.33). Medial and lateral load-bearing portions of the femoral and tibial condyles were sectioned into three (anterior, central and posterior) regions of interest (ROIs). T1rho relaxation times in the ACL-R knee were normalized to the same regions of interest in the non-surgical knees. Alpha levels were set at P≤0.05. RESULTS Worse KOOS outcomes were significantly associated with greater T1rho relaxation time ratios in the posterior-lateral femoral condyle [pain (r=-0.54), ADL (r=-0.56), Sport (r=-0.62) and QOL (r=-0.59)] central-lateral femoral condyle [Sport (r=-0.48) and QOL (r=-0.42)], and the anterior-medial femoral condyle [Sport (r=-0.46) and QOL (r=-0.40)]. There were no significant associations between the KOOS and T1rho outcomes for tibial ROI. CONCLUSIONS Lower PGD of the femoral cartilage in the ACL-R knees was associated with worse patient-reported outcomes.