Eric Garshick

A prospective assessment of mortality in chronic spinal cord injury

Study design:Prospective mortality study.Objective:To assess the relationship between comorbid medical conditions and other health-related factors to mortality in chronic spinal cord injury (SCI).Setting:Boston, MA, USA.Methods:Between 1994 and 2000, 361 males ⩾1 year after injury completed a respiratory health questionnaire and underwent pulmonary function testing. Cause-specific mortality was assessed over a median of 55.6 months (range 0.33–74.4 months) through 12/31/2000 using the National Death Index.Results:At entry, mean (±SD) age was 50.6±15.0 years (range 23–87) and years since injury was 17.5±12.8 years (range 1.0–56.5). Mortality was elevated (observed/expected deaths=37/25.1; SMR=1.47; 95% CI=1.04–2.03) compared to US rates. Risk factors for death were diabetes (RR=2.62; 95% CI=1.19–5.77), heart disease (RR=3.66; 95% CI=1.77–7.78), reduced pulmonary function, and smoking. The most common underlying and contributing causes of death were diseases of the circulatory system (ICD-9 390–459) in 40%, and of the respiratory system in 24% (ICD-9 460-519).Conclusions:These results suggest that much of the excess mortality in chronic SCI is related to potentially treatable factors. Recognition and treatment of cardiovascular disease, diabetes, and lung disease, together with smoking cessation may substantially reduce mortality in chronic SCI.

Lung Cancer in Railroad Workers Exposed to Diesel Exhaust

Diesel exhaust has been suspected to be a lung carcinogen. The assessment of this lung cancer risk has been limited by lack of studies of exposed workers followed for many years. In this study, we assessed lung cancer mortality in 54,973 U.S. railroad workers between 1959 and 1996 (38 years). By 1959, the U.S. railroad industry had largely converted from coal-fired to diesel-powered locomotives. We obtained work histories from the U.S. Railroad Retirement Board, and ascertained mortality using Railroad Retirement Board, Social Security, and Health Care Financing Administration records. Cause of death was obtained from the National Death Index and death certificates. There were 43,593 total deaths including 4,351 lung cancer deaths. Adjusting for a healthy worker survivor effect and age, railroad workers in jobs associated with operating trains had a relative risk of lung cancer mortality of 1.40 (95% confidence interval, 1.30–1.51). Lung cancer mortality did not increase with increasing years of work in these jobs. Lung cancer mortality was elevated in jobs associated with work on trains powered by diesel locomotives. Although a contribution from exposure to coal combustion products before 1959 cannot be excluded, these results suggest that exposure to diesel exhaust contributed to lung cancer mortality in this cohort.

Traumatic spinal cord injury in the United States, 1993-2012

IMPORTANCE Acute traumatic spinal cord injury results in disability and use of health care resources, yet data on contemporary national trends of traumatic spinal cord injury incidence and etiology are limited. OBJECTIVE To assess trends in acute traumatic spinal cord injury incidence, etiology, mortality, and associated surgical procedures in the United States from 1993 to 2012. DESIGN, SETTING, AND PARTICIPANTS Analysis of survey data from the US Nationwide Inpatient Sample databases for 1993-2012, including a total of 63,109 patients with acute traumatic spinal cord injury. MAIN OUTCOMES AND MEASURES Age- and sex-stratified incidence of acute traumatic spinal cord injury; trends in etiology and in-hospital mortality of acute traumatic spinal cord injury. RESULTS In 1993, the estimated incidence of acute spinal cord injury was 53 cases (95% CI, 52-54 cases) per 1 million persons based on 2659 actual cases. In 2012, the estimated incidence was 54 cases (95% CI, 53-55 cases) per 1 million population based on 3393 cases (average annual percentage change, 0.2%; 95% CI, -0.5% to 0.9%). Incidence rates among the younger male population declined from 1993 to 2012: for age 16 to 24 years, from 144 cases/million (2405 cases) to 87 cases/million (1770 cases) (average annual percentage change, -2.5%; 95% CI, -3.3% to -1.8%); for age 25 to 44 years, from 96 cases/million (3959 cases) to 71 cases/million persons (2930 cases), (average annual percentage change, -1.2%; 95% CI, -2.1% to -0.3%). A high rate of increase was observed in men aged 65 to 74 years (from 84 cases/million in 1993 [695 cases] to 131 cases/million [1465 cases]; average annual percentage change, 2.7%; 95% CI, 2.0%-3.5%). The percentage of spinal cord injury associated with falls increased significantly from 28% (95% CI, 26%-30%) in 1997-2000 to 66% (95% CI, 64%-68%) in 2010-2012 in those aged 65 years or older (P < .001). Although overall in-hospital mortality increased from 6.6% (95% CI, 6.1%-7.0%) in 1993-1996 to 7.5% (95% CI, 7.0%-8.0%) in 2010-2012 (P < .001), mortality decreased significantly from 24.2% (95% CI, 19.7%-28.7%) in 1993-1996 to 20.1% (95% CI, 17.0%-23.2%) in 2010-2012 (P = .003) among persons aged 85 years or older. CONCLUSIONS AND RELEVANCE Between 1993 and 2012, the incidence rate of acute traumatic spinal cord injury remained relatively stable but, reflecting an increasing population, the total number of cases increased. The largest increase in incidence was observed in older patients, largely associated with an increase in falls, and in-hospital mortality remained high, especially among elderly persons.

Osteoporotic fractures and hospitalization risk in chronic spinal cord injury

SummaryOsteoporosis is a well acknowledged complication of spinal cord injury. We report that motor complete spinal cord injury and post-injury alcohol consumption are risk factors for hospitalization for fracture treatment. The clinical assessment did not include osteoporosis diagnosis and treatment considerations, indicating a need for improved clinical protocols.IntroductionTreatment of osteoporotic long bone fractures often results in lengthy hospitalizations for individuals with spinal cord injury. Clinical features and factors that contribute to hospitalization risk have not previously been described.MethodsThree hundred and fifteen veterans ≥ 1 year after spinal cord injury completed a health questionnaire and underwent clinical exam at study entry. Multivariate Cox regression accounting for repeated events was used to assess longitudinal predictors of fracture-related hospitalizations in Veterans Affairs Medical Centers 1996–2003.ResultsOne thousand four hundred and eighty-seven hospital admissions occurred among 315 participants, and 39 hospitalizations (2.6%) were for fracture treatment. Median length of stay was 35 days. Fracture-related complications occurred in 53%. Independent risk factors for admission were motor complete versus motor incomplete spinal cord injury (hazard ratio = 3.73, 95% CI = 1.46–10.50). There was a significant linear trend in risk with greater alcohol consumption after injury. Record review indicated that evaluation for osteoporosis was not obtained during these admissions.ConclusionsAssessed prospectively, hospitalization in Veterans Affairs Medical Centers for low-impact fractures is more common in motor complete spinal cord injury and is associated with greater alcohol use after injury. Osteoporosis diagnosis and treatment considerations were not part of a clinical assessment, indicating the need for improved protocols that might prevent low-impact fractures and related admissions.

Lung Cancer and Vehicle Exhaust in Trucking Industry Workers

Background An elevated risk of lung cancer in truck drivers has been attributed to diesel exhaust exposure. Interpretation of these studies specifically implicating diesel exhaust as a carcinogen has been limited because of limited exposure measurements and lack of work records relating job title to exposure-related job duties. Objectives We established a large retrospective cohort of trucking company workers to assess the association of lung cancer mortality and measures of vehicle exhaust exposure. Methods Work records were obtained for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. We assessed lung cancer mortality through 2000 using the National Death Index, and we used an industrial hygiene review and current exposure measurements to identify jobs associated with current and historical use of diesel-, gas-, and propane-powered vehicles. We indirectly adjusted for cigarette smoking based on an industry survey. Results Adjusting for age and a healthy-worker survivor effect, lung cancer hazard ratios were elevated in workers with jobs associated with regular exposure to vehicle exhaust. Mortality risk increased linearly with years of employment and was similar across job categories despite different current and historical patterns of exhaust-related particulate matter from diesel trucks, city and highway traffic, and loading dock operations. Smoking behavior did not explain variations in lung cancer risk. Conclusions Trucking industry workers who have had regular exposure to vehicle exhaust from diesel and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work.

Long-Term Ambient Multipollutant Exposures and Mortality

RATIONALE population-based studies have demonstrated associations between ambient air pollution exposures and mortality, but few have been able to adjust for occupational exposures. Additionally, two studies have observed higher risks in individuals with occupational dust, gas, or fume exposure. OBJECTIVES we examined the association of ambient residential exposure to particulate matter less than 10 microm in diameter (PM(10)), particulate matter less than 2.5 microm in diameter (PM(2.5)), NO(2), SO(2), and mortality in 53,814 men in the U.S. trucking industry. METHODS exposures for PM(10), NO(2), and SO(2) at each residential address were assigned using models combining spatial smoothing and geographic covariates. PM(2.5) exposures in 2000 were assigned from the nearest available monitor. Single and multipollutant Cox proportional hazard models were used to examine the association of an interquartile range (IQR) change (6 microg/m(3) for PM(10), 4 microg/m(3) for PM(2.5), 4ppb for SO(2), and 8ppb for NO(2)) and the risk of all-cause and cause-specific mortality. MEASUREMENTS AND MAIN RESULTS an IQR change in ambient residential exposures to PM(10) was associated with a 4.3% (95% confidence interval [CI], 1.1-7.7%) increased risk of all-cause mortality. The increase for an IQR change in SO(2) was 6.9% (95% CI, 2.3-11.6%), for NO(2) was 8.2% (95% CI, 4.5-12.1%), and for PM(2.5) was 3.9% (95% CI, 1.0-6.9%). Elevated associations with cause-specific mortality (lung cancer, cardiovascular and respiratory disease) were observed for PM(2.5), SO(2), and NO(2), but not PM(10). None of the pollutants were confounded by occupational exposures. In multipollutant models, overall, the associations were attenuated, most strongly for PM(10). In sensitivity analyses excluding long-haul drivers, who spend days away from home, larger hazard ratios were observed. CONCLUSIONS in this population of men, residential ambient air pollution exposures were associated with mortality.

Residence near a major road and respiratory symptoms in U.S. Veterans.

Background: There is evidence that exposure to motor vehicle exhaust is associated with respiratory disease. Studies in children have observed associations with wheeze, hospital admissions for asthma, and decrements in pulmonary function. However, a relationship of adult respiratory disease with exposure to vehicular traffic has not been established. Methods: We studied a sample of U.S. male veterans drawn from the general population of southeastern Massachusetts. Information on respiratory symptoms and potential risk factors was collected by questionnaire. We assessed distance from residential addresses to major roadways using geographic information system methodology. Results: Adjusting for cigarette smoking, age, and occupational exposure to dust, men living within 50 m of a major roadway were more likely to report persistent wheeze (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0–1.7) compared with those living more than 400 m away. The risk was observed only for those living within 50 m of heavily trafficked roads (≥10,000 vehicles/24 h): OR = 1.7; CI = 1.2–2.4). The risk of patients experiencing chronic phlegm while living on heavily trafficked roads also increased (OR = 1.4; CI = 1.0–2.0), although there was little evidence for an association with chronic cough. This association was not dependent on preexisting doctor-diagnosed chronic respiratory or heart disease. Conclusions: Exposure to vehicular emissions by living near busy roadways might contribute to symptoms of chronic respiratory disease in adults.

Free-Living Physical Activity in COPD: Assessment with Accelerometer and Activity Checklist

To assess physical activity and disability in chronic obstructive pulmonary disease (COPD), we evaluated the use of an accelerometer and checklist to measure free-living physical activity. Seventeen males with stable COPD completed a daily activity checklist for 14 days. Ten subjects concurrently wore an Actiped accelerometer (FitSense, Southborough, Massachussetts) that records steps per day. Regression models assessed relationships between steps per day, number of daily checklist activities performed, and clinical measures of COPD status. The average steps per day ranged from 406 to 4,856. The median intrasubject coefficient of variation for steps per day was 0.52 (interquartile range [IQR] 0.41-0.58) and for number of daily checklist activities performed was 0.28 (IQR 0.22-0.32). A higher number of steps per day was associated with a greater distance walked on the 6-minute walk test and better health-related quality of life. A higher number of daily checklist activities performed was associated with a higher force expiratory volume in 1 s percent predicted and lowerbody mass index, airflow obstruction, dyspnea, exercise capacity (BODE) index. Prospectively measuring free-living physical activity in COPD using an unobtrusive accelerometer and simple activity checklist is feasible. Low intrasubject variation was found in free-living physical activity, which is significantly associated with clinical measures of COPD status.

Daily Step Count Predicts Acute Exacerbations in a US Cohort with COPD

Background COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs). Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations. Methods In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count. We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St. Georges Respiratory Questionnaire Activity Score (SGRQ-AS). AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months. Results Mean daily step count was 5804±3141 steps. Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3±1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56±1.09 per person-year). Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003–1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08–1.42). There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003). Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01–1.14) for AEs and 1.18 (95%CI = 1.07–1.30) for COPD-related hospitalizations. Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01–1.09) for AEs and 1.10 (95%CI = 1.02–1.17) for COPD-related hospitalizations. Conclusions Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD–related hospitalizations, independent of pulmonary function and previous AE history. These results support the importance of assessing PA in patients with COPD, and provide the rationale to promote PA as part of exacerbation-prevention strategies.

Association between sclerostin and bone density in chronic spinal cord injury.

Spinal cord injury (SCI) results in profound bone loss due to muscle paralysis and the inability to ambulate. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short‐term studies in rodent models have shown increased sclerostin in response to mechanical unloading that is reversed with reloading. These studies suggest that complete spinal cord injury, a condition resulting in mechanical unloading of the paralyzed lower extremities, will be associated with high sclerostin levels. We assessed the relationship between circulating sclerostin and bone density in 39 subjects with chronic SCI and 10 without SCI. We found that greater total limb bone mineral content was significantly associated with greater circulating levels of sclerostin. Sclerostin levels were reduced, not elevated, in subjects with SCI who use a wheelchair compared with those with SCI who walk regularly. Similarly, sclerostin levels were lower in subjects with SCI who use a wheelchair compared with persons without SCI who walk regularly. These findings suggest that circulating sclerostin is a biomarker of osteoporosis severity, not a mediator of ongoing bone loss, in long‐term, chronic paraplegia. This is in contrast to the acute sclerostin‐mediated bone loss shown in animal models of mechanical unloading in which high sclerostin levels suppress bone formation. Because these data indicate important differences in the relationship between mechanical unloading, sclerostin, and bone in chronic SCI compared with short‐term rodent models, it is likely that sclerostin is not a good therapeutic target to treat chronic SCI‐induced osteoporosis.