Identifying factors associated with physical therapy use versus non-use among injured workers with back pain in Washington State.

BACKGROUND: There is little information about predictors of physical therapy (PT) use among injured workers with back pain. The primary objective of this study is to investigate the associations between PT use and baseline factors not routinely captured in workers' compensation (WC) data. METHODS: We conducted a secondary analysis using the Washington State Workers' Compensation Disability Risk Identification Study Cohort, which combines self-reported surveys with claims data from the Washington State Department of Labor and Industries State Fund. Workers with an accepted or provisional WC claim for back injury between June 2002 and April 2004 were eligible. Baseline factors for PT use were selected from six domains (socio-demographic, pain and function, psychosocial, clinical, health behaviors, and employment-related). The outcome was a binary measure for PT use within 1 year of injury. Bivariate and multivariable logistic regression models were conducted to evaluate the associations between PT use and baseline factors. RESULTS: Among the 1370 eligible study participants, we identified 673 (49%) who received at least one PT service. Baseline factors from five of the six domains (all but health behaviors) were associated with PT use, including gender, income, pain and function measures, injury severity rating, catastrophizing, recovery expectations, fear avoidance, mental health score, body mass index, first provider seen for injury, previous injury, and several work-related factors. CONCLUSION: We identify baseline factors that are associated with PT use, which may be useful in addressing disparities in access to care for injured workers with back pain in a WC system.

Intensity of physical therapy services: Association with work and health outcomes in injured workers with back pain in Washington State.

BACKGROUND: Associations between the intensity of physical therapy (PT) treatments and health outcomes among individuals with back pain have been examined in the general population; however, few studies have explored these associations in injured workers. Our study objective was to examine whether intensity of PT treatments is positively associated with work and health outcomes in injured workers with back pain. METHODS: We conducted a secondary analysis of prospective data collected from the Washington State Workers' Compensation (WC) Disability Risk Identification Study Cohort (D-RISC). D-RISC combined survey results with WC data from the Washington State Department of Labor and Industries. Workers with a State Fund WC claim for back injuries between June 2002 and April 2004 and who received PT services within the first year of injury were eligible. Intensity of PT treatment was measured as the type and amount of PT services within 28 days from the first PT visit. Outcome measures included work disability and self-reported measures for working for pay, pain intensity, and functional status at 1-year follow-up. We conducted linear and logistic regression models to test associations. RESULTS: We identified 662 eligible workers. In adjusted models, although the intensity of PT treatment was not significantly associated with work disability at 1-year follow-up, it was associated with lower odds of working for pay, decreased pain intensity, and improved functional status. CONCLUSIONS: Our findings suggest that there may be small benefits from receiving active PT, manual therapy, and frequent PT treatments within 28 days of initiating PT care.

Potential Impacts of Different Occupational Outdoor Heat Exposure Thresholds among Washington State Crop and Construction Workers and Implications for Other Jurisdictions.

Occupational heat exposure is associated with substantial morbidity and mortality among outdoor workers. We sought to descriptively evaluate spatiotemporal variability in heat threshold exceedances and describe potential impacts of these exposures for crop and construction workers. We also present general considerations for approaching heat policy-relevant analyses. We analyzed county-level 2011-2020 monthly employment (Bureau of Labor Statistics Quarterly Census of Employment and Wages) and environmental exposure (Parameter-elevation Relationships on Independent Slopes Model (PRISM)) data for Washington State (WA), USA, crop (North American Industry Classification System (NAICS) 111 and 1151) and construction (NAICS 23) sectors. Days exceeding maximum daily temperature thresholds, averaged per county, were linked with employment estimates to generate employment days of exceedances. We found spatiotemporal variability in WA temperature threshold exceedances and crop and construction employment. Maximum temperature exceedances peaked in July and August and were most numerous in Central WA counties. Counties with high employment and/or high numbers of threshold exceedance days, led by Yakima and King Counties, experienced the greatest total employment days of exceedances. Crop employment contributed to the largest proportion of total state-wide employment days of exceedances with Central WA counties experiencing the greatest potential workforce burden of exposure. Considerations from this analysis can help inform decision-making regarding thresholds, timing of provisions for heat rules, and tailoring of best practices in different industries and areas.

Heat Exposure and Occupational Injuries: Review of the Literature and Implications.

PURPOSE OF REVIEW: The burden of heat-related adverse occupational health effects, as well as traumatic injuries, is already substantial. Projected increases in mean temperatures and extreme events may increase the risk of adverse heat health effects and enhance disparities among exposed workers. This article reviews the emerging literature on the relationship between heat exposure and occupational traumatic injuries and discusses implications of this work. RECENT FINDINGS: A recent meta-analysis of three case-crossover and five time series studies in industrialized settings reported an association of increasing occupational injuries with increasing heat exposure, with increased effect estimates for male gender and age less than 25 years, although heterogeneity in exposure metrics and sources of bias were demonstrated to varying degrees across studies. A subsequent case-crossover study in outdoor construction workers reported a 0.5% increase in the odds of traumatic injuries per 1 °C increase in maximum daily humidex (odds ratio 1.005 [95% CI 1.003-1.007]). While some studies have demonstrated reversed U-shaped associations between heat exposure and occupational injuries, different risk profiles have been reported in different industries and settings. Studies conducted primarily in industrialized settings suggest an increased risk of traumatic injury with increasing heat exposure, though the exact mechanisms of heat exposure's effects on traumatic injuries are still under investigation. The effectiveness of heat-related injury prevention approaches has not yet been established. To enhance the effectiveness of prevention efforts, prioritization of approaches should take into account not only the hierarchy of controls, social-ecological models, community and stakeholder participation, and tailoring of approaches to specific local work settings, but also methods that reduce local and global disparities and better address the source of heat exposure, including conservation-informed land-use planning, built environment, and prevention through design approaches. Participation of occupational health experts in transdisciplinary development and integration of these approaches is needed.

Plasma polychlorinated biphenyl concentrations and immune function in postmenopausal women.

BACKGROUND: Polychlorinated biphenyl (PCB) exposure has been associated with non-Hodgkin lymphoma in several studies, and the immune system is a potential mediator. OBJECTIVES: We analyzed associations of plasma PCBs with immune function measures. We hypothesized that higher plasma PCB concentrations are associated with lower immune function cross-sectionally, and that increases in PCB concentrations over a one year period are associated with decreases in immune function. METHODS: Plasma PCB concentrations and immune function [natural killer (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were measured at baseline and one year in 109 postmenopausal overweight women participating in an exercise intervention study in the Seattle, Washington (USA) area. Mixed models, with adjustment for body mass index and other potential confounders, were used to estimate associations of PCBs with immune function cross-sectionally and longitudinally. RESULTS: Associations of PCBs with immune function measures differed across groups of PCBs (e.g., medium- and high-chlorinated and dioxin-like [mono-ortho-substituted]) and by the time frame for the comparison (cross-sectional vs. longitudinal). Higher concentrations of medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross-sectionally but not longitudinally. The mean decrease in 0.5 µg/mL PHA-TLP/50.0 pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and NK cytotoxicity. CONCLUSIONS: These results do not provide strong evidence of impaired cellular immunity from PCB exposure. Larger longitudinal studies with greater variability in PCB exposures are needed to further examine temporal associations of PCBs with immune function.

Pre-surgery disability compensation predicts long-term disability among workers with carpal tunnel syndrome.

BACKGROUND: We sought to identify early risk factors for work disability compensation prior to and after carpal tunnel syndrome (CTS) surgery, and to determine whether pre-surgery disability compensation is associated with long-term disability. METHODS: Washington State workers' compensation administrative data and data from interviews with workers 18 days (median) after submitting new workers' compensation claims for CTS were examined. Baseline risk factors for pre-surgery disability compensation and for long-term disability (>365 days of work disability compensation prior to 2 years after claim filing) were evaluated for workers who underwent CTS surgery and had at least 1 day of disability compensation (N = 670). RESULTS: After adjustment for baseline long-term disability risk factors, workers with pre-surgery disability compensation had over five times the odds of long-term disability. Baseline factors in multiple domains, including job, psychosocial, clinical, and worker pain and function, were associated with both pre-surgery disability compensation and long-term disability. CONCLUSIONS: Risk factors for work disability prior to and after CTS surgery are similar, and early work disability is a risk factor for long-term CTS-related disability. An integrated approach to CTS-related disability prevention could include identifying and addressing combined risk factors soon after claim filing, more efficient use of conservative treatments and appropriate work modifications to minimize early work loss, and, when indicated, timely surgical intervention.

Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C.

Cadmium is a well-known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) µg/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73 m2, respectively. The eGFR measures were moderately correlated (rs=0.5; p<0.001). After adjustment, ln (urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln (urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient=4.1 mL/min/1.73 m2; 95% confidence interval=1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential.

Associations of blood lead with estimated glomerular filtration rate using MDRD, CKD-EPI and serum cystatin C-based equations.

BACKGROUND: Low-level lead exposure is widespread and has been implicated as a chronic kidney disease (CKD) risk factor. However, studies evaluating associations of lead dose with newer, potentially more accurate, estimates of kidney function, in participants with a wide range of glomerular filtration rates (GFRs), are scarce. METHODS: We compared associations of blood lead and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and cystatin C single variable, multivariable and combined creatinine/cystatin C equations in 3941 adults who participated in the 1999-2002 National Health and Nutrition Examination Survey cystatin C subsample. RESULTS: Geometric mean blood lead was 1.7 µg/dL. After multivariable adjustment, differences [95% confidence interval (CI)] in mean eGFR for a doubling of blood lead were -1.9 (-3.2, -0.7), -1.7 (-3.0, -0.5) and -1.4 (-2.3, -0.5) mL/min/1.73 m(2), using the cystatin C single variable, multivariable and combined creatinine/cystatin C equations, respectively, reflecting lower eGFR with increased blood lead. The corresponding differences (95% CI) were -0.9 (-1.9, 0.02) and -0.9 (-1.8, 0.01) using the creatinine-based MDRD and CKD-EPI equations, respectively. In participants aged ≥60 years, differences in mean eGFR ranged from -3.0 to -4.5 mL/min/1.73 m(2), and odds of reduced eGFR (<60 mL/min/1.73 m(2)) were increased for all estimates of GFR. CONCLUSIONS: These results support the inclusion of cystatin C-based eGFR in future lead research and provide additional evidence for environmental lead exposure as a CKD risk factor.

Matrix metalloproteinase 13 (MMP13) and tissue inhibitor of matrix metalloproteinase 1 (TIMP1), regulated by the MAPK pathway, are both necessary for Madin-Darby canine kidney tubulogenesis.

A classic model of tubulogenesis utilizes Madin-Darby canine kidney (MDCK) cells. MDCK cells form monoclonal cysts in three-dimensional collagen and tubulate in response to hepatocyte growth factor, which activates multiple signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway. It was shown previously that MAPK activation is necessary and sufficient to induce the first stage of tubulogenesis, the partial epithelial to mesenchymal transition (p-EMT), whereas matrix metalloproteinases (MMPs) are necessary for the second redifferentiation stage. To identify specific MMP genes, their regulators, tissue inhibitors of matrix metalloproteinases (TIMPs), and the molecular pathways by which they are activated, we used two distinct MAPK inhibitors and a technique we have termed subtraction pathway microarray analysis. Of the 19 MMPs and 3 TIMPs present on the Canine Genome 2.0 Array, MMP13 and TIMP1 were up-regulated 198- and 169-fold, respectively, via the MAPK pathway. This was confirmed by two-dimensional and three-dimensional real time PCR, as well as in MDCK cells inducible for the MAPK gene Raf. Knockdown of MMP13 using short hairpin RNA prevented progression past the initial phase of p-EMT. Knockdown of TIMP1 prevented normal cystogenesis, although the initial phase of p-EMT did occasionally occur. The MMP13 knockdown phenotype is likely because of decreased collagenase activity, whereas the TIMP1 knockdown phenotype appears due to increased apoptosis. These data suggest a model, which may also be important for development of other branched organs, whereby the MAPK pathway controls both MDCK p-EMT and redifferentiation, in part by activating MMP13 and TIMP1.

Intracellular signaling via ERK/MAPK completes the pathway for tubulogenic fibronectin in MDCK cells.

A classic in vitro model of branching morphogenesis utilizes the Madin-Darby canine kidney (MDCK) cell line. MDCK Strain II cells form hollow monoclonal cysts in a three-dimensional collagen matrix over the course of 10 days and tubulate in response to hepatocyte growth factor (HGF). We and our colleagues previously showed that activation of the extracellular-signal regulated kinase (ERK, aka MAPK) pathway is necessary and sufficient to induce tubulogenesis in MDCK cells. We also showed in a microarray study that one of the genes upregulated by HGF was the known tubulogene fibronectin. Given that HGF activates a multitude of signaling pathways, including ERK/MAPK, to test the intracellular regulatory pathway, we used two distinct inhibitors of ERK activation (U0126 and PD098059). Following induction of MDCK Type II cells with HGF, tubulogenic fibronectin mRNA was upregulated fourfold by real-time PCR, and minimal or no change in fibronectin expression was seen when HGF was added with either U0126 or PD098059. We confirmed these results using an MDCK cell line inducible for Raf, which is upstream of ERK. Following activation of Raf, fibronectin mRNA and protein expression were increased to a similar degree as was seen following HGF induction. Furthermore, MDCK Strain I cells, which originate from collecting ducts and have constitutively active ERK, spontaneously initiate tubulogenesis. We show here that MDCK Strain I cells have high levels of fibronectin mRNA and protein compared to MDCK Strain II cells. When U0126 and PD098059 were added to MDCK Strain I cells, fibronectin mRNA, and protein levels were decreased to levels seen in MDCK Strain II cells. These data allow us to complete what we believe is the first description of a tubulogenic pathway from receptor/ligand (HGF/CMET), through an intracellular signaling pathway (ERK/MAPK), to transcription and, finally, secretion of a critical tubuloprotein (fibronectin).