Random drug and alcohol testing for preventing injury in workers.

BACKGROUND: Drug- and alcohol-related impairment in the workplace has been linked to an increased risk of injury for workers. Randomly testing populations of workers for these substances has become a practice in many jurisdictions, with the intention of reducing the risk of workplace incidents and accidents. Despite the proliferation of random drug and alcohol testing (RDAT), there is currently a lack of consensus about whether it is effective at preventing workplace injury, or improving other non-injury accident outcomes in the work place. OBJECTIVES: To assess the effectiveness of workplace RDAT to prevent injuries and improve non-injury accident outcomes (unplanned events that result in damage or loss of property) in workers compared with no workplace RDAT. SEARCH METHODS: We conducted a systematic literature search to identify eligible published and unpublished studies. The date of the last search was 1 November 2020. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, two other databases, Google Scholar, and three trials registers. We also screened the reference lists of relevant publications known to us. SELECTION CRITERIA: Study designs that were eligible for inclusion in our review included randomised controlled trials (RCTs), cluster-randomised trials (CRTs), interrupted time-series (ITS) studies, and controlled before-after (CBA) studies. Studies needed to evaluate the effectiveness of RDAT in preventing workplace injury or improving other non-injury workplace outcomes. We also considered unpublished data from clinical trial registries. We included employees working in all safety-sensitive occupations, except for commercial drivers, who are the subject of another Cochrane Review. DATA COLLECTION AND ANALYSIS: Independently, two review authors used a data collection form to extract relevant characteristics from the included study. They then analysed a line graph included in the study of the prevalence rate of alcohol violations per year. Independently, the review authors completed a GRADE assessment, as a means of rating the quality of the evidence. MAIN RESULTS: Although our searching originally identified 4198 unique hits, only one study was eligible for inclusion in this review. This was an ITS study that measured the effect of random alcohol testing (RAT) on the test positivity rate of employees of major airlines in the USA from 1995 to 2002. The study included data from 511,745 random alcohol tests, and reported no information about testing for other substances. The rate of positive results was the only outcome of interest reported by the study. The average rate of positive results found by RAT increased from 0.07% to 0.11% when the minimum percentage of workers who underwent RAT annually was reduced from 25% to 10%. Our analyses found this change to be a statistically significant increase (estimated change in level, where the level reflects the average percentage points of positive tests = 0.040, 95% confidence interval 0.005 to 0.075; P = 0.031). Our GRADE assessment, for the observed effect of lower minimum testing percentages associating with a higher rate of positive test results, found the quality of the evidence to be 'very low' across the five GRADE domains. The one included study did not address the following outcomes of interest: fatal injuries; non-fatal injuries; non-injury accidents; absenteeism; and adverse effects associated with RDAT. AUTHORS' CONCLUSIONS: In the aviation industry in the USA, the only setting for which the eligible study reported data, there was a statistically significant increase in the rate of positive RAT results following a reduction in the percentage of workers tested, which we deem to be clinically relevant. This result suggests an inverse relationship between the proportion of positive test results and the rate of testing, which is consistent with a deterrent effect for testing. No data were reported on adverse effects related to RDAT. We could not draw definitive conclusions regarding the effectiveness of RDAT for employees in safety-sensitive occupations (not including commercial driving), or with safety-sensitive job functions. We identified only one eligible study that reflected one industry in one country, was of non-randomised design, and tested only for alcohol, not for drugs or other substances. Our GRADE assessment resulted in a 'very low' rating for the quality of the evidence on the only outcome reported. The paucity of eligible research was a major limitation in our review, and additional studies evaluating the effect of RDAT on safety outcomes are needed.

Work-related outcomes in randomized, double blind, placebo-controlled trials in osteoarthritis - are they adequately reported in journal publications? A systematic review.

BACKGROUND: Osteoarthritis (OA) has a high prevalence in Western societies and can affect an individual's life in a number of domains, including work. In our experience, treatment trials on OA, however, rarely report work-related outcomes. Here we conducted a systematic review to assess the reporting of work-related outcomes in randomized, double blind, placebo-controlled trials in OA. Our systematic review also compared two search strategies for identifying eligible publications, one where work-related terms were included in the database search string (A) and one where this was not the case and work-related outcomes were identified by searches of full text Portable Document Formats (PDFs) (B). Search strategy A would conventionally be used and would only identify publications where work-related terms were mentioned in the title or abstract. Search strategy B presents the innovation of full text PDF searching and would identify publications were work-related terms were reported in the full text, regardless of whether they are mentioned in the title and abstract or not. We hypothesize that search strategy B identifies more relevant publications than search strategy A. METHODS: Electronic database searching was performed in Medline (Pubmed) from database inception to February 23, 2017 to identify peer-reviewed articles of randomized, double blind, placebo-controlled treatment trials in OA of the hand, hip, or knee, available as full-text PDFs. For search strategy A, search terms to identify work-related outcomes were included in the database search string, while search strategy B did not have these terms included in the database search string, but instead involved full text PDF searching. We included English language articles only and only those articles where searchable PDFs were available, to enable a comparison between search strategies A and B. Additionally, included studies also needed to report on pain intensity in relation to the work-related outcomes. RESULTS: Search strategy A yielded 50 hits combined for hand, hip or knee OA that mentioned some work-related concept in the title or abstract; 12 articles had to be excluded because they were not available as searchable PDFs. Screening of the remaining 38 articles resulted in only two articles that satisfied our inclusion criteria. Search strategy B yielded 986 hits, out of which 201 articles were excluded because searchable full text PDFs were not available. PDF full text searching and further screening resulted in 10 articles that were considered eligible for our review. CONCLUSIONS: Work-related outcomes are rarely reported in journal publication on randomized, double blind, placebo-controlled trials of hand, hip or knee OA. Searching full text PDFs yields more eligible articles than searching titles and abstracts only.

Occupational interventions for the prevention of back pain: Overview of systematic reviews.

INTRODUCTION: We conducted an overview of systematic reviews of interventions for the prevention of low back pain (LBP) that can be conducted in a workplace setting. METHODS: An electronic literature search was performed in Medline, EMBASE, and the Cochrane Library. Published peer-reviewed systematic reviews and meta-analyses, which described interventions for the primary or secondary prevention of LBP applicable to a workplace setting, were eligible for inclusion. The methodological quality of the included systematic reviews was assessed with the AMSTAR tool. The primary outcome of interest was the incidence of LBP; secondary outcomes were LBP-associated absenteeism, activity interference, and costs related to LBP. RESULTS: Twenty-eight eligible articles published between 1994 and 2016 were included in a qualitative synthesis following our screening of abstracts and full-text articles. The AMSTAR rating revealed 14 reviews of high, 10 of moderate, and 4 of low methodological quality. The identified interventions included workplace modifications (6 reviews, 10 studies, 6,751 subjects); shoe insoles (4 reviews, 6 studies, 2,356 subjects); and lumbar supports and other assistive devices (15 reviews, 18 studies, 60,678 subjects). Educational interventions investigated were back schools (10 reviews, 30 studies, 9,973 subjects); manual material handling techniques/advice (6 reviews, 24 studies, 10,505 subjects); and other forms of instruction including pamphlets, booklets, and other media (four reviews, 14 studies, 11,991 subjects). Exercise interventions, investigated in 12 reviews (35 studies, 19,330 subjects), showed moderate quality evidence of effectiveness for exercise interventions alone or in conjunction with educational interventions; no other type of intervention was consistently effective in the prevention of LBP or LBP-associated outcomes of interest. CONCLUSIONS: Our overview provides evidence of effectiveness for exercise with or without educational interventions in the prevention of LBP. PRACTICAL APPLICATIONS: Exercise interventions with or without educational interventions that can be applied in the workplace have the potential to prevent LBP.

Vitamin D levels and deficiency with different occupations: a systematic review.

BACKGROUND: Vitamin D deficiency is prevalent worldwide, but some groups are at greater risk. We aim to evaluate vitamin D levels in different occupations and identify groups vulnerable to vitamin D deficiency. METHODS: An electronic search conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, and CINAHL Plus with Full Text generated 2505 hits; 71 peer-reviewed articles fulfilled the inclusion criteria. Occupations investigated included outdoor and indoor workers, shiftworkers, lead/smelter workers, coalminers, and healthcare professionals. We calculated the pooled average metabolite level as mean ± SD; deficiency/insufficiency status was described as % of the total number of subjects in a given category. RESULTS: Compared to outdoor workers, indoor workers had lower 25-hydroxyvitamin D (25-(OH)D) levels (40.6 ± 13.3 vs. 66.7 ± 16.7 nmol/L; p < 0.0001). Mean 25-(OH)D levels (in nmol/L) in shiftworkers, lead/smelter workers and coalminers were 33.8 ± 10.0, 77.8 ± 5.4 and 56.6 ± 28.4, respectively. Vitamin D deficiency (25-(OH)D < 50 nmol/L), was high in shiftworkers (80%) and indoor workers (78%) compared to outdoor workers (48%). Among healthcare professionals, medical residents and healthcare students had the lowest levels of mean 25-(OH)D, 44.0 ± 8.3 nmol/L and 45.2 ± 5.5 nmol/L, respectively. The mean 25-(OH)D level of practising physicians, 55.0 ± 5.8 nmol/L, was significantly different from both medical residents (p < 0.0001) and healthcare students (p < 0.0001). Nurses and other healthcare employees had 25-(OH)D levels of 63.4 ± 4.2 nmol/L and 63.0 ± 11.0 nmol/L, respectively, which differed significantly compared to practising physicians (p = 0.01), medical residents (p < 0.0001) and healthcare students (p < 0.0001). Rates of vitamin D deficiency among healthcare professionals were: healthcare students 72%, medical residents 65%, practising physicians 46%, other healthcare employees 44%, and nurses 43%. Combined rates of vitamin D deficiency or insufficiency (25-(OH)D < 75 nmol/L) were very high in all investigated groups. Potential confounders such as gender and body composition were not consistently reported in the primary studies and were therefore not analyzed. Furthermore, the descriptions of occupational characteristics may be incomplete. These are limitations of our systematic review. CONCLUSIONS: Our review demonstrates that shiftworkers, healthcare workers and indoor workers are at high risk to develop vitamin D deficiency, which may reflect key lifestyle differences (e.g. sunlight exposure). This may help target health promotion and preventive efforts.

Resistance to cardiomyocyte hypertrophy in ae3-/- mice, deficient in the AE3 Cl-/HCO3- exchanger.

BACKGROUND: Cardiac hypertrophy is central to the etiology of heart failure. Understanding the molecular pathways promoting cardiac hypertrophy may identify new targets for therapeutic intervention. Sodium-proton exchanger (NHE1) activity and expression levels in the heart are elevated in many models of hypertrophy through protein kinase C (PKC)/MAPK/ERK/p90RSK pathway stimulation. Sustained NHE1 activity, however, requires an acid-loading pathway. Evidence suggests that the Cl-/HCO3- exchanger, AE3, provides this acid load. Here we explored the role of AE3 in the hypertrophic growth cascade of cardiomyocytes. METHODS: AE3-deficient (ae3-/-) mice were compared to wildtype (WT) littermates to examine the role of AE3 protein in the development of cardiomyocyte hypertrophy. Mouse hearts were assessed by echocardiography. As well, responses of cultured cardiomyocytes to hypertrophic stimuli were measured. pH regulation capacity of ae3-/- and WT cardiomyocytes was assessed in cultured cells loaded with the pH-sensitive dye, BCECF-AM. RESULTS: ae3-/- mice were indistinguishable from wild type (WT) mice in terms of cardiovascular performance. Stimulation of ae3-/- cardiomyocytes with hypertrophic agonists did not increase cardiac growth or reactivate the fetal gene program. ae3-/- mice are thus protected from pro-hypertrophic stimulation. Steady state intracellular pH (pHi) in ae3-/- cardiomyocytes was not significantly different from WT, but the rate of recovery of pHi from imposed alkalosis was significantly slower in ae3-/- cardiomyocytes. CONCLUSIONS: These data reveal the importance of AE3-mediated Cl-/HCO3- exchange in cardiovascular pH regulation and the development of cardiomyocyte hypertrophy. Pharmacological antagonism of AE3 is an attractive approach in the treatment of cardiac hypertrophy.

An intramolecular transport metabolon: fusion of carbonic anhydrase II to the COOH terminus of the Cl(-)/HCO(3)(-)exchanger, AE1.

Anion exchanger 1 (AE1) is the plasma membrane Cl(-)/HCO(3)(-) exchanger of erythrocytes. Carbonic anhydrases (CA) provide substrate for AE1 by catalyzing the reaction, H(2)O + CO(2) ↔ HCO(3)(-) + H(+). The physical complex of CAII with AE1 has been proposed to maximize anion exchange activity. To examine the effect of CAII catalysis on AE1 transport rate, we fused either CAII-wild type or catalytically inactive CAII-V143Y to the cytoplasmic COOH terminus of AE1 to form AE1.CAII and AE1.CAII-V143Y, respectively. When expressed in transfected human embryonic kidney 293 cells, AE1.CAII had a similar Cl(-)/HCO(3)(-) exchange activity to AE1 alone, as assessed by the flux of H(+) equivalents (87 ± 4% vs. AE1) or rate of change of intracellular Cl(-) concentration (93 ± 4% vs. AE1), suggesting that CAII does not activate AE1. In contrast, AE1.CAII-V143Y displayed transport rates for H(+) equivalents and Cl(-) of 55 ± 2% and of 40 ± 2%, versus AE1. Fusion of CAII to AE1 therefore reduces anion transport activity, but this reduction is compensated for during Cl(-)/HCO(3)(-) exchange by the presence of catalytically active CAII. Overexpression of free CAII-V143Y acts in a dominant negative manner to reduce AE1-mediated HCO(3)(-) transport by displacement of endogenous CAII-wild type from its binding site on AE1. To examine whether AE1.CAII bound endogenous CAII, we coexpressed CAII-V143Y along with AE1 or AE1.CAII. The bicarbonate transport activity of AE1 was inhibited by CAII-V143Y, whereas the activity of AE1.CAII was unaffected by CAII-V143Y, suggesting impaired transport activity upon displacement of functional CAII from AE1 but not AE1.CAII. Taken together, these data suggest that association of functional CAII with AE1 increases Cl(-)/HCO(3)(-) exchange activity, consistent with the HCO(3)(-) transport metabolon model.

High rates of residual fatty acid oxidation during mild ischemia decrease cardiac work and efficiency.

It is unknown what effects high levels of fatty acids have on energy metabolism and cardiac efficiency during milder forms of ischemia. To address this issue, isolated working rat hearts perfused with Krebs-Henseleit solution (5 mM glucose, 100 muU/mL insulin, and 0.4 (Normal Fat) or 1.2 mM palmitate (High Fat)) were subjected to 30 min of aerobic perfusion followed by 30 min of mild ischemia (39% reduction in coronary flow). Both groups had similar aerobic function and rates of glycolysis, however the High Fat group had elevated rates of palmitate oxidation (150%), and decreased rates of glucose oxidation (51%). Mild ischemia decreased cardiac work (56% versus 40%) and efficiency (29% versus 11%) further in High Fat hearts. Palmitate oxidation contributed a greater percent of acetyl-CoA production during mild ischemia in the High Fat group (81% versus 54%). During mild ischemia glycolysis remained at aerobic levels in the Normal Fat group, but was accelerated in the High Fat group. Triglyceride, glycogen and adenine nucleotide content did not differ at the end of mild ischemia, however glycogen turnover was double in the High Fat group (248%). Addition of the pyruvate dehydrogenase inhibitor dichloroacetate to the High Fat group resulted in a doubling of the rate of glucose oxidation and improved cardiac efficiency during mild ischemia. We demonstrate that fatty acid oxidation dominates as the main source of residual oxidative metabolism during mild ischemia, which is accompanied by suppressed cardiac function and efficiency in the presence of high fat.

Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy.

Hypertrophic cardiomyocyte growth contributes substantially to the progression of heart failure. Activation of the plasma membrane Na+-H+ exchanger (NHE1) and Cl- -HCO3- exchanger (AE3) has emerged as a central point in the hypertrophic cascade. Both NHE1 and AE3 bind carbonic anhydrase (CA), which activates their transport flux, by providing H+ and HCO3-, their respective transport substrates. We examined the contribution of CA activity to the hypertrophic response of cultured neonatal and adult rodent cardiomyocytes. Phenylephrine (PE) increased cell size by 37 +/- 2% and increased expression of the hypertrophic marker, atrial natriuretic factor mRNA, twofold in cultured neonatal rat cardiomyocytes. Cell size was also increased in adult cardiomyocytes subjected to angiotensin II or PE treatment. These effects were associated with increased expression of cytosolic CAII protein and the membrane-anchored isoform, CAIV. The membrane-permeant CA inhibitor, 6-ethoxyzolamide (ETZ), both prevented and reversed PE-induced hypertrophy in a concentration-dependent manner in neonate cardiomyocytes (IC50=18 microm). ETZ and the related CA inhibitor methazolamide prevented hypertrophy in adult cardiomyocytes. In addition, ETZ inhibited transport activity of NHE1 and the AE isoform, AE3, with respective EC50 values of 1.2 +/- 0.3 microm and 2.7 +/- 0.3 microm. PE significantly increased neonatal cardiomyocyte Ca2+ transient frequency from 0.33 +/- 0.4 Hz to 0.77 +/- 0.04 Hz following 24 h treatment; these Ca2+ -handling abnormalities were completely prevented by ETZ (0.28 +/- 0.07 Hz). Our study demonstrates a novel role for CA in mediating the hypertrophic response of cardiac myocytes to PE and suggests that CA inhibition represents an effective therapeutic approach towards mitigation of the hypertrophic phenotype.