Prevalence of Comorbid Factors in Patients With Recurrent Clostridioides difficile Infection in ECOSPOR III, a Randomized Trial of an Oral Microbiota-Based Therapeutic.

BACKGROUND: Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter "VOS," formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI. METHODS: Adults with rCDI were randomized to receive VOS or placebo (4 capsules daily for 3 days) following standard-of-care antibiotics. In this post hoc analysis, the rate of rCDI through week 8 was assessed in VOS-treated participants compared with placebo for subgroups including (i) Charlson comorbidity index (CCI) score category (0, 1-2, 3-4, ≥5); (ii) baseline creatinine clearance (<30, 30-50, >50 to 80, or >80 mL/minute); (iii) number of CDI episodes, inclusive of the qualifying episode (3 and ≥4); (iv) exposure to non-CDI-targeted antibiotics after dosing; and (v) acid-suppressing medication use at baseline. RESULTS: Of 281 participants screened, 182 were randomized (59.9% female; mean age, 65.5 years). Comorbidities were common with a mean overall baseline age-adjusted CCI score of 4.1 (4.1 in the VOS arm and 4.2 in the placebo arm). Across all subgroups analyzed, VOS-treated participants had a lower relative risk of recurrence compared with placebo. CONCLUSIONS: In this post hoc analysis, VOS reduced the risk of rCDI compared with placebo, regardless of baseline characteristics, concomitant medications, or comorbidities.

Evolution of a US County System for Acute Comprehensive Stroke Care.

BACKGROUND AND PURPOSE: In Orange County, California, patients with suspected acute stroke are taken to stroke neurology receiving centers that are designated by County Emergency Medical Services authorities as either hubs or spokes based on endovascular treatment capability. We examined relationships between stroke details, reperfusion therapies, hospital transfers, and their change over time. METHODS: All patients from January 1, 2013, to December 31, 2015, for whom 911 was called within 7 hours of onset in whom Emergency Medical Services personnel suspected acute stroke were evaluated. RESULTS: Among 6132 patients, 3924 (64%) had confirmed diagnosis of stroke (74% ischemic/26% hemorrhagic), yielding diagnostic precision of 64% in the field. Of the 2892 patients with acute ischemic stroke, acute reperfusion therapy was given to 29.2% (21.7% intravenous tPA [tissue-type plasminogen activator] only and 7.5% endovascular treatment). Rates of endovascular treatment of patients with ischemic stroke increased over time, more than doubling from 5.6% in 2013 to 12.5% (odds ratio per 3-month quarter=1.09; 95% confidence interval, 1.04-1.14; P<0.0001). Only 3.4% of patients with acute ischemic stroke were transferred from a spoke to a hub hospital; transfer rates were inversely related to age (P<0.0001), and reperfusion therapy rates did not vary according to transfer status. CONCLUSIONS: Favorable features of this acute stroke care system include reperfusion therapy in 29.2% of patients with ischemic stroke and substantial increases in endovascular treatment rates over time. Continued efforts to optimize acute stroke systems of care can be directed toward improving access to best acute stroke therapies.

Higher risks when working unusual times? A cross-validation of the effects on safety, health, and work-life balance.

PURPOSE: Replication and cross-validation of results on health and safety risks of work at unusual times. METHODS: Data from two independent surveys (European Working Conditions Surveys 2005 and 2010; EU 2005: n = 23,934 and EU 2010: n = 35,187) were used to examine the relative risks of working at unusual times (evenings, Saturdays, and Sundays) on work-life balance, work-related health complaints, and occupational accidents using logistic regression while controlling for potential confounders such as demographics, work load, and shift work. RESULTS: For the EU 2005 survey, evening work was significantly associated with an increased risk of poor work-life balance (OR 1.69) and work-related health complaints (OR 1.14), Saturday work with poor work-life balance (OR 1.49) and occupational accidents (OR 1.34), and Sunday work with poor work-life balance (OR 1.15) and work-related health complaints (OR 1.17). For EU 2010, evening work was associated with poor work-life balance (OR 1.51) and work-related health complaints (OR 1.12), Saturday work with poor work-life balance (OR 1.60) and occupational accidents (OR 1.19) but a decrease in risk for work-related health complaints (OR 0.86) and Sunday work with work-related health complaints (OR 1.13). Risk estimates in both samples yielded largely similar results with comparable ORs and overlapping confidence intervals. CONCLUSIONS: Work at unusual times constitutes a considerable risk to social participation and health and showed structurally consistent effects over time and across samples.

A structural equation modelling approach examining the pathways between safety climate, behaviour performance and workplace slipping.

OBJECTIVE: Safety climate has previously been associated with increasing safe workplace behaviours and decreasing occupational injuries. This study seeks to understand the structural relationship between employees' perceptions of safety climate, performing a safety behaviour (ie, wearing slip-resistant shoes) and risk of slipping in the setting of limited-service restaurants. METHODS: At baseline, we surveyed 349 employees at 30 restaurants for their perceptions of their safety training and management commitment to safety as well as demographic data. Safety performance was identified as wearing slip-resistant shoes, as measured by direct observation by the study team. We then prospectively collected participants' hours worked and number of slips weekly for the next 12 weeks. Using a confirmatory factor analysis, we modelled safety climate as a higher order factor composed of previously identified training and management commitment factors. RESULTS: The 349 study participants experienced 1075 slips during the 12-week follow-up. Confirmatory factor analysis supported modelling safety climate as a higher order factor composed of safety training and management commitment. In a structural equation model, safety climate indirectly affected prospective risk of slipping through safety performance, but no direct relationship between safety climate and slips was evident. CONCLUSIONS: Results suggest that safety climate can reduce workplace slips through performance of a safety behaviour as well as suggesting a potential causal mechanism through which safety climate can reduce workplace injuries. Safety climate can be modelled as a higher order factor composed of safety training and management commitment.

Duration of slip-resistant shoe usage and the rate of slipping in limited-service restaurants: results from a prospective and crossover study.

Several studies have indicated that slip-resistant shoes may have a positive effect on reducing the risk of slips and falls, a leading cause of injury at work. Few studies, however, have examined how duration of shoe usage affects their slip-resistance properties. This study examined the association between the duration of slip-resistant shoes usage and the self-reported rate of slipping in limited-service restaurant workers. A total of 475 workers from 36 limited-service restaurants in the USA were recruited to participate in a 12-week prospective study of workplace slipping. Of the 475 participants, 83 reported changing to a new pair of shoes at least once during the 12-week follow-up. The results show that slip-resistant shoes worn for less than six months were moderately more effective than those worn for more than six months. Changing to a new pair of shoes among those wearing slip-resistant shoes at baseline was associated with a 55% reduction in the rate of slipping (RR = 0.45, 95% CI = 0.23-0.89). Further research is needed to develop criteria for the replacement of slip-resistant shoes.

Post Hoc Analysis of Lung Function Improvement and Patient-Reported Outcomes With Revefenacin in Adults With Moderate-to-Very Severe COPD and Comorbid Anxiety or Depression.

Background: Revefenacin, a once-daily, nebulized, long-acting muscarinic antagonist approved in the United States for the maintenance of chronic obstructive pulmonary disease (COPD), significantly improves lung function and quality of life versus placebo in patients with moderate-to-very severe COPD. Comorbid anxiety and/or depression may alter patients' symptom perception and response to bronchodilators. The impact of revefenacin in patients with COPD with comorbid anxiety and/or depression has not been previously investigated. Methods: This post hoc subgroup analysis examined data from two 12-week, randomized, phase 3 trials in patients with moderate-to-very severe COPD with the following self-reported subgroups: anxiety only (A), depression only (D), anxiety and depression (+A/+D), and neither anxiety nor depression (-A/-D). We assessed change from baseline in trough forced expiratory volume in 1 second (FEV1) at Day 85 and health status by the St George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT). Results: Of 812 patients, 90 (11%), 110 (14%), 141 (17%), and 471 (58%) had A, D, +A/+D, and -A/-D respectively. In revefenacin versus placebo, trough FEV1 significantly improved from baseline at Day 85 across all subgroups as well as the SGRQ and CAT scores in patients with A, +A/+D, and -A/-D. Revefenacin was well tolerated regardless of A/D status, with a minimal incidence of treatment-emergent antimuscarinic adverse events across subgroups. Conclusion: In this analysis, revefenacin versus placebo significantly improved health outcomes in patients with moderate-to-very severe COPD with A, +A/+D, and -A/-D, but not in patients with D. The safety profile of revefenacin was not affected by comorbid anxiety/depression status.

Clinical Burden of Chronic Obstructive Pulmonary Disease in Patients with Suboptimal Peak Inspiratory Flow.

Introduction: Many patients with chronic obstructive pulmonary disease (COPD) may derive inadequate benefit from dry powder inhalers (DPIs) because of suboptimal peak inspiratory flow (sPIF). Objectives: To assess the clinical burden of COPD by characterizing the clinical characteristics of participants with sPIF against medium-low resistance DPIs versus those with optimal PIF (oPIF) from two phase 3 clinical trials. Methods: Baseline data were collected from two randomized, controlled, phase 3 trials (NCT03095456; NCT02518139) in participants with moderate-to-severe COPD. oPIF (60 L/min) against the medium-low resistance DPIs was used as the threshold for defining the PIF subgroups (<60 L/min (sPIF) vs ≥60 L/min (oPIF)). Results: Most participants included in this analysis were White (92%) and male (63%); the mean (range) age was 65 (43-87) years. Participants with sPIF had significantly greater dyspnea than those with oPIF as measured using the modified Medical Research Council scoring (mean (95% CI): 2.1 (2.0-2.2) vs 1.6 (1.4-1.7); P < 0.001) and baseline dyspnea index (mean (95% CI): 5.1 (4.9-5.4) vs 6.1 (5.8-6.3); P < 0.001). Based on COPD Assessment Test scores, participants with sPIF had a higher COPD symptom burden than those with oPIF (mean (95% CI): 21.5 (19.7-23.3) vs 19.5 (18.6-20.4); P = 0.05). Conclusion: In these trials, participants with COPD who had sPIF against the medium-low resistance DPIs had more dyspnea and worse health status than those with oPIF. These results demonstrate that sPIF is associated with a higher clinical burden as measured by patient-reported outcomes.

Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI.

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI. OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities. METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24. RESULTS: TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6-13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression. CONCLUSIONS: VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03183128 and NCT03183141.

Perception of slipperiness and prospective risk of slipping at work.

OBJECTIVES: Falls are a leading cause of injury at work, and slipping is the predominant cause of falling. Prior research has suggested a modest correlation between objective measures (such as coefficient of friction, COF) and subjective measures of slipperiness (such as worker perceptions) in the workplace. However, the degree of association between subjective measures and the actual risk of slipping at the workplace is unknown. This study examined the association between perception of slipperiness and the risk of slipping. METHODS: 475 workers from 36 limited-service restaurants participated in a 12-week prospective cohort study. At baseline, demographic information was collected, participants rated floor slipperiness in eight areas of the restaurant, and work environment factors, such as COF, were measured. Restaurant-level and area-level mean perceptions of slipperiness were calculated. Participants then reported their slip experience at work on a weekly basis for the next 12 weeks. The associations between perception of slipperiness and the rate of slipping were assessed. RESULTS: Adjusting for age, gender, body mass index, education, primary language, mean COF, use of slip-resistant shoes, and restaurant chain, each 1-point increase in mean restaurant-level perception of slipperiness (4-point scale) was associated with a 2.71 times increase in the rate of slipping (95% CI 1.25 to 5.87). Results were similar for area-level perception within the restaurant (rate ratios (RR) 2.92, 95% CI 2.41 to 3.54). CONCLUSIONS: Perceptions of slipperiness and the subsequent rate of slipping were strongly associated. These findings suggest that safety professionals, risk managers and employers could use aggregated worker perceptions of slipperiness to identify slipping hazards and, potentially, to assess intervention effectiveness.

Improvements in health status with revefenacin, a once-daily, nebulized, long-acting muscarinic antagonist for chronic obstructive pulmonary disease.

BACKGROUND: Replicate, 12-week, phase 3 trials (0126 and 0127) of once-daily nebulized revefenacin 175 µg vs placebo demonstrated significant bronchodilation and improvements in health status in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). This post hoc analysis evaluated improvement in patient-reported outcomes (PROs), including the St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and Clinical COPD Questionnaire (CCQ) in both women and men. METHODS: Participants were pooled from the two 12-week studies (411 [51%] women and 401 [49%] men). Changes in PROs were assessed overall and separately in men and women. RESULTS: Revefenacin improved SGRQ and CAT total scores from baseline in both studies; improvement in CCQ total score reached significance only in 0126. In pooled data, a greater proportion of patients achieved clinically meaningful response in SGRQ score (≥4-unit decrease from baseline) with revefenacin vs placebo (odds ratio, 1.5; 95% confidence interval, 1.1-2.1; P = 0.012). Clinically meaningful responses were also seen in CAT (≥2-unit decrease from baseline) and CCQ (≥0.4-unit decrease from baseline) scores with revefenacin vs placebo. When stratified by sex, improvements from baseline in SGRQ, CAT, and CCQ scores following revefenacin vs placebo reached statistical significance only in women. CONCLUSIONS: Maintenance treatment with revefenacin improved health status in patients with moderate to very severe COPD; however, the effect was more pronounced for women than men. CLINICALTRIALS: GOV: NCT02459080; NCT02512510.

Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial.

BACKGROUND: The inhaled lung-selective pan-Janus kinase inhibitor nezulcitinib had favourable safety and potential efficacy signals in part 1 of a phase 2 trial in patients with severe COVID-19, supporting progression to part 2. METHODS: Part 2 was a randomised, double-blind phase 2 study (NCT04402866). Hospitalised patients aged 18-80 years with confirmed symptomatic COVID-19 requiring supplemental oxygen (excluding baseline invasive mechanical ventilation) were randomised 1:1 to nebulised nezulcitinib 3 mg or placebo for up to 7 days with background standard-of-care therapy (including corticosteroids). Efficacy endpoints included respiratory failure-free (RFF) days through day 28 as the primary endpoint. Secondary endpoints included safety and change from baseline oxygen saturation (SaO2)/fraction of inspired oxygen (FiO2) ratio on day 7, and 28-day mortality rate was a prespecified exploratory endpoint. RESULTS: Between June 2020 and April 2021, 205 patients were treated (nezulcitinib, 103; placebo, 102). There was no statistically significant difference between nezulcitinib versus placebo in the primary endpoint (RFF days; median, 21.0 vs 21.0; p=0.6137) or secondary efficacy endpoints. Nezulcitinib was generally well tolerated with a favourable safety profile. CONCLUSIONS: Although the prespecified primary, secondary and exploratory efficacy endpoints, including RFF through day 28, change from baseline SaO2/FiO2 ratio on day 7, and 28-day mortality rate, were not met, nezulcitinib was generally well tolerated and had a favourable safety profile. Further studies are required to determine if treatment with nezulcitinib confers clinical benefit in specific inflammatory biomarker-defined populations of patients with COVID-19.

Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial.

Importance: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. Objectives: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. Design, Setting, and Participants: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. Interventions: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. Main Outcomes and Measures: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. Results: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). Conclusions and Relevance: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. Trial Registration: ClinicalTrials.gov identifier: NCT03183141.

A structural equation modeling approach to fatigue-related risk factors for occupational injury.

Occupational injury is associated with numerous individual and work-related risk factors, including long working hours and short sleep duration; however, the complex mechanisms causing such injuries are not yet fully understood. The authors used structural equation modeling (SEM) as a novel approach to examine fatigue-related direct and indirect potential risk factors for occupational injury. The study sample contained 89,366 employed workers from the National Health Interview Survey (pooled across 6 years, 2004-2009), an annual survey of a representative cross-sectional sample of the US population. Direct and indirect effects of weekly hours worked and usual sleep duration on occupational injuries were modeled using SEM procedures for dichotomous outcomes and a complex sampling design. Confounding and mediating effects of gender, age, race/ethnicity, occupation, industry, type of pay, body mass index (BMI), and psychological distress were simultaneously examined. Long working hours and short sleep duration independently increased the risk of injury. Additional direct risk factors were gender, occupation, type of pay, and BMI. At the same time, sleep duration mediated the adverse relations of long working hours, high psychological distress, and high BMI with injury. These findings indicate that SEM is a useful approach with which to examine dichotomous outcomes and indirect effects in complex samples, and it offers a comprehensive new model of injury prediction.

Factors associated with use of slip-resistant shoes in US limited-service restaurant workers.

OBJECTIVES: Slips and falls are a leading cause of injury at work. Several studies have indicated that slip-resistant shoes can reduce the risk of occupational slips and falls. Few studies, however, have examined the determinants of slip-resistant shoe use. This study examined the individual and workplace factors associated with slip-resistant shoe use. METHODS: 475 workers from 36 limited-service restaurants in the USA participated in a study of workplace slipping. Demographic and job characteristic information about each participant was collected. Restaurant managers provided information on whether slip-resistant shoes were provided and paid for by the employer and whether any guidance was given regarding slip-resistant shoe use when they were not provided. Kitchen floor coefficient of friction was measured. Slip-resistant status of the shoes was determined by noting the presence of a 'slip-resistant' marking on the sole. Poisson regression with robust SE was used to calculate prevalence ratios. RESULTS: 320 participants wore slip-resistant shoes (67%). In the multivariate analysis, the prevalence of slip-resistant shoe use was lowest in 15-19-year age group. Women were more likely to wear slip-resistant shoes (prevalence ratio 1.18, 95% CI 1.07 to 1.31). The prevalence of slip-resistant shoe use was lower when no guidance regarding slip-resistant shoes was given as compared to when they were provided by the employer (prevalence ratio 0.66, 95% CI 0.55 to 0.79). Education level, job tenure and the mean coefficient of friction had no significant effects on the use of slip-resistant shoes. CONCLUSION: Provision of slip-resistant shoes was the strongest predictor of their use. Given their effectiveness and low cost, employers should consider providing slip-resistant shoes at work.

Chronotypes in the US: Influence of longitude position in a time zone.

The availability of electrical light has altered modern light exposure, affecting the synchronization process ('entrainment') of the circadian clock to the natural light-dark cycle. The discrepancy between the natural light-dark cycle and self-selected light exposure has raised the question whether humans entrain to sun time (as most organisms do) vs. social time. None of the studies addressing this question have been conducted in the US in a large-scale, nationally representative sample. In this brief report, we aimed at estimating the relationship between individual chronotype (the result of the entrainment process) and longitude position in a time zone, using 12 years (2003-2014) of pooled diary data (n = 50,753) from the American Time Use Survey (ATUS). Chronotype was estimated based on mid-sleep time on weekends (MSFWe), a proxy that was previously shown to replicate known age and sex differences in chronotype in the ATUS. Longitude position was derived from state-level information (e.g., average state border outline). Regression results showed a progressive delay in MSFWe from east to west within three of the four US continental time zones (delay per degree of longitude): Eastern, 1.8 min; Central, 1.2 min; Mountain, 2.4 min (all p < .01). The findings suggest that humans entrain to sun time, leading to an increasing discrepancy between social time and biological time ("circadian misalignment") towards the west of a time zone. Such a misalignment induced by where people live within a time zone may affect a large share of the population, with implications for health and safety.

A prospective study of floor surface, shoes, floor cleaning and slipping in US limited-service restaurant workers.

OBJECTIVES: Slips and falls are a leading cause of injury at work. Few studies, however, have systematically examined risk factors of slipping outside the laboratory environment. This study examined the association between floor surface characteristics, slip-resistant shoes, floor cleaning frequency and the risk of slipping in limited-service restaurant workers. METHODS: 475 workers from 36 limited-service restaurants from three major chains in six states in the USA were recruited to participate in a prospective cohort study of workplace slipping. Kitchen floor surface roughness and coefficient of friction (COF) were measured in eight working areas and then averaged within each restaurant. The use of slip-resistant shoes was determined by examining the participant's shoes and noting the presence of a 'slip-resistant' marking on the sole. Restaurant managers reported the frequency of daily kitchen floor cleaning. Participants reported their slip experience and work hours weekly for up to 12 weeks. The survey materials were made available in three languages: English, Spanish and Portuguese. The associations between rate of slipping and risk factors were assessed using a multivariable negative binomial generalised estimating equation model. RESULTS: The mean of individual slipping rate varied among the restaurants from 0.02 to 2.49 slips per 40 work hours. After adjusting for age, gender, BMI, education, primary language, job tenure and restaurant chain, the use of slip-resistant shoes was associated with a 54% reduction in the reported rate of slipping (95% CI 37% to 64%), and the rate of slipping decreased by 21% (95% CI 5% to 34%) for each 0.1 increase in the mean kitchen COF. Increasing floor cleaning frequency was significantly associated with a decreasing rate of slipping when considered in isolation but not after statistical adjustment for other factors. CONCLUSION: These results provide support for the use of slip-resistant shoes and measures to increase COF as preventive interventions to reduce slips, falls and injuries.

Rushing, distraction, walking on contaminated floors and risk of slipping in limited-service restaurants: a case--crossover study.

OBJECTIVES: This nested case-crossover study examined the association between rushing, distraction and walking on a contaminated floor and the rate of slipping, and whether the effects varied according to weekly hours worked, job tenure and use of slip-resistant shoes. METHODS: At baseline, workers from 30 limited-service restaurants in the USA reported average work hours, average weekly duration of exposure to each transient risk factor and job tenure at the current location. Use of slip-resistant shoes was determined. During the following 12 weeks, participants reported weekly their slip experience and exposures to the three transient exposures at the time of slipping. The case-crossover design was used to estimate the rate ratios using the Mantel-Haenszel estimator for person-time data. RESULTS: Among 396 participants providing baseline information, 210 reported one or more slips with a total of 989 slips. Rate of slipping was 2.9 times higher when rushing as compared to working at a normal pace (95% CI 2.5 to 3.3). Rate of slipping was also significantly increased by distraction (rate ratio (RR) 1.7, 95% CI 1.5 to 2.0) and walking on a contaminated floor (RR 14.6, 95% CI 12.6 to 17.0). Use of slip-resistant shoes decreased the effects of rushing and walking on a contaminated floor. Rate ratios for all three transient factors decreased monotonically as job tenure increased. CONCLUSION: The results suggest the importance of these transient risk factors, particularly floor contamination, on rate of slipping in limited-service restaurant workers. Stable characteristics, such as slip-resistant shoes, reduced the effects of transient exposures.

Real-World Clinical Use and Outcomes of Telavancin for the Treatment of Bone and Joint Infections: Results from the Telavancin Observational Use Registry (TOUR™).

BACKGROUND: Additional antibiotic options are needed to treat bone and joint infections caused by penicillin-resistant Gram-positive pathogens. OBJECTIVE: This subanalysis of the Telavancin Observational Use Registry (TOUR™) aimed to record real-world telavancin usage patterns in patients with bone and joint infections treated with telavancin. METHODS: TOUR was a multicenter observational-use registry study conducted at 45 US sites between January 2015 and March 2017. Patient characteristics, infection type, infecting pathogen(s), previous treatment, telavancin dosing and duration, clinical response, and adverse event data were collected by retrospective medical chart reviews. As such, inclusion/exclusion criteria were limited, and any patient receiving at least one dose of telavancin at the discretion of the treating physician was eligible. Patients were assessed as either positive clinical response, failed treatment, or indeterminate outcome. RESULTS: Of the 1063 patients enrolled in TOUR, 27.4% (291/1063) were patients with bone and joint infections including osteomyelitis (with or without prosthetic material), acute septic arthritis, and prosthetic joint infections. Most of these patients had osteomyelitis without prosthetic material (191/291; 66.0%). Among patients assessed at the end of treatment, 211/268 (78.7%) achieved a positive clinical response, 26/268 (9.7%) failed treatment, and 31/268 (11.6%) had an indeterminate outcome. The most frequent pathogen was methicillin-resistant Staphylococcus aureus (110/291; 37.8%). The median (interquartile range [IQR as Q1, Q3]) telavancin dose was 750.0 mg (IQR, 750, 750 mg) or 8.2 mg/kg (IQR, 6.8, 9.7 mg/kg) administered for a median of 26 days (IQR, 12, 42 days). These assessments were recorded in the registry ≥ 30 days after the last dose of telavancin was administered. CONCLUSIONS: Real-world data from the TOUR study show that clinicians are using once-daily telavancin with positive clinical outcomes for the treatment of bone and joint infections caused by Gram-positive pathogens. CLINICAL TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02288234) on 11 November, 2014.

Reliability of job-title based physical work exposures for the upper extremity: comparison to self-reported and observed exposure estimates.

OBJECTIVES: To evaluate the agreement between job-title based estimates for upper extremity physical work exposures and exposure estimates from work observation and worker self-report. METHODS: Self-reported exposure questionnaires were completed by 972 workers, and exposure estimates based on worksite observation were completed for a subset of 396 workers. Job-title based estimates were obtained from O*NET, an American database of job demands. Agreement between self-reported, observed and job-title based physical work exposures was assessed using Spearman correlations and intraclass correlation coefficients. RESULTS: Job-title based exposure estimates from O*NET, self-reported and observer-rated exposures showed moderate to good levels of agreement for some upper extremity exposures, including lifting, forceful grip, use of vibrating tools and wrist bending. CONCLUSIONS: Job-title based physical work exposure variables may provide useful surrogate measures of upper extremity exposure data in the absence of other individual level data such as observed or self-reported exposure. Further validation of these data is necessary to determine the utility of the O*NET databases in future epidemiological studies.