Personal protective equipment for preventing asbestos exposure in workers.

BACKGROUND: Asbestos exposure can lead to asbestos-related diseases. The European Union (EU) has adopted regulations for workplaces where asbestos is present. The EU occupational exposure limit (OEL) for asbestos is 0.1 fibres per cubic centimetre of air (f/cm3) as an eight-hour average. Different types of personal protective equipment (PPE) are available to provide protection and minimise exposure; however, their effectiveness is unclear. OBJECTIVES: To assess the effects of personal protective equipment (PPE), including donning and doffing procedures and individual hygienic behaviour, compared to no availability and use of such equipment or alternative equipment, on asbestos exposure in workers in asbestos demolition and repair work. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, and Scopus (September 2022), and we checked the reference lists of included studies. SELECTION CRITERIA: We included studies that measured asbestos concentration outside and inside PPE (considering outside concentration a surrogate for no PPE), exposure to asbestos after doffing PPE, donning and doffing errors, nonadherence to regulations, and adverse effects of PPE. DATA COLLECTION AND ANALYSIS: Two review authors selected studies, extracted data, and assessed risk of bias using ROBINS-I. We categorised PPE as full-face filtering masks, supplied air respirators (SARs), and powered air-purifying respirators (PAPRs). Values for asbestos outside and inside PPE were transformed to logarithmic values for random-effects meta-analysis. Pooled logarithmic mean differences (MDs) were exponentiated to obtain the ratio of means (RoM) and 95% confidence interval (95% CI). The RoM shows the degree of protection provided by the respirators (workplace protection factor). Since the RoM is likely to be much higher at higher outside concentrations, we presented separate results according to the outside asbestos concentration, as follows. • Below 0.01 f/cm3 (band 1) • 0.01 f/cm3 to below 0.1 f/cm3 (band 2) • 0.1 f/cm3 to below 1 f/cm3 (band 3) • 1 f/cm3 to below 10 f/cm3 (band 4) • 10 f/cm3 to below 100 f/cm3 (band 5) • 100 f/cm3 to below 1000 f/cm3 (band 6) Additionally, we determined whether the inside concentrations per respirator and concentration band complied with the current EU OEL (0.1 f/cm3) and proposed EU OEL (0.01 f/cm3). MAIN RESULTS: We identified six studies that measured asbestos concentrations outside and inside respiratory protective equipment (RPE) and one cross-over study that compared the effect of two different coveralls on body temperature. No studies evaluated the remaining predefined outcomes. Most studies were at overall moderate risk of bias due to insufficient reporting. The cross-over study was at high risk of bias. Full-face filtering masks Two studies evaluated full-face filtering masks. They provided insufficient data for band 1 and band 6. The results for the remaining bands were as follows. • Band 2: RoM 19 (95% CI 17.6 to 20.1; 1 study, 3 measurements; moderate certainty) • Band 3: RoM 69 (95% CI 26.6 to 175.9; 2 studies, 17 measurements; very low certainty) • Band 4: RoM 455 (95% CI 270.4 to 765.1; 1 study, 16 measurements; low certainty) • Band 5: RoM 2752 (95% CI 1236.5 to 6063.2;1 study, 3 measurements; low certainty) The inside measurements in band 5 did not comply with the EU OEL of 0.1 f/cm3, and no inside measurements complied with the proposed EU OEL of 0.01 f/cm3. Supplied air respirators Two studies evaluated supplied air respirators. They provided no data for band 6. The results for the remaining bands were as follows. • Band 1: RoM 11 (95% CI 7.6 to 14.9; 1 study, 134 measurements; moderate certainty) • Band 2: RoM 63 (95% CI 43.8 to 90.9; 1 study, 17 measurements; moderate certainty) • Band 3: RoM 528 (95% CI 368.7 to 757.5; 1 study, 38 measurements; moderate certainty) • Band 4: RoM 4638 (95% CI 3071.7 to 7044.5; 1 study, 49 measurements; moderate certainty) • Band 5: RoM 26,134 (16,647.2 to 41,357.1; 1 study, 22 measurements; moderate certainty) All inside measurements complied with the current OEL of 0.1 f/cm3 and the proposed OEL of 0.01 f/cm3. Powered air-purifying respirators Three studies evaluated PAPRs. The results per band were as follows. • Band 1: RoM 8 (95% CI 3.7 to 19.1; 1 study, 23 measurements; moderate certainty) • Band 2: RoM 90 (95% CI 64.7 to 126.5; 1 study, 17 measurements; moderate certainty) • Band 3: RoM 104 (95% CI 23.1 to 464.1; 3 studies, 14 measurements; very low certainty) • Band 4: RoM 706 (95% CI 219.2 to 2253.0; 2 studies, 43 measurements; very low certainty) • Band 5: RoM 1366 (544.6 to 3428.9; 2 studies, 8 measurements; low certainty) • Band 6: RoM 18,958 (95% CI 4023.9 to 90,219.4; 2 studies, 13 measurements; very low certainty) All inside measurements complied with the 0.1 f/cm3 OEL when the outside concentration was below 10 f/cm3 (band 1 to band 4). From band 3, no measurements complied with the proposed OEL of 0.01 f/cm3. Different types of coveralls One study reported the adverse effects of coveralls. A polyethylene suit may increase the body temperature more than a ventilated impermeable polyvinyl (PVC) coverall, but the evidence is very uncertain (MD 0.17 °C, 95% CI -0.08 to 0.42; 1 study, 11 participants; very low certainty). AUTHORS' CONCLUSIONS: Where the outside asbestos concentration is below 0.1 f/cm3, SARS and PAPRs likely reduce exposure to below the proposed OEL of 0.01 f/cm3. For outside concentrations up to 10 f/cm3, all respirators may reduce exposure below the current OEL, but only SAR also below the proposed OEL. In band 5 (10 to < 100 f/cm3), full-face filtering masks may not reduce asbestos exposure below either OEL, SARs likely reduce exposure below both OELs, and there were no data for PAPRs. In band 6 (100 f/cm3 to < 1000 f/cm3), PAPRs may not reduce exposure below either OEL, and there were no data for full-face filtering masks or SARs. Some coveralls may increase body temperature more than others. Randomised studies are needed to directly compare PAPRs and SARs at higher asbestos concentrations and to assess adverse effects. Future studies should assess the effects of doffing procedures.

Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study.

BACKGROUND: Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC. METHODS: The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries. RESULTS: 47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000. CONCLUSION: Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.

Exploring occupational toxicant exposures in patients with metabolic dysfunction-associated steatotic liver disease: A prospective pilot study.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been traditionally associated with insulin resistance and obesity. Recently, pollutants have been shown to contribute to the development of MASLD. Given the global burden of MASLD, understanding whether pollutants are merely associated with steatosis or contribute to its progression to advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC) is critical. Workers exposed to occupational toxicants represent an ideal population for assessing the potentially hazardous consequences of professional exposure. Confirming a link between occupational exposure and ACLD/HCC may not only provide further elements in understanding MASLD, but also contribute to preventive strategies for exposed workers. OBJECTIVE: This study aimed to assess the prevalence of self-reported occupational exposure to toxicants in patients with MASLD. METHODS: This hospital-based prospective pilot study included 201 patients with MASLD. Data on workplace toxicant exposure were collected systematically using a structured questionnaire. Subsequently, patients with ACLD and/or HCC (n = 55) were compared to controls (n = 146). Logistic regression analysis and propensity score models were used to investigate the associations between self-reported occupational exposure and ACLD and/or HCC. RESULTS: Patients with ACLD/HCC reported exposure to metals, halogenated refrigerants, pain/resins, and fuel emissions more often than the controls. After controlling for confounders, durations of 21-30 years and >30 years of occupational exposure to toxicants showed odds ratios (ORs) of 2.31 (95 % confidence interval [CI]: 1.09-4.88, p = 0.029) and 4.47 (95 % CI: 2.57-7.78, p<0.001), respectively. CONCLUSIONS: In this pilot study, patients with MASLD complications were more likely to report workplace toxicant exposure. Our results warrant future multicentre confirmatory studies, as implementing prevention policies may reduce the risk of life-threatening diseases among exposed populations.

Cause specific mortality in an Italian pool of asbestos workers cohorts.

BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.

Recognition of COVID-19 with occupational origin: a comparison between European countries.

OBJECTIVES: This study aims to present an overview of the formal recognition of COVID-19 as occupational disease (OD) or injury (OI) across Europe. METHODS: A COVID-19 questionnaire was designed by a task group within COST-funded OMEGA-NET and sent to occupational health experts of 37 countries in WHO European region, with a last update in April 2022. RESULTS: The questionnaire was filled out by experts from 35 countries. There are large differences between national systems regarding the recognition of OD and OI: 40% of countries have a list system, 57% a mixed system and one country an open system. In most countries, COVID-19 can be recognised as an OD (57%). In four countries, COVID-19 can be recognised as OI (11%) and in seven countries as either OD or OI (20%). In two countries, there is no recognition possible to date. Thirty-two countries (91%) recognise COVID-19 as OD/OI among healthcare workers. Working in certain jobs is considered proof of occupational exposure in 25 countries, contact with a colleague with confirmed infection in 19 countries, and contact with clients with confirmed infection in 21 countries. In most countries (57%), a positive PCR test is considered proof of disease. The three most common compensation benefits for COVID-19 as OI/OD are disability pension, treatment and rehabilitation. Long COVID is included in 26 countries. CONCLUSIONS: COVID-19 can be recognised as OD or OI in 94% of the European countries completing this survey, across different social security and embedded occupational health systems.

Comparison between available early antiviral treatments in outpatients with SARS-CoV-2 infection: a real-life study.

PURPOSE: To investigate the clinical impact of three available antivirals for early COVID-19 treatment in a large real-life cohort. METHODS: Between January and October 2022 all outpatients tested positive for SARS-CoV-2 referring to IRCCS S. Orsola hospital treated with an early antiviral therapy were enrolled. A comparison between patients treated with nirmatrelvir/ritonavir (NTV/r), molnupiravir (MPV) and remdesivir (RDV) was conducted in term of indications and outcome. To account for differences between treatment groups a propensity score analysis was performed. After estimating the weights, we fitted a survey-weighted Cox regression model with inverse-probability weighting with hospital admission/death versus clinical recovery as the primary outcome. RESULTS: Overall 1342 patients were enrolled, 775 (57.8%), 360 (26.8%) and 207 (15.4%) in MPV, NTV/r and RDV group, respectively. Median age was 73 (59-82) years, male sex was 53.4%. Primary indication was immunosuppression (438, 32.6%), the median time from symptom onset to drug administration was 3 [2-4] days. Overall, clinical recovery was reached in 96.9% of patients, with hospital admission rate of 2.6%. No significant differences were found in clinical recovery nor hospitalization. Cox regression showed a decreased probability of hospital admission/ death among prior vaccinated patients compared with unvaccinated (HR 0.31 [95%CI 0.14-0.70], p = 0.005]). No difference in hospitalization rates in early treatment compared to late treatment were found. CONCLUSIONS: No differences among MPV, NTV/r and RDV in terms of clinical recovery or hospitalization were found. Patients not vaccinated had a significant increased risk of hospitalization.

Pleural mesothelioma risk in the construction industry: a case-control study in Italy, 2000-2018.

OBJECTIVES: Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers. DESIGN: Case-control study. SETTING: Cases from the National Mesothelioma Registry (2000-2018), controls from three previous case-control studies. METHODS: We selected male PM incident cases diagnosed in 2000-2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002-2004 and 2012-2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses. RESULTS: The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower. CONCLUSIONS: We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.

Shoulder Tendinopathies and Occupational Biomechanical Overload: A Critical Appraisal of Available Evidence.

BACKGROUND: The aim of this study is to evaluate the association between occupational exposure to biomechanical risk factors and shoulder tendinopathies. METHODS: We updated recent systematic reviews about specific shoulder disorders and work-related risk factors. MEDLINE was searched up to September 2022. Studies satisfying the following criteria were included: i) the diagnosis was based on physical examination plus imaging data (when available), and ii) the exposure assessment was based on video analysis and/or directly measured. RESULTS: Five studies met the inclusion criteria: three cross-sectional studies identified from published systematic reviews and two cohort studies retrieved from the update. Two studies investigated shoulder tendinitis, one supraspinatus tendinitis, and the other two rotator cuff syndrome. The diagnosis was based on physical examination, not supported by imaging techniques for all the included studies. In four out of five studies, the exposure was assessed by experienced ergonomists with the support of video recordings. In two studies, the exposure assessment was further supplemented by force gauge measurements or direct measurements of upper arm elevation. Only the combined exposure of working with arms above shoulder level with forceful hand exertion appears to be associated with rotator cuff syndrome: i) a cohort study reported an HR=1.11 (95%CI 1.01-1.22) for each unit increase in forceful repetition rate when the upper arm is flexed ≥45° for ≥29% of the working time; and ii) a cross-sectional study showed an OR=2.43 (95%CI 1.04-5.68) for the combination of upper arm flexion ≥45° for more than 15% of the time with a duty cycle of forceful exertions more than 9% of the time. CONCLUSIONS: There is moderate evidence of a causal association between shoulder tendinopathy and combined exposures of working above shoulder level with forceful hand exertion. The evidence is insufficient for any single biomechanical exposure on its own. High-quality cohort studies with direct exposure measures and objective diagnostic criteria are needed. The occupational origin of shoulder tendinopathies is still an open question that must be properly answered.

Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection.

BACKGROUND: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking. METHODS: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out. RESULTS: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score ≥ 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE ≥ 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score ≥ 11 and SOFA score ≥ 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective. CONCLUSIONS: Both INCREMENT-SOT-CPE ≥ 11 and SOFA ≥ 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.

Asbestos exposure as an additional risk factor for small duct intrahepatic cholangiocarcinoma: a pilot study.

Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy, recently classified in small duct and large duct morphological subtypes. Growing evidence suggests asbestos as a putative risk factor for iCCA, albeit no correlation between asbestos and iCCA morphology has been investigated so far. The aim of the present study was to assess the relationship between asbestos exposure and iCCA morphological subtype. Forty patients with surgically removed iCCA were prospectively enrolled: asbestos exposure was assessed according to the Italian National Mesothelioma Register questionnaire. From the surgical iCCA specimens the main histopathological variables were collected, including the small duct (sd-iCCA, 32 patients) and large duct subtypes (ld-iCCA, 8 patients). Five sd-iCCA cases had a definite/probable occupational exposure to asbestos, while no cases of ld-iCCA were classified as being occupationally exposed (definite/probable). Other kind of asbestos exposure (i.e. possible occupational, familial, environmental) were recorded in 16 sd-iCCA and 3 ld-iCCA. Cases with unlikely exposure to asbestos were 11 sd-iCCA (35.5%) and 5 ld-iCCA (62.5%). In conclusion, these findings seem to indicate that sd-iCCA might be more frequently associated to asbestos exposure rather than ld-iCCA, suggesting that asbestos fibres might represent a parenchymal, rather than a ductal risk factor for iCCA. This pilot study must be confirmed by further case-control studies or large independent cohorts.

Is Smoking Associated with Carpal Tunnel Syndrome? A Meta-Analysis.

To date, the role of smoking in carpal tunnel syndrome (CTS) is unclear. The aim of this systematic review and meta-analysis was to assess the association between smoking and CTS. The literature searches were conducted in PubMed, Embase, and Scopus, from inception until October 2021. Three reviewers screened the titles, abstracts, and full-text articles and evaluated the methodological quality of the included studies. A random-effects meta-analysis was used, and heterogeneity across studies was examined using I2 statistic. A total of 31 (13 cross-sectional, 10 case-control, and 8 cohort) studies were qualified for meta-analysis. In a meta-analysis of cohort studies, the risk of CTS did not differ between current and never smokers (pooled hazard ratio (HR) 1.09, 95% CI 0.84-1.43), current and past/never smokers (HR 1.07, 95% CI 0.94-1.23), and past and never smokers (HR 1.12, 95% CI 0.83-1.49). Furthermore, a meta-analysis of case control studies found no difference in the risk of CTS between current and never smokers (pooled odds ratio (OR) 0.92, 95% CI 0.56-1.53), current and past/never smokers (OR 1.10, 95% CI 0.51-2.36), and past and never smokers (OR 0.91, 95% CI 0.59-1.39). However, a meta-analysis of cross-sectional studies showed the associations of ever (OR 1.36, 95% CI 1.08-1.72) and current smoking (OR 1.52, 95% CI 1.11-2.09) with CTS. However, the association between ever smoking and CTS disappeared after limiting the meta-analysis to higher quality studies or after adjusting for publication bias. The association between current smoking and CTS also attenuated after limiting the meta-analysis to studies that confirmed CTS by a nerve conduction study or studies with low attrition bias. This meta-analysis does not support an association between smoking and CTS. The association between smoking and CTS observed in cross-sectional studies could be due to biases and/or confounding factors.

Exposure to Asbestos and Increased Intrahepatic Cholangiocarcinoma Risk: Growing Evidences of a Putative Causal Link.

To date the true global incidence of intrahepatic cholangiocarcinoma (iCCA) and the underlying risk factors remain to be fully defined, in particular, the role of occupational and environmental factors. Currently, the putative role of asbestos exposure as a risk factor for iCCA is gaining increased attention in the international scientific community and agencies. In this commentary we review and integrate available epidemiological and mechanistic evidences that support a potential role of asbestos exposure in iCCA etiology.

Predictive model for bacterial co-infection in patients hospitalized for COVID-19: a multicenter observational cohort study.

OBJECTIVE: The aim of our study was to build a predictive model able to stratify the risk of bacterial co-infection at hospitalization in patients with COVID-19. METHODS: Multicenter observational study of adult patients hospitalized from February to December 2020 with confirmed COVID-19 diagnosis. Endpoint was microbiologically documented bacterial co-infection diagnosed within 72 h from hospitalization. The cohort was randomly split into derivation and validation cohort. To investigate risk factors for co-infection univariable and multivariable logistic regression analyses were performed. Predictive risk score was obtained assigning a point value corresponding to ß-coefficients to the variables in the multivariable model. ROC analysis in the validation cohort was used to estimate prediction accuracy. RESULTS: Overall, 1733 patients were analyzed: 61.4% males, median age 69 years (IQR 57-80), median Charlson 3 (IQR 2-6). Co-infection was diagnosed in 110 (6.3%) patients. Empirical antibiotics were started in 64.2 and 59.5% of patients with and without co-infection (p = 0.35). At multivariable analysis in the derivation cohort: WBC ≥ 7.7/mm3, PCT ≥ 0.2 ng/mL, and Charlson index ≥ 5 were risk factors for bacterial co-infection. A point was assigned to each variable obtaining a predictive score ranging from 0 to 5. In the validation cohort, ROC analysis showed AUC of 0.83 (95%CI 0.75-0.90). The optimal cut-point was ≥2 with sensitivity 70.0%, specificity 75.9%, positive predictive value 16.0% and negative predictive value 97.5%. According to individual risk score, patients were classified at low (point 0), intermediate (point 1), and high risk (point ≥ 2). CURB-65 ≥ 2 was further proposed to identify patients at intermediate risk who would benefit from early antibiotic coverage. CONCLUSIONS: Our score may be useful in stratifying bacterial co-infection risk in COVID-19 hospitalized patients, optimizing diagnostic testing and antibiotic use.

Towards harmonisation of case definitions for eight work-related musculoskeletal disorders - an international multi-disciplinary Delphi study.

BACKGROUND: International consensus is needed on case definitions of work-related musculoskeletal disorders and diseases (MSDs) for use in epidemiological research. We aim to: 1) study what information is needed for the case definition of work-related low back pain (LBP), lumbosacral radicular syndrome (LRS), subacromial pain syndrome (SAPS), carpal tunnel syndrome (CTS), lateral and medial elbow tendinopathy, and knee and hip osteoarthritis, and to 2) seek consensus among occupational health professionals/researchers regarding the case definitions of these work-related MSDs. METHODS: A two-round Delphi study was conducted with occupational health professionals/researchers from 24 countries. Definition of work-related MSDs were composed of a case definition with work exposures. Round 1 included 32 case definitions and round 2, 60 case definitions. After two rounds, consensus required 75% of the panellists to rate a case definition including work exposures ≥7 points on a 9-point rating scale (completely disagree/completely agree). RESULTS: Fifty-eight panellists completed both rounds (response rate 90%). Forty-five (70%) panellists thought that for LBP a case definition can be based on symptoms only. Consensus was only reached for work-related medial elbow tendinopathy, while the lowest agreement was found for knee osteoarthritis. Where consensus was not reached, this was - except for LBP - related to physical examination and imaging rather than disagreement on key symptoms. CONCLUSION: Consensus on case definitions was reached only for work-related medial elbow tendinopathy. Epidemiological research would benefit from harmonized case definitions for all MSDs including imaging and physical examination for LRS, SAPS, CTS, lateral elbow tendinopathy and hip and knee osteoarthritis.

Effectiveness of preventive interventions and Randomised Controlled Trials in Occupational Health: an overview of the last five decades.

INTRODUCTION: Evidence-Based Medicine, as a new scientific paradigm, modified the approach to diagnosis, -treatment and prevention of diseases based on the best available scientific evidence synthesized in systematic reviews since the last decade of the past century. To evaluate its influence, we assessed the trend in the number and proportion of -randomised controlled trials (RCTs) and systematic reviews of preventive interventions in occupational health (OH) over the last five decades. METHODS: PubMed has been searched using established search filters regarding occupational determinants of diseases, OH preventive interventions, RCTs and systematic reviews. The number of hits were -assessed per decade. We estimated the number of pertinent studies in the systematically recruited samples of retrieved citations. RESULTS: Over the years, the number of studies concerning the effectiveness of preventive interventions in OH increased 3.5-fold from 986 in 1970-1979 to 3,428 in 2010-2019. RCTs of preventive interventions increased more than 60-fold from 6 in the seventies to 370 in the last decade. Systematic reviews first appeared at the end of the past century with a 30-fold increase (from 4 to 120) over the last three decades. DISCUSSION: The number of high-quality studies, such as RCTs and systematic reviews evaluating the effectiveness of preventive interventions in OH, has increased more rapidly than other studies on this topic. The Evidence-Based Medicine philosophy, diffused by researchers worldwide, has promoted the evaluation of the effectiveness of preventive interventions in OH.

Diagnostic criteria for musculoskeletal disorders for use in occupational healthcare or research: a scoping review of consensus- and synthesised-based case definitions.

BACKGROUND: The aim of this study was to identify case definitions of diagnostic criteria for specific musculoskeletal disorders (MSDs) for use in occupational healthcare, surveillance or research. METHODS: A scoping review was performed in Medline and Web of Science from 2000 to 2020 by an international team of researchers and clinicians, using the Arksey and O'Malley framework to identify case definitions based on expert consensus or a synthesis of the literature. Seven MSDs were considered: non-specific low back pain (LBP), lumbosacral radicular syndrome (LRS), subacromial pain syndrome (SAPS), carpal tunnel syndrome (CTS), lateral or medial elbow tendinopathy, and knee and hip osteoarthritis (OA). Case definitions for occupational healthcare or research were charted according to symptoms, signs and instrumental assessment of signs, and if reported, on work-related exposure criteria. RESULTS: In total, 2404 studies were identified of which 39 were included. Fifteen studies (38%) reported on non-specific LBP, followed by knee OA (n = 8;21%) and CTS (n = 8;21%). For non-specific LBP, studies agreed in general on which symptoms (i.e., pain in lower back) and signs (i.e., absence of red flags) constituted a case definition while for the other MSDs considerable heterogeneity was found. Only two studies (5%), describing case definitions for LBP, CTS, and SAPS and lateral and medial elbow tendinopathy respectively, included work-related exposure criteria in their clinical assessment. CONCLUSION: We found that studies on non-specific LBP agreed in general on which symptoms and signs constitute a case definition, while considerable heterogeneity was found for the other MSDs. For prevention of work-related MSDs, these MSD case definitions should preferably include work-related exposure criteria.

Elbow tendinopathy and occupational biomechanical overload: A systematic review with best-evidence synthesis.

OBJECTIVES: To evaluate the evidence of an association between occupational and non-occupational exposure to biomechanical risk factors and lateral elbow tendinopathy, medial elbow tendinopathy, and olecranon bursitis. METHODS: We carried out a systematic review of the literature. We searched MEDLINE (up to November 2019) and checked the reference lists of relevant articles/reviews. We aimed to include studies where (a) the diagnosis was based on physical examination (symptoms plus clinical signs) and imaging data (if any); and (b) the exposure was evaluated with video analysis and/or direct measurements. A quality assessment of the included studies was performed along with an evaluation of the level of evidence of a causal relationship. RESULTS: We included four studies in the qualitative synthesis: two prospective cohorts and two cross-sectional studies. All the included studies investigated "lateral/medial epicondylitis", albeit the diagnosis was not supported by imaging techniques. Two cohort studies suggested that a combination of biomechanical risk factors for wrist/forearm is associated with increased risk of "lateral epicondylitis". This association was not observed in the two included cross-sectional studies. The cohort studies suggested that a Strain Index score higher than 5 or 6.1 could double the risk of "lateral epicondylitis". No association with increased risk of "medial epicondylitis" was observed. CONCLUSIONS: There is limited evidence of a causal relationship between occupational exposure to biomechanical risk factors and lateral elbow tendinopathy. For medial elbow tendinopathy, the evidence is insufficient to support this causal relationship. No studies on olecranon bursitis and biomechanical overload were identified.

Authors' response: Mezei et al's "Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis".

Mezei et al's letter (1) is an opportunity to provide more details about our study on pericardial and tunica vaginalis testis (TVT) mesothelioma (2), which is based on the Italian national mesothelioma registry (ReNaM): a surveillance system on mesothelioma, with individual asbestos exposure assessment. Incidence of pericardial mesothelioma has been estimated around 0.5 and 0.2 cases per 10 million person-years in men and women, respectively, and around 1 case for TVT mesothelioma. ReNaM collected 138 cases thanks to its long period of observation (1993-2015) and national coverage. Conducting a population-based case-control study with incidence-density sampling of controls across Italy and over a 23 year time-span should have been planned in 1993 and would have been beyond feasibility and ReNaM scope. We rather exploited two existing series of controls (3). The resulting incomplete time- and spatial matching of cases and controls is a limitation of our study and has been acknowledged in our article. The analysis of case-control studies can nevertheless be accomplished in logistic models accounting for the variables of interest, in both individually and frequency matched studies (4). Furthermore, analyses restricted to (i) regions with enrolled controls, (ii) cases with definite diagnosis, (iii) incidence period 2000-2015, and (iv) subjects born before 1950 have been provided in the manuscript, confirming the strength of the association with asbestos exposure (supplemental material tables S4-7). Following Mezei et al's suggestion, we performed further sensitivity analyses by restriction to regions with controls and fitting conditional regression models using risk-sets made of combinations of age and year of birth categories (5-year classes for both). We confirmed positive associations with occupational exposure to asbestos of pericardial mesothelioma, with odds ratios (OR) (adjusted for region) of 9.16 among women [95% confidence interval (CI) 0.56-150] and 5.63 (95% CI 1.02-31.0) among men; for TVT mesothelioma the OR was 7.70 (95% CI 2.89-20.5). Using risk sets of age categories and introducing year of birth (5-year categories) as a covariate (dummy variables) the OR were similar: OR (adjusted for region) of 9.17 among women (95% CI 0.56-150) and 5.76 (95% CI 1.07-31.0) among men; for TVT the OR was 9.86 (95% CI 3.46-28.1). Possible bias from incomplete geographical overlap between cases and controls has been addressed in the paper (table S4) and above. In spatially restricted analyses, OR were larger than in those including cases from the whole country, indicating that bias was towards the null. Mezei et al further noted that "the regional distribution of controls is different from that of person-time observed". This objection is not relevant because the above analyses were adjusted by region. Our controls were provided by a population-based study on pleural mesothelioma (called MISEM) and a hospital-based study on cholangiocarcinoma (called CARA). In MISEM, the response rate was 48.4%, a low but not unexpected rate as participation among population controls is usually lower and has been declining over time (5). It is important to underline that ReNaM applied the same questionnaire that was used for interviews and carried out the same exposure assessment as both MISEM and CARA. As repeatedly stated in ReNaM papers (6-7), each regional operating center assesses asbestos exposure based on the individual questionnaire, other available information, and knowledge of local industries. Occupational exposure to asbestos is classified as definite, probable or possible. Occupational exposure is (i) definite when the subject`s work was reported or otherwise known to have involved the use of asbestos or asbestos-containing materials (MCA); (ii) probable when subjects worked in factories where asbestos or MCA were used, but their personal exposure could not be documented; and (iii) possible when they were employed in industrial activities known to entail the use of asbestos or MCA. Hence, the definite and probable categories are closer to one another and were combined in our analyses. In any case, restricting analyses to subjects with definite occupational exposure and using each set of controls separately, as suggested by Mezei et al, yielded elevated OR for TVT and pericardial mesothelioma among men using both the above described modelling strategies; the OR could not be calculated for women. There were 70 (25 pericardial and 45 TVT) occupationally exposed mesothelioma cases. In population-based studies, analyses by occupation are limited by the low prevalence of most specific jobs. As briefly reported in our paper, for purely descriptive purposes, the industrial activity of exposure (cases may have multiple exposures), were construction (22 exposures, 7 and 15 for pericardial and TVT mesotheliomas, respectively), steel mills and other metal working industries (4 and 11), textile industries (2 and 3), and agriculture (2 and 5); other sectors had lower exposure frequencies. The absence of industries like asbestos-cement production, shipbuilding and railway carriages production/repair should not be surprising and had already been observed (7). In the Italian multicenter cohort study of asbestos workers (8), given the person-years of observation accrued by workers employed in these industries and gender- and site-specific crude incidence rates, approximately 0.1 case of pericardial and 0.2 of TVT mesothelioma would have been expected from 1970 to 2010. Even increasing ten-fold such figures to account for higher occupational risks among these workers would not change much. Asbestos exposure in agriculture has been repeatedly discussed in ReNaM reports (9: pages 70, 73, 128, 164 and 205). Exposure opportunities included the presence of asbestos in wine production, reuse of hessian bags previously containing asbestos, or construction and maintenance of rural buildings. Similarly, mesothelioma cases and agricultural workers exposed to asbestos have been noted in France (10). In conclusion, the additional analyses we performed according to Mezei et al's suggestions confirm the association between asbestos exposure and pericardial and TVT mesothelioma, supporting the causal role of asbestos for all mesotheliomas. ReNaM`s continuing surveillance system with national coverage is a precious platform for launching analytical studies on pleural and extra pleural mesothelioma. References 1. Mezei G, Chang ET, Mowat FS, Moolgavkar SH. Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis Scand J Work Environ Health. 2021;47(1):85-86. https://doi.org/10.5271/3909 2. Marinaccio A, Consonni D, Mensi C, Mirabelli D, Migliore E, Magnani C et al.; ReNaM Working Group. Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks. Scand J Work Environ Health. 2020;46(6):609-617. https://doi.org/10.5271/sjweh.3895. 3. Greenland S. Control-initiated case-control studies. Int J Epidemiol 1985 Mar;14(1):130-4. https://doi.org/10.1093/ije/14.1.130. 4. Pearce N. Analysis of matched case-control studies. BMJ 2016 Feb;352:i969. https://doi.org/10.1136/bmj.i969. 5. Bigert C, Gustavsson P, Straif K, Pesch B, Brüning T, Kendzia B et al. Lung cancer risk among cooks when accounting for tobacco smoking: a pooled analysis of case-control studies from Europe, Canada, New Zealand, and China. J Occup Environ Med 2015 Feb;57(2):202-9. https://doi.org/10.1097/JOM.0000000000000337. 6. Marinaccio A, Binazzi A, Marzio DD, Scarselli A, Verardo M, Mirabelli D et al.; ReNaM Working Group. Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int J Cancer 2012 May;130(9):2146-54. https://doi.org/10.1002/ijc.26229. 7. Marinaccio A, Binazzi A, Di Marzio D, Scarselli A, Verardo M, Mirabelli D et al. Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register. Occup Environ Med 2010 Nov;67(11):760-5. https://doi.org/10.1136/oem.2009.051466. 8. Ferrante D, Chellini E, Merler E, Pavone V, Silvestri S, Miligi L et al.; the working group. Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure. Occup Environ Med 2017 Dec;74(12):887-98. https://doi.org/10.1136/oemed-2016-104100. 9. ReNaM VI Report. Available from: https://www.inail.it/cs/internet/docs/alg-pubbl-registro-nazionale-mesoteliomi-6-rapporto.pdf. Italian 10. Marant Micallef C, Shield KD, Vignat J, Baldi I, Charbotel B, Fervers B et al. Cancers in France in 2015 attributable to occupational exposures. Int J Hyg Environ Health 2019 Jan;222(1):22-9. https://doi.org/10.1016/j.ijheh.2018.07.015.

The effectiveness of removal from exposure and reduction of exposure for managing occupational asthma: Summary of an updated Cochrane systematic review.

BACKGROUND: The objective was to update the 2011 Cochrane systematic review on the effectiveness of workplace interventions for the treatment of occupational asthma. METHODS: A systematic review was conducted with the selection of articles and reports through 2019. The quality of extracted data was evaluated, and meta-analyses were conducted using techniques recommended by the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Data were extracted from 26 nonrandomized controlled before-and-after studies. The mean number of participants per study was 62 and the mean follow-up time was 4.5 years. Compared with continued exposure, removal from exposure had an increased likelihood of improved symptoms and change in spirometry. Reduction of exposure also had more favorable results for symptom improvement than continued exposure, but no difference for change in spirometry. Comparing exposure removal to reduction revealed an advantage for removal with both symptom improvement and change in spirometry for the larger group of patients exposed to low-molecular-weight agents. Also, the risk of unemployment was greater for exposure removal versus reduction. CONCLUSIONS: Exposure removal and reduction had better outcomes than continued exposure. Removal from exposure was more likely to improve symptoms and spirometry than reduction among patients exposed to low-molecular-weight agents. The potential benefits associated with exposure removal versus reduction need to be weighed against the potential for unemployment that is more likely with removal from exposure. The findings are based on data graded as very low quality, and additional studies are needed to generate higher quality data.