Incidence, risk and protective factors of symptoms after colonoscopy.

BACKGROUND: Few studies focused on minor adverse events which may develop after colonoscopy. AIMS: To investigate the incidence and factors associated to post-colonoscopy symptoms. METHODS: This is a prospective study conducted in 10 Italian hospitals. The main outcome was a cumulative score combining 10 gastrointestinal (GI) symptoms occurring the week following colonoscopy. The analyses were conducted via multivariate logistic regression. RESULTS: Of 793 subjects included in the analysis, 361 (45.5%) complained the new onset of at least one GI symptom after the exam; one symptom was reported by 202 (25.5%), two or more symptoms by 159 (20.1%). Newly developed symptoms more frequently reported were epigastric/abdominal bloating (32.2%), pain (17.3%), and dyspeptic symptoms (17.9%). Symptoms were associated with female sex (odds ratio [OR]=2.54), increasing number of symptoms developed during bowel preparation intake (OR=1.35) and somatic symptoms (OR=1.27). An inverse association was observed with better mood (OR=0.74). A high-risk profile was identified, represented by women with bad mood and somatic symptoms (OR=8.81). CONCLUSION: About half of the patients develop de novo GI symptoms following colonoscopy. Improving bowel preparation tolerability may reduce the incidence of post-colonoscopy symptoms, especially in more vulnerable patients.

Determinants of symptom burden related to bowel preparation for colonoscopy.

BACKGROUND: Symptoms developing during bowel preparation are major concerns among subjects who refuse the procedure. AIMS: We aimed to explore the determinants of symptoms occurring during preparation among patients undergoing elective colonoscopy. METHODS: This is a prospective multicenter study conducted in 10 Italian hospitals. A multidimensional approach collecting socio-demographic, clinical, psychological and occupational information before colonoscopy through validated instruments was used. Outcome was a four-category cumulative score based on symptoms occurring during preparation, according to the Mayo Clinic Bowel Prep Tolerability Questionnaire, weighted by intensity. Missing values were addressed through multiple imputation. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through multivariate logistic regression models. RESULTS: 1137 subjects were enrolled. Severe symptoms were associated with female sex (OR=3.64, 95%CI 1.94-6.83), heavier working hours (OR=1.13, 95% CI=1.01-1.25), previous gastrointestinal symptoms (OR=7.81, 95% CI 2.36-25.8 for high score), somatic symptoms (OR=2.19, 95% CI=1.06-4.49 for multiple symptoms), day-before regimen (OR=2.71, 95%CI 1.28-5.73). On the other hand, age ≥60 years (OR=0.10, 95% CI 0.02-0.44) and good mood (p=0.042) were protective factors. A high-risk profile was identified, including women with low mood and somatic symptoms (OR=15.5, 95%CI 4.56-52.7). CONCLUSIONS: We identified previously unreported determinants of symptoms burdening bowel preparation and identified a particularly vulnerable phenotype. Symptoms during preparation especially impact heavier working activity.

Impact of colonoscopy on working productivity: a prospective multicenter observational study.

BACKGROUND AND AIMS: Patients undergoing colonoscopy are often in the workforce. Therefore, colonoscopy may affect patients' work productivity in terms of missed working days and/or reduced working efficiency. We aimed to investigate the impact of colonoscopy on work productivity and factors influencing this impact. METHODS: We conducted a prospective, observational, multicenter study in 10 Italian hospitals between 2016 and 2017. We collected information on individual characteristics, work productivity, symptoms, and conditions before, during, and after the procedure from patients undergoing colonoscopy for several indications using validated tools. Outcomes were interference of preparation with work, absenteeism, and impaired work performance after the procedure. We fitted multivariate logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for potential predictors of the outcomes. RESULTS: Among 1137 subjects in the study, 30.5% reported at least 1 outcome. Impaired work performance was associated with bowel preparation regimen (full dose on the day of colonoscopy vs split dose: OR, 4.04; 95% CI, 1.43-11.5), symptoms during bowel preparation (high symptom score: OR, 3.21; 95% CI, 1.15-8.95), and pain during the procedure (OR, 2.47; 95% CI, 1.40-4.35). Increasing number of working hours and less comfortable jobs were associated with absenteeism (P for trend = .06) and impairment of working performance (P for trend = .01) and GI symptoms both before and after colonoscopy. CONCLUSIONS: Occupational and individual characteristics of patients should be considered when scheduling colonoscopy because this procedure may impair work productivity in up to one-third of patients. Split-dose bowel preparation, performing a painless colonoscopy, and preventing the occurrence of GI symptoms may minimize the impact of colonoscopy on work productivity.

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.

The role of the occupational physician in controlling gastric cancer attributable to Helicobacter pylori infection: A review.

This review aimed to describe the potential role of occupational physician in the implementation of a screening program for Helicobacter pylori (Hp) infection for gastric cancer prevention. We reviewed the epidemiological background of gastric cancer and its association with Hp, exploring the hypothesis of a "test-and-treat" protocol among working population. Clinical trials and model-based studies were collected to provided empirical evidence of the feasibility of eradication on large scale. In particular, previous studies conducted in occupational settings were discussed. Hp prevalence ranges between about 20 and 90%, with higher rates in Asia and Latin America and lower rates in Europe and North America. Large-scale trials on screening and treatment of infection have been conducted especially in East Asia, lacking elsewhere. Only few studies investigated Hp prevalence among workers. The benefit of eradication at occupational level has not yet been adequately studied. The design of a workplace-based Hp screening program appears to be innovative and could contribute to controlling gastric cancer. The benefit would involve not only high-risk subjects, but also their families, since the route of transmission is principally within the household. An occupational setting for a Hp screening would have positive consequences in terms of individual and public health.

Occupational exposure to antineoplastic drugs in hospital environments: potential risk associated with contact with cyclophosphamide- and ifosfamide-contaminated surfaces.

BACKGROUND: Cyclophosphamide (CP) and ifosfamide (IP) contaminations have been detected in hospital environments. This study was conducted to determine if there was any contamination in the spaces (floors and door handles) between the hospital exit and the antineoplastic drugs (ADs) preparation and administration units. At the same time, the authors proposed a new automation of the analytical procedure to considerably decrease the time needed for sample preparation and analysis. MATERIAL AND METHODS: To evaluate the ADs contamination of surfaces, 829 wipe tests were performed in a campaign involving 3 hospitals located in Italy. Sampling was performed using an innovative kit. The levels of ADs were measured in each wipe sample using liquid chromatography/triple quadrupole. RESULTS: On-line solid-phase extraction guarantees the construction of a robust and reproducible analytical method. The CP and IP recoveries from stainless steel, polycarbonate and polyvinyl chloride ranged >80%, and the wipe holders and the automation tested ensured desorption efficiencies close to 100% for both the ADs. Of the 552 wipes taken on the spaces between the hospital exit and the preparation, administration and pharmacy warehouse units, 22 were greater than or equal to the limit of quantification, all adjacent to the administration units. CONCLUSIONS: This study provides an insight into the exposure situation against ADs residues. In order to improve environmental monitoring programs, the authors propose to evaluate the ADs contamination also outside the preparation, administration and pharmacy warehouse units. Med Pr. 2020;71(5):519-29.

Health risk assessment related to hydrogen peroxide presence in the workplace atmosphere - analytical methods evaluation for an innovative monitoring protocol.

OBJECTIVES: Hydrogen peroxide (HP) accounts for 15% of the total global chemical revenue. According to the National Institute of Occupational Safety and Health, the HP concentration immediately dangerous to human life or health is 75 ppm. Operators exposed to HP should pay attention when choosing the monitoring technique that should be specific and sensitive enough to discriminate the exposure levels from background concentrations. In order to assess the long- and short-term exposure to HP in disinfection processes, the authors compared 6 industrial hygiene monitoring methods to evaluate their efficiency in measuring airborne HP concentrations. MATERIAL AND METHODS: Airborne HP concentrations were evaluated using an on-fiber triphenylphosphine solid-phase microextraction method, and they were compared with those obtained using a 13-mm Swinnex titanium oxysulfate filter holder and 4 portable direct-reading electrochemical sensors. A survey carried out in wood pulp bleaching, food and beverage disinfection processing, and in a hospital department to reduce the risk of spreading nosocomial infections, was performed during routine operations to access the risk of HP occupational exposure. RESULTS: Through the generation of HP gaseous dynamic atmospheres (0.1-85 ppm), the authors evaluated the consistency of the results obtained using the 6 methods described. The monitoring campaigns showed that the increase in HP could be relatively high (until 67 ppm) in food and beverage processing. CONCLUSIONS: In the authors' opinion, the current 8-h time-weighted average limits of 1 ppm for HP do not reflect the actual risk; a short-term exposure limit would, therefore, provide a much better protection. 2020;33(2):137-50.

Application of epidemiological findings to individuals.

Three types of issues need to be considered in the application of epidemiology results to individuals. First, epidemiology results are subject to random error, and can be applied only to an ideal subject with average values of all variables under study, including potential confounders included in the regression models. Second, the observational nature of epidemiology makes it susceptible to systematic error, and any extrapolation to individuals would mirror the validity of the original results. Quantitative bias analysis has been proposed to assess the likelihood, direction and magnitude of bias, but this has not yet become part of the normal practice of epidemiology. Finally, external validity of the results (i.e., their application to individuals and populations other than those included in the underlying studies) needs to be addressed, including population-based factors, such as heterogeneity in exposure or disease circumstances, and individual-based factors, such as interaction of the risk factors of interest with other determinants of the disease. Similar considerations apply to the application of results of clinical trials to individual patients, although in these studies sources of systematic error are better controlled.

Carpal tunnel syndrome in cardiac amyloidosis: implications for early diagnosis and prognostic role across the spectrum of aetiologies.

AIMS: We aimed to assess carpal tunnel syndrome (CTS) prevalence in transthyretin (TTR)-related and light-chain amyloidosis (AL), comparing it to the general population, adjusted for age and gender. In TTR-related amyloidosis (ATTR) we investigated (i) CTS prevalence in relation to genotype, cardiac amyloidosis (CA), age and gender; (ii) CTS role as an incremental risk factor for CA; (iii) temporal relationship between CTS and CA; and (iv) CTS prognostic role. METHODS AND RESULTS: Data from 538 subjects (166 hereditary ATTR, 107 wild-type ATTR, 196 AL amyloidosis, and 69 TTR mutation carriers; 64% male, median age 62.4 years), evaluated at our centre (Bologna, Italy), were analysed and compared to a published cohort of 14.9 million people, in which incidence rates of CTS had been estimated. CTS prevalence was highest in ATTR patients with CA (20.3% vs. 4.1% in the general population), while it was comparable to the general population when CA was absent and in AL patients. CTS standardized incidence rates were markedly elevated in ATTR males in the eighth decade of life (13.08 in hereditary ATTR, 15.5 in wild-type ATTR). The risk of developing CA was greater in ATTR patients with CTS; the probability of having CTS was highest 5-9 years prior to CA diagnosis. CTS was an independent mortality risk factor in ATTR. CONCLUSIONS: Compared to general population the adjusted prevalence of CTS is higher among elderly men with ATTR; CTS is a prognostic marker in ATTR, independently of cardiac involvement, and precedes CA diagnosis by 5-9 years. The awareness of this association and time delay offers the possibility of an early pre-clinical ATTR-CA diagnosis.

Occupational exposure to airborne formaldehyde in hospital: setting an automatic sampling system, comparing different monitoring methods and applying them to assess exposure.

BACKGROUND: In recent years, under-vacuum sealing (UVS) and containers with formalin encapsulated in the lid have been proposed for the reduction of occupational exposure to airborne formaldehyde (FA) in healthcare environments. OBJECTIVES: We are presenting a study focused on the assessment of FA in hospitals: an automatic sampling system was set, different sampling devices were compared, and the concentration of FA was assessed, following its use in different scenarios. METHODS: Three different devices for sampling/measuring FA were compared. They are based on: 1. silica gel cartridges impregnated with 2,4-dinitrophenylhydrazine (2,4-DNPH); 2. SPME® fiber using O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine; 3. direct reading commercial instrumentation. Three typical scenarios using FA were investigated: operating theatres where small biopsies are soaked into closed-circuit system 4% FA containers, secretariat of pathology laboratories during the registration of biopsies and pathology laboratories during the filling procedure by UVS and the slicing of biopsies. RESULTS: The automatic sampling system allowed short-, long-, and in continuous-sampling time to measure airborne FA. Different sampling devices provided comparable results when tested to assess FA concentration ranging from 0.020-0.320 ppm in a test chamber, although  the devices based on 2,4-DNPH were  the best in terms of sensitivity and accuracy. The results of 246 samples showed that the FA concentration was less than 0.04 ppm in 91% of the measurements. CONCLUSIONS: The automatic methods efficiently allow sampling and measurement of FA in hospital settings. When using safe practices, the concentration of FA is well below occupational limit values.

Position Paper on Asbestos of the Italian Society of Occupational Medicine.

The Position Paper (PP) on asbestos of the Italian Society of Occupational Medicine (SIML) aims at providing a tool to the occupational physician to address current diagnostic criteria and results of epidemiological studies, and their consequences in terms of preventive and evaluation actions for insurance, compensation and litigation. The PP was based on an extensive review of the scientific literature and was compiled by a Working Group comprising researchers who have contributed to the international literature on asbestos-related diseases, as well as occupational physicians with extensive experience in the evaluation of risks and the medical surveillance of workers currently and formerly exposed to asbestos. The PP was drafted and reviewed between 2017 and 2018; its final version was prepared according to the guidelines of AGREE Reporting Checklist. All the members of the Working Group subscribed to the document, which was eventually approved by SIML's Executive Committee. The first section addresses industrial hygiene issues, such as methods for environmental monitoring, advantages and limitations of different microscopy techniques, the potential role of microfibers and approaches for retrospective assessment of exposure, in particular in epidemiological studies. The second section reviews the biological effects of asbestos with particular attention to the diagnostic aspects of asbestosis, pleural changes, mesothelioma and lung cancer. In the following section the criteria of causal attribution are discussed, together with different hypotheses on the form of the risk functions, with a comparison of the opinions prevalent in the literature. In particular, the models of the risk function for mesothelioma were examined, in the light of the hypothesis of an acceleration or anticipation of the events in relation to the dose. The last section discusses topics of immediate relevance for the occupational physician, such as health surveillance of former exposed and of workers currently exposed in remediation activities.

Association Between Push-up Exercise Capacity and Future Cardiovascular Events Among Active Adult Men.

Importance: Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Robust evidence indicates an association of increased physical fitness with a lower risk of CVD events and improved longevity; however, few have studied simple, low-cost measures of functional status. Objective: To evaluate the association between push-up capacity and subsequent CVD event incidence in a cohort of active adult men. Design, Setting, and Participants: Retrospective longitudinal cohort study conducted between January 1, 2000, and December 31, 2010, in 1 outpatient clinics in Indiana of male firefighters aged 18 years or older. Baseline and periodic physical examinations, including tests of push-up capacity and exercise tolerance, were performed between February 2, 2000, and November 12, 2007. Participants were stratified into 5 groups based on number of push-ups completed and were followed up for 10 years. Final statistical analyses were completed on August 11, 2018. Main Outcomes and Measures: Cardiovascular disease-related outcomes through 2010 included incident diagnoses of coronary artery disease and other major CVD events. Incidence rate ratios (IRRs) were computed, and logistic regression models were used to model the time to each outcome from baseline, adjusting for age and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared). Kaplan-Meier estimates for cumulative risk were computed for the push-up categories. Results: A total of 1562 participants underwent baseline examination, and 1104 with available push-up data were included in the final analyses. Mean (SD) age of the cohort at baseline was 39.6 (9.2) years, and mean (SD) BMI was 28.7 (4.3). During the 10-year follow up, 37 CVD-related outcomes (8601 person-years) were reported in participants with available push-up data. Significant negative associations were found between increasing push-up capacity and CVD events. Participants able to complete more than 40 push-ups were associated with a significantly lower risk of incident CVD event risk compared with those completing fewer than 10 push-ups (IRR, 0.04; 95% CI, 0.01-0.36). Conclusions and Relevance: The findings suggest that higher baseline push-up capacity is associated with a lower incidence of CVD events. Although larger studies in more diverse cohorts are needed, push-up capacity may be a simple, no-cost measure to estimate functional status.

Prognostic Impact of Presurgical CA19-9 Level in Pancreatic Adenocarcinoma: A Pooled Analysis.

BACKGROUND: Presurgical carbohydrate antigen 19-9 (CA19-9) level predicts overall survival (OS) in resected pancreatic adenocarcinoma (PaC). The aim of this pooled analysis was to evaluate if presurgical CA19-9 level can also predict local control (LC) and distant metastasis-free survival (DMFS). METHODS: Seven hundred patients with PaC from eight institutions who underwent surgical resection ± adjuvant treatment between 2000 and 2014 were analyzed. Patients were divided based on four presurgical CA19-9 level cutoffs (5, 37, 100, 353 U/ml). Weibull regression model to identify independent predictors of OS on 404 patients with complete information was fitted. RESULTS: Median follow-up was 17 months (range: 2-225 months). Univariate analysis showed a better prognosis in pT1-2, pN0, diameter <30 mm, or grade 1 tumors and in patients undergoing R0 resection, distal pancreatectomy, or adjuvant chemotherapy and with lower CA19-9 levels. Five-year OS, LC, and DMFS were as follows: CA19-9 <5.0: 5.7%, 47.2%, 17.0%; CA19-9 5.1-37.0: 37.9%, 63.3%, 46.0%; CA19-9 37.1-100.0: 27.1%, 59.4%, 39.0%; CA19-9 100.1-353.0: 17.4%, 43.4%, 26.7%; CA19-9 >353.1: 10.9%, 50.2%, and 23.4%, respectively. At multivariate analysis, CA19-9 >100 and <353 level (P=.002), CA19-9 ≥353.1 (P<.001) level, G3 tumor (P=.002), and tumor diameter >30 mm (P<.001) correlated with worse OS. Patients treated with postoperative chemoradiation doses >50.0 Gy showed improved OS (P<.001). CONCLUSION: Presurgical CA19-9 predicts both OS and pattern of failure. Therefore, CA19-9 should be included in predictive models in order to customize treatments based on prognostic factors. Moreover, future studies should stratify patients according to presurgical CA19-9 level.

Hypofractionated radiotherapy after conservative surgery may increase low-intermediate grade late fibrosis in breast cancer patients.

AIM: To compare late toxicity after postoperative hypofractionated radiotherapy (RT) and standard fractionated RT in patients with early-stage breast carcinoma. METHODS: This retrospective study included 447 patients (Modulated Accelerated Radiotherapy [MARA-1]: 317 patients, and control group [CG]: 130 patients). In the CG, the whole breast received 50.4 Gy in 28 fractions (fx) using 3D-radiotherapy, plus a sequential electron boost (10 Gy in 4 fx) to tumor bed. In MARA-1 group, a forward-planned intensity-modulated radiotherapy technique with 40 Gy in 16 fx with a concomitant boost of 4 Gy to breast was used. The primary endpoint was to evaluate late toxicity, and secondary endpoints were acute toxicity, local control, and survival. ClinicalTrials.gov: NCT03461224. RESULTS: Median follow-up was 52 months (range: 3-115 months). Late skin and subcutaneous toxicity were acceptable: 5-year actuarial cumulative incidence of Grade (G) 3 late skin toxicity was 1.5% in CG and 0.0% in MARA-1. Five-year actuarial cumulative incidence of G3 late subcutaneous toxicity was 0.8% in CG and 0.3% in MARA-1. On multivariate analysis, tobacco smoking and planning target volume were associated with an increased risk of late G1 skin toxicity (HR: 2.15, 95% CI: 1.38-3.34 and HR: 1.12, 95% CI: 1.07-1.18, respectively), whereas patients with a larger planning target volume also showed an increased risk of G1 and G2 late subcutaneous toxicity (HR: 1.14, CI 95%: 1.08-1.20 and HR: 1.14, 95% CI: 1.01-1.28, respectively). MARA-1 patients also showed an increased risk of late G1 and G2 subcutaneous toxicity (HR: 2.35, 95% CI: 1.61-3.41 and HR: 3.07, 95% CI: 1.11-8.53, respectively) compared to CG. CONCLUSION: In this retrospective analysis, postoperative accelerated-hypofractionated RT for early-stage-breast carcinoma was associated with higher incidence of subcutaneous side effects. However, this increase was limited to G1-G2 toxicity. In the future, development of predictive models could help in tailoring dose and fractionation based on the risk of toxicity.

Tailored postoperative treatment of prostate cancer: final results of a phase I/II trial.

BACKGROUD: The European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP. MATERIALS AND METHODS: This phase I/II trial treatment was designed to improve 5-year bDFS from ~ 75 to 90%. Patients were consecutively enrolled using the following inclusion criteria: age < 80 years, histological diagnosis of prostate adenocarcinoma without known metastases, stage pT2-4N0-1, and Eastern Cooperative Oncology Group performance status of 0-2. All patients had at least one of these pathologic features: capsular perforation, positive surgical margins, seminal vesicle invasion, and pelvic lymph nodes involvement. A minimum dose of 64.8 Gy to the tumor bed was delivered in all patients. Depending on tumor characteristics at diagnosis, patients received a higher dose (70.2 Gy; 85.4%) and/or prophylactic pelvic lymph nodes irradiation (57.7%) and/or HT (69.1%). Biochemical relapse was defined as two consecutive rising prostate-specific antigen (PSA) values > 0.2 ng/ml. RESULTS: A total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06 ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37-120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively. CONCLUSION: A higher 5-year bDFS (92.9%) was recorded compared to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. (ClinicalTrials.gov: NCT03169933).

Authors' response: Letter to the Editor concerning OCRA as preferred method in ISO standards on biomechanical risk factors.

We thank Drs. Colombini and Occhipinti for their personal reply to our Discussion Paper (1, 2). We share the overall goal of preventing workplace injuries and welcome a discussion of the ISO process on workplace ergonomics standards; this was the primary aim of the Discussion Paper. We hope that other members of the relevant ISO working groups will also participate in the discussion. However, Drs. Colombini and Occipinti misinterpret our paper. Our aim was not to "addresses the scientific basis of ISO standards on biomechanical risk factors and more specifically the OCRA methodology". The purpose was to point out that "while the ISO process has value, it has also clear limitations when it comes to developing occupational health and safety standards that should be based on scientific principles". It is true that our paper discussed the OCRA method, but only as an example, in a single paragraph. We noted that the OCRA method was promoted as the preferred method by the ISO working group even though there were other risk assessment methods which, at the time (and currently), were at least as scientifically valid (3). The discovery that, while on the ISO working group, Drs. Colombini and Occipinti elevated the risk assessment method that they developed (OCRA) over the other methods, demonstrates one of several limitations of the ISO process, namely, the lack of attention to conflict of interest. Finally, we would like to draw attention to the note by Drs. Colombini and Occhipinti that "the ISO standards in question were actually developed by the working group, as mandated by ISO, over the period 2000‒2004". This long-elapsed time, without an update to the standard, should be a concern for all scientists given the large quantity of quality scientific literature published since then (eg, 3‒6). Fourteen years is well beyond what is recommended in the ISO guidelines. References 1. Colombini D, Occhipinti E. Scientific basis of the OCRA method for risk assessment of biomechanical overload of the upper limb, as preferred method in ISO standards on biomechanical risk factors. Scand J Work Environ Health ‒ online first. https://doi.org.10.5271/sjweh.3746 2. Armstrong T J, Burdorf I A, Descatha A, Farioli A, Graf M, Horie S, Marras W S, Potvin J R, Rempel D, Spatari G, Takala E P, Verbeek J, Violante FS. Scientific basis of ISO standards on biomechanical risk factors. Scand J Work Environ Health ‒ online first. https://doi.org/10.5271/sjweh.3718 3. Takala EP, Pehkonen I, Forsman M, Hansson GA, Mathiassen SE, Neumann WP, Sjøgaard G, Veiersted KB, Westgaard RH, Winkel J. Systematic evaluation of observational methods assessing biomechanical exposures at work. Scand J Work Environ Health. 2010;36:3-24. https://doi.org/10.5271/sjweh.2876 4. Paulsen R, Gallu T, Gilkey D, Reiser R, Murgia L, Rosecrance J. The inter-rater reliability of Strain Index and OCRA Checklist task assessments in cheese processing. Applied Ergonomics. 2015; 51,199-204. https://doi.org/10.1016/j.apergo.2015.04.019 5. Kapellusch JM, Gerr FE, Malloy EJ, Garg A, Harris-Adamson C, Bao SS, Burt SE, Dale AM, Eisen EA, Evanoff BA, Hegmann KT, Silverstein BA, Theise MS, Rempel DM. Exposure-response relationships for the ACGIH threshold limit value for hand-activity level: results from a pooled data study of carpal tunnel syndrome. Scand J Work Environ Health. 2014;40:610-20. https://doi.org/10.5271/sjweh.3456 6. Violante FS, Farioli A, Graziosi F, Marinelli F, Curti S, Armstrong TJ, Mattioli S, Bonfiglioli R. Carpal tunnel syndrome and manual work: the OCTOPUS cohort, results of a ten-year longitudinal study. Scand J Work Environ Health. 2016;42:280-90. https://doi.org/10.5271/sjweh.3566.

Observed Differences between Males and Females in Surgically Treated Carpal Tunnel Syndrome Among Non-manual Workers: A Sensitivity Analysis of Findings from a Large Population Study.

Objectives: We aimed at assessing whether differences among males and females in carpal tunnel syndrome (CTS) epidemiology might be attributable to segregation with respect to occupational biomechanical exposures or differential access to care by sex. Methods: We analysed surgically treated cases of CTS occurring among non-manual workers in Tuscany between 1997 and 2000. We conducted a Monte Carlo simulation to estimate the difference in occupational biomechanical exposures between males and females necessary to explain the observed incidence rate ratios. We also accounted for the sex-specific probability of receiving surgery after the diagnosis of CTS, as women were reported to be more likely to undergo surgery in a subset of our study population. We quantified the hypothetical biomechanical overload through the hand activity level (HAL) metric proposed by the American Conference of Governmental Industrial Hygienists. To quantify the effect of HAL on CTS risk, we assumed a prior distribution based on findings from two large cohort studies of industrial workers. Results: After adjustment for the probability of receiving surgery, women showed a 4-fold incidence of CTS as compared with men. To explain this association among non-manual workers, women should have an average value of HAL at least 5 points higher. Conclusions: Our analysis does not support the hypothesis that the difference in CTS incidence between males and females is entirely attributable to occupational risk factors or to differential access to surgery. The causal pathway between sex and CTS might include more determinants such as hormonal factors, anthropometric characteristics, and non-occupational exposure to biomechanical overload (e.g. household tasks).

Phase I-II Study of Short-course Accelerated Radiotherapy (SHARON) for Palliation in Head and Neck Cancer.

AIM: To determine the maximum tolerated dose (MTD) of a short-course accelerated radiotherapy and its feasibility for symptomatic palliation of advanced head and neck cancer or head and neck metastases from any primary site. PATIENTS AND METHODS: A phase I trial in four dose-escalation steps was planned: total dose ranged between 14 and 20 Gy in a total of four fractions administered twice a day. The dose-limiting toxicity (DLT) was determined as grade 3 or more toxicity occurring during treatment. The MTD obtained was used to plan a phase II trial. RESULTS: A total of 48 patients were treated. In the phase I trial, the 20 Gy dose level was determined to be the MTD. In the phase II trial, the palliative response rate was 82.7%, with a median duration of palliation of 3 months. CONCLUSION: Short-course accelerated radiotherapy was well tolerated and effective for palliation. These findings may help design future prospective randomized studies.