Primary mitochondrial myopathy: 12-month follow-up results of an Italian cohort.

OBJECTIVES: To assess natural history and 12-month change of a series of scales and functional outcome measures in a cohort of 117 patients with primary mitochondrial myopathy (PMM). METHODS: Twelve months follow-up data of 117 patients with PMM were collected. We analysed the 6-min walk test (6MWT), timed up-and-go test (× 3) (3TUG), five-times sit-to-stand test (5XSST), timed water swallow test (TWST), and test of masticating and swallowing solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional pain inventory as patient-reported outcome measures. PMM patients were divided into three phenotypic categories: mitochondrial myopathy (MiMy) without extraocular muscles involvement, pure chronic progressive external ophthalmoplegia (PEO) and PEO&MiMy. As 6MWT is recognized to have significant test-retest variability, we calculated MCID (minimal clinically important difference) as one third of baseline 6 min walking distance (6MWD) standard deviation. RESULTS: At 12-month follow-up, 3TUG, 5XSST and FSS were stable, while TWST and the perceived pain severity (WHYMPI) worsened. 6MWD significantly increased in the entire cohort, especially in the higher percentiles and in PEO patients, while was substantially stable in the lower percentile (< 408 m) and MiMy patients. This increase in 6MWD was considered not significant, as inferior to MCID (33.3 m). NMDAS total score showed a slight but significant decline at 12 months (0.9 point). The perceived pain severity significantly worsened. Patients with PEO performed better in functional measures than patients with PEO&MiMy or MiMy, and had lower values of NMDAS. CONCLUSIONS: PMM patients showed a slow global decline valued by NMDAS at 12 months; 6MWT was a more reliable measurement below 408 m, substantially stable at 12 months. PEO patients had better motor performance and lower NMDAS than PEO&MiMy and MiMy also at 12 months of follow-up.

Incidence of occupational contact dermatitis in healthcare workers: a systematic review.

Healthcare workers (HCWs) can be considered at an increased risk of developing occupational contact dermatitis (OCD) due to repetitive hand washing with soaps and disinfectants and extended use of gloves for many hours during the day. The aim of this study was to summarize the incidence of OCD in HCWs. We searched the databases PubMed/MEDLINE (1980-present), EMBASE (1980-present) and Cochrane Library (1992-present) through May 2020 using the search term 'incidence of contact dermatitis in HCWs' according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Overall, 16 studies (six cohorts; 10 register-based) with follow-up periods between 1987 and 2013 fulfilled the inclusion criteria. The incidence of OCD reported in studies using registers of occupational diseases ranged from 0.6 to 6.7 per 10 000 person-years. The cohort studies reported incidence from 15.9 to 780.0 per 10 000 person-years; the incidence was higher in studies which included apprentice nurses. A higher incidence was also observed amongst dental practitioners, particularly dental technicians and nurses, compared to other HCWs. Studies reporting incidence data are very scarce and results differed by study design, type of contact dermatitis and investigated HCWs. Our study highlighted the dearth of high-quality data on the incidence of OCD and the possible underestimation of disease burden. Prospective cohort studies with harmonized designs, especially exposure assessment and outcome ascertainment, are required to provide more accurate, valid and recent estimates of the incidence of OCD. A high incidence amongst specific occupational groups suggests the need to undertake intervention studies with a focus on prevention, particularly during pandemics such as COVID-19.

Global evidence on occupational sun exposure and keratinocyte cancers: a systematic review.

Individual studies have suggested that the association between occupational exposure to solar ultraviolet radiation (UVR) and the development of keratinocyte cancers (KCs) may only be valid in populations of European ancestry living in certain geographical regions. Comparative global data are scarce and so this review aimed to summarize current evidence on the association between occupational exposure to solar UVR and the development of KCs, with a specific focus on geographical location and skin colour. Ovid MEDLINE, PubMed, Embase and Web of Science were searched for potentially relevant records. Extracted data were summarized by study, country and region. We included one prospective cohort study and 18 case-control studies (n = 15 233) from 12 countries in regions where the majority of the population is white skinned (Americas, Europe and Oceania). Eighteen of the 19 studies reported effect estimates suggesting an increased risk of basal cell carcinoma (BCC) and/or squamous cell carcinoma (SCC) among outdoor workers. Only 11 studies found a significantly increased risk and many had imprecise estimates. There was a significantly increased risk of BCC and SCC in individual studies in North America, Latin America and the Caribbean, Western Europe and Southern Europe, but not across regions or countries. Overall, 95% of studies reported higher risks among outdoor workers, although the increases in risk were statistically significant in just over half of the studies. Well-designed and sufficiently powered occupational case-control and cohort studies with adequate adjustment for confounding factors and other risk factors are required to provide more accurate risk estimates for occupational KC.

Personal solar ultraviolet radiation dosimetry in an occupational setting across Europe.

BACKGROUND: Work-related solar ultraviolet radiation (UVR) is an important factor in the pathogenesis of non-melanoma skin cancer (NMSC). The World Health Organization, through the International Agency for Research on Cancer, has classified solar UVR as a group 1 carcinogen since 2012. The main problems encountered so far in the study of occupationally induced skin cancer include the lack of accurate occupational UVR dosimetry as well as insufficient distinction between occupational and leisure UVR exposure and underreporting of NMSC. OBJECTIVES: The aim of this study was to collect long-term individual UVR measurements in outdoor workers across European countries. METHODS: A prospective study was initiated through the European Academy of Dermatology and Venereology, Healthy Skin@Work Campaign, measuring UVR exposure doses at occupational settings of masons from five European countries. Measurements were performed for several consecutive months using the GENESIS-UV measurement system. RESULTS: The results identified alarming UVR exposure data. Average daily UVR doses ranged 148.40-680.48 J/m2 in Romania, 342.4-640.8 J/m2 in Italy, 165.5-466.2 J/m2 in Croatia, 41.8-473.8 J/m2 in Denmark and 88.15-400.22 J/m2 in Germany. Results showed an expected latitude dependence with increasing UVR yearly dosage from the north to the south of Europe. CONCLUSIONS: This study shows that outdoor workers from EU countries included in this study are exposed to high levels of occupational solar UVR, vastly exceeding the occupational exposure limits for solar UVR exposure, considered to be 1-1.33 SED/day in the period from May to September. This finding may serve as an evidence-based recommendation to authorities on implementing occupational skin cancer prevention strategies.

Skin cancer in outdoor workers exposed to solar radiation: a largely underreported occupational disease in Italy.

BACKGROUND: Solar UV radiation (sUVR) is one of the main carcinogen exposures in occupational settings, and UV-induced skin cancers are the most frequent tumours in fair-skinned individuals worldwide. OBJECTIVES: According to this premise, we should expect a high number of occupational skin cancers reported to the national workers' compensation authorities each year, also considering that the incidence of skin cancers has been constantly increased in recent years METHODS: We examined the data on reported non-melanoma skin cancers (NMSC) and actinic keratoses (AK) to the Italian National Workers Compensation Authority (INAIL) from 2012 to 2017, and we compared the number of reported skin cancers for outdoor workers with the expected numbers, obtained from currently available NMSC incidence rates for the Italian population applied to the occupational sUVR-exposed workers estimated with the CAREX methodology in Italy in 2005. RESULTS: The cases of NMSC reported each year to INAIL in Italy are 34 per year on average, while for AK the mean number of reported cases is of only 15/year. We estimated a number of expected NMSC cases in Italy for solar UV-exposed workers ranging between 432 and 983, representing a proportion between reported vs. expected skin cancers of only 3.5-6.2%. CONCLUSIONS: Our study clearly shows that occupational skin cancers in Italy are largely underreported, and, accordingly, urgent initiatives should be taken to raise appropriate awareness to the problem of occupational sUVR-induced skin cancers, so that adequate preventive measures can be implemented rapidly.

Questionnaire-based evaluation of occupational and non-occupational solar radiation exposure in a sample of Italian patients treated for actinic keratosis and other non-melanoma skin cancers.

BACKGROUND: An adequate evaluation of the ultraviolet (UV) cumulative exposure is a major problem in epidemiological studies on chronic skin damage. Questionnaires may be applied as useful tools. OBJECTIVE: We developed an original questionnaire to evaluate individual cumulative exposure to solar radiation (SR) in patients affected by actinic keratosis (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHOD: The questionnaire, considering both working and leisure exposure, was applied to evaluate the whole life history of solar UV radiation exposure in a group of patients of the Dermatologic Clinic of UNIMORE. RESULTS: In outdoor workers (OW), the co-presence of AK/in situ SCC and invasive non-melanoma skin cancers (NMSCs) was increased compared to indoor workers (IW), as was the frequency of multiple skin lesions. The prevalence of skin lesions of the face was significantly higher in OW. Work 'sometimes' or 'often' in the shades was associated with an absence of skin lesions on the shoulders and neck, while workers adopting 'sometimes' or 'often' a downward bent position were more likely to develop lesions on the top of the head. Considering leisure activities, the use of tanning beds was associated to the presence of skin lesions on the shoulders, neck and chest. Considering vacation periods, subjects spending at least 2 h outdoor in the period 11 am to 1 pm presented earlier diagnoses of skin cancers. CONCLUSION: Results of the original questionnaire developed are coherent with current knowledge and confirm the important role of UV exposure, both occupational and recreational, in the development of AK and NMSCs. Data support the hypothesis that this questionnaire can be applied as useful tool for the evaluation of cumulative UV exposure in future epidemiological studies.

The European Status Quo in legal recognition and patient-care services of occupational skin cancer.

BACKGROUND: Skin cancer is the most common malignancy in Caucasian populations worldwide and ultraviolet radiation (UVR) is known for being the number one carcinogen. As, especially in outdoor workers, UVR is an inevitable carcinogen, the prevention and management of UVR-related skin cancers in these at-risk populations represent a collective challenge for dermatologists and healthcare policymakers likewise. OBJECTIVE: To provide an overview on the current regulations on the acknowledgement and management of work-related skin cancer in 11 European countries. METHODS: Dermatologists from 11 countries networking within the EU Horizon 2020 COST Action TD1206 'StanDerm' contributed to a standardized survey regarding current national regulations, implemented for the recognition, prevention and management as well as possible compensation regulations in their individual country of residence. RESULTS: Ten of 11 participating countries in this survey reported the existence of an established programme available on certain occupational diseases; work-related skin diseases were only specifically recognized in eight countries. Seven of 11 countries recognize cutaneous squamous cell carcinoma in outdoor workers as 'occupational skin cancer'. Basal cell carcinoma (6 of 11), actinic keratosis (5 of 11), Bowen's disease (5 of 11) and malignant melanoma (5 of 11) are not as regularly approved as potentially 'work-induced'. Only a few of the countries included into this survey established a general documentation system (national registry) on occupational skin diseases. So far, representatives of only three countries of this survey referred to a specific established national programme for the prevention, management or compensation of occupational skin cancers acquired during work-related UVR exposure. CONCLUSION: This survey highlights the need for mandatory regulations on the prevention, management and potential compensation of work-related UV-induced skin cancer across Europe. Against the background of a joint European domestic market, equal standards of occupational safety across Europe should include binding regulations for the protection and management of work-related skin cancer. The design of a common regulation to meet the increasing incidence of skin cancers in outdoor workers should become part of the European agenda, ensuring equal working and living conditions in the member states.

Rehabilitation procedures in the management of gait disorders in the elderly.

Gait disorders are common and very disabling in elderly people, leading to an increase of risk of falling and reductions in quality of life. So far, many clinical classifications of gait disorders in the elderly population have been proposed. Here we suggest a novel categorization of gait disorders in elderly people, which takes into account the several resources required during gait. The biomechanical constraints, movement and sensory strategies, orientation in space, control of dynamics and cognitive processing are essential to perform safely gait. Moreover, the strictly connection between gait and balance has been discussed. According to this perspective, a literature search was performed including studies investigating the rehabilitation procedures in the management of balance and gait disorders in elderly people. Training aimed at improving muscle strength and flexibility, movement strategies, sensorimotor integration and sensory reweighting processes, balance in static and dynamic conditions and cognitive strategies have been proposed as possible therapeutic approaches in elderly people affected by gait disorders. Moreover, the role of new technological devices in improving balance and gait control has been also described. A multidisciplinary and interdisciplinary approach is fundamental for the management of gait disorders in elderly people. Rehabilitation procedures should take into consideration all the potential constraints involved in gait disorders in order to select the most appropriate intervention.

[Occupational risk related to optical radiation exposure in construction workers]. / Rischio da radiazione ottica in edilizia.

Optical Radiation is a relevant occupational risk in construction workers, mainly as a consequence of the exposure to the ultraviolet (UV) component of solar radiation (SR). Available data show that UV occupational limits are frequently exceeded in these workers, resulting in an increased occupational risk of various acute and chronic effects, mainly to skin and to the eye. One of the foremost is the carcinogenic effect: SR is indeed included in Group 1 IARC (carcinogenic to humans). UV exposure is related to an increase of the incidence of basal cell carcinoma, squamous cell carcinoma of the skin and cutaneous malignant melanoma (CMM). The incidence of these tumors, especially CMM, is constantly increasing in Caucasians in the last 50 years. As a conclusion, an adequate evaluation of the occupational risk related to SR, and adequate preventive measures are essential in construction workers. The role of occupational physicians in prevention is fundamental.

[Heat stroke in the workplace: description of a case with fatal outcome]. / Colpo di calore in ambito lavorativo: descrizione di un caso con esito fatale.

BACKGROUND: Heat exposure represents an occupational risk factor in various work settings. Adverse effects may range from mild symptoms, like muscular cramps, to life threatening conditions, like heat stroke. Data on the occurrence of work-related adverse effects of heat exposure in Italy are lacking. OBJECTIVES: To highlight the risk of heat stroke in a common working activity. METHODS: The case of a fatal heat stroke in a 19-year-old worker, in apparently good health, employed in maintenance of open park spaces is presented. After working 7 hours outdoors on a sunny day he was found unconscious. He was immediately taken to the local Emergency Department, where he arrived in hyperthermic and comatose conditions, and died due to multiple organ failure after 36 hours. After excluding other main causes of hyperthermia, heatstroke was identified as the initial cause of death. RESULTS: The case presented describes the possible extreme consequences of an underestimation of the risk related to occupational heat exposure, even in young and apparently healthy workers. Heat-related adverse effects may occur in a number of common activities, not necessarily involving heavy workload or extreme temperatures. Different methods, including simplified methods, are available for heat stress risk evaluation. The main preventive measures include adequate acclimatization, periodic interruption of exposure, sufficient fluid intake, adequate clothing and appropriate Personal Protective Equipment. Adequate training and workers' health surveillance are also essential. CONCLUSIONS: Heat exposure may be a significant occupational risk, potentially inducing life-threatening conditions, in a number of common activities but is frequently underestimated. An example of undervaluation of the risk and of the possible consequences, are presented and discussed in this case report.

Multicentre evaluation of KONE Optima analysis system.

Optima from KONE Instruments Corporation is a new selective laboratory analyzer for turbidimetric, colorimetric and ion selective electrode measurements. Overall analytical performance of Optima and reagents provided by KONE was evaluated according to ECCLS guidelines, in a multicentre study involving four different laboratories, including substrates (cholesterol, high-density lipoprotein-cholesterol, creatinine), specific proteins (transferrin, IgG), enzyme activities (gamma-glutamyltransferase, alanine aminotransferase) and electrolytes (sodium, potassium, chloride). The results obtained attest good precision of the system for all the analytes tested: the range of within-run CV is 0.5 %-4.3 %, and range of between-day CV % is 0.8 %-7.9 % (median of four laboratories). Except for total cholesterol (5 % overestimation compared to the reference method) accuracy of measurement is adequate. Creatinine and uric acid assays were subjects of interference (defined as deviation > 10 % from target value) by bilirubin and haemoglobin respectively.

Reference standardization and triglyceride interference of a new homogeneous HDL-cholesterol assay compared with a former chemical precipitation assay.

A homogeneous HDL-c assay (HDL-H), which uses polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin, was assessed for precision, accuracy, and cholesterol and triglyceride interference. In addition, its analytical performance was compared with that of a phosphotungstic acid (PTA)/MgCl2 precipitation method (HDL-P). Within-run CVs were < or = 1.87%; total CVs were < or = 3.08%. Accuracy was evaluated in fresh normotriglyceridemic sera using the Designated Comparison Method (HDL-H = 1.037 Designated Comparison Method + 4 mg/L; n = 63) and in moderately hypertriglyceridemic sera by using the Reference Method (HDL-H = 1.068 Reference Method - 17 mg/L; n = 41). Mean biases were 4.5% and 2.2%, respectively. In hypertriglyceridemic sera (n = 85), HDL-H concentrations were increasingly positively biased with increasing triglyceride concentrations. The method comparison between HDL-H and HDL-P yielded the following equation: HDL-H = 1.037 HDL-P + 15 mg/L; n = 478. We conclude that HDL-H amply meets the 1998 NCEP recommendations for total error; its precision is superior compared with that of HDL-P, and its average bias remains below +/-5% as long as triglyceride concentrations are < or = 10 g/L and in case of moderate hypercholesterolemia.

Creatinine measurement proficiency testing: assignment of matrix-adjusted ID GC-MS target values.

The results of an external quality-assessment experiment for serum creatinine measurement are described. Fifty-one laboratories performed quintuplicate analyses during three different analytical runs on six lyophilized sera and two frozen human serum pools. Isotope dilution gas chromatography-mass spectrometry (ID GC-MS) target values were assigned to all the materials. Intralaboratory within- and between-run imprecision results were very similar for all the materials tested (CV < or = 2.20% and < or = 4.70%, respectively). The overall imprecision obtained was high (CV 6.5-20.0%) because of increased interlaboratory-intermethod variability. A significant positive bias (+ 9.2-+43.7%) was found for all the materials at lower creatinine concentration. By using two human sera at different concentrations, we could calculate the constant and the proportional calibration bias displayed by each peer group. The majority of the lyophilized materials showed a behavior divergent from the frozen pools, indicating matrix-related problems. We propose a new algorithm for calculating matrix bias correction factor instrument-reagent specific for each material.

Accuracy of cholesterol measurements in Italian clinical laboratories. Joint project GISSI prevention--Italian Society of Clinical Biochemistry. SIBioC GISSI Prevenzione Group.

We report the results of an external quality assessment scheme for serum total cholesterol measurement involving about 100 Italian laboratories participating in an epidemiological study of post myocardial infarction. Two frozen human serum pools with Abell-Kendall assigned values are distributed quarterly at the laboratories (up to now seven events occurred); the obtained results are evaluated and discussed. In one exercise (# 5) duplicated measurements were repeated on three different days. Eighty-five to 98% of the laboratories obtained results within the total error limits (+/- 8.9%). But, while precision (calculated on the six replicates of exercise # 5) is good (90% of the laboratories obtained CV < 3%), inaccuracy problems are evident in every event. Indeed the mean bias from the reference method value ranged from 1.54 and 3.49% in the various events.

Behavior of frozen serum pools and lyophilized sera in an external quality-assessment scheme.

To further improve analytical accuracy in clinical chemistry, proficiency testing needs amelioration in the quality of materials tested and in target value assignment. To obtain information on the actual state-of-the-art in the Lombardy region of Italy, and to examine the behavior of different types of control materials (fresh-frozen human sera and lyophilized materials), we developed the following experimental design. Two human serum pools and two lyophilized sera were distributed to 32 laboratories for determination of glucose, creatinine, cholesterol, sodium, potassium, and gamma-glutamyltransferase (gamma-GT). Each analyte was measured in triplicate on each of 3 days. Target values for the controls were obtained with Reference Methods. The results show a good intralaboratory precision for every component but some accuracy problems for glucose, creatinine, cholesterol, and gamma-GT. Lyophilized materials showed some commutability problems for glucose, electrolytes, and gamma-GT, mainly with dry chemistry technology.

Clinical utility of fractionating erythrocytes into "Percoll" density gradients.

Two rapid methods for fractionating the RBC into five or nine layers of increasing density are reported. These procedures have been used to monitor the decline of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) activity during the process of red cell aging in normal subjects and in beta-thal carriers, to study transfused patients with G6PD and pyruvate kinase (PK) deficiency and to test the effects of inositol hexaphosphate (IHP) encapsulation on RBC subpopulations.