[Role of the occupational medicine in the prevention of diseases and accidents]. / Rôle de la Médecine du travail dans la prévention des maladies et des accidents.

Occupational medicine is an essential branch of preventive medicine that aims to protect the health of workers in the workplace. Any work situation exposes the worker to occupational hazards. The three levels of prevention applied in occupational medicine make it possible, together, to control risks. Primary prevention aims to prevent the occurrence of damage related to occupational risks, secondary prevention aims to early detect work-related health problems and in tertiary prevention, the objective is to limit the consequences of occupational risks or diseases already developed. It is not always possible to completely eliminate an occupational hazard. Regular medical examinations, at a frequency appropriate to the risks identified, meet this objective and therefore make it possible to detect work-related health problems or problems that could influence work. A proactive approach focused on prevention helps to reduce occupational risks, prevent work-related diseases, and to promote a healthy and safe work environment for all.

La médecine du travail est une branche essentielle de la médecine préventive qui vise à protéger la santé des travailleurs sur leur lieu de travail. Toute situation de travail expose le travailleur à des dangers professionnels. Les trois niveaux de prévention appliqués en médecine du travail permettent, ensemble, de maîtriser les risques. La prévention primaire vise à empêcher l'apparition des dommages liés aux risques professionnels, la prévention secondaire vise à détecter précocement les problèmes de santé liés au travail et en prévention tertiaire, l'objectif est de limiter les conséquences des risques professionnels ou des maladies déjà développées. Il n'est pas toujours possible de supprimer complètement un risque professionnel. Les examens médicaux réguliers, à une périodicité adaptée aux risques identifiés, répondent à cet objectif et permettent donc de détecter les éventuels problèmes de santé liés au travail ou qui pourraient influencer le travail. Une approche proactive axée sur la prévention contribue à réduire les risques professionnels, à prévenir les maladies liées au travail, et à promouvoir un environnement de travail sain et sécurisé pour tous.

Liver blood marker testing in UK primary care: a UK wide cohort study, 2004-2016.

OBJECTIVE: We aimed to determine (1) the temporal trends of liver enzyme testing in UK general practice and (2) how these vary among different subgroups at risk of chronic liver disease (CLD). DESIGN: Retrospective cohort study. SETTING: UK primary care database (Clinical Practice Research Datalink (CPRD)), 2004-2016. PARTICIPANTS: Patients aged 18 years or over, registered in the CPRD from 1 January 2004 to 31 December 2016. OUTCOME MEASURES: The frequency of testing recorded within the study period in general practice was calculated for: alanine aminotransferase (ALT); aspartate aminotransferase (AST); gamma glutamyl transferase (GGT); alkaline phosphatase (ALP); bilirubin and platelets. Analyses were conducted in subgroups of patients at high risk of developing liver disease. RESULTS: The study cohort included 2 912 066 individuals with median follow-up of 3.2 years. The proportion of patients with at least one measurement for ALT, ALP, bilirubin or platelet test gradually increased over the course of the study period and fell for AST and GGT. By 2016, the proportion of the population receiving one of more tests in that year was: platelet count 28.0%, ALP 26.2%, bilirubin 25.6%, ALT 23.7%, GGT 5.1% and AST 2.2%. Those patients with risk factors for CLD had higher proportions receiving liver marker assessments than those without risk factors. CONCLUSIONS: The striking finding that AST is now only measured in a fraction of the population has significant implications for routine guidance which frequently expects it. A more nuanced approach where non-invasive markers are targeted towards individuals with risk factors for CLD may be a solution.

ALARP: when does reasonably practicable become rather pricey?

The Ionising Radiations Regulations 2017 require employers to restrict radiation doses to their employees and the public to be As Low As Reasonably Practicable. This article looks at the boundary between what might be considered to be reasonable and unreasonable in protecting staff and the general public in the field of hospital-based diagnostic radiology. A simple test for locating this boundary based on a cost-benefit approach is devised and its use illustrated using hospital-based radiation protection examples. It is concluded that a cost-benefit calculation based on the legal definition of As Low As Reasonably Practicable may have some use in the support of radiation protection decision-making in the hospital environment, but only within the context of existing legal, practical and ethical considerations.

Trends in indirect liver function marker testing in Wales from 2000 to 2017 and their association with age and sex: an observational study.

OBJECTIVE: If non-invasive markers of liver fibrosis were recorded frequently enough in clinical practice, it might be feasible to use them for opportunistic community screening for liver disease. We aimed to determine their current pattern of usage in the national primary care population in Wales. DESIGN: Using the Secure Anonymised Information Linkage (SAIL) Databank at Swansea University (2000-2017), we quantified the frequency of common liver blood tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count and albumin) used in fibrosis marker algorithms. We examined measurement variation by age and sex. RESULTS: During the 18-year study period, there were 2 145 178 adult patients with at least one blood test available for analysis. Over the study period, the percentage of SAIL patients receiving an ALT test in each year increased from 2% to 33%, with platelet count and albumin measurement increasing by a similar factor. AST testing, although initially rising, had decreased to 1% by the end of the study. AST and ALT values varied by age and sex, particularly in males with the upper normal range of ALT values decreasing rapidly from 90 U/L at age 30 to 45 U/L by age 80. CONCLUSION: The reduction in AST testing to only 1% of the adult population limits the use of many non-invasive liver marker algorithms. To enable widespread screening, alternative algorithms for liver fibrosis that do not depend on AST should be developed. Liver fibrosis markers should be modified to include age-specific and sex-specific normal ranges.

Predictors of endometrial carcinoma in patients with atypical endometrial hyperplasia at a tertiary gynaecological cancer centre in Western Australia.

AIM: Our objective was to assess clinical and pathological factors associated with a final diagnosis of endometrial carcinoma in patients with atypical endometrial hyperplasia with a particular emphasis on the grading of atypia. MATERIALS AND METHODS: A retrospective review over five years on patients (N = 97) who underwent hysterectomy for a diagnosis of atypical endometrial hyperplasia at a statewide public tertiary gynaecologic oncology centre. Clinical and pathological characteristics were obtained. RESULTS: The rate of concurrent endometrial carcinoma was 34% (n = 33) with most being stage 1A endometrioid. A significant group difference was reported for age at diagnosis (t = -2.20 P = 0.031 d = 0.43) with carcinoma patients on average older (Mage  = 60.2 (8.9) years) than patients without carcinoma (Mage  = 55.5 (12.3) years). No significant group differences were found for body mass index, endometrial thickness or time between diagnosis and treatment. Significantly higher rates of carcinoma were reported in patients with moderate atypical hyperplasia (27.6%) and severe atypical hyperplasia (66.7%), compared to mild atypical hyperplasia (7.1%). Only severe atypical hyperplasia (odds ratio (OR) = 21.5, 95% CI 2.8-163.1, P = 0.003) and postmenopausal status (OR = 13.2, 95% CI 1.3-139.0, P = 0.032) significantly increased the risk of carcinoma in a multivariate model. CONCLUSION: Severe atypical hyperplasia and postmenopausal status were significant predictors of concurrent endometrial carcinoma in patients with atypical endometrial hyperplasia. The grading of atypical hyperplasia may be utilised by gynaecologic oncologists in the triage and referral process of managing these patients; however, the grading system requires external validation in larger prospective studies.

Clinical Application of 3D-CISS MRI Sequences for Diagnosis and Surgical Planning of Spinal Arachnoid Diverticula and Adhesions in Dogs.

OBJECTIVE: Abnormalities within the spinal arachnoid space are often treated surgically, but they can be challenging to detect with conventional magnetic resonance imaging (MRI) sequences. 3D-CISS sequences are considered superior in evaluating structures surrounded by cerebrospinal fluid (CSF) due to the high signal-to-noise ratio, high contrast-to-noise ratio and intrinsic insensitivity to motion with minimal signal loss due to CSF pulsations. Our objective was to describe findings and advantages in adding 3D-CISS sequences to routine MRI in patients affected by spinal arachnoid diverticula (SAD) or arachnoid adhesions. MATERIAL AND METHODS: This article is a retrospective review of medical records of 19 dogs admitted at Fitzpatrick Referrals between 2013 and 2017 that were diagnosed with SAD and confirmed surgically. Inclusion criterions were the presence of clinical signs compatible with compressive myelopathy and an MRI diagnosis, which included the 3D-CISS sequence. Our database was searched for additional 19 dogs diagnosed with other spinal lesions other than SAD that had the same MR sequences. All MR images were anonymized and evaluated by two assessors. CONCLUSION AND CLINICAL RELEVANCE: 3D-CISS sequence appears to improve confidence in diagnosing and surgical planning (Mann-Whitney U-test: p < 0.0005), delineating SAD from other changes associated with abnormal CSF hydrodynamics and providing more anatomical details than conventional MRI sequences. The clinical data in combination with imaging findings would limit over interpretation, when concurrent pathology within the arachnoid space is present.

The NHS Bowel Cancer Screening Program: current perspectives on strategies for improvement.

Colorectal cancer (CRC) is the third most common cancer in the UK. The English National Health Service (NHS) Bowel Cancer Screening Program (BCSP) was introduced in 2006 to improve CRC mortality by earlier detection of CRC. It is now offered to patients aged 60-74 years and involves a home-based guaiac fecal occult blood test (gFOBt) biennially, and if positive, patients are offered a colonoscopy. This has been associated with a 15% reduction in mortality. In 2013, an additional arm to BCSP was introduced, Bowelscope. This offers patients aged 55 years a one-off flexible sigmoidoscopy, and if several adenomas are found, the patients are offered a completion colonoscopy. BCSP has been associated with a significant stage shift in CRC diagnosis; however, the uptake of bowel cancer screening remains lower than that for other screening programs. Further work is required to understand the reasons for nonparticipation of patients to ensure optimal uptake. A change of gFOBt kit to the fecal immunochemical tests (FIT) in the English BCSP may further increase patient participation. This, in addition to increased yield of neoplasia and cancers with the FIT kit, is likely to further improve CRC outcomes in the screened population.

Reversible DNA i-motif to hairpin switching induced by copper(II) cations.

i-Motif DNA structures have previously been utilised for many different nanotechnological applications, but all have used changes in pH to fold the DNA. Herein we describe how copper(II) cations can alter the conformation of i-motif DNA into an alternative hairpin structure which is reversible by chelation with EDTA.

Excess long-term mortality following non-variceal upper gastrointestinal bleeding: a population-based cohort study.

BACKGROUND: It is unclear whether an upper gastrointestinal bleed is an isolated gastrointestinal event or an indicator of a deterioration in a patient's overall health status. Therefore, we investigated the excess causes of death in individuals after a non-variceal bleed compared with deaths in a matched sample of the general population. METHODS AND FINDINGS: Linked longitudinal data from the English Hospital Episodes Statistics (HES) data, General Practice Research Database (GPRD), and Office of National Statistics death register were used to define a cohort of non-variceal bleeds between 1997 and 2010. Controls were matched at the start of the study by age, sex, practice, and year. The excess risk of each cause of death in the 5 years subsequent to a bleed was then calculated whilst adjusting for competing risks using cumulative incidence functions. 16,355 patients with a non-variceal upper gastrointestinal bleed were matched to 81,523 controls. The total 5-year risk of death due to gastrointestinal causes (malignant or non-malignant) ranged from 3.6% (≤ 50 years, 95% CI 3.0%-4.3%) to 15.2% (≥ 80 years, 14.2%-16.3%), representing an excess over controls of between 3.6% (3.0%-4.2%) and 13.4% (12.4%-14.5%), respectively. In contrast the total 5-year risk of death due to non-gastrointestinal causes ranged from 4.1% (≤ 50 years, 3.4%-4.8%) to 46.6% (≥ 80 years, 45.2%-48.1%), representing an excess over controls of between 3.8% (3.1%-4.5%) and 19.0% (17.5%-20.6%), respectively. The main limitation of this study was potential misclassification of the exposure and outcome; however, we sought to minimise this by using information derived across multiple linked datasets. CONCLUSIONS: Deaths from all causes were increased following an upper gastrointestinal bleed compared to matched controls, and over half the excess risk of death was due to seemingly unrelated co-morbidity. A non-variceal bleed may therefore warrant a careful assessment of co-morbid illness seemingly unrelated to the bleed.

Comorbidities affect risk of nonvariceal upper gastrointestinal bleeding.

BACKGROUND & AIMS: The incidence of upper gastrointestinal bleeding (GIB) has not been reduced despite the decreasing incidence of peptic ulcers, strategies to eradicate Helicobacter pylori infection, and prophylaxis against ulceration from nonsteroidal anti-inflammatory drugs. Other factors might therefore be involved in the pathogenesis of GIB. Patients with GIB have increasing nongastrointestinal comorbidity, so we investigated whether comorbidity itself increased the risk of GIB. METHODS: We conducted a matched case-control study using linked primary and secondary care data collected in England from April 1, 1997 through August 31, 2010. Patients older than 15 years with nonvariceal GIB (n = 16,355) were matched to 5 controls by age, sex, year, and practice (n = 81,636). All available risk factors for GIB were extracted and modeled using conditional logistic regression. Adjusted associations with nongastrointestinal comorbidity, defined using the Charlson Index, were then tested and sequential population attributable fractions calculated. RESULTS: Comorbidity had a strong graded association with GIB; the adjusted odds ratio for a single comorbidity was 1.43 (95% confidence interval [CI]: 1.35-1.52) and for multiple or severe comorbidity was 2.26 (95% CI: 2.14%-2.38%). The additional population attributable fraction for comorbidity (19.8%; 95% CI: 18.4%-21.2%) was considerably larger than that for any other measured risk factor, including aspirin or nonsteroidal anti-inflammatory drug use (3.0% and 3.1%, respectively). CONCLUSIONS: Nongastrointestinal comorbidity is an independent risk factor for GIB, and contributes to a greater proportion of patients with bleeding in the population than other recognized risk factors. These findings could help in the assessment of potential causes of GIB, and also explain why the incidence of GIB remains high in an aging population.

Defining upper gastrointestinal bleeding from linked primary and secondary care data and the effect on occurrence and 28 day mortality.

BACKGROUND: Primary care records from the UK have frequently been used to identify episodes of upper gastrointestinal bleeding in studies of drug toxicity because of their comprehensive population coverage and longitudinal recording of prescriptions and diagnoses. Recent linkage within England of primary and secondary care data has augmented this data but the timing and coding of concurrent events, and how the definition of events in linked data effects occurrence and 28 day mortality is not known. METHODS: We used the recently linked English Hospital Episodes Statistics and General Practice Research Database, 1997-2010, to define events by; a specific upper gastrointestinal bleed code in either dataset, a specific bleed code in both datasets, or a less specific but plausible code from the linked dataset. RESULTS: This approach resulted in 81% of secondary care defined bleeds having a corresponding plausible code within 2 months in primary care. However only 62% of primary care defined bleeds had a corresponding plausible HES admission within 2 months. The more restrictive and specific case definitions excluded severe events and almost halved the 28 day case fatality when compared to broader and more sensitive definitions. CONCLUSIONS: Restrictive definitions of gastrointestinal bleeding in linked datasets fail to capture the full heterogeneity in coding possible following complex clinical events. Conversely too broad a definition in primary care introduces events not severe enough to warrant hospital admission. Ignoring these issues may unwittingly introduce selection bias into a study's results.

Identifying adverse events of vaccines using a Bayesian method of medically guided information sharing.

BACKGROUND: The detection of adverse events following immunization (AEFI) fundamentally depends on how these events are classified. Standard methods impose a choice between either grouping similar events together to gain power or splitting them into more specific definitions. We demonstrate a method of medically guided Bayesian information sharing that avoids grouping or splitting the data, and we further combine this with the standard epidemiological tools of stratification and multivariate regression. OBJECTIVE: The aim of this study was to assess the ability of a Bayesian hierarchical model to identify gastrointestinal AEFI in children, and then combine this with testing for effect modification and adjustments for confounding. STUDY DESIGN: Reporting odds ratios were calculated for each gastrointestinal AEFI and vaccine combination. After testing for effect modification, these were then re-estimated using multivariable logistic regression adjusting for age, sex, year and country of report. A medically guided hierarchy of AEFI terms was then derived to allow information sharing in a Bayesian model. SETTING: All spontaneous reports of AEFI in children under 18 years of age in the WHO VigiBase™ (Uppsala Monitoring Centre, Uppsala, Sweden) before June 2010. Reports with missing age were included in the main analysis in a separate category and excluded in a subsequent sensitivity analysis. EXPOSURES: The 15 most commonly prescribed childhood vaccinations, excluding influenza vaccines. MAIN OUTCOME MEASURES: All gastrointestinal AEFI coded by WHO Adverse Reaction Terminology. RESULTS: A crude analysis identified 132 signals from 655 reported combinations of gastrointestinal AEFI. Adjusting for confounding by age, sex, year of report and country of report, where appropriate, reduced the number of signals identified to 88. The addition of a Bayesian hierarchical model identified four further signals and removed three. Effect modification by age and sex was identified for six vaccines for the outcomes of vomiting, nausea, diarrhoea and salivary gland enlargement. CONCLUSION: This study demonstrated a sequence of methods for routinely analysing spontaneous report databases that was easily understandable and reproducible. The combination of classical and Bayesian methods in this study help to focus the limited resources for hypothesis testing studies towards adverse events with the strongest support from the data.

The placement of South African strains of Beauveria in a phylogeny inferred from rDNA ITS1-5.8S-ITS2 sequences.

This study aimed to confirm the identity of three strains of the entomopathogenic fungus Beauveria bassiana from South African soils and to investigate their phylogenetic relationship with non-indigenous strains from other geographic regions. Sequences of the rDNA ITS1-5.8S-ITS2 region of 23 strains were compared with the Genbank reference sequences of 20 other cosmopolitan strains. Fitch parsimony and neighbor-joining analyses of the ITS1-5.8S-ITS2 regions resolved the strains into two distinct clades and matched them to four species groups/lineages: Beauveria bassiana, B. cf. bassiana (pseudobassiana), B. brongniartii and B. caledonica. Two of the South African strains initially identified as B. bassiana grouped with B. caledonica, whereas the third strain was confirmed as B. bassiana. Because of the paucity of Genbank references for B. caledonica, we have designated the two South African B. caledonica strains as B. sp. aff. caledonica. Other reassignments included two strains from Norway, originally classified as B. bassiana, being grouped with B. brongniartii, and three of the B. brongniartii reference taxa from Brazil which were clearly placed in the B. bassiana clade. The study provides a first report of the presence of the B. caledonica lineage in Africa and confirms current Beauveria phylogenies inferred from molecular data.

Current advances in understanding of immunopathology of atherosclerosis.

The importance of the involvement of the immune system in the development and progression of atherosclerosis was first suggested after the discovery of T cells in atherosclerotic lesions in 1990s. In order to be activated, T cell needs to be presented with an antigen but how this occurs in atherosclerosis has been unclear until recently. Current research has recognised dendritic cells as key initiators and regulators of immune processes in atherosclerosis. Accumulating evidence has revealed novel functions of several subsets of regulatory T cells, which have been shown to maintain immunological tolerance to self-antigens and to inhibit atherosclerosis development by suppressing the inflammatory response of effector T cells. Recent studies have also revealed the importance of natural killer T cells and their interaction with dendritic cells in atherogenesis. This review briefly summarises recent advances in the understanding of immune mechanisms in atherosclerosis and highlights the perspective of immunisation as an approach against this disease.

Cyclin D1 immunoreactivity in normal endocervix and diagnostic value in reactive and neoplastic endocervical lesions.

It may be difficult to distinguish reactive glandular lesions from adenocarcinoma in situ of the uterine cervix, and although several immunohistochemical markers have established value in this diagnostic setting, none is completely reliable. We have noted that neoplastic endocervical lesions often show loss of nuclear cyclin D1 expression in contrast to benign glandular cells. Therefore, we investigated cyclin D1 staining in a series of 64 cervical biopsy specimens including examples of normal and reactive endocervical epithelium, adenocarcinoma in situ, stratified mucin-producing intraepithelial lesions, and invasive adenocarcinoma. Thirteen specimens also included a component of high-grade cervical squamous intraepithelial neoplasia. Normal endocervical epithelium usually expressed cyclin D1, although staining was typically focal, and there was increased immunoreactivity in reactive and metaplastic glandular cells including tubo-endometrioid metaplasia. In contrast, most cases of adenocarcinoma in situ were completely negative and, therefore, cyclin D1 staining distinguished benign from neoplastic epithelial cells. Although focal cyclin D1 expression was observed in 5/19 cases of adenocarcinoma in situ, the staining was associated with more marked cytological atypia precluding confusion with a reactive process. The invasive adenocarcinomas were mainly negative for cyclin D1. However, focal staining was observed in 10/19 cases and was mainly restricted to cells at the deep tumor margin, or to small infiltrative glands and detached cell clusters within the stroma. In conclusion, cyclin D1 can be included within an immunohistochemical panel to aid in the distinction between reactive cervical glandular lesions and adenocarcinoma in situ. The localized distribution of staining within invasive lesions suggests that cyclin D1 up-regulation has a specific role during the progression of some endocervical adenocarcinomas.