Consideration of hereditary effects in the radiological protection system: evolution and current status.

PURPOSE: The purpose of this paper is to provide an overview of the methodology used to estimate radiation genetic risks and quantify the risk of hereditary effects as outlined in the ICRP Publication 103. It aims to highlight the historical background and development of the doubling dose method for estimating radiation-related genetic risks and its continued use in radiological protection frameworks. RESULTS: This article emphasizes the complexity associated with quantifying the risk of hereditary effects caused by radiation exposure and highlights the need for further clarification and explanation of the calculation method. As scientific knowledge in radiation sciences and human genetics continues to advance in relation to a number of factors including stability of disease frequency, selection pressures, and epigenetic changes, the characterization and quantification of genetic effects still remains a major issue for the radiological protection system of the International Commission on Radiological Protection. CONCLUSION: Further research and advancements in this field are crucial for enhancing our understanding and addressing the complexities involved in assessing and managing the risks associated with hereditary effects of radiation.

French guidelines for the management of oral lichen planus (excluding pharmacological therapy).

INTRODUCTION: Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. MATERIALS AND METHODS: Working groups from the Groupe d'Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the "formal consensus" method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. RESULTS: Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of "induced oral lichenoid lesions" were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. CONCLUSION: This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

[HIV prevention with PrEP: Challenges and prospects]. / Prévenir le VIH par la PrEP : enjeux et perspectives.

Pre-exposure prophlaxis (PrEP) is the use of antiretroviral drugs by uninfected people to prevent human immunodeficiency virus (HIV) infection. PrEP is used by people who are at substantial risk of being exposed to HIV. Numerous clinical trials have confirmed its effectiveness in reducing HIV acquisition and PrEP has been approved and allowed in several countries including France. However, PrEP uptake remains low as concerns about increase in sexual risk behaviour with PrEP use in the wake of a growing epidemic of sexually transmitted infections, and fear of drug resistance have been expressed. As a result, the difference between the proportion of people on PrEP and the proportion of people who would be very likely to use PrEP if they could access it -otherwise known as the PrEP gap- remains high. Nowadays, studies continue to explore long-term effects of PrEP as well as expand the array of available technologies and regimens.

Topical rapamycin versus betamethasone dipropionate ointment for treating oral erosive lichen planus: a randomized, double-blind, controlled study.

BACKGROUND: Although superpotent topical corticosteroids are the first-line treatment for oral erosive lichen planus (OELP), topical rapamycin was found efficient in a previous case series. OBJECTIVES: To compare the efficacy and safety of topical rapamycin and betamethasone dipropionate ointment for OELP in a randomized, double-blind trial. METHODS: Patients were randomized to receive treatment with betamethasone dipropionate ointment 0.05% in Orabase® or topical rapamycin solution (1 mg/mL) on lesions twice daily for 3 months, followed by 3 months of observation. The primary outcome was clinical remission after 3 months of treatment. Secondary outcomes were clinical remission after 1 and 2 months, reduced oral pain and reduced impact on food intake after 3 months, clinical recurrence after treatment withdrawal, and adverse events. RESULTS: During a 4-year period, 76 patients were randomized and 75 received treatment (rapamycin, n = 39; betamethasone, n = 36). At 3 months, 39.4% of patients with betamethasone and 27.3% with rapamycin showed clinical remission (odds ratio 0.68, 95% CI [0.24; 1.89]; P = 0.46). Rates of remission after 1 and 2 months, reduction in pain and impact on food intake after 3 months, were higher with betamethasone than rapamycin. Recurrence of oral erosions was similar between groups. Adverse events occurred in 43.6% of patients with rapamycin (mostly burning sensation, impaired taste) and 27.8% with betamethasone (mostly oral candidiasis). CONCLUSION: Although the study was limited by insufficient recruitment, we did not find any superiority of topical rapamycin over betamethasone dipropionate ointment for OELP. Given the rapid remission and pain improvement in the betamethasone group, it appears that superpotent topical corticosteroids should remain the first-line treatment for OELP.

Awareness among French healthcare workers of the transmission of multidrug resistant organisms: a large cross-sectional survey.

Background: Much effort has been made over the last two decades to educate and train healthcare professionals working on antimicrobial resistance in French hospitals. However, little has been done in France to assess perceptions, attitudes and knowledge regarding multidrug resistant organisms (MDROs) and, more globally, these have never been evaluated in a large-scale population of medical and non-medical healthcare workers (HCWs). Our aim was to explore awareness among HCWs by evaluating their knowledge of MDROs and the associated control measures, by comparing perceptions between professional categories and by studying the impact of training and health beliefs. Methods: A multicentre cross-sectional study was conducted in 58 randomly selected French healthcare facilities with questionnaires including professional and demographic characteristics, and knowledge and perception of MDRO transmission and control. A knowledge score was calculated and used in a logistic regression analysis to identify factors associated with higher knowledge of MDROs, and the association between knowledge and perception. Results: Between June 2014 and March 2016, 8716/11,753 (participation rate, 74%) questionnaires were completed. The mean knowledge score was 4.7/8 (SD: 1.3) and 3.6/8 (SD: 1.4) in medical and non-medical HCWs, respectively. Five variables were positively associated with higher knowledge: working in a university hospital (adjusted odds ratio, 1.41, 95% CI 1.16-1.70); age classes 26-35 years (1.43, 1.23-1.6) and 36-45 years (1.19, 1.01-1.40); medical professional status (3.7, 3.09-4.44), working in an intensive care unit (1.28, 1.06-1.55), and having been trained on control of antimicrobial resistance (1.31, 1.16-1.48). After adjustment for these variables, greater knowledge was significantly associated with four cognitive factors: perceived susceptibility, attitude toward hand hygiene, self-efficacy, and motivation. Conclusions: We found a low level of MDRO awareness and knowledge of associated control measures among French HCWs. Training on hand hygiene and measures to control MDRO spread may be helpful in shaping beliefs and perceptions on MDRO control among other possible associated factors. Messages should be tailored to professional status and their perception. Other approaches should be designed, with more effective methods of training and cognitive interventions. Trial registration: Clinical Trials.gov NCT02265471. Registered 16 October 2014 - Retrospectively registered.

Prescribers' experience and opinions on antimicrobial stewardship programmes in hospitals: a French nationwide survey.

OBJECTIVES: To assess prescribers' experiences and opinions regarding antimicrobial stewardship programme (ASP) activities. METHODS: A cross-sectional paper-based survey was conducted among prescribers in 27 out of 35 randomly selected large hospitals in France. RESULTS: All 27 investigated hospitals (20 non-university public, 4 university-affiliated and 3 private hospitals) had an ASP and an appointed antibiotic advisor (AA), with a median of 0.9 full-time equivalents per 1000 acute-care beds (IQR 0-1.4). Of the 1963 distributed questionnaires, 920 were completed (46.9%). Respondents were mainly attending physicians (658/918, 71.7%) and medical specialists (532/868, 61.3%). Prescribers identified two main ASP objectives: to limit the spread of resistance (710/913, 77.8%) and to improve patient care and prognosis (695/913, 76.1%). The presence of an AA constituted a core element of ASP (96.2% agreement between answers of ASP leader and respondents). Respondents acknowledged an AA's usefulness especially on therapeutic issues, i.e. choosing appropriate antibiotic (agreement 84.7%) or adapting treatment (89.6%), but less so on diagnostic issues (31.4%). Very few respondents reported unsolicited counselling and post-prescription controls. Three-quarters of prescribers identified local guidelines (692/918, 75.4%). Prescribers did not approve of measures counteracting their autonomy, i.e. automatic stop orders (agreement 23.4%) or pre-approval by AAs (28.8%). They agreed more with educational interventions (73.0%) and clinical staff meetings (70.0%). CONCLUSIONS: Prescribers perceived ASP mainly through its 'on-demand' counselling activities. They preferred measures that did not challenge their clinical autonomy. High levels of antibiotic consumption in French hospitals bring into question the effectiveness of such an approach. However, limited ASP staffing and resources may preclude extended activities.

Prevalence of carriage of extended-spectrum ß-lactamase-producing enterobacteria and associated factors in a French hospital.

OBJECTIVES: Our aim was to evaluate the prevalence and associated factors for carriage of extended-spectrum ß-lactamase-producing enterobacteria (ESBL-PE) in a healthcare facility. METHODS: In 2016 a serial cross-sectional survey of ESBL-PE carriage in a French university hospital was conducted. All patients present on the day of the survey were screened for ESBL-PE carriage. Demographic characteristics and risk factors for ESBL-PE carriage were collected. RESULTS: In all, 146/844 patients (17%) were digestive carriers of ESBL-PE; of these, 96 (66%) had not previously been identified. Among patients carrying ESBL-PE, Escherichia coli (62%) and CTX-M type (94%) predominated. Greater age, recent travel abroad, receipt of antibiotic, and prolonged hospitalization were associated with ESBL-PE carriage. CONCLUSION: Given the high prevalence of ESBL-PE and the high proportion of unknown carriers, our results strongly suggest reinforcing standard precautions rather than contact precautions for controlling the spread of ESBL-PE.

Salivary scintigraphy for Sjögren's syndrome in patients with xerostomia: A retrospective study.

OBJECTIVES: The value of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome remains controversial. The primary aim of this study was to estimate the diagnostic accuracy of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome among 237 patients with xerostomia. METHODS: We retrospectively compared eight scintigraphy parameters between 106 Sjögren patients and 131 non-Sjögren patients. RESULTS: Seven of the eight parameters were significantly decreased in patients with Sjögren; however, their diagnostic accuracy was low, with areas under the curves (AUCs) ranging from 0.58 (95% CI 0.50-0.65) to 0.63 (95% CI: 0.55-0.70). The prestimulatory oral activity index allowed discrimination between primary and secondary Sjögren's syndrome (AUC 0.73, 95% CI: 0.62-0.84), and the secretion velocity for parotid glands allowed discrimination between patients with Sjögren and burning mouth syndrome (AUC 0.71, 95% CI 0.59-0.82). CONCLUSION: The accuracy of scintigraphy parameters for the diagnosis of Sjögren's syndrome among patients with xerostomia was low; however, some functional indices appeared to assist discrimination between primary and secondary SS patients and between subgroups of patients with different causes of xerostomia.

High-frequency ultrasound quantification of acute radiation dermatitis: pilot study of patients undergoing radiotherapy for breast cancer.

BACKGROUND: Acute radiation dermatitis (ARD) is a frequent complication after breast cancer radiotherapy and is usually assessed by semi-quantitative clinical scores, which may be subject to inter-observer variability. High-frequency ultrasound imaging of the skin can reliably quantify thickness and edema in diseased skin. We aimed to compare the relative increase in dermal thickness of the irradiated zone in breast-cancer patients undergoing radiotherapy, with clinical severity. METHODS: A consecutive series of patients undergoing treatment for breast cancer by lumpectomy and radiotherapy in a 6-month period also underwent clinical and ultrasound evaluation of ARD. RESULTS: We included 34 female patients 17 had grade 1 (group 1), 17 had grade 2 or grade 3 ARD (group 2). The mean relative increase in dermal thickness in irradiated skin (RIDTIS) was greater for group 2 than 1: 0.53 vs 0.29 mm (P=.023). On univariate analysis, ARD was associated with skin phototype, breast volume and RIDTIS, and on multivariable analysis, breast volume and age remained predictive of the disease. CONCLUSION: Patients with more severe dermatitis showed significantly increased dermal thickness. Dermal thickness is a quantitative variable that could help quantify the efficacy of drugs and improve the treatment of this disease in patients undergoing radiotherapy.

Focal role of tolerability and reasonableness in the radiological protection system.

The concepts of tolerability and reasonableness are at the core of the International Commission on Radiological Protection (ICRP) system of radiological protection. Tolerability allows the definition of boundaries for implementing ICRP principles, while reasonableness contributes to decisions regarding adequate levels of protection, taking into account the prevailing circumstances. In the 1970s and 1980s, attempts to find theoretical foundations in risk comparisons for tolerability and cost-benefit analysis for reasonableness failed. In practice, the search for a rational basis for these concepts will never end. Making a wise decision will always remain a matter of judgement and will depend on the circumstances as well as the current knowledge and past experience. This paper discusses the constituents of tolerability and reasonableness at the heart of the radiological protection system. It also emphasises the increasing role of stakeholder engagement in the quest for tolerability and reasonableness since Publication 103.

Early Low Urinary CXCL9 and CXCL10 Might Predict Immunological Quiescence in Clinically and Histologically Stable Kidney Recipients.

We monitored the urinary C-X-C motif chemokine (CXCL)9 and CXCL10 levels in 1722 urine samples from 300 consecutive kidney recipients collected during the first posttransplantation year and assessed their predictive value for subsequent acute rejection (AR). The trajectories of urinary CXCL10 showed an early increase at 1 month (p = 0.0005) and 3 months (p = 0.0009) in patients who subsequently developed AR. At 1 year, the AR-free allograft survival rates were 90% and 54% in patients with CXCL10:creatinine (CXCL10:Cr) levels <2.79 ng/mmoL and >2.79 ng/mmoL at 1 month, respectively (p < 0.0001), and 88% and 56% in patients with CXCL10:Cr levels <5.32 ng/mmoL and >5.32 ng/mmoL at 3 months (p < 0.0001), respectively. CXCL9:Cr levels also associate, albeit less robustly, with AR-free allograft survival. Early CXCL10:Cr levels predicted clinical and subclinical rejection and both T cell- and antibody-mediated rejection. In 222 stable patients, CXCL10:Cr at 3 months predicted AR independent of concomitant protocol biopsy results (p = 0.009). Although its positive predictive value was low, a high negative predictive value suggests that early CXCL10:Cr might predict immunological quiescence on a triple-drug calcineurin inhibitor-based immunosuppressive regimen in the first posttransplantation year, even in clinically and histologically stable patients. The clinical utility of this test will need to be addressed by dedicated prospective clinical trials.

[Frequency of lymphoscintigraphic anomalies in the contralateral limb and progression of unilateral primary lymphedema in children]. / Fréquence des anomalies lymphoscintigraphiques infracliniques controlatérales et évolution des lymphœdèmes primaires unilatéraux de l'enfant.

BACKGROUND: Primary lymphoedema (LE) is the consequence of lymphatic insufficiency, usually associated with hypoplasia of the lymph vessels and/or nodes. Lymphoscintigraphy allows early diagnosis. OBJECTIVES: To assess the frequency of contralateral LE by lymphoscintigraphy in children with unilateral primary LE of one limb; to assess facets of clinical bilateralization of LE. METHODS: This retrospective single-centre study included children with unilateral LE followed up at the Tours university hospital centre between 2004 and 2014. Parents were contacted by phone to obtain follow-up data. RESULTS: Of the 13 children included, 6 (46%) displayed bilateral lymphatic anomalies on lymphoscintigraphy. Within a median follow-up period of 6 years, clinical bilateralization was observed in one girl after progression of her LE for 7 years; in her case, bilateral lymphatic insufficiency was detected at the initial lymphoscintigraphy. CONCLUSION: While contralateral subclinical lymphatic insufficiency is frequent in children with unilateral primary LE of the limbs, clinical bilateralization appears only rarely.

Serial lymphoscintigraphic findings in a patient with Gorham's disease with lymphedema.

Gorham's disease is a rare disorder characterized by vascular, "lymphangio- matous" and/or "hemangiomatous" lesions in bone and surrounding soft tissues. Associated lymphedema has not been reported and clinical evolution is unpredictable. Plain radiographs, CT, MRI, and occasionally bone scintigraphy, are used to detect the bone and soft tissues changes. Biopsy is a major component of the diagnostic process. We report the findings of serial lymphoscintigraphy in a young boy with a polyostotic Gorham's disease associated with lymphangioma of the thigh and lower limb lymphedema. In this patient, lymphoscintigraphy was useful for diagnosis and follow-up of primary lymphedema. It provided valuable information concerning the occurrence, location, and progression of lymphatic lesions in both bone and soft tissues.

Prospective multicentre observational study of lymphedema therapy: POLIT study.

OBJECTIVE: Lymphedema treatment is based on Decongestive Lymphedema Therapy (DLT) with an intensive phase followed by a long-term maintenance phase. This study aimed to observe volume variation over the intensive phase and 6 months later. METHODS: Prospective multicentre observational study of patients with unilateral lymphedema. The primary objective was to assess lymphedema volume variation between baseline, the end of intensive phase and 6 months later. Secondary objectives were to assess the frequency of heaviness limiting limb function and treatments safety predictors for volume reduction. RESULTS: Three hundred and six patients (89.9% women; 59.9±14.3 years old) with upper/lower (n=184/122) limb lymphedema were included. At the end of the intensive phase, median excess lymphedema volume reduction was 31.0% (41.7-19.9) followed by a 16.5% (5.9-42.3) median increase over the 6-month maintenance period phase. Previous intensive treatment was the only significant predictor of this response. As compared to baseline, heaviness limiting limb use was much less frequently reported at the end of the reductive phase (75.5% versus 42.3% respectively), and was more frequent at the end of the maintenance phase (62.6%). The most frequent adverse events reported were skin redness and compression marks (18.4 and 15.7% of patients, respectively). Blisters requiring treatment stoppage were rare (1.4%). CONCLUSIONS: Intensive phase decreases lymphedema volume and heaviness limiting limb function. The benefit is partially abolished after the first 6 months of maintenance. There is a need to consider how to provide optimal patient care for the long-term control of lymphedema.

Measurement of skin thickness and skin elasticity to evaluate the effectiveness of intensive decongestive treatment in patients with lymphoedema: a prospective study.

BACKGROUND: Complex decongestive physiotherapy (CDP) is used to treat patients with severe lymphoedema. The efficacy of CDP is usually quantified by calculating limb volume from repeated measurements of circumference at least 10 points before and after treatment of an affected limb. Measurement is time-consuming and operator-dependent. OBJECTIVES: To determine whether decreased dermal thickness is correlated with decreased volume after intensive CDP. METHODS: A consecutive series of patients admitted for intensive CDP were studied over a 6-month period. Before and after CDP, we measured circumference, dermal thickness elasticity and finally improvement in quality of life using a visual analogue scale (VAS). RESULTS: Thirty patients were included in the study. Only three patients were previously untreated. The average relative reduction in limb volume was 4% and the reduction in the dermal thickness was 15% (correlation: r = 0.37, P = 0.05). Viscoelasticity was decreased by 13%. VAS quality of life score was improved by 30%. CONCLUSION: Changes in dermal thickness are slightly correlated with volume changes before and after 5-day intensive CDP in a selected series of patients previously treated at home.

[D-penicillamine-induced pemphigus: changes in anti-32-2B immunostaining patterns]. / Autonomisation d'un pemphigus induit par la D-pénicillamine: évolution de l'immunomarquage par l'anticorps anti-32-2B.

BACKGROUND: It has been reported that D-penicillamine causes pemphigus that is typically superficial. Immunostaining with monoclonal anti-32-2B antibody targeting desmoglein 1 and 3 can help differentiate between drug-induced and classical auto-immune pemphigus. Absence of specific staining militates in favour of drug-induced pemphigus whilst positive staining suggests an auto-immune aetiology that is ongoing despite discontinuation of drug therapy. PATIENTS AND METHODS: A 59-year-old male patient was referred for management of superficial pemphigus 1 year after starting D-penicillamine treatment for scleroderma. The diagnosis of pemphigus was confirmed histologically (intra-epidermal cleavage, acantholysis and perikeratinocytes, deposition of IgG and complement C3). Immunochemical staining with anti-32-2B antibody was initially normal, in keeping with drug-induced pemphigus. Despite discontinuation of D-penicillamine, pemphigus recurred in 2008. A further skin biopsy was undertaken and anti-32-2B staining was abnormal, which is consistent with auto-immune pemphigus. DISCUSSION: Numerous cases of drug-induced pemphigus have been described in the literature. In approximately half of all cases, the pemphigus recedes after cessation of the causative drug. However, there have been no previous reports that changes over time in the immunostaining with anti-32-2B antibodies can mirror a change in form of pemphigus from a drug-induced type to an idiopathic type as well as the associated clinical feature of persistence after drug withdrawal. CONCLUSION: Normal staining with anti-32-2B antibody is associated with a favourable prognosis as regards resolution of drug-induced pemphigus. When, as in this case, status changes to abnormal staining, there is a risk that the pemphigus may become chronic despite discontinuation of therapy.

An overview of internet biosurveillance.

Internet biosurveillance utilizes unstructured data from diverse web-based sources to provide early warning and situational awareness of public health threats. The scope of source coverage ranges from local media in the vernacular to international media in widely read languages. Internet biosurveillance is a timely modality that is available to government and public health officials, healthcare workers, and the public and private sector, serving as a real-time complementary approach to traditional indicator-based public health disease surveillance methods. Internet biosurveillance also supports the broader activity of epidemic intelligence. This overview covers the current state of the field of Internet biosurveillance, and provides a perspective on the future of the field.

[Persistent aphthous mouth ulcers associated with tocilizumab: two cases]. / Ulcérations buccales aphtoïdes persistantes associées au tocilizumab: deux cas.

BACKGROUND: Tocilizumab, a humanized monoclonal antibody that blocks interleukin-6 receptor, is approved for use in rheumatological diseases. The most frequent adverse events reported are infections. We describe for the first time the occurrence of recurrent aphthous mouth ulcers in two patients on TCZ. PATIENTS AND METHODS: Two patients were treated with TCZ for rheumatological disease. A few weeks after administration of TCZ, they presented with multiple painful mouth ulcers that would not heal until TCZ had been withdrawn. In both cases, the oral ulcers resolved 6 to 7weeks after withdrawal of TCZ and readministration of the drug led to recurrence of oral ulcers within 10days in both patients. DISCUSSION: We describe for the first time the occurrence of aphthous mouth ulcers induced by TCZ. The causative role of TCZ was established by positive rechallenge. These cases were similar to a recently reported case of multiple intestinal aphthous ulcers occurring during TCZ treatment. Such mucosal side effects may be explained by similar inflammatory mechanisms but appear paradoxical because TCZ inhibits a pro-inflammatory cytokine, interleukin 6. TCZ treatment can be maintained if necessary, in combination with colchicine, as reported for one of our patients.

Contributions of SPECT/CT imaging to the lymphoscintigraphic investigations of the lower limb lymphedema.

Lymphoscintigraphy is a safe and reliable technique for investigating lymphedema. However, interpretation of delayed planar conventional imaging may be questionable due to the superimposition of soft tissues. Therefore, the aim of this retrospective study was to evaluate the contribution of single photon emission computed tomography/computed tomography (SPECT/CT) to lymphoscintigraphic investigation in a selected population with abnormal interstitial activity. Forty one patients with lower limb lymphedema either primary (n=17) or secondary (n=5), or associated with chronic venous insufficiency (n=19) underwent lymphoscintigraphy according to a standard protocol. SPECT/CT imaging that started immediately after planar imaging covered the part of the lower limbs with the most significant interstitial activity. The CT images were also analyzed separately to identify the typical honeycomb pattern of lymphedema. SPECT/CT identified additional abnormalities in vessels and soft tissues in 19 patients (46%). The additional information, primarily related to dermal collateralization of flow, dermal backflow, lymphangioma, and lymphorrhea, aided in understanding the physiopathology of edema and may have influenced management in 35 patients (85%). The honeycomb appearance of the soft tissues was noted on CT in most patients (90%). This study suggests that SPECT/CT is a promising addition to planar imaging in lymphoscintigraphic investigations of lymphedema.