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Monitoring of anti-drug antibodies in patients on ustekinumab is not routinely recommended in patients with inflammatory bowel disease (IBD) due to low rates of immunogenicity. Aim of study: The purpose of this study was to investigate the relationship between anti-drug antibodies detected by a drug-tolerant assay and loss of response (LOR) to therapy in a cohort of patients with IBD being treated with ustekinumab. Patients and Methods: This retrospective study consecutively enrolled all adult patients with moderate to severe active IBD who had at least 2 years of follow-up after ustekinumab was initiated. LOR was defined as CDAI > 220 or HBI > 4 for Crohn’s disease (CD) and partial Mayo subscore > 3 for ulcerative colitis (UC) and with a modification in disease management. Results: Ninety patients were included (78 CD and 12 UC; mean age 37 years). Median levels of anti-ustekinumab antibodies (ATU) were significantly higher in patients with LOR compared to those with ongoing clinical response (15.2 µg/mL-eq CI (7.9–21.5) and 4.7 µg/mL-eq CI (2.1–10.5), respectively; p = 0.04). The area under the ROC curve (AUROC) for ATU in predicting LOR was 0.76. The optimal cut-off point for identifying patients with LOR was 9.5 µg/mL-eq with a sensitivity of 80% and specificity of 85%. Uni- and multivariate analyses showed that serum ATU ≥ 9.5 µg/mL-eq (hazard ratio (HR) 2.54, 95%CI (1.80–5.93)), p = 0.022, prior vedolizumab (HR 2.78, 95%CI (1.09–3.34), p = 0.019) and prior azathioprine (HR 0.54, 95%CI (0.20–0.76), p = 0.014) exposures were the only factors independently associated with LOR to UST. Conclusion: In our real-life cohort, ATU was identified as an independent predictor of LOR to ustekinumab in patients with IBD.

Background: The FLURESP project is a public health research funded by the European Commission, with the objective to design a methodological framework to assess and compare the cost-effectiveness of existing public health measures against human influenza pandemics in four target countries: France, Italy, Poland and Romania. This article presents the results relevant to the Italian health system using a dataset specifically collected for this purpose. As most of interventions against human influenza are relavant against other respiratory diseases pandemics, potential interests in COVID-19 are discussed.Methods: Eight public health measures against human influenza pandemics pandemic were selected to be also relevant to other respiratory virus pandemics such as COVID 19: 1) individual (hand washing, using masks), 2) border control (quarantine, fever screening, border closure), 3) community infection (school closure, class dismissal, social distancing, limitation of public transport), 4) reduction of secondary infections (implementation of antibiotic therapy guidelines), 5) pneumococcal vaccination for at-risk people, 6) development of Intensive Care Unit (ICU) capacity, 7) implementation of life support equipments in ICU and 8) screening interventions (virus testing).The outcome "achieving a mortality reduction of higher or equal to 40%” has been selected as a meaningful effectiveness criteria from the public health perspective. Cost distributions have been taken into account according to the Italian health system using a uniform distribution. Results: In the frame of the major pandemic event observed in Italy in 2020, the most cost-effective strategies are “reduction of secondary infections” and “implementation of life support equipment in ICU”. The least cost-effective option during a major pandemic event is screening interventions.Conclusions: A number of intervention strategies against human influenza pandemics appears relevant against respiratory virus pandemics in general such as the COVID-19 pandemic. These pandemics are imposing a substantial economic burden in Italy, confirming the interest of considering the cost-effectiveness of public health measures to enlighten decision making.

Background Subungual squamous cell carcinoma (SU-SCC) is the most common malignant tumour of the nail unit. Intraoperative nail dermoscopy has been described only for pigmented tumours, onychomatricoma and glomus tumours. Aim To establish a description of intraoperative dermoscopic features of SU-SCC. Methods A single-centre retrospective cohort of 53 SU-SCC cases over a 5-year period was reviewed by six examiners who individually scored 31 intraoperative dermoscopic features as present or absent. For each feature, the frequency and interobserver agreement was evaluated, then the data were compared and a consensus was reached. Results No feature had perfect or substantial interobserver agreement. Regarding anatomy and architecture, most tumours involved both the nail bed and nail matrix (n = 34, 64.2%) and had nonparallel lateral side edges (n = 36, 67.9%). Regarding vascular features, several different patterns were found: dotted vessels (n = 49, 92.5%), irregular vessels (n = 47, 88.7%), curved vessels (n = 46, 86.8%), sagittal vessels (n = 45, 84.9%), milky-red areas (n = 42, 79.2%), linear and regular vessels (n = 30, 56.6%), coiled and hairpin vessels (n = 23, 43.4%), and arborizing vessels (n = 16, 30.2%). Pigmented dermoscopy structures included dotted purpura, grey granulation and splinter haemorrhages, which were found in 49 (20.8%), 9 (17%) and 9 (17%) cases, respectively. Other dermoscopic signs were pink background, translucent structureless area, whitish scaly areas, distal plug, yellowish scales and dots, and 'digitiform' proximal edge, which were found in 49 (84.9%), 49 (84.9%), 43 (81.1%), 37 (69.8%), 28 (52.8%) and 22 (41.5%) cases, respectively. Conclusion Analysis of this first large series of SU-SCC studied by intraoperative dermoscopy suggests that it gives useful information to better approach the diagnosis and to target biopsies.

Background: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. Objective: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). Methods: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. Results: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar (“brush-like”) pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. Limitations: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. Conclusion: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar (“brush-like”) pattern is a suggestive feature of congenital and congenital-type NMN.

Golimumab is a monoclonal anti-tumor necrosis factor alpha antibody, which is used in ulcerative colitis with an exposure-response relationship. The goal of this study was to compare results obtained with different immunoassays (golimumab and antigolimumab antibodies trough levels).This study was based on samples from 78 ulcerative colitis patients on golimumab treatment. Golimumab was quantified by either an anti-IgG detection antibody (Theradiag, Marne la Vallée, France) or an antibody directed against golimumab (Sanquin, Amsterdam, The Netherlands, KU Leuven, Leuven, Belgium, and Janssen RD, San Diego, CA). Bridging drug-sensitive enzyme-linked immunosorbent assays (Theradiag, Janssen RD, and KU Leuven), a bridging drug-tolerant enzyme-linked immunosorbent assay (Janssen RD), and a radioimmunoassay (Sanquin) were used to quantify antidrug antibody.Median serum golimumab levels were 4.5, 3.5, 4.9, and 2.4 mcg/mL with Theradiag, Sanquin, KU Leuven, and Janssen RD assay, respectively (P0.05). Correlation coefficients between assays ranged from 0.9 to 0.97. When using the KU Leuven and Janssen RD assays, 86% of samples were in the same quartile of distribution of values, and for Sanquin and Janssen RD assays, this overlap was 80%. The concordance observed for the other pairs was 83% (Sanquin/KU Leuven RD), 71% (Theradiag/KU Leuven), and 68% (Theradiag/Janssen RD and Theradiag/Sanquin). The specificity of assays for golimumab was demonstrated. Antidrug antibodies were detected in 28.2% of the samples with the Janssen RD drug-tolerant assay and in the same 2 patients by the 3 other assays.Performances of these immunoassays were similar in terms of quality, but differences in the quantitative results point to the importance of using the same assay consistently to monitor a patient's treatment.

Aim The aim of this study was to evaluate prospectively the clinical outcomes and pharmacokinetics of a second anti-TNF according to the pharmacokinetics of the first anti-TNF in patients with inflammatory bowel disease (IBD). Methods In patients in loss of response (LOR) to a first optimized anti-TNF and switched to a second anti-TNF, pharmacokinetics of anti-TNF were measured at the switch time, 30 weeks later, at the time of LOR, or at the end of the study (102 weeks). Results At the switch time, patients (n = 59) belonged to 4 groups according to the pharmacokinetics of the first anti-TNF: group 1 (n = 18), therapeutic trough levels; group 2 (n = 13) undetectable trough levels with antibodies against anti-TNF; group 3 (n = 13) without antibodies against anti-TNF; and group 4 (n = 15) subtherapeutic trough levels. After switching, the failure rates at week 30 and during the follow-up were as follows, respectively: in group 1 with therapeutic levels, 50% and 78%, despite therapeutic levels of the second anti-TNF in 83% of cases; in group 2 with undetectable levels and antibodies, 15% and 69% with undetectable levels of the second anti-TNF and antibodies in 85% of cases; in group 3 with undetectable levels without antibodies, 0% and 31% with therapeutic levels in 77% of cases; in group 4 with subtherapeutic levels, 13% and 33% with therapeutic levels in 73% of cases. Clinical remission rates were significantly lower (P ≤ 0.05) in groups 1 and 2 with therapeutic or undetectable levels with antibodies than in the 2 other groups. Conclusion In the case of LOR with therapeutic levels of the first anti-TNF or undetectable levels with antibodies, the switch to a second anti-TNF results in pharmacokinetic profile similar to the first one and again in LOR in most of the patients.

International audience; BACKGROUND: Several studies have reported a strong correlation between infliximab (IFX) trough levels (trough levels of infliximab [TLI]) and clinical remission (CR). We aimed to determine threshold values of TLI associated with the occurrence of CR, with or without normal inflammatory biomarkers, including serum C-reactive protein (CRP) and fecal calprotectin (fCal). METHODS: We included prospectively all consecutive patients with inflammatory bowel disease under IFX therapy (5 mg/kg every 8 wk) for at least 6 months. Disease activity (using the Crohn's Disease Activity Index or Mayo score) was recorded, and TLI, CRP, and fCal were measured before IFX infusion. RESULTS: Two hundred thirteen patients (131 Crohn's disease) were included. The median TLIs were higher in patients who achieved CR compared with those in patients who did not (2.6 versus 1.2 μg/mL, P \textless 0.01). The median TLI were higher in patients achieving CR with CRP normalization or CR with fCal \textless250 μg/g in comparison with patients with persistent elevated CRP or fCal (3.5 versus 1.6 μg/mL, P \textless 0.01 and 4.9 versus 1.8 μg/mL, P \textless 0.001, respectively). Finally, the median TLIs were higher in patients achieving CR with normal CRP and fCal \textless50 μg/g in comparison with patients without strictly normal biomarkers (5.9 versus 2.1 μg/mL, P \textless 0.001). The more the expected level of response to IFX was stringent, the more the median TLI and optimal thresholds were high. CONCLUSIONS: Threshold values of TLI differ according to therapeutic outcomes expected in patients with inflammatory bowel disease under maintenance therapy with IFX.

ObjectivesIn patients with IBD experiencing an immune-mediated loss of response (LOR) to antitumour necrosis factor (anti-TNF), algorithms recommend a switch of anti-TNF without immunosuppressive drug. The aim of our study was to compare in these patients two strategies: either switch to a second anti-TNF alone or with addition of azathioprine (AZA). After randomisation outcomes (time to clinical and pharmacokinetic failure) were compared between the two groups during a 2-year follow-up period.DesignConsecutive IBD patients in immune-mediated LOR to a first optimised anti-TNF given in monotherapy were randomised to receive either AZA or nothing with induction by a second anti-TNF in both arms. Clinical failure was defined for Crohn’s disease (CD) as a Harvey-Bradshaw index ≥5 associated with a faecal calprotectin level >250 µg/g stool and for UC as a Mayo score >5 with endoscopic subscore >1 or as the occurrence of adverse events requiring to stop treatment. Unfavourable pharmacokinetics of the second anti-TNF were defined by the appearance of undetectable trough levels of anti-TNF with high antibodies (drug-sensitive assay) or by that of antibodies (drug-tolerant assay).ResultsNinety patients (48 CDs) were included, and 45 of them received AZA after randomisation. The second anti-TNF was adalimumab or infliximab in 40 and 50 patients, respectively. Rates of clinical failure and occurrence of unfavourable pharmacokinetics were higher in monotherapy compared with combination therapy (p24 months). At 24 months, survival rates without clinical failure and without appearance of unfavourable pharmacokinetics were respectively 22 versus 77% and 22% versus 78% (pConclusionIn case of immune-mediated LOR to a first anti-TNF, AZA should be associated with the second anti-TNF.Trial registration number03580876.

BACKGROUND Vulvar melanosis can occasionally be clinically challenging by mimicking an early melanoma. OBJECTIVE To report our experience of initial evaluation and follow-up in this peculiar subset of vulvar melanosis using reflectance confocal microscopy (RCM). METHODS We retrospectively evaluated 18 consecutive cases referred for atypical vulvar pigmentation or for which melanoma was considered and that underwent both RCM examination and histopathological assessment. In 13 cases with available dermoscopic pictures, RCM classification was compared to dermoscopic diagnosis, and in all cases, the density of melanocytes was evaluated on biopsies using MelanA immunostaining. RESULTS Among the 18 atypical pigmented lesions, 17 vulvar melanosis and one melanoma were histologically determined. RCM concluded a benign vulvar melanosis in 10 of 17 cases, whereas dermoscopy did so in three of 12 cases. RCM identified the only early malignant lentiginous melanoma. In several cases of vulvar melanosis, RCM could identify foci of melanocytic hyperplasia in an otherwise benign pattern. CONCLUSIONS In this clinically and dermoscopically challenging subset of vulvar pigmentations, RCM appears relevant for initial extensive evaluation, especially to target initial biopsy sampling, and to perform non-invasive monitoring of foci of melanocytic hyperplasia.

International audience; PURPOSE: Vemurafenib (VMF) is a B-RAF inhibitor used in the treatment of B-RAF-V600-mutant metastatic melanomas. Reports of acute kidney injury (AKI) in patients treated with VMF are scarce. METHODS: To investigate the incidence and severity of AKI, we conducted a retrospective, observational, monocentric study in the Lyon Sud Hospital University, France, which included 74 patients with metastatic B-RAF-mutated melanomas treated with VMF, between June 2011 and August 2014. According to the Kidney Disease Improving Global Outcomes Guidelines, AKI is defined as an increase in serum creatinine concentration exceeding the baseline concentration by 1.5 fold. Serum creatinine was thus determined before treatment, on a monthly basis during treatment, and 3 months after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI-) and further subdivided into three groups according to AKI severity (stage 1, 2 or 3). To visualize the tissue damage caused by VMF, kidney biopsies were performed for two stage 1 AKI+ patients. RESULTS: Of the 74 patients, 30 (40.5 %) were AKI-, and of the 44 AKI+ patients (59.5 %), 29 (66 %) were diagnosed within the first three months of treatment. There were significantly more men in the AKI+ group: n = 33 (75 %) versus n = 12 (40 %) women, p = 0.004 with an odds ratio for developing AKI of 4.6 (95 % CI 1.48-14.23). Most AKI + cases were considered as stage 1 (n = 40; 91 %) and the remaining four (9 %) as stage 2 AKI. Kidney biopsies revealed interstitial fibrosis and acute focal tubular damage. However, renal failure was reversible in 80 % of patients within 3 months of VMF discontinuation. CONCLUSIONS: We observed frequent, reversible, moderately severe AKI with some histological evidence of tubular and interstitial damage in VMF-treated patients, suggesting that renal function should be carefully monitored in male patients, especially during the first 3 months.

International audience; BACKGROUND: Anti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in advanced melanoma. To date, no prospective data are available to give the best sequence of treatment. The objective of this study was to evaluate in real-life the efficacy of anti-PD-1 after BRAFi, ipilimumab, or chemotherapy failure. METHODS: This was a single institution cohort analysis in patients treated with anti-PD-1 right after BRAFi, ipilimumab, or chemotherapy failure. Melanoma evolution after anti-PD-1 initiation was analyzed in BRAF-mutated and BRAF wild-type patients. The efficacy of treatment was evaluated by Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS). RESULTS: Seventy-four patients were included: 33 wild-type and 41 BRAF-mutated melanoma. ORR to anti-PD-1 was significantly lower in BRAF-mutated patients (12.2% vs. 45.5%, p = 0.002). After anti-PD-1 initiation, the median PFS and OS was significantly shorter in the BRAF mutated group (2 vs. 5~months and 7 vs. 20~months, p = 0.001). The hazard ratio for disease progression was of 2.3 (95%CI:1.3-3.9; p = 0.003) and 2.5 (95%CI:1.3-4.5; p = 0.005) for death. Thirty-nine percent of BRAF-mutated-patients died within 3~months after anti-PD-1 initiation. Rapid death (

Background Drug de-escalation is considered in Crohn’s disease patients in sustained remission on optimized infliximab treatment. Aim We built a model to evaluate the magnitude of cost savings in patients’ disease course with or without drug de-escalation guided by infliximab trough levels. Methods We designed 4 virtual cohorts (P1–P4) of 10,000 patients in clinical remission on optimized infliximab treatment followed for 2 years. P1: no drug de-escalation — 10 mg/kg/8 weeks; P2: drug de-escalation from 10 mg/kg/8 weeks to 5 mg/kg/8 weeks according to trough levels; P3: no drug de-escalation — 10 mg/kg/6 weeks; and P4: drug de-escalation from 10 mg/kg/6 weeks to 10 mg/kg/8 weeks according to trough levels. For P2 and P4 cohorts, drug de-escalation was decided if trough levels were ≥7 μg/mL and no de-escalation if trough levels were Results The cost differences when comparing P1 versus P2 and P3 versus P4 were 7.6% and 4.6%, respectively, corresponding to costs savings of €30.5 millions and €20.3 million for 10,000 patients. Conclusion Over a 2-year period, infliximab de-escalation according to trough levels led to cost saving of about 6%, corresponding to around €25.4 million.

Background The increasing use of psychotropic drugs to treat anxiety and depressive disorders (ADDs) is concerning. According to the study, ‘Etude Pharmacoépidémiologique de l'Impact de Santé Publique des modes de prise en charge pour 3 groupes de pathologies’ (EPI3)-LASER, adult ADD patients who consult a general practitioner prescribing homeopathic medicines (GP-Ho) report less psychotropic drug use and are marginally more likely to experience clinical improvement than those receiving conventional care. We determined whether these observations also apply to patients ≥ 65 years old in the EPI3 cohort. Methods The EPI3-LASER study, conducted in France between March 2007 and July 2008, was a nationwide, observational survey of the three most common reasons for primary care consultation, including ADD, and the impact of the GPs' prescribing preferences: homeopathy (GP-Ho), conventional medicines (GP-CM) or mixed prescriptions (GP-Mx). This sub-analysis included 110 patients ≥ 65 years old with ADD from the EPI3 cohort who consulted either a GP-CM or GP-Ho. Socio-demographic and medical data and details of any medications prescribed were collected at inclusion. Information regarding the patients' functional status (Hospital Anxiety and Depression Scale [HADS)]) was obtained via a telephone interview 72 hours after inclusion, and at 1, 3 and 12 months post-inclusion. Medication use and outcome were determined over the 12-month period. Differences between the GP-CM and GP-Ho groups were assessed by multivariate logistic regression analysis. Results One hundred and ten patients were recruited and 87 (79.1%) with ADD (HADS ≥ 9) at the 72-hour interview were evaluated (age range: 65–93 years, 82.8% female). Patients who consulted a GP-Ho were more likely (odds ratio [OR] = 10.38, 95% confidence interval [CI]: 1.33–81.07) to have clinical improvement (HADS Conclusions Management of ADD patients aged ≥ 65 years by GP-Ho appears to have a real public health interest in terms of effectiveness and lower psychotropic drug use.

The wide use of cosmetics and their perceived benefits upon well-being imply objective descriptions of their effects upon the different dimensions contributing to the quality of life (QoL). Such a goal pleas for using relevant and validated scientific instruments with robust measurement methods. This paper discusses the interest of the new validated questionnaire BeautyQoL specifically designed to assess the effect of cosmetic products on physical appearance and QoL. After conducting a review of skin appearance and QoL, three phases of the international codevelopment have been carried out in the following sequence: semi-directed interviews (Phase 1), acceptability study (Phase 2), and validation study (Phase 3). Data collection and validation process have been carried out in 16 languages. This review confirms that QoL instruments developed in dermatology are not suitable to assess cosmetic products, mainly because of their lack of sensitivity. General acceptability of BeautyQol was very good. Forty-two questions have been structured in five dimensions that explained 76.7% of the total variance: Social Life, Self-confidence, Mood, Vitality, and Attractiveness. Cronbach's alpha coefficients are between 0.932 and 0.978, confirming the good internal consistency of the results. The BeautyQol questionnaire is the first international instrument specific to cosmetic products and physical appearance that has been validated in 16 languages and could be used in a number of clinical trials and descriptive studies to demonstrate the added value of these products on the QoL.

Background Utilization of sedative hypnotic drugs for sleeping disorders (SD) raises concerns, particularly among older people. This study compared utilization of conventional psychotropic drugs for SD among patients seeking care from general practitioners (GPs) who strictly prescribe conventional medications (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). Methods This was a French population-based cohort study of GPs and their patients consulting for SD, informed through the Pittsburgh sleep quality index (PSQI) questionnaire. Information on psychotropic drugs utilization was obtained from a standardized telephone interview at inclusion, one, three and 12 months. Results 346 patients consulting for SD were included. Patients in the GP-Ho group experienced more often severe SD (41.3%) than patients in the GP-CM group (24.3%). Adjusted multivariate analyses showed that patients who chose to be managed by GP-Ho were less likely to use psychotropic drugs over 12 months as opposed to the GP-CM group, with Odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.14 to 0.42. Patients in the GP-Mx group also used less psychotropic drugs but the result was not statistically significant (OR = 0.67; 95% CI: 0.39–1.16). Rates of clinical improvement of the SD did not differ between groups. Conclusions Patients with SD who chose to consult GPs certified in homeopathy consumed less psychotropic drugs and had a similar evolution of their condition to patients treated with conventional medical management. This result may translate in a net advantage with reduction of adverse events related to psychotropic drugs.

Background: Onychomatricoma is a benign tumor of the nail matrix with a precise histopathological definition but many different clinical features and differential diagnoses. Objectives: The diagnosis of onychomatricoma is based on the pathological examination of a surgical specimen. The objective of this study was to define preoperative diagnostic criteria using noninvasive investigations: observation and dermoscopy. Methods: A total of 34 cases of onychomatricoma were studied. In detail, 6 observers evaluated 12 clinical and 12 dermoscopical criteria as present or absent. Results: For clinical criteria, the highest mean values were leuconychia (3.21), splinter hemorrhages (3.45), and thickening of the plate (3.0). Dermoscopical criteria were more often found present, such as longitudinal parallel white lines (4.33), parallel lesion edges (4.61), splinter hemorrhages (4.48), dark dots (3.96), free-edge nail pitting (4.5), and thickening of the free edge (5.27). Conclusion: Dermoscopical criteria for onychomatricoma are more frequently present and less subject to divergent interpretation. This offers new and original preoperative reliable diagnostic criteria and should be used in the evaluation of nail tumors.

Importance The best surgical treatment modalities for subungual squamous cell carcinoma (SUSCC) without bone invasion need to be determined. The limited available data on Mohs micrographic surgery do not demonstrate its use as a standard procedure. A previous study in a limited series of patients has shown that wide surgical excision of the nail unit was associated with a low rate of recurrence. Objectives To confirm the efficiency of wide surgical excision of the nail unit with full-thickness skin graft reconstruction on a series of patients with SUSCC with an extended follow-up and to evaluate short- and long-term postoperative morbidity and patient satisfaction. Design, Setting, and Participants A consecutive series of 55 patients with biopsy-proven SUSCC without bone invasion treated by wide surgical excision of the nail unit followed by full-thickness skin graft reconstruction from January 1, 2000, to August 31, 2012 were included. After a minimum follow-up of 5 years, the recurrences were collected from the referring physicians. Statistical analysis was conducted from January 1 to June 30, 2016. Main Outcomes and Measures Demographic data, pathologic characteristics of tumors, postoperative follow-up, and recurrences were collected from medical records. Patients’ satisfaction with surgery, quality of life, and delayed postoperative morbidity (functional outcome and sensory disorders) were assessed from a questionnaire mailed to patients and physicians. Results Among the 55 patients (23 women and 32 men; mean age, 64 years), the mean follow-up was 6.6 years (range, 5.0-11.2 years), with a minimum follow-up of 5 years. Fifty-two questionnaires (95%) were returned. Two recurrences were observed. Minor early postoperative complications, such as graft infection and delayed wound healing, were seen in 6 patients; 8 patients experienced severe pain. Late postoperative complications included hypersensitivity to mechanical shocks (39 of 51 patients [76%]), mildly increased sensitivity to cold (38 of 51 patients [75%]), loss of fine touch sensation (17 of 35 patients [49%]), and epidermal inclusion cysts (9 of 51 patients [18%]). Most patients were very satisfied with cosmetic and global outcomes of the surgery. Conclusions and Relevance Total excision of the nail unit followed by a full-thickness skin graft is a safe and efficient treatment for SUSCC without bone involvement, with satisfying cosmetic and functional outcomes.

Background: Subungual squamous cell carcinoma (SSCC) is the most frequent tumor of the nail apparatus. Its diagnosis is often missed or delayed because the clinical presentation is atypical and can mimic other conditions. Accurate diagnosis can only be made by performing an appropriate surgical biopsy, but biopsy is painful and often leaves definitive dystrophic scars. The use of dermoscopy, a noninvasive technique, has been described to be useful for the preoperative evaluation of nail diseases. Objectives: To define the different clinical and dermoscopic presentations of SSCC and to compare them with onychomatricoma-associated clinical and dermoscopic features published in our previous study. Methods: A retrospective review of 44 cases of SSCC seen in our institution over an 8-year period. Six observers scored 19 clinical criteria and 14 dermoscopic criteria as present or absent. Then, we compared those data to a previously published study about the preoperative diagnosis of onychomatricoma. Results: Only 1 dermoscopic criterion was significantly associated with SSCC compared to onychomatricoma: localized hyperkeratosis (odds ratio, OR = 6.25, p = 0.012, 95% confidence interval CI = 1.50-26.01). In contrast, parallel edges (OR = 0.03, p < 0,001, 95% CI = 0.003-0.20) and sharp demarcation of the lesion (OR = 0.24, p = 0.004, 95% CI = 0.09-0.63) can statistically significantly be considered as in favor of onychomatricoma. By contrast, we believe that the presence of unparalleled lateral edges of the nail lesion or of fuzzy edges are more in favor of SSCC. Conclusions: Dermoscopy of the nail plate and of the nail free edge in SSCC provides useful information in order to better select cases to be submitted to biopsy.

Background: Pharmacists play a key role in primary healthcare, but the characteristics of patients who consult a pharmacist directly rather than going to their general practitioner (GP) are unknown. Our aim was to describe the socio-demographic and clinical characteristics of patients who seek direct therapeutic advice from a pharmacist for influenza-like illness (ILI) or ear, nose and throat (ENT) disorders, the types of medicines dispensed and patient satisfaction with the advice received. Methods: This prospective, observational study was carried out on arandom sampleof French pharmacies between November 2010 and March 2011. Patients (‡12-years) with early symptoms of ILI or ENT disorders (

Cognitive dysfunction is increasingly recognized as a symptom in mental conditions including schizophrenia, major depressive disorder (MDD), and bipolar disorder (BPD). Despite the many available cognitive assessment instruments, consensus is lacking on their appropriate use in clinical trials. We conducted a systematic literature review in Embase, PubMed/Medline and PsychINFO to identify appropriate cognitive function instruments for use in clinical trials of schizophrenia, MDD, and BPD. Instruments were identified from the articles. Instruments and articles were excluded if they did not address schizophrenia, MDD, or BPD. Instrument appropriateness was further assessed by the criteria of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative: test-retest reliability, utility, relationship to functional status, potential changeability to pharmacological agents, and tolerability and practicality for clinical trials. The database search yielded 173 articles describing 150 instruments used to assess cognitive function. Seventeen additional instruments were identified through Google and clinicaltrials.gov. Among all these, only 30 (18%) were deemed appropriate for use in the diseases of interest. Of these, 27 were studied in schizophrenia, one in MDD and two in BPD. These findings suggest the need for careful selection of appropriate cognitive assessment instruments, as not all may be valid in these disorders.

Blastic plasmacytoid dendritic cell neoplasm is a rare clinicopathologic entity, characterized by strong skin tropism and a poor prognosis. The diagnosis is generally made by skin biopsy with appropriate immunohistochemical studies. To identify potential biological prognostic factors for blastic plasmacytoid dendritic cell neoplasm, we performed an extended clinico-immunohistochemical study on a series of 91 well-documented cases collected since 1995 by the French Study Group on Cutaneous Lymphomas. Skin biopsies were analyzed using a panel of 12 immunohistochemical markers (CD4, CD56, CD123, CD303, TCL1, CD68, CD2, CD7, TdT, Ki-67, S100, and MX-1). The results were correlated with survival. The 5 most characteristic markers of this entity (CD4, CD56, CD123, CD303, and TCL1) were expressed simultaneously in only 46% of patients. However, when 4 markers were expressed the diagnosis could still be reliably made without resorting to any additional stains. Expression of TdT and/or S100 correlated with varying degrees of maturation. Statistical survival analyses showed that CD303 expression and high proliferative index (Ki-67) were significantly associated with longer survival.

In France, there are large discrepancies regarding flu between the severe disease described by Health Authorities and the disease that people face, considered as usual and benign. Flu prevention is useful, mainly through vaccination. For a well-established influenza-like illness, both individual measures dedicated to the limitation of the disease propagation and symptomatic treatment are to be initiated. Few clinical data are available regarding the most often used treatments for influenza-like illness (paracetamol, homeopathic and symptomatic treatments). The analysis did not show any decrease in the chances of success for patients with more often used drugs, either being under medical prescription, pharmacist advice or self-medication. In front of an influenza-like illness, the recommendations for daily practice can be based on 2 well-defined clinical situations: a specific management for patients at risk, and the influenza-like illness symptoms relief for the others, using a treatment specific for each patient.

The best noninvasive method predicting clinical relapse remains undetermined in infliximab (IFX)-treated patients with Crohn's disease.All patients with CD on IFX maintenance treatment and in clinical remission for at least 16 weeks, between 2011 and 2014, were enrolled in a prospective single-center study. The Crohn's Disease Activity Index (CDAI), fecal calprotectin, C-reactive protein levels, antibodies (ATI), and trough level (TLI) of IFX were measured at every IFX infusion. The best thresholds of TLI (2 versus 3 μg/mL) and calprotectin (50 versus 250 μg/g stools) were identified across four logistic regression models.One hundred nineteen patients (mean age: 34 ± 12 yrs, mean disease duration: 7.8 yrs) were included. Mean follow-up was 20.4 months, and 17% of the patients were on IFX and azathioprine at inclusion. During follow-up, 37 patients (31.1%) relapsed, 78% within the first 6 months. The clinical characteristics of the relapsed and nonrelapsed patients were similar. After logistic regression, fecal calprotectin250 μg/g stools (OR: 4.09; 95% CI, 1.01-16.21; P = 0.049) and TLI2 μg/mL (OR: 14.85; 95% CI, 3.67-60; P0.0001) were associated with loss of response. A training cohort of 55 patients was isolated randomly to implement prediction rules for loss of response. The best predictive rules were the combination of a TLI2 μg/mL and a fecal calprotectin level250 μg/g stools (78.3%). These rules were validated on a test cohort of 64 patients with an accuracy of 87%, (sensitivity = 0.94, specificity = 0.84, positive predictive value = 0.73, and negative predictive value = 0.97).In IFX-treated patients with CD in clinical remission, a combination of TLI (2 μg/mL) and fecal calprotectin (250 μg/g of stools) is a good model for predicting loss of response. In contrast with previous data, low TLIs ranging from 2 to 3 μg/mL should neither systematically lead to the optimization of IFX use nor a switch in the treatment.

Dermoscopy improves diagnostic accuracy in melanoma, as shown by several meta-analyses. Although it is used by general practitioners (GPs) in Australia, Canada and Italy, no published data on this topic are available in France.To review the opinions and use of dermoscopy by GPs in France and to understand their practice of skin examination.We designed a descriptive and cross-sectional survey and conducted it between 26 November and 26 December 2014. An anonymous, multiple-choice questionnaire about the demographic characteristics, skin examination modalities and use and training in dermoscopy was sent to 4057 GPs in four large regions of France. Pearson, χ(2) , Student, Welch and Fisher tests were used for cross-tabulation statistical analysis.Only 8% of respondents had access to a dermoscope; most were male practitioners and aged50 years. Dermoscopy increased self-confidence in analysing pigmented lesions (P = 0·004), and dermoscopy users referred fewer patients to dermatologists. The number of biopsies was reduced in the dermoscopy users group (P = 0·004). In total, 425 questionnaires were returned and analysed. Dermoscopy users took more time to evaluate a single pigmented lesion (P = 0·015). Only 16·9% of physicians declared having received some training on dermoscopy, yet this number reached 47% for those owning a dermoscope. Their training was mostly short and recent. Overall 29·2% of the respondents said the main advantage was to reduce the number of referrals to the dermatologists (P = 0·004), while its main disadvantage was the necessity of training (54·6%). Our responders declared they could spend seven working days on a dermoscopy training course.Our study demonstrates positive opinions regarding dermoscopy, despite a minority of French GPs using this technique in the areas surveyed. The need for formal training appears to be the main limitation to wider use. Appropriate and specifically designed training programmes should be offered.

Summary Background Dermoscopy is now recognized as an essential tool for discriminating melanoma from other pigmented lesions, as corroborated by several robust meta-analyses. Although it is considered to be widely used in European countries, no published data on this topic are available to date, unlike in Australia and the U.S.A. Objectives To describe and quantify the use and learning of dermoscopy among French private practice dermatologists. Methods A questionnaire of 19 items regarding demographic characteristics, dermoscopy use and training, and physician’s judgment on dermoscopy was mailed to all French private practice dermatologists. Only questionnaires with an answer to the key item, ‘Do you use dermoscopy?’ were taken into account. Results Of 3179 mailed questionnaires, 1611 were returned and 1576 were analysable (49·6%). Most respondents declared using dermoscopy (94·6%), using their dermoscope several times a day (82·7%) and/or for the diagnosis of nonpigmented lesions (87·7%). Physicians learned dermoscopy mainly through books (75·8%) and/or conferences (88·6%); 12·8% reported a dedicated university degree. Dermoscopy helps to detect melanoma earlier and to perform fewer biopsies according to 86·6% and 74·6%, respectively. On multivariate analysis, female sex and age under 45 years were significantly associated with higher utilization rate of dermoscopy [odds ratio 1·89, 95% confidence interval (CI) 1·15–3·10; and 2·85, 95% CI 1·14–7·11, respectively]. Conclusions This is the first published nationwide survey of dermoscopy practice in Europe. Despite potential classification and/or selection bias, the particularly high penetration rate found in our study suggests that dermoscopy is now widely accepted by French private practice dermatologists for the routine management of both pigmented and nonpigmented lesions.

Introduction L’etude moleculaire des genes de predisposition au melanome est actuellement proposee en France, pays de faible a moyenne incidence, en presence d’au moins 2 cas de melanomes cutanes invasifs ou cancers associes, avant 75 ans, chez un meme individu ou apparente au 1er ou 2e degre. L’objectif, defini par l’ASCO a partir d’etudes precliniques sur des populations selectionnees, est de s’approcher du seuil de 10 % de probabilite de trouver une mutation. Le but de cette etude etait de reevaluer ces criteres dans une etude de pratique clinique incluant 1032 patients. Materiel et methodes Les patients ayant fait l’objet d’une recherche de mutation sur les genes de predisposition au melanome CDKN2A, CDK4, MC1R et MITF dans les CHU de Lyon et d’Angers entre 2004 et 2015 ont ete recenses. Ils repondaient tous a la « regle des 2 », a savoir 2 cas de melanomes ou cancers associes chez un meme patient ou apparente au 1er ou 2e degre. Le critere d’evaluation principal etait le pourcentage de mutation positive dans les groupes « regle des 2, 3 ou 4 cas ». Le critere secondaire etait l’impact de l’âge au premier melanome sur le taux de mutation. Les incertitudes anamnestiques etaient repertoriees afin de mesurer l’importance du biais de classification sur l’acces au depistage. Resultats Une mutation etait presente chez 67/1032 patients (6,5 %) ; 38/408 (9,3 %), dans le groupe repondant a la « regle des 3 » (p = 0,677) et 32/263 (12,1 %, p = 0,12) dans le groupe avec âge inferieur a 40 ans au premier melanome. Sept patients porteurs d’une mutation CDKN2A n’auraient pas ete detectes en suivant la « regle des 3 » ou la « regle des 2 » et âge inferieur a 40 ans au 1er melanome. Des incertitudes anamnestiques etaient relevees chez 8,5 % des patients. Si celles-ci avaient conduit a ne pas realiser de test genetique, un patient porteur d’une mutation MITF n’aurait pas ete depiste. Discussion Il s’agit de la premiere etude de « vraie vie » reevaluant la pratique du depistage moleculaire des genes de predisposition au melanome. L’objectif de 10 % de mutation positive n’est pas atteint en suivant la « regle des 2 ». Le passage a la regle des 3 serait donc recommande en France. L’ajout d’une exception en cas d’âge au premier melanome inferieur a 40 ans permet de reduire le nombre de patients non depistes. Une recente etude internationale de population trouve un taux de 6,5 % de mutations positives pour les pays europeens, proche de nos resultats. Les autres etudes europeennes obtiennent des taux plus eleves, sur des populations tres selectionnees ou avec presence d’un effet fondateur. Conclusion Cette premiere etude de terrain conduit a proposer un depistage genetique selon la « regle des 3 » cas de melanomes ou cancers associes chez un meme patient ou apparentes au 1er ou 2e degre, sauf en cas de melanome avant l’âge de 40 ans ou la regle des 2 reste indiquee.

Summary Background The dermoscopic criteria for benign and malignant lesions on the vulva are not well established due to the lack of large series of such lesions. Melanoma should always be included in the differential diagnosis of pigmented lesions on the vulva especially when they are wide, or of recent onset. Elsewhere on the skin dermoscopy plays an important role in the selection of suspicious pigmented lesions, as well as in the selection of the best site to perform the biopsy. Objectives To analyse the dermoscopic patterns observed in pigmented lesions of the vulva. Methods We analysed a nonselected consecutive series of 68 histopathologically proven cases comprising five melanomas, 16 naevi, 20 lentigos, 12 benign vulval melanoses, 11 cases of postinflammatory pigmentation, three pigmented cases of usual vulval intraepithelial neoplasia (VIN) and one seborrhoeic keratosis seen at our institution. The dermoscope was covered by translucent disposable food wrap and/or antibacterial gel to prevent possible transmission of infections. Descriptive statistics were performed using multiple correspondence analysis. Results The parallel (37%), ring-like (9%), homogeneous (22%), globular-like (13%) and reticular-like (6%) patterns were observed on benign lesions (naevi, lentigo, vulval melanosis and postinflammatory pigmentation). The cerebriform pattern (6%) was observed only on VIN and seborrhoeic keratosis. The multicomponent pattern (6%) was associated with melanoma (60%). In cases of melanoma we also occasionally observed an irregular pattern, a whitish or blue-whitish veil, irregularly distributed dots and globules and atypical vascular pattern. Using multiple correspondence analysis, we designed a new algorithm for the early detection of vulval melanomas. Conclusions Dermoscopy can play a role in the noninvasive classification of vulval melanosis. However, further studies of larger collaborative series are needed to validate our vulval melanoma diagnostic algorithm. VIN and seborrhoeic keratosis share the same dermoscopic features and biopsy should be considered for seborrhoeic-like keratosis. In case of doubt pathological examination of a biopsy remains mandatory.

National audience; Information systems are recognized like precious tools of strategic scheduling and help to the decision, especially in the sector of health. They don a particular interest for the developing countries, even though their performance to this level is even insufficient. The moribund functionality of the health systems in sub-Saharan Africa seems to be for most of the time justified by a lack of resources (human, financial, material, techniques, etc.) and occult the survivals of the cultural and social practices that constitute heavy burdens, or even of the necks in which these systems of information himself stall. The essential objective of this work consists in demonstrating how the elements of the oral tradition constitute some handicaps in the support, the transmission, the storage of information and help to the decision in a process of scheduling and working of the sanitary structures.; Les systèmes d'information sont reconnus comme des outils précieux de planification stratégique et d'aide à la décision, particulièrement dans le secteur de la santé. Ils revêtent un intérêt particulier pour les pays en voie de développement, même si leur performance à ce niveau reste encore insuffisante. La fonctionnalité irrégulière des systèmes de santé en Afrique subsaharienne semble la plupart du temps être justifiée par un manque de ressources (humaines, financières, matérielles, techniques, etc.) et occulte les survivances des pratiques culturelles et sociales qui constituent de lourds fardeaux, voire des goulots dans lesquels ces systèmes d'information s'enlisent. L'objectif essentiel de ce travail consiste à démontrer comment les éléments de la tradition orale constituent des handicaps dans le support, la transmission, le stockage de l'information et l'aide à la décision dans un processus de planification et de fonctionnement des structures sanitaires.

Resume Introduction Aucune etude prospective n’a ete menee a l’echelle de la France pour decrire la prise en charge therapeutique des keratoses actiniques (KA) et des carcinomes basocellulaires superficiels (CBC-S). Le but de l’etude etait de decrire les modalites de traitement des KA multiples et des CBC-S par les dermatologues francais et d’estimer la totalite des couts directs induits par leur prise en charge therapeutique initiale. Malades et methodes Il s’agissait d’une etude observationnelle prospective, menee en France de janvier a juin 2004 aupres d’un echantillon representatif de dermatologues qui devaient inclure les cinq premiers malades ayant un ou plusieurs CBC-S et le premier malade ayant au moins quatre KA sur 4 semaines non consecutives. Les donnees suivantes etaient colligees : date de naissance, sexe, habitat, profession, regime d’assurance-maladie, siege, nombre et taille maximale des lesions. Les modalites de prise en charge therapeutique, les praticiens impliques et les examens complementaires demandes etaient recueillis prospectivement sur les 3 mois suivant le diagnostic. Les couts engendres etaient estimes selon les indicateurs habituels (NGAP, Vidal, PMSI). Resultats Cinq cent douze malades ayant un CBC-S (âge moyen : 69 ans ; sex-ratio H/F : 0,92) ont ete inclus. Le CBC-S etait unique dans 80 p. 100 des cas, inferieur a 2 cm dans 90 p. 100, situe sur la tete et le cou dans 51 p. 100 et sur le tronc dans 37 p. 100. Une confirmation histologique a ete documentee dans 85 p. 100 des cas. Le traitement a ete l’exerese chirurgicale dans 70 p. 100 des cas, la cryotherapie dans 13 p. 100, l’application d’un topique dans 7 p. 100 et l’electrocoagulation dans 4 p. 100. Un suivi clinique a ete realise dans 79 p. 100 des cas. D’autre part, 226 malades avec au moins quatre KA (âge moyen : 76 ans ; sex-ratio H/F : 2,1) ont ete inclus. Les KA etaient situees sur la tete ou le cou dans 74 p. 100 des cas et sur le tronc dans 6 p. 100. Le traitement a ete la cryotherapie dans 92 p. 100 des cas. Le nombre moyen de consultation sur 3 mois etait de 1,53. Un audit de controle des donnees, mene sur site chez 5 p. 100 des investigateurs, montrait un taux de concordance de 98,8 p. 100. Discussion Il s’agit de la premiere etude prospective menee en France sur les modalites de prise en charge des CBC-S et des KA multiples, motifs frequents de consultation en dermatologie. Le traitement des CBC-S est le plus souvent chirurgical, en accord avec les recentes recommandations ANAES ; celui des KA est presque exclusivement represente par la cryotherapie. Par extrapolation, on peut estimer de 10,2 a 10,6 M€ le cout annuel de prise en charge des CBC-S par les dermatologues en France.

The provision of care for patients with end-stage chronic renal failure is an important medical and economic challenge for the Health Insurance. Previous studies have shown a lower cost for home dialysis. More recently, studies have confirmed identical short-term survival rates between haemodialysis and peritoneal dialysis. Notwithstanding, home dialysis techniques utilization remains weak in France. This work aims at: determining the average annual cost of dialysis, per patient and per technique of dialysis, and assessing the global annual cost of dialysis in France, from the Health Insurance perspective. Methodologically, this article provides a static estimation of the cost of dialysis. Costs related to co-morbidities of end-stage chronic renal failure have not been considered. Standard patient care schemes have been outlined by a multidisciplinary expert committee, for each dialysis technique, and have been valorised using publicly available data and tariffs recorded in 2005. Our result show that home dialysis techniques are the less costly, with an average annual cost per patient of 49.9, 49.7 and 50.0 k euro respectively for home haemodialysis, automated peritoneal dialysis, and continuous ambulatory peritoneal dialysis. Autodialysis, autonomous in-center haemodialysis and in-center haemodialysis respectively cost 59.5, 62.3 and 81.5 k euro per patient and per annum. The total 2005 cost of dialysis for the Health Insurance is estimated at 2.1 billion euro. Therefore, the development of alternative techniques to in-center haemodialysis, such as home dialysis or autonomous in-center haemodialysis, autodialysis being already well developed, could generate savings for the Health Insurance. From the patient's perspective, it could also allow the enlightened choice of the best customized technique, less guided by local offer than by medical or social criteria, as well as by the patient's own opinion.

Background : The use of pharmacokinetics is associated with cost savings in anti-tumor necrosis factor (anti-TNF) therapy, but the long-term cost savings in a large cohort of Crohn’s disease (CD) patients are unknown. Aim : The goal of this study was to compare the cost of anti-TNF therapy in two cohorts of CD patients losing response to infliximab, one using a test-based strategy and one an empirical dose escalation. Methods : We used a selected mathematical model to describe the trajectories of CD patients based on a discrete event system. This design allowed us to track over a given period a double cohort of patients who moved randomly and asynchronously from one state to another, while keeping all the information on their entire trajectory. Both cohorts were modeled using state diagram parameters where transition probabilities from one state to another are derived from literature data. Costs were estimated based on the French health care system. Results : Cost savings among the 10,000 CD patients using a test-based strategy were €131,300,293 at 5 years. At 5 years the mean cost saving was €13,130 per patient. The direct cost of the test had no impact on the results until the cost per test reached €2,000. Conclusions : A test-based strategy leads to major cost savings related to anti-TNF therapy in CD. Keywords: infliximab; pharmacokinetics; adalimumab; Crohn’s disease; cost saving (Published: 30 October 2015) Citation: Journal of Market Access & Health Policy 2015, 3 : 29229 - http://dx.doi.org/10.3402/jmahp.v3.29229

Skin pigmentary disorders and uneven skin tone represent common cosmetic concerns in Japan where fairer skin is culturally desirable. As the demographics of Asian countries continue to evolve, there is a need to understand the impact of cosmetic skin concerns on quality of life (QoL). 199 Japanese women self-claiming facial skin pigmentation disorders were asked to complete the BeautyQoL questionnaire, and the results were compared with those of a control group of 200 women. Of the fi ve dimensions of the BeautyQoL questionnaire, the dimension “ mood ” appeared to be signifi cantly lower in the group presenting facial dark spots, as compared with the control group ( p 0.05). In the group presenting facial dark spots, the fi ve dimensions and the global score showed that subjects concerned had lower scores than subjects less concerned, even if statistical signifi cance was not reached. This study confi rms that common pigmentary disorders such as facial black spots may negatively impact QoL. Further comparative studies with a controlled randomized design would be necessary to confi rm these fi ndings.

Health authorities are constantly searching for new ways to stabilise health expenditures. To explore this issue, we compared the costs generated by different types of medical practice in French general medicine: i.e. conventional (CM-GP), homeopathic (Ho-GP), or mixed (Mx-GP). Data from a previous cross-sectional study, EPI3 La-Ser, were used. Three types of cost were analysed: (i) consultation cost (ii) prescription cost and (iii) total cost (consultation + prescription). Each was evaluated as: (i) the cost to Social Security (ii) the remaining cost (to the patient and/or supplementary health insurance); and (iii) health expenditure (combination of the two costs). With regard to Social Security, treatment by Ho-GPs was less costly (42.00 € vs 65.25 € for CM-GPs, 35 % less). Medical prescriptions were two-times more expensive for CM-GPs patients (48.68 € vs 25.62 €). For the supplementary health insurance and/or patient out-of-pocket costs, treatment by CM-GPs was less expensive due to the lower consultation costs (6.19 € vs 11.20 € for Ho-GPs) whereas the prescription cost was comparable between the Ho-GPs and the CM-GPs patients (15.87 € vs 15.24 € respectively) . The health expenditure cost was 20 % less for patients consulting Ho-GPs compared to CM-GPs (68.93 € vs 86.63 €, respectively). The lower cost of medical prescriptions for Ho-GPs patients compared to CM-GPs patients (41.67 € vs 63.72 €) was offset by the higher consultation costs (27.08 € vs 22.68 € respectively). Ho-GPs prescribed fewer psychotropic drugs, antibiotics and non-steroidal anti-inflammatory drugs. In conclusions management of patients by homeopathic GPs may be less expensive from a global perspective and may represent an important interest to public health.

Resume Introduction Les hemorragies liees au traitement par antivitamines K (AVK) ont en France la premiere place des accidents iatrogenes. Objectifs L’etude internationale, observationnelle, longitudinale et retrospective ISAM avait pour but d’evaluer l’utilisation des AVK et la qualite de leur suivi biologique en pratique medicale courante. Methodes Dans l’etude francaise, des medecins generalistes et des cardiologues representatifs ont selectionne des patients traites pendant au moins 60 jours au cours des 12 derniers mois par des AVK pour fibrillation auriculaire non valvulaire. Les donnees retrospectives sur un an ont ete recueillies a l’aide de questionnaires standardises aupres des medecins et de leurs patients. Resultats Au total, 43 generalistes et 20 cardiologues ont inclus 278 patients qui ont complete les questionnaires. Deux cent soixante-quatre patients ont eu au moins 2 INR (International Normalized Ratio) pendant la periode de l’etude. Dans l’annee precedant l’inclusion, les patients ont passe 59% du temps avec un INR dans l’intervalle therapeutique 2,0–3,0et 27% du temps avec un INR > 3. Les medecins declaraient donner des recommandations ecrites concernant la posologie des AVK a pres de la moitie de leurs patients, mais seuls 3% leur remettaient un carnet d’information et de surveillance de traitement par AVK. L’information du traitement etait assuree par le medecin generaliste pour 65% des patients. Toutefois, 18 % des patients disaient ne pas etre informes sur leur traitement, 44% ne connaissaient pas leur INR cible et 66% ne savaient pas qu’un saignement devait les alerter. Le port d’une carte indiquant le traitement par AVK a ete rapporte par 45% des patients. Conclusion II existe une place importante a l’education therapeutique pour ameliorer la prise en charge, le bon usage et le suivi biologique du traitement par AVK aupres des medecins et des patients.

Le pharmacien joue un role important en tant que professionnel de sante de premier recours dans le cadre des affections hivernales respiratoires. Les personnes presentant des symptomes averes s’adressant directement aux pharmaciens veulent etre soulagees rapidement et efficacement. Le conseil associe des medicaments homeopathiques a des antalgiques et des antipyretiques chez un quart des personnes, avec pour objectif d’apporter le soulagement attendu. Celui-ci survient effectivement en trois jours en moyenne, ce qui satisfait les clients.

In France, non-homeopathic general practitioners (GPs) often use antibacterials to treat children with recurrent acute viral rhinopharyngitis; whereas homeopathic GPs tend to use homeopathic medicines. We compared the effectiveness, the quality of life of the parents, and the direct and indirect costs associated with treatment from homeopathic and non-homeopathic GPs. We assessed the direct (consultations, medicines, further tests) and indirect (time off work) costs of the two types of treatment to society, the patient, and social security. We also assessed the effectiveness of the treatment received and the quality of life of the parents. Of the 499 children included, 231 were treated by 62 non-homeopathic GPs and 268 by 73 homeopathic GPs. The effectiveness (assessed as complications/patient, total number of adverse events, and quality of life) [mean overall Parents of children with Ear, Nose, and Throat infections Quality of Life questionnaire© scale score] was better in the homeopathic GP group than in the non-homeopathic GP group. No significant difference was found between the two groups for the total costs to social security (€98.55 for homeopathic GPs vs €96.17 for non-homeopathic GPs). Homeopathic GPs initiated preventive treatment in 82.2% of their patients and used antibacterials in 20.9% of their patients, while non-homeopathic GPs initiated preventive treatment in 43.3% of patients and prescribed antibacterials for 89.6% of patients. This study produced new findings that indicate that, in France, acute rhinopharyngitis is handled differently by homeopathic GPs and non-homeopathic GPs: homeopathic GPs prescribe fewer antibacterials than non-homeopathic GPs for the treatment of recurrent acute rhinopharyngitis in children aged between 18 months and 4 years. Moreover, homeopathic treatment gave better results in terms of pragmatic medical effectiveness (fewer episodes and fewer complications) and the parents’ quality of life, with similar total medical costs to social security. However, this study is potentially biased by the lack of homogeneity of the two patient-samples in terms of the ‘passive smoking’, ‘patient age’, ‘childcare’, and ‘type of occupation’ criteria because our study protocol did not provide for prior matching of the two patient-samples with respect to these criteria. The observations found in this study need to be confirmed by randomized clinical trials.

Background: Migraine is a prevalent and incapacitating condition that affects individuals in the prime of their productive life, thus generating an economic burden for both society and healthcare systems. The direct annual healthcare costs of migraine in France were assessed over 10 years ago, and the current study updates these figures. Objective: The objective of this study was to determine the economic cost (primarily direct costs) of migraine and other episodic headache in France based on a general population survey of headache, the GRIM2000 (Groupe de Researche Interdisciplinaire sur la Migraine). Design: From a representative general population sample of 10 585 individuals aged ≥15 years in France in 1999, 1486 individuals experiencing headaches were identified and interviewed regarding healthcare resource consumption in the previous 6 months. By applying unit costs to the resource data, costings (in 1999 values) were determined for physician consultations, hospitalisation, medication use and diagnostic/laboratory tests, and evaluated from a healthcare system perspective. Information on absenteeism and lost productivity was derived from the Migraine Disability Assessment Score (MIDAS) questionnaire. Results: The prevalence of migraine (including migrainous disorder) was determined to be 17%. Total annual direct healthcare costs were estimated to be €128 per individual with migraine in 1999, corresponding to €1044 million when extrapolated to all individuals experiencing migraine and aged ≥15 years. Around two-thirds of this cost accrued to the social security system (€698 million; €85 per individual). The total annual direct cost of other forms of episodic headache was much lower at €28 per individual (social security cost €18); with a prevalence of 9.2%, the annual national direct cost for other forms of episodic headache totalled €124 million. The principal cost element was physician consultations. However, it was found that many individuals had never consulted a physician for their headaches, and self-medication contributed substantially to the medication costs (the second greatest cost factor for migraine). The cost per individual rose steeply with increasing severity of headache. Conclusion: The direct healthcare costs of migraine do not seem to have risen significantly over the past decade. A small minority of individuals with more severe headaches consume most of the healthcare resources devoted to migraine, while most individuals generate relatively low direct costs. The total annual direct costs in France for migraine are almost 10-fold higher than those of other episodic headache.

International audience; The objective of this study was to describe the epidemiology, clinical presentation and consequences of chronic daily headache (CDH) in France. A representative nation-wide sample of the general population was identified using a stratified sampling method. Ten thousand five hundred and eight-five subjects were screened in face-to-face interviews, and data collected using a standard questionnaire. An overall point prevalence of CDH in the general population of 2.98% was observed. Two-thirds of these subjects presented migraine-like features. Severity, functional impact and healthcare consumption were higher than in subjects reporting episodic migraine in the same sample. Of the subjects, 28.2% reported the most severe migraine disability assessment scores (Grades 3 and 4), compared to 12% of episodic migraineurs. A qualité de vie et migraine score of 68.4 was observed, indicating severely attenuated quality of life. Only 6.6% of subjects were taking prophylactic treatment, whilst 88% were using non-specific acute headache treatments. The frequency of physician consultations and laboratory examinations was significantly higher than in individuals with episodic headache. CDH is thus a relatively prevalent condition in the general French population, associated with an important burden of suffering and with considerable expenditure in the health service. Management of this condition is generally inappropriate.

Importance Genetic testing for melanoma-prone mutation in France, a country with low to moderate incidence of melanoma, is proposed in cases with 2 invasive cutaneous melanomas and/or related cancers in the same patient, or in first- or second-degree relatives (rule of 2). In preclinical studies, these rules led to disclosure of mutation(s) in more than 10% of these families, the threshold widely accepted to justify genetic testing for cancers. Objective To reconsider these criteria in a general population testing of patients. Design, Setting, and Participants This was a retrospective study, performed from 2004 to 2015 at Angers and Lyons University Hospitals, of a cohort of 1032 patients who underwent genetic testing. Main Outcomes and Measures Frequency of mutation in high ( CDKN2A , CDK4 , and BAP1 ) and intermediate ( MITF ) susceptibility genes; statistical effect of histologic subtype, age, dysplastic nevi syndrome, and associated cancers on mutation rate; and evaluation of cases with anamnestic uncertainty. Results The mutation rate was 67 of 1032 patients (6.5%). Their mean (SD) age was 54.5 (14.2) years [range, 18-89 years], and 543 (52.6%) were men. It increased to 38 of 408 patients (9.3%) when applying a rule of 3 (those with ≥3 primary melanomas or genetically related cancers) ( P = .68) and to 27 of 150 patients (18.0%) with a rule of 4 (4 primary melanomas or related cancer) ( P P = .12) for the rule of 2 and 22 of 121 (18.2%) ( P = .001) for the rule of 3. Use of the rule of 2 in patients younger than 40 years reduced the number of missed CDKN2A -mutated-families when applying the rule of 3 from 14 of 43 to 7 of 43. Anamnestic uncertainty, found in 88 families (8.5%), if excluded, would have led us to withdraw of only 21 cases (23.8%), and only 1 mutation would have been missed. Conclusions and Relevance We propose using the rule of 3 to recommend genetic testing in France and countries with low to moderate incidence of melanoma, except in families and patients with a first melanoma occurrence before age 40 years in whom the rule of 2 could be maintained.

Objective: To test the validity of the techniques used to calculate quality-adjusted life-year (QALY) values based on utility functions, using a real population dataset. Design: Using the standard gamble technique, we gathered the preferences of a population sample of 189 individuals on a combination of probabilities concerning four simple health states (no physical disability, limp, walk with crutches and need a wheelchair), and three life-year spans (5, 10 and 15 years). Each of the four assumptions of the multiplicative model was tested based on the results of the experiment. Results: The utility of the health state ‘limp’ was high at 0.89 and that of ‘walk with crutches’ only slightly lower at 0.85. However, of the 189 individuals, only 57 are not in contradiction with the assumption of mutual utility independence since they strictly preferred (15 years, ‘need a wheelchair’) over (10 years, ‘need a wheelchair’) and (15 years, ‘need a wheelchair’) over (5 years, ‘need a wheelchair’). For these 57 individuals, the results of this study do not fit the assumptions underpinning the multiplicative model. Conclusion: This work suggests that the techniques used as a basis from which to calculate QALY values are flawed. In particular, the underlying assumptions of the multiattribute utility model do not correspond to behaviour patterns observed in a real population. It therefore appears that use of the QALY technique should be questioned in healthcare decision-making settings.