The FLURESP European commission project: cost-effectiveness assessment of ten public health measures against influenza in Italy: is there an interest in COVID-19 pandemic?

BACKGROUND: The FLURESP project is a public health research funded by the European Commission, with the objective to design a methodological framework to assess the cost-effectiveness of existing public health measures against human influenza pandemics. A dataset has been specifically collected in the frame of the Italian health system. As most of interventions against human influenza are relavant against other respiratory diseases pandemics, potential interests in COVID-19 are discussed. METHODS: Ten public health measures against human influenza pandemics pandemic were selected to be also relevant to other respiratory virus pandemics such as COVID 19: individual (hand washing, using masks), border control (quarantine, fever screening, border closure), community infection (school closure, class dismissal, social distancing, limitation of public transport), reduction of secondary infections (implementation of antibiotic therapy guidelines), pneumococcal vaccination for at-risk people, development of Intensive Care Unit (ICU) capacity, implementation of life support equipments in ICU, screening interventions, vaccination programs targeting health professional and targeting general population. RESULTS: Using mortality reduction as effectiveness criteria, the most cost-effective strategies are "reduction of secondary infections" and "implementation of life support equipment in ICU". The least cost-effective option whatever the level of pandemic events are screening interventions and mass vaccination. CONCLUSIONS: A number of intervention strategies against human influenza pandemics appears relevant against every respiratory virus, including the COVID-19 event. Measures against pandemics should be considered according to their expected effectiveness but also their costs for the society because they impose substantial burden to the population, confirming the interest of considering cost-effectiveness of public health measures to enlighten decision making.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

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.

Addition of azathioprine to the switch of anti-TNF in patients with IBD in clinical relapse with undetectable anti-TNF trough levels and antidrug antibodies: a prospective randomised trial.

OBJECTIVES: In 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. DESIGN: Consecutive 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). RESULTS: Ninety 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 (p<0.001; median time of clinical failure since randomisation 18 vs >24 months). At 24 months, survival rates without clinical failure and without appearance of unfavourable pharmacokinetics were respectively 22 versus 77% and 22% versus 78% (p<0.001 for both) in monotherapy versus combination therapy. Only the use of combination therapy was associated with favourable outcomes after anti-TNF switch. CONCLUSION: In case of immune-mediated LOR to a first anti-TNF, AZA should be associated with the second anti-TNF. TRIAL REGISTRATION NUMBER: 03580876.

Comparison of Immunoassays for Measuring Serum Levels of Golimumab and Antibodies Against Golimumab in Ulcerative Colitis: A Retrospective Observational Study.

BACKGROUND: 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). METHODS: 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 R&D, San Diego, CA). Bridging drug-sensitive enzyme-linked immunosorbent assays (Theradiag, Janssen R&D, and KU Leuven), a bridging drug-tolerant enzyme-linked immunosorbent assay (Janssen R&D), and a radioimmunoassay (Sanquin) were used to quantify antidrug antibody. RESULTS: Median serum golimumab levels were 4.5, 3.5, 4.9, and 2.4 mcg/mL with Theradiag, Sanquin, KU Leuven, and Janssen R&D assay, respectively (P < 0.05). Correlation coefficients between assays ranged from 0.9 to 0.97. When using the KU Leuven and Janssen R&D assays, 86% of samples were in the same quartile of distribution of values, and for Sanquin and Janssen R&D assays, this overlap was 80%. The concordance observed for the other pairs was 83% (Sanquin/KU Leuven R&D), 71% (Theradiag/KU Leuven), and 68% (Theradiag/Janssen R&D and Theradiag/Sanquin). The specificity of assays for golimumab was demonstrated. Antidrug antibodies were detected in 28.2% of the samples with the Janssen R&D drug-tolerant assay and in the same 2 patients by the 3 other assays. CONCLUSIONS: 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.

Management of Anxiety and Depressive Disorders in Patients ≥ 65 Years of Age by Homeopath General Practitioners versus Conventional General Practitioners, with Overview of the EPI3-LASER Study Results.

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 < 9) after 12 months than those in the GP-CM group. Patients who consulted a GP-Ho reported less psychotropic drug use (OR = 22.31 [95% CI: 2.20-226.31]) and benzodiazepine use (OR = 60.63 [95% CI: 5.75-639.5]) than GP-CM patients. 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.

Dermoscopic Features of Subungual Squamous Cell Carcinoma: A Study of 44 Cases.

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.

Hidradenitis suppurativa (HS): An unrecognized paradoxical effect of biologic agents (BA) used in chronic inflammatory diseases.

BACKGROUND: Paradoxical hidradenitis suppurativa (HS) induced by biologic agents (BA) is scarcely reported. OBJECTIVE: We sought to describe the clinical characteristics and outcome of patients developing paradoxical HS under BA. METHODS: This was a multicenter nationwide retrospective study asking physicians to report all cases of HS, confirmed by a dermatologist, occurring during treatment of an inflammatory disease by a BA. RESULTS: We included 25 patients (15 inflammatory rheumatism, 9 Crohn's disease, 1 psoriasis) treated by 5 BA (adalimumab = 12, infliximab = 6, etanercept = 4, rituximab = 2, tocilizumab = 1). Median duration of BA exposure before HS onset was 12 (range 1-120) months. Patients were mostly Hurley stage I (n = 13) or II (n = 11). Simultaneously to HS or within 1 year, 11 patients developed additional inflammatory diseases, including paradoxical reactions (psoriasis = 9, Crohn's disease = 3, alopecia areata = 1, erythema elevatum diutinum = 1). Complete improvement of HS was more frequently obtained after BA discontinuation or switch (n = 6/10, 60%) rather than maintenance (n = 1/14, 7%). Reintroducing the same BA resulted in HS relapse in 3 of 3 patients. LIMITATIONS: Retrospective nature and lack of complete follow-up for some patients are limitations. CONCLUSION: HS is a rare paradoxical adverse effect of BA, but fortuitous association cannot be excluded in some cases. We observed a trend toward better outcome when the BA was discontinued or switched.

Homeopathic medical practice for anxiety and depression in primary care: the EPI3 cohort study.

BACKGROUND: The purpose of the study was to compare utilization of conventional psychotropic drugs among patients seeking care for anxiety and depression disorders (ADDs) from general practitioners (GPs) who strictly prescribe conventional medicines (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHODS: This was one of three epidemiological cohort studies (EPI3) on general practice in France, which included GPs and their patients consulting for ADDs (scoring 9 or more in the Hospital Anxiety and Depression Scale, HADS). Information on all medication utilization was obtained by a standardised telephone interview at inclusion, 1, 3 and 12 months. RESULTS: Of 1562 eligible patients consulting for ADDs, 710 (45.5 %) agreed to participate. Adjusted multivariate analyses showed that GP-Ho and GP-Mx patients were less likely to use psychotropic drugs over 12 months, with Odds ratio (OR) = 0.29; 95 % confidence interval (CI): 0.19 to 0.44, and OR = 0.62; 95 % CI: 0.41 to 0.94 respectively, compared to GP-CM patients. The rate of clinical improvement (HADS <9) was marginally superior for the GP-Ho group as compared to the GP-CM group (OR = 1.70; 95 % CI: 1.00 to 2.87), but not for the GP-Mx group (OR = 1.49; 95 % CI: 0.89 to 2.50). CONCLUSIONS: Patients with ADD, who chose to consult GPs prescribing homeopathy reported less use of psychotropic drugs, and were marginally more likely to experience clinical improvement, than patients managed with conventional care. Results may reflect differences in physicians' management and patients' preferences as well as statistical regression to the mean.

Motivations of patients seeking supportive care for cancer from physicians prescribing homeopathic or conventional medicines: results of an observational cross-sectional study.

BACKGROUND & AIMS: The motivations of patients who consult a homeopathic (GP-Ho) or conventional (GP-CM) general practitioner for supportive care during cancer treatment have not been widely studied. We investigated the reasons why cancer patients consult a GP-Ho versus a GP-CM for supportive care and the GPs' motivations for their prescriptions. METHODS: This observational survey was carried out in France between October 2008 and October 2011. GPs across France were randomly selected and asked to recruit four cancer patients each. At inclusion, the sociodemographic and clinical (including psychological) characteristics and medical history of the patients were recorded by the GPs and the patients noted their quality of life (QoL) and anxiety/depression using the Quality of Life Questionnaire-C30 (QLQ-C30) and Hospital Anxiety and Depression Scale (HADS) self-questionnaires. The main motivations of the patients regarding the type of GP consultation and the main reasons for the GPs' prescriptions were recorded. RESULTS: Six hundred and forty four patients were included in the analysis: 399 consulted a GP-CM (n = 112) and 245 a GP-Ho (n = 73). Patients consulting a GP-Ho were more often female [OR = 1.93; 95%CI: 1.11-3.35; p = 0.02], employed in a professional capacity [OR = 6.57; 95%CI: 1.96-21.99; p = 0.002], have a shorter time since cancer diagnosis [OR = 2.19; 95%CI: 1.24-3.87; p = 0.007], have received targeted anticancer therapy [OR = 3.70; 95%CI: 1.67-8.18; p = 0.001] and have a high QLQ-C30 score for constipation [OR = 1.01; 95%CI: 1.00-1.02; p = 0.001]. Patients mainly consulted a GP-Ho to receive overall care (73.5% vs. 64.9%; p = 0.024) and medicines to prevent anticancer treatment-related side-effects (63.7% vs. 41.4%; p < 0.0001). In contrast, patients consulted a GP-CM to receive psychological care (50.1% vs. 40.8%; p = 0.021) and more information regarding the oncologists' strategic decisions (p < 0.0001). There was a significantly greater prescription of psychotropic drugs by GP-CM (53.7% vs. 22.4%, p < 0.0001). CONCLUSIONS: Patients consulting a GP-Ho or GP-CM had different motivations for seeking supportive care. There was a significantly greater prescription of psychotropic drugs by GP-CM.

Dermoscopic Features of Onychomatricoma: A Study of 34 Cases.

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.

Impact of pigmentary disorders on quality of life in Japan: Interest of the BeautyQoL instrument.

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 five dimensions of the BeautyQoL questionnaire, the dimension "mood" appeared to be significantly 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 five dimensions and the global score showed that subjects concerned had lower scores than subjects less concerned, even if statistical significance was not reached. This study confirms 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 confirm these findings.

Utilization of psychotropic drugs by patients consulting for sleeping disorders in homeopathic and conventional primary care settings: the EPI3 cohort study.

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.

Management of the early symptoms of influenza-like illnesses and ear, nose and throat (ENT) disorders by pharmacists.

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 a random sample of French pharmacies between November 2010 and March 2011. Patients (≥12-years) with early symptoms of ILI or ENT disorders (<36 h duration) who received treatment were included. Socio-demographic data, symptom severity and disease impact on daily activities and sleep were recorded at inclusion. Symptom evolution and patient satisfaction were assessed after 3 days of treatment. RESULTS: 573 patients (mean age: 42.5 ± 16.2 years; 61.9% female) were recruited by 133 pharmacies. Two-thirds of patients (63.2%) visited the pharmacy early (<24 h) after symptom onset. The most common symptoms were runny nose (56.4%), sore throat (54.6%) and cough (49.0%). Patients were given 2.6 ± 1.2 medications; 98.4% of patients received allopathic (usually paracetamol, 33.5%) and 25.3% homeopathic (Oscillococcinum, 56.6%) treatment, usually combined with allopathy. Compliance was good and 77.2% of patients continued treatment for 3 days. Most symptoms improved significantly after 3 days and quality of life was enhanced. 85.9% of patients were satisfied with the advice received. CONCLUSIONS: Seeking a pharmacist's advice for the management of ILI and ENT disorders has several public health benefits. The clinical improvement and high patient satisfaction observed validate the role of the pharmacist as a health professional of first resort.

Characteristics of patients consulting their regular primary care physician according to their prescribing preferences for homeopathy and complementary medicine.

BACKGROUND: Homeopathic care has not been well documented in terms of its impact on patients' utilization of drugs or other complementary and alternative medicines (CAM). The objective of this study was to describe and compare patients who visit physicians in general practice (GPs) who prescribe only conventional medicines (GP-CM), regularly prescribe homeopathy within a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). MATERIAL AND METHODS: The EPI3-LASER study was a nationwide observational survey of a representative sample of GPs and their patients from across France. Physicians recorded their diagnoses and prescriptions on participating patients who completed a self-questionnaire on socio-demographics, lifestyle, quality of life Short Form 12 (SF-12) and the complementary and alternative medicine beliefs inventory (CAMBI). RESULTS: A total of 6379 patients (participation rate 73.1%) recruited from 804 GP practices participated in this survey. Patients attending a GP-Ho were slightly more often female with higher education than in the GP-CM group and had markedly healthier lifestyle. They did not differ greatly in their comorbidities or quality of life but exhibited large differences in their beliefs in holistic medicine and natural treatments, and in their attitude toward participating to their own care. Similar but less striking observations were made in patients of the GP-Mx group. CONCLUSION: Patients seeking care with a homeopathic GP did not differ greatly in their socio-demographic characteristics but more so by their healthier lifestyle and positive attitude toward CAM. Further research is needed to explore the directionality of those associations and to assess the potential economic benefits of homeopathic management in primary care.

Evaluation of the Knowledge of Primary Care Physicians About Important Nail Diseases Before and After a Short Online Training.

INTRODUCTION: Nail diseases are often diagnosed late with a potential prognostic and functional impact. This could be partly due to knowledge gaps among primary care physicians (PCPs). OBJECTIVES: To evaluate the knowledge about diagnosis and management of ten common/important nail conditions in a population of French PCPs and its improvement after a 31-minute online training session. METHODS: We submitted 10 pre-test and post-test clinical cases and an educative online course on the diagnosis and the management of nail diseases to 138 volunteer PCPs; 73 completed the whole training path. RESULTS: Compared to pre-test, more PCPs in the post-test required an urgent second opinion to dermatologist for pigmented melanoma (100% versus 80.3%; P <0.05) and use of inappropriate/dangerous systemic treatment for trauma-induced nail changes was reduced after the training program (0% versus 6.8%; P <0.05). A lack of knowledge remained after training for amelanotic melanoma with an increase of mycological/bacteriological tests (9.6% versus 0%; P <0.05). CONCLUSIONS: Management of nail diseases by our panel of PCPs was suboptimal and was improved after a short online training.

Development of Antibodies to Ustekinumab Is Associated with Loss of Response in Patients with Inflammatory Bowel Disease.

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.

Higher serum infliximab concentrations following subcutaneous dosing are associated with deep remission in patients with inflammatory bowel disease.

BACKGROUND: The relationship between SC-IFX concentrations and favorable therapeutic outcomes in patients with Crohn's disease (CD) and ulcerative colitis (UC) remain elusive. PATIENTS AND METHODS: This cross-sectional trial study included consecutive IBD adult patients with IBD treated with SC-IFX at maintenance dose of 120mg/2 weeks. Investigated therapeutic outcomes included sustained clinical remission; composite clinical and biomarker remission [clinical remission and CRP < 5mg/L]; biochemical remission [FC < 250 µg/g]; and deep remission [clinical, biological and biochemical remission]. RESULTS: Of 91 patients identified, 71 patients qualified for inclusion in the study (70% with CD; 27% with concomitant immunomodulators). At the time of drug concentration measurement (median 13.5 months after switch), 55 (77%) patients had sustained clinical remission; n=44 (62%) composite clinical and biomarker remission; n=40 (56%) biochemical remission; and n=31 (43%) patients deep remission. The mean SC-IFX concentrations were significantly higher in patients with sustained clinical remission [p=0.014]; composite clinical and biomarker remission [p=0.003]; biochemical remission [p<0.001] and deep remission [p<0.001] compared to patients without having these outcomes. In multivariate analysis, SC-IFX concentration was the only factor independently associated with sustained clinical remission [odds ratio (OR): 4.7, 95% CI: 3.1-12.2, p=0.005)]; clinical and biomarker remission (OR: 9.21, 95%CI: 6.09-18.7, p=0.006); biochemical remission (OR: 37, 95%CI: 14-39.3), p<0.001); and deep remission (OR: 29, 95%CI:15.7-37.4, p<0.001). The optimal SC-IFX concentration cut-off associated with deep remission based on ROC analysis was 20µg/mL (sensitivity: 0.91, specificity: 0.80, accuracy: 0.85). Combination with an IMM failed to improve SC-IFX pharmacokinetics. CONCLUSION: Higher SC-IFX concentrations are associated with higher rates of favorable therapeutic outcomes in IBD patients. Serum SC-IFX concentrations higher than 20µg/mL were significantly associated with deep remission.

Impact of physician preferences for homeopathic or conventional medicines on patients with musculoskeletal disorders: results from the EPI3-MSD cohort.

OBJECTIVE: The objective of this study was to assess the effect of physician practicing preferences (PPP) in primary care for homeopathy (Ho), CAM (Complementary and alternative medicines) with conventional medicine (Mx) or exclusively conventional medicine (CM) on patients with musculoskeletal disorders (MSDs), with reference to clinical progression, drug consumption, side effects and loss of therapeutic opportunity. METHODS: The EPI3-MSD study was a nationwide observational cohort of a representative sample of general practitioners (GP) and their patients in France. Recruitment of GP was stratified by PPP, which was self-declared. Diagnoses and comorbidities were recorded by GP at inclusion. Patients completed a standardized telephone interview at inclusion, one, three and twelve months, including MSD-functional scales and medication consumption. RESULTS: 1153 MSD patients were included in the three PPP groups. Patients did not differ between groups except for chronicity of MSDs (>12 weeks), which was higher in the Ho group (62.1%) than in the CM (48.6%) and Mx groups (50.3%). The twelve-month development of specific functional scores was identical across the three groups after controlling for baseline score (p > 0.05). After adjusting for propensity scores, NSAID use over 12 months was almost half in the Ho group (OR, 0.54; 95%CI, 0.38-0.78) as compared to the CM group; no difference was found in the Mx group (OR, 0.81; 95% CI: 0.59-1.15). CONCLUSION: MSD patients seen by homeopathic physicians showed a similar clinical progression when less exposed to NSAID in comparison to patients seen in CM practice, with fewer NSAID-related adverse events and no loss of therapeutic opportunity.

Significance of Primary Melanoma Regression on Local Infiltrate and Outcome.

INTRODUCTION: The characteristics and the prognostic value of regression in primary melanomas are controversial. OBJECTIVES: To further characterize "hot" and "cold" tumor's stromas and to investigate the association between dermoscopy, pathology, and the prognostic implications of regression. METHODS: A 14-year-collection-based retrospective analysis was carried out on 40 patients with confirmed regressive melanomas. RESULTS: The extent of regression in dermoscopy was associated with the stage of the regression (P = 0.05) and with the MelanA patterns in histology (P = 0.02). Blue-gray and gray-brown color of the peppering (P = 0.01), and the eccentric, multifocal character of the dermoscopic regression (P = 0.05) were associated with "hot" stromas (CD8+, Granzym B+). Focal histologic regression (regressing melanomas) was associated with a good outcome (P < 0.001), while a complete regression (regressed melanomas) was associated with melanoma-related death (P < 0.001). "Hot" stromas (CD8+ were significantly associated with survival at 10 years (P = 0.044), while "hot" stromas (Granzyme B+) were associated with the locoregional extension (P = 0.016), and the initial distant metastasis (P = 0.016). CONCLUSIONS: Dermoscopic features of regression in primary melanomas were associated with the stage of regression, its extent, and the "hot" or "cold" nature of the tumor stroma, with prognostic implications.

Quality of life impairment, disability and economic burden associated with chronic daily headache, focusing on chronic migraine with or without medication overuse: a systematic review.

OBJECTIVE: To evaluate the evidence for quality of life (QoL) impairment, disability, healthcare resource use and economic burden associated with chronic daily headache (CDH), focusing on chronic migraine (CM) with or without medication overuse. METHODS: A systematic review and qualitative synthesis of studies of patients/subjects with CDH that included CM, occurring on at least 15 days per month. MAIN FINDINGS: Thirty-four studies were included for review (25 studies of patients and nine of subjects from the general population). CDH and CDH with medication overuse headache (MOH) were consistently associated with a lower QoL compared to control or episodic headache (EH) and CDH without MOH. CDH was consistently associated with greater disability and productivity loss, more consultations, more or longer hospitalizations and higher direct costs than EH. Data were not amenable to statistical pooling. PRINCIPAL CONCLUSIONS: The findings of this review underline the detriment to QoL and the disabling nature of CDH, and in particular CM and CDH with MOH, and negative impact on workplace productivity compared to other types of headache.