Introduction: Nail diseases are often diagnosed late with a potential prognostic and functional i... more 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.
Background: Musculoskeletal pain is common in elderly persons. Analgesic use is high in the elder... more Background: Musculoskeletal pain is common in elderly persons. Analgesic use is high in the elderly and may involve unacceptable risk in individuals with chronic pain. Our aim was to compare the socio-demographic characteristics of elderly subjects with musculoskeletal disorders (MSD) and to assess medication use and clinical evolution of musculoskeletal pain according to physician prescribing preference: homeopathy (Ho) group, conventional medicine (CM) group, or mixed prescription (MX) group. Methods: The EPI3 study was a 1 year observational survey carried out among general practitioners in France between March 2007 and July 2008. This sub-analysis was carried out on elderly subjects aged $70 years from the original EPI3 cohort. Socio-demographic data were collected at inclusion using a self-administered patient questionnaire and medical data were recorded for each patient. Quality of life was measured using the Short Form-12 questionnaire. Patients completed a structured telephone interview on their functional status (evaluated with the QuickDash questionnaire, EIFEL scale or Lequesne index) within 72 hours of inclusion. This telephone interview was repeated at 1, 3, and 12 months. Drug exposure was also assessed during these interviews. Results: 146 patients (mean age ± standard deviation: 75.8±4.8 years) were analyzed (80.1% female, 74.7% MSD of the spine or lower limbs, 64.4% chronic MSD). Patients in the CM and MX groups were 3.7 times or 2.5 times more likely (odds ratio [OR] =3.71, 95% confidence interval [CI]: 1.12−12.30; OR =2.52, 95% CI: 1.05−6.05; respectively) to have used non-steroidal anti-inflammatory drugs (NSAIDs) than those in the Ho group. In contrast, analgesic use was comparable in the three groups (OR =1.06 [CM versus Ho], 95% CI: 0.09−12.11; OR =0.34 [MX versus Ho], 95% CI: 0.07−1.57). Overall functional score evolution was similar in the three groups over time (P=0.16). Conclusion: NSAID use was significantly higher in elderly MSD patients consulting a conventional practice general practitioner. In contrast, analgesic use and MSD evolution were similar in the three groups. Consulting a homeopathic physician for MSD management does not appear to represent a loss of therapeutic opportunity, and decreases the use of NSAIDs.
Background: The impact of proton pump inhibitors (PPIs) on the evolution of inflammatory bowel di... more Background: The impact of proton pump inhibitors (PPIs) on the evolution of inflammatory bowel disease (IBD) remains debated with only sparse data available. The primary objective of this study was to analyze the impact of PPIs on the course of IBD. Methods: This was a single-center, retrospective cohort study. We included consecutive adult patients diagnosed with Crohn disease (CD) or ulcerative colitis (UC) who were followed prospectively in our day hospital over a 4-month period (from May to August 2022). PPI exposure was defined as PPI use for a cumulative duration of more than seven days from the date of IBD diagnosis until the end of follow-up. We performed a time to event analysis to investigate the association of PPI exposure with treatment failure defined as an IBD-related surgery or hospitalization and/or failure for more than four biologic treatment (Anti TNF, Vedolizumab, Ustekinumab). Results: Among the 281 patients identified, 244 patients were eligible for analysis of the primary objective (152 with CD, mean age 45 years, sex ratio 1:1). 113 (46%) patients had been previously exposed to a PPI. PPI-exposed patients were significantly older (p=0.013), more often women (p=0.029), with more frequent active smoking (p=0.001). A total of 152 patients (62%) had treatment failure. Using Cox regression analysis, (Table 1), PPI use identified as an independent factor associated with treatment failure (HR = 1.920; 95% CI [1.084-3.403]; p0.025). In a subgroup analysis by IBD type, this remained statistically significant only for CD (HR = 3.190; 95% CI (1.412-7.206); p 0.005) but not for UC (HR = 0.981; 95% CI (0.384-2.504); p0.968). Survival without treatment failure (Figure 1) was significantly higher in patients without PPI exposure compared to patients with PPI exposure, (325 months vs. 228 months, respectively, p=0.022 (Log-Rank). In a subgroup analysis of infliximab-treated patients, PPI use was not associated with risk of immunogenicity (HR = 1.071; 95% CI (0.515-2.226); p0.854). Conclusion: This study demonstrates the negative impact of PPIs on the disease course in patients with CD. The use PPIs should better be discussed on a case-by-case basis.
Background: Anti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in ... more 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 wildtype 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 (≤3 months) was significantly higher in BRAF-mutated patients (55.2% vs. 20.0%, p = 0.014). Discussion: This is the largest series of unselected patients treated in real-life with anti-PD-1 as second-or-higher line of treatment. Anti-PD-1 was less effective in BRAF-mutated cases as a majority of patients presented aggressive tumor evolution after BRAFi discontinuation. These data are consistent with previous studies suggesting a negative impact of BRAFi prior to immunotherapy.
Background Dermoscopy improves diagnostic accuracy in melanoma, as shown by several meta-analyses... more Background 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. Objectives To review the opinions and use of dermoscopy by GPs in France and to understand their practice of skin examination. Methods 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, v 2 , Student, Welch and Fisher tests were used for cross-tabulation statistical analysis. Results Only 8% of respondents had access to a dermoscope; most were male practitioners and aged > 50 years. Dermoscopy increased self-confidence in analysing pigmented lesions (P = 0Á004), and dermoscopy users referred fewer patients to dermatologists. The number of biopsies was reduced in the dermoscopy users group (P = 0Á004). In total, 425 questionnaires were returned and analysed. Dermoscopy users took more time to evaluate a single pigmented lesion (P = 0Á015). Only 16Á9% 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 29Á2% of the respondents said the main advantage was to reduce the number of referrals to the dermatologists (P = 0Á004), while its main disadvantage was the necessity of training (54Á6%). Our responders declared they could spend seven working days on a dermoscopy training course. Conclusions 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. What's already known about this topic? • National surveys regarding the use of dermoscopy by general practitioners have been conducted mainly in Australia and Italy. • The use by French general practitioners has never previously been described, despite dermoscopy being a useful tool for the diagnosis of melanoma.
9093 Background: Vemurafenib is the first approved by the FDA BRAF V600 inhibitor for the treatme... more 9093 Background: Vemurafenib is the first approved by the FDA BRAF V600 inhibitor for the treatment of metastatic melanoma. Many cutaneous side-effects such as squamous cell carcinoma, xerosis, photosensitivity are observed. We first reported the occurrence of second primary melanomas (SPM) under BRAF inhibition. These SPM were shown to be wild-type for BRAF. The exact occurrence of these changes is still unknown. We wanted then to explore prospectively the impact of vemurafenib on cutaneous pigmented lesions using sequential digital dermoscopy. Methods: We registered prospectively following inform consent the pigmented lesions of patients under vemurafenib. We examined the total body surface and captured from 9 to 134 pigmented lesions on 24 patients. Each single lesion was followed monthly from vemurafenib initiation to vemurafenib disruption due to disease progression. Dermoscopic modifications of the melanocytic lesions including external diameter, dermoscopical pattern, pigment...
ObjectivesIn patients with IBD experiencing an immune-mediated loss of response (LOR) to antitumo... more 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 ph...
Background: Golimumab is a monoclonal anti–tumor necrosis factor alpha antibody, which is used in... more 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...
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, Jan 5, 2018
Drug de-escalation is considered in Crohn's disease patients in sustained remission on optimi... more Drug de-escalation is considered in Crohn's disease patients in sustained remission on optimized infliximab treatment. 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. 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 <7 μg/mL. Only costs related to drug administration were considered. The cost differences when comparing P1 versus P2 and P3 versus P4 were 7.6% and 4.6%, respective...
IMPORTANCE Genetic testing for melanoma-prone mutation in France, a country with low to moderate ... more 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 Ն3 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 < .001). The impact of age at first melanoma was observed only in those younger than 40 years, with a rate of 32 of 263 (12.1%) (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.
L'optimisation de la prise en charge de l'insuffisance renale chronique (IRC) a pour but ... more L'optimisation de la prise en charge de l'insuffisance renale chronique (IRC) a pour but de diminuer la morbidite et la mortalite des patients en insuffisance renale chronique, directement liees a la progression vers l'IRC terminale, et aux complications mettant en jeu le pronostic vital et/ou fonctionnel. La progression spontanee' vers l'IRC terminale resulte de facteurs propres a la nephropathie initiale, et de facteurs non specifiques lies notamment a l'hypertension arterielle, et aux adaptations fonctionnelles a la reduction nephronique. La prevention secondaire de l'IRC passe ainsi par l'identification precoce de la nephropathie en vue d'un eventuel traitement specifique; le traitement de l'hypertension; la normalisation des apports en proteines; la prevention des evenements notamment iatrogenes susceptibles d'aggraver irreversiblement la fonction renale, Les evenements cliniques n'apparaissent que tres tardivement au cours de l'IRC, a la suite d'anomalies presentes longtemps avant le stade de la dialyse (hypertension, dyslipidemies, anomalies phosphocalciques, anemie, malnutrition) qui doivent etre depistees et traitees dans une demarche de prevention tertiaire. Enfin, lorsque la dialyse apparait inevitable, une information precoce et une preparation medicale planifiee du patient sont necessaires pour donner a la methode choisie, les meilleures chances de succes, Malbeureusement, de nombreux patients ne sont encore pris en charge qu'a un stade d'IRC severe, auquel les effets des interventions therapeutiques sont plus limites: ces patients ont des durees d'hospitalisation plus longues, une incidence plus elevee de complications durant les premiers mois de dialyse, et ont deux fois moins de chances de pouvoir etre autonomises sur une methode de dialyse hors-centre type autodialyse, dialyse a domicile, ou dialyse peritoneale.
Homeopathy : the journal of the Faculty of Homeopathy, 2014
Pharmacists play a key role in primary healthcare, but the characteristics of patients who consul... more 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. 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. 573 patients (mean age: 42.5 ± 16.2 years; 61.9% female...
Integrating complete lower limb venous ultrasound into diagnostic strategies for pulmonary emboli... more Integrating complete lower limb venous ultrasound into diagnostic strategies for pulmonary embolism: a cost-effectiveness analysis -
To test the validity of the techniques used to calculate quality-adjusted life-year (QALY) values... more 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. 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. The utility of the health state &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;limp&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; was high at 0.89 and that of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;walk with crutches&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; 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, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;need a wheelchair&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) over (10 years, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;need a wheelchair&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) and (15 years, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;need a wheelchair&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) over (5 years, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;need a wheelchair&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;). For these 57 individuals, the results of this study do not fit the assumptions underpinning the multiplicative model. 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.
determined after adjustments for the known prognostic factors listed in the following section. Re... more determined after adjustments for the known prognostic factors listed in the following section. Results: The pregnancy rates (PR) were 29.9% in the Autumn (September-November), 30.6% in the Winter (December-February), 31.7% in the Spring (March-May), and 37.8% (Pϭ0.008) in the Summer (June-August). The corresponding delivery rates (DR) were 18.5%, 16.5%, 15.4% and 20.2% (Pϭ0.31, NS). The correlation between the PR and the DR and other factors are summarized in the table: Embryo quality, as measured by the average cell number and the degree of fragmentation at the day of ET on 2107 cycles during the years 2000-2, was not affected by the various seasons of the year. Conclusions: Our results suggest that IVF outcome may be affected by seasonal changes with a peak in pregnancy and implantation rates during the summer. During this season the higher PR (44%) was observed during the months of June. Since most of our patients underwent down regulation by GnRH agonists we believe that these observations are related to variability in endometrial receptivity modulated by yet unknown input and pathways such as the dark-light cycle. This down regulation of the ovarian-hypothesis axis may, however, interfere with maintenance of early pregnancy and lead to a uniform delivery rate throughout all seasons. Comparable studies especially from the Southern Hemisphere may shed more light on our observations.
Background &amp; Objective: In France, non-homeopathic general practitioners (GPs) often use ... more Background &amp; Objective: 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. Method: 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. Results: 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(C) 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 ( Conclusion: 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&#x27; 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
Introduction: Nail diseases are often diagnosed late with a potential prognostic and functional i... more 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.
Background: Musculoskeletal pain is common in elderly persons. Analgesic use is high in the elder... more Background: Musculoskeletal pain is common in elderly persons. Analgesic use is high in the elderly and may involve unacceptable risk in individuals with chronic pain. Our aim was to compare the socio-demographic characteristics of elderly subjects with musculoskeletal disorders (MSD) and to assess medication use and clinical evolution of musculoskeletal pain according to physician prescribing preference: homeopathy (Ho) group, conventional medicine (CM) group, or mixed prescription (MX) group. Methods: The EPI3 study was a 1 year observational survey carried out among general practitioners in France between March 2007 and July 2008. This sub-analysis was carried out on elderly subjects aged $70 years from the original EPI3 cohort. Socio-demographic data were collected at inclusion using a self-administered patient questionnaire and medical data were recorded for each patient. Quality of life was measured using the Short Form-12 questionnaire. Patients completed a structured telephone interview on their functional status (evaluated with the QuickDash questionnaire, EIFEL scale or Lequesne index) within 72 hours of inclusion. This telephone interview was repeated at 1, 3, and 12 months. Drug exposure was also assessed during these interviews. Results: 146 patients (mean age ± standard deviation: 75.8±4.8 years) were analyzed (80.1% female, 74.7% MSD of the spine or lower limbs, 64.4% chronic MSD). Patients in the CM and MX groups were 3.7 times or 2.5 times more likely (odds ratio [OR] =3.71, 95% confidence interval [CI]: 1.12−12.30; OR =2.52, 95% CI: 1.05−6.05; respectively) to have used non-steroidal anti-inflammatory drugs (NSAIDs) than those in the Ho group. In contrast, analgesic use was comparable in the three groups (OR =1.06 [CM versus Ho], 95% CI: 0.09−12.11; OR =0.34 [MX versus Ho], 95% CI: 0.07−1.57). Overall functional score evolution was similar in the three groups over time (P=0.16). Conclusion: NSAID use was significantly higher in elderly MSD patients consulting a conventional practice general practitioner. In contrast, analgesic use and MSD evolution were similar in the three groups. Consulting a homeopathic physician for MSD management does not appear to represent a loss of therapeutic opportunity, and decreases the use of NSAIDs.
Background: The impact of proton pump inhibitors (PPIs) on the evolution of inflammatory bowel di... more Background: The impact of proton pump inhibitors (PPIs) on the evolution of inflammatory bowel disease (IBD) remains debated with only sparse data available. The primary objective of this study was to analyze the impact of PPIs on the course of IBD. Methods: This was a single-center, retrospective cohort study. We included consecutive adult patients diagnosed with Crohn disease (CD) or ulcerative colitis (UC) who were followed prospectively in our day hospital over a 4-month period (from May to August 2022). PPI exposure was defined as PPI use for a cumulative duration of more than seven days from the date of IBD diagnosis until the end of follow-up. We performed a time to event analysis to investigate the association of PPI exposure with treatment failure defined as an IBD-related surgery or hospitalization and/or failure for more than four biologic treatment (Anti TNF, Vedolizumab, Ustekinumab). Results: Among the 281 patients identified, 244 patients were eligible for analysis of the primary objective (152 with CD, mean age 45 years, sex ratio 1:1). 113 (46%) patients had been previously exposed to a PPI. PPI-exposed patients were significantly older (p=0.013), more often women (p=0.029), with more frequent active smoking (p=0.001). A total of 152 patients (62%) had treatment failure. Using Cox regression analysis, (Table 1), PPI use identified as an independent factor associated with treatment failure (HR = 1.920; 95% CI [1.084-3.403]; p0.025). In a subgroup analysis by IBD type, this remained statistically significant only for CD (HR = 3.190; 95% CI (1.412-7.206); p 0.005) but not for UC (HR = 0.981; 95% CI (0.384-2.504); p0.968). Survival without treatment failure (Figure 1) was significantly higher in patients without PPI exposure compared to patients with PPI exposure, (325 months vs. 228 months, respectively, p=0.022 (Log-Rank). In a subgroup analysis of infliximab-treated patients, PPI use was not associated with risk of immunogenicity (HR = 1.071; 95% CI (0.515-2.226); p0.854). Conclusion: This study demonstrates the negative impact of PPIs on the disease course in patients with CD. The use PPIs should better be discussed on a case-by-case basis.
Background: Anti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in ... more 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 wildtype 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 (≤3 months) was significantly higher in BRAF-mutated patients (55.2% vs. 20.0%, p = 0.014). Discussion: This is the largest series of unselected patients treated in real-life with anti-PD-1 as second-or-higher line of treatment. Anti-PD-1 was less effective in BRAF-mutated cases as a majority of patients presented aggressive tumor evolution after BRAFi discontinuation. These data are consistent with previous studies suggesting a negative impact of BRAFi prior to immunotherapy.
Background Dermoscopy improves diagnostic accuracy in melanoma, as shown by several meta-analyses... more Background 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. Objectives To review the opinions and use of dermoscopy by GPs in France and to understand their practice of skin examination. Methods 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, v 2 , Student, Welch and Fisher tests were used for cross-tabulation statistical analysis. Results Only 8% of respondents had access to a dermoscope; most were male practitioners and aged > 50 years. Dermoscopy increased self-confidence in analysing pigmented lesions (P = 0Á004), and dermoscopy users referred fewer patients to dermatologists. The number of biopsies was reduced in the dermoscopy users group (P = 0Á004). In total, 425 questionnaires were returned and analysed. Dermoscopy users took more time to evaluate a single pigmented lesion (P = 0Á015). Only 16Á9% 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 29Á2% of the respondents said the main advantage was to reduce the number of referrals to the dermatologists (P = 0Á004), while its main disadvantage was the necessity of training (54Á6%). Our responders declared they could spend seven working days on a dermoscopy training course. Conclusions 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. What's already known about this topic? • National surveys regarding the use of dermoscopy by general practitioners have been conducted mainly in Australia and Italy. • The use by French general practitioners has never previously been described, despite dermoscopy being a useful tool for the diagnosis of melanoma.
9093 Background: Vemurafenib is the first approved by the FDA BRAF V600 inhibitor for the treatme... more 9093 Background: Vemurafenib is the first approved by the FDA BRAF V600 inhibitor for the treatment of metastatic melanoma. Many cutaneous side-effects such as squamous cell carcinoma, xerosis, photosensitivity are observed. We first reported the occurrence of second primary melanomas (SPM) under BRAF inhibition. These SPM were shown to be wild-type for BRAF. The exact occurrence of these changes is still unknown. We wanted then to explore prospectively the impact of vemurafenib on cutaneous pigmented lesions using sequential digital dermoscopy. Methods: We registered prospectively following inform consent the pigmented lesions of patients under vemurafenib. We examined the total body surface and captured from 9 to 134 pigmented lesions on 24 patients. Each single lesion was followed monthly from vemurafenib initiation to vemurafenib disruption due to disease progression. Dermoscopic modifications of the melanocytic lesions including external diameter, dermoscopical pattern, pigment...
ObjectivesIn patients with IBD experiencing an immune-mediated loss of response (LOR) to antitumo... more 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 ph...
Background: Golimumab is a monoclonal anti–tumor necrosis factor alpha antibody, which is used in... more 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...
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, Jan 5, 2018
Drug de-escalation is considered in Crohn's disease patients in sustained remission on optimi... more Drug de-escalation is considered in Crohn's disease patients in sustained remission on optimized infliximab treatment. 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. 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 <7 μg/mL. Only costs related to drug administration were considered. The cost differences when comparing P1 versus P2 and P3 versus P4 were 7.6% and 4.6%, respective...
IMPORTANCE Genetic testing for melanoma-prone mutation in France, a country with low to moderate ... more 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 Ն3 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 < .001). The impact of age at first melanoma was observed only in those younger than 40 years, with a rate of 32 of 263 (12.1%) (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.
L'optimisation de la prise en charge de l'insuffisance renale chronique (IRC) a pour but ... more L'optimisation de la prise en charge de l'insuffisance renale chronique (IRC) a pour but de diminuer la morbidite et la mortalite des patients en insuffisance renale chronique, directement liees a la progression vers l'IRC terminale, et aux complications mettant en jeu le pronostic vital et/ou fonctionnel. La progression spontanee' vers l'IRC terminale resulte de facteurs propres a la nephropathie initiale, et de facteurs non specifiques lies notamment a l'hypertension arterielle, et aux adaptations fonctionnelles a la reduction nephronique. La prevention secondaire de l'IRC passe ainsi par l'identification precoce de la nephropathie en vue d'un eventuel traitement specifique; le traitement de l'hypertension; la normalisation des apports en proteines; la prevention des evenements notamment iatrogenes susceptibles d'aggraver irreversiblement la fonction renale, Les evenements cliniques n'apparaissent que tres tardivement au cours de l'IRC, a la suite d'anomalies presentes longtemps avant le stade de la dialyse (hypertension, dyslipidemies, anomalies phosphocalciques, anemie, malnutrition) qui doivent etre depistees et traitees dans une demarche de prevention tertiaire. Enfin, lorsque la dialyse apparait inevitable, une information precoce et une preparation medicale planifiee du patient sont necessaires pour donner a la methode choisie, les meilleures chances de succes, Malbeureusement, de nombreux patients ne sont encore pris en charge qu'a un stade d'IRC severe, auquel les effets des interventions therapeutiques sont plus limites: ces patients ont des durees d'hospitalisation plus longues, une incidence plus elevee de complications durant les premiers mois de dialyse, et ont deux fois moins de chances de pouvoir etre autonomises sur une methode de dialyse hors-centre type autodialyse, dialyse a domicile, ou dialyse peritoneale.
Homeopathy : the journal of the Faculty of Homeopathy, 2014
Pharmacists play a key role in primary healthcare, but the characteristics of patients who consul... more 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. 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. 573 patients (mean age: 42.5 ± 16.2 years; 61.9% female...
Integrating complete lower limb venous ultrasound into diagnostic strategies for pulmonary emboli... more Integrating complete lower limb venous ultrasound into diagnostic strategies for pulmonary embolism: a cost-effectiveness analysis -
To test the validity of the techniques used to calculate quality-adjusted life-year (QALY) values... more 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. 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. The utility of the health state &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;limp&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; was high at 0.89 and that of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;walk with crutches&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; 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, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;need a wheelchair&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) over (10 years, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;need a wheelchair&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) and (15 years, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;need a wheelchair&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) over (5 years, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;need a wheelchair&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;). For these 57 individuals, the results of this study do not fit the assumptions underpinning the multiplicative model. 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.
determined after adjustments for the known prognostic factors listed in the following section. Re... more determined after adjustments for the known prognostic factors listed in the following section. Results: The pregnancy rates (PR) were 29.9% in the Autumn (September-November), 30.6% in the Winter (December-February), 31.7% in the Spring (March-May), and 37.8% (Pϭ0.008) in the Summer (June-August). The corresponding delivery rates (DR) were 18.5%, 16.5%, 15.4% and 20.2% (Pϭ0.31, NS). The correlation between the PR and the DR and other factors are summarized in the table: Embryo quality, as measured by the average cell number and the degree of fragmentation at the day of ET on 2107 cycles during the years 2000-2, was not affected by the various seasons of the year. Conclusions: Our results suggest that IVF outcome may be affected by seasonal changes with a peak in pregnancy and implantation rates during the summer. During this season the higher PR (44%) was observed during the months of June. Since most of our patients underwent down regulation by GnRH agonists we believe that these observations are related to variability in endometrial receptivity modulated by yet unknown input and pathways such as the dark-light cycle. This down regulation of the ovarian-hypothesis axis may, however, interfere with maintenance of early pregnancy and lead to a uniform delivery rate throughout all seasons. Comparable studies especially from the Southern Hemisphere may shed more light on our observations.
Background &amp; Objective: In France, non-homeopathic general practitioners (GPs) often use ... more Background &amp; Objective: 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. Method: 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. Results: 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(C) 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 ( Conclusion: 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&#x27; 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
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Papers by Gerard Duru