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Aims: Gabapentin and pregabalin bind to α2-δ subunit of voltage-gated calcium channels (Ca v ). Other drugs targeting Ca v include cardiovascular calcium channel blockers (CCBs) and anticonvulsants (levetiracetam, ethosuximide and zonisamide). In addition to pharmacodynamics, the safety profile of gabapentinoids seems to overlap with the one of cardiovascular CCBs (oedema) and Ca v -blocking anticonvulsants (suicide and ataxia). The objective of this study was to cluster the safety profile of different Ca v -ligand drugs by focusing on whether gabapentinoids present a distinct adverse drug reaction (ADR) signature from cardiovascular CCBs and anticonvulsants., Methods: We extracted all ADRs with at least one significant disproportionate reporting (reporting odds ratio) related to gabapentinoids, CCBs or anticonvulsants in VigiBase. After principal component analysis preprocessing, a hierarchical ascendent classification was performed to cluster gabapentinoids and other Ca v -ligand drugs that share a similar ADR signature. The robustness of the results was determined through four sensitivity analyses, varying on the dataset or the clustering method., Results: A total of 16 drugs and 65 ADRs were included. Gabapentinoids were in Cluster #1, which included eight other drugs (isradipine, nicardipine, lacidipine, lercanidipine, ethosuximide, levetiracetam, zonisamide and nimodipine). Cluster #2 contained two drugs (diltiazem and verapamil) and Cluster #3 contained four drugs (amlodipine, felodipine, nifedipine and nitrendipine). The clustering results were consistent in all sensitivity analyses., Conclusions: The safety profile of gabapentinoids overlaps with those of some dihydropyridine CCBs and Ca v -blocking anticonvulsants. These results could be used to anticipate some unidentified ADRs of gabapentinoids from information accumulated with older drugs and sharing a common molecular target and ADR signature., (© 2023 British Pharmacological Society.)

Aims: The aim of this study was to assess whether a pharmacist intervention associating medication reconciliation at discharge with a link to the community pharmacist reduces drug-related problems (DRP) in adult patients during the 7 days after hospital discharge in 22 university or general hospitals in France., Methods: We conducted a cluster randomised cross-over superiority trial with hospital units as the cluster unit. The primary outcome was a composite of any kind of DRP (prescription/dispensation, patient error or gap due to no medication available) during the 7 days after discharge, assessed by phone with the patient and community pharmacist. Among secondary outcomes, we studied self-reported unplanned hospitalisations at day 35 after discharge and severe iatrogenic problems., Results: A total of 1092 patients were enrolled in 48 units (538 in the experimental periods and 554 in the control periods). Three patients refused to have their data analysed and were excluded from the analyses. As compared with usual care, the pharmacist intervention led to a lower proportion of patients with at least one DRP (44.0% vs 50.6%; odds ratio [OR] 0.77, 95% confidence interval [CI] 0.61-0.98) and severe iatrogenic problems (5.2% vs 8.7%; OR 0.57, 95% CI 0.35-0.93) but no significant difference in unplanned hospitalisations at day 35 (5.8% vs 4.5%; OR 1.46, 95% CI 0.91-2.35)., Conclusion: Medication reconciliation associated with communication between the hospital and community pharmacist may decrease patient exposure to DRP and severe iatrogenic problems but not unplanned hospitalisation. However, this intervention could be recommended in health policies to improve drug management., (© 2020 The British Pharmacological Society.)

Background: We lack data on how physicians can instill confidence in patients., Objectives: We aimed to determine whether dress style (professional white coat or formal, semiformal or casual attire) affects confidence in the physician by patients (children, teenagers, adults) with dermatology complaints consulting in the hospital or private practice., Methods: Design. Descriptive prospective cross sectional study carried out from July 1, 2008 to July 1, 2009. Setting. Outpatients in the department of dermatology of a French tertiary care hospital, and two dermatological private consulting rooms. Participants and design. Consulting patients were ≥ 7 years and classified as children 7-11 years old, accompanying parents, teenagers (12-17 years), and adults ≥ 18 years consulting alone. Subjects viewed two iconographic boards containing 4 photographs in a random order of a male physician on 1 board and a female physician on the other board in 4 different dress styles: professional (white coat and stethoscope), formal (shirt and tie for men), semiformal, and casual (T-shirt, jeans). Subjects then completed a questionnaire asking them to rate, on a scale of 0-10, their confidence in the physicians portrayed and answered whether they considered physician dress important. Main outcomes and measures. The main outcome was subjects' ranking of photos of physicians by dress style, according to the confidence they felt. For children 7-11 years old, we considered the frequency of the chosen dress style. The secondary outcome was whether physician dress was important to patients., Results: We included 329 patients. Children at the hospital most frequently chose the photo of the physician, both male (62%) and female (64%), with the white coat. Teenagers' choices were professional dress, then semiformal, formal, and casual attire. Accompanying adults and adults consulting alone had the same ranking., Conclusions: In France, patients of all ages who consult for dermatology complaints in hospital and in private practice have the most confidence in a physician who wears a professional white coat., (© 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.)

Objective: To assess the impact, in terms of statistical power and bias of treatment effect, of approaches to dealing with missing data in randomized controlled trials of rheumatoid arthritis with radiographic outcomes., Methods: We performed a simulation study. The missingness mechanisms we investigated copied the process of withdrawal from trials due to lack of efficacy. We compared 3 methods of managing missing data: all available data (case-complete), last observation carried forward (LOCF), and multiple imputation. Data were then analyzed by classic t-test (comparing the mean absolute change between baseline and final visit) or F test (estimation of treatment effect with repeated measurements by a linear mixed-effects model)., Results: With a missing data rate close to 15%, the treatment effect was underestimated by 18% as estimated by a linear mixed-effects model with a multiple imputation approach to missing data. This bias was lower than that obtained with the case-complete approach (-25%) or LOCF approach (-35%). This statistical approach (combination of multiple imputation and mixed-effects analysis) was moreover associated with a power of 70% (for a 90% nominal level), whereas LOCF was associated with a power of 55% and a case-complete power of 58%. Analysis with the t-test gave qualitatively equivalent but poorer quality results, except when multiple imputation was applied., Conclusion: Our simulation study demonstrated multiple imputation, offering the smallest bias in treatment effect and the highest power. These results can help in planning trials, especially in choosing methods of imputation and data analysis.

Aims: Toxicity and response are correlated with plasma 5-fluorouracil (5-FU) concentration in patients treated with 5-FU at a dose of 1000 mg m(-2) day(-1). Head and neck cancer patients are treated with various therapeutic regimens, including chemotherapy with 5-FU at a dose of 600 mg m(-2) day(-1) with radiotherapy. We investigated the plasma concentration-effect relationship for this regimen, with the aim of developing recommendations for dose adjustment., Methods: Patients received 5-FU at doses of 600 or 1000 mg m(-2) day(-1), as a continuous infusion over 4 or 5 days, with or without radiotherapy for the 600 mg m(-2) day(-1) regimen. The area under the curve (AUC) for 5-FU concentration was estimated, based on a single morning blood sample taken each day during treatment. AUC values were compared between patients with and without toxicity. This simplified method for AUC estimation was compared with the standard two-samples-per-day method in an independent group of 50 patients., Results: Forty-six patients, corresponding to 115 courses, were included in this prospective study. Considerable interindividual variability in estimated AUC was observed for both doses. Grade 3-4 toxicity occurred in 10 and 21% of patients given doses of 600 and 1000 mg m(-2) day(-1), respectively. Ths study confirmed the relationship between plasma 5-FU concentration and toxicity previously reported for 1000 mg m(-2) day(-1), but found no such relationship for the 600 mg m(-2) day(-1) regimen with concomitant radiotherapy., Conclusions: Our results do not support the use of therapeutic drug monitoring to improve tolerance for the 600 mg m(-2) day(-1) regimen with concomitant radiotherapy. A simplified method is proposed for 5-FU monitoring for the 1000 mg m(-2) day(-1) regimen.

Objective: To evaluate the methodologic quality of and identify methodologic issues in superiority trials assessing structural outcomes in rheumatic diseases., Methods: We searched Medline and the Cochrane Central Register of Controlled Trials for reports of randomized controlled trials assessing structural outcomes in osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis (OP) published between January 1994 and December 2003 in high-impact factor general medical and specialty journals. One reader extracted data (quality assessment, intent-to-treat analysis [ITT analysis], rate of missing data, and methods of handling missing data), using a standardized form., Results: A total of 81 reports were included in the analysis (37 on OP, 34 on RA, and 10 on OA). The mean +/- SD methodologic quality scores on the Jadad scale (possible range 0-5) and the Delphi list (possible range 0-9) were 2.9 +/- 1.2 and 6.4 +/- 1.3, respectively. Although it was reported in 54 articles (66.7%) that the analysis was done on an ITT basis, full ITT analysis was performed in only 6 of the studies (7.4%), modified ITT analysis in 11 (13.6%), and case-complete analysis in 48 (59.3%); the analysis was unclear in 16 articles (19.8%). The rate of missing data on structural outcomes could be determined in only 63 articles (77.8%) and was >20% in approximately one-third of these reports. Methods for handling missing data on structural outcomes were described in 19 articles (23.5%) and were, in general, inappropriate., Conclusion: Lack of ITT analysis and a high rate of missing data in superiority trials assessing structural outcomes may bias results from such trials. Our recommendations for improving these shortcomings may help researchers plan, analyze, and report the results of such trials.

Objectives: To assess clinical failure and symptom recurrence after uterine artery embolisation (UAE) and to define predictive factors., Design: Prospective study of a case series., Setting: Gynaecology and radiology departments of a French University Hospital., Population: Eighty-five women who underwent embolisation for the treatment of uterine fibroids., Method: Vascular access was obtained via the right common femoral artery. Free-flow embolisation was performed using 150-250 mum polyvinyl alcohol particles and an absorbable particle sponge., Main Outcome Measures: Clinical failure was defined as persistence of symptoms at three months of follow up and recurrence as return of symptoms. The main outcome measure was the need for further treatment after UAE., Results: Results are available for 81 patients. Median follow up was 30 months. There were 15 clinical failures and recurrences requiring further treatment (eight hysterectomies, five hysteroscopic resections for submucous fibroids, one second embolisation and one woman refusing further treatment). Recurrence-free survival rate at 30 months (no clinical failure, no recurrence) was 82.8% (95% CI 73.7-91.8%). Multivariate analysis identified two predictive factors: dominant fibroid size on ultrasound imaging (each 1 cm increase: HR = 1.68, 95% CI 1.10-2.69) and number of fibroids (each additional fibroid: HR = 1.34, 95% CI 1.08-1.66)., Conclusions: Symptom recurrence rate 30 months after fibroid embolisation was 17.2%. Fibroid size and number were predictive factors for recurrence. As most recurrences occurred after two years, we recommend that patients be monitored clinically and that imaging be for more than two years after UAE.

Aims: To assess the equivalence of amoxicillin/clavulanic acid and placebo in the prevention of acute otitis media in children at high risk of acute otitis media who develop upper respiratory tract infection., Methods: This was a multicentre, equivalence, randomized, double-blind trial of two parallel groups comparing 5 days of amoxicillin/clavulanic acid 75 mg kg-1 day-1 (i.e. 25 mg kg-1 every 8 h) and placebo. The main outcome measure was acute otitis media occurring within 8-12 days of initiating treatment., Results: Two hundred and three infants, aged 3 months-3 years with upper respiratory tract infection over 36 h and a history of recurrent acute otitis media were included over 8.5 months. Two children were lost to follow-up. Patient characteristics were similar in both groups. In the intention to treat analysis the frequency of acute otitis media was 16.2% (16/99) in the placebo group and 9.6% (10/104) in the amoxicillin/clavulanic acid group (P = 0.288). The difference between acute otitis media rates was 6.6% (one-sided 95% confidence interval of 14.3%). The occurrence of side-effects was similar in the amoxicillin/clavulanic acid and placebo groups., Conclusions: The difference in effectiveness between antibiotic and placebo was not greater than 14.3%, and we calculated that 94 children would need to be exposed to antibiotics to avoid six cases of acute otitis media. In view of the risk of development of resistance due to frequent exposure to antibiotics, our study supports the need for reduction in the administration of antibiotics in upper respiratory tract infection even in children at high risk of acute otitis media.

Aims: To assess the frequency of adverse drug reactions (ADRs) in children in France., Methods: In a prospective study over a period of 1 week, we evaluated the incidence of ADRs (1) as a cause of admission to a regional children's hospital; (2) occurring during hospitalization in a regional children's hospital; and (3) as a cause of consultation with private paediatricians., Results: Four out of 260 children were admitted to the regional children's hospital for ADRs (1.53% [0.42, 3.89]) and six developed ADRs during hospitalization (2.64% [0.97, 5.66]), 4/428 attended the Accident and Emergency Department for ADRs (0.93% [0.25, 2.37]) and 8/1192 consulted a private paediatrician for ADRs (0.67% [0.29, 1.31])., Conclusions: Our results are in agreement with the incidence of ADRs in children found in others countries.

Objective: To evaluate the efficacy of joint lavage and intraarticular steroid injection, alone and in combination, in the treatment of patients with symptomatic knee osteoarthritis (OA)., Methods: Ninety-eight patients with painful tibiofemoral OA were enrolled in a prospective, randomized, controlled, 2 x 2 factorial-design trial of 6 months' duration. The 4 treatment groups consisted of 1) intraarticular placebo (1.5 ml of 0.9% normal saline), 2) intraarticular corticosteroids (3.75 mg of cortivazol in 1.5 ml), 3) joint lavage and intraarticular placebo, and 4) joint lavage and intraarticular corticosteroid. Outcome measures evaluated at baseline, week 1, week 4, week 12, and week 24 included severity of pain (100-mm visual analog scale [VAS]), global status (100-mm VAS), and Lequesne's functional index., Results: No interaction between steroid injection and joint lavage was demonstrated. Patients who had undergone joint lavage had significantly improved pain VAS scores at week 24 (P = 0.020). In contrast, corticosteroid injection had no long-term effect (P = 0.313); corticosteroid injection was associated with a decrease in pain only at week 1 (P = 0.003) and week 4 (P = 0.020). After week 4, Lequesne's functional index was not significantly improved regardless of the assigned treatment., Conclusion: Compared with placebo, both treatments significantly relieved pain but did not improve functional impairment. The effects of the 2 treatments were additive. Cortivazol provided short-term relief of pain (up to week 4). The effects of joint lavage persisted up to week 24.