[18F]FDG PET/CT for therapeutic assessment of Abatacept in early-onset polymyalgia rheumatica.

PURPOSE: Evaluate the benefit of 2-deoxy-2-[18F]-fluoro-D-glucose ([18F] FDG) positron emission tomography/computed tomography (PET/CT) for the therapeutic assessment of Abatacept (ABA) as first-line therapy in early-onset polymyalgia rheumatica (PMR) patients. METHODS: This was an ancillary study of ALORS trial (Abatacept in earLy Onset polymyalgia Rheumatica Study) assessing the ability of ABA versus placebo to achieve low disease activity (C-Reactive Protein PMR activity score (CRP PMR-AS) ≤ to 10) without glucocorticoid (GC) at week 12 in patients with early-onset PMR. The patients underwent [18F] FDG PET/CT at baseline and after 12 weeks of treatment. Responses to treatments were evaluated according to CRP PMR-AS, Erythrocyte Sedimentation Rate (ESR) PMR-AS, Clin PMR-AS, and CRP-Imputed (Imput-CRP) PMR-AS. Quantitative score by maximal standardized uptake value (SUVmax) and combined qualitative scores according to liver uptake (Leuven, Leuven/Groningen, and Besançon Scores) were used for assessment of [18F] FDG uptake in regions of interest (ROI) usually affected in PMR. Student's t-test was applied to evaluate the clinical, biological, and [18F] FDG uptake variation difference in ABA and placebo groups between W0 and W12. Subgroup analysis by GC rescue was performed. RESULTS: At W12, there was no significant difference according to SUVmax between the ABA and the placebo groups in all ROI. Subgroup analysis according to GC administration demonstrated a significant (p 0.047) decrease in SUVmax within the left sternoclavicular joint ROI in the ABA group (- 0.8) compared to the placebo group (+ 0.6) without GC rescue. Other results did not reveal any significant difference between the ABA and placebo groups. According to combined qualitative scores, there was no significant difference between ABA and placebo groups for the direct comparison analysis and subgroup analysis according to GC rescue. CONCLUSION: [18F] FDG PET/CT uptake did not decrease significantly after ABA compared to placebo in anatomical areas usually affected in PMR patients. These results are correlated with the clinical-biological therapeutic assessment. CLINICAL TRIAL REGISTRATION: The study was approved by the appropriate ethics committee (CPP Sud-Est II Ref CPP: 2018-33), and all patients gave their written informed consent before study enrollment. The protocol was registered on Clinicaltrials.gov (NCT03632187).

Effect of Different Modalities of Purgative Preparation on the Diagnostic Yield of Small Bowel Capsule for the Exploration of Suspected Small Bowel Bleeding: A Multicenter Randomized Controlled Trial.

INTRODUCTION: The aim of our study was to compare clear liquid diet with 2 different polyethylene glycol (PEG)-based bowel preparation methods regarding diagnostic yield of small bowel capsule endoscopy (SBCE) in patients with suspected small bowel bleeding (SBB). METHODS: In this prospective multicenter randomized controlled trial, consecutive patients undergoing SBCE for suspected SBB between September 2010 and February 2016 were considered. Patients were randomly assigned to standard regimen, that is, clear fluids only (prep 1), standard regimen plus 500 mL PEG after SBCE ingestion (prep 2), or standard regimen plus 2 L PEG plus 500 mL PEG after SBCE ingestion (prep 3). The primary outcome was the detection of at least one clinically significant lesion in the small bowel. The quality of small bowel cleansing was assessed. A questionnaire on the clinical tolerance was filled by the patients. RESULTS: We analyzed 834 patients. No significant difference was observed for detection of P1 or P2 small bowel lesions between prep1 group (40.5%), prep 2 group (40.2%), and prep 3 group (38.5%). Small bowel cleansing was improved in prep 2 and 3 groups compared with that in prep 1 group. Compliance to the preparation and tolerance was better in prep 2 group than in prep 3 group. DISCUSSION: Small bowel purgative before SBCE allowed better quality of cleansing. However, it did not improve diagnostic yield of SBCE for suspected SBB.

Hospitalization for adverse events under abiraterone or enzalutamide exposure in real-world setting: A French population-based study on prostate cancer patients.

AIMS: Safety profiles of abiraterone and enzalutamide rely mainly on Phase III clinical trials. Our objective was to estimate the incidence rate ratio (IRR) for certain adverse events leading in real life to hospitalization (atrial fibrillation, acute heart failure, ischaemic heart disease, acute kidney injury [AKI], ischaemic stroke, torsade de pointe/QT interval prolongation, hepatitis and seizure), comparing abiraterone to enzalutamide. We also set out to discuss previously identified safety signals. METHOD: Using the French National Health Insurance System database, all patients newly exposed to abiraterone or enzalutamide between 2013 and 2017 and followed until 31 December 2018 were targeted. IRRs for each event were estimated using a Poisson model in a sub-population of patients without contraindications or precautions for use for either treatment. RESULTS: Among 11 534 new users of abiraterone and enzalutamide, AKI (IRR 1.42, 95% CI: 1.01-2.00), liver monitoring suggestive of hepatic damage (IRR 3.06, 95% CI: 2.66-3.53) and atrial fibrillation (IRR 1.12, 95% CI: 1.05-1.19) were significantly more often observed with abiraterone than with enzalutamide. CONCLUSION: Our study provides knowledge on abiraterone and enzalutamide real-life safety profiles, especially for events leading to hospitalization. Despite several limitations, including the lack of clinical data, the safety signal for AKI under abiraterone is in line with results of an analysis of the French pharmacovigilance database, which requires further specific investigations. Enlightening the clinicians' therapeutic choices for patients treated for prostate cancer, our study should lead to clinicians being cautious in the use of abiraterone.

Effect of neuromuscular electrical stimulation on exercise capacity in patients with severe chronic obstructive pulmonary disease: A randomised controlled trial.

OBJECTIVE: To compare strengthening by neuromuscular electrical stimulation versus cycle ergometer training during a pulmonary rehabilitation program, in patients with severe to very severe chronic obstructive pulmonary disease. DESIGN: A prospective randomized controlled study. SETTING: Two inpatient pulmonary rehabilitation centers. SUBJECTS: Patients with severe to very severe chronic obstructive pulmonary disease and multidimensional index to predict risk of death ≥5, were randomly assigned to receive neuromuscular electrical stimulation or cycle ergometer training during pulmonary rehabilitation. MAIN MEASURES: The primary endpoint was the change in exercise capacity using 1-min sit-to-stand test Secondary endpoints were the changes in exercise capacity using 6-min walk test, quadriceps strength, quality of life and dyspnea. RESULTS: 102 patients were included. After 3 weeks, 47 patients in the neuromuscular electrical stimulation group, and 45 in the cycle ergometer training group were able to be analyzed. No significant difference was seen in the evolution of exercise capacity using 1-min sit-to-stand test (3.3 ± 3.8 and 2.6 ± 4.1) and 6-min walk test (37.8 ± 58.4 and 33.1 ± 46.7), in the evolution of quadriceps strength and endurance (9.2 ± 12.9 and 6.6 ± 16.1; 9.0 ± 13.2 and 6.2 ± 17.0), in the evolution of quality of life (St George's Respiratory Questionnaire: -11.3 ± 11.7 and -8.1 ± 11.6; COPD Assessment Test: -5.7 ± 7.1 and -4.7 ± 7.0), or in the evolution of dyspnea using Dyspnea 12 (-5.5 ± 10.2 and -5.9 ± 8.5) except using modified medical research council scale (95% confidence interval: 0.48 [0.05; 0.91], p = 0.027). CONCLUSION: We found no significant difference between the two programs on exercise capacity, quadriceps strength and quality of life.

Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial.

Importance: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica. Objective: To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day. Interventions: Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone. Main Outcomes and Measures: The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone. Results: Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, -7.5 [95% CI, -11.2 to -3.8]; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group. Conclusions and Relevance: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms. Trial Registration: ClinicalTrials.gov Identifier: NCT02908217.

Additional, Mechanized Upper Limb Self-Rehabilitation in Patients With Subacute Stroke: The REM-AVC Randomized Trial.

Background and Purpose: Additional therapy may improve poststroke outcomes. Self-rehabilitation is a useful means to increase rehabilitation time. Mechanized systems are usual means to extend time for motor training. The primary aim was to compare the effects of self-rehabilitation using a mechanized device with control self-exercises on upper extremity impairment in patients with stroke. Methods: Phase III, parallel, concealed allocation, randomized controlled, multicenter trial, with 12-month follow-up. Patients aged 18 to 80 years, 3 weeks to 3 months poststroke with a Fugl-Meyer Assessment score of 10 to 40 points, were randomized to the Exo or control groups. All undertook two 30-minute self-rehabilitation sessions/day, 5 days/wk for 4 weeks in addition to usual rehabilitation. The Exo group performed games-based exercises using a gravity-supported mechanical exoskeleton (Armeo Spring). The control group performed stretching plus basic active exercises. Primary outcome was change in upper extremity Fugl-Meyer Assessment score at 4 weeks. Results: Two hundred fifteen participants were randomly allocated to the Exo group (107) or the control group (108). Mean age (SD), 58.3 (13.6) years; mean time poststroke, 54.8 (22.1) days; and mean baseline Fugl-Meyer Assessment score, 26.1 (9.5). There was no between-group difference in mean change in Fugl-Meyer Assessment score following the intervention: 13.3 (9.0) in the Exo group and 11.8 (8.8) in the control group (P=0.22). There were no significant between-group differences in changes for any of the other outcomes at any time point (except for perception of the self-rehabilitation). There was no between-group difference in cost utility at 12 months. Conclusions: In patients with moderate-to-severe impairment in the subacute phase of stroke, the purchase and use of complex devices to provide additional upper limb training may not be necessary: simply educating patients to regularly move and stretch their limbs appears sufficient. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01383512.

Overall Survival Among Chemotherapy-Naive Patients With Castration-Resistant Prostate Cancer Under Abiraterone Versus Enzalutamide: A Direct Comparison Based on a 2014-2018 French Population Study (the SPEAR Cohort).

Abiraterone acetate (ABI) and enzalutamide (ENZ) are considered to be clinically relevant comparators among chemotherapy-naive patients with castration-resistant prostate cancer. No clinical trials comparing overall survival with ABI versus ENZ in a head-to-head approach have been published so far. A few observational studies with low power suggested a potential benefit of ENZ. We used the French National Health Data System to compare overall survival of new users of ABI and ENZ among chemotherapy-naive patients with castration-resistant prostate cancer in 2014-2017, followed through 2018 (the SPEAR cohort, a 2014-2018 cohort study). With an intent-to-treat approach, a survival analysis was performed, estimating hazard ratios for overall survival with the inverse probability weighted Cox model method. Among 10,308 new users, 64% were treated with ABI and 36% with ENZ. The crude mortality rate was 25.2 per 100 person-years (95% confidence interval (CI): 24.4, 26.0) for ABI and 23.7 per 100 person-years (95% CI: 22.6, 24.9) for ENZ. In the weighted analysis, ENZ was associated with better overall survival compared with ABI (hazard ratio = 0.90 (95% CI: 0.85, 0.96) with a median overall survival of 31.7 months for ABI and 34.2 months for ENZ). When restricting to 2015-2017 new users, the effect estimate shifted up to a hazard ratio of 0.93 (95% CI: 0.86, 1.01).

Impact of recommendations on sodium valproate prescription among women with epilepsy: An interrupted time-series study.

BACKGROUND: The European Medicines Agency (EMA) has developed risk minimization measures (RMMs) to reduce the use of the teratogenic drug, sodium valproate (VPA). The objective was to assess the impact of these RMMs among females with epilepsy in France. METHODS: We used data from the French National Health Insurance Database (SNDS), including 114,936 females aged under 50, with a reimbursement claim for an antiepileptic drug from January 2011 to December 2017, and identified as people with epilepsy. We used a controlled interrupted time series stratifying on age: girls (0-14 years old) and women of childbearing age (15-49 years), and with 129,917 males as controls. RESULTS: VPA prevalent use among girls and women of childbearing age with epilepsy decreased significantly after the issue of the RMMs (trend changes of, respectively, -5 and -4 users per 1000 females at-risk per quarter in comparison to the control group). We did not detect any significant change in VPA incident use. CONCLUSIONS: VPA use decreased over the study period among females with epilepsy but there were still 317 women and 206 girls started on VPA therapy VPA in 2017 (8 per 1000 at-risk and 18 per 1000, respectively). This suggests that either the measures should be strengthened or that the lowest level of VPA use has been reached. In this context, the introduction of a new RMM (in 2018) needs to be evaluated.

Gender difference of geographic distribution of the stroke incidence affected by socioeconomic, clinical and urban-rural factors: an ecological study based on data from the Brest stroke registry in France.

BACKGROUND: Mapping the spatial distribution of disease occurrence is a strategy to identify contextual factors that could be useful for public health policies. The purpose of this ecological study was to examine to which extent the socioeconomic deprivation and the urbanization level can explain gender difference of geographic distribution in stroke incidence in Pays de Brest, France between 2008 and 2013. METHODS: Stroke cases aged 60 years or more were extracted from the Brest stroke registry and combined at the census block level. Contextual socioeconomic, demographic, and geographic variables at the census block level come from the 2013 national census. We used spatial and non-spatial regression models to study the geographic correlation between socioeconomic deprivation, degree or urbanization and stroke incidence. We generated maps using spatial geographically weighted models, after longitude and latitude smoothing and adjustment for covariates. RESULTS: Stroke incidence was comparable in women and men (6.26 ± 3.5 vs 6.91 ± 3.3 per 1000 inhabitants-year, respectively). Results showed different patterns of the distribution of stroke risk and its association with deprivation or urbanisation across gender. For women, stroke incidence was spatially homogeneous over the entire study area, but was associated with deprivation level in urban census blocks: age adjusted risk ratio of high versus low deprivation = 1.24, [95%CI 1.04-1.46]. For men, three geographic clusters were identified. One located in the northern rural and deprived census blocks with a 9-14% increase in the risk of stroke. Two others clusters located in the south-eastern (mostly urban part) and south-western (suburban and rural part) with low deprivation level and associated with higher risk of stroke incidence between (3 and 8%) and (8.5 and 19%) respectively. There were no differences in profile of cardiovascular risk factors, stroke type and stroke severity between clusters, or when comparing clusters cases to the rest of the study population. CONCLUSIONS: Understanding whether and how neighborhood and patient's characteristics influence stroke risk may be useful for both epidemiological research and healthcare service planning.

The efficacy of a targeted PREVENTION programme for addictive behaviour (PREVENTURE) among vulnerable ADOlescents in France - study procotol.

BACKGROUND: Alcohol use is a major public health challenge in France, where at the age of 17 half the young people report an episode of severe alcohol intoxication in the month preceding the survey. Numerous prevention programmes have a general objective, but in adolescence individual vulnerabilities towards addictions differ significantly with personality traits. Prevention targeting personality traits enables work on risk factors for addictive behaviours, and has shown genuine efficacy. Among existing programmes, PREVENTURE has shown an effect on the reduction in alcohol consumption by targeting four personality traits: impulsivity, sensation-seeking, negative thoughts and anxiety. This programme has been tested on samples recruited in adolescent populations in school environments, identifying adolescents at risk, but it has not been tested on a more targeted recruitment of adolescents seen in consultation. METHODS: The main hypothesis of this study is that the targeted prevention programme PREVENTURE will have an impact on the prevalence of binge-drinking episodes. The secondary hypotheses explore other factors such as associated substance use, anxiety and depression, as well as the acceptability of the programme. This article presents the study protocol of "PREVADO" study. We intend to assess the impact of the targeted intervention programme PREVENTURE on the prevalence of binge-drinking episodes among adolescents aged 14 to 17 years consulting in one of the participating centres or referred by a school doctor. The study will be prospective, randomised, controlled and open-label, and will comprise an intervention group and a control group. The adolescents will then be followed and assessed 1, 3, 6 and 12 months after the intervention. The study needs to include 700 subjects in order to reach 340 adolescents randomised, 170 in each group. It will concern 33 centres. DISCUSSION: This project could favour the targeting of addictive behaviours among vulnerable adolescents, and its application on a larger scale could be envisaged. TRIAL REGISTRATION: The Trial registration number is NCT04599270 , and it was registered on the ClinicalTrials.gov public website.

Major bleeding risk associated with oral anticoagulant in real clinical practice. A multicentre 3-year period population-based prospective cohort study.

AIMS: The objective was to compare major bleeding risk of direct oral anticoagulants (DOACs; per type and dose) with vitamin K antagonists (VKAs), irrespective of indication, using real-world data. METHODS: A population-based prospective cohort study, using the French national health data system (SNIIRAM), identified 47 469 adults living within 5 well-defined geographical areas, who were new users of oral anticoagulants in the period 2013-2015: 20 205 VKA users, 19 579 rivaroxaban users, 4225 dabigatran users and 3460 apixaban users. From all emergency departments within these areas, clinical data for all adults referred for bleeding was collected and medically validated. The databases were linked for common key variables. The main outcome measure was major bleeding: intracranial haemorrhage, major gastrointestinal bleeding and other major bleeding events. Hazard ratios were derived from adjusted Cox proportional hazard models. We used propensity score weighting as a sensitivity analysis, with separate analyses according to indications (atrial fibrillation or venous thromboembolism). RESULTS: Compared to VKAs, high and low-dose DOACs were associated with a reduced risk of intracranial haemorrhage (adjusted hazard ratio 0.55, 95% confidence interval 0.37-0.82 and 0.54, 0.26-1.12 respectively), and a reduced risk of other major bleeding events (0.41, 0.29-0.58 and 0.41, 0.22-0.79 respectively), irrespective of duration and indication. Neither DOAC dose evidenced any significant difference from VKAs in terms of risk of major gastrointestinal bleeding. CONCLUSION: There is a clear benefit of using DOACs with regard to intracranial haemorrhage. The study provides new insight into major gastrointestinal and other major bleeding events.

Protocol of changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with bilateral cerebral palsy: a multisite randomized controlled trial.

BACKGROUND: Cerebral palsy (CP), which is the leading cause of motor disability during childhood, can produce sensory and cognitive impairments at different degrees. Most recent therapeutic interventions for these patients have solely focused on upper extremities (UE), although more than 60% of these patients present lower extremities (LE) deficits. Recently, a new therapeutic concept, Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE), has been proposed, involving the constant stimulation of UE and LE. Based on motor skill learning principles, HABIT-ILE is delivered in a day-camp setting, promoting voluntary movements for several hours per day during 10 consecutive week days. Interestingly, the effects of this intervention in a large scale of youngsters are yet to be observed. This is of interest due to the lack of knowledge on functional, neuroplastic and biomechanical changes in infants with bilateral CP. The aim of this randomized controlled study is to assess the effects of HABIT-ILE adapted for pre-school children with bilateral CP regarding functional, neuroplastic and biomechanical factors. METHODS: This international, multicentric study will include 50 pre-school children with CP from 12 to 60 months of age, comparing the effect of 50 h (2 weeks) of HABIT-ILE versus regular motor activity and/or customary rehabilitation. HABIT-ILE presents structured activities and functional tasks with continuous increase in difficulty while the child evolves. Assessments will be performed at 3 period times: baseline, two weeks later and 3 months later. The primary outcome will be the Gross Motor Function Measure 66. Secondary outcomes will include Both Hands Assessment, Melbourne Assessment-2, Semmes-Weinstein Monofilament Test, algometry assessments, executive function tests, ACTIVLIM-CP questionnaire, Pediatric Evaluation of Disability Inventory (computer adaptative test), Young Children's Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, neuroimaging and kinematics. DISCUSSION: The results of this study should highlight the impact of a motor, intensive, goal-directed therapy (HABIT-ILE) in pre-school children at a functional, neuroplastic and biomechanical level. In addition, this changes could demonstrated the impact of this intervention in the developmental curve of each child, improving functional ability, activity and participation in short-, mid- and long-term. NAME OF THE REGISTRY: Evaluation of Functional, Neuroplastic and Biomechanical Changes Induced by an Intensive, Playful Early-morning Treatment Including Lower Limbs (EARLY-HABIT-ILE) in Preschool Children With Uni and Bilateral Cerebral Palsy (HABIT-ILE). TRIAL REGISTRATION: NCT04017871 REGISTRATION DATE: July 12, 2019.

Stroke Incidence and Case Fatality According to Rural or Urban Residence: Results From the French Brest Stroke Registry.

Background and Purpose- Recent findings suggest that in the United States, stroke incidence is higher in rural than in urban areas. Similar analyses in other high-income countries are scarce with conflicting results. In 2008, the Brest Stroke Registry was started in western France, an area that includes about 366 000 individuals living in various urban and rural settings. Methods- All new patients with stroke included in the Brest Stroke Registry from 2008 to 2013 were classified as residing in town centers, suburbs, isolated towns, or rural areas. Poisson regression was used to analyze stroke incidence and 30-day case fatality variations in the 4 different residence categories. Models with case fatality as outcome were adjusted for age, stroke type, and stroke severity. Results- In total, 3854 incident stroke cases (n=2039 women, 53%) were identified during the study period. Demographic and socio-economic characteristics and primary healthcare access indicators were significantly different among the 4 residence categories. Patterns of risk factors, stroke type, and severity were comparable among residence categories in both sexes. Age-standardized stroke rates varied from 2.90 per thousand (95% CI, 2.59-3.21) in suburbs to 3.35 (95% CI, 2.98-3.73) in rural areas for men, and from 2.14 (95% CI, 2.00-2.28) in town centers to 2.34 (95% CI, 2.12-2.57) in suburbs for women. Regression models suggested that among men, stroke incidence was significantly lower in suburbs than in town centers (incidence rate ratio =0.87; 95% CI, 0.77-0.99). Case fatality risk was comparable across urban categories but lower in rural patients (relative risk versus town centers: 0.76; 95% CI, 0.60-0.96). Conclusions- Stroke incidence was comparable, and the 30-day case fatality only slightly varied in the 4 residence categories despite widely different socio-demographic features covered by the Brest Stroke Registry.

Use of 5α-reductase inhibitors for benign prostate hypertrophy and risk of high grade prostate cancer: a French population-based study.

OBJECTIVE: To assess the association between 5α-reductase inhibitor (5-ARI) use and high grade (Gleason score 8-10) prostate cancer. PATIENTS AND METHODS: We conducted a population-based nested matched case-control study using the French national health insurance database linked to data from all pathology laboratories in Brittany, France. Among 74 596 patients with ≥1 drug reimbursement for symptomatic benign prostate hypertrophy (BPH) between 1 January 2010 and 31 December 2011, 767 incident prostate cancer cases between 1 January 2012 and 31 December 2013 were matched according to age and delay between the first observed delivery of drug for BPH (5-ARIs, α-blockers or phytotherapy) and diagnostic date of the case to five control patients, using an incidence density sampling design. RESULTS: A total of 963 patients (153 cases, 810 controls) had been exposed to 5-ARIs. A significant heterogeneity (P = 0.005) was detected across cancer grades when estimating the association between prostate cancer and long-term (≥2 years) 5-ARI use vs no 5-ARI exposure: adjusted conditional odds ratio 1.76 (95% confidence interval [CI] 0.97-3.21) for Gleason score ≥8 and 0.64 (95% CI 0.44-0.93) for Gleason score < 8. CONCLUSION: Our results indicate an increased risk of high grade and a decreased risk of low grade prostate cancer associated with 5-ARI use. Patients treated for >2 years with 5-ARIs should be informed about the increased risk of development of high grade disease.

Risk factors for immersion pulmonary edema in recreational scuba divers: a case-control study.

BACKGROUND: Immersion can cause immersion pulmonary edema (IPE) in previously healthy subjects. We performed a case-control study to better identify IPE risk factors. METHODS: We prospectively included recreational scuba divers who had presented signs of IPE and control divers who were randomly chosen among diving members of the French Underwater Federation. We sent an anonymous questionnaire to each diver, with questions on individual characteristics, as well as the conditions of the most recent dive (controls) or the dive during which IPE occurred. Univariate logistic regressions were performed for each relevant factor. Then, multivariate logistic regression was performed. RESULTS: Of the 882 questionnaires sent, 480 (54%) were returned from 88 cases (90%) and 392 control divers (50%). Multivariate analysis identified the following independent risk factors associated with IPE: being aged over 50 years ((OR) 3.30, (95%CI) 1.76-6.19); female sex (OR 2.20, 95%CI 1.19-4.08); non-steroidal anti-inflammatory drug (NSAID) intake before diving (OR 24.32, 95%CI 2.86-206.91); depth of dive over 20 m (OR 2.00, 95%CI 1.07-3.74); physical exertion prior to or during the dive (OR 5.51, 95%CI 2.69-11.28); training dive type (OR 5.34, 95%CI 2.62-10.86); and daily medication intake (OR 2.79, 95%CI 1.50-5.21); this latter factor appeared to be associated with hypertension in the univariate analysis. CONCLUSION: To reduce the risk of experiencing IPE, divers over 50 years of age or with hypertension, especially women, should avoid extensive physical effort, psychological stress, deep dives and NSAID intake before diving.

Non-adherence to treatment with cytoreductive and/or antithrombotic drugs is frequent and associated with an increased risk of complications in patients with polycythemia vera or essential thrombocythemia (OUEST study).

The purpose of this study was to identify the incidence, causes and impact of non-adherence to oral and subcutaneous chronic treatments for patients with polycythemia vera or essential thrombocythemia. Patients receiving cytoreductive drugs for polycythemia vera or essential thrombocythemia were recruited at our institution (Observatoire Brestois des Néoplasies Myéloprolifératives registry). They completed a one-shot questionnaire designed by investigators (Etude de l'Observance Thérapeutique et des Effets Secondaires des Traitements study). Data about complications (thrombosis, transformation and death) at any time in the patient's life (before diagnosis, up until consultation and after the completion of the questionnaire) were collected. Sixty-five (22.7%) of 286 patients reported poor adherence (<90%) to their treatment with cytoreductive drugs and 46/255/18%) also declared non-adherence to antithrombotic drugs. In total, 85/286 patients (29.7%) declared they did not adhere to their treatment. Missing an intake was rare and was mostly due to forgetfulness especially during occupational travel and holidays. Patients who did not adhere to their treatment were characterized by younger age, living alone, having few medications but a high numbers of pills and determining their own schedule of drug intake. Having experienced thrombosis or hematologic evolution did not influence the adherence rate. Non-adherence to oral therapy was associated with a higher risk of phenotypic evolution (7.3 versus 1.8%, P=0.05). For patients treated for polycythemia vera or essential thrombocythemia, non-adherence to cytoreductive and/or antithrombotic therapies is frequent and is influenced by age, habitus and concomitant treatments, but not by disease history or treatment side effects. Phenotypic evolution seems to be more frequent in the non-adherent group.

Comparison between preprandial vs. postprandial insulin aspart in patients with type 1 diabetes on insulin pump and real-time continuous glucose monitoring.

BACKGROUND: The objective was to compare glycemic control between preprandial and postprandial bolus administration (15 min before [PRE] or immediately after the meal [POST]) in patients with type 1 diabetes using insulin pump and real-time continuous glucose monitoring. METHODS: Between September 2015 and February 2016, a single-centre, open randomized, 2-way crossover study of patients on bolus insulin aspart administration was conducted during two 14-day periods and according to 2 administration regimen schedules (PRE/POST or POST/PRE). Inclusion criteria were as follows: patients with type 1 diabetes, ≥18 and ≤ 65 years old, treated with insulin aspart using a Medtronic® insulin pump and trained on functional insulin therapy. Patients were randomly assigned to either regimen schedule. At the beginning of each period, each patient was provided with a standardized high fat meal. Primary outcome was the area under the curve for interstitial glucose above 140 mg/dL per minute (AUC > 140 mg/dL/min) during each period. Secondary outcomes were time spent in hypo/eu/hyperglycemia, glycemic variability indices, and AUC during 4 hours after high fat meal calculated with continuous glucose monitoring data. RESULTS: Twenty-two patients were included. Mean AUC > 140 mg/dL/min was statistically higher in patients on POST (43.70 mg/dL/min; 95%CI: 34.08 to 53.31) versus PRE insulin aspart regimen (37.24 mg/dL/min 95%CI: 27.63 to 46.85) (P = 0.03). Mean interstitial glycemia and glycemic variability indices were also increased (P < 0.05) on POST regimen. The mean AUC 4 hours after the high fat meal was higher on POST regimen but not statistically different (P = 0.06). CONCLUSIONS: In our study, postprandial administration of insulin aspart appears to mildly increase glycemic excursion and glycemic variability.

Responsiveness and Minimally Important Difference of the 6-Minute Stepper Test in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: The validity and reproducibility of the 6-minute stepper test (6MST) have already been demonstrated in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: The aim of this study was to evaluate the responsiveness of the 6MST to pulmonary rehabilitation (PR) in patients with COPD, to determine a minimal important difference (MID) for the 6MST, and to compare the 6MST and the 6-minute walk test (6MWT). METHODS: Sixty-two patients with COPD were included in a prospective experimental study. Participants underwent a 3-week inpatient PR program. The primary outcome was the change in the number of steps during the 6MST measured before and after PR. The secondary outcome included the change in the 6-minute walking distance (6MWD) pulse oximetry, heart rate, dyspnea, and leg discomfort during the tests measured before and after PR. MID was determined by anchor-based and distribution approaches. RESULTS: After PR, we observed a significant increase in the number of steps during the 6MST (22.5 steps; 95% CI 13.8-31.3; p < 0.0001) and in the 6MWD (26.6 m; 95% CI 17.6-35.5; p < 0.0001). The 6MST and 6MWT were improved by 10.1 and 6.5%, respectively. The number of steps during the 6MST was significantly correlated with the 6MWD before (r = 0.72; p < 0.0001) and after PR (r = 0.66; p < 0.0001). MID was estimated to be around 20 steps. CONCLUSION: The 6MST appears to be as responsive as the 6MWT in assessing functional improvement during PR in patients with COPD. The 6MST is a low-cost assessment and requires limited space.

Development of a clinical prediction score for congestive heart failure diagnosis in the emergency care setting: The Brest score.

OBJECTIVE: To derive and validate a clinical prediction rule of acute congestive heart failure obtainable in the emergency care setting. DESIGN: Derivation of the score was performed on a retrospective 927 patients cohort admitted to our Emergency Department for dyspnea. The prediction model was externally validated on an independent 206-patient prospective cohort. INTERVENTIONS AND MEASURES: During the derivation phase, variables associated with acute congestive heart failure were included in a multivariate regression model. Logistic regression coefficients were used to assign scoring points to each variable. During the validation phase, every diagnosis was confirmed by an independent adjudication committee. RESULTS: The score comprised 11 variables: age ≥65 years (1 point), seizure dyspnea (2 points), night outbreak (1 point), orthopnea (1 point), history of pulmonary edema (2 points), chronic pulmonary disease (-2 points), myocardial infarction (1 point), crackles (2 points), leg edema (1 point), ST-segment abnormality (1 point), atrial fibrillation/flutter (1 point) on electrocardiography. In the validation step, 30 patients (14.6%) had a low clinical probability of acute congestive heart failure (score ≤3), of which only 2 (6.7%) had a proven acute cardiogenic pulmonary edema. The prevalence of acute congestive heart failure was 58.5% in the 94 patients with an intermediate probability (score of 4-8) and 91.5% in the 82 patients (39.8%) with a high probability (score ≥9). CONCLUSION: This score of acute congestive heart failure based on easily available and objective variables is entirely standardized. Applying the score to dyspneic adult emergency patients may enable a more rapid and efficient diagnostic process.

Reliability of histopathological salivary gland biopsy assessment in Sjögren's syndrome: a multicentre cohort study.

OBJECTIVE: The aim of this study was to assess intraobserver and interobserver reliability of minor salivary gland biopsy (MSGB) in SS. METHODS: All MSGBs available from the Tolerance and Efficacy of Rituximab in Primary Sjögren's Syndrome (TEARS) study were subjected to a standardized blinded assessment by a single specifically trained pathologist twice at a 2 month interval; both the Chisholm-Mason (CM) grade and the focus score (FS) were determined. Baseline histopathological reports by local pathologists at each study centre were compared with the first standardized blinded assessment. Agreement was assessed for the dichotomized FS (dFS) and dichotomized CM (dCM) grade, as well as for nine other histopathological features. RESULTS: Eighty-nine MSGBs were studied. Intraobserver κ values were 1 for dFS, 0.80 for dCM, 0.67 for germinal centre-like structures, 0.44 for fibrosis and 0.29 for confluent foci. Most of the local histopathological reports based their diagnosis on the CM grade, although the FS was often reported or the data needed to determine it were provided. Interobserver agreement κ values were 0.71 for dFS, 0.64 for dCM, 0.46 for focal lymphocytic sialadenitis, 0.42 for non-specific chronic inflammation and 0.16 for fibrosis. CONCLUSION: Although FS reliability was good, disparities were noted in the assessment methods used by local pathologists. The protocol for FS determination was not followed routinely, with the result that the FS was often overestimated. Germinal centre-like structures, which predict lymphoma, showed good reliability but were inconsistently reported.