Spirometry practice by French general practitioners between 2010 and 2018 in adults aged 40 to 75 years.

In France, most spirometries are performed by pneumologists. Spirometry is difficult to access due to the distance to medical office and long delays for appointments. This lack of accessibility contributes to the underdiagnosis of chronic obstructive pulmonary disease (COPD) among patients aged between 40 and 75 years. In recent years, general practitioners (GPs) have been performing spirometry in private practice. However, the extent of this practice is unknown. A French retrospective, repetitive transversal study analysed data from the "Système National des Données de Santé" (SNDS) database. The targeted population was GPs in primary care that performed spirometries between 2010 and 2018, in patients aged between 40 and 75 years. Between 2010 and 2018, 302,674 (7.2%) spirometries were performed in France by GPs in private practices, in patients 40 to 75 years old. 5.4% by "expert GPs" (>60 spirometries/year) and 1.8% by "non-expert GPs". In "non-expert GPs" (2.8% of French GPs in 2018), the annual number of spirometries increased by 701 each year (p < 2.104), the annual number of GPs performing spirometries increased by 114 each year (p < 2.10-5). Overall, 24.9% of the spirometries performed by GPs were referrals from other GPs. The number of spirometries performed by GPs and the number of GPs performing spirometries has gradually increased over time. However, this increase is inadequate considering the need to early detect and follow up respiratory disorders.

Factors associated with early relapse of infantile haemangioma in children treated for at least six months with oral propranolol: A case-control study using the 2014-2021 French Ouest DataHub.

BACKGROUND: The factors associated with early relapse of infantile haemangioma (IH) after a first course of treatment with oral propranolol for at least six months (initiated after the marketing authorization had been granted) have not previously been investigated. OBJECTIVES: To identify factors associated with the risk of early relapse in children with IH treated with oral propranolol according to the current prescribing guidelines. METHODS: We performed a multicentre, retrospective, case-control study, using the Ouest Data Hub database. All children treated for at least 6 months with oral propranolol for IH between 31 June 2014 and 31 December 2021, and with a follow-up visit at least three months after treatment discontinuation were included. A case was defined as relapse of IH within three months of treatment discontinuation; each case was matched for age at treatment initiation and for centre, with four (relapse-free) controls. The association between relapse and treatment or IH characteristics was expressed as an odds ratio (OR) from univariate and multivariate conditional logistic regressions. RESULTS: A total of 225 children were included. Of these, 36 (16%) relapsed early. In a multivariate analysis, a deep IH component was a risk factor for early relapse [OR = 8.93; 95%CI: 1.0-78.9, p = 0.05]. A propranolol dosage level of less than 3 mg/kg/day protected against early relapse [OR = 0.11; 95%CI: 0.02-0.7, p = 0.02]. Tapering before propranolol discontinuation was not associated with a lower risk of early relapse. CONCLUSION: The risk factors for late and early relapse are probably different. Investigation of the risk factors for early vs. late IH relapse is now warranted.

The cardiovascular safety of oral alitretinoin: a population-based cohort study involving 19 513 patients exposed to oral alitretinoin.

BACKGROUND: Oral alitretinoin is a retinoid used for severe chronic hand eczema. Although caution is recommended for patients with uncontrolled dyslipidaemia or cardiovascular risk factors, the actual atherothrombotic risk has not been investigated thus far. OBJECTIVES: To detect any excess of atherothrombotic events among patients exposed to alitretinoin, during treatment or in the 2 years following initiation. METHODS: Using the French Health Insurance database, we compared the number of patients who had an atherothrombotic event (coronary artery disease, ischaemic stroke or peripheral artery disease requiring revascularization) in the population exposed to oral alitretinoin vs. the general population of the same age, sex and baseline cardiovascular risk, using standardized morbidity ratios (SMRs). RESULTS: Between 2009 and 2017, 19 513 patients were exposed to oral alitretinoin in France. Sixty-four (0·3%) patients had an atherothrombotic event while on alitretinoin. Patients receiving alitretinoin experienced no more atherothrombotic events than the general population: patients without cardiovascular risk factors or previous atherothrombotic events had a SMR of 0·65 [95% confidence interval (CI) 0·26-1·34] during alitretinoin treatment, and 1·21 (95% CI 0·90-1·59) in the 2 years following initiation; patients with cardiovascular risk factors or previous atherothrombotic events had a SMR of 0·82 (95% CI 0·60-1·08) during alitretinoin treatment and 0·95 (95% CI 0·82-1·09) in the 2 years following initiation. Taken separately, SMRs for each outcome did not increase either. CONCLUSIONS: These data from an exhaustive nationwide population-based study do not support an increase in the incidence of atherothrombotic events with alitretinoin use, regardless of the baseline cardiovascular risk of the patient.

Isotretinoin and risk factors for suicide attempt: a population-based comprehensive case series and nested case-control study using 2010-2014 French Health Insurance Data.

BACKGROUND: Although the causal role of isotretinoin in suicidal behaviour is controversial, suicide attempts (SA) do occur among patients taking isotretinoin. OBJECTIVES: To describe patient profiles and the management of isotretinoin among patients who committed or attempted suicide under treatment. To assess the risk factors for SA under isotretinoin. METHODS: We performed a comprehensive case series of suicides and SAs under isotretinoin, and a case-control study, using Nationwide French Health Insurance database. The main analysis compared cases (subjects with a SA during a course of isotretinoin) to controls, individually matched for age, gender and rank of the current course; controls were to be exposed to isotretinoin at the index date (date of SA for the corresponding cases). The patients' psychiatric history at isotretinoin initiation was studied. In a secondary analysis, patients who continued their isotretinoin treatment after their SA were compared to patients who discontinued it. RESULTS: In all, 328 018 subjects started a course of isotretinoin between 1 January 2010 and 31 December 2014 and 184 patients were hospitalized for a SA; half of them had a psychiatric history at initiation. In the multivariate analysis, psychiatric history and history of anxiety alone were risk factors for SA [Odds ratio (OR), 18.21; 95% confidence interval (CI), 9.96-33.30 and 4.78; 95% CI, 2.44-9.33, respectively]. Among 176 cases of SA with sufficient follow-up, 103 (58.5%) carried on with their treatment after their SA. Treatment initiation by a dermatologist was inversely associated with the continuation of the treatment after a SA (OR, 0.38; 95% CI, 0.18-0.80). CONCLUSIONS: Suicide attempts under isotretinoin are rare events, and our results suggest that most of the patients concerned have a risk-prone profile detectable at the time of treatment initiation. The risk-benefit ratio of continuing isotretinoin after a SA warrants further careful evaluation.

[Impact of robotic assistance on the use and the outcomes of nephron-sparing surgery: A single center experience]. / Impact de l'assistance robotique sur la pratique et les résultats de la chirurgie rénale conservatrice : une expérience monocentrique.

INTRODUCTION: The aim of this study was to assess the impact of the acquisition of a Da Vinci® robot on the use and outcomes of partial nephrectomy (PN). PATIENTS AND METHODS: It was a single center retrospective study including 280 patients who underwent PN from January 2006 to May 2013. The number of PN, tumors and patients' characteristics and perioperative outcomes have been assessed over 3 periods defined according to the main surgical approach: 2006-2008 (open PN), 2008-2010 (laparoscopic PN) and 2010-2013 (robotic PN). RESULTS: Over the study period, the surgical approach has changed significantly in favor of minimally-invasive surgery and especially robotic approach. The PN/nephrectomy rate has also evolved to a higher proportion of PN over radical nephrectomy (P=0.002). No significant difference was noted between the three periods in terms of tumor size but there was a higher rate of highly complex tumors (RENAL score≥10) during the last period (10.7%; 18.6% and 33.2%; P=0.04). Warm ischemia time increased from 2006-2008 to 2008-2010 (26 vs. 23minutes) but decreased thereafter during the robotic era (14.5minutes; P<0.001). Regarding postoperative outcomes, the only change was a decreased length of stay over time (P=0.003). CONCLUSION: In this single center series, the robotic approach was associated with a spread of PN and with an improvement of nephron-sparing surgery outcomes. LEVEL OF EVIDENCE: 4.

Prognostic and predictive values of oncogenic BRAF, NRAS, c-KIT and MITF in cutaneous and mucous melanoma.

BACKGROUND: Mutations of BRAF, NRAS and c-KIT oncogenes are preferentially described in certain histological subtypes of melanoma and linked to specific histopathological features. BRAF-, MEK- and KIT-inhibitors led to improvement in overall survival of patients harbouring mutated metastatic melanoma. OBJECTIVES: To assess the prevalence and types of BRAF, NRAS, c-KIT and MITF mutations in cutaneous and mucous melanoma and to correlate mutation status with clinicopathological features and outcome. METHODS: Clinicopathological features and mutation status of 108 samples and of 98 consecutive patients were, respectively, assessed in one retrospective and one prospective study. Clinicopathological features were correlated with mutation status and the predictive value of these mutations was studied. RESULTS: This work identified significant correlations between BRAF mutations and melanoma occurring on non-chronic sun-damaged skin and superficial spreading melanoma (P < 0.05) on one hand, and between NRAS mutations and nodular melanoma (P < 0.05) on the other hand. Younger age (P < 0.05), microscopic (P < 0.05) and macroscopic (P < 0.05) lymphatic involvement at diagnosis of primary melanoma were significantly linked to BRAF mutations. A mutated status was a positive predictive factor of a response to BRAF inhibitors (OR = 3.44). Mutated melanoma showed a significantly (P = 0.038) higher objective response rate to cytotoxic chemotherapy (26.3%) than wild-type tumours (6.7%). CONCLUSION: Clinical and pathological characteristics of the primary melanoma differed between wild-type and BRAF- or NRAS-mutated tumours. Patients with BRAF-mutated tumours were younger at diagnosis of primary melanoma. Patients carrying mutations showed better responses better to specific kinase inhibitors and interestingly also to systemic cytotoxic chemotherapy.

[Ischemia is not an independent predictive factor of chronic renal failure after partial nephrectomy in a solitary kidney in patients without pre-operative renal insufficiency]. / L'ischémie a un impact limité sur la fonction rénale après néphrectomie partielle sur rein unique chez les patients sans insuffisance rénale préopératoire.

OBJECTIVE: To assess the influence of vascular clamping and ischemia time on long-term post-operative renal function following partial nephrectomy (PN) for cancer in a solitary kidney. PATIENTS AND METHODS: This is a retrospective study including 259 patients managed by PN between 1979 and 2010 in 13 centers. Clamping use, technique choice (pedicular or parenchymal clamping), ischemia time, and peri-operative data were collected. Pre-operative and last follow-up glomerular filtration rates were compared. A multivariate analysis using a Cox model was performed to assess the impact of ischemia on post-operative chronic renal failure risk. RESULTS: Mean tumor size was 4.0±2.3cm and mean pre-operative glomerular filtration rate was 60.8±18.9mL/min. One hundred and six patients were managed with warm ischemia (40.9%) and 53 patients with cold ischemia (20.5%). Thirty patients (11.6%) have had a chronic kidney disease. In multivariate analysis, neither vascular clamping (P=0.44) nor warm ischemia time (P=0.1) were associated with a pejorative evolution of renal function. Pre-operative glomerular filtration rate (P<0.0001) and blood loss volume (P=0.02) were significant independent predictive factors of long-term renal failure. CONCLUSION: Renal function following PN in a solitary kidney seems to depend on non-reversible factors such as pre-operative glomerular filtration rate. Our findings minimize the role of vascular clamping and ischemia time, which were not significantly associated with chronic renal failure risk in our study. LEVEL OF EVIDENCE: 5.

High completeness of the brest stroke registry evidenced by analysis of sources and capture-recapture method.

BACKGROUND: Population-based stroke registries are necessary to evaluate the precise burden of stroke. The methodology used in the Brest Stroke Registry and an estimation of its completeness are described. METHODS: 'Hot pursuit' as well as 'cold pursuit' were used, and five sources of identification were included: emergency wards, brain imaging, practitioners, death certificates and hospital-based electronic research. Ascertainment for each case was certified by a neurologist. Inclusion criteria were: (1) age >15 years; (2) a stroke defined by WHO criteria or all neurological deficits lasting at least 1 h. Completeness was estimated using capture-recapture method. RESULTS: For 2008, 2009 and 2010, 851, 898, 823 patients were collected, respectively. The number of sources of identification per patient was as follows: one source: 30.8, 24.1 and 18.7%; two sources: 54.5, 42.9 and 31.0%; three sources: 13.4, 30.1 and 46%; four sources: 1.3, 3.0 and 3.8%. Capture-recapture analysis showed data completeness over 90%. Standardized cumulative first-ever stroke incidence using a world standard population was 87 in 2008, 87 in 2009 and 84 in 2010. CONCLUSIONS: Case ascertainment by a neurologist, numerous sources, as well as 'hot' and 'cold' pursuit can provide a reliably large data set suitable for further epidemiological studies.

Predictive factors of hemorrhagic complications after partial nephrectomy.

OBJECTIVES: To identify the predictive factors of hemorrhagic complications (HC) in a contemporary cohort of patients who underwent partial nephrectomy (PN). MATERIALS AND METHODS: Records of 199 consecutive patients who underwent PN between 2008 and 2012 at our institution were retrospectively analyzed. HC was defined as a hematoma requiring transfusion, an arterio-veinous fistula, a false aneurysm or a post-operative decrease of hemoglobin >3 g/dl. Patients with or without HC were compared using Wilcoxon and Fisher exact tests for continuous and categorical variables, respectively. We performed a univariate and multivariate analysis with a logistic regression model using the occurrence of an HC as the dependent variable. RESULTS: 54% of the patients were male with a median age of 61 (22-86) years. Median BMI was 26 (18-47) kg/m(2). Surgery was done open, laparoscopically or with robotic assistance in 106, 54 and 39 cases, respectively. Global complication rate was 40% including 21.6% HC. There were more complex tumors (75.6% vs. 66.5%, p = 0.04) and median length of stay was increased (11 days compared to 7 days, p < 0.0001) in case of a HC. In univariate analysis, imperative indication (p = 0.08), RENAL score (p = 0.07), operating time (p = 0.07) and operative blood loss > 250 ml (p = 0.002) were statistically relevant. In multivariate analysis, only operative blood loss >250 ml was identified as a predictive factor of HC (p = 0.0007). CONCLUSION: Patients who underwent a procedure with estimated blood loss >250 ml should be carefully monitored in the postoperative course.

Predictive factors of chronic kidney disease stage V after partial nephrectomy in a solitary kidney: a multi-institutional study.

OBJECTIVE: Partial Nephrectomy (PN) in a solitary kidney is at risk of chronic kidney disease (CKD) stage V and/or haemodialysis (HD). Our objective was to determine predictive factors of CKD stage V in this population. MATERIAL & METHODS: Data from 300 patients were retrospectively collected from 16 tertiary centres. Clinical and operative parameters, tumor characteristics and renal function before surgery were analyzed. Patients with and without CKD stage V (defined as MDRD<1 5 ml/min) were compared using χ2 and Student-t tests for qualitative and quantitative variables, respectively. Predictive factors of CKD stage V were evaluated with a multivariable analysis using a Cox regression model. RESULTS: Median age and BMI were 63 years old and 26 kg/m², respectively. Most of the patients (65%) were male with an anatomic solitary kidney (88.3%). Median tumor size was 4 cm and 98% were malignant tumors. Median operative time, blood loss and clamping time were 180 min, 350 ml and 20 min respectively. Renal cooling was used in 19.3% and clamping of the pedicle was performed in 61.6%. Twenty five patients (8.5%) presented post operative CKD stage V at last follow-up and 18 underwent HD (6%) post-operatively because of acute renal insufficiency. There was no difference between CKD stage V and non CKD stage V patients concerning Charlson index, operative time (180 min vs 179 min, p = 0.39), blood loss (475 ml vs 350 ml, p = 0.51), use of renal cooling and type of clamping. Patients with CKD stage V were older (70 vs 63 years old, p = 0.005), had a lower baseline renal function (clearance MDRD 41 vs. 62 ml/min, p<0.0001) and an increased tumor size (p = 0.02). Complications occurred in 91 patients (30%) with 16% of minor (Clavien 1-2) and 14% of major (Clavien > 2) complications, respectively. In multivariable analysis, baseline MDRD, BMI, and the occurrence of a minor complication were independent predictive factors of post operative CKD stage V. CONCLUSION: PN in a solitary kidney is at risk of post-operative CKD stage V and HD. Pre-operative altered renal function and post operative complications are the main predictive factors of permanent CKD stage V.

Estrogen and progestogen effect on venous thromboembolism in menopausal women.

Prior to 1996, the use of postmenopausal estrogen was not believed to increase the risk of venous thrombosis. Subsequent studies, particularly the prospective, randomized, double-blind, clinical trial of the Women's Health Initiative, have clearly shown an increase in the incidence and risk of venous thrombosis in postmenopausal women using conjugated equine estrogens with or without medroxyprogesterone acetate. The risk of venous thrombosis in postmenopausal women is also increased by obesity and age. Oral hormone therapy has been used principally for management of menopausal symptoms. Transdermal estrogens have not been used as extensively in the United States but have a significant use in Europe. Recent observational studies have indicated no increased risk of venous thrombosis with use of transdermal estrogens. Norpregnane derivatives have been associated with an increased risk of venous thrombosis, suggesting that progestins may contribute to the increased risk in postmenopausal women using estrogen plus progestin therapy.

Antihypertensive drugs and risk of venous thromboembolism: results from the EDITH case-control study.

Previous studies evaluating the association between arterial blood pressure and venous thromboembolism (VTE) reported conflicting results. The relationship between antihypertensive therapy and VTE has never been specifically evaluated. This report from a hospital-based case-control study included 785 cases with confirmed unprovoked VTE and their 785 age- and sex-matched controls. Cases and controls were asked for drug exposure in a one-to-one standardized interview using the same questionnaire. Drug exposure was defined as current use of drugs at admission with onset at least 1 week ago. Three hundred and eighty-four out of 785 cases (48.9%) and 379 out 785 controls (48.3%) reported that they were currently using at least one antihypertensive drug. Among all antihypertensive therapies, only angiotensin II receptor blockers were significantly associated with a reduced risk for VTE: adjusted conditional odds ratio (OR) 0.45 (95% CI, 0.29-0.70). In this hospital-based case-control study, a preventive role for angiotensin II receptor blockers as regards VTE risk was suggested. More studies are needed in order to further elucidate the biological mechanisms involved.

Materno-fetal transmission of human coronaviruses: a prospective pilot study.

This prospective pilot study investigates the possibility of materno-fetal transmission of human coronaviruses (HCoV) responsible for cases of neonatal infection. This vertical transmission was studied with 159 samples from mother-child couples: maternal vaginal (MV) and respiratory (MR) samples during labor; and newborn gastric sample (NG) with detection of HCoV (229E, OC-43, NL-63, HKU1) via real time RT PCR. HCoV was detected in 12 samples (229E: 11; HKU1: 1) from seven mother-child couples. For three couples, only MR tested positive (cases 1-3). For two other couples all three samples (MV, MR and NG) tested positive (cases 4 and 5). For case 6, only MV and NG tested positive. In case 7, only MV was positive. Possible vertical transmission of HCoV was hypothesized in this pilot study and requires further investigation on a larger scale.