Post-traumatic stress disorder in hospital doctors after the COVID-19 pandemic.

BACKGROUND: Prior studies showed that during the coronavirus disease 2019 (COVID-19) pandemic healthcare workers had a higher risk of developing post-traumatic stress disorder (PTSD) symptoms. However, studies conducted among doctors several years after the beginning of the COVID-19 pandemic are scarce. AIMS: To evaluate the prevalence of PTSD among hospital doctors and to describe potential explanatory factors. METHODS: The Protec-Cov study was an observational, cross-sectional, multicentre study, which used an anonymous online questionnaire to evaluate PTSD in doctors from six hospitals in France between December 2021 and March 2022. The presence of PTSD was assessed using the Post-traumatic Stress Disorder Checklist Scale (PCLS) questionnaire with a cut-off of 44. RESULTS: Among the 307 doctors included, 18% presented a PCLS ≥44. The multivariate analysis showed that factors associated with a PCLS ≥44 were having a higher workload than before the COVID-19 pandemic (odds ratio [OR] = 4.75; 95% confidence interval [CI] 1.68-13.38), not feeling recognized within the professional environment (OR = 2.83; 95% CI 1.26-6.33), and feeling isolated because of the lockdown (OR = 4.2; 95% CI 1.97-8.95). Approximately 30% of hospital doctors (n = 91) felt a need for psychological support but only 31% of them (n = 28) received support. CONCLUSIONS: Based on our findings, a high prevalence of PTSD was observed among hospital doctors 2 years after the beginning of the COVID-19 pandemic. This study supports an early diagnosis of PTSD in this category of healthcare workers and warrants further study.

International multicentre observational study to assess the efficacy and safety of a 0·5 mg kg-1 per day starting dose of oral corticosteroids to treat bullous pemphigoid.

BACKGROUND: European guidelines propose a 0·5 mg kg-1 per day dose of oral prednisone as initial treatment for bullous pemphigoid (BP). We assessed the safety and efficacy of this regimen depending on BP extent and general condition of the patients. METHODS: In a prospective international study, we consecutively included all patients diagnosed with BP. Patients received a 0·5 mg kg-1 per day dose of prednisone, which was then gradually tapered 15 days after disease control, with the aim of stopping prednisone or maintaining minimal treatment (0·1 mg kg-1 per day) within 6 months after the start of treatment. The two coprimary endpoints were control of disease activity at day 21 and 1-year overall survival. Disease severity was assessed according to the Bullous Pemphigoid Disease Area Index (BPDAI) score. RESULTS: In total, 198 patients were included between 2015 and 2017. The final analysis comprised 190 patients with a mean age of 80·9 (SD 9·1) years. Control of disease activity was achieved at day 21 in 119 patients [62·6%, 95% confidence interval (CI) 55·3-69.5]; 18 of 24 patients (75%, 95% CI 53·3-90·2), 75 of 110 patients (68·8%, 95% CI 59·2-77·3) and 26 of 56 patients (46.4%, 95% CI 33·0-60·3) had mild, moderate and severe BP, respectively (P = 0·0218). A total of 30 patients died during the study. The overall Kaplan-Meier 1-year survival was 82·6% (95% CI 76·3-87·4) corresponding to 90·9%, 83·0% and 80·0% rates in patients with mild, moderate and severe BP, respectively (P = 0·5). Thresholds of 49 points for BPDAI score and 70 points for Karnofsky score yielded maximal Youden index values with respect to disease control at day 21 and 1-year survival, respectively. CONCLUSIONS: A 0·5 mg kg-1 per day dose of prednisone is a valuable therapeutic option in patients with mild or moderate BP whose general condition allows them to be autonomous.

Comparison of real costs in the French healthcare system in newly diagnosed patients with pemphigus for first-line treatment with rituximab vs. standard corticosteroid regimen: data from a national multicentre trial.

BACKGROUND: Rituximab has been demonstrated to be highly effective as a first-line treatment for moderate-to-severe pemphigus; however, its high cost can be considered a limitation of this treatment. OBJECTIVES: To compare direct costs of two regimens, rituximab + short-term prednisone vs. prednisone alone, tested in the Ritux3 trial. METHODS: Patients were randomly assigned to receive 2 g of rituximab and two 500-mg maintenance infusions at month 12 and month 18 along with low doses of prednisone for 3-6 months, or high doses of prednisone alone tapered over 12-18 months. We estimated the direct costs related to (i) protocol (treatments, consultations, hospitalizations); (ii) unfavourable disease course (relapse); and (iii) adverse events in both treatment groups during a 3-year follow-up. RESULTS: Annual individual cost discrepancies related to drugs decreased from +€3597 to -€1589 from the first to the third year, which corresponded to an initially higher cost in the rituximab group, counterbalanced during follow-up by costs related to treatment of patients with persistent disease activity/relapses in the standard corticosteroid (CS) group. Individual costs relating to treatment of adverse events were higher in the standard CS group (€4352) than in the rituximab group (€2468). Overall, mean individual total cost over the 3 years of follow-up was €13 997 in the standard CS arm vs. €14 818 in the rituximab arm, corresponding to a difference of €821 more per patient (+6%). CONCLUSIONS: First-line treatment of pemphigus with rituximab results in a slightly greater cost compared with a standard CS regimen. What's already known about this topic Rituximab is the most effective treatment for moderate-to-severe pemphigus. Rituximab cost might be considered as a limitation of this treatment. What does this study add? After 3 years of follow-up, mean individual total cost for a patient with first-line treatment with rituximab was €14 818 vs. €13 997 with standard corticosteroids (CS), resulting in a slightly higher cost of €821 (+6%). The initially greater cost of rituximab was counterbalanced by costs related to management of flares/relapses in patients treated with a standard CS regimen.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

Risk factors for treatment failure in scabies: a cohort study.

BACKGROUND: Treatment failure, which occurs in about one-third of cases, is considered as a major factor in the increasing incidence of scabies in developed countries. OBJECTIVES: To identify predictors of treatment failure of scabies in ambulatory populations. METHODS: This multicentre study compared the clinical characteristics and treatment modalities between a group of patients with scabies treated successfully and another group who were not cured 3 months after antiscabies treatment. RESULTS: In total 210 patients with a diagnosis of scabies were included, comprising 98 patients in the treatment success group and 112 in the treatment failure group. The main risk factors for treatment failure were (i) the use of only one type of treatment, topical benzyl benzoate (BB) or oral ivermectin, vs. the combination of both treatments [odds ratio (OR) 2·15, 95% confidence interval (CI) 1·22-3·77]; (ii) the use of a single intake (vs. two) of oral ivermectin (OR 10·2. 95% CI 4·49-23·2); (iii) intake of ivermectin during a meal vs. on an empty stomach (OR 4·31, 95% CI 1·89-9·84); (iv) absence of decontamination of furnishings (OR 8·72, 95% CI 3·50-21·8), in particular sofa and cushions (OR 5·90, 95% CI 2·34-14·9), mattresses (OR 4·16, 95% CI 1·35-12·8) or car seats (OR 6·57, 95% CI 3·27-13·2) and (v) absence of written documents explaining treatment modalities (OR 5·18, 95% CI 2·57-10·4). In multivariate analysis, treatment failure was mainly associated with (i) use of a single intake (vs. two) of ivermectin (OR 6·62, 95% CI 2·71-16·2); (ii) use of BB alone vs. two intakes of ivermectin (OR 3·51, 95% CI 1·55-7·95) and (iii) absence of decontamination of furniture with acaricides (OR 5·81, 95% CI 1·96-16·7). CONCLUSIONS: Use of topical BB alone and a single intake (vs. two) of ivermectin are predictors of treatment failure.

[Association between the violence in the community and the aggressive behaviors of psychotics during their hospitalizations]. / Relation entre la violence intra-hospitalière des patients avec psychoses et la violence dans la communauté.

BACKGROUND: Violence is a common issue in psychiatry and has multiple determiners. The aim of this study is to assess the psychotic inpatients' violence in association with the violence of the neighborhood from which the patients are drawn and to estimate the impact of this environmental factor with regard to other factors. METHOD: A prospective multicenter study was led in nine French cities. Eligible patients were psychotic involuntary patients hospitalized in the cities' psychiatric wards. During their treatments, any kind of aggressive behavior by the patients has been reported by the Overt Aggression Scale (OAS). RESULTS: From June 2010 to May 2011, 95 patients have been included. Seventy-nine per cent of the patients were violent during their hospitalizations. In a bivariate analysis, inpatient violence was significantly associated with different factors: male gender, patient violence history, substance abuse, manic or mixed disorder, the symptoms severity measured by the BPRS, the insight degree and the city crime rate. In a multivariate analysis, the only significant factors associated with the patients' violence were substance abuse, the symptoms severity and the crime rates from the different patients' cities. CONCLUSION: These results suggest that violence within the psychotic patients' neighborhood could represent a risk of violence during their treatments.

Calculation of cut-off values based on the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI) pemphigus scoring systems for defining moderate, significant and extensive types of pemphigus.

BACKGROUND: Two pemphigus severity scores, Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI), have been proposed to provide an objective measure of disease activity. However, the use of these scores in clinical practice is limited by the absence of cut-off values that allow differentiation between moderate, significant and extensive types of pemphigus. OBJECTIVES: To calculate cut-off values defining moderate, significant and extensive pemphigus based on the ABSIS and PDAI scores. METHODS: In 31 dermatology departments in six countries, consecutive patients with newly diagnosed pemphigus were assessed for pemphigus severity, using ABSIS, PDAI, Physician's Global Assessment (PGA) and Dermatology Life Quality Index (DLQI) scores. Cut-off values defining moderate, significant and extensive subgroups were calculated based on the 25th and 75th percentiles of the ABSIS and PDAI scores. The median ABSIS, PDAI, PGA and DLQI scores of the three severity subgroups were compared in order to validate these subgroups. RESULTS: Ninety-six patients with pemphigus vulgaris (n = 77) or pemphigus foliaceus (n = 19) were included. The median PDAI activity and ABSIS total scores were 27·5 (range 3-84) and 34·8 points (range 0·5-90·5), respectively. The respective cut-off values corresponding to the first and third quartiles of the scores were 15 and 45 for the PDAI, and 17 and 53 for ABSIS. The moderate, significant and extensive subgroups were thus defined, and had distinguishing median ABSIS (P < 0·001), PDAI (P < 0·001), PGA (P < 0·001) and DLQI (P = 0·03) scores. CONCLUSIONS: This study suggests cut-off values of 15 and 45 for PDAI and 17 and 53 for ABSIS, to distinguish moderate, significant and extensive pemphigus forms. Identifying these pemphigus activity subgroups should help physicians to classify and manage patients with pemphigus.

[Benefits and usability of a pharmaceutical record in medical practice. A survey of hospital doctors and pharmacists (MATRIX study)]. / Intérêt et utilisabilité du dossier pharmaceutique en pratique médicale. Enquête auprès de médecins et pharmaciens hospitaliers (étude MATRIX).

BACKGROUND: To evaluate the impact of the pharmaceutical patient record use in emergency, geriatric and anaesthesia and intensive care departments, an experimentation was launched in 2013 in 55 hospitals. The purpose of the study was to assess the opinions of physicians and pharmacists about the benefits and usability of the patient pharmaceutical record. METHODS: An e-mailed self-administered questionnaire was sent to all the pharmacists, anaesthesiologists, geriatricians and emergency physicians of the 55 hospitals involved in the patient pharmaceutical record experimentation. The questionnaire assessed the usability of the patient pharmaceutical record using the "System Usability Scale", as well as its use, its benefits and limitations perceived in clinical practice, and overall user satisfaction. Questionnaires were collected from November 2014 to January 2015. RESULTS: Ninety-six questionnaires were collected, from 47 hospitals, representing 86% of the hospitals involved in the experimentation. The patient pharmaceutical record was effectively operational in 36 hospitals. Data from 73 questionnaires filled by physicians and pharmacists with potential experience with the patient pharmaceutical record were used for evaluation. Forty-two respondents were pharmacists (57%) and 31 were physicians (43%), including 13 geriatricians, 11 emergency physicians and 7 anaesthesiologists. Patient pharmaceutical record overall usability score was 62.5 out of 100. It did not vary with the profession or seniority of the respondent. It was positively correlated with the frequency of use. More than half of respondents reported that they never or uncommonly used the patient pharmaceutical record. The length of access to data period was considered as insufficient. Main obstacles to more utilization of the patient pharmaceutical record were the lack of information about the dosage of dispensed drugs, the low number of patients in possession of their health card and the low number of patients with an activated patient pharmaceutical record. CONCLUSION: Two years after the beginning of the experiment aiming to broaden the access to the patient pharmaceutical record to physicians, these first evaluation results are encouraging. The evaluation of the consequences of the access to the patient pharmaceutical record for physicians remains necessary.

Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects.

OBJECTIVES: The aim of this study was to investigate whether the quadrivalent human papillomavirus (HPV) vaccine Gardasil is associated with a change in the risk of autoimmune disorders (ADs) in young female subjects. DESIGN: Systematic case-control study of incident ADs associated with quadrivalent HPV vaccination in young women across France. PARTICIPANTS AND SETTING: A total of 113 specialised centres recruited (from December 2007 to April 2011) females aged 14-26 years with incident cases of six types of ADs: idiopathic thrombocytopenic purpura (ITP), central demyelination/multiple sclerosis (MS), Guillain-Barré syndrome, connective tissue disorders (systemic lupus erythematosus, rheumatoid arthritis/juvenile arthritis), type 1 diabetes mellitus and autoimmune thyroiditis. Control subjects matched to cases were recruited from general practice. ANALYSIS: Multivariate conditional logistic regression analysis; factors included age, geographical origin, smoking, alcohol consumption, use of oral contraceptive(s) or vaccine(s) other than Gardasil received within 24 months before the index date and personal/family history of ADs. RESULTS: Overall, 211 definite cases of ADs were matched to 875 controls. The adjusted odds ratio (OR) for any quadrivalent HPV vaccine use was 0.9 [95% confidence interval (CI) 0.5-1.5]. The individual ORs were 1.0 (95% CI 0.4-2.6) for ITP, 0.3 (95% CI 0.1-0.9) for MS, 0.8 (95% CI 0.3-2.4) for connective disorders and 1.2 (95% CI 0.4-3.6) for type 1 diabetes. No exposure to HPV vaccine was observed in cases with either Guillain-Barré syndrome or thyroiditis. CONCLUSIONS: No evidence of an increase in the risk of the studied ADs was observable following vaccination with Gardasil within the time periods studied. There was insufficient statistical power to allow conclusions to be drawn regarding individual ADs.

Increased prevalence of psoriasis in patients with coronary artery disease: results from a case-control study.

BACKGROUND: The incidence of myocardial events has been reported to be increased in patients with psoriasis. OBJECTIVES: To investigate whether psoriasis is an independent risk factor for coronary artery disease (CAD). METHODS: We compared the prevalence of psoriasis between case patients with a diagnosis of CAD based on coronary angiography findings and control patients with no CAD referred to the emergency surgery department for an acute noncardiovascular condition. Case and control patients were examined for the presence of psoriasis by two dermatologists. The prevalence of psoriasis was compared among patients with CAD according to CAD severity. Five-hundred cases and 500 age- and sex-matched controls were included. RESULTS: Using matched univariate analysis, the prevalence of psoriasis was about twofold higher in CAD case patients than in control patients [8·0% vs. 3·4%, odds ratio (OR) 2·64; 95% confidence interval (CI) 1·42-4·88]. Using unconditional multivariate analysis, the association of psoriasis with CAD appeared to be borderline significant (OR 1·84; 95% CI 0·99-3·40). Psoriasis in patients with CAD was significantly associated with three-vessel involvement relative to one-or two-vessel involvement (13·1% vs. 6·1%; OR 3·07; 95% CI 1·50-6·25). CONCLUSIONS: The prevalence of psoriasis is twofold higher in patients with CAD than in control patients without CAD. It is associated with a more severe coronary artery involvement.

Comparative analysis of quality scores images between second- and third-trimester ultrasound scan.

OBJECTIVES: To evaluate whether the quality scores validated for second-trimester ultrasound scan can be used for third-trimester ultrasound scan. METHODS: Prospective multicenter ancillary study using data from the RECRET study. Nulliparous women, with no reported history, with second- and third-trimester ultrasound examinations performed by the same ultrasonographer and using the same ultrasound machine were recruited. The global score and the individual score of each ultrasound image were compared between second- and third-trimester ultrasound scan. The sample size was calculated for a non-inferiority (one-sided) paired Student t test. RESULTS: 103 women with 1606 anonymized ultrasound images were included. The median term at second- and third-trimester ultrasound scan was 22.2 weeks gestation (22.0-22.7) and 31.6 weeks gestation (30.7-34.7), respectively. The mean global score of ultrasound images was comparable between the second- and the third-trimester ultrasound examination (32.37 ± 2.62 versus 31.80 ± 3.27, p = 0.13). Means scores for each biometric parameters i.e. head circumference, abdominal circumference, and femur diaphysis length were comparable. The scores for the four-chamber view (5.11 ± 0.91 versus 5.36 ± 0.75, p = 0.02) and the spine (4.18 ± 1.17 versus 5.22 ± 1.02, p < 0.001) were significantly lower in the third trimester compared to the second trimester. The score for the kidney image was significantly higher for third trimester images compared to second trimester images (4.73 ± 0.51 versus 4.32 ± 0.67, p < 0.001. CONCLUSIONS: Biometrics parameters quality scores images previously validated for the second trimester ultrasound scan can be also used for the third trimester scan. However, anatomical quality scores images performances may vary between the second and the third trimester scan.

Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients.

BACKGROUND: Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels. METHODS: CREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5-2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m2 rituximab once weekly for 4 weeks. The primary endpoint was complete remission over 18 months. Secondary endpoints included time to achieve complete remission, relapse occurrence, mortality, infections and bleeding, and severe adverse events. RESULTS: Recruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL-1), significantly more remissions were observed with cyclophosphamide (22 patients, 78.6 %) than with rituximab (12 patients, 48.0 %; p = 0.02). Relapse rates, deaths, severe infections, and bleeding were similar in the 2 groups. In patients with severe infection, cumulative doses of steroids were significantly higher than in patients without infection (p = 0.03). CONCLUSION: Cyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive. FUNDING: French Ministry of Health. CLINICALTRIALS: gov number: NCT01808911.

Meningococcal carriage during a clonal meningococcal B outbreak in France.

The aim of this study performed in Normandy, France, was to analyze the pharyngeal meningococcal carriage at the peak of a clonal meningococcal B outbreak, which was subsequently controlled using an outer membrane vesicle vaccination. This cross-sectional study included randomly selected subjects aged 1-25 years. Carriers and non carriers were compared using unconditional logistic regression. Among the 3,522 volunteers, there were 196 (standardized rate: 6.46 %) Neisseria meningitidis carriers, of which there were only five with the outbreak strain (B:14:P1.7,16/ST-32; standardized rate: 0.18 %). From the multivariate analysis, older age, smoking, higher degree of socialization, and social deprivation appear to favor the carriage of all the strains included. Prior antibiotic treatment up to 12 months before swabbing, even with ß-lactam, was protective against carriage. Our data indicate a low overall meningococcal carriage rate with a surprising protective effect of prior antibiotic exposure. The observed low carriage rate of the epidemic strain (B:14:P1.7,16/ST-32) contrasts with the high incidence of invasive meningococcal diseases (IMD) due to this strain. Hence, our data underline the high virulence of the strain and suggest a low level of natural immunity of the population against this strain. Although highly resource-consuming, carriage studies are helpful in guiding the implementation of control measures of IMD, such as mass vaccination or chemoprophylaxis.

Targeted disruption of otog results in deafness and severe imbalance.

Genes specifically expressed in the inner ear are candidates to underlie hereditary nonsyndromic deafness. The gene Otog has been isolated from a mouse subtractive cDNA cochlear library. It encodes otogelin, an N-glycosylated protein that is present in the acellular membranes covering the six sensory epithelial patches of the inner ear: in the cochlea (the auditory sensory organ), the tectorial membrane (TM) over the organ of Corti; and in the vestibule (the balance sensory organ), the otoconial membranes over the utricular and saccular maculae as well as the cupulae over the cristae ampullares of the three semi-circular canals. These membranes are involved in the mechanotransduction process. Their movement, which is induced by sound in the cochlea or acceleration in the vestibule, results in the deflection of the stereocilia bundle at the apex of the sensory hair cells, which in turn opens the mechanotransduction channels located at the tip of the stereo-cilia. We sought to elucidate the role of otogelin in the auditory and vestibular functions by generating mice with a targeted disruption of Otog. In Otog-/- mice, both the vestibular and the auditory functions were impaired. Histological analysis of these mutants demonstrated that in the vestibule, otogelin is required for the anchoring of the otoconial membranes and cupulae to the neuroepithelia. In the cochlea, ultrastructural analysis of the TM indicated that otogelin is involved in the organization of its fibrillar network. Otogelin is likely to have a role in the resistance of this membrane to sound stimulation. These results support OTOG as a possible candidate gene for a human nonsyndromic form of deafness.

[Changes in the incidence and mortality rates of malignant melanoma in the Seine-Maritime region over a 20-year period]. / Évolution de l'incidence et de la mortalité du mélanome en Seine-Maritime sur une période de 20ans.

BACKGROUND: The aim of this study was to assess changes in the incidence and mortality rates of malignant melanoma (MM) over a 20-year period in a region without a cancer registry. METHODS: All cases of MM studied were collected retrospectively from the databases of six private and three hospital-based histopathology laboratories in the Seine-Maritime region covering three 24-month periods each 10years apart: 1988-1989, 1998-1999 and 2008-2009, The incidence and mortality rates were estimated based on data provided by French National Institute for Statistics and Economic Studies (Insee) and French National Institute of Health and Medical Research (Inserm). RESULTS: Over the 20-year period, the incidence of MM increased from 8.6 to 21.2/100,000inhabitants per year (+147%, P<0.0001) while the mortality rate rose from 1.3 to 2.8/100,000inhabitants per year (+115%, P=0.0003). The incidence of invasive MM increased by +110%, while the incidence of MM in situ increased by +456%. The incidence and overall mortality rate of invasive MM increased particularly during the first 10-year period: +62% (P<0.0001) and +77% (P=0.01) respectively, and to a much lesser extent during the last 10-year period: +30% (P=0.0007) and +22% (P=0.22) respectively. This slowdown in the incidence of invasive MM and in overall mortality rates was even more pronounced in women over the last 10years (+17 and +9%), whereas these rates continued to increase in men (+49% and +35%, respectively). In contrast, the incidence of MM in situ increased above all during this same period (+257%). CONCLUSION: This study shows that while the incidence and mortality rate of invasive MM has increased little over the last 10years in the Seine-Maritime region, the incidence of MM in situ continues to rise sharply.

[Virological diagnosis of anterior herpetic ocular disease on tear sample: A simple and non-invasive technique]. / Diagnostic virologique des atteintes oculaires herpétiques antérieures sur prélèvement lacrymal : une technique simple et non invasive.

INTRODUCTION: Virological diagnosis of anterior ocular herpetic disease (AOHD) is essential for the management of these often-chronic pathologies that may require long-term therapy. PCR has become the gold standard, but the type of sampling (tears, corneal scraping, aqueous tap) has not been standardized. In this study, we studied the technique of tear sampling for the diagnosis of AOHD. MATERIALS AND METHOD: We retrospectively analyzed the medical files of patients with a positive tear sample (Schirmer strip) for herpes simplex 1 virus (HSV-1) in the Department of Ophthalmology of Paris-Saclay Bicêtre Hospital between January 2018 and December 2020. We studied the clinical and virological characteristics (viral loads) of these cases of proven AOHD. RESULTS: Thirty-six samples (33 patients) were included: 12 epithelial keratitis, 9 stromal HSK with ulceration, 5 uveitis, 4 stromal HSK without ulceration, 3 blepharitis, 1 endothelial HSK, 1 neurotrophic keratitis, and 1 conjunctivitis. The mean viral load was 3.9×105 copies/mL. Viral load was higher in cases of corneal ulceration (5.2×105±9.4×105 versus 1.2×102±1.7×102 copies/mL, P<1×10-4). There was no significant difference between primary episodes and relapses. CONCLUSION: Tear sampling using Schirmer strips is a simple, non-invasive method that can be useful for the virological diagnosis of various clinical forms of AOHD.

Variable selection methods were poorly reported but rarely misused in major medical journals: Literature review.

Objective This work presents a review of the literature on reporting, practice and misuse of knowledge-based and data-driven variable selection methods, in five highly cited medical journals, considering recoding and interaction unlike previous reviews. Study Design and Setting Original observational studies with a predictive or explicative research question with multivariable analyses published in N. Engl. J. Med., Lancet, JAMA, Br. Med. J. and Ann. Intern. Med. between 2017 and 2019 were searched. Article screening was performed by a single reader, data extraction was performed by two readers and a third reader participated in case of disagreement. The use of data-driven variable selection methods in causal explicative questions was considered as misuse. Results 488 articles were included. The variable selection method was unclear in 234 (48%) articles, data-driven in 78 (16%) articles and knowledge-based in 176 (36%) articles. The most common data-driven methods were: Univariate selection (n = 22, 4.5%) and model comparisons or testing for interaction (n = 17, 3.5%). Data-driven methods were misused in 51 (10.5%) of articles. Conclusion Overall reporting of variable selection methods is insufficient. Data-driven methods seem to be used only in a minority of articles of the big five medical journals.

[Micropulsed diode laser transscleral cyclophotocoagulation: An effective technique whose role remains to be defined]. / Cycloaffaiblisement au laser diode micropulsé : une technique efficace, mais dont la stratégie reste à définir.

Micropulse Transscleral Cyclophotocoagulation (MP-TSCP) is a recently developed cyclodestructive procedure less aggressive than conventional TSCP. In this study, we aimed to evaluate the safety and efficacy of MP-TSCP in a real-life setting. MATERIAL AND METHODS: We retrospectively included all MP-TSCP cases performed in the Bicêtre Hospital Ophthalmology department between January 2017 and September 2019. Intraocular pressure (IOP) and hypotensive medications were recorded preoperatively, at month 1, 3, 6 and at the conclusion of follow-up, as well as postoperative adverse events. Success was defined as an IOP between 6 and 21mmHg with a decrease of at least one medication or an IOP reduction>20%. RESULTS: Thirty eyes (28 patients) were included. Preoperative IOP was 27.2±10.6mmHg, with 3.5±0.6 hypotensive medications, the mean deviation on the Humphrey 24-2 visual field was -21.9±6.9dB, and 43% of eyes had a past history of filtering surgery. The mean follow-up was 13.5±8.1 months. Eleven patients (37%) had to be retreated with MP-TSCP during follow-up. At 3 and 6 months and at the conclusion of follow-up, the IOP was 18.3±7.3mmHg (-33%; P<0.0001), 22.5±11.8mmHg, (-17%; P=0.052), 22.7±12.0mmHg (-16,5%; P<0.050), respectively. The success rates were 57%, 50% et 53% at 3 months, 6 months and at the conclusion of follow-up, respectively. Severe adverse events included 3 cases of corneal ulcers and 2 cases of severe but transient ocular hypotony without visual impairment. CONCLUSION: MP-TSCP is an effective procedure for severe and/or refractory glaucoma, but retreatments are required in more than one-third of cases. Further studies are warranted to define factors predictive of success and indications for retreatment.

[Multimodal evaluation of the ocular surface using a the new Lacrydiag device]. / Place du NIBUT automatisé dans l'évaluation multimodale de la surface oculaire dans le syndrome sec avec le Lacrydiag.

INTRODUCTION: Dry eye disease is a very frequent condition with a significant impact on patients' quality of life. The most common clinical sign is fluorescein break up time (BUT). Recently, non-invasive measurement of BUT (NIBUT) by Placido disc analysis has been proposed to replace FBUT. We performed an automated NIBUT analysis using Lacrydiag and compared the values obtained with other typical dry eye criteria. METHODS AND MATERIALS: A retrospective study was carried out in the Bicêtre ophthalmology department from July 1 through October 30. Dry eye patients over 18 years of age with Oxford scores>1 and OSDI scores>22 were included. They underwent slit lamp examination to determine fluorescein BUT, Oxford and Arita MGD scores. On the same day, they were tested with the Lacrydiag to assess NIBUT, tear lake height and meibography. OSDI and Schirmer's testing were performed on the date of examination. In this study, only patients' right eyes were included. The correlation between NIBUT and OSDI, Schirmer's testing and tear lake height was analyzed by Pearson's test. The correlation between NIBUT and fluorescein BUT was analysed by both Pearson and Bland-Altman statistical tests. RESULTS: Thirty right eyes (21 women, 9 men) were included. The mean age was 62.3 years (SD 16.0), mean OSDI 49.4 (SD=20.1), mean Oxford score 3.33 (SD 2.1), mean NIBUT 6.91sec (SD 3.4), and mean FBUT 3.6sec (SD 1.8). The NIBUT and FBUT were significantly correlated (R=0.139; P=0.042), with an even more significant concordance (r=0.55; P=0.001) on Bland-Altman graphic analysis, but the mean NIBUT was 2.7 seconds higher than the FBUT (P=0.001 on Bland-Altman analysis). In addition, NIBUT was correlated with the Oxford score (R=0.156; P=0.031), but not with Schirmer I score (R=0.120; P=0.061), OSDI score (R=0.018; P=0.48), tear lake height (R=0.04; P=0.148), or Arita meibomian gland dysfunction score (R=0; P=0.933). CONCLUSION: NIBUT is a possible alternative to FBUT for the measurement of tear film stability, with the advantage of lack of dependence on the amount of fluorescein instilled. In addition, modern imaging methods allow for automated, and thus reproducible, measurement. However, its role in the diagnostic tool kit remains to be precisely defined, especially given its weak correlation with other markers of dry eye and its significant difference from FBUT. The definitive diagnosis of dry eye thus remains based on the combined analysis of signs and symptoms.