[Pharmacogenetics of aminoglycoside ototoxicity: State of knowledge and practices - Recommendations of the Francophone Network of Pharmacogenetics (RNPGx)]. / Pharmacogénétique de l'ototoxicité des aminosides : état des connaissances et des pratiques ­ recommandations du Réseau francophone de pharmacogénétique (RNPGx).

The administration of aminoglycosides can induce nephrotoxicity or ototoxicity, which can be monitored through pharmacological therapeutic drug monitoring. However, there are cases of genetic predisposition to ototoxicity related to the MT-RNR1 gene, which may occur from the first administrations. Pharmacogenetic analysis recommendations have recently been proposed by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The Francophone Pharmacogenetics Network (RNPGx) provides a bibliographic synthesis of this genetic predisposition, as well as professional recommendations. The MT-RNR1 gene codes for mitochondrial 12S rRNA, which constitutes the small subunit of the mitochondrial ribosome. Three variants can be identified: the variants m.1555A>G and m.1494C>T of the MT-RNR1 gene have a 'high' level of evidence regarding the risk of ototoxicity. The variant m.1095T>C has a 'moderate' level of evidence. The search for these variants can be performed in the laboratory if the administration of aminoglycosides can be delayed after obtaining the result. However, if the treatment is urgent, there is currently no rapid test available in France (a 'point-of-care' test is authorized in Great Britain). RNPGx considers: (1) the search for the m.1555A>G, m.1494C>T variants as 'highly recommended' and the m.1095T>C variant as 'moderately recommended' before the administration of an aminoglycoside (if compatible with the medical context). It should be noted that the level of heteroplasmy detected does not modify the recommendation; (2) pharmacogenetic analysis is currently not feasible in situations of short-term aminoglycoside administration, in the absence of an available analytical solution (rapid test to be evaluated in France); (3) the retrospective analysis in case of aminoglycoside-induced ototoxicity is 'recommended'; (4) analysis of relatives is 'recommended'. Through this summary, RNPGx proposes an updated review of the MT-RNR1-aminoglycoside gene-drug pair to serve as a basis for adapting practices regarding pharmacogenetic analysis related to aminoglycoside treatment.

Identification of newborns at risk of early-onset neonatal infection: New French guidelines and practices at Nantes University Hospital.

New French guidelines in 2017 aimed to improve the identification of newborns at risk of early-onset neonatal infection (EONI). Identification is based on perinatal risk factors, management of perinatal antibiotic prophylaxis, and standardized clinical assessment. We conducted a retrospective cross-study at the University Hospital of Nantes. The main objective was to assess implementation of the French guidelines. Of 1240 births included, 40% (501) required perinatal antibiotic prophylaxis (adequate in 67.3%) and 306 (24.7%) needed a standardized clinical assessment (performed in 69.2%). Only two newborns (0.16%) included in the study received neonatal antibiotic therapy. On the basis of the assessment conducted in our maternity ward, implementation of the recommendations seems to be effective.

[Which management for anterior urethral stricture in male? 2021 guidelines from the uro-genital reconstruction urologist group (GURU) under the aegis of CAMS-AFU (Committee of Andrology and Sexual Medicine of the French Association of Urology)]. / Quelle prise en charge pour les sténoses de l'urètre antérieur chez l'homme ? Recommandations 2021 du Groupe d'urologue de reconstruction uro-génitale (GURU) sous l'égide du CAMS-AFU (Comité d'andrologie et de médecine sexuelle de l'association française d'urologie).

OBJECTIVE: The purpose of this first french guideline is to provide a clinical framework for the diagnosis, treatment and follow-up of anterior urethral strictures. The statements are established by the subgroup working on uro-genital reconstruction surgery (GURU) from the CAMS-AFU (Andrology and Sexual Medicine Committee from the French Association of Urology). MATERIAL AND METHODS: These guidelines are adapted from the Male Urethral Stricture : American Urological Association Guideline 2016, updated by an additional bibliography from January 2016 to December 2019. Twenty-seven main scenarios seen in clinical practice are identified: from diagnosis, to treatment and follow-up. In addition, this guidelines are powered by anatomical diagrams, treatment algorithms, summaries and follow-up tables. RESULTS: Anterior urethral strictures are a common condition (0,1 à 1,4 %) in men. The diagnosis is based on a trifecta including an examination with patient reported questionnaires, urethroscopy and retrograde urethrography with voiding cystourethrography. Short meatal stenosis can be treated by dilation or meatotomy, otherwise a urethroplasty can be performed. First line treatment of penile strictures is urethroplasty. Short bulbar strictures (<2cm) may benefit from endourethral treatment (direct visual internal urethrotomy or dilation). In case of recurrence or when the stenosis measures more than 2 cm, a urethroplasty will be proposed. Repeated endourethral treatment management are no longer recommended except in case of palliative option. Urethroplasty is usually done with oral mucosa graft as the primary option, in one or two stages approach depending on the extent of the stenosis and the quality of the tissues. Excision and primary anastomosis or non-transecting techniques are discussed for bulbar urethra strictures. Follow-up by clinical monitoring with urethroscopy, or retrograde urethrography with voiding cystourethrography, is performed at least the first year and then on demand according to symptoms. CONCLUSION: Anterior urethral strictures need an open surgical approach and should be treated by urethroplasty in most cases. This statement requires a major paradigm shift in practices. Training urologist through reconstructive surgery is the next challenge in order to meet the demand.

Validation of the French IVF guidelines during the COVID-19 pandemic.

RESEARCH QUESTION: Is a symptom questionnaire as per the French IVF guidelines adequate for screening patients during the COVID-19 pandemic? DESIGN: Patients planning IVF from June 2020 to February 2021 were included in the study. In compliance with French IVF guidelines, all patients fever-free on the day of oocyte retrieval were screened for risk of COVID-19 by completing a symptom questionnaire after being counselled regarding the importance of a COVID-19-free medical practice. Patients with IVF planned between June and September 2020 only completed the questionnaire (group 1), while those planning IVF after September 2020 also underwent the RT-PCR test for SARS-CoV-2 RNA (group 2). Cycle cancellation rates between groups were compared. Group 1 patients consented for follicular fluid testing for SARS-CoV-2 and an interview after cycle completion to determine COVID-19 exposure during the 6 months before and after retrieval. RESULTS: Cycle cancellation rates for groups 1 and 2 were 0% (0/214) versus 1.4% (8/577), respectively, (P = 0.116). All 183 follicular fluid samples from group 1 were negative for SARS-CoV-2 RNA. Of 171 patients interviewed post-IVF, 16 (93.4%) developed COVID-19 symptoms or a positive real-time PCR (RT-PCR) RT-PCR test, but none within 2 months pre- or post-retrieval. CONCLUSIONS: These results provide reassurance that, consistent with the COVID-19 French IVF guidelines, use of a symptom questionnaire is effective in screening patients planning to undergo IVF. Failure to detect viral RNA in any follicular fluid sample does not negate the possibility that follicular fluid is a viral reservoir. However, the findings provide reassurance that the follicular environment in this study's carefully screened population was COVID-free.

French Society of Cardiology guidelines on exercise tests (part 2): Indications for exercise tests in cardiac diseases.

The exercise test is performed routinely in cardiology; its main indication is the diagnosis of myocardial ischemia, evaluated along with the subject's pretest probability and cardiovascular risk level. Other criteria, such as analysis of repolarization, must be taken into consideration during the interpretation of an exercise test, to improve its predictive value. An exercise test is also indicated for many other cardiac diseases (e.g. rhythm and conduction disorders, severe asymptomatic aortic stenosis, hypertrophic cardiomyopathy, peripheral artery disease, hypertension). Moreover, an exercise test may be indicated for specific populations (women, the elderly, patients with diabetes mellitus, patients in a preoperative context, asymptomatic patients and patients with congenital heart defects). Some cardiac diseases (such as chronic heart failure or arterial pulmonary hypertension) require a cardiopulmonary exercise test. Finally, an exercise test or a cardiopulmonary exercise test is indicated to prescribe a cardiac rehabilitation programme, adapted to the patient.

French Society of Cardiology guidelines on exercise tests (part 1): Methods and interpretation.

The exercise test is still a key examination in cardiology, used for the diagnosis of myocardial ischemia, as well as for the clinical evaluation of other heart diseases. The cardiopulmonary exercise test can further define functional capacity and prognosis for any given cardiac pathology. These new guidelines focus on methods, interpretation and indications for an exercise test or cardiopulmonary exercise test, as summarized below. The safety rules associated with the exercise test must be strictly observed. Interpretation of exercise tests and cardiopulmonary exercise tests must be multivariable. Functional capacity is a strong predictor of all-cause mortality and cardiovascular events. Chest pain, ST-segment changes and an abnormal ST/heart rate index constitute the first findings in favor of myocardial ischemia, mostly related to significant coronary artery disease. Chronotropic incompetence, abnormal heart rate recovery, QRS changes (such as enlargement or axial deviations) and the use of scores (based on the presence of various risk factors) must also be considered in exercise test interpretation for a coronary artery disease diagnosis. Arrhythmias or conduction disorders arising during the exercise test must be considered in the assessment of prognosis, in addition to a decrease or low increase in blood pressure during the exercise phase. When performing a cardiopulmonary exercise test, peak oxygen uptake and the volume of expired gas/carbon dioxide output slope are the two main variables used to evaluate prognosis.

Patterns of direct oral anticoagulant drug prescription in France in 2010-2013: a study in the Midi-Pyrénées area.

AIM: The aim of our study was to study the pattern of prescription of direct-acting oral anticoagulants (DOACs) according to the French recommendations. METHODS: We performed a cross-sectional study using anonymous data of patients covered by the French National Health Insurance information system (SNIIRAM) from 1 January 2010 to 31 December 2013 in the area of Midi-Pyrénées (southwest of France). RESULTS: Of the 355,608 patients identified, 325,216 (91.5%) were included, of whom 22,142 received at least one DOAC. About 39.1% (8,652 patients) had DOAC in an orthopedic indication, 46.5% (10,303 patients) in a cardiac indication, and 16.1% (3568 patients) in an indeterminate indication. Overall, guidelines were largely followed as for renal function monitoring, prescribing in orthopedic indications, in cardiac indications in patients aged 80 years and older, and in the case of concomitant use of verapamil. However, inappropriate prescriptions were observed for cardiac indications, and for dosage adjustments in orthopedic indications, with respect to both the age of patients (75 years and older) and those taking verapamil or amiodarone concomitantly. Guidelines were more followed in women and patients aged 80 or more. CONCLUSIONS: Among patients receiving DOACs, 58% were exposed to a prescription falling outside the guidelines. This study on DOAC prescription patterns revealed insufficiencies in the compliance with the French guidelines in certain indications.

[HIV and pregnancy: 2013 guidelines from the French expert working group]. / Infection par le VIH et grossesse: nouvelles recommandations 2013 du groupe d'experts français.

With effective antiretroviral therapy, the risk of mother to child transmission (MTCT) is now under 1%. The 2013 French guidelines emphasize early antiretroviral lifelong antiretroviral therapy. Thus, the current trend for women living with HIV is to take antiretroviral therapy before, during and after their pregnancies. A major issue today is the choice of antiretroviral drugs, to maximize the benefits and minimize the risks of fetal exposure. This requires interdisciplinary care. The use of effective therapies permits gradual but profound changes in obstetric practice. When maternal plasma viral load is controlled (<50 copies/ml), obstetrical care can be more similar to standards in HIV-negative women. Prophylactic cesarean section is recommended when the viral load in late pregnancy is above 400 copies/mL. Intravenous zidovudine during labor is recommended only if the last maternal viral load is>400 copies/mL or in case of complications such as preterm delivery, bleeding or chorio-amnionitis during labor. In case of premature rupture of membranes before 34 weeks, a multidisciplinary decision should be made, based on gestational age and control of maternal viral load; if the woman is under antiretroviral therapy and especially if her viral load is undetectable, steroids and antibiotics should be offered and pregnancy can be continued except in case of signs or symptoms of chorio-amnionitis. Breastfeeding is not recommended in women living with HIV in France, as in industrialized countries. Prophylaxis in the newborn is usually zidovudine for 1 month. In case of significant exposure to HIV perinatally, in particular when, maternal viral load is>1000 copies/mL, prophylactic combination therapy is recommended. Monitoring of the child is necessary to determine whether or not it is free of HIV infection and to monitor possible adverse effects of perinatal exposure to antiretroviral drugs.