[Written action plans for asthma control: How are they used by pulmonologists in France?] / Les plans d'action écrits pour l'asthme : quel usage en font les pneumologues en France ?

INTRODUCTION: Despite evidence of the benefits of the written asthma action plans (WAP) in asthma control, they remain poorly applied. The aim of our study was to assess the practices of French-speaking pulmonologists and paediatricians in their use of WAP for asthma control and to analyse the contents of several WAPs routinely consulted in treatment of asthma patients. METHODS: Members of three French medical societies (SPLF, G2A, SP2A) were requested to share their WAPs for asthma patients and to participate in an online survey about the possible influence of these documents on their practices. RESULTS: Most (95%) of the 41 WAPs taken into consideration were symptom-based and 34% included peak expiratory flow measurement. All of these action plans were in full compliance with current guidelines. Among the 110 survey respondents, while 65% systematically provided a WAP to their asthma patients, only 30% often or always supplemented the written document with therapeutic education sessions. In almost every case, it was the doctor who presented the WAP to the patient, generally devoting to less than 10minutes to explanation of what they were handing out. CONCLUSIONS: In France, WAPs are generally presented to the patient by the physician, which probably limits the time devoted to explanation of their contents. Furthermore, WAPs are rarely reinforced with therapeutic education. The current study suggests ways of improving the utilization of WAPs in asthma care and treatment.

Publishing in pandemic times: A bibliometric analysis of early medical publications on Kawasaki-like disease (MIS-C, PIMS-TS) related to SARS-CoV-2.

INTRODUCTION: At the end of April 2020, three European pediatric societies published an alert on a new hyperinflammatory disorder linked to SARS-CoV-2. This disease has alternatively been called Kawasaki-like disease, pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), and multisystem inflammatory syndrome in children (MIS-C). These alerts provide a clear starting point from which to study the early response of the medical and scientific community to a new disease in terms of scientific publications, and to compare the timeline of this response with levels of general public interest. To this aim, we conducted a bibliometric analysis of articles on this disease published between 1 April and 5 July 2020. METHOD: A literature search was performed using PubMed and in three preprint repositories. For each article, the name used for the disease in the title, the number of authors, the number of patients, the citations according to Google Scholar, the journal impact factor, and the Altmetric score were retrieved. Google search trends for the terms "Kawasaki" and "COVID," "COVID-19," and "coronavirus" were also retrieved, as was the number of Reuters news articles published on the topic. These data were compared longitudinally on a weekly basis. The quality of the reporting of the study was evaluated using the STROBE guidelines for observational studies with more than three patients and using the CARE guidelines for case reports of three or fewer patients. RESULTS: Eighty-six articles were included, among which ten were preprints (three of which were subsequently published) and 49 were clinical articles (57%). A total of 857 patients were described. The median number of authors per article was five (range, 1-45), the median number of patients was four (1-186), the median number of citations was one (0-170), the median Altmetric score was 12 (0-7242), and the median journal impact factor was 3.7 (1-74.7). For the clinical articles, the median percentage of STROBE or CARE checklist items satisfied was 70% (IQR, 56.75-79.25; range, 40-90). Guideline adherence was significantly higher for observational studies than for case reports (median percentage of checklist items satisfied, 78.5% vs 61.5%; P<0.001); however, guideline adherence did not differ significantly between peer-reviewed and preprint articles (median percentage of checklist items satisfied, 57% vs 72%; P=0.205). The only statistically significant difference between clinical articles and other types of articles was the number of authors (median, 7 vs 2; P=2.53E-9). Fifty-seven of the 86 articles were authored by researchers from just three countries (the USA, 31; France, 14; and the UK, 12). The names most frequently used in the title were Kawasaki-like disease (n=37), followed by MIS-C (n=27), PIM-TS (n=14), and other names involving the term "inflammatory" (n=12). Google searches for related terms peaked between weeks 18 and 21, following the initial alerts and decreased rapidly thereafter. The number of Reuters articles on the subject was correlated with Google search trends (ρ: 0.86, 95% CI [0.59; 0.96]; P=0.00016), but the number of medical articles published was not (ρ: -0.54, 95% CI [-0.87; 0.14]; P=0.11). The first small case series was published less than 2 weeks after the initial alert; however, if all articles had been deposited as preprints when they were submitted to journals, the cumulative number of reported cases would have been 300% higher in week 18 (3 vs 1), 400% higher in week 19 (44 vs 11), 70% higher in week 20 (124 vs 73), and 54% higher in week 21 (129 vs 84). CONCLUSION: In a period of 9 weeks after the initial alerts from European pediatric societies, 85 medical articles were published, involving 856 patients (one case report was published before the alerts), allowing rapid dissemination of research information. However, general public interest followed the news cycle rather than scientific releases. The quality of the reporting, as assessed by adherence to STROBE or CARE guidelines, was adequate with more than two-thirds of checklist items satisfied. Learned societies play an important role in the early dissemination of up-to-date peer-reviewed information. Preprint deposition should be encouraged to accelerate the dissemination of research information.

[Inhaled corticosteroids: Which regimens are appropriate?]. / Corticoïdes inhalés : quels schémas ?

Inhaled corticosteroids are the cornerstone of asthma management. Inhaled corticosteroid regimens differ slightly in various international guidelines on asthma management but are based on the principles of continuous treatment and titration to the lowest effective dose. Several recent studies, nevertheless, appear to demonstrate the potential value of preemptive or "pro re nata" regimens in infants and children. These studies were included in GINA 2015 for children 5 years of age and younger in whom discontinuous treatment is proposed as a second-line option. Should we change our practices after a critical reading of these studies?

[Acute cough in infants: impact of national guidelines on medical practices in a French department]. / Recommandations de l'Agence nationale de sécurité du médicament concernant le traitement de la toux aiguë du nourrisson : évaluation des pratiques médicales dans les Alpes-Maritimes.

CONTEXT AND AIM: Guidelines have been published regularly since 2010 by the ANSM (the Health Products Safety Agency) advising against antitussive drugs for infants because of their inefficacy and their side effects (convulsions, respiratory congestion). Antihistamines, mucolytics, and terpene-based suppositories have theoretically disappeared from infant pharmacopoeia. We assessed the degree of compliance with these guidelines on the part of health professionals. MATERIALS AND METHODS: From June 2012 to August 2012, 198 general practitioners and 44 pediatricians were assessed in the Alpes-Maritimes department of France by means of questionnaires. At the same time, an analysis of medical prescriptions was sought from the Regional Directorate of Medical Services (RDMS) of the PACA-Corse region Health Insurance. RESULTS: The rate of noncompliance with the contraindications was 14.9% (17.7% general practitioners and 2.3% pediatricians). The RDMS study showed a slight decrease in prescriptions for antitussives not recommended from 2011 to 2012: -21% for pediatricians, -15.5% for generalist physicians. CONCLUSION: Continued educational and informative campaigns are therefore needed to stop medical prescriptions of cough medicines for infants, which should also involve parents.

[Acute cough in infants: impact on families and pharmacists of contraindications of the Agence nationale de sécurité du médicament et des produits de santé (ANSM)]. / Recommandations de l'Agence nationale de sécurité du médicament et des produits de santé (ANSM) concernant la prise en charge de la toux aiguë du nourrisson : impact sur les familles et les pharmacies.

CONTEXT AND OBJECTIVE: Although commonplace and usually not serious, acute cough in the context of upper respiratory tract infection is a frequent reason for consultation and generates significant parental anxiety. Parents often request active drug intervention. Following the contraindications in infants of mucolytics, Hélicidine(®), antihistamines, and terpene-based suppositories, issued between 2010 and 2011 by the Agence nationale de sécurité du médicament et des produits de santé (ANSM), we wished to assess whether these contraindications were known by parents and applied in pharmacies. MATERIALS AND METHODS: An assessment of compliance with these contraindications was made by a double declarative prospective observational study in Nice, first with 29 pharmacists and pharmacy technicians (4-25 August 2012) and then with 289 parents of infants (December 2011 to April 2012). RESULTS: The rate of noncompliance with contraindications was 23.8 % for parents and 34.5 % of pharmacists and pharmacy technicians. Consumption of cough medicines was inversely correlated to the ability to perform a correct nasal wash (OR=2.3). Only 21 % of parents used nasal wash properly. Full-time work was a risk factor for noncompliance with contraindications (OR=1.91). CONCLUSION: ANSM contraindications still have a limited impact on pharmacists and families. Therefore, efforts must be pursued to stop delivering cough medicines for infants. The information and educational campaigns should also involve parents and help to improve nasal wash use.

[Impact on the indoor environment of allergic children of the medical counselor on indoor environment, after two successive visits at 6 months interval]. / Impact sur l'habitat de l'enfant atteint d'une affection respiratoire allergique du conseiller médical en environnement intérieur après deux visites successives à 6 mois d'intervalle.

BACKGROUND: The aim of this retrospective study was to assess the impact of a medical indoor environment counselor (MIEC) on the allergic child's indoor home environment, as well as the real-life experience of patients' families. METHODS: We enrolled 50 children (age, 4-18 years) with allergic respiratory illness (96 % asthmatics) from March 2011 to January 2012. During the first visit, the CMEI gave advice according to the results of the assessment. Home environmental exposures were assessed 6 months later. A satisfaction questionnaire was completed by the parents. RESULTS: We found a significant decrease in the presence of house dust mites (P = 0.0047), humidity, and molds (P = 0.0047) as well as volatile organic compounds (P = 0.0047). Smoking habits were not significantly changed (P = 0.083), nor was the presence of domestic pets (P = 0.3173). Over 74 % of the families were very satisfied with the CMEI's intervention. DISCUSSION: According to de Blay's study, a home visit by the MEIC increased compliance with mite reduction. The intervention to advise parents of asthmatic children on the risks of passive smoking was ineffective in reducing their children's exposure to environmental tobacco smoke. The advice given by the MEIC was better understood by the patients than that expressed by the medical teams. CONCLUSION: A targeted home-based environmental intervention increased the compliance to mite, humidity, and mold reduction. The role of the CMEI will undoubtedly develop: follow-up studies are necessary to justify their activity (cost-efficacy ratio of their intervention).

Sequential research-related biopsies in phase I trials: acceptance, feasibility and safety.

BACKGROUND: Sequential tumour biopsies are of potential interest for the rational development of molecular targeted therapies. PATIENTS AND METHODS: From June 2004 to July 2009, 186 patients participated in 14 phase I clinical trials in which sequential tumour biopsies (13 trials) and/or sequential normal skin biopsies (6 trials) were optional. All patients had to sign an independent informed consent for the biopsies. RESULTS: Tumour biopsies were proposed to 155 patients and 130 (84%) signed the consent while normal skin biopsies were proposed to 70 patients and 57 (81%) signed the consent. Tumour biopsies could not be carried out in 41 (31%) of the 130 consenting patients. Tumour biopsies were collected at baseline in 33 patients, at baseline and under treatment in 56 patients. Tumour biopsies were obtained using an 18-gauge needle, under ultrasound or computed tomography guidance. Only nine minor complications were recorded. Most tumour biopsy samples collected were intended for ancillary molecular studies including protein or gene expression analysis, comparative genomic hybridization array or DNA sequencing. According to the results available, 70% of the biopsy samples met the quality criteria of each study and were suitable for ancillary studies. CONCLUSIONS: In our experience, the majority of the patients accepted skin biopsies as well as tumour biopsies. Sequential tumour and skin biopsies are feasible and safe during early-phase clinical trials, even when patients are exposed to anti-angiogenic agents. The real scientific value of such biopsies for dose selection in phase I trials has yet to be established.

Persistent disease and recurrence in differentiated thyroid cancer patients with undetectable postoperative stimulated thyroglobulin level.

(131)I is given in differentiated thyroid cancer (DTC) without taking into account thyroglobulin (Tg) levels at the time of ablation, whereas 6-18 months later it is a major criterion for cure. This single-center retrospective study assessed the frequency and risk factors for persistent disease on postablation whole body scan (WBS) and postoperative neck ultrasonography (n-US) and for recurrent disease during the subsequent follow-up, in patients with DTC and undetectable TSH-stimulated Tg level (TSH-Tg) in the absence of Tg antibodies (TgAb) at the time of ablation. Among 1031 patients ablated, 242 (23%) consecutive patients were included. Persistent disease occurred in eight cases (3%) (seven abnormal WBS and one abnormal n-US), all with initial neck lymph node metastases (N1). N1 was a major risk factor for persistent disease. Among 203 patients with normal WBS and a follow-up over 6 months, TSH-Tg 6-18 months after ablation was undetectable in the absence of TgAb in 173 patients, undetectable with TgAb in 1 patient and equal to 1.2  ng/ml in 1 patient. n-US was normal in 152 patients and falsely positive in 3 patients. After a mean follow-up of 4 years, recurrence occurred in two cases (1%), both with aggressive histological variants. The only risk factor for recurrence was an aggressive histological variant (P = 0.03). In conclusion, undetectable postoperative TSH-Tg in the absence of TgAb at the time of ablation is frequent. In these patients, repeating TSH-Tg 6-18 months after ablation is not useful. (131)I ablation could be avoided in the absence of N1 and aggressive histological variant.

Sunitinib efficacy in the treatment of metastatic skin adnexal carcinomas: report of two patients with hidradenocarcinoma and trichoblastic carcinoma.

BACKGROUND: Adnexal carcinomas are rare and diverse cutaneous tumours. They are locally aggressive and have the potential for distant metastasis. Metastatic adnexal carcinomas are very resistant to conventional chemotherapies. Sunitinib, an oral tyrosine kinase inhibitor, is reportedly effective for the treatment of various solid cancers. Its use in adnexal carcinomas has never been reported. OBSERVATIONS: The first patient had metastatic clear cell hidradenocarcinoma and was stabilized over 8 months with sunitinib, before she relapsed. The second patient had a metastatic malignant hair follicle tumour (trichoblastic carcinoma) and achieved a partial remission with sunitinib, and disease stabilized after 10 months. Dynamic contrast-enhanced ultrasound (DCE-US) performed to evaluate tumour vascularization during treatment depicted a dramatic and early decrease in the tumour blood volume. CONCLUSIONS: Sunitinib was effective in controlling the disease in our two patients. DCE-US using linear raw data may have an early predictive value for tumour response to sunitinib. Further studies involving larger cohorts of patients are warranted in order to confirm the efficacy of sunitinib in these rare tumours.

[Real-time contrast-enhanced ultrasound in the evaluation of focal liver lesions: diagnostic efficacy and economical issues from a French multicentric study]. / Echographie de contraste temps réel dans la prise en charge diagnostique des lésions nodulaires hépatiques: évaluation des performances diagnostiques et de l'impact économique sur une étude multicentrique française.

The recent introduction of high-end ultrasound equipment combined with recent contrast agents provides marked improvements in the characterization of focal liver lesions as previously reported by monocentric studies. The aim of the present study was to evaluate the diagnostic performance of Contrast-Enhanced Ultrasonography (CEUS) using SonoVue as well as its medico-economic value for characterization of focal liver lesions. These nodules were not characterized on previous CT or conventional sonography. This prospective multicentric study conducted in 15 French centres found diagnostic performances similar to those reported for CT and MRI, with a concordance rate of 84.5%, sensitivity greater than 80% and specificity greater than 90% for all types of lesions. Higher acceptance was found for CEUS compared to other imaging modalities. Economical assessment based on examination reimbursment and contrast agent cost showed a lower cost for contrast ultrasound versus CT and MRI. This French multicentric study confirmed the high diagnostic value of CEUS for focal liver lesion characterization and demonstrated a lower economical impact compared to other imaging modalities such as CT and MRI.

[Evaluation of early response to antiangiogenic treatment with dynamic contrast enhanced ultrasound]. / Evaluation précoce des traitements anti-angiogéniques par échographie dynamique de contraste.

Early functional imaging evaluation of targeted treatments in oncology is of major importance. Dynamic contrast enhanced US is now recognized as a functional imaging technique able to evaluate new antiangiogenic drugs targeting superficial and deep seated lesions. This evaluation is based on an analysis of the curve of signal intensity over time after injection of the contrast agent. The availability of quantification software allows objective quantification of tumor perfusion parameters from linear raw data, prior to logarithmic signal compression, including maximum intensity of enhancement, mean transit time, time to peak, and wash-in slope coefficient. Dynamic contrast enhanced US, a sensitive, reproducible and readily available technique, allows early prediction of tumor response to treatment based on changes in vascularity, before morphological changes (RECIST) become apparent.

The potential contribution of fluorescent in situ hybridization analysis to the cytopathological diagnosis of Merkel cell carcinoma.

We report the cases of two patients with head and neck Merkel cell carcinoma (MCC) who developed local recurrences confirmed by cytopathology. Interphase fluorescent in situ hybridization (FISH) analysis was performed for research purposes using centromeric probes of chromosomes 6 and 8, on cytological slides. Trisomy of chromosome 6 was found in 85% of tumour cells in the first case of MCC and case 2 exhibited trisomy 8 in 77% of tumour cells. In the absence of specific molecular markers, detection of trisomy 6 and/or trisomy 8 could help in identifying MCC. FISH analysis is easily and quickly performed on interphase nuclei obtained through fine needle aspiration and may be extended to the study of other relevant genetic abnormalities.

[Percutaneous mitral commissurotomy and Lutembacher syndrome]. / Commissurotomie mitrale percutanée et syndrome de Lutembacher.

INTRODUCTION: Lutembacher syndrome refers to the rare combination of congenital atrial septal defect and acquired mitral stenosis. This condition is usually treated surgically by mitral valve operation with concomitant closure of the atrial septal defect. MATERIALS AND METHODS: Between 1993 and 2003, 4 patients with congenital Lutembacher syndrome had percutaneous mitral commissurotomy without closure of the atrial septal defect at our institution. The 4 patients were very symptomatic with right-sided heart failure signs and NYHA functional class III-IV. RESULTS: The procedure was carried out successfully for the four patients. Mitral valve area increased from 0.87 to 1.97 cm2 at mean; left atrial pressure decreased from 28.2 to 12.7 mmHg and the mean valve mitral gradient was reduced from 15.5 to 3.9 mmHg. Functional and clinical improvement was observed in all the cases. During a mean follow up of 55 +/- 29 months, our 4 patients remain pauci symptomatic under medical treatment. CONCLUSION: The percutaneous treatment of the Lutembacher syndrome is currently a possible alternative to the surgery among patients having an anatomy favourable to the procedure.

Doppler US with perfusion software and contrast medium injection in the early evaluation of isolated limb perfusion of limb sarcomas: prospective study of 49 cases.

BACKGROUND: The aim of this study was to prospectively evaluate the use of Doppler ultrasonography with perfusion software and contrast agent injection (DUPC) during isolated limb perfusion (ILP) with high-dose chemotherapy and TNF-alpha(biochemotherapy) in patients with locally advanced extremity soft tissue sarcoma (STS). PATIENTS AND METHODS: Fifty-two patients were prospectively included in this monocentric imaging trial. Three were excluded because the study was incomplete in two patients and one tumour did not exhibit any contrast uptake. DUPC was performed before ILP and on days 1, 7, 15, 30 and 60 after ILP. A total of 292 DUPC were performed on 55 target lesions in 49 evaluable patients. The percentage of contrast uptake was evaluated at each tumour site by two radiologists. The criterion tested was a decrease of more than 50% in intra-tumour contrast uptake compared to the pre-ILP examination. Results were compared with both MRI and histological analysis after resection of residual disease. RESULTS: According to MRI and the histological analysis, 25 (51%) patients were good responders (no difference between the four treatment arms) with tumour necrosis exceeding 90% and 24 (49%) were poor responders. As of day +1, the accuracy of DUPC in predicting tumour response was 82% (18/25 good responders and 22/24 poor responders) increasing to 91% at day +7, 95% at day +15 and 96% at day +30. At day +15, DUPC was predictive of a good response in 100% of the cases. CONCLUSION: DUPC is a simple technique, allowing early prediction of tumour response after ILP. A new treatment planning scheme can be proposed based on the results of this study.