Impact of the first wave of the COVID-19 pandemic on French Health students.

CONTEXT: In France, care workers and health students have been intensely mobilized during the first wave of the COVID-19 pandemic. But few studies have evaluated psychological distress on non-medical health students, in addition to the challenges posed by pedagogical continuity while universities are closed following health and safety regulations. OBJECTIVES: This study aims to assess COVID-19's impact on health students in France on different levels: psychological, educational and social. METHODS: An online national cross-sectional study, from April 11 to May 30 2020, included sociodemographic, work conditions and numeric scales. RESULTS: A total of 4411 students answered. Regarding the K6 scale, 39% of students had moderate distress, and 21% had a high level of distress. Risk factors of psychological distress included being a woman (P<0.001), being between 19 and 21 years old (P<0.001), living alone (P=0.008), and not having the ability to isolate (P<0.001). Students on the frontline had less psychological distress (57 vs 62%, P=0.003), better quality of sleep (34% vs 28% high quality, P<0.001) but a higher consumption of medical (8.5% vs 6.5%, P=0.044) and non-medical (18% vs 10%, P<0.001) psychotropic drugs. Nurse and medical students had more distress and used more non-medical psychotropic substances than other health students (15% vs 9.2%). DISCUSSION: COVID-19' crisis had an important impact on health students' mental health, social life and training with discrepancies regarding the speciality whether they were on the frontline or not. There is an urgent need for psychological and pedagogical support for students, and even more so regarding the prolongation of the COVID-19 epidemic.

First-line treatment with sunitinib for type 1 and type 2 locally advanced or metastatic papillary renal cell carcinoma: a phase II study (SUPAP) by the French Genitourinary Group (GETUG)†.

BACKGROUND: Papillary renal cell carcinoma (PRCC), type 1 and type 2, represents 10%-15% of renal cell carcinomas (RCC). There is no standard first-line treatment of metastatic PRCC (mPRCC). Anti-angiogenics have shown activity in retrospective studies but no prospective studies in pure papillary histology have been reported, but one with foretinib. PATIENTS AND METHODS: A prospective phase II study evaluated sunitinib in first-line treatment of mPRCC. The primary end point was overall response rate (ORR). Secondary end points were progression-free survival (PFS) and overall survival (OS). RESULTS: Fifteen and 46 patients, respectively, with type 1 and type 2 mPRCC were enrolled. Using the MSKCC scoring system: 12 (20%), 33 (55%) and 9 (15%) patients were, respectively, in the favourable, intermediate or poor risk group and 7 undetermined. Median follow-up is 51.4 months. In type 1, 2 patients 13% [95% confidence interval (CI) 0.1-30.5] had a partial response (PR), 10 had stable disease (SD) with 5 (33%) ≥12 weeks. In type 2, 5 patients 11% (95% CI 1.9-20.3) had a PR, 25 had SD with 10(22%) ≥12 weeks. Median PFS was 6.6 months (95% CI 2.8-14.8) in type 1 and 5.5 months (95% CI 3.8-7.1) in type 2. Median OS was 17.8 (95% CI 5.7-26.1) and 12.4 (95% CI 8.2-14.3) months, respectively, in type 1 and 2. Safety was as expected with sunitinib for metastatic RCC. CONCLUSION: Sunitinib showed activity in treatment of type 1 and 2 mPRCC but lower than in clear-cell mRCC. Both PFS and OS are longer in type I PRCC. Sunitinib represents an acceptable option in first-line treatment of mPRCC.

Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project†.

BACKGROUND: In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions. MATERIALS AND METHODS: A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. RESULTS: Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression). CONCLUSIONS: The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in all RCC clinical trials, thus facilitating reporting and increasing precision in between trial comparisons.

Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial.

BACKGROUND: The standard treatment of patients with metastatic germ-cell tumor (GCT) relapsing after first-line chemotherapy is based on a cisplatin and ifosfamide-containing three-drug regimen, which usually yields a complete response (CR) rate <50%. As gemcitabine consistently displayed activity in patients with advanced GCT and as synergy with cisplatin was reported, we integrated this drug into the salvage triplet regimen and assessed its activity in this phase II study. PATIENTS AND METHODS: The GIP regimen consisted in gemcitabine 1000 mg/m(2) day 1 and 5, ifosfamide 1200 mg/m(2)/day day 1-5, cisplatin 20 mg/m(2)/day day 1-5, and granulocyte colony-stimulating factor 263 µg/day day 7-15, repeated every 3 weeks for four cycles. Eligibility criteria were that patients had favorable prognostic factors to conventional-dose salvage chemotherapy including a testis primary tumor and a previous CR to first-line chemotherapy for metastatic disease. The primary end point was the CR rate and a two-stage Simon design was used. RESULTS: Thirty-seven patients were accrued and 29 (78%) achieved a favorable response, including a CR in 20 (54%) and a partial response with normalization of tumor markers (PRm-) in 9 (24%). With a median follow-up of 53 months (13-81), the 2-year overall survival rate is 73% (57%-84%) and the continuous progression-free survival rate is 51% (35%-66%). Myelosuppression was the main toxicity including febrile neutropenia in 8 (22%) patients and 18 (50%) cases required platelet infusion. No grade 3 and 4 peripheral neurotoxicity or renal toxicity occurred. Two patients died of treatment-related toxicity, one of them with cancer progression. CONCLUSION: In a multicenter context, four cycles of the GIP regimen achieved a high CR rate in patients with relapsed testicular GCT. The GIP regimen avoided severe neurotoxicity and yielded a high survival rate. CLINICAL TRIAL NUMBER: NCT00127049.

[New concepts in the management of upper tract urinary carcinoma in 2010]. / Prise en charge et suivi des tumeurs de la voie excrétrice supérieure en 2010.

The aim of this article is to make a synthesis of news headlines concerning the management of upper tract urinary carcinoma. For non muscle-invasive upper tract urinary tumors, ureteroscopy with biopsies is a part of the systematic diagnostic assessment in case of suspicious imaging. For muscle-invasive upper tract urinary tumors, there is low level of evidence of expert's opinion guidelines about neoadjuvant or adjuvant chemotherapy. These therapeutic strategies can be sometimes discussed, by arguing analogy with bladder tumors.

Glucose-sensing mechanisms in eukaryotic cells.

Glucose not only serves as a nutrient but also exerts many hormone-like regulatory effects in a wide variety of eukaryotic cell types. Recently, interest in identifying general mechanisms and principles used to sense the presence of glucose has significantly increased and promising advances have been made: in yeast, the first proteins with an apparently specific function in glucose detection have been discovered; in plant cells, there is increasing evidence for a diverse array of glucose-induced signalling mechanisms; and in mammals, glucose-sensing phenomena have turned out to be much more widespread than just in the well-known example of pancreatic beta cells.

[Rating of tumoral growth in non-operated primary or recurrent extra-abdominal aggressive fibromatosis]. / Etude de la croissance tumorale des tumeurs desmoïdes extra-abdominales (FDEA) primitives ou récidivées non opérées.

PURPOSE OF THE STUDY: Extra-abdominal aggressive fibromatosis (EAAF) is a benign desmoid tumor with a potentially aggressive behavior. Surgical treatment is compromised by a very high rate of recurrence, sometimes with significant morbidity. We conducted a prospective surveillance of our patients (clinical and MRI) with EAAF to search for prognostic factors. MATERIAL AND METHODS: This cohort included 17 patients with EAAF. For nine patients, biopsy alone was performed. For eight, the tumor was a recurrence after surgical removal. Patients were seen for a clinical assessment and MRI every six months. RESULTS: Median follow-up was 42 months (range 6-114). Three patients worsened clinically with pain or functional impairment. One patient required neurosurgery to control pain (good stable outcome). MRI showed progression for two tumors (12%) but with a short follow-up since diagnosis (9 and 14 months), in one case despite medical treatment. Three tumors regressed and twelve remained stable on successive MRI. On average the tumor growth lasted ten months. DISCUSSION: Tumor growth was never noted beyond 36 months. This notion of an interruption in tumor growth is mentioned sporadically in reports on EAAF, which have generally included recurrent tumors. To our knowledge this is the first series reporting tumors left in place a followed with modern imaging techniques. The high rate of spontaneous interruption of tumor growth must be counterbalanced with the difficult task of local treatment: the risk of recurrence is particularly high after surgery and functional sequelae can be significant when wide resection is proposed in an anatomically difficult localization. The precise role for surgery, and combined radiotherapy, remain to be determined. There are only scarce reports on general treatments. Considering these facts, we propose that surgical resection should not be considered the only solution for the treatment of EAAF. Further work is needed to define the useful contribution of simple surveillance of these benign tumors.

Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases.

BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. RESULTS: With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. CONCLUSIONS: Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy.

Long-term update of the 24954 EORTC phase III trial on larynx preservation.

The long-term results of the EORTC 24954 trial comparing sequential versus alternating chemotherapy and radiotherapy (RT) for patients with locally advanced laryngeal and hypopharyngeal cancer are reported. From 1996 to 2004, 450 patients were randomly assigned (1-1) to a sequential arm (SA = induction cisplatin-5fluorouracil followed by a 70Gy-RT for the responders or a total laryngectomy and post-operative RT for the non-responders) and an alternating arm (AA = cisplatin-5fluorouracil alternated with three 2-week courses of 20 Gy-RT for a total dose of 60 Gy). Median follow-up was 10.2 years. Ten-year survival with functional larynx (primary end-point) and overall survival were similar in both arms (18.7% and 33.6% in SA versus 18.3% and 31.6% in AA). Late toxicity was also similar; however, a trend for higher larynx preservation and better laryngeal function was observed in AA.

Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas.

A significant link between 5-fluorouracil (5FU) plasma concentration and its therapeutic activity has been demonstrated in colon and head and neck cancer patients for 5FU used as a continuous infusion. Dose adjustment based on pharmacokinetic follow-up has been proposed to decrease hematological and digestive toxicities, but the clinical impact of this approach has not yet been demonstrated. A randomized multicentric study was conducted to evaluate the clinical interest of 5FU dose adaptation guided by pharmacokinetics. One hundred twenty-two head and neck cancer patients were randomly assigned to receive induction chemotherapy with cisplatin (100 mg/m2, day 1) and 5FU (96-h continuous infusion), either at standard dose (St-arm; 4 g/m2) or at a dose adjusted according to the 5FU area under the curve (AUC0-48h; PK-arm). In total, 106 patients were evaluable for toxicity and response. In the PK-arm (n = 49), 5FU doses and area under the curve were significantly reduced during cycle 2 and cycle 3 (P < 0.001) as compared with the St-arm (n = 57). Grade 3-4 neutropenia and thrombopenia were significantly more frequent in the St-arm as compared with the PK-arm (17.5% versus 7.6%, respectively; P = 0.013). No grade 3-4 mucositis occurred in the PK-arm, whereas 5.1% was observed in the St-arm (P < 0.01). The objective response rate was comparable in the two treatment arms: 77.2% in the St-arm versus 81.7% in the PK-arm. The present study is the first to demonstrate, in a randomized design, the clinical interest of an individual 5FU dose adaptation based on pharmacokinetic survey, in terms of therapeutic index improvement.

[Noninvasive ventilation for acute respiratory failure in a pulmonary department]. / Ventilation non invasive dans l'insuffisance respiratoire aiguë en service de pneumologie.

INTRODUCTION: Noninvasive ventilation (NIV) is considered as the first choice treatment for selected patients with acute respiratory failure (ARF), but many hospitals are forced to start NIV on medical wards. METHODS: The aim of this retrospective study was to assess the outcomes of NIV initiated for ARF on a respiratory ward and to find the criteria predictive of failure. All patients were treated in a four-bed ward specifically dedicated to NIV. Failure of NIV was defined as the need for intubation and transfer to ICU, or death. RESULTS: Among 105 admissions with ARF, 49 episodes needed NIV. These episodes were divided into 2 groups: PaCO2<45mmHg (10) and PaCO2>45mmHg (39). The overall failure rate of NIV and overall in-hospital mortality rate were 26.5% and 17% respectively. On multivariate analysis, SAPS II and respiratory acidosis with a pH less than 7.30 were significantly associated with failure of NIV. CONCLUSIONS: NIV is practicable and is effective in the management of mild to moderate ARF on a respiratory ward. However, patients with respiratory acidosis and a pH less than 7.30 are at risk of NIV failure.

Phase II study of OSI-211 (liposomal lurtotecan) in patients with metastatic or loco-regional recurrent squamous cell carcinoma of the head and neck. An EORTC New Drug Development Group study.

The purpose of this study was to evaluate the activity and safety of OSI-211, the liposomal form of lurtotecan, in patients ineligible for curative surgery or radiotherapy and with metastatic/locoregional recurrent squamous cell carcinoma of the head and neck (SCCHN) and target lesions either within a previously irradiated field ("within") or outside a previously irradiated field ("outside"). OSI-211 was given intravenously over 30 min on days 1 and 8 at 2.4 mg/m2/day, repeated every 21 days (1 cycle). From July 2001 to March 2002, 32 patients from 14 institutions were enrolled in the "within" arm and 18 in the "outside" arm. In the "within" arm, two patients were ineligible because their tumour site was not allowed in the protocol (nasopharynx, skin) and two other patients never started treatment. Of the 46 eligible patients who started treatment, there was one objective response (response rate: 2.2% (95% Confidence Interval (CI): [0-11.5%]). Twelve patients in the "within" arm and 6 in the "outside" arm had stable disease, with a median duration of 18 weeks, 95% CI (12.7-25.7). The median time to progression was 6 weeks (95%CI: [5.9-12.7] weeks). Haematological toxicity was moderate in both arms. The most common haematological toxicity was grade 1-2 anaemia in 79% of patients. Non-haematological toxicity was mild in both arms. The most common grade 3-4 non-haematological toxicity was infection in 8.5% of patients. OSI-211 administered on d1 and d8, every 3 weeks, is well tolerated, but shows only minimal activity in locally advanced/metastatic SCCHN.

Ondansetron suppository: an effective treatment for the prevention of emetic disorders induced by cisplatin-based chemotherapy. French Ondansetron Study Group.

This multicentre, randomised, double-blind, double-dummy, parallel group study was investigated in order to compare on 3 days the efficacy and the safety of the 16 mg once a day (od) ondansetron suppository (suppository group) with the recommended ondansetron treatment, i.e. 8 mg intravenous (i.v.) ondansetron on day 1 followed by 8 mg tablet (p.o.) twice daily (i.v. + p.o. group) on days 2 and 3 in patients receiving cisplatin (> or = 50 mg/m2) containing chemotherapy. In the 420 patients included in the intent-to-treat population, 209 received the 16 mg suppository and 211 the i.v. + p.o. treatment. The number of emetic episodes and the nausea score were recorded each day. Concerning the primary criterion, both treatments provided good anti-emetic control with 87% of all patients having a complete or major response (0-2 emetic episodes) on day 1 in the suppository group and 92% in the i.v. + p.o. group (P = 0.058). The 90% confidence interval for the difference between the two treatments for complete or major control was included in the interval (-15%, 15%) and showed that the treatment groups could be regarded as equivalent. Small differences in favour of the i.v. + p.o. group were observed concerning the secondary parameters. Both treatments were well tolerated. The results of this study show that both treatments are equivalent in the prevention of cisplatin-containing chemotherapy induced emesis for the primary efficacy criteria and that the ondansetron suppository is efficient and well tolerated and is a suitable alternative to the anti-emetic treatment combining the intravenous and oral routes.

Clinical randomized study of 5FU monitoring versus standard dose in patients with head and neck cancer: preliminary results.

Prospective studies of dose adaptation of continuous 5FU infusion combined with cisplatin have shown that pharmacologically guided dosing was feasible in the treatment of head and neck carcinomas. Adaptative dosing results in reduced haematological toxicity, but few data are available for clinical response rate. Preliminary results (38 patients) of a randomized trial comparing standard dose of 5FU (20 patients) and monitoring of 5FU based on pharmacokinetic information (half-cycle area under the curve, 18 patients) indicate that haematological tolerance and complete response rate were improved. Severe (GIII-GIV) thrombocytopenia and neutropenia were significantly reduced during cycle 2 (0% versus 11.1% and 5.5% versus 27.7% respectively, p < 0.01) and cycle 3 (0% versus 27.7% and 6.6% versus 33.3% respectively, p < 0.001). The complete response rate was increased in the group with monitoring of 5FU doses (55.5% versus 40.0%, p < 0.001). These interesting results will be confirmed at the end of the trial, which is expected to include 126 patients.

[Predictive value of the hemogram for myelotoxicity induced by the association of carboplatin-fluorouracil on the 4th day of the therapeutic regimen]. / Valeur prédictive de l'hémogramme du 4e jour pour la myélotoxicité induite par l'association carboplatine-5-fluorouracile.

The aim of this study was to determine the value of haematological counts at the 4th day of a chemotherapy cycle, in order to foresee neutro and/or thrombocytopenia during the same chemotherapy cycle. One hundred and ten cycles of chemotherapeutic regimens with carboplatin (400 mg/m2, dl) and 5-fluorouracile (1 g/m2/d, by iv continuous infusion for 96 hours) every 3 weeks, were analyzed for 42 patients with locally advanced but non metastatic squamous cell carcinoma of head and neck, without prior chemotherapy. Lymphocyte counts were significantly decreased at the 4th day but normalized at the 8th day (P < 10(-6)). Decreases of lymphocyte and neutrophil counts at the 4th day were significantly correlated to grade > 2 neutropenia. The positive predictive value of lymphocyte or neutrophil counts is about 50% for some cut-off values but not high enough, with the schedule of chemotherapy in our study, to justify the systematic prophylactic therapy with haematopoietic growth factors.

[Randomized placebo trial of myeloprotection with goralatide in patients with squamous cell carcinoma of the upper respiratory and digestive tracts or esophagus, treated with a carboplatin-fluorouracil combination]. / Essai randomisé avec placebo de myéloprotection par le goralatide des patients présentant un carcinome épidermoïde des voies aérodigestives supérieures ou de l'oesophage, traités par l'association carboplatine-5 fluorouracile.

Eighty-four patients with locally advanced, non metastatic squamous cell carcinoma of head and neck or esophagus, were included in a multicentric double-blind randomized trial, comparing goralatide (12.5 or 62.5 micrograms/kg/day, d1-d4) to placebo, associated with carboplatin (400 mg/m2, d1) and 5-fluorouracile (1 g/m2/d continuous IV over 96 hours). Haematological toxicity was analysed on 221 cycles of chemotherapy. All but one patient were evaluable because of early death without haematological toxicity. No significant difference was observed for mean nadir of leukocytes, granulocytes, platelets counts and hemoglobin level. Duration of haematological toxicity was no significantly different for the two groups of patients. Anemia and lymphopenia were more frequent in the goralatide treated patients. Clinical and biological tolerability of goralatide was excellent.

[Development of antihypertensive drug consumption in the Toulouse University Regional Hospital Center from 1981 to 1989]. / Evolution de la consommation des antihypertenseurs au Centre Hospitalier Régional Universitaire de Toulouse de 1981 à 1989.

Eighties were characterized by the introduction of two new pharmacological class of antihypertensive drugs [converting enzyme inhibitors (CEI) and calcium channel blockers] and the publication of several large scale antihypertensive trials. The consumption of antihypertensive drugs at the Toulouse Universitary Hospital was evaluated during the ten last years. Total consumption remained stable until 1985 (560,000 pinch units) and raised to 650,000 in 1988. This number decreased to 580,000 in 1989. Consumption of diuretics remained stable during these years whereas beta-blocking agents slightly decreased. The global increase of prescription was explained by the introduction of CEI and a marked rise in calcium channel blockers from 1986. In contrast, consumption of central antihypertensive drugs crushed from 1982 to equal vasodilators (direct + alpha-blocking agents) in 1989.

[Cutaneous ulcer from Mycobacterium ulcerans. Apropos of 1 case in French Guiana]. / L'ulcère cutané à Mycobacterium ulcerans. A propos d'une observation en provenance de Guyane française.

Skin ulcer due to Mycobacterium ulcerans is presented. The patient come from East of French Guyana. Growth of this mycobacteria is obtained with diphasic Lowenstein medium at 30 degrees C. Diagnostic of M. ulcerans results from mycolic acids study.