Multicenter randomized trial comparing cisplatin-mitomycin-vinorelbine versus cisplatin-mitomycin-vindesine in advanced non-small cell lung cancer. 'Groupe Français de Pneumo-Cancérologie'.

The study was designed to evaluate the value of vinorelbine in a cisplatin-mitomycin-vinca alkaloid regimen for treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). A group of 227 patients with inoperable NSCLC in stage III (58%) or stage IV (42%) were included in this randomized multicenter trial comparing a reference regimen (VDS group, n = 113) cisplatin (120 mg/m2 on day 1, day 29 and day 71), mitomycin (8 mg/m2 on day 1, day 29 and day 71) and vindesine (3 mg/m2/week for 5 weeks and then every 2 weeks up to the 15th week) to a cisplatin-mitomycin-vinorelbine combination (VNB group, n = 114), with cisplatin and mitomycin at the same doses, and vinorelbine 25 mg/m2/week for 16 weeks. The objective response rate (evaluated at 17th week) was 17% in the VDS group and 25% in the VNB group (P = 0.15). Median survival was 33.4 weeks and 34.5 weeks in the VDS and VNB arms, respectively. Overall survival duration was not significantly different between the two arms (logrank test, P = 0.20) despite a trend to an increased survival in the VNB group. This essentially benefited the patients with stage III disease with a clear-cut lengthening of median (45.9 vs. 33.4 weeks) and 1 year survival (44.6% vs. 26.2%, P < 0.05) in favor of the VNB group. Nevertheless, there was no significant difference in overall survival (logrank, P = 0.13). Survival duration of the patients with stage IV disease was comparable in the two arms (logrank test, P = 0.90). Grade 3 or 4 neutropenia was found in 61% and 87% of the VDS and VNB groups, respectively (P < 0.01). Grade 2-4 peripheral neuropathy was observed in 23% of the patients in the VDS group and in 6% of the patients in the VNB group (P < 0.01). Replacement of vindesine by vinorelbine in a cisplatin-mitomycin-vinca alkaloid chemotherapeutic regimen did not lead to a significant improvement in objective response rate or in duration of survival. There was a reduction in neurotoxicity at the expense of an increased hematologic toxicity. However, for patients with stage III disease there was an increase in 1 year survival with the vinorelbine combination.

Lower respiratory tract infections in adults: non-antibiotic prescriptions by GPs.

BACKGROUND: The AIR II study is a prospective multicentre assessing management of lower respiratory tract infections (LRTIs) in adults by general practitioners (GPs). Epidemiological studies generally address the prescriptions of antibiotics. To our knowledge, little is known about the real impact of non-antibiotic therapeutic prescriptions (defined here as co-prescriptions) in LRTI. Therefore, the aim of the study was to evaluate non-antibiotic prescriptions in LRTIs. METHODS: Two thousand general practitioners (GPs) were randomly selected and asked to participate in each of 30 predefined areas covering mainland France. The patient's sociomedical record was completed by the GP during the consultation and sent to the data processing centre at the same time as an anonymous copy of his prescription. The GP also had to report the inclusion by telephone and agree to a telephone appointment with an interviewer. RESULTS: GPs (n = 3144) reported 5469 evaluable cases. Pneumonia accounted for 9.6% of diagnoses, acute exacerbations of chronic bronchitis 14.9% and acute bronchitis 72.5%. Antibiotics were prescribed to 96.5% of patients. In addition to the 5270 prescriptions of antibiotics, co-prescriptions proved to be twice as numerous as prescriptions of antibiotics (10,027 prescriptions for 5115 patients). Mucomodifiers, steroidal anti-inflammatory drugs and bronchodilators were significantly more prescribed in AECB than others. Non-steroidal anti-inflammatory drugs and antitussives were significantly more prescribed in acute bronchitis than AECB or CAP. CONCLUSIONS: Our results suggest that recommendations of management in LRTIs need to take into account co-prescriptions.

Cognitive skill acquisition and transfer in younger and older adults.

The acquisition of cognitive skills often depends on 1 of (or a combination of) 2 processes, the execution of an algorithm, and the retrieval of problem instances. This study examined the effects of age and repetition of problem instances on the production and verification of solutions to 2 serially presented sets of alphabet arithmetic problems. Analyses of the parameters derived from power-function fits for individuals revealed age differences favoring young adults in improvement span, learning rate, and asymptote. For both age groups, the beneficial effects of repetitions on 1st-set response times were attributable to algorithmic speedup and to the retrieval of instances, whereas improvements in the speed of 2nd-set response times were attributable primarily to item retrieval.

Pirarubicin phase II study in untreated metastatic small-cell lung carcinoma. A cooperative study of the Groupe Français de Pneumo-Cancérologie (GFPC).

Pirarubicin (THP) (Roger Bellon Laboratory, France) is a new anthracycline under clinical development. In order to assess the efficacy and toxicity of the drug in small-cell lung carcinoma (SCLC), we have undertaken this trial in front-line therapy in patients with metastatic disease, PS less than 3 and at least one evaluable lesion. Responses were assessed after two cycles of THP (60 mg/m2 i.v. bolus every 3-4 weeks) and a further cross over to VP16 + CDDP (three cycles) was systematic whatever the response to THP. This crossover was performed after only one cycle in case of obvious progression. From June 1988 to April 1990, 32 patients were enrolled: 6 were ineligible (4 non-SCLC, 2 M0), 26 patients were fully evaluable for THP and 18 patients for VP16-CDDP. The characteristics of the patients were as follows: mean age 57.4 years (38-71); T4: 54%; T3: 27%; T2: 19%; N3: 62%; N2: 35%; No: 4%. The efficacy was as follows 1 complete response and 2 partial responses (confirmed by endoscopy); 12 patients received only one cycle because of obvious progression; the overall response rate is 12% (95% confidence interval 0-24%). The patient who had complete response after pirarubicin remained in CR after VP16-CDDP, whereas the 2 patients who had partial response achieved CR for one and PR for the other; among the 15 who did not respond 1 CR and 7 PR were observed. The only significant toxicity of THP was granulopenia without infection. THP seems to be an effective anthracycline in SCLC, and the study is continuing. A response could be reached in 50% of the nonresponders with standard therapy and 10 of 24 patients (42%) finally responded. Therefore, this schedule for testing new drugs in metastatic SCLC appears ethically acceptable.

Five-Day Spiramycin vs Seven-Day Penicillin V in the Treatment of Streptococcal Tonsillitis in Children.

Because of the frequency of penicillin allergies in children receiving ß-lactam antibacterial agents, the macrolides are frequently chosen as alternatives in patients with group A ß-haemolytic streptococcal (GABHS) infections. Spiramycin, amacrolide widely used in paediatrics, achieving remarkably high tonsillar tissue concentrations, was evaluated in this study in comparison with penicillin V (Phenoxymethylpenicillin). 298 children aged 1.5 to 14 years with acute tonsillitis and a positive rapid antigen test for GABHS were randomised to receive either a 5-day course of spiramycin 100 000 IU/kg twice daily or a 7-day course of penicillin V 25 000 IU/kg 3 times daily. Clinical and bacteriological assessments were recorded at inclusion (day 1), at the end of the treatment visit (days 8 to 12), and at the follow-up visit (days 25 to 35). GABHS isolated during the study were analysed by total DNA restriction fragment length polymorphism analysis. Of the 237 children with a positive GABHS culture at day 1,210 (88.6%) were evaluable for complete clinical and bacteriological efficacy at the end of treatment. Clinical efficacy was evident in 96.1% (98 of 102) for spiramycin and in 98.1% (106 of 108) for penicillin V. Bacteriological eradication was achieved in 79.4% (81 of 102) for spiramycin and in 89.8% (97 of 108) for penicillin V. Three failures occurred in the spiramycin group. In intent-to-treat analysis, the success rate (clinical cure and bacteriological eradication) for spiramycin was 77.9% (116 of 149) and that for penicillin V was 83.9% (125 of 149). At the follow-up visit, 182 children were evaluable for efficacy. Clinical cure with or without asymptomatic carriage of GABHS was observed in 97.7% (86 of 88) for spiramycin and in 89.4% (89 of 94) for penicillin V. Three relapses and 1 reinfection occurred in the penicillin V group. Adverse events, mainly gastrointestinal, occurred in 10.7% of spiramycin patients versus 12.8% of penicillin V patients. These results show that a 5-day treatment regimen with spiramycin twice daily is effective and well tolerated in GABHS tonsillitis, and is an alternative to penicillin V when necessary in children.

[Development over 3 years of asthma recently diagnosed in a cohort of children (ASMA study). Factors related to improvement in clinical status]. / Evolution sur 3 ans de l'asthme récemment diagnostiqué dans une cohorte d'enfants (étude ASMA). Facteurs liés à l'amélioration de l'état clinique.

OBJECTIVE: The objective of the ASMA study was to describe the evolution of light to moderate asthma, newly or recently (12 Pounds months) diagnosed in private pneumology centers, and to search for the predictive factors. METHODS: In 1995, 251 private pneumologists, throughout Metropolitan France, recruited 396 asthmatic children, 6 to 12 years old (64% boys). The 334 patients eligible for the study were examined every 4 months during 3 years (a mean of 6 controls were conducted out of the expected 9). The data were collected on standardized questionnaires completed by the physicians and notebooks filled-in by the patients the week before each control. This questionnaire comprised two asthma 'control' criteria: "control" of the clinical state, defined as asthma attacks < 1 per week AND nocturnal awakening < 1 per week AND absence of asthma symptoms between attacks on every control visit; "control" of the need for b2 mimetics on request, defined as the non-use throughout the week preceding the control visit. RESULTS: The global clinical state of the cohort rapidly improved once care was initiated: the proportion of children exhibiting at least one attack of asthma per week rapidly dropped to 43% on inclusion and to 13% on the first control visit (4 months), 10% on the second control visit, and then fluctuated at around 8% up until the last control visit. A similar evolution was noted regarding nocturnal asthma attacks. The proportion of patients with prescriptions for inhaled corticosteroids and long-lasting b2-mimetics increased over the three years of follow-up. Analysis of the factors related to the individual 'control' of the clinical state showed a negative effect in family histories of asthma (father) and the presence of smokers in the home, but above all a positive effect of compliance to treatment and particularly its understanding (OR = 2.5; p = 0.03) and respect of the doses (OR = 2.7; p < 0.01). The positive effect of compliance was confirmed by analysis of the factors related to the use of b2 mimetics on request. CONCLUSION: Smoking should be avoided in the home. Compliance to treatment could be improved by making sure that the patients and their parents fully understand the disease and its treatment, and by persuading them to strictly follow the treatments prescribed.

[Diagnostic and therapeutic strategies in acute pneumopathies in urban practice]. / Stratégies diagnostiques et thérapeutiques devant les pneumopathies aiguës en pratique de ville.

The consensus conference of the French Language Society of Infectious Disease convened at Lille in 1991 stressed the fact that "in the management of pneumonia, neither the clinical features nor the bacteriological information would enable a prediction of the responsible and effective agent with sufficient accuracy" and that antibiotic therapy should be empirical, based on the probabilities linked to the epidemiology and locality. The object of this study was to ascertain the diagnosis and therapeutic attitude of the general practitioner (GP) dealing with an acute infectious pneumonia in a 40 year old adult, previously well without any critical signs, which was the model taken for the consensus conference. One hundred GPs were selected at random from the general medical list in the city of Bordeaux and registered with the local medical council in Gironde. They were invited to answer a questionnaire containing 69 questions. The results were analysed for the two phases of the enquiry. The strategy of first intention and the method of re-evaluating for treatment instituted. Secondly the strategy used when faced with a patient who did not improve with the initial treatment. Eighty eight GPs answered the questionnaire and thus we are able to give the following information: the differential diagnosis was not clearly made between bronchial and pulmonary pathology when faced with a lower respiratory tract infection; two thirds of the GPs had a diagnostic and therapeutic approach which was in agreement with the recommendations of the consensus.(ABSTRACT TRUNCATED AT 250 WORDS)

[Factors predicting the severity and the degree of symptom control of asthma in a recently diagnosed cohort of adult patients (A.S.M.A study)]. / Facteurs liés à la sévérité et au contrôle de l'asthme récemment diagnostiqué dans une cohorte de patients adultes.

INTRODUCTION: The aim of this cohort study was to describe the evolution of recently diagnosed (<12 months) asthma, and to identify outcome predictive factors. This paper describes the evolution of an adult cohort and the factors related to asthma severity and control. METHODS: In 1995, 251 chest specialists from throughout France, recruited 347 asthmatic adults (subjects with severe asthma were excluded). 220 eligible patients were examined every four months over a three year period. Data (socio-demographic characteristics, asthma history, results of atopy testing and lung function tests, treatment, drug compliance, respiratory infections, changes in lifestyle and environment, and major life events) were collected by means of detailed standardised questionnaires completed by physicians. Asthma severity, recorded one year after study inclusion, and asthma control, assessed at each follow-up visit in the second and third year, were defined according to the international guidelines. RESULTS: The clinical status of these adult patients generally improved rapidly. Asthma severity correlated closely with allergy, with a history of childhood asthma and with sensitisation to indoor allergens. After adjusting for severity, poor asthma control was associated with poor compliance, with respiratory infections, and, to a lesser extent, with animals inside the home. CONCLUSIONS: This cohort study highlights the association of asthma severity with allergy, and of poor asthma control with poor compliance and respiratory infections.

[Management of lower respiratory tract infections by general practitioners in France]. / Prise en charge des infections respiratoires basses en médecine générale en France.

OBJECTIVE: The purpose of this study was to describe the diagnostic and therapeutic strategies used by general practitioners (GPs) in patients with lower respiratory tract infections (LRTI). METHODS: Four hundred fifty GPs practicing in France participated in the study; they included 804 patients. The GP recorded social and demographic data and their prescription on a data sheet and responded to a phone questionnaire about their strategy. RESULTS: Most of the LRTI were acute bronchitis (72%); pneumonia and acute exacerbations of chronic bronchitis were observed respectively in 11% of the patients recruited. Diagnostic criteria used by the GPs were generally auscultation signs in patients with fever, cough and expectoration. Specialized advice (always a chest physician) and hospitalization were exceptional. Prescription of complementary exams was strongly related to the diagnosis of pneumonia (OR = 33.3; CI0.95: 15.48-70.4). Sick leaves were related to general symptoms (fever, asthenia). Antibiotics were prescribed in 95.7% of the patients, mainly aminopenicillin (40.4%) and macrolides (33.2%). Nonsteroidal or steroidal antiinflammatory drugs were prescribed in 72.5% of the patients irrespective of the LRTI diagnosis. DISCUSSION: The fact that GPs do not often refer patients to specialists or order hospitalization confirms their important role in setting up recommendations. It would also be necessary to develop an education program on better use of antibiotics targeted to GPs and patients.

[Acute sinusitus in adults. Management by general practitioners]. / Sinusites aiguës de l'adulte. Prise en charge par les médecins généralistes.

OBJECTIVE: Acute sinusitis is a common condition encountered in general practice and raises the question of appropriate management. Sufficient data are still lacking in the literature to provide a fully satisfactory response. METHODS: We conducted a survey among 193 physicians representative of the general practitioners in France to collect 755 cases of acute sinusitis treated in the outpatient setting from January 6 through March 15, 1999. We recorded clinical features and therapeutic management. RESULTS: Pain was the predominant clinical sign (97% of the patients). Facial pain with a highly suggestive localization and aggravated by pressure and headache were the most frequent. Most of the patients also had a nasal symptom (77%) and an infectious context (90%). Three circumstances had been pre-defined by the experts: unique acute sinusitis, acute episode of chronic sinusitis, and recurrent acute sinusitis. In 67% of the cases of unique acute sinusitis, the diagnosis of the general practitioner was confirmed a posterori by the experts. Few complementary tests were ordered (in 17% of the patients) mainly in fragile patients and mainly limited to a radiography of the sinus (81% of the complementary tests ordered). An oral antibiotic was almost always prescribed (96% of the patients) although antibiotics comprised only 29% of all prescriptions. General corticosteroid therapy (41%), local treatment (73%) and anti-cough or expectoration medications (52%) were also prescribed. Despite the painful nature of sinusitis, analgesics were only prescribed for 36% of the patients. CONCLUSION: This observational survey enabled us to describe the diagnostic and therapeutic strategy used by French general practitioners for acute sinusitis in adults. There was general agreement on the strategy that was well adapted to the patient profiles. An evaluation of the different classes of drugs prescribed, and their efficacy in the outpatient setting, that remains to be determined, was not however attempted.

[Pristinamycin versus oxacillin in the treatment of superficial pyoderma. A multicenter randomized study in 293 outpatients]. / Pristinamycine (Pyostacine 500) versus oxacilline (Bristopen) dans le traitement des pyodermites superficielles. Etude randomisée multicentrique chez 293 malades ambulatoires.

BACKGROUND: Superficial pyoderma occurs frequently. Generally, the benign infection is caused by Staphylococcus aureus and/or a group A streptococci. The subject is controversial, but treatment usually is based on narrow-spectrum antibiotics active against both germs. PATIENTS AND METHODS: A multicentric, randomized, double-blind, double-placebo study was conducted to compare pristinamycin (1 g b.i.d.) with a reference antibiotic, oxacillin (1 g b.i.d.) for 10 days. Inclusion criteria were: both sexes, age 15-80 years, clinical diagnosis of superficial pyoderma (impetigo, wound infection within the last 15 days, furunculosis, carbuncle, perionyxis), informed consent. The general practitioner investigators (n = 52) were assisted by 9 dermatologist-coordinators. Clinical diagnosis was validated by a committee of experts at the end of the study after analyzes of the photos and bacteriological results obtained on samples taken at the practitioner's office on visit 1 (D0), visit 3 (D14 +/- 3) and visit 4 (D25 +/- 3). Successful treatment was defined by clinical, bacteriological and photographic efficacy at visit 3 (equivalence analysis: one-way 95 p. 100 confidence interval). RESULTS: There were 293 included patients given pristinamycin (n = 151) or oxacillin (n = 142). Mean age of analyzed patients was 40 +/- 17 years. Diagnosis was confirmed in 255 patients in accordance with the protocol: furunculosis or carbuncle (n = 100), recently superinfected wound (n = 97), impetigo (n = 41), acute perionyxis (n = 17). Thirty-five patients (12 p. 100) were considered to have been wrongly included. The germs most often isolated were: Staphylococcus aureus (n = 126), group A streptococci (n = 13), group B streptococci (n = 5) and P. multocida (n = 3). At visit 3, the two treatments were found to be equivalent with a success rate of 86.7 p. 100 for pristinamycin and 89.8 p. 100 for oxacillin (CI [*9.97]). Tolerance was statistically comparable between the two treatments (27 to 32 percent minor side effects). DISCUSSION: This study is the first performed in outpatients attended by general practitioners with diagnostic confirmation on both bacteriological and photographic evidence of superficial pyoderma. The results obtained demonstrate the good reliability of such studies although 12 p. 100 of the patients were wrongly included, a factor which should be taken into account for future studies. The efficacy and tolerance of pristinamycin were statistically equivalent to those of oxacillin for all the patients with superficial pyoderma. Nevertheless, the subgroup of patients with folliculitis gave rather heterogeneous bacteriology and therapeutic results.

[Epidemiology of asthma]. / Epidémiologie de l'asthme.

Asthma epidemiology aims to provide answers to the following questions: what is the prevalence? what are the consequences? what are the risk factors of asthma? Questionnaires indicate that asthma prevalence averages 6 to 8% whereas assessment of bronchial reactivity reveals that approximately 15% of the population exhibit bronchial hyperesponsiveness; these figures have been increasing in many western countries. Asthma is an important cause of impairment in children physical development, school-related problems along with increased number and duration of hospitalizations. Asthma mortality averages 3/100,000 in France and is mainly focused on people more than 50 years old; its increase is very likely in some countries, but is still controversial in France. Environmental and socio-economic factors play a major role in the development of asthma and genetic factors are now under investigation. Although both understanding and drug treatment of asthma have dramatically improved in the recent past, no positive change has been observed so far in terms of morbidity and mortality. Nevertheless, knowledge of factors specific to France requires further investigations.

Asthma in adults: comparison of adult-onset asthma with childhood-onset asthma relapsing in adulthood.

The prevalence of asthma in children and young adults is rising. Although the general features of asthma are similar in children and adults, there are several differences. Studies of the differences between childhood- and adult-onset asthma may provide new insight into the phenotypic heterogeneity of asthma. The aim of this cross-sectional study was to compare the characteristics of asthmatic adults who reported having (n = 84) or not having (n = 235) asthma in childhood. The participating patients were recruited by chest specialists throughout France and were examined from March to November 1995. The specialists completed a standardized questionnaire, and carried out a clinical examination and spirometric tests. Male sex; greater severity, particularly lower spirometry values related to small airways; greater severity and earlier onset of allergy; and maternal history of atopic dermatitis and perennial rhinitis were found to be associated with reported childhood asthma. This study exhibits highly internally consistent results and indicates that subjects who did have childhood asthma and relapse in adulthood appeared to have a potentially more severe form of asthma.

Treatment compliance, passive smoking, and asthma control: a three year cohort study.

AIMS: To study the role of treatment compliance and parents' smoking on asthma control in children with recently diagnosed mild or moderate persistent asthma who were prescribed inhaled anti-inflammatory treatment. METHODS: Prospective cohort study of 167 children aged 6-12 years (64% boys). Patients were examined at inclusion and followed up for three years with a visit every four months. Peak expiratory flow (PEF) was measured twice a day during the week before each visit. Two control criteria were monitored: (1) symptom control = having diurnal or nocturnal exacerbations less than once a week and no symptoms between exacerbations, at all visits; and (2) PEF control = daily PEF variability <20% on each of the seven days before each visit. RESULTS: Symptom control was achieved by 25.1% of children and PEF control by 53.3%. Symptom control was positively related to having understood the way in which the medication worked and taking the prescribed doses (odds ratios (OR) = 3.38 and 4.82 respectively). It was inversely related to smoking within the home (OR = 0.34). PEF control was positively related to taking the prescribed doses (OR = 3.58). It was less frequently achieved if the mother smoked within the home (OR = 0.34). CONCLUSIONS: Results suggest that, to maximise the benefits of available asthma medication and to improve health outcomes, further efforts should be made to convince the parents of asthmatic children not to smoke in the house, and to improve compliance by increasing the patients' understanding of the disease and its treatment.