[Evaluation of the prescription of furosemide in persons aged 75years and older in a geriatric acute-care unit]. / Évaluation de la prescription du furosémide chez la personne âgée de 75 ans et plus dans un service de gériatrie aiguë.

INTRODUCTION: Furosemide is very often prescribed in France. It may cause important adverse effects especially in elderly persons. In order to limit its misuse and excessive expenditure for health insurance organizations, the European Society of Cardiology drafted strict guidelines for its prescription. We conducted a study in this population to determine the rate of prescription of furosemide in elderly persons outside the guidelines. METHOD: This was a prospective, single-centre, observational study bearing on elderly persons aged 75years and more admitted to a geriatric acute-care unit over a period of 6months. The prevalence of furosemide prescription and the proportion of prescriptions outside guidelines were calculated. The sociodemographic and medical characteristics of patients treated with furosemide were studied as were the modalities of furosemide prescription. RESULTS: In the 818 patients hospitalized during the period of the study, 267 were taking furosemide at admission (32.6%). Among these prescriptions, 69.2% were outside the guidelines. Arterial hypertension was the leading indication for furosemide (38.2%), followed by chronic heart failure (24.3%). CONCLUSION: This study confirmed the high prevalence of furosemide prescription and its misuse. Furosemide is often re-prescribed with no medical re-evaluation.

Smoking cessation attempts: is it useful to treat hard core smokers?

BACKGROUND: Hard core smokers have been studied in many countries but only a few trials have compared the effectiveness of smoking cessation with other smokers. The objective of this study was to compare the frequencies of success in smoking cessation between hard-core smokers and other smokers. METHODS: Data were collected in Clermont-Ferrand from the Emile Roux dispensary 'Pneumology and Tobaccology Centre' between 1999 and 2009. Assistance with smoking cessation was proposed to 1367 patients but only 1296 patients were included: 219 HCS and 1077 other smokers. Smoking cessation was considered a success when patients were abstinent 6 months after the beginning of cessation. The profiles of the two types of smokers were compared using Chi square test and Student's t test. Multivariate logistic regression was used to investigate the association between the smoking cessation result and the type of smokers. RESULTS: HCS more frequently consumed other psychoactive substances (41.1 % vs 25.7 % for other smokers; p < 0.001). Current depression was more frequent in HCS (46.6 % vs 34.8 % for other smokers; p = 0.001). Smoking cessation was less frequent in HCS (45.2 % vs 56.5 % for other smokers ; p = 0.002). In multivariate analysis, after controlling for other factors, the frequency of smoking cessation was not significantly associated with the type of smokers (p = 0.47). After limiting to initial factors (present before the beginning of smoking cessation), the frequency of smoking cessation was still not significantly associated with the type of smokers (p = 0.78). CONCLUSION: Smoking cessation is possible for hard core smokers, who should be treated as other types of smokers taking into account other factors:the problem is how to encourage them to try to stop smoking.

Impact of microbiological samples in the hospital management of community-acquired, nursing home-acquired and hospital-acquired pneumonia in older patients.

We investigated the positivity rate, the detection rates for non-covered pathogens and the therapeutic impact of microbiological samples (MS) in community-acquired pneumonia (CAP), nursing home-acquired pneumonia (NHAP) and hospital-acquired pneumonia (HAP) in elderly hospitalised patients. Patients aged 75 years and over with pneumonia and hospitalised between 1/1/2013 and 30/6/2013 in the departments of medicine (5) and intensive care (1) of our university hospital were included. Microbiological findings, intra-hospital mortality and one-year mortality were recorded. Among the 217 patients included, there were 138 CAP, 56 NHAP and 23 HAP. MS were performed in 89.9, 91.1 and 95.6 % of CAP, NHAP and HAP, respectively. Microbiological diagnosis was made for 29, 11.8 and 27.3 % of patients for CAP, NHAP and HAP, respectively (p = 0.05). Non-covered pathogens were detected for 8 % of CAP, 2 % of NHAP and 13.6 % of HAP (p = 0.1). The antimicrobial spectrum was significantly more frequently reduced when the MS were positive (46.7 % vs. 10.8 % when MS were negative, p = 10(-7)). The MS positivity rate was significantly lower in NHAP than in CAP and HAP. MS revealed non-covered pathogens in only 2 % of NHAP. These results show the poor efficiency and weak clinical impact of MS in the management of pneumonia in hospitalised older patients and suggest that their use should be rationalised.

[Comparison of British and French expatriate doctors' characteristics and motivations]. / Comparaison des caractéristiques et des motivations des médecins expatriés français et britanniques.

BACKGROUND: Migration of medical practitioners is rarely studied despite its importance in medical demography: the objective of this study was to analyze the characteristics and motivations of the French doctors settled in the United Kingdom and of the British doctors settled in France. METHODS: This cross-sectional study was conducted using a self-completed questionnaire sent to all French doctors practicing in the United Kingdom (in 2005) and all British medicine doctors practicing in France (in 2009). The doctors were identified with official data from the National Medical Councils: 244 French doctors practicing in the United Kingdom and 86 British doctors practicing in France. The questionnaire was specifically developed to determine the reasons of moving to the other country, and the level of satisfaction after expatriation. RESULTS: A total of 98 French doctors (out of 244) and 40 British doctors (out of 86) returned the questionnaire. Respondents were mainly general practitioners with a professional experience of 8 to 9 years. The sex ratio was near 1 for both groups with a majority of women among physicians under 50 years. The motivations were different between groups: French doctors were attracted by the conditions offered at the National Health Service, whereas British doctors were more interested in opportunities for career advancement, joining husband or wife, or favourable environmental conditions. Overall, the respondents considered expatriation as satisfactory: 84% of French doctors, compared with only 58% of British doctors, were satisfied with their new professional situation. CONCLUSION: This study, the first in its kind, leads to a clearer understanding of the migration of doctors between France and the United Kingdom.

Test-retest reliability of 3D kinematic gait variables in hip osteoarthritis patients.

OBJECTIVES: (1) to investigate the test-retest reliability of 3D gait analysis (3DGA) in hip Osteoarthritis (OA) patients; (2) to find the minimum number of gait trials needed to overcome intrinsic variability; (3) to check the accuracy of angles measured by the 3D system. DESIGN: 23 Patients suffering from hip OA with no other major disease were recruited. We evaluated the reliability of spatio-temporal variables and body angles (lower-limb joints, trunk and pelvis angles) during two sessions of 3DGA using intra-class correlation coefficients (ICC). The minimum number of trials needed to overcome intrinsic variability was evaluated using an exponential fit model and the Bland and Altman coefficient of repeatability (CoR). The accuracy of measurement was evaluated using a manual goniometer and the recording of 18 different angles. RESULTS: Spatio-temporal variables and most of the kinematic joint and trunk angles calculated demonstrated good to excellent reliability (ICC from 0.77 to 0.97). This was not the case for pelvic angles. The fitting model combined with the CoR showed that 5-10 trials are sufficient to obtain good reliability [ICC>0.7; CoR<2 standard deviation (SD)] for most of the spatio-temporal variables. All body angles showed good reliability (ICC>0.7) and low CoR (<2 SD) after five trials except for the pelvic angles. The reliability of marker positioning was found to be good (ICC>0.7) to excellent (ICC>0.9). Differences between angles measured using 3DGA and angles measured with a manual goniometer were found to be less than one percent. CONCLUSION: The present study shows that most of variables obtained using 3DGA in hip OA patients are reliable. Moreover, for most variables, 5-10 trials are needed to obtain good reliability and to overcome intrinsic variability, rather than 30 or more, thus improving the feasibility of measurement.

[First intention management of obstructive sleep apnea syndrome (OSAS) by custom-made mandibular advancement device: the medium-term results. Prospective study by the General Hospital Pneumologists College (CPHG)]. / Traitement du syndrome d'apnées obstructives du sommeil (SAOS) par orthèse d'avancée mandibulaire sur mesure, en première intention: quels résultats à moyen terme? Etude prospective du Collège des pneumologues des hôpitaux généraux (CPHG).

OBJECTIVES: To demonstrate the efficacy and tolerance of present generation mandibular advancement devices in the first intention treatment for obstructive sleep apnea syndrome (OSAS), even when severe, after one year. METHODS: Between June 2006 and December 2007, 152 patients (male: 77%; age: 50.9±10.9 years; BMI: 26.3±3.6 kg/m(2); AHI: 25.5±13.9), without previous treatment, requesting management other than continuous positive pressure and dentally apt for a mandibular advancement device, were pre-included in a prospective one-year multicenter study (13 general hospitals). RESULTS: One hundred and twenty-nine patients were assessed at least once after fitting. The efficacy was noted as of day 90: the overall AHI fell from 24.8 to 10.8 (from 40.6 to 17.7 in the 40 patients with AHI>30) and the Epworth index decreased from 11.2 to 6.9 (12.8 to 8.1 for AHI>30). The AHI reduction was independent of gender, age, BMI and baseline AHI. The efficacy was maintained throughout the study period. Only eight patients withdrew for adverse events and seven for reasons of therapeutic failure. CONCLUSION: Mandibular advancement devices proved effective in first intention, including severe OSAS. No predictive individual efficacy factors emerged.

Recurent and de novo membranous glomerulopathy after kidney transplantation.

The aim of this study was to compare the clinical characteristics of recurrent and de novo membranous glomerulopathy (MG) among a cohort of 614 recipients transplanted between 1989 and 2006. Lupus nephritides were excluded. The diagnosis was established on protocol biopsies performed 1, 2, 4, or 8 years after transplantation or because of proteinuria/nephrotic syndrome and/or an increased serum creatinine level. HCV infection, cryoglobulinemia, monoclonal gammopathy, skin cancers, Kaposi sarcoma, diabetes mellitus, anti-HLA antibodies, and graft survival were not significantly different between the groups. Seventeen MG were diagnosed in 15 patients (2.45% of the whole group), including 6 recurrent MG (35%) and 11 de novo MG (75%). Recurrent MG occurred earlier than de novo MG (15.58 +/- 19.13 vs 49.27 +/- 32.71 months). Recipients with de novo MG were more frequently infected with HCV, which seemed to be the main etiologic factor for de novo MG, and may be linked to a Th2 polarization of the immune response.

[Impact of influenza rapid diagnostic tests (IRDT) on the diagnosis of influenza and on the management of influenza in children in ambulatory pediatric setting]. / Impact des tests de diagnostic rapide de la grippe dans la prise en charge des enfants en période d'épidémie en pédiatrie de ville.

OBJECTIVE: Several studies have highlighted the assets of the influenza rapid diagnostic tests (IRDT) for the emergency department management of febrile children. The objective of this study was to determine in ambulatory pediatric setting impact of IRDT on the management of febrile children during an epidemic, especially on other diagnostic testing performed, antibiotic and antiviral treatments. METHODS: During an influenza epidemic, 37 paediatricians in three different areas of France included all children presenting fever with respiratory illnesses; they performed IRDT (test QuickVue for Influenza A and B, Quidel). Data collected were antiflu vaccination, previous asthma, symptoms, clinical signs, other diagnostic testing performed, and a follow-up two weeks later. RESULTS: Between December, 2006 and April, 2007, 695 children entered the program. The average age of those children was 4.1 years old (SD 3.4), median 3.2 (0.07-17.5). In 41.6% of the cases, the tests proved positive. Among 13 symptoms of influenza, only five were significantly more present in the group IRDT+: shiver (68.1% versus 57.4%), asthenia (87% versus 79.9%), cough (87.5% versus 70.1%), rhinorrhea (93.4% versus 83.3%), and sleepiness (54.2% versus 43.4%). The number of laboratory tests and radiographs ordered were less frequent in group IRDT+ than in group IRDT-: respectively 0.7% versus 11.6%, and 0.7% versus 8.6% (p<0.0001). IRDT+ group received antibiotics in 7.6% of cases (22 patients, 20 for OMA) and antiviral in 64.7%. IRDT- group received respectively 18.5% antibiotics, and no antiviral (p<0.0001). CONCLUSION: This study confirms the difficulty of clinical influenza diagnosis, and suggests the assets of IRDT to diagnose influenza and to improve the management of influenza in ambulatory paediatric setting.

[French doctors working in Great Britain: a study of their characteristics and motivations for migration]. / Caractéristiques et motivations des médecins français ayant choisi d'émigrer en Grande-Bretagne.

BACKGROUND: As member states in the European Union now recognize the national qualifications of other member states, doctors will be able to move more freely within Europe according to the opportunities on offer and the constraints imposed by the different health-care systems. The aim of this study is to understand the reasons why French doctors choose to work in Great Britain. METHOD: A self-completed questionnaire was used to conduct a survey among French doctors registered with the British Medical Council in 2005 who had done their studies in France and for whom the address was correct. RESULTS: The response rate, which was difficult to assess (impossible to distinguish between incorrect addresses and absence of response), was about 37%. The results show that doctors move to Britain for various reasons. In most cases (59%), the decision to emigrate is made for both professional and personal reasons. The second most common profile (29%), including essentially women, comprises those who emigrate to join a spouse. The third profile (12%) concerns those who emigrate for purely professional reasons: this group is made up of men who, for the most part, are disappointed with conditions in the French-hospital system: lack of recognition, poor pay and limited career prospects. Doctors who are dissatisfied with working conditions and low revenues in France seem to find that the National Health Service provides a better environment. Whatever the original reasons for expatriation, doctors particularly appreciate the salaried status, organization of working hours and teamwork, as well as more recognition of the work done. CONCLUSION: Because of uncertainties in the representativity of the returned questionnaires, the results of our study cannot be generalized to the whole population of French doctors currently working in Britain, but it does bring to light the principal reasons for their move to Britain. Though few doctors emigrate, the trend testifies to the dissatisfaction felt by certain doctors in the French health-care system. The study also underlines the dependence of the NHS on the immigration of health-care professionals.

The Dijon Physical Activity Score: reproducibility and correlations with physical fitness in patients with coronary artery disease.

OBJECTIVES: To study the clinimetric properties of the Dijon Physical Activity Score (PAS) in patients with coronary artery disease (CAD). PATIENTS: Two populations of patients with CAD: one group of stabilized patients from the RICO county-wide monitoring program and one group in the initial phase of a cardiovascular rehabilitation program (CVR group). METHODS: The patients carried out a maximal effort test on a cycle ergometer, plus two walking tests (a six-minute walk test and a 200 m fast walk test). They completed the Dijon PAS questionnaire on two occasions at an interval of 10 days. The reproducibility of the score and the latter's correlations with physical parameters were analyzed. RESULTS: Sixty-seven subjects were included and 52 answered the questionnaire both times. The average time spent answering the questionnaire was 173+/-37 seconds and reproducibility was satisfactory in the RICO group only. In this group, there were significant correlations between total score and maximal power during the effort test (r=0.41; P<0.05) and between the "sports/leisure activities" sub-score and maximal power (r=0.57; P<0.01). No correlations were found in the CVR group. CONCLUSION: The Dijon PAS is a simple, generic, reproducible and reliable score for measuring physical activity in patients with stable coronary artery disease but, because of the conjunction of confounding factors, it is not suitable for subjects who experienced a recent acute cardiac event. It could thus be used in epidemiological studies to determine the impact of a sedentary lifestyle and the efficacy of methods intended to counter sedentariness and to help design personalized secondary prevention programs.

Array-CGH in a series of 30 patients with mental retardation, dysmorphic features, and congenital malformations detected an interstitial 1p22.2-p31.1 deletion in a patient with features overlapping the Goldenhar syndrome.

Genosensor Array 300 (Abbott) is a multiplex platform for array-based comparative genomic hybridization that detects unbalanced genomic aberrations including whole chromosome gains/losses, microdeletions, duplications and unbalanced subtelomeric rearrangements. A series of 30 patients with unexplained mental retardation, dysmorphic features, congenital abnormalities and normal high resolution karyotype and FISH subtelomeric studies were analyzed using Genosensor Array 300 array-CGH. We identified a chromosomal aberration in one patient with an interstitial 1p31.1 deletion. FISH analysis with BACs specific probes of the 1p region confirmed the interstitial 1p22.2-p31.1 deletion. The patient was a 20-year-old man with short stature, facial dysmorphism including asymmetry, scoliosis, severe psychomotor delay and an epibulbar dermoid cyst. The phenotype was compatible with Goldenhar syndrome despite the absence of asymmetric ears. This observation is of interest since it could be a clue in the search for the genes responsible for Goldenhar syndrome. This study demonstrates the utility of the array-CGH technology in detecting interstitial deletions.

Changes in meibomian fatty acids and clinical signs in patients with meibomian gland dysfunction after minocycline treatment.

AIMS: To assess the changes in ocular surface abnormalities and meibomian fatty acid composition in patients suffering from meibomian gland dysfunction (MGD) after treatment with oral minocycline associated with lid hygiene versus lid hygiene only. METHODS: We evaluated the break-up time, corneal staining and quality of meibomian excreta, and collected meibomian oil in 20 individuals suffering from MGD before and after 8 weeks of minocycline associated with lid hygiene (n = 10) or lid hygiene only (n = 10). Meibomian fatty acids were directly transmethylated and analysed by gas chromatography (GC) and GC mass spectrometry. RESULTS: The meibomian fatty acid composition was slightly modified after 8 weeks in both groups. The decrease in a branched-chain fatty acid (isoC20) was greater after minocycline treatment than after lid hygiene only (-65% and -25%, respectively; p<0.05). Other fatty acids were unchanged. A significant improvement in the BUT was observed after minocycline treatment (p = 0.03). CONCLUSION: This study showed better tear film stability after minocycline treatment and a biological effect on meibomian fatty acid composition in MGD patients. Minocycline was more effective than lid hygiene alone. Both interventions partly corrected fatty acid composition abnormalities. Among the fatty acids, isoC20 could be a biological marker of MGD.

Pneumococcal meningitis in the era of pneumococcal conjugate vaccine implementation.

The French Pediatric Infectious Diseases Group set up an active surveillance network to analyze the clinical and biological features of pneumococcal meningitis and the impact of the seven-valent pneumococcal conjugate vaccine (PCV7). From 2001 to 2005, 234 pediatric wards working with 166 microbiology laboratories enrolled all children with pneumococcal meningitis. Risk factors, signs and symptoms, vaccination status, cerebrospinal fluid analysis, treatments and case fatality rates were recorded. One hundred and sixty-nine centers (169/234) reported 616 cases, median age was 0.9 years and 67.2% of children were < or =2 years old. Underlying conditions were present in 13.1% of cases. The proportion of penicillin non-susceptible strains was 48.7%. Vancomycin plus a third-generation cephalosporin was prescribed in 92.7% of cases, and steroids were given before antibiotic treatment in 16.5% of cases. The case fatality rate was 10.8% overall and was not related to age, antibiotic susceptibility or steroid use. In children 2 to 24 months old compared to the prevaccinal period (2001-2002) a decrease of 28.4% of the number of cases was observed in 2005 (P < 0.05). Among children 2 to 24 months old, the proportion of serotypes covered by the PCV7 fell from 39/57 (68.4%) in 2001-2002 to 19/45 (42.2%) in 2005, while the proportion of non-vaccine serotypes and related serotypes increased respectively from 9/57 (15.8%) and 9/57 (15.8%) in 2001-2002 to 14/45 (31.1%) and 12/45 (26.7%) in 2005. Among 52 cases of pneumococcal meningitis that have occurred in vaccinated children (> or =1 dose) with PCV7, 7 were due by vaccine serotypes. This study provides data on underlying conditions, penicillin susceptibility, serotype evolution according to vaccination status and risk factors for mortality for pneumococcal meningitis in children from 2001-2005 in France.

[Impact of the rapid diagnosis downtown in the assumption of responsibility of the children in period of influenza]. / Impact des tests de diagnostic rapide en ville dans la prise en charge des enfants en période de grippe.

Several studies in children showed at the paediatric emergency hospital the interest of influenza rapid diagnostic tests (IRDT) in this disease for which the clinical diagnosis is difficult in children. The purpose of this prospective study carried out in ambulatory paediatric setting was to evaluate impact of the IRDT in the assumption of responsibility of children suspected of Influenza infection. Thirty paediatricians (14 without IRDT, 16 with IRDT) included 602 children between 2004 and 2005. The influenza was confirmed by IRDT in 54% of the cases. Among the 13 symptoms or signs recorded, only 4 - chills (61.6 vs 48.4%), cough (89.8 vs 71.1%), rhinorrhea (97.9 vs 86.2%), and anorexia (50.3 vs 34.8%) - were significantly more frequent (P

Paediatric varicella hospitalisations in France: a nationwide survey.

Paediatric patients hospitalised with varicella (n = 1575) were reported to a French national network between March 2003 and July 2005. Superinfection was identified in 50.3% of cases, principally of skin and soft-tissue (36.5%). The risk of superinfection increased with fever relapse, use of non-steroidal anti-inflammatory drugs, prolonged fever, an age of 1-5 years, and contamination at the childminder's home. Neurological complications were observed in 7.8% of cases, while pulmonary complications were less frequent (3.1%). Forty-nine patients had sequelae and eight patients died. Surveillance should continue in France with a view to the future implementation of a universal vaccination programme.

Reliability of computed tomographic angiography in the diagnosis of brain death.

OBJECTIVE: This study examined the validity of cerebral computed tomographic (CT) angiography in the diagnosis of brain death (BD) compared with conventional cerebral angiography. METHODS: This prospective, monocentric study was performed over a 24-month period and included 43 patients, at least 18 years of age, with clinical criteria of BD. All patients underwent cerebral CT angiography and then cerebral angiography. To confirm BD, the CT scan had to show the absence of perfusion of A2 anterior cerebral artery segments (A2-ACA), M4 middle cerebral artery segments (M4-MCA), P2 posterior cerebral artery segments (P2-PCA), basilar artery, internal cerebral veins, and finally the great cerebral vein. Cerebral angiography showed cerebral blood flow arrest at the level of the foramen magnum for posterior circulation and carotid siphon for anterior circulation. RESULTS: For 30 patients, BD was confirmed by both examinations. For 13 patients, cerebral angiography confirmed BD, whereas CT angiography still showed cerebral perfusion; the divergence rate was 30.2%. CONCLUSIONS: CT angiography seems to be a promising exam to confirm BD. However, the divergence with cerebral angiography is significant mainly concerning A2-ACA, which are proximal. It may be possible to only use the absence of opacification of M4-MCA, P2-PCA, basilar artery, and venous blood return to remain in conformity with the French law. In all cases, the international medical community should obtain a consensus for the interpretation of CT angiography to use it extensively as a complementary exam for BD.

[Impact of CRP rapid test in management of febrile children in paediatric emergency units of Ile-de-France]. / Impact de la protéine C-réactive (CRP) en microméthode sur la prise en charge des enfants fébriles aux urgences pédiatriques en Ile-de-France.

OBJECTIVE: Fever is a common cause of children visits to emergency units. Clinical evaluation does not always eliminate a bacterial infection. Among blood markers, several publications showed the interest of CRP. This study was undertaken to evaluate correlation between two techniques of CRP, one by usual technique at the laboratory and the other by a rapid test, and to evaluate the impact of this rapid test for febrile children at the emergency room, when a hospitalization was not immediately decided. MATERIAL AND METHODS: The study was undertaken in 2004-2005 in eight emergency paediatric units in Ile-de-France concerning febrile children during two periods. In period A, children had at the same time a CRP dosage through two methods, whereas in period B, only a rapid CRP test was first managed. The test used was NycoCard CRP Single test (Progen Biotechnique). RESULTS: Between September 2004 and June 2005, 572 children were included, 268 in period A and 304 in period B. Comparison of CRP results by the two methods showed for 247 children (93%) a fairly good linear correlation (r: 0.929). Blood cell count was the most often prescribed test (99.4 vs 10.5%). Conversely to chest radiography, blood culture, fibrinogen and urinary test were significantly most frequent in period A. The average cost of the additional examinations was 2.6 times more important during the first period. Duration of children management in the units was approximately two times shorter when rapid CRP test was used (199.7+/-92.8 vs 103.5+/-98.6 min). CONCLUSION: This study shows the interest of rapid CRP test for febrile children in the emergency units, and has to be confirmed in ambulatory paediatric practice.

[SPA-1: semiology for phenotyping AMD: precursors]. / SPA-1: sémiologie du phénotype de la dégénérescence maculaire liée à l'âge: précurseurs.

PURPOSE: A reliable classification of AMD subgroups is necessary prior to any genetic or clinical investigation. For this purpose, we evaluated a selected list of items for AMD based on color photographs of the fundus but also on fluorescein and ICG angiographies and OCT. The first step (SPA-1) is to evaluate the interobserver agreement for AMD precursors. METHODS: The 30 items for AMD precursors, choroidal neovascularization and atrophy, were chosen from the literature. We selected 20 eyes from 20 consecutive patients affected by various forms of these precursors from the prospective NAT-2 study. Grading was based on color photographs of fundus, red-free frames, and fluorescein angiography. For each eye, five grids were filled in by four independent, experienced readers from our reading center and one expert. Within-subject variance was studied. RESULTS: Within subject variance showed the greatest agreement between graders for drusenoid pigment epithelial detachment (variance=0.000). The worst value for within subject variance (0.255) was recorded for the item "intermediate drusen between 5 and 20." CONCLUSION: This evaluation of our first grid for AMD precursors shows high agreement between graders for most of the items. The item with the lowest agreement should be modified according to the comments of the physicians. This grid could be implemented for phenotypic classification of ARM and AMD in future clinical or genetic studies.

Relationship between clinical signs and symptoms and nasopharyngeal flora in acute otitis media.

Possible links between the clinical signs and symptoms of acute otitis media and the composition of the nasopharyngeal flora were investigated by reviewing the files of 1807 children enrolled in four randomised, multicentre trials. A standard protocol was used, nasopharyngeal samples were cultured, and signs and symptoms were recorded. Carriage of Haemophilus influenzae was associated positively with conjunctivitis (OR 4.83, 95% CI 3.76-6.20) and negatively with fever (OR 0.69, 95% CI 0.56-0.86). Carriage of pneumococci was associated positively with fever (OR 1.32, 95% CI 1.08-1.63) and negatively with conjunctivitis (OR 0.50, 95% CI 0.40-0.63).