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Screening of the Roche compound library led to the identification of the benzoylpiperazine 7 as a structurally novel GlyT1 inhibitor. The SAR which was developed in this series resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform, drug-like properties, and in vivo efficacy after oral administration.

Presentation of a 57-year-old female patient with fever of unknown origin, asthenia, and weight loss for I month. History and examination were unremarkable. Blood analysis showed an important inflammatory syndrome. Other paraclinic tests were all normal. Finally, sophisticated exams (CT-scan, and FDG PET-scan) allowed the diagnosis of giant cell arteritis, confirmed by biopsy of the temporal arteries. Differential diagnosis and treatment are discussed.

Objectives: To assess adherence to recommended standards of diabetes care by Swiss primary care physicians., Methods: Medical files of community-based primary care physician were reviewed to assess adherence to recommended standards of diabetes care. These standards of care were based on a uniform set of definitions addressing medical care processes involved in the detection and follow-up of pre-diabetic and diabetic patients., Results: 186 physicians agreed to participate and 3,682 medical files were assessed. The prevalence of diabetes was 11% and 5% had impaired glucose tolerance (pre-diabetic). Screening of diabetes based on family or personal history was reported for 83% of the patients and on cardiovascular risk factors for 69%. Counselling for dietary changes was reported for 91% of diabetic patients and for 79% for physical activity, but only for 66% and respectively 60% of pre-diabetic patients. Among diabetic patients, regular HbA1c control was reported for 65%, yearly fundoscopy for 62%, yearly feet examination for 65%, yearly microalbuminuria control for 49%, regular blood pressure control for 96%, and yearly lipid profile for 89%. Regular screening of microangiopathic complications was reported for only 33% of diabetic patients., Conclusion: Adherence to recommended standards of diabetes care displayed important variations among this convenience sample of Swiss primary care patients. Screening and counselling of diabetic patients were frequent, whereas counselling for lifestyle changes of pre-diabetic patients and regular follow-up of microangiopathic complications among diabetic patients were suboptimal. These results could help to target areas of diabetes care that need to be addressed to improve adherence to recommended standards.

Five diagnostic techniques performed on skin biopsies (shoulder region) and/or serum were compared for detection of bovine viral diarrhea virus infection in 224 calves 0-3 months of age, 23 calves older than 3 months but younger than 7 months, and 11 cattle older than 7 months. The diagnostic methods used were immunohistochemistry (IHC), 2 commercial antigen ELISAs, 1 commercial antibody ELISA, and real-time RT-PCR. Results of 249 out of 258 skin and serum samples were identical and correlated within the 3 antigen detection methods and the real-time RT-PCR used. Twenty-six of these 249 samples were BVDV-positive with all antigen detection methods and the real-time RT-PCR. Nine out of 258 samples yielding discordant results were additionally examined by RT-PCR, RT-PCR Reamplification (ReA), and antigen ELISA I on serum and by immunohistochemistry on formalin fixed and paraffin-embedded skin biopsies. Virus isolation and genotyping was performed as well on these discordant samples. In 3 cases, transiently infected animals were identified. Two samples positive by real-time RT-PCR were interpreted as false positive and were ascribed to cross-contamination. The antigen ELISA II failed to detect 2 BVDV-positive calves due to the presence of maternal antibodies; the cause of 2 false-positive cases in this ELISA remained undetermined. Only persistently infected animals were identified in skin samples by IHC or antigen ELISA I. The 3 antigen detection methods and the real-time RT-PCR used in parallel had a high correlation rate (96.5%) and similar sensitivity and specificity values.

To limit drug adverse effects, the use of a limited choice of drugs is desirable. We identified 29 frequent health problems and selected first and second choice medication based on the following criteria: clinical efficacy based on medical evidence or expert consensus, safety profile, and costs. For each substance, adverse effect, contraindication, interaction risk, specific dosing, and safety use during pregnancy and lactation were reviewed. More than seventy substances were identified. This list is available for download at the following address (in French): http://www.hcuge.

As physicians, we apply and teach linear thinking. This approach permits to dissect the patient's problem to the molecular level and has contributed enormously to the knowledge and progress of medicine. The linear approach is particularly useful in medical education, in quantitative research and helps to resolve simple problems. However, it risks to be rigid. Living beings (such as patients and physicians!) have to be considered as complex systems. A complex system cannot be dissected into its parts without losing its identity. It is dependent on its past and interactions with the outside are often followed by unpredictable reactions. The patient-centred approach in medicine permits the physician, a complex system himself, to integrate the patient's system and to adapt to his reality. It is particularly useful in general medicine.

Patients' evaluation of care is an important element of quality of care, especially for patients with chronic conditions. Our objective was to expose physicians in training to a quality improvement program and study how continuity of care could influence patients' experience of care. Physicians in training valued this approach, but deplored no to be actively involved in its planning. They also underlined the importance of keeping physicians' individual results absolutely confidential. Positive patients' reports toward communication and physician-patient relationship were associated with longer duration of follow-up at the medical outpatient clinic. Following this project, several changes have been made to improve aspects of care that were problematic.

Objective: To identify diabetic patients' characteristics and medical care factors associated with recommended glycaemic control (HbA(1c) < or =7%)., Methods: As part of a cross-sectional assessment of diabetes care involving 204 Swiss primary care physicians, we identified 366 diabetic patients with a recent HbA(1c) value. Cross-tabulations and X(2) tests were used to explore the association of patients' sociodemographic and disease characteristics and medical care characteristics with HbA(1c) < or =7%. Significant factors were included in a regression logistic model to identify multivariate predictors of HbA(1c) < or =7%., Results: HbA(1c) values were in the recommended range for 57% of the patients. A less than five years' history of diabetes, absence of followup by a diabetes specialist, absence of microalbuminuria or retinopathy, adherence to dietary and physical activity counselling, no participation in a diabetic education programme, no glycaemic self-monitoring, oral or no antidiabetic therapy and influenza vaccine in the last 12 months were associated with HbA(1c) < or =7%. In the multivariate analysis, HbA(1c) < or =7% remained associated with a less than five years diabetes history (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.5-4.3), as well as patients' adherence to dietary (OR 1.9, 95% CI 1.2-3.0) and physical activity counselling (OR 1.8, 95% CI 1.1-2.9)., Conclusion: In this sample of diabetic patients, adherence to dietary and physical activity counselling were associated with better glycaemic control. Further research should focus on the importance of appropriate lifestyle counselling by Swiss primary care physicians, ideally in prospective trials using objective and reproducible measures of patients' observance.

A novel class of 4-substituted-8-(2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu opioid receptor as well as the nociceptin/orphanin FQ peptide (NOP) receptor. A novel, straightforward and efficient synthetic strategy for the assembly of the target molecules is also presented.

Bovine viral diarrhea virus (BVDV), together with Classical swine fever virus (CSFV) and Border disease virus (BDV) of sheep, belongs to the genus Pestivirus of the Flaviviridae. BVDV is either cytopathic (cp) or noncytopathic (ncp), as defined by its effect on cultured cells. Infection of pregnant animals with the ncp biotype may lead to the birth of persistently infected calves that are immunotolerant to the infecting viral strain. In addition to evading the adaptive immune system, BVDV evades key mechanisms of innate immunity. Previously, we showed that ncp BVDV inhibits the induction of apoptosis and alpha/beta interferon (IFN-alpha/beta) synthesis by double-stranded RNA (dsRNA). Here, we report that (i) both ncp and cp BVDV block the induction by dsRNA of the Mx protein (which can also be induced in the absence of IFN signaling); (ii) neither biotype blocks the activity of IFN; and (iii) once infection is established, BVDV is largely resistant to the activity of IFN-alpha/beta but (iv) does not interfere with the establishment of an antiviral state induced by IFN-alpha/beta against unrelated viruses. The results of our study suggest that, in persistent infection, BVDV is able to evade a central element of innate immunity directed against itself without generally compromising its activity against unrelated viruses ("nonself") that may replicate in cells infected with ncp BVDV. This highly selective "self" and "nonself" model of evasion of the interferon defense system may be a key element in the success of persistent infection in addition to immunotolerance initiated by the early time point of fetal infection.

Background: Primary care physicians are well positioned to provide counselling for overweight and obese patients, but no prospective study has assessed the effectiveness of this counselling in primary care. We aimed to evaluate weight reduction counselling by primary care physicians, and its relationship with weight change and patients' behaviour to control weight., Design: A prospective cohort study., Methods: We enrolled 523 consecutive overweight and obese patients from two Swiss academic primary care clinics. Physicians and patients were blinded to the study aims. We assessed the use of 10 predefined counselling strategies for weight reduction, and weight change and behaviour to control weight after 1 year., Results: Sixty-five per cent of patients received some form of weight reduction counselling whereas 35% received no counselling. A total of 407 patients completed the 1-year follow-up. Those who received counselling lost on average (SD) 1.0 (5.0) kg after 1 year, whereas those who were not advised gained 0.3 (5.0) kg (P = 0.02). In multivariate analysis, each additional counselling strategy was associated with a mean weight loss of 0.2 kg (95% confidence interval 0.03-0.4, P = 0.02). Patients counselled by their physician had more favourable behaviour to control weight than those not counselled, such as setting a target weight (56 versus 36%) or visiting a dietician (23 versus 10%, both P < 0.001)., Conclusions: Weight reduction counselling by primary care physicians is associated with a modest weight loss and favourable behaviour to control weight. However, many obese and overweight patients receive no advice on weight loss during primary care visits.

Background: How to use clinical score, the rapid streptococcal antigen test (RSAT), and culture results is uncertain for efficient management of acute pharyngitis in adults., Methods: This prospective cohort study included 372 adult patients with pharyngitis treated at a Swiss university-based primary care clinic. In eligible patients with 2 to 4 clinical symptoms and signs (temperature >or=38 degrees C, tonsillar exudate, tender cervical adenopathy, and no cough or rhinitis), we performed an RSAT and obtained a throat culture. We measured sensitivity and specificity of RSAT with culture as a gold standard and compared appropriate antibiotic use with cost per patient appropriately treated for the following 5 strategies: symptomatic treatment, systematic RSAT, selective RSAT, empirical antibiotic treatment, and systematic culture., Results: RSAT had high sensitivity (91%) and specificity (95%) for the diagnosis of streptococcal pharyngitis. Systematic throat culture resulted in the highest antibiotic use, in 38% of patients with streptococcal pharyngitis. Systematic RSAT led to nearly optimal treatment (94%) and antibiotic prescription (37%), with minimal antibiotic overuse (3%) and underuse (3%). Empirical antibiotic treatment in patients with 3 or 4 clinical symptoms or signs resulted in a lower rate of appropriate therapy (59%) but higher rates of antibiotic use (60%), overuse (32%), and underuse (9%). Systematic RSAT was more cost-effective than strategies based on empirical treatment or culture: 15.00 dollars, 26.00 dollars, and 32.00 dollars, respectively, per patient appropriately treated., Conclusions: The RSAT we used is a valid test for diagnosis of pharyngitis in adults. A clinical approach combining this RSAT and clinical findings efficiently reduces inappropriate antibiotic prescription in adult patients with acute pharyngitis. Empirical therapy in patients with 3 or 4 clinical symptoms or signs results in antibiotic overuse.

Screening of the Roche compound library led to the identification of cis-N-(2-phenyl-cyclohexyl)-spiropiperidine 1 as structurally novel GlyT1 inhibitor. The SAR, which was developed in this series, resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform.

During SAR exploration of N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of an hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the mu opioid receptors was achieved.

The international review board was set up as the scientific advisory body of the Swiss Complementary Medicine Evaluation Programme (PEK) in 2002. It has met several times and has given advice with respect to the most important aspects of the programme. It would have been the normal procedure for the review board to have had the opportunity to comment on the drafts of the final scientific products as well as the draft of the summary report, in order to advise on them, before the documents became publicly available and formed the basis for political decision making. But the responsible authorities changed this process. In the following, the review board comments both on this process and on the products.

We have genetically analyzed ruminant pestiviruses. All >150 bovine viral diarrhea (BVD) viruses isolated from cattle in Switzerland belonged to genotype 1, with subgenogroups e, h, k and b found in decreasing frequency. To date, representatives of subgenogroup k have been detected in Switzerland only. Despite serological evidence of Border disease in sheep, only few Border disease viruses have been isolated, all of which belong to the novel group 3. Serological evidence suggested that pestivirus infections may occur also in wild ruminants in Switzerland but no isolates are available for analysis. In addition, we describe two pestiviruses, one a cell culture contaminant and the other isolated from a buffalo, that cluster with a recently proposed novel pestivirus species.

Global migration patterns have led to increasingly diverse populations, and physicians must learn to work effectively with patients from diverse backgrounds. However, some aspects of medical education may actually reinforce the idea that physicians do not need to take social and cultural differences into consideration in their work. In order to train physicians who are capable of providing quality care to patients from diverse backgrounds, it will be important to integrate the concept of cultural competence into all aspects of medical training, such that it will cease to be perceived as an "optional" aspect of medicine.

Health care professionals are in contact with patients of all social horizons. Healthcare professionals come into contact with patients from all social backgrounds. Low socio-economic status is a well-known determinant of morbidity and mortality. A mobile community health care unit ("Umsco") was created in Geneva in 1996 with the aim of providing health care to very low-income patients who aren't catered for by the traditional healthcare system in Switzerland. The Mobile Unit's patients are mainly female South American illegal immigrants, but also the city' homeless. This article explains how the Unit functions on a day-to-day basis. We describe socio-demographic characteristics of the patients and their main presenting complaints. We also discuss how health care professionals in general can adapt to the specific needs of socially deprived and vulnerable patients.

Little is known about the conditions of life and the specific health problems of pregnant, undocumented immigrants. This study describes the socio-demographic characteristics and health problems encountered during pregnancy among uninsured, undocumented immigrants in Geneva, Switzerland. A socio-demographic questionnaire was completed by 134 pregnant and undocumented women (mean age 27.8 years) who attended a free antenatal facility between October 2002 and October 2003. The first control of pregnancy was at a median of 10.5 weeks (range 5-33) of amenorrhoea. They were mostly Latino-American (78%), had a median 12 years of education but almost exclusively performed domestic work (91%) after an average residence in Geneva of 18 months. Half of the 62 mothers had left at least one child in their home country. One out of three had never had a cervical smear test and 13% were not immune to rubella. Unintended pregnancies (83%), mostly resulted from lack of contraception (70%). All but one delivery were simple, with a median maternity inpatient stay of 5 days (range 2-10). This population of undocumented, pregnant immigrants comprised mostly highly educated, young, Latino-American women living in poor housing conditions and wages below the legal minimum. The study identified the high proportion of unintended pregnancies as a major health issue. Future research should target these issues and programs addressing lack of access to preventive measures. As well as this, the specific needs of this hard-to-reach population, such as contraception advice, rubella vaccination and cervical cancer screening, should be supported.

Objectives: To conduct an assessment of perceived dietary changes and problems by African asylum seekers, in order to develop appropriate nutritional education interventions., Methods: A cross-sectional qualitative study among a convenience sample. Analysis compared and contrasted reported dietary changes and migration-related difficulties., Results: Nineteen interviews were analysed. After migration, main dietary changes were the decrease in different fruits and vegetables consumed weekly from 10 to 2 and 17 to 10 respectively. The number of respondents drinking sweetened beverages more than 3 times a week increased from 3 to 18. Reasons for changes were related to prices, taste, choice and accessibility., Conclusion: These dietary changes may have serious health consequences. Future remedial interventions based on suggestions of the respondents could easily be implemented.

Objectives: To compare frequency and patterns of hormone replacement therapy (HRT) between primary care patients and the local community., Methods: Comparison of data from a questionnaire survey of 107 peri- and postmenopausal patients in an academic primary care clinic during 1998 to similar data from a sample (n = 241) of an ongoing annual epidemiological survey representative of the general population., Results: Mean age, menopause status, age of initiation of HRT, and prior use of contraceptive pill were similar in both groups. Current HRT use tended to be lower among patients in the clinic than in the community. HRT users in the clinic were more likely to have had a surgical menopause (34.4% vs. 16.1%, p = 0.04) and to have used hormones for shorter periods than in the general population. Differences remained significant after adjustment in multivariate analysis., Conclusions: Compared to the general population, patterns of HRT use in the outpatient clinic were more restrictive than recommendations on HRT that were published at the time. This is an example of how comparison of health issues between patients in medical care and a local epidemiological survey can help to understand clinical practice.

We report on 4 new cases of valvular heart disease in Parkinson's disease patients treated with the ergot derivative dopamine agonists pergolide and cabergoline. Noninflammatory fibrotic degeneration of cardiac valves has been reported to occur in patients with carcinoid syndrome and to occasionally complicate therapies with the anti-migraine ergot alkaloid ergotamine and methysergide and with the appetite suppressants fenfluramine and dexfenfluramine. In these cases, the pathogenesis is suspected to involve serotonin-mediated abnormal fibrogenesis by means of the 5-HT2B receptors, which are expressed in the fibroblasts of heart valves. Based on strikingly similar echocardiographic and histopathological features, we strongly suspect that ergot-derived dopamine agonists may cause a valvular heart disease nearly identical to that seen in those conditions. These cases add to a rapidly growing and worrying list of similar published reports, suggesting that we may well be facing a novel, yet unrecognized, complication of this class of agents, which are widely used not only in Parkinson's disease but also in restless legs syndrome and various common endocrine dysfunctions. Therefore, until more is known about the true prevalence of this side effect, we propose that an assessment of cardiac function be performed before and in the course of a long-term therapy with ergot derivative dopamine agonists., (Copyright 2004 Movement Disorder Society)

Background: The use of oral contraceptives is associated with an increased risk of developing hypertension but the mechanisms of this hypertensive effect are not completely defined. The purpose of the present study was to assess prospectively the systemic and renal hemodynamic and tubular responses to salt in women taking oral contraceptives., Methods: Twenty seven young healthy normotensive women taking oral contraceptives containing monophasic combination of 30 microg ethynilestradiol and 150 microg desogestrel for>6 months were enrolled. All women were assigned at random to receive a low (40 mmol/day) or a high (250 mmol/day) sodium diet for 1 week on two consecutive menstrual cycles during the active oral contraceptive phase. At the end of each diet period, 24-hour ambulatory blood pressure, renal hemodynamics, sodium handling, and hormonal profile were measured., Results: The blood pressure response to salt on oral contraceptives was characterized by a salt-resistant pattern with a normal circadian rhythm. Salt loading results in an increase in glomerular filtration rate (GFR) (P < 0.05 vs. low salt), with no change in the renal plasma flow, thus leading to an increase in the filtration fraction (P < 0.05). At the tubular level, women on oral contraceptives responded to a low salt intake with a marked increased in proximal sodium conservation (P < 0.01 vs. high salt) and with an almost complete reabsorption of sodium reaching the distal tubule. After sodium loading, both the proximal and the distal reabsorption of sodium decreased significantly (P < 0.01)., Conclusion: The use of oral contraceptives is not associated with an increased blood pressure response to salt in young normotensive women. However, oral contraceptives affect the renal hemodynamic response to salt, a high salt intake leading to an increase in GFR and filtration fraction. This effect is possibly mediated by the estrogen-induced activation of the renin-angiotensin system. Oral contraceptives also appear to increase the tubular responsiveness to changes in sodium intake. Taken together, these data point out evidence that synthetic sex steroids have a significant impact on renal function in women. The renal effects of oral contraceptives should be taken into account when managing young women with renal diseases.

Background: Communication between physicians and patients is particularly challenging when patients do not speak the local language (in Switzerland, they are known as allophones)., Aim: To assess the effectiveness of an intervention to improve communication skills of physicians who deal with allophone patients., Design of Study: 'Before-and-after' intervention study, in which both patients (allophone and francophone) and physicians completed visit-specific questionnaires assessing the quality of communication., Setting: Two consecutive samples of patients attending the medical outpatient clinic of a teaching hospital in French-speaking Switzerland., Method: The intervention consisted of training physicians in communicating with allophone patients and working with interpreters. French-speaking patients served as the control group. The outcomes measured were: patient satisfaction with care received and with communication during consultation; and provider (primary care physician) satisfaction with care provided and communication during consultation., Results: At baseline, mean scores of patients' assessments of communication were lower for allophone than for francophone patients. At follow-up, five out of six of the scores of allophone patients showed small increases (P < 0.05) when compared with French-speaking patients: explanations given by physician; respectfulness of physician; communication; overall process of the consultation; and information about future care. In contrast, physicians' assessments did not change significantly. Finally, after the intervention, the proportion of consultations with allophone patients in which professional interpreters were present increased significantly from 46% to 67%., Conclusions: The quality of communication as perceived by allophone patients can be improved with specific training aimed at primary care physicians.

Currently, the genus Pestivirus comprises the four approved species Bovine viral diarrhea virus 1 (BVDV-1), BVDV-2, Classical swine fever virus (CSFV), and Border disease virus (BDV) and one tentative fifth species represented by a single strain (H138) isolated from a giraffe in Kenya more than 30 years ago. To further address the issue of heterogeneity of pestiviruses we have determined the entire N(pro) and E2 coding sequences for several new pestivirus isolates. Interestingly, phylogenetic analysis revealed that one pestivirus isolated in the 1990s in Africa is closely related to strain H138. Moreover, several novel pestiviruses isolated from sheep group together with the previously described strain V60 (Reindeer-1) isolated from a reindeer, whereas one ovine pestivirus strain (Gifhorn) significantly differs from all previously described pestiviruses, including BDV. We propose to term these mainly sheep-derived pestiviruses BDV-2 (V60-like isolates) and BDV-3 (Gifhorn); consequently, the "classical" BDV isolates should be termed BDV-1. As an additional criterion for segregation of pestiviruses, the antigenic relatedness of pestivirus isolates covering all observed major genotypes was studied by cross-neutralization assays. Analysis of the antigenic similarities indicated the presence of seven major antigenic groups corresponding to BVDV-1, BVDV-2, CSFV, BDV-1, BDV-2, BDV-3, and "giraffe". Taking into account the host origin, the lack of differences concerning the course of disease, and the results of our genetic and antigenic analyses, we suggest that BDV-1, BDV-2, and BDV-3 should be considered as major genotypes within the species BDV.

The mission of the Department of Community Medicine at the Geneva University Hospitals is to offer the underserved and marginalised populations guaranteed access to the health system and to promote education and research in general and internal medicine (primary care). The activity with a two-fold focus--medical-social and academic--demonstrated by the type of care offered to homeless people and other clandestine groups allows for the achievement of a number of objectives of the Towards Unity for Health programme. However, evidence to date emphasises that such a structure remains fragile.

Background: Though influenza is a serious health problem for elderly people, their influenza vaccination rate remains low in Switzerland., Objective: Our aim was to assess the impact of an intervention combining multiple strategies to promote influenza vaccination of elderly patients in primary care., Methods: We conducted a pre-/post-intervention study in a university-based primary care clinic in Geneva, Switzerland, where an annual community-wide campaign promotes influenza vaccination of people at high risk. We included 318 and 346 patients aged over 64 years attending the clinic during the last trimesters of 1995 and 1996, respectively. The intervention included: patient information by leaflets and posters, a walk-in vaccination clinic, a training workshop for physicians, record reminders and peer comparison feedback on vaccination performance. Using the computerized database, medical records and the vaccination register, we measured influenza immunization rates and relative benefits (RBs) of the intervention., Results: Influenza vaccine uptake globally increased from 21.7% before the intervention to 51.7% thereafter. Among 144 patients attending in both phases, the immunization rate rose from 29.2 to 69.4% [matched RB estimate () = 2.4; 95% confidence interval (CI) 1.9-3.0]; vaccine uptake increased particularly among all chronic patients ( = 3.2; 95% CI 2.2-4.6), cardiac patients ( = 3.4; 95% CI 2.1-5.4) and diabetics ( = 3.3; 95% CI 1.9-5.9). For 376 patients attending in a single phase, the vaccination rate rose from 15.5 to 39.1% (adjusted RB = 2.8; 95% CI 1.8-4.4), particularly among the elderly aged 65-75 years (adjusted RB = 5.7; 95% CI 2.7-12.4)., Conclusion: An intervention combining strategies targeting patients, physicians and care delivery significantly increased influenza vaccine uptake of elderly patients in primary care, particularly those at high risk.

This report describes border disease in a flock of sheep in Switzerland. In April 2001, three ewes in a flock of 41 sheep gave birth to lambs that had generalized tremors and excessively hairy fleece. One of these, a three-week-old female lamb, was referred to our clinic for further diagnostic work-up. The lamb was very nervous, bleated constantly and had generalized muscle tremors, which were more pronounced in the head region. Hind end ataxia was observed, and the lamb was slow to correct its posture when the hind limbs were abducted, adducted or crossed. Blood samples were collected every six weeks to determine antibody titres to pestivirus and for virus isolation via cell culture. A skin biopsy sample was also collected and examined immunohistochemically for pestivirus antigen. Antibody titres in the first tests were suspicious and those of the second were negative. Pestivirus was identified in cell culture, and the skin biopsy sample was positive for pestivirus antigen. Blood samples were collected from all of the ewes and lambs and the buck for virus isolation via cell culture and determination of pestivirus antibody titres. Thirty-one animals were seropositive, six had borderline antibody titres and four were seronegative. Pestivirus was isolated from eight animals, which included the lamb described in this report. Of the virus-positive animals, three were seronegative, three others had borderline titres and two were seropositive. Six of the eight viruses isolated from cell culture were further characterized genetically via retrotranscription and polymerase chain reaction and subsequent sequencing. The phylogenetic analysis revealed that the causative agent was border disease virus. This is the first time that border disease virus has been isolated in Switzerland. The lamb referred to our clinic was observed for three months; it was then euthanatised and a postmortem examination was performed. Immunohistochemical examination of numerous organs revealed pestivirus antigen. The source of infection was though to be infected sheep from another flock, which shared a pasture. All antigen-positive animals were slaughtered.

Background: New educational programs must be developed to improve physicians' skills and effectiveness in counseling patients about smoking cessation., Objective: To assess the efficacy of an educational program based on behavioral theory, active learning methods, and practice with standardized patients in helping patients abstain from smoking and changing physicians' counseling practices., Design: Cluster randomized, controlled trial., Setting: Two general internal medicine clinics in Switzerland., Participants: 35 residents and 251 consecutive smoking patients., Intervention: A training program administered over two half-days, during which physicians learned to provide counseling that matched smokers' motivation to quit and practiced these skills with standardized patients acting as smokers at different stages of change. The control intervention was a didactic session on management of dyslipidemia., Measurements: Self-reported abstinence from smoking at 1 year of follow-up, which was validated by exhaled carbon monoxide testing at one clinic; score of overall quality of counseling based on use of 14 counseling strategies; patient willingness to quit; and daily cigarette consumption., Results: At 1 year of follow-up, abstinence from smoking was significantly higher in the intervention group than in the control group (13% vs. 5%; P = 0.005); this corresponded to a cluster-adjusted odds ratio of 2.8 (95% CI, 1.4 to 5.5). Residents who received the study training provided better counseling than did those who received the control training (mean score, 4.0 vs. 2.7; P = 0.002). Smokers' willingness to quit was also higher in the intervention group (94% vs. 80%; P = 0.007). A nonsignificant trend toward lower daily cigarette consumption in the intervention group was observed., Conclusion: A training program in smoking cessation administered to physicians that was based on behavioral theory and practice with standardized patients significantly increased the quality of physicians' counseling, smokers' motivation to quit, and rates of abstinence from smoking at 1 year.

A minority of patients with upper respiratory tract infections (URTI) have a bacterial infection and may benefit from antibiotherapy. In previous investigations we showed that in patients suffering from acute rhinosinusitis associated with the presence of Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis in their nasopharygeal secretions, resolution of symptoms was significantly improved by antibiotic treatment. The present analysis was performed to determine whether specific clinical symptoms or signs observed during careful endoscopic examination of the nasal cavities could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis infected with pathogenic bacteria. Detailed clinical histories were obtained and medical examinations performed in 265 patients (138 females, 127 males; mean age 35 years) presenting with a < 4-week history of URTI symptoms but who did not require immediate antibiotic therapy for severe rhinosinusitis. The presence of three pathogenic bacteria (S. pneumoniae, H. influenzae and M. catarrhalis) was determined in all patients by culture of nasopharyngeal secretions. Azithromycin (500 mg/day for 3 days; n = 133) or placebo (n = 132) were randomly given to all patients in a double-blind manner. Pathogenic bacteria were found in 77 patients (29%). The clinical signs and symptoms significantly associated in a multivariate model with the presence of bacteria included colored nasal discharge (p < 0.003), facial pain (p < 0.032) and radiologically determined maxillary sinusitis (complete opacity, air-fluid level or mucosal thickening > 10 mm) (p < 0.001). This best predictive model had a sensitivity of 69% and a specificity of 64% and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis. In the group of patients with positive bacterial cultures, resolution of symptoms at Day 7 was observed in 73% of patients treated with azithromycin and in 47% of patients in the placebo group (p < 0.007). We conclude that signs and symptoms of acute rhinosinusitis in patients with mild-to-moderate clinical presentations are poor predictors of the presence of bacteria.

Background: It has been suggested that women gain weight and develop peripheral edema during the luteal phase of the menstrual cycle because they tend to retain sodium and water. However, there is actually no clear evidence for physiological, cyclic variations in renal sodium handling during the menstrual cycle. We prospectively assessed the changes in segmental renal sodium handling occurring during the menstrual cycle in response to changes in salt intake., Methods: Thirty-five normotensive women were enrolled. Seventeen women were randomized and studied in the follicular and 18 in the luteal phases of their menstrual cycle. All women were assigned at random to receive a low (40 mmol/day) or a high (250 mmol/day) sodium diet for seven days on two consecutive menstrual cycles. Renal sodium handling and hemodynamics were measured at the end of each diet period., Results: The changes in sodium intake induced comparable variations in sodium excretion in both phases of the menstrual cycle. In the follicular phase, the increase in salt intake was associated with no change in renal hemodynamics, an increased fractional excretion of lithium (FELi) and a decreased fractional distal reabsorption of sodium (FDRNa), suggesting that sodium reabsorption is reduced both in the proximal and the distal tubules. In contrast, in the luteal phase, the renal response to salt was characterized by a significant renal vasodilation and a marked salt escape from the distal nephron, compared to the women investigated in the follicular phase (P < 0.01). Sodium reabsorption by the proximal nephron was not reduced as indicated by the unchanged FELi., Conclusions: These results show that the segmental renal handling of sodium differs markedly in the two phases of the menstrual cycle. They suggest that the female hormones modulate the renal handling of sodium at the proximal and distal segments of the nephron in young normotensive women.

A computer-based method was developed for rapid and automatic identification of potential "frequent hitters". These compounds show up as hits in many different biological assays covering a wide range of targets. A scoring scheme was elaborated from substructure analysis, multivariate linear and nonlinear statistical methods applied to several sets of one and two-dimensional molecular descriptors. The final model is based on a three-layered neural network, yielding a predictive Matthews correlation coefficient of 0.81. This system was able to correctly classify 90% of the test set molecules in a 10-times cross-validation study. The method was applied to database filtering, yielding between 8% (compilation of trade drugs) and 35% (Available Chemicals Directory) potential frequent hitters. This filter will be a valuable tool for the prioritization of compounds from large databases, for compound purchase and biological testing, and for building new virtual libraries.

The purpose of the present study was to evaluate prospectively blood pressure and the renal haemodynamic response to salt during the normal menstrual cycle. A total of 35 healthy normotensive young women not on oral contraceptives were enrolled; 17 were studied in the follicular phase and 18 in the luteal phase of the menstrual cycle. The women in each group were then randomly allocated to receive a low-sodium (40 mmol/day) or a high-sodium (250 mmol/day) diet for a 7-day period in two consecutive menstrual cycles. At the end of each dietary period, 24 h ambulatory blood pressure, urinary sodium excretion, plasma renin activity, plasma catecholamine levels and renal haemodynamics were measured. Our results show that the blood pressure response to salt is comparable during the luteal and the follicular phases of the normal menstrual cycle and is characterized by a salt-resistant pattern. In the kidney, effective renal plasma flow was significantly greater and the filtration fraction lower (P<0.05) after salt loading in women studied in the luteal phase compared with women investigated in the follicular phase. This study thus demonstrates that the female hormone status does not affect the blood pressure response to sodium in young normotensive women. However, in contrast with systemic haemodynamics, the renal response to salt varies during the normal menstrual cycle, suggesting that female sex hormones play a role (direct or indirect) in the regulation of renal haemodynamics.

A minority of patients with common cold and upper respiratory tract infections have a bacterial infection and may benefit from antibiotic therapy. The present analysis set out to determine whether there were clinical symptoms or signs which could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis who are infected with pathogenic bacteria. Detailed clinical history and medical examination were obtained from 265 patients (mean age 35 years, 138 females and 127 males) presenting symptoms of upper respiratory tract infections but no fever above 38 degrees C. The presence of three pathogenic bacteria (S. pneumoniae, H. influenzae or M. catarrhalis) was determined in all patients by culture of nasopharyngeal secretions. Aggravating factors for severity of rhinosinusitis, such as severe nasal obstruction, inferior and/or middle turbinate hypertrophy, oedema of the middle meatus mucosa and septal defects, were not associated with the presence of bacteria. Pathogenic bacteria were found in 77 patients (29%). The clinical signs and symptoms which were significantly associated in a multivariate model with the presence of bacteria included facial pain (p < 0.003), coloured nasal discharge (p < 0.003) and radiological maxillary sinusitis (complete opacity, air-fluid level or mucosal thickening greater than 10 mm) (p < 0.002). This, the best predictive model, had a sensitivity of 69% and a specificity of 64% and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis. We conclude that signs and symptoms of acute rhinosinusitis in patients with a mild to moderate clinical presentation are poor predictors of the presence of bacteria. In agreement with previous studies, culture of nasopharyngeal secretions may identify patients who would benefit from antibiotic treatment. Thus, antibiotic therapy should not be prescribed in the absence of bacteriological evidence.

Introduction: The analysis of drug prescription in a primary care clinic is a useful tool to evaluate the quality of medical care provided to outpatients., Methodology: We analysed drug prescriptions of the first consultations with 701 patients attending between May 14 and June 6 1997, and compared this data to previous surveys conducted in 1988, 1991 and 1993., Results and Discussion: The three most common diagnoses were hypertension, lumbar pain and diabetes. The prescription of non steroidal antiinflammatory drugs (NSAID) increased from 7.1% in 1988 to 20% in 1997. For acute lumbar pain physicians prescribed NSAID to 58% of patients and paracetamol only to 33%. Further, doctors often prescribed muscle relaxants although an additional antalgic effect has not been proven. The prescription of psychotropic drugs decreased from 22.5% in 1988 to 12.7% in 1997. ACE inhibitors and calcium antagonists were the most frequently prescribed antihypertensive drugs. Therefore physicians do not follow the American (JNC VI) and our institutional guidelines, which recommend beta-blockers and diuretics as first line agents.

This small-scale study attempts to examine the languages spoken in medical consultations during a one-month period in an outpatient clinic in Geneva and the ways health professionals use to communicate with their allophone patients, in particular by using interpreters. Patients of foreign origin accounted for 58% of all the consultations during the survey. Of these, 37% were Non-French-speakers (NFS). The four major language groups of NFS were Albanian, Somali, Tamil and Serbo-croat. Qualified interpreters were used in 24% of the consultations, relatives acting as interpreters in 17%, and in the other consultations without anyone interpreting (59%), a common language had to be negotiated: French, English, Italian, Spanish or German. In only 14% of the consultations without interpreters, both patient's and doctors ability to speak a common language was rated as good. Our data suggest that there has been an increasing awareness of the possible language barriers in the medical outpatient clinic. Even if proxy solutions (informal interpreters or the use of a common language) still play an important role, access to an interpreter service has been widely used. This calls for systematic and regular interpreter use, planning the interpreting needs in a timely manner. In the future, training in working with interpreters should become an integral part to the introductory sessions for the junior physicians assigned to the outpatient clinic.

Problem: There is little knowledge of the practices of private physicians in Switzerland. However, this knowledge is a prerequisite for definition of the learning objectives in post-graduate and continuous education., Objective: To ascertain the procedural skills of family physicians and general internists and compare them with variables such as education and the location of practice., Method: Questionnaire containing 68 procedural skills sent to all family physicians and general internists in the Cantons of Valais (VS) and Geneva (GE)., Results: 142/204 questionnaires (69%) were analyzed. A mean of 28.7 skills are practiced by the physicians. The internists use fewer procedures than the generalists. There is no difference between generalists practising in VS and GE, nor between location of the practice (urban or rural). The internists in GE and/or those practising in urban settings use fewer procedures than those practising in VS and in rural locations. Internists practising in rural setting use the same number of procedures than the generalists. Fifteen procedures are used by > or = 75% of physicians, 6 of these concern X-ray procedures. 60% of the procedures are used more frequently by the generalists, in particular surgical, ENT and gynecological procedures. There is no difference between generalists and internists as far emergency procedures or procedures in the cardiological and pneumological domain are concerned., Conclusions: The number of procedures depends nor only on the speciality of the private physician (generalist or general internist), but also and mainly on the location of the practice, the density of physicians and emergency practice. These findings can be used in defining the learning objectives of the primary care curriculum.

Objective: To ascertain the educational goals of internal medicine teachers in the domain of clinical skills, the realization of these objectives and their pertinence for the practice of primary care physicians., Methods: Questionnaire containing 44 clinical skills sent to the chiefs of the services of internal medicine of public hospitals in French-speaking Switzerland and the 5 Swiss university hospitals. Comparison of these results with an earlier study concerning the practice of clinical skills of the primary care physicians., Results: The participation was 82%. The educational goals were identical for all the chiefs of internal medicine independently of whether they were university-dependent or not, or in a large or small hospital. 22 of the proposed clinical skills were considered as teaching goals for > or = 70% of the heads of medicine. However, they thought that only 8 of these 22 skills were acquired by the majority of their residents. 8 of these 22 skills were considered to be indispensable for proper functioning of the service. There was a good correlation between the acquired skills and those considered to be indispensable for proper functioning of the service. The medical chiefs considered most of the skills practiced by the primary care physicians were also educational objectives. However, they thought that only 23% of these skills were acquired by their residents. Only half of the skills considered as acquired were practiced by a majority of the primary care physicians., Conclusions: Many clinical skills are considered as educational goals by the medical chiefs of hospital services in internal medicine. However, they consider only a third of these goals as acquired by their residents at the end of their residency. There was a good correlation between the skills thought to be acquired and those considered to be indispensable for proper functioning of their service, and a poor correlation between the skills considered as acquired and those practiced by primary care physicians.

Background: Patient satisfaction is increasingly used to evaluate the performance of health services. Validated French-language instruments to measure satisfaction are currently lacking. This study was designed to validate a questionnaire of this kind and to identify factors associated with patient satisfaction., Methods: Mail survey of 1027 patients who consulted at 4 different ambulatory health care settings in Geneva, Switzerland. The participation rate was 81%. The questionnaire measured 7 dimensions of satisfaction using 16 items adapted from other sources., Results: The questionnaire was easy to respond to (scores were available for 95 to 99% of respondents, depending on the scale). The internal consistency of the scales was satisfactory (Cronbach alpha between 0.65 and 0.82) for 5 of 6 multi-item scales; it was lower for the scale which measures satisfaction with access to care. Factor analysis identified two principal components corresponding roughly to the "process" and to the "organization" of care. Open comments also confirmed the validity of the multi-item scales. Several patient or visit characteristics were independently associated with the level of satisfaction: older patients, those who were born in Switzerland, who had a visit appointment, who consulted a specialist, and those who saw the same physician as at their previous visit were more satisfied than other patients., Conclusions: The brief satisfaction questionnaire described in this paper is easy to use, and its reliability and validity are good. Its use can be recommended in ambulatory health care settings. Several variables associated with the level of satisfaction were identified; they should be measured in satisfaction surveys to allow correct appraisal of the results.