Showing papers in "Swiss Medical Weekly in 2010"

Cathepsins and their involvement in immune responses

Abstract: The immune system is composed of an enormous variety of cells and molecules that generate a collective and coordinated response on exposure to foreign antigens, called the immune response. Within the immune response, endo-lysosomal proteases play a key role. In this review we cover specific roles of cathepsins in innate and adaptive immunity, as well as their implication in the pathogenesis of several diseases.

Interprofessional collaboration among nurses and physicians: making a difference in patient outcome.

Abstract: Deficiencies in collaboration and communication between healthcare professionals have a negative impact on the provision of healthcare and on patient outcomes. Policymakers and healthcare managers, as well as clinicians and practitioners, are aware of this and have a growing interest in improving these relationships. To establish new models of care delivery, it is necessary to determine the interventions that are most effective in furthering interprofessional collaboration. This article provides an overview of the evidence base for interprofessional collaboration involving doctors and nurses and new models of care in relation to patient outcomes. Two authors conducted independent literature searches in PubMed, CINAHL, and Cochrane Library and selected fourteen randomised controlled trials (RCT) for review. All of the RCTs originated from Western countries, and the majority tested collaborative care management models against usual care within the elderly population. The major components of the interventions involved individual evidence-based treatment plans, care coordination, health status monitoring, coaching in self-management and promotion of community-based services. They varied between a few days' and three years' duration. Outcome measures incorporated mortality, clinical, functional and social outcomes, and utilisation of medical services. Some studies also used patient-reported outcomes. While the results of the fourteen RCTs included were mixed, all but one study reported at least one statistically significant improvement in outcome following interventions based on interprofessional collaboration. More rigorous research in this field and expansion of areas of interprofessional collaboration are needed. Nevertheless, up to now the evidence base of interprofessional collaboration shows promising results in relation to patient outcomes.

The stress hormone copeptin: a new prognostic biomarker in acute illness.

Abstract: Stress is defined as anything that throws the body out of homeostatic balance; for example an acute illness. Any stressor which activates the hypothalamo-pituitary-adrenal (HPA) axis leads to an increase in concentrations of the adrenal stress hormone, cortisol. One of the major hypothalamic stress hormones, which is stimulated by different stressors, is vasopressin (AVP). However, measurement of circulating AVP levels is challenging because it is released in a pulsatile pattern, it is unstable and is rapidly cleared from plasma. AVP derives from a larger precursor peptide (pre-provasopressin) along with copeptin which is released in an equimolar ratio to AVP and is more stable in the circulation and easy to determine. Copeptin levels were found to closely mirror the production of AVP. We have shown that copeptin more subtly mirrors the individual stress level compared to cortisol. Due to the positive association of copeptin with the severity of illness and outcome, copeptin has been proposed as a prognostic marker in acute illness. The prognostic accuracy of copeptin has been analysed in sepsis, pneumonia, lower respiratory tract infections, stroke and other acute illnesses. Thereby, copeptin was found to accurately mirror disease severity and to discriminate patients with unfavourable outcomes from patients with favourable outcomes. Copeptin improves the prognostic information provided by commonly used clinical scoring instruments. Importantly, interpretation of copeptin levels must always consider the clinical setting. An accurate prognostic assessment has the potential to guide interventions and effectively plan and monitor rehabilitation and, thus optimise the management of individual patients and the allocation of limited health care resources. Future intervention studies must prove the value of copeptin in clinical decision making and in improving the overall medical management of patients with acute illnesses.

Multifaceted roles of peroxisome proliferator-activated receptors (PPARs) at the cellular and whole organism levels

Abstract: Chronic disorders, such as obesity, diabetes, inflammation, non-alcoholic fatty liver disease and atherosclerosis, are related to alterations in lipid and glucose metabolism, in which peroxisome proliferator-activated receptors (PPAR)α, PPARβ/δ and PPARγ are involved. These receptors form a subgroup of ligand-activated transcription factors that belong to the nuclear hormone receptor family. This review discusses a selection of novel PPAR functions identified during the last few years. The PPARs regulate processes that are essential for the maintenance of pregnancy and embryonic development. Newly found hepatic functions of PPARα are the mediation of female-specific gene repression and the protection of the liver from oestrogen induced toxicity. PPARα also controls lipid catabolism and is the target of hypolipidaemic drugs, whereas PPARγ controls adipocyte differentiation and regulates lipid storage; it is the target for the insulin sensitising thiazolidinediones used to treat type 2 diabetes. Activation of PPARβ/δ increases lipid catabolism in skeletal muscle, the heart and adipose tissue. In addition, PPARβ/δ ligands prevent weight gain and suppress macrophage derived inflammation. In fact, therapeutic benefits of PPAR ligands have been confirmed in inflammatory and autoimmune diseases, such as encephalomyelitis and inflammatory bowel disease. Furthermore, PPARs promote skin wound repair. PPARα favours skin healing during the inflammatory phase that follows injury, whilst PPARβ/δ enhances keratinocyte survival and migration. Due to their collective functions in skin, PPARs represent a major research target for our understanding of many skin diseases. Taken altogether, these functions suggest that PPARs serve as physiological sensors in different stress situations and remain valuable targets for innovative therapies.

Domestic violence against women: Definitions, epidemiology, risk factors and consequences.

Abstract: Domestic violence is considered one of the most common forms of gender-related violence, and various studies estimate that between 10 and 35% of women experience domestic violence at some point in their lives. Nevertheless, it is a frequently neglected problem in crisis intervention centres, emergency wards, and obstetrics and gynaecological emergency rooms. This paper contributes to clarifying the definition, epidemiology, risk factors and consequences of domestic violence against women as well as the psychopathological profile of victims with a focus on Central European countries. Although different studies on domestic violence report different risk factors, such as younger age, being unmarried, lower education, violence experienced during childhood and alcohol/drug abuse of the partner or the victim herself, the results show no overall consistency. There seems to be neither a definite risk profile nor a specific association with a psychopathological profile. Women who have been victimised find it hard to share their experiences and seek help. It is often difficult for medical personnel who encounter these women to recognise violence and discuss this problem with them, just as it is difficult to offer adequate help. Medical personnel should be alerted to this subject and prepare guidelines for the further management and treatment of abused women. Infor-mation and support for medical staff can help to identify domestic violence, and encourage communication about this problem, thereby leading to a better and more efficient use of available services and resources.

Improving intelligence: a literature review.

Abstract: Intelligence is associated with performance on a wide range of cognitive tasks and is a reliable predictor for educational and professional success. Therefore, the development of effective training regimens that aim to improve intelligence is of high interest. In recent years, there has been accumulating evidence that certain interventions have a positive impact on intelligence. The aim of the present paper is to provide a literature review on such studies. Despite promising results, we conclude that there are still many unknown variables and that the mechanisms that underlie improvements in intelligence are not well understood. More work is needed in order to disentangle these involved processes and to further refine existing training regimens.

Three decades of endothelium research: from the detection of nitric oxide to the everyday implementation of endothelial function measurements in cardiovascular diseases.

Abstract: Summary The endothelium is more than just a passive interface between the blood and the vessel wall. Since the pioneering discovery of nitric oxide as an important endothelium-derived vasorelaxing molecule three decades ago, vascular research has developed exponentially and remains fascinating for the entire research community. Endothelial dysfunction is a pathological condition characterized by an imbalance between vasodilatating and vasoconstricting substances. Most, if not all, cardiovascular risk factors have been attributed with endothelial dysfunction and their therapeutic modification with an improvement in vascular function. This overview aims to provide a glimpse into this fascinating research field with the emphasis on vasoactive substances and the assessment of endothelial function.

Liver injury caused by drugs: an update

Abstract: Although severe idiosyncratic drug-induced liver injury (DILI) is a rare event, it has a large impact on the fate of affected patients and the incriminated drug. Hepatic metabolism of drugs, which occurs in the generation of chemically reactive metabolites in critical amounts, seems to underlie most instances of DILI. Genetic polymorphisms in activating and detoxifying enzymes determine, in part, the extent of cellular stress. A cascade of events, where the pathogenetic relevance of single steps is likely to vary from drug to drug, leads to the disturbance of cellular homeostasis, to mitochondrial dysfunction, to the activation of cell death promoting pathways and the release of drug-modified macromolecules and/or danger signals that initiate an innate and/or adaptive immune response. The patient's response to the initial drug-induced cellular dysfunction determines whether adaptation to the drug-induced cellular stress or DILI in one of its many forms of clinical presentation occurs. Although risk factors for developing DILI have been identified and many pathogenetic mechanisms have been elucidated in model systems, idiosyncratic drug reactions remain unpredictable.

Hormones, immune response, and pregnancy in healthy women and SLE patients.

Abstract: During pregnancy the maternal immune system is modified in order to achieve immune tolerance toward paternal antigen expressed on foetal cells. These modifications, which occur both at the foeto-maternal interface and in the systemic circulation, are driven by oestrogens and progesterone whose blood concentrations increase during pregnancy. The cytokine profile is also modified. Th2 cytokines are enhanced while the Th1 response is inhibited. This could explain why Th1-mediated autoimmune diseases tend to improve and Th2-mediated diseases, such as systemic lupus erythematosus (SLE), tend to worsen during pregnancy. However, whether or not SLE relapses more frequently during pregnancy is still a matter of debate. Steroid hormone and cytokine profiles differ in SLE patients compared with healthy subjects during pregnancy leading to a dysregulation of the balance between cell-mediated and humoral immune response, which, in turn, could explain the variability of the SLE course during gestation. This review focuses on hormonal-related cytokine changes observed during pregnancy in healthy subjects and SLE patients.

General practitioner's adherence to the COPD GOLD guidelines: baseline data of the Swiss COPD Cohort Study.

Abstract: PRINCIPLES: Chronic obstructive pulmonary disease (COPD) is a major burden on patients and healthcare systems. Diagnosis and the management of COPD are often administered by general practitioners (GPs). This analysis investigated the adherence of GPs in Switzerland to the Global Initiative for Chronic Obstructive Lung Diseases (GOLD) guidelines. METHODS: As part of an ongoing investigation into the effect of GPs prescriptions on the clinical course of COPD, 139 GPs submitted a standardised questionnaire for each COPD patient recruited. Information requested included spirometric parameters, management and demographic data. Participating GPs were provided with and received instruction on a spirometer with automatic feedback on quality. Patients were grouped by the investigators into the GOLD COPD severity classifications, based on spirometric data provided. Data from the questionnaires were compared between the groups and management was compared with the recommendations of GOLD. RESULTS: Of the 615 patients recruited, 44% did not fulfil GOLD criteria for COPD. Pulmonary rehabilitation was prescribed to 5% of all patients and less than one-third of patients exercised regularly. Less than half the patients in all groups used short-acting bronchodilators. Prescribing long-acting bronchodilators or inhaled corticosteroids conformed to GOLD guidelines in two-thirds of patients with GOLD stage III or IV disease, and approximately half of the less severe patients. Systemic steroids were inappropriately prescribed during stable disease in 6% of patients. CONCLUSIONS: Adherence to GOLD (COPD) guidelines is low among GPs in Switzerland and COPD is often misdiagnosed or treated inappropriately. This is probably due to poor knowledge of disease definitions.

Trend of burnout among Swiss doctors.

Abstract: Summary Question under study: Over the last decade the Swiss health care system has undergone several changes, resulting in stronger economic constraints, heavier administrative workload and limited work autonomy for doctors. In this context we examined the change in burnout prevalence over time among Swiss doctors surveyed during this period. Methods: Cross-sectional survey data collected by mail in 2002, 2004 and 2007 throughout the country were used. Measures included the Maslach Burnout Inventory (MBI), several socio-demographics (gender, living alone, having children), and work-related characteristics (number of years in current workplace, hours worked). Answers to the MBI were used to classify respondents into moderate (high score on either the emotional exhaustion or the depersonalisation/cynicism subscales) and high degree of burnout (scores in the range of burnout in all three subscales). Results: Rates of moderate degree burnout increased from 33% to 42% among general practitioners (p = 0.002) and from 19% to 34% among paediatricians (p = 0.001) (high degree of burnout: 4% to 6% [p = 0.17] and 2% to 4% [p = 0.42] respectively). After adjustment for significant socio-demographic and work-related characteristics, an increased risk of moderate burnout was found for doctors surveyed in 2004 and 2007 (OR 1.6, 95%CI 1.3 to 2.0), general practitioners (OR 1.6, 95%CI 1.3 to 2.0) and French-speaking doctors (OR 1.5, 95%CI 1.3 to 1.9). An increased risk of high-degree burnout was found only for general practitioners (OR 1.8, 95%CI 1.05 to 3.0). Conclusions: Burnout levels among Swiss doctors have increased over the last decade, in particular among Frenchspeaking doctors.

Comparison of MALDI TOF with conventional identification of clinically relevant bacteria.

Abstract: Summary BACKGROUND: A completely new approach to diagnose microbial agents at least one day earlier based on mass spectrometric analysis becomes possible in the microbiology laboratory: MALDI TOF: matrix-assisted laser desorption/ionisation time-of-flight. Comparison between results of the new procedure with those obtained by conventional testing is mandatory. METHODS: 204 clinical isolates grown on agar plates were analysed both, by the MALDI TOF Bruker microflex apparatus and by conventional identification using the VITEK II and API systems, both from bioMerieux. RESULTS: Of the identified isolates, 72 were grampositive and 130 gram-negative; 2 were yeasts (candida). Concordance was seen with 61/72 (85%) of the Gram-positive bacteria and with 115/130 (88%) of the Gram-negative bacteria. In 27 samples (13.2%), a discrepancy of the species and/or genus was obvious. The discrepancy appeared with 16 gram-negative (12.2%) and with 11 grampositive germs (15.3%, n.s.). In the latter group, 6 samples showed discordance with Streptococcus pneumoniae (MALDI) and Streptococcus mitis/oralis (conventional identification) constellation. Among gram-negative samples, most differences occurred on the species level only, e.g. Enterobacter cloacae versus Enterobacter kobei. In 5 cases, discordance was major and appeared on the genus level: Enterobacter/Raoultella, Streptococcus/ Gemella, Pseumdomonas/Burkholderia, Microbacter/ Sphingomonas and Candida/Cryptococcus. The most outstanding difference was Microbacterium arborescens (MALDI TOF) and Sphingomonas paucimobilis (conventional). Molecular biological identification of two Streptococcus mitis group bacteria confirmed the erroneous diagnosis by MALDI TOF of Streptococcus pneumoniae. CONCLUSION: Good comparability between MALDI TOF analysis and conventional identification procedures (86.8%) but special caution is needed when identifying streptococcal species.

Mental health and healthcare utilization in adult asylum seekers.

Abstract: Summary We assessed a sample of unselected adult asylum seekers to determine their current mental health status and patterns of healthcare utilisation. METHOD: We included 78 unselected adult asylum seekers after their first year of residence in the Zurich area of Switzerland. The Swiss Federal Office for Migration provided their names and addresses. The current mental health of the participants was assessed through diagnostic interviews. Their use of healthcare services and the resultant costs over a 12-month period were established by reference to the records of the responsible health insurance company. RESULTS: Forty-one percent of participants had at least one psychiatric disorder, primarily major depression and posttraumatic stress disorder. Healthcare costs were about 1.8 times those of the average resident population. Asylum seekers sought medical advice more than twice as often as did average residents. While they presented high psychiatric morbidity, they received very little specific treatment. CONCLUSION: Asylum seekers incur higher healthcare costs than comparable residents. Mentally ill asylum seekers are underdiagnosed and often inadequately treated.

5% lidocaine medicated plaster in painful diabetic peripheral neuropathy (DPN): a systematic review.

Abstract: BACKGROUND Several pharmacological treatments are used to manage painful diabetic peripheral neuropathy (DPN). OBJECTIVE To compare 5% lidocaine medicated plaster (5%LMP) for the relief of DPN with other relevant interventions and placebo. METHODS Six databases were searched up to June 2009. Quantitative methods for data synthesis were used and a network meta-analysis was conducted. RESULTS Twenty-three studies (38 publications) were included. One study compared 5%LMP with pregabalin and indicated the non-inferiority of 5%LMP for pain reduction. DPN patients experienced a greater improvement in quality of life when using 5%LMP compared to pregabalin. Adverse events were significantly fewer in patients treated with 5%LMP. In the network meta-analysis, all interventions remained effective in comparison with placebo (mean difference in change of pain from baseline compared with placebo, amitriptyline: -12.58 [95% CI -16.66 to -8.50]; capsaicin: -9.40 [95% CI -13.92 to -4.88]; gabapentin: -10.22 [95% CI -17.25 to -3.19]; pregabalin: -10.53 [95% CI -14.74 to -6.32]; 5%LMP: -9.10 [95% CI -13.93 to -4.26]) and 5%LMP was comparable to all other interventions (amitriptyline: 3.48 [95% CI -0.78 to 7.75]; capsaicin: 0.31 [95% CI -4.39 to 5.00]; gabapentin: 1.12 [95% CI -6.02 to 8.27]; pregabalin: 1.43 [95% CI -2.96 to 5.83]). CONCLUSIONS The results suggest that the effects in pain reduction of 5% lidocaine medicated plaster are comparable to those of amitriptyline, capsaicin, gabapentin and pregabalin. Topical agents such as 5%LMP may be associated with fewer and less clinically significant adverse events than is the case for systemic agents. However, the results are limited by the number and size of studies included, and thus further studies are needed.

Predictors of early mortality after acute ischaemic stroke.

Abstract: BACKGROUND The study set out to identify clinical, laboratory and radiological predictors of early mortality after an acute ischaemic stroke (AIS) and to analyse medical and neurological complications that caused death. METHODS A total of 479 consecutive patients (mean age 63+/-14 years) with AIS underwent stroke examination and treatment. Examination included clinical evaluation, laboratory tests, and brain CT and/or MRI. Follow-up data at 30 days were available for 467 patients (93%) who were included in the present analysis. RESULTS The median National Institute of Health Stroke Study (NIHSS) score on admission was 6. A total of 62 patients (13%) died within 30 days. The cause of death was the initial event in 43 (69%), pneumonia in 12 (19%), intracerebral haemorrhage in 9 (15%), recurrent stroke in 6 (10%), myocardial infarction in 2 (3%), and cancer in 1 (2%) of the patients. In univariate comparisons, advanced age (p<0.001), hypertension (p=0.013), coronary disease (p=0.001), NIHSS score (p<0.001), undetermined stroke etiology (p=0.031), relevant co-morbidities (p=0.008), hyperglycemia (p<0.001), atrial fibrillation (p<0.001), early CT signs of ischemia (p<0.001), dense artery sign (p<0.001), proximal vessel occlusion (p<0.001), and thrombolysis (p=0.008) were associated with early mortality. In multivariate analysis, advanced age (HR=1.12; 95% CI 1.05-1.19; p<0.001) and high NIHSS score on admission (HR=1.15, 95% CI 1.05-1.25; p=0.002) were independent predictors of early mortality. CONCLUSIONS We report 13% mortality at 30 days after AIS. More than two thirds of the deaths are related to the initial stroke. Advanced age and high NIHSS score are the only independent predictors of early mortality in this series.

New horizons in osteoarthritis.

Abstract: Osteoarthritis (OA), also known as degenerative joint disease, is the most frequent chronic musculoskeletal disease and the leading cause of disability in elderly persons. There are currently at least 27 million persons afflicted with OA in the United States, and the annual cost to society in medical care and wage loss is expected to reach nearly $100 billion dollars by 2020, with consequent increased spending on its diagnosis and treatment, side effect prevention, and loss of productivity. Despite this enormous burden, many aspects of OA are still unknown, with implications not only in terms of diagnosis and assessment but also with regard to therapy. Awareness of this state of affairs has attracted many researchers to this field, making OA one of the most actively studied sectors of rheumatology. Although some clinicians are unaware of recent advances, there is a large body of publications indicating that much has been achieved. Major progress has been made in formulating better definitions of risk factors, in particular in indicating the responsibility of biomechanical and genetic factors, and, with regard to pathogenesis, underlining the role of subchondral bone, cytokines and proteinases. Assessment of OA activity and its progression has been improved with the advent of biomarkers and new imaging procedures, in particular sonography and magnetic resonance imaging (MRI), but also of better clinical instruments, including more reliable patient questionnaires. Information from ongoing studies may improve the to some extent incomplete definition of OA phenotypes. Finally, promising new horizons have been opened up even with regard to the treatment of OA, which is still for the most part unsatisfactory except for surgical replacement therapy. Numerous new substances have been formulated and the findings of trials studying their effects are encouraging, although much has yet to be done.

Meniere’s disease and the use of proton pump inhibitors

Abstract: PRINCIPLES On the basis of previous observations we examined the possibility of a favourable effect of proton pump inhibitors (PPI) on Meniere's disease (MD). A preliminary step was made by retrospectively analysing the number of menieric crisis in group of patients suffering from MD and using PPI for other reasons as compared to a group of menieric subjects who had never used PPI. METHODS Between January 2001 and December 2006, 42 patients affected by MD were examined in the tertiary referral centre at the University Hospital of Bologna, Italy and in the private office of an ENT specialist in Cassino, Italy. Within the study group, 18 patients had used PPI for various reasons for at least 12 consecutive months, whilst 24 patients had never been prescribed them. We recorded the number of menieric crises reported in the observation period. The mean follow-up period was 21.9 months. Statistical analysis was performed by means of the x2 test and significance was defined when p<0.05. RESULTS Most of MD patients (72%) using PPI suffered less than one episode of menieric crisis/year. On the other hand patients who had never used a PPI, experienced considerably more episodes only 16.7% having less than one crisis per year. This difference was statistically significant (p<0, 001). CONCLUSIONS Even taking the limitations of this retrospective study into account the reported data nevertheless strongly suggest a possible role for proton pumps in the pathogenesis of MD. This could lead to interesting developments and contribute to a better definition of MD and the therapeutic possibilities.

Vaccine hypersensitivity--update and overview.

Abstract: Concerns about possible reactions to vaccines or vaccinations are frequently raised. However, the rate of reported vaccine-induced adverse events is low and ranges between 4.8-83.0 per 100,000 doses of the most frequently used vaccines. The number of true allergic reactions to routine vaccines is not known; estimations range from 1 per 500,000 to 1 per 1,000,000 doses for most vaccines. When allergens such as gelatine or egg proteins are components of the formulation, the rate for serious allergic reactions may be higher. Nevertheless, anaphylactic, potentially life-threatening reactions to vaccines are still a rare event (approximately 1 per 1,500,000 doses). The variety of reported vaccine-related adverse events is broad. Most frequently, reactions to vaccines are limited to the injection site and result from a non specific activation of the inflammatory system by, for example, aluminium salts or the active microbial components. If allergy is suspected, an accurate examination followed by algorithms is the key for correct diagnosis, treatment and the decision regarding revaccination in patients with immediate-type reactions to vaccines.

Making pulmonary rehabilitation a success in COPD.

Abstract: A truly successful pulmonary rehabilitation entails implementing physical activity maintenance. This article reviews the current knowledge on pulmonary rehabilitation and the expected benefits, the setting, the relationship between self-management and pulmonary rehabilitation, in order to develop and implement clinically-effective physical activity maintenance interventions. The effectiveness of pulmonary rehabilitation is well-established. However, access to pulmonary rehabilitation is limited. Home-based pulmonary rehabilitation has been shown to be an effective, equivalent alternative to outpatient pulmonary rehabilitation in COPD patients. The opportunity to offer different pulmonary rehabilitation settings tailored to individual needs should improve accessibility to this intervention. Sustained long-term physical activity remains the most important challenge for COPD patients. We need a dependable system of coordinated health care interventions and communication, and components that include self-management support. Self-management should be an integrated part of pulmonary rehabilitation and remain long after the pulmonary rehabilitation is completed. By early identification of patients who may have difficulty maintaining exercise and implementing appropriate self-management interventions during and after the rehabilitation program, it may be possible to promote better long-term involvement in physical activity. Pulmonary rehabilitation should not stand alone; the best program is that which can be maintained to translate into a continuous increase in the activities of daily living. Future research should evaluate the effect of self-management interventions combined with pulmonary rehabilitation to improve long-term activity and exercise maintenance.

Stabilization of the prevalence of childhood obesity in Switzerland

Abstract: This present study clearly confirms the stabilisation of the prevalence of childhood overweight and obesity in Switzerland.

Superparamagnetic nanoparticles - a tool for early diagnostics

Abstract: Nanoparticles show several interesting new physical and biological properties and therefore play an increasing role in pharmaceutics and medicine. For more than 30 years this research field has been developing slowly but steadily from physical and biological interest (bench) to applications in clinics (bedside). However, many of these particles for biomedical applications are still in the pre-clinical or clinical phase. Combined with drugs or genes these nanoparticles may change the viability of or the transcription processes in cells, which make them interesting for the pharmaceutical industry, cell biology and diagnostics. Because most of the application of superparamagnetic nanoparticles as therapeutic tool, like non-viral vector, drug delivery, are still far from clinical use, this review will concentrate on superparamagnetic nanoparticles as versatile agent for early diagnosis, including the use of such particles as contrast agent for MR imaging and as vehicle for the detection of biomarkers.

The Year of the Lung: outdoor air pollution and lung health.

Abstract: With reference to the Year of the Lung, current knowledge of the respiratory effects of current ambient air pollution is reviewed. Acute respiratory effects are well established. Studies such as SAPALDIA and others now shed light on the long-term effects on chronic pathologies and on the health benefit of air quality improvements. The identification of those at highest risk and of local effects of not yet regulated traffic-related pollutants remains a research priority.

Chronic age-related diseases share risk factors : do they share pathophysiological mechanisms and why does that matter?

Abstract: The World Health Organization (WHO) assigns high priority to the prevention of non-communicable age-related diseases such as heart disease, cancer, diabetes, stroke and chronic lower respiratory diseases. They are now the leading causes of death, in both industrialised and developing countries, mostly due to increased life expectancy and urbanisation with associated changes in lifestyle and environment. Tobacco smoking, physical inactivity and resulting obesity are established risk factors for many chronic diseases. Yet, the aetiology of age-related diseases is complex and varies between individuals. This often makes it difficult to identify causal risk factors, especially if their relative effects are weak. For example, the associations of both obesity and air pollution with several age-related diseases remain poorly understood with regard to causality and biological mechanisms. Exposure to both, excess body fat and particulate matter, is accompanied by systemic low-grade inflammation as well as alterations in insulin/insulin-like growth factor signalling and cell cycle control. These mechanisms have also been associated in animal and some human studies with longevity and ageing in more general terms. In this paper, it is therefore hypothesised that they may, at least in part, be responsible for the adverse health effects of obesity and air pollution. It is argued that molecular and genetic epidemiology now offer novel instruments to improve the understanding of these pathophysiological pathways and their link to disease aetiology. Understanding the causality of exposure disease associations and differences in susceptibilities to environment and lifestyle is an important aspect for effective prevention.

Functional multidisciplinary rehabilitation versus outpatient physiotherapy for non specific low back pain: randomized controlled trial.

Abstract: INTRODUCTION: In recent decades the treatment of non-specific low back pain has turned to active modalities, some of which were based on cognitive-behavioural principles. Non-randomised studies clearly favour functional multidisciplinary rehabilitation over outpatient physiotherapy. However, systematic reviews and meta-analysis provide contradictory evidence regarding the effects on return to work and functional status. The aim of the present randomised study was to compare long-term functional and work status after 3-week functional multidisciplinary rehabilitation or 18 supervised outpatient physiotherapy sessions. METHODS: 109 patients with non-specific low back pain were randomised to either a 3-week functional multidisciplinary rehabilitation programme, including physical and ergonomic training, psychological pain management, back school and information, or 18 sessions of active outpatient physiotherapy over 9 weeks. Primary outcomes were functional disability (Oswestry) and work status. Secondary outcomes were lifting capacity (Spinal Function Sort and PILE test), lumbar range-of-motion (modified-modified Schober and fingertip-to-floor tests), trunk muscle endurance (Shirado and Biering-Sorensen tests) and aerobic capacity (modified Bruce test). RESULTS: Oswestry disability index was improved to a significantly greater extent after functional multidisciplinary rehabilitation compared to outpatient physiotherapy at follow-up of 9 weeks (P = 0.012), 9 months (P = 0.023) and 12 months (P = 0.011). Work status was significantly improved after functional multidisciplinary rehabilitation only (P = 0.012), resulting in a significant difference compared to outpatient physiotherapy at 12 months' follow-up (P = 0.012). Secondary outcome results were more contrasted. CONCLUSIONS: Functional multidisciplinary rehabilitation was better than outpatient physiotherapy in improving functional and work status. From an economic point of view, these results should be backed up by a cost-effectiveness study.

Bach flower remedies: a systematic review of randomised clinical trials

Abstract: Bach flower remedies continue to be popular and its proponents make a range of medicinal claims for them. The aim of this systematic review was to critically evaluate the evidence for these claims. Five electronic databases were searched without restrictions on time or language. All randomised clinical trials of flower remedies were included. Seven such studies were located. All but one were placebo-controlled. All placebo-controlled trials failed to demonstrate efficacy. It is concluded that the most reliable clinical trials do not show any differences between flower remedies and placebos.

Mesenchymal stem cells and innate tolerance: biology and clinical applications.

Abstract: The properties of mesenchymal stem cells (MSC) have been widely investigated during the last decade, from their differentiation capacity to their immunosuppressive effect on any type of immune cell. These properties have been successfully harnessed for the treatment of inflammatory diseases such as graft versus host disease (GvHD). Different mechanisms have been proposed for their immunosuppressive properties, although it seems likely that they are used in concert. The inflammatory environment to which MSC are exposed plays a pivotal role in activating their functions. Conversely, the interplay of MSC with the immunoregulatory networks recruited during inflammation is fundamental to the delivery of immunosuppression. Since other types of terminally differentiated stromal cells share these properties, it is plausible that stemness is not a required feature. Therefore these functions may be involved in the physiological control of acute inflammation in various tissues. These notions highlight the importance of investigating the role of stromal cells as modulators of immune responses.

Outcomes of elderly hip fracture patients in the Swiss healthcare system: A survey prior to the implementation of DRGs and prior to the implementation ofa Geriatric Fracture Centre.

Abstract: PROBLEM AND QUESTIONS: The consequences for elderly patients with hip fractures are well known. In Switzerland, the introduction of diagnosis related groups (DRG) will bring additional challenges. New models of care, such as Geriatric Fracture Centres (GFC), may be the key to minimising negative outcomes. This study documents outcomes of hip fracture patients in the Swiss healthcare system, for use as baseline data prior to DRG- and GFC-implementation, and compares them to results reported in the literature, for example by Cooper (1997).

Cost of dementia in Switzerland.

Abstract: Questions under study The aim of this study was (a) to estimate the cost of dementia in Switzerland, (b) to compare the average annual cost for people with dementia who live at home and those living in an institution and (c) to analyse how the average cost per person with dementia who lives at home increases with the severity of dementia. Methods This prevalence-based cost-of-illness study from a societal perspective combined top-down and bottom-up approaches and included both direct and indirect costs of dementia. Cost estimations were based on Swiss national statistics and surveys, as well as international reviews and expert interviews. Results The total annual cost of dementia amounted up to CHF 6.3 billion for the year 2007. Together, institutional and informal care accounted for over 90% of the cost. The average annual cost was estimated at CHF 55'300 per person with dementia who lives at home and at CHF 68'900 per person who lives in an institution. The cost per person living at home with severe dementia was nearly five times the cost per person with mild dementia. Conclusions The present study indicates that dementia imposes a considerable economic burden on Swiss society. The cost of dementia is dominated by the costs of care. Diagnosis and treatment related costs are minor. These findings are consistent with contemporary international studies on the subject. The contribution of informal caregivers is substantial since they account for 44% of the total cost of dementia (based on market cost valuation). Given demographic developments in Switzerland, healthcare decision making should have an interest in securing this potential for the future.

Assessment of potential drug-drug interactions at hospital discharge.

Abstract: Summary Objective: The evaluation of the prevalence of potential drug-drug interactions and assessment of their clinical relevance in patients’ discharge medication in the medical ward of a community teaching hospital. The relevant clinical information was reported to the treating physicians. Methods: 200 patients at discharge from a medical ward were included. Prescribed drugs were analysed for interactions using commercially available software (Pharmavista ® ). Clinical pharmacists and a physician assessed the clinical relevance of detected interactions, eliminated those which were not considered clinically relevant and formulated recommendations for those considered clinically relevant. A written recommendation was given to the physician to provide rapid feedback before discharge. Results: The median age of the 200 patients studied was 69 years. At discharge, patients took an average of 7 different drugs. 62.5% of patients had at least one potential drug-drug interaction. In total, 373 potential drug-drug interactions were identified: 223 (60%) of minor severity, 143 (38%) of moderate severity and 7 (2%) of major severity. Conclusions: A computerised drug-drug interaction program (detection) together with clinical pharmacological experience (interpretation/evaluation) can be useful for decreasing the number of potentially harmful drug combinations. This approach may lead to an improvement in the quality of prescription, reducing possible risks and thus contributing to patient safety.

Are tyrosine kinase inhibitors promising for the treatment of systemic sclerosis and other fibrotic diseases

Abstract: Tissue fibrosis causes organ failure and death in patients with systemic sclerosis (SSc), but clearly effective anti-fibrotic therapies are not available. The tyrosine kinase inhibitor (TKI) imatinib, which blocks the pro-fibrotic c-Abl kinase and PDGF receptor, is currently evaluated in clinical proof-of-concept trials for the treatment of patients with SSc. In experimental models, imatinib efficiently prevented and reduced tissue fibrosis. First clinical case studies demonstrated anti-fibrotic effects of imatinib in selected patients with SSc and other fibrotic diseases, and observational studies in sclerotic chronic graft-versus-host disease showed promising results. Besides imatinib, the two novel TKIs of c-Abl and PDGF receptor nilotinib and dasatinib have recently proven efficacy in experimental models of SSc. The potential of TKIs of the VEGF receptor (e.g., semaxinib, vatalanib, sutent, and sorafenib) and the EGF receptor (e.g., erlotinib, gefitinib, lapatinib, and canertinib) as anti-fibrotic treatments are also discussed in this review. Prior to clinical use, however, controlled trials need to address efficacy as well as tolerability of TKIs in patients with different fibrotic diseases.