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Volume 140, No. 3536

Published August 30, 2010

Review article: Biomedical intelligence

  1. V Stavropoulou, L Brault, J Schwaller (Author)

    Insights into molecular pathways for targeted therapeutics in acute leukaemia

    Despite the development of modern chemotherapeutic regimens, acute leukaemia remains incurable in the majority of adult patients and potential cure is associated with considerable side effects. Clinical and experimental research of the last two decades has demonstrated that acute leukaemia is the consequence of multiple collaborative molecular aberrations affecting protein kinases and transcriptional regulators induced by genetic alterations and/or epigenetic mechanisms. New technologies have been developed to detect aberrations of the entire (epi)genome of a leukaemic blast that will result in a long list of potential therapeutic targets needing to be functionally validated in cellular and animal leukaemia models. Using these methods, several "druggable” protein kinases have been identified. These kinases exert their oncogenic potential not only through expansion of the leukaemic clone, but also by regulating critical interactions of leukaemic stem cells with the microenvironment. Due to the molecular complexity of acute leukaemia, new functional genome-wide screens have been established and may help to identify targets that when blocked result in synthetic lethality of the leukaemic blasts harbouring distinct (epi)genomic lesions. A close interaction between the academic and the pharmaceutical biomedical research will be essential to translate these exciting new molecular findings into improved therapies for acute leukaemia.

  2. C Beyer, O Distler, JH Distler (Author)

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

    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.

  3. B Rothen-Rutishauser, AD Lehmann, MJ Clift, F Blank, P Gehr (Author)

    Laser scanning microscopy combined with image restoration to analyse a 3D model of the human epithelial airway barrier

    A laser scanning microscope collects information from a thin, focal plane and ignores out of focus information. During the past few years it has become the standard imaging method to characterise cellular morphology and structures in static as well as in living samples. Laser scanning microscopy combined with digital image restoration is an excellent tool for analysing the cellular cytoarchitecture, expression of specific proteins and interactions of various cell types, thus defining valid criteria for the optimisation of cell culture models. We have used this tool to establish and evaluate a three dimensional model of the human epithelial airway wall.

  4. M Flury, E Nyberg (Author)

    Domestic violence against women: definitions, epidemiology, risk factors and consequences

    Background: 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.

  5. Nicole M. Probst-Hensch (Author)

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

    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.

  6. J Bourbeau (Author)

    Making pulmonary rehabilitation a success in COPD

    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.

  7. JS Martin, W Ummenhofer, T Manser, R Spirig (Author)

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

    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.

  8. Angelo Auricchio, Tiziano Moccetti (Author)

    Electronic cardiac medicine: present and future opportunities

    The second half of the 20th century witnessed a revolution in electronic medicine similar to that in pharmacology in the decades before. The advent of the implantable pacemaker, implantable cardioverter-defibrillators, cardiac resynchronisation therapies, insertable loop recorders and more, have improved diagnoses and reduced mortality and morbidity in millions of patients suffering from cardiac disease. The possibility to monitor patients continually without need for frequent office visits has the potential to reduce follow-up burden on physicians, facilitate increased use of home-based care and further improve the safety for patients. This review summarises the role of cardiac device therapies today and some of the developments which we can hope for in the nearest future.

Original article

  1. E Kraft, M Marti, S Werner, H Sommer (Author)

    Cost of dementia in Switzerland

    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.

  2. M Janner, P Ballinari, PE Mullis, CE Flück (Author)

    High prevalence of vitamin D deficiency in children and adolescents with type 1 diabetes

    Background: Vitamin D is important for bone health. An inadequate supply of vitamin D to the body is associated with a higher fracture risk in the elderly. Young adults with type 1 diabetes are reported to have a lower peak bone mass than healthy individuals, which could possibly lead to an increased fracture risk in the future. The prevalence of vitamin D deficiency in healthy young people is high. Thus, optimal supply of vitamin D may be of particular importance for bone health in children with type 1 diabetes.

    Methods: In this prospective cross-sectional study we measured serum 25-hydroxy-vitamin D, iPTH, total and ionised calcium, phosphate, and alkaline phosphatase in 129 Swiss children and adolescents with type 1 diabetes.

    Results: Of the 129 subjects 78 (60.5%) were vitamin D deficient, defined as a 25-hydroxy-vitamin-D level below 50 nmol/L. During the winter this number rose to 84.1%. 25-hydroxy-vitamin-D levels showed marked seasonal fluctuations, whereas there was no correlation with diabetes control. Despite the high prevalence of vitamin D deficiency, we found a low prevalence of secondary hyperparathyroidism in vitamin D deficient diabetic children and adolescents.

    Conclusions:Prevalence of vitamin D deficiency in diabetic children and adolescents is high. Therefore, screening for vitamin D deficiency and supplementation in children with low vitamin D levels may be considered.

  3. D Faeh, M Bopp (Author)

    Excess weight in the canton of Zurich, 1992–2009: harbinger of a trend reversal in Switzerland?

    BACKGROUND/OBJECTIVE: In Switzerland, as in most developed countries, there has been a growing prevalence of excess weight in recent decades. However, within the country there may be regional variations. We investigated whether the trends in excess weight prevalence in the largest urban region differed from that in the rest of German Switzerland (GS).

    METHODS: We used individual data from four nationally representative Swiss Health Surveys (1992–2007) and from one survey conducted in the Canton of Zurich (ZH) in 2009. All studies used self-reported height and weight(18–74 years, N = 41 628). Prevalence rates of excess weight (BMI ≥ 25 kg/m2) were age standardised and population weighted. Odds ratios (OR: normal vs. excess weight) were obtained with weighted multivariable logistic regression.

    RESULTS: The prevalence of excess weight was lower in ZH than in GS, with increasing differences over time. In GS, OR increased in men (p trend 1992–2007 <0.001) and stagnated in women. In contrast, in ZH, OR stagnated in men and decreased in women (p trend 1997–2009 = 0.005). Within ZH, compared to the capital city, OR were higher in men in the less privileged part of the Metropolitan Area (p = 0.046) and in women not living in the Zurich Metropolitan Area (p = 0.049).

    CONCLUSION: In ZH, the prevalence of excess weight stagnated in men and decreased after having reached a peak in 1997 in women. This is the first study showing a decrease in Swiss adults, a population with internationally low excess weight prevalence. There is room for speculation whetherZH is a harbinger of the future situation in other regions of Switzerland and possibly other developed countries.