Debast S.B.,Radboud University Nijmegen |
Bauer M.P.,Leiden University |
Kuijper E.J.,Leiden University |
Allerberger F.,Austrian Agency for Health and Food Safety AGES |
And 9 more authors.
Clinical Microbiology and Infection | Year: 2014
In 2009 the first European Society of Clinical Microbiology and Infection (ESCMID) treatment guidance document for Clostridium difficile infection (CDI) was published. The guideline has been applied widely in clinical practice. In this document an update and review on the comparative effectiveness of the currently available treatment modalities of CDI is given, thereby providing evidence-based recommendations on this issue. A computerized literature search was carried out to investigate randomized and non-randomized trials investigating the effect of an intervention on the clinical outcome of CDI. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The ESCMID and an international team of experts from 11 European countries supported the process. To improve clinical guidance in the treatment of CDI, recommendations are specified for various patient groups, e.g. initial non-severe disease, severe CDI, first recurrence or risk for recurrent disease, multiple recurrences and treatment of CDI when oral administration is not possible. Treatment options that are reviewed include: antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, and faecal or bacterial intestinal transplantation. Except for very mild CDI that is clearly induced by antibiotic usage antibiotic treatment is advised. The main antibiotics that are recommended are metronidazole, vancomycin and fidaxomicin. Faecal transplantation is strongly recommended for multiple recurrent CDI. In case of perforation of the colon and/or systemic inflammation and deteriorating clinical condition despite antibiotic therapy, total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.
De Munter J.P.J.M.,Amarna Stem Cells |
Journal of Neural Transmission | Year: 2013
Stem cells seem very promising in the treatment of degenerative neurological diseases for which there are currently no or limited therapeutic strategies. However, their clinical application meets many regulatory hurdles. This article gives an overview of stem cells, their potential healing capacities as well as their identified and potential risks, such as tumor formation, unwanted immune responses and the transmission of adventitious agents. As there is no clinical experience with embryonic and induced pluripotent stem cells (as the result of their unacceptable risk on tumor formation), most attention will be paid to fresh autologous adult stem cells (ASCs). To evaluate eventual clinical benefits, preclinical studies are essential, though their value is limited as in these studies, various types of stem cells, with different histories of procurement and culturing, are applied in various concentrations by various routes of administration. On top of that, in most animal studies allogenic human, thus non-autologous, stem cells are applied, which might mask the real effects. More reliable, though small-sized, clinical trials with autologous ASCs did show satisfying clinical benefits in regenerative medicine, without major health concerns. One should wonder, though, why it is so hard to get compelling evidence for the healing and renewing capacities of these stem cells when these cells indeed are really essential for tissue repair during life. Why so many hurdles have to be taken before health authorities such as the European Medicine Agency (EMA) and/or the Food and Drug Administration (FDA) approve stem cells in the treatment of (especially no-option) patients. © 2012 Springer-Verlag Wien.
De Munter J.P.J.M.,Maastricht University |
Melamed E.,Tel Aviv University |
Wolters E.C.,Maastricht University |
Parkinsonism and Related Disorders | Year: 2014
Parkinson's disease is a devastating, progressive neurodegenerative disorder that affects the central and peripheral nervous systems. Although recent advancements have led to a better understanding of the disorder, there is currently no long-term disease-modifying strategy. Recently, preclinical data have identified the significant effects of pluripotent stem cell grafting in 6-OHDA and MPTP animal models of motor parkinsonism; there have also been some clinical data in patients with motor parkinsonism. Pluripotent stem cells can nestle in affected organs and can differentiate into a variety of cells, including neural (dopamine producing) cells. Depending on the environment into which they are grafted, these stem cells can also influence immune responses by regulating the activity of B-cells, T-cells, and NK-cells. Pluripotent stem cells can also produce chemotrophins, including BDNF (brain-derived neurotrophic factor), GDNF (glial-derived neurotrophic factor), NGF (nerve growth factor), TGF-β (transforming growth factor-β), IGF-1 (insulin-like growth factor 1), NT-3 (neurotrophin 3), and SCF-1 (stem cell factor 1). Influencing these trophic factors can influence plasticity. This article explores the potential of pluripotent stem cells in the treatment of PD. We will explore the utilization of pluripotent stem cells in the immunomodulation of B-cells, T-cells and NK-cells, the transdifferentiation of pluripotent stems cells into DA-cells, and the secretion of trophic factors and its relation to plasticity. We will also cover how best to conduct a clinical trial, which stem cells can be safely used in patients, what are the methods of induction before application, and how to re-apply stem cells in patients by intravasal, intrathecal or intracerebral methods. Finally, we will describe how to objectively record the clinical results. © 2013 Elsevier Ltd.
Von Kanel R.,Universitatsspital |
Von Kanel R.,University of Bern
Praxis | Year: 2014
The prevalence of a major depressive disorder in patients after myocardial infarction is 20%. Depression is a risk factor for incident coronary heart disease and poor prognosis after myocardial infarction. Poor lifestyle habits and adherence to cardiac therapy as well as metabolic and pathophysiologic changes may partially explain this link. The threatening experience of an acute coronary event and immune and inflammatory changes may be unique features contributing to incident depression after myocardial infarction. While psychotherapy, antidepressants, and physical exercise may alleviate depressive symptoms in patients with coronary heart disease, cardiac rehabilitation additionally reduces mortality risk. Attempts are being undertaken to identify the cardiotoxic characteristics of depression to develop even more effective therapies in the future. © 2014 Verlag Hans Huber, Hogrefe AG, Bern.
De Munter J.P.J.M.,Amarna Therapeutics |
Journal of Neural Transmission | Year: 2013
Ischemic and traumatic insults of the central nervous system both result in definite chronic disability, only to some extent responsive to rehabilitation. Recently, the application of autologous stem cells (fresh bone marrow-derived mononuclear cells including mesenchymal and hematopoietic stem cells) was suggested to provide a strategy to further improve neurological recovery in these disorders. During the acute phase, stem cells act mainly by neuroprotection with prevention of apoptosis, whereas during the chronic situation they provide neurorestoration by transdifferentiation and/or the secretion of neurotrophic factors. To reach these goals, in the acute phase, stem cells (10 million mononuclear cells per kg body weight) might be best applied intravenously, as during the first 7 days after the lesion, the blood-brain barrier permits passage of cells from the blood into the brain or the spinal cord. In the more chronic situation, though, those cells might be applied best intrathecally by lumbar puncture. Based on the reported results so far, it seems justified to develop well-designed clinical double-blind trials in chronic spinal cord injury and ischemic stroke patients, as efficacy and safety concerns might not be answered by preclinical studies. © 2012 Springer-Verlag.
Hautarzt | Year: 2010
Component-resolved diagnosis of allergies allows disease-specific patterns of sensitization in some conditions such as allergic bronchopulmonary aspergillosis ABPA). By determination of IgE against important pollen allergens such as Bet v 1, Ole e 1 or Phl p1/Phl p 5, more precise guidance for allergen-specific immunotherapy may be achieved, as pollen extracts contain mostly these major allergens. Sensitizations against minor allergens such as profilins or polcalcins influence the outcome of IgE measurements against full allergen sources, but are often of limited clinical relevance. In food allergy, frequent cross reactivity between pollens such as birch pollen via Bet v 1/PR10 proteins can be identified. Sensitization against some storage proteins such as peanut (Ara h 2) or lipid transfer proteins of peach (Pru p 3) or hazelnut (Cor a 8) may indicate an increased risk of severe anaphylactic reactions. Exercise-induced anaphylaxis, unclear sensitizations against latex or double-positivity in insect allergy are other useful indications for component-resolved diagnosis. Microarray-based allergen chip diagnosis makes possible today the detection of IgE against more than 100 allergens in tiny amounts of serum and is very promising, but still needs evaluation and optimization in regard to allergen selection and sensitivity. © 2010 Springer-Verlag.
Journal fur Kardiologie | Year: 2010
Transcatheter treatment of coronary artery disease (PCI) has transformed the purely diagnostic discipline cardiology into a semi-surgical specialty. The berth of the so-called interventional cardiology was the first PCI performed by Grüntzig in Zurich, Switzerland, on September 16, 1977. The patient was 38 years old and he is still in excellent health, 33 years later. Meanwhile, PCI has matured to the most important medical intervention worldwide considering its clinical and economical potential. It is estimated that globally 2-3 million PCIs are performed. In Austria over 20,000 PCIs are performed per year, in about 34 centers dispersed across the country. Today PCI numbers are 2-4 times larger than the numbers of the classical coronary artery by-pass operations, available since the 60ies. An increasingly early detection and invasive work-up of coronary artery disease favors PCI over by-pass surgery, which can be reserved to the advanced cases that have escaped early detection. In the 3 decades of its existence PCI has seen only one major change of paradigm, i. e., the introduction of the coronary stent in 1986. For the past 7 years, drug-eluting stents have gradually replaced conventional bare metal stents. They effectively contain the inner scaring after stent implantation and thereby reduce the need for reinterventions due to restenosis. Other techniques meant to replace or complement the balloon (laser, drills etc.), have come and gone. PCI sees itself squeezed between medical therapy for mild coronary artery disease and surgical therapy for advanced coronary artery disease. There is significant overlap to both sides and the debate about what best to do with these patients is ongoing.
Bollini P.,Services for Medical Research Formed |
Journal of Evaluation in Clinical Practice | Year: 2013
Rationale, aims and objectives No comprehensive measurement of quality of antenatal care is available. Late booking or low number of checks are often used as surrogate for poor quality, leaving uncertainty on the actual content of the care received. In order to fill this gap, we have reviewed two sets of clinical guidelines and developed corresponding indicators of quality. Method A group of clinicians and methodologists reviewed the National Institute for Clinical Excellency Clinical Guidelines on antenatal care, and the list of prenatal care interventions recommended by the Research and Development Group, both based on evidence of effectiveness of specific interventions. We identified single aspects in three domains: (1) services utilization; (2) screening; and (3) interventions. For each indicator, we defined: (1) eligibility, that is the characteristics of the women to whom the indicator applies; (2) standard, that is the situation when the target is met; and (3) moderators, that is all conditions which legitimately hamper the fulfilment of the standard. Results We developed four indicators of service utilization, 25 of screening and 17 of intervention. The respective eligibility, standard and moderators criteria were described for each indicator. While many indicators could be retrospectively evaluated from medical charts, quality of communication with provider, screening for sensible issues and counselling on behaviours to be avoided could only be obtained with a prospective data collection. Conclusions The indicators of quality of antenatal care, complemented by measures of social position, social support and immigrant/ethnic status, allow for a careful description of the gaps in quality of care for specific groups of women. © 2013 John Wiley & Sons Ltd.
Praxis | Year: 2012
Prostate cancer (PCa) is one of the most common solid cancers and one of the most important causes of morbidity and mortality worldwide in men. So far, several efforts have been devoted to identify prostate cancer biomarkers, which allow a discrimination between indolent and clinically significant diseases, however with scarce results. The prostate-specific antigen (PSA) still remains the marker of choice for PCa diagnosis, prognosis, and "active surveillance". Thus, a sensitive and specific independent indicator, easy to screen in blood or urine is still not available. This review will provide a new insight into the role of previous (i.e. PSA) and new biomarkers, to use separately or in combination for prostate cancer screening and early detection programs. © 2012 Verlag Hans Huber, Hogrefe AG.
Therapeutische Umschau | Year: 2011
The pharmacological treatment of chronic pain differs from acute pain management. In chronic non-cancer pain patients pharmacological treatment is only one element of an interdisciplinary approach. Not pain reduction only but gain in physical and social functioning is mandatory for continuation of therapy. The developpement of a strategy is the most important and difficult step toward an individual and sustained pharmacological pain treatment. Simple practical guidelines can help to find an individual therapeutic straight. Outcome parameters have to be determined. Check-ups for discontinuation of the therapy have to be done periodically. Exact documentation of effect and side effects prevents ungrateful and potential dangerous treatments. The WHO ladder remains the cornerstone of pharmacological pain treatment. Further analgesics as antidepressants and anticonvulsants are important in treatment of neuropathic or mixed pain states. Special considerations have to be done in opioid treatment of non-cancer pain regarding the lack of evidence in long term outcome and possible side effects and risks. © 2011 by Verlag Hans Huber, Hogrefe AG, Bern.