Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011).

On the traces of XPD: cell cycle matters - untangling the genotype-phenotype relationship of XPD mutations

Abstract Mutations in the human gene coding for XPD lead to segmental progeria - the premature appearance of some of the phenotypes normally associated with aging - which may or may not be accompanied by increased cancer incidence. XPD is required for at least three different critical cellular functions: in addition to participating in the process of nucleotide excision repair (NER), which removes bulky DNA lesions, XPD also regulates transcription as part of the general transcription factor IIH (TFIIH) and controls cell cycle progression through its interaction with CAK, a pivotal activator of cyclin dependent kinases (CDKs). The study of inherited XPD disorders offers the opportunity to gain insights into the coordination of important cellular events and may shed light on the mechanisms that regulate the delicate equilibrium between cell proliferation and functional senescence, which is notably altered during physiological aging and in cancer. The phenotypic manifestations in the different XPD disorders are the sum of disturbances in the vital processes carried out by TFIIH and CAK. In addition, further TFIIH- and CAK-independent cellular activities of XPD may also play a role. This, added to the complex feedback networks that are in place to guarantee the coordination between cell cycle, DNA repair and transcription, complicates the interpretation of clinical observations. While results obtained from patient cell isolates as well as from murine models have been elementary in revealing such complexity, the Drosophila embryo has proven useful to analyze the role of XPD as a cell cycle regulator independently from its other cellular functions. Together with data from the biochemical and structural analysis of XPD and of the TFIIH complex these results combine into a new picture of the XPD activities that provides ground for a better understanding of the patophysiology of XPD diseases and for future development of diagnostic and therapeutic tools.

Relationship between bispectral index values and volatile anesthetic concentrations during the maintenance phase of anesthesia in the B-Unaware trial

Hypnotic depth during anesthesia affects electroencephalography waveforms and electroencephalogram-derived indices, such as the bispectral index (BIS). Titrating anesthetic administration against the BIS assumes reliable relationships between BIS values, electroencephalogram waveforms, and effect site concentration, beyond loss of responsiveness. Associations among BIS, end-tidal anesthetic concentrations (ETAC), and patient characteristics were examined during anesthetic maintenance, using B-Unaware trial data.

Chapter I: Definitions, epidemiology, clinical presentation and prognosis

The concept of chronic critical limb ischaemia (CLI) emerged late in the history of peripheral arterial occlusive disease (PAOD). The historical background and changing definitions of CLI over the last decades are important to know in order to understand why epidemiologic data are so difficult to compare between articles and over time. The prevalence of CLI is probably very high and largely underestimated, and significant differences exist between population studies and clinical series. The extremely high costs associated with management of these patients make CLI a real public health issue for the future. In the era of emerging vascular surgery in the 1950s, the initial classification of PAOD by Fontaine, with stages III and IV corresponding to CLI, was based only on clinical symptoms. Later, with increasing access to non-invasive haemodynamic measurements (ankle pressure, toe pressure), the need to prove a causal relationship between PAOD and clinical findings suggestive of CLI became a real concern, and the Rutherford classification published in 1986 included objective haemodynamic criteria. The first consensus document on CLI was published in 1991 and included clinical criteria associated with ankle and toe pressure and transcutaneous oxygen pressure (TcPO(2)) cut-off levels <50 mmHg, <30 mmHg and <10 mmHg respectively). This rigorous definition reflects an arterial insufficiency that is so severe as to cause microcirculatory changes and compromise tissue integrity, with a high rate of major amputation and mortality. The TASC I consensus document published in 2000 used less severe pressure cut-offs (≤ 50-70 mmHg, ≤ 30-50 mmHg and ≤ 30-50 mmHg respectively). The thresholds for toe pressure and especially TcPO(2) (which will be also included in TASC II consensus document) are however just below the lower limit of normality. It is therefore easy to infer that patients qualifying as CLI based on TASC criteria can suffer from far less severe disease than those qualifying as CLI in the initial 1991 consensus document. Furthermore, inclusion criteria of many recent interventional studies have even shifted further from the efforts of definition standardisation with objective criteria, by including patients as CLI based merely on Fontaine classification (stage III and IV) without haemodynamic criteria. The differences in the natural history of patients with CLI, including prognosis of the limb and the patient, are thus difficult to compare between studies in this context. Overall, CLI as defined by clinical and haemodynamic criteria remains a severe condition with poor prognosis, high medical costs and a major impact in terms of public health and patients' loss of functional capacity. The major progresses in best medical therapy of arterial disease and revascularisation procedures will certainly improve the outcome of CLI patients. In the future, an effort to apply a standardised definition with clinical and objective haemodynamic criteria will be needed to better demonstrate and compare the advances in management of these patients.

Patient adjustment to reduced olfactory function

To compare the importance of olfaction in daily life between patients with olfactory disorders and healthy normosmic individuals.

Communication about standard treatment options and clinical trials: can we teach doctors new skills to improve patient outcomes?

BACKGROUND: The International Breast Cancer Study Group conducted a phase III trial in Australian/New Zealand (ANZ) and Swiss/German/Austrian (SGA) centres on training doctors in clear and ethical information delivery about treatment options and strategies to encourage shared decision making. METHODS: Medical, surgical, gynaecological and radiation oncologists, and their patients for whom adjuvant breast cancer therapy was indicated, were eligible. Doctors were randomised to participate in a workshop with standardised teaching material and role playing. Patients were recruited in the experimental and control groups before and after the workshop. RESULTS: In ANZ centres, 21 eligible doctors recruited a total of 304 assessable patients. In SGA centres, 41 doctors recruited 390 patients. The training was well accepted. There was no overall effect on patient decisional conflict (primary endpoint) 2 weeks after the consultation. Overall, patients were satisfied with their treatment decision, their consultation and their doctors' consultation skills. Considerable variation was observed in patient outcomes between SGA and ANZ centres; the effect sizes of the intervention were marginal (<0.2). CONCLUSIONS: Shared decision making remains a challenge. A sustained training effect may require more intensive training tailored to the local setting. Cross-cultural differences need attention in conducting trials on communication interventions.

Advanced heart failure - treatment options beyond medical management

Improvement of heart failure therapy has led to a far better survival and quality of life of patients. Treatment of the underlying disease, patient education and improvement of compliance and consequent upgrading of medical heart failure therapy often delays further progression to an advanced stage of heart failure. Nevertheless heart failure remains a chronic progressive disease and it is up to the treating clinician to identify the signs of advanced heart failure in a timely manner in order to evaluate patients for further treatment strategies such as heart transplantation. This article should help define advanced heart failure and illustrate how patients are evaluated for further therapy. Outcome of heart transplantation or mechanically assisted circulatory support is strongly associated to proper patient selection and timing.

Benefits of communication skills training after real patient exposure

The established communication skills training (CST) curriculum consists of continuous education, frequent practice with real patients, supervision and feedback from medical teachers. The limitation of this curriculum is that students have to directly apply the theoretical basis they are provided with to real patients. To improve the existing CST curriculum a CST module involving simulated patients was introduced in order to develop more complex communication skills.

Relationship between chronic stress and carotid intima-media thickness (IMT) in elderly Alzheimer's disease caregivers

The stress associated with providing care for a spouse diagnosed with Alzheimer's disease can have adverse effects on cardiovascular health. One potential explanation is that chronic caregiving stress may contribute to the development of atherosclerosis. The purpose of this study was to determine whether the duration that one has provided care is associated with the degree of atherosclerotic burden, as measured by carotid artery intima-media thickness (IMT). One hundred and ten Alzheimer caregivers [mean age 74 ± 8 (SD) years, 69% female] underwent in-home assessment of carotid artery IMT via B-mode ultrasonography. Data regarding medical history, blood pressure, and multiple indicators of caregiving stress were also collected. Multiple regression indicated that duration of care was positively associated with IMT measured in the internal/bifurcation segments of the carotid artery (β = 0.202, p = 0.044) independent of risk factors such as age, gender, body mass index, smoking history, sleep quality, hypertension status, and caregiving stressors. Duration of care was positively associated with IMT in the common carotid artery, but the relationship was not significant. These findings provide more evidence of the link between chronic caregiving stress and cardiovascular disease and indicate that enduring the experience of caregiving over a period of years might be associated with atherosclerotic burden.

[How to assess the nutritional status of my patient]

Protein-energy-malnutrition is a growing problem in industrialised countries. Many studies have found malnourishment in 20-60% of hospitalized medical or surgical patients, as well as out-patients. Malnutrition negatively influences patients' prognosis, immune system, muscle strength, and quality of life. As it is a largely treatable co-morbidity, systematic screening for malnutrition and effective management will improve patient outcomes and reduce healthcare costs. Early diagnosis and assessment depends on a simple and standardised screening tool that identifies at-risk patients, allowing the medical team in charge to solve patients' nutritional problems with an interdisciplinary approach.

E.A.O. guidelines for the use of diagnostic imaging in implant dentistry 2011. A consensus workshop organized by the European Association for Osseointegration at the Medical University of Warsaw

Diagnostics imaging is an essential component of patient selection and treatment planning in oral rehabilitation by means of osseointegrated implants. In 2002, the EAO produced and published guidelines on the use of diagnostic imaging in implant dentistry. Since that time, there have been significant developments in both the application of cone beam computed tomography as well as in the range of surgical and prosthetic applications that can potentially benefit from its use. However, medical exposure to ionizing radiation must always be justified and result in a net benefit to the patient. The as low a dose as is reasonably achievable principle must also be applied taking into account any alternative techniques that might achieve the same objectives. This paper reports on current EAO recommendations arising from a consensus meeting held at the Medical University of Warsaw (2011) to update these guidelines. Radiological considerations are detailed, including justification and optimization, with a special emphasis on the obligations that arise for those who prescribe or undertake such investigations. The paper pays special attention to clinical indications and radiographic diagnostic considerations as well as to future developments and trends.

Patient safety--who cares?

Medical errors and adverse events are a serious threat to patients worldwide. In recent years methodologically sound studies have demonstrated that interventions exist, can be implemented and can have sustainable, measurable positive effects on patient safety. Nonetheless, system-wide progress and adoption of safety practices is slow and evidence of improvements on the organisational and systems level is scarce and ambiguous. This paper reports on the Swiss Patient Safety Conference in 2011 and addresses emerging issues for patient safety and future challenges.

Threats to patient safety in the primary care office: concerns of physicians and nurses

Little is known about primary care professionals' concerns about risks to patient safety.