How Are the Interests of Incapacitated Research Participants Protected through Legislation? An Italian Study on Legal Agency for Dementia Patients

Patients with dementia may have limited capacity to give informed consent to participate in clinical research. One possible way to safeguard the patients' interests in research is the involvement of a proxy in the recruitment process. In Italy, the system of proxy is determined by the courts. In this study we evaluate the timing for appointment of a legal proxy in Italy and identify predictive variables of appointment.Subjects were recruited among the outpatients seeking medical advice for cognitive complaints at the Centre for Research and Treatment of Cognitive Dysfunctions, University of Milan, "Luigi Sacco" Hospital. The Centre was participating to the AdCare Study, a no-profit randomised clinical trial coordinated by the Italian National Institute of Health. The requirement that informed consent be given by a legal representative dramatically slowed down the recruitment process in AdCare, which was prematurely interrupted. The Centre for Research and Treatment of Cognitive Dysfunctions collected data on the timing required to appoint the legal representatives. Patients diagnosed with dementia and their caregivers were provided information on the Italian law on legal agency (law 6/2004). At each scheduled check-up the caregiver was asked whether she/he had applied to appoint a legal proxy for the patient and the time interval between the presentation of the law, the registration of the application at the law court chancellery and the sentence of appointment was registered. The study involved 169 demented patients. Seventy-eight patients (46.2%) applied to appoint a legal proxy. These subjects were usually younger, had been suffering from dementia for a longer time, had less than two children and made more use of memantine. The mean interval time between the presentation of the law and the patients' application to the law court chancellery was two months. The mean interval time between the patient's application to the law court chancellery and the sentence of appointment was four months.In Italy the requirement that legal representatives be appointed by the courts slows down subjects' participation in research. Other procedures for legal agency of the incapacitated patients may be adopted, taking as examples other EU countries' systems

Views on primary prevention of cardiovascular disease - an interview study with Swedish GPs

Background: General practitioners (GPs) have gradually become more involved in the prevention of cardiovascular disease (CVD), both through more frequent prescribing of pharmaceuticals and by giving advice regarding lifestyle factors. Most general practitioners are now faced with decisions about pharmaceutical or non-pharmaceutical treatment for primary prevention every day. The aim of this study was to explore, structure and describe the views on primary prevention of cardiovascular disease in clinical practice among Swedish GPs. Methods: Individual interviews were conducted with 21 GPs in southern Sweden. The interview transcripts were analysed using a qualitative approach, inspired by phenomenography. Results: Two main categories of description emerged during the analysis. One was the degree of reliance on research data regarding the predictability of real risk and the opportunities for primary prevention of CVD. The other was the allocation of responsibility between the patient and the doctor. The GPs showed different views, from being convinced of an actual and predictable risk for the individual to strongly doubting it; from relying firmly on protection from disease by pharmaceutical treatment to strongly questioning its effectiveness in individual cases; and from reliance on prevention of disease by non-pharmaceutical interventions to a total lack of reliance on such measures. Conclusions: The GPs' different views, regarding the rationale for and practical management of primary prevention of CVD, can be interpreted as a reflection of the complexity of patient counselling in primary prevention in clinical practice. The findings have implications for development and implementation of standard treatment guidelines, regarding long-time primary preventive treatment

Language, Truth, and Logic and the Anglophone reception of the Vienna Circle

A. J. Ayer’s Language, Truth, and Logic had been responsible for introducing the Vienna Circle’s ideas, developed within a Germanophone framework, to an Anglophone readership. Inevitably, this migration from one context to another resulted in the alteration of some of the concepts being transmitted. Such alterations have served to facilitate a number of false impressions of Logical Empiricism from which recent scholarship still tries to recover. In this paper, I will attempt to point to the ways in which LTL has helped to foster the various mistaken stereotypes about Logical Empiricism which were combined into the received view. I will begin by examining Ayer’s all too brief presentation of an Anglocentric lineage for his ideas. This lineage, as we shall see, simply omits the major 19th century Germanophone influences on the rise of analytic philosophy. The Germanophone ideas he presents are selectively introduced into an Anglophone context, and directed towards various concerns that arose within that context. I will focus on the differences between Carnap’s version of the overcoming of metaphysics, and Ayer’s reconfiguration into what he calls the elimination of metaphysics. Having discussed the above, I will very briefly outline the consequences that Ayer’s radicalisation of the Vienna Circle’s doctrines had on the subsequent Anglophone reception of Logical Empiricism

Add-on topiramate reduces weight in overweight patients with affective disorders: a clinical case series

BACKGROUND: The weight-gain caused by many psychotropic drugs is a major cause for poor compliance with such medications and could also increase cardio-vascular morbidity among psychiatric patients. Recent reports have shown that the anticonvulsant topiramate causes weight loss in various patient groups. The drug has also shown effectiveness in open trials as a mood stabilizer in patients with affective disorders, but not in controlled trials in the acute treatment of mania. We used topiramate to treat 12 patients with affective disorders who had a body-mass index >30 kg/m(2). METHODS: Topiramate was prescribed as part of our routine clinical practice, as an add-on medication, or as a replacement of a mood stabilizer. Patients' weight was recorded in 1 to 2 monthly intervals. Patients were followed up for between 6 and 12 months. The final dose of topiramate varied from 200 to 600 mg/day. RESULTS: Topiramate was effective in reducing the weight in 10 out of the 12 patients. At six months the 12 patients had lost a mean of 7.75 kg (SD = 6.9 kg, p < 0.001) and at 12 months 9 patients had lost a mean of 9.61 kg (SD = 6.7 kg, p = 0.003). Three patients stopped the treatment: one due to side effects, one due to possible side effects, and one suffered a manic relapse and showed no sustained weight loss. There were no other clear changes in the course of illness of the patients. CONCLUSION: The evidence of a strong weight-reducing potential of topiramate is indisputable and clinically significant. Topiramate could be considered in the treatment of bipolar patients who are overweight, or whose concerns about weight gain compromise their compliance with long-term prophylactic medication. So far there is no evidence that topiramate has anti-manic effect and it should not be used as monotherapy

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R0-resected gastric adenocarcinomas and non-cancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n=175), whereas only 56% of gastric cancer specimens showed CAR positivity (P<0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor

A Flat Universe from High-Resolution Maps of the Cosmic Microwave Background Radiation

The blackbody radiation left over from the Big Bang has been transformed by the expansion of the Universe into the nearly isotropic 2.73K Cosmic Microwave Background. Tiny inhomogeneities in the early Universe left their imprint on the microwave background in the form of small anisotropies in its temperature. These anisotropies contain information about basic cosmological parameters, particularly the total energy density and curvature of the universe. Here we report the first images of resolved structure in the microwave background anisotropies over a significant part of the sky. Maps at four frequencies clearly distinguish the microwave background from foreground emission. We compute the angular power spectrum of the microwave background, and find a peak at Legendre multipole $\ell_{peak}=(197 \pm 6)$, with an amplitude $DT_{200}=(69 \pm 8)\mu K$. This is consistent with that expected for cold dark matter models in a flat (euclidean) Universe, as favoured by standard inflationary scenarios

Aberrant Herpesvirus-Induced Polyadenylation Correlates With Cellular Messenger RNA Destruction

Inhibition of host cell gene expression by the human herpesvirus KSHV occurs via a novel mechanism involving polyadenylation-linked RNA turnover