The cost of monitoring warfarin in patients with chronic atrial fibrillation in primary care in Sweden

BACKGROUND: Warfarin is used for the prevention of stroke in chronic atrial fibrillation. The product has a narrow therapeutic index and to obtain treatment success, patients must be maintained within a given therapeutic range (International Normalised Ratio;INR). To ensure a wise allocation of health care resources, scrutiny of costs associated with various treatments is justified. The objective of this study was to estimate the health care cost of INR controls in patients on warfarin treatment with chronic atrial fibrillation in primary care in Sweden. METHODS: Data from various sources were applied in the analysis. Resource consumption was derived from two observational studies based on electronic patient records and two Delphi-panel studies performed in two and three rounds, respectively. Unit costs were taken from official databases and primary health care centres. RESULTS: The mean cost of one INR control was SEK 550. The mean costs of INR controls during the first three months, the first year and during the second year of treatment were SEK 6,811, SEK 16,244 and SEK 8,904 respectively. CONCLUSION: INR controls of patients on warfarin treatment in primary care in Sweden represent a substantial cost to the health care provider and they are particularly costly when undertaken in home care. The cost may however be off-set by the reduced incidence of stroke

Increasing walking in patients with intermittent claudication: Protocol for a randomised controlled trial

Background: People with intermittent claudication are at increased risk of death from heart attack and stroke compared to matched controls. Surgery for intermittent claudication is for symptom management and does not reduce the risk of cardiovascular morbidity and mortality. Increasing physical activity can reduce claudication symptoms and may improve cardiovascular health. This paper presents the pilot study protocol for a randomised controlled trial to test whether a brief psychological intervention leads to increased physical activity, improvement in quality of life, and a reduction in the demand for surgery, for patients with intermittent claudication. Methods/Design: We aim to recruit 60 patients newly diagnosed with intermittent claudication, who will be randomised into two groups. The control group will receive usual care, and the treatment group will receive usual care and a brief 2-session psychological intervention to modify illness and walking beliefs and develop a walking action plan. The primary outcome will be walking, measured by pedometer. Secondary outcomes will include quality of life and uptake of surgery for symptom management. Participants will be followed up after (a) 4 months, (b) 1 year and (c) 2 years. Discussion: This study will assess the acceptability and efficacy of a brief psychological intervention to increase walking in patients with intermittent claudication, both in terms of the initiation, and maintenance of behaviour change. This is a pilot study, and the results will inform the design of a larger multi-centre trial. Trial Registration: Current Controlled Trials ISRCTN2805187

Hypertension in the very old; prevalence, awareness, treatment and control: a cross-sectional population-based study in a Spanish municipality

<p>Abstract</p> <p>Background</p> <p>Information on hypertension in the very elderly is sparse. Until recently evidence of benefits from pharmacological treatment was inconclusive. We estimated the prevalence of hypertension in subjects aged 80 or more, the proportion of awareness, treatment and control. Explanatory variables associated with good control were also studied.</p> <p>Methods</p> <p>Cross sectional, population-based study, conducted in Martorell, an urban Spanish municipality, in 2005. By simple random sampling from the census, 323 subjects aged 80 or more were included. Patients were visited at home or in the geriatric institution and after giving informed consent, the study variables were collected. These included: supine and standing blood pressure and information about diagnosis and treatment of hypertension. The estimation and 95% confidence interval were obtained and a logistic regression model was used to study explanatory variables associated with blood pressure below 140/90 mm Hg.</p> <p>Results</p> <p>The prevalence of hypertension was 72.8% (95%CI: 69.5 – 76.6%) and 93% of the patients were aware of this condition, of whom 96.3% (95%CI: 93.65 – 97.9%) had been prescribed pharmacological treatment and 30.7% (95%CI: 25.8 – 36.1%) had blood pressure below 140/90 mm Hg. Some of the patients (43%) had one antihypertensive drug and 39.5% had two in combination. Explanatory variables associated with blood pressure below 140/90 mm Hg included prescription of a diuretic, OR: 0.31 (95%CI: 0.14 – 0.66), and history of ischemic heart disease, OR: 0.21 (95%CI: 0.1 – 0.47).</p> <p>Conclusion</p> <p>The prevalence of hypertension in population aged 80 or more was over 70%. Most patients were aware of this condition and they had antihypertensive medication prescribed. Approximately one third of treated patients had blood pressure below 140/90 mm Hg. Patients with heart disease and with diuretics had more frequently blood pressure below this value.</p

Estimating the effectiveness and cost-effectiveness of establishing additional endovascular Thrombectomy stroke Centres in England::a discrete event simulation

Background We have previously modelled that the optimal number of comprehensive stroke centres (CSC) providing endovascular thrombectomy (EVT) in England would be 30 (net 6 new centres). We now estimate the relative effectiveness and cost-effectiveness of increasing the number of centres from 24 to 30. Methods We constructed a discrete event simulation (DES) to estimate the effectiveness and lifetime cost-effectiveness (from a payer perspective) using 1 year’s incidence of stroke in England. 2000 iterations of the simulation were performed comparing baseline 24 centres to 30. Results Of 80,800 patients admitted to hospital with acute stroke/year, 21,740 would be affected by the service reconfiguration. The median time to treatment for eligible early presenters (< 270 min since onset) would reduce from 195 (IQR 155–249) to 165 (IQR 105–224) minutes. Our model predicts reconfiguration would mean an additional 33 independent patients (modified Rankin scale [mRS] 0–1) and 30 fewer dependent/dead patients (mRS 3–6) per year. The net addition of 6 centres generates 190 QALYs (95%CI − 6 to 399) and results in net savings to the healthcare system of £1,864,000/year (95% CI -1,204,000 to £5,017,000). The estimated budget impact was a saving of £980,000 in year 1 and £7.07 million in years 2 to 5. Conclusion Changes in acute stroke service configuration will produce clinical and cost benefits when the time taken for patients to receive treatment is reduced. Benefits are highly likely to be cost saving over 5 years before any capital investment above £8 million is required

Production and perception of situationally variable alarm calls in wild tufted capuchin monkeys (Cebus apella nigritus)

Many mammalian and avian species produce conspicuous vocalizations upon encountering a predator, but vary their calling based on risk urgency and/or predator type. Calls falling into the latter category are termed “functionally referential” if they also elicit predator-appropriate reactions in listeners. Functionally referential alarm calling has been well documented in a number of Old World monkeys and lemurs, but evidence among Neotropical primates is limited. This study investigates the alarm call system of tufted capuchin monkeys (Cebus apella nigritus) by examining responses to predator and snake decoys encountered at various distances (reflecting differences in risk urgency). Observations in natural situations were conducted to determine if predator-associated calls were given in additional contexts. Results indicate the use of three call types. “Barks” are elicited exclusively by aerial threats, but the call most commonly given to terrestrial threats (the “hiccup”) is given in nonpredatory contexts. The rate in which this latter call is produced reflects risk urgency. Playbacks of these two call types indicate that each elicits appropriate antipredator behaviors. The third call type, the “peep,” seems to be specific to terrestrial threats, but it is unknown if the call elicits predator-specific responses. “Barks” are thus functionally referential aerial predator calls, while “hiccups” are better seen as generalized disturbance calls which reflect risk urgency. Further evidence is needed to draw conclusions regarding the “peep.” These results add to the evidence that functionally referential aerial predator alarm calls are ubiquitous in primates, but that noncatarrhine primates use generalized disturbance calls in response to terrestrial threats

A randomized trial to assess the impact of an antithrombotic decision aid in patients with nonvalvular atrial fibrillation: the DAAFI trial protocol [ISRCTN14429643]

BACKGROUND: Decision aids are often advocated as a means to assist patient and health care provider decision making when faced with complicated treatment or screening decisions. Despite an exponential growth in the availability of decision aids in recent years, their impact on long-term treatment decisions and patient adherence is uncertain due to a paucity of rigorous studies. The choice of antithrombotic therapy for nonvalvular atrial fibrillation (NVAF) is one condition for which a trade-off exists between the potential risks and benefits of competing therapies, and the need to involve patients in decision making has been clearly identified. This study will evaluate whether an evidence-based patient decision aid for patients with NVAF can improve the appropriateness of antithrombotic therapy use by patients and their family physicians. DESIGN: A multi-center, two-armed cluster randomized trial based in community family practices in which patients with NVAF will be randomized to decision aid or usual care. Patients will receive one of four decision aids depending on their baseline stroke risk. The primary outcome is the provision of "appropriate antithrombotic therapy" at 3 months to study participants (appropriateness defined as per the 2001 American College of Chest Physicians recommendations for NVAF). In addition, the impact of this decision aid on patient knowledge, decisional conflict, well-being, and adherence will be assessed after 3 months, 6 months, and 12 months

Cancer metabolism: current perspectives and future directions

Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how ‘metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer′s ‘Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells

Innateness as genetic adaptation: Lorenz redivivus (and revised)

In 1965, Konrad Lorenz grounded the innate–acquired distinction in what he believed were the only two possible sources of information that can underlie adaptedness: phylogenetic and individual experience. Phylogenetic experience accumulates in the genome by the process of natural selection. Individual experience is acquired ontogenetically through interacting with the environment during the organism's lifetime. According to Lorenz, the adaptive information underlying innate traits is stored in the genome. Lorenz erred in arguing that genetic adaptation is the only means of accumulating information in phylogenetic (i.e., intergenerational) experience. Cultural adaptation also occurs over a phylogenetic time scale, and cultural tradition is a third source from which adaptive information can be extracted. This paper argues that genetic adaptation can be distinguished from individual and cultural adaptation in a species like Homo sapiens, in which even adaptations with a genetic component require cultural inputs and scaffolding to develop and be expressed. Examination of the way in which innateness is used in science suggests that scientists use the term, as Lorenz suggested, to designate genetic adaptations. The search for innate traits plays an essential role in generating hypotheses in ethology and psychology. In addition, designating a trait as innate establishes important facts that apply at the information-processing level of description

Discovery and progress in our understanding of the regulated secretory pathway in neuroendocrine cells

In this review we start with a historical perspective beginning with the early morphological work done almost 50 years ago. The importance of these pioneering studies is underscored by our brief summary of the key questions addressed by subsequent research into the mechanism of secretion. We then highlight important advances in our understanding of the formation and maturation of neuroendocrine secretory granules, first using in vitro reconstitution systems, then most recently biochemical approaches, and finally genetic manipulations in vitro and in vivo