Statins for cardiovascular prevention according to different strategies: a cost analysis.

Background: Several studies have shown that treatment with HMG-CoA reductase inhibitors (statins) can reduce coronary heart disease (CHD) rates. However, the cost effectiveness of statin treatment in the primary prevention of CHD has not been fully established. Objective: To estimate the costs of CHD prevention using statins in Switzerland according to different guidelines, over a 10-year period. Methods: The overall 10-year costs, costs of one CHD death averted, and of 1 year without CHD were computed for the European Society of Cardiology (ESC), the International Atherosclerosis Society (IAS), and the US Adult Treatment Panel III (ATP-III) guidelines. Sensitivity analysis was performed by varying number of CHD events prevented and costs of treatment. Results: Using an inflation rate of medical costs of 3%, a single yearly consultation, a single total cholesterol measurement per year, and a generic statin, the overall 10-year costs of the ESC, IAS, and ATP-III strategies were 2.2, 3.4, and 4.1 billion Swiss francs (SwF [SwF1 = $US0.97]). In this scenario, the average cost for 1 year of life gained was SwF352, SwF421, and SwF485 thousand, respectively, and it was always higher in women than in men. In men, the average cost for 1 year of life without CHD was SwF30.7, SwF42.5, and SwF51.9 thousand for the ESC, IAS, and ATP-III strategies, respectively, and decreased with age. Statin drug costs represented between 45% and 68% of the overall preventive cost. Changing the cost of statins, inflation rates, or number of fatal and non-fatal cases of CHD averted showed ESC guidelines to be the most cost effective. Conclusion: The cost of CHD prevention using statins depends on the guidelines used. The ESC guidelines appear to yield the lowest costs per year of life gained free of CHD.

Structural macro factors and the affine term structure of interest rates

This work consists of three essays investigating the ability of structural macroeconomic models to price zero coupon U.S. government bonds. 1. A small scale 3 factor DSGE model implying constant term premium is able to provide reasonable a fit for the term structure only at the expense of the persistence parameters of the structural shocks. The test of the structural model against one that has constant but unrestricted prices of risk parameters shows that the exogenous prices of risk-model is only weakly preferred. We provide an MLE based variance-covariance matrix of the Metropolis Proposal Density that improves convergence speeds in MCMC chains. 2. Affine in observable macro-variables, prices of risk specification is excessively flexible and provides term-structure fit without significantly altering the structural parameters. The exogenous component of the SDF is separating the macro part of the model from the term structure and the good term structure fit has as a driving force an extremely volatile SDF and an implied average short rate that is inexplicable. We conclude that the no arbitrage restrictions do not suffice to temper the SDF, thus there is need for more restrictions. We introduce a penalty-function methodology that proves useful in showing that affine prices of risk specifications are able to reconcile stable macro-dynamics with good term structure fit and a plausible SDF. 3. The level factor is reproduced most importantly by the preference shock to which it is strongly and positively related but technology and monetary shocks, with negative loadings, are also contributing to its replication. The slope factor is only related to the monetary policy shocks and it is poorly explained. We find that there are gains in in- and out-of-sample forecast of consumption and inflation if term structure information is used in a time varying hybrid prices of risk setting. In-sample yield forecast are better in models with non-stationary shocks for the period 1982-1988. After this period, time varying market price of risk models provide better in-sample forecasts. For the period 2005-2008, out of sample forecast of consumption and inflation are better if term structure information is incorporated in the DSGE model but yields are better forecasted by a pure macro DSGE model.

PulseCath iVAC 3LTM hemodynamic performance for simple assisted flow.

The PulseCath iVAC 3L? left ventricular assist device is an option to treat transitory left heart failure or dysfunction post-cardiac surgery. Assisted blood flow should reach up to 3 l/min. In the present in vitro model exact pump flow, depending on various frequencies and afterload was examined. Optimal flow was achieved with inflation/deflation frequencies of about 70-80/min. The maximal flow rate was achieved at about 2.5 l/min with a minimal afterload of 22 mmHg. Handling of the device was easy due to the connection to a standard intra-aortic balloon pump console. With increasing afterload (up to a simulated mean systemic pressure of 66 mmHg) flow rate and cardiac support are in some extent limited.

Resting metabolic rate and protein turnover in apparently healthy elderly Gambian men.

Body composition, resting energy expenditure (REE), and whole body protein metabolism were studied in 26 young and 28 elderly Gambian men matched for body mass index during the dry season in a rural village in The Gambia. REE was measured by indirect calorimetry (hood system) in the fasting state and after five successive meals. Rates of whole body nitrogen flux, protein synthesis, and protein breakdown were determined in the fed state from the level of isotopic enrichment of urinary ammonia over a period of 12 h after a single oral dose of [15N]glycine. Expressed in absolute value, REE was significantly lower in the elderly compared with the young group (3.21 +/- 0.07 vs. 4.04 +/- 0.07 kJ/min, P < 0.001) and when adjusted to body weight (3.29 +/- 0.05 vs. 3.96 +/- 0.05 kJ/min, P < 0.0001) and fat-free mass (FFM; 3.38 +/- 0.01 vs. 3.87 +/- 0.01 kJ/min, P < 0.0001). The rate of protein synthesis averaged 207 +/- 13 g protein/day in the elderly and 230 +/- 13 g protein/day in the young group, whereas protein breakdown averaged 184 +/- 13 g protein/day in the elderly and 203 +/- 13 g protein/day in the young group (nonsignificant). When values were adjusted for body weight or FFM, they did not reveal any difference between the two groups. It is concluded that the reduced REE adjusted for body composition observed in elderly Gambian men is not explained by a decrease in protein turnover.

Reduction of small infrarenal abdominal aortic aneurysm expansion rate by statins.

BACKGROUND: To evaluate the effect of statins on the annual expansion rate (ER) of small infrarenal abdominal aortic aneurysms (AAA). PATIENTS AND METHODS: All patients under regular surveillance for small AAA between January 2000 and September 2007, in the Department of Angiology, Lausanne University Hospital, were included. Inclusion criteria were baseline abdominal aortic diameter between 25 and 55 mm, at least two measurements of AAA diameter and a minimum follow up of 6 months. Patients with Marfan disease, infectious or inflammatory AAA, and patients with prior AAA repair were excluded. The influence of statin use and other factors on ER were examined by bivariate and multivariate analysis. RESULTS: Among 589 patients who underwent an abdominal aorta evaluation, 94 patients (89 % men, mean age 69.1 years) were finally included in the analysis. Baseline AAA size was 39.9 ± 7.7 mm (mean±SE) and 48.7 ± 8.4 mm at end of follow-up. Patients had a regular aneurysm size assessment during 38.5 ± 27.7 months. Mean ER was 3.59 mm/y (± 2.81). The 50 patients who were treated with statin during the study period had a lower ER compared to the 44 controls (2.91 vs 4.37 mm/year, p = 0.01). CONCLUSIONS: This study confirms the considerable individual variations in the AAA expansion rate, and emphasizes the need for regular aortic diameter assessments. In this study, patients treated with statin demonstrate a significant decrease in the ER compared to controls. This finding need to be evaluated in prospective interventional studies powered to demonstrate the potential benefit of statin treatment.

Stochastic demography and the neutral substitution rate in class-structured populations.

The neutral rate of allelic substitution is analyzed for a class-structured population subject to a stationary stochastic demographic process. The substitution rate is shown to be generally equal to the effective mutation rate, and under overlapping generations it can be expressed as the effective mutation rate in newborns when measured in units of average generation time. With uniform mutation rate across classes the substitution rate reduces to the mutation rate.

Pregnancy-related changes in activity energy expenditure and resting metabolic rate in Switzerland.

BACKGROUND/OBJECTIVES: To measure resting metabolic rate (RMR), activity energy expenditure (AEE), total energy expenditure (TEE) and physical activity pattern, that is, duration and intensity (in metabolic equivalents, METs) of activities performed in late pregnancy compared with postpartum in healthy, well-nourished women living in Switzerland. SUBJECTS/METHODS: Weight, height, RMR, AEE, TEE and physical activity patterns were measured longitudinally in 27 healthy women aged 23-40 years at 38.2+/-1.5 weeks of gestation and 40.0+/-7.2 weeks postpartum. RESULTS: The RMR during late pregnancy was 7480 kJ per day, that is, 1320+/-760 kJ per day (21.4%) higher than the postpartum RMR (P<0.001). Absolute changes in RMR were positively correlated with the corresponding changes in body weight (r=0.61, P<0.001). RMR per kg body weight was similar in late pregnancy vs postpartum (P=0.28). AEE per kg during pregnancy and postpartum was 40+/-13 and 50+/-20 kJ/kg, respectively (P=0.001). There were significant differences in daily time spent at METs<1.5 (1067 vs 998 min, P=0.045), at 2.5< or =METs <3.0 (58 vs 82 min, P=0.002) and METs> or =6 (1 vs 6 min, P=0.014) during pregnancy and postpartum, respectively. CONCLUSIONS: Energy expenditure in healthy women living in Switzerland increases in pregnancy compared with the postpartum state. Additional energy expenditure is primarily attributed to an increase in RMR, which is partly compensated by a decrease in AEE. The decrease in physical activity-related energy costs is achieved by selecting less demanding activities and should be taken into account when defining extra energy requirements for late pregnancy in Switzerland.

Parental heart rate variability during pediatric consultation

OBJECTIVE: Research regarding communication between pediatricians and parents in pediatric consultation has mainly focused on parental satisfaction, on its influence on compliance and on communication techniques used by pediatricians. However, there is paucity in research regarding parental stress levels during pediatric consultation. Therefore, the aim of our study was to measure parental heart rate variability related as a measure of stress levels during pediatric consultation. METHODS: Video recordings with simultaneous monitoring and recording of parental heart rate were obtained from 38 pediatric consultations in the ambulatory or hospital setting of the department of pediatrics (HFR, Fribourg, Switzerland). Pulse variation was measured every 5 seconds and heart rate variability (increase or decrease were analyzed) in relation to various sections of the consultation. RESULTS: Heart rate significantly decreased at the end of the consultation compared to the beginning of the consultation (p= 0.0567). In addition, heart rate significantly decreased at the beginning of clinical examination (p= 0.0476) compared to psychosocial history taking. During the discussion of laboratory findings and diagnosis, heart rate was significantly elevated compared to the discussion of the prognosis (p=0.0505). CONCLUSION: We conclude that pediatric consultation has a significant impact on parental stress levels shown by parental heart variability. In general, it can be shown that stress levels significantly decrease at the end of the consultation compared to the beginning of the consultation. In addition, stress levels decrease at the beginning of clinical examination and increase during psychosocial history taking and discussion of laboratory findings and diagnosis. Therefore, our findings highlight the importance of a thorough consultation which include a comprehensive clinical examination with special care taken regarding psychosocial issues and information given regarding the diagnosis.

Change in individual growth rate and its link to gill-net fishing in two sympatric whitefish species

Size-selective fishing is expected to affect traits such as individual growth rate, but the relationship between the fishery-linked selection differentials and the corresponding phenotypic changes is not well understood. We analysed a 25-year monitoring survey of sympatric populations of the two Alpine whitefish Coregonus albellus and C. fatioi. We determined the fishing-induced selection differentials on growth rates, the actual change of growth rates over time, and potential indicators of reproductive strategies that may change over time. We found marked declines in adult growth rate and significant selection differentials that may partly explain the observed declines. However, when comparing the two sympatric species, the selection differentials on adult growth were stronger in C. albellus while the decline in adult growth rate seemed more pronounced in C. fatioi. Moreover, the selection differential on juvenile growth was significant in C. albellus but not in C. fatioi, while a significant reduction in juvenile growth over the last 25 years was only found in C. fatioi. Our results suggest that size-selective fishing affects the genetics for individual growth in these whitefish, and that the link between selection differentials and phenotypic changes is influenced by species-specific factors.

Confounding effects of heart rate on pulse wave velocity in paced patients with a low degree of atherosclerosis.

BACKGROUND: Pulse wave velocity (PWV), an index of arterial wall stiffness, is modulated by blood pressure (BP). Whether heart rate (HR) is also a modulator of PWV is controversial. Recent research involving mainly patients with high aortic PWV have found either no change or a positive correlation between the two. Given that PWV is increasingly being measured in cardiovascular studies, the relationship between HR and PWV should be known in patients with preserved arterial wall elasticity. OBJECTIVE: The aim of this study was to evaluate the importance of HR as a determinant of the variability in PWV in patients with a low degree of atherosclerosis. DESIGN AND METHODS: Fourteen patients (five female, nine male; aged 68 +/- 8 years) were evaluated post pacemaker implantation due to sick sinus or carotid hypersensitivity syndromes. Carotid-femoral PWV was measured at rest and during atrial pacing at 80, 90 and 100 bpm (paced HR). Arterial femoral blood flow (AFBF) was measured by echodoppler. RESULTS: PWV increased from 6.2 +/- 1.5 m/s (mean +/- SD) during resting sinus rhythm (HR 62 +/- 8 bpm; mean +/- SD) to 6.8 +/- 1.0, 7.0 +/- 0.9, and 7.6 +/- 1.1 m/s at pacing rates of 80, 90 and 100 bpm, respectively (P < 0.0001). Systolic (SBP) and mean blood pressure (MBP) remained constant at all HR levels, whereas AFBF increased in a linear fashion. CONCLUSIONS: These results demonstrate that even in patients with a low degree of atherosclerosis, HR is a potential modulator of carotid-femoral PWV.

The difference between the basal metabolic rate and the sleeping metabolic rate in Japanese.

Previous studies have demonstrated the difference between the basal metabolic rate (BMR) and the sleeping metabolic rate (SMR): however, the difference in the Japanese population has not yet been explored. This study examined the relationship between the BMR and SMR in ninety-four healthy Japanese subjects (37 males and 57 females, 39 +/- 12 y of age and 22.0 +/- 7.4% body fat) in a respiratory chamber. The SMR was significantly lower than the BMR (1416 +/- 245 vs. 1492 +/- 256 kcal/d): however, there was a highly significant correlation between the two (r = 0.867; p < 0.001). The ratio of SMR/BMR largely varied among individuals (0.95 +/-0.08, 8.4% of the coefficient of variation). The ratio was significantly lower in males than in females (0.93 +/- 0.10 vs. 0.97 +/- 0.06, p < 0.05). None of the anthropometric measures (age, weight, body mass index, body surface area or percent body fat) correlated with the ratio. These results showed that SMR was 95%, of BMR on average in a healthy Japanese group. However, when applied over a longer time period (24 h or more), the difference tends to become negligible for most analyses in a group. Although the difference between SMR and BMR will induce a 5% gap of physical activity level defined as the total energy expenditure divided by the BMR or SMR, this factor seems to have little practical importance in epidemiological research.

Anaesthesia for electroconvulsive therapy: time for a change?

Introduction: Electroconvulsive therapy (ECT) may be used to treat severe depression and needs a specific general anaesthesia. Important cardiovascular changes occur during the ECT with a parasympathetic induced bradycardia followed by a sympathetic response. A dedicated protocol was designed 6 years ago. The goal of this study was to analyse the management of anaesthesia for ECT in our institution, the adherence to the protocol and the occurrence of adverse events during anaesthesia. Methods: After Institutional Ethics Committee approval, we conducted a retrospective analysis of our anaesthesia protocol for patients scheduled for electroshock therapy during a five years period (2004- 2008). The protocol includes administration of atropine subcutaneously 30 minutes before the procedure, followed by general anaesthesia induced with etomidate (0.2 mg/kg). Suxamethonium (1 mg/kg) is administered after the inflation of a pneumatic tourniquet on the opposite arm, in order to observe the electroshocks convulsive effects. The psychiatrist initiates the convulsive crisis once curarisation is achieved. Face mask ventilation is then applied during the post-ictal phase with closed blood pressure monitoring. : 228 ECT were performed in 25 patients. The median dosage of etomidate was 0.37 mg/kg and suxamethonium 1.20 mg/kg. Hypertension during the ECT procedure was present in 62.7% of cases, tachycardia 23.2% and bradycardia 10.5%. Esmolol was administered in 73.4% of hypertensive patients in a range of 0 to 30 mg. The protocol was followed in half of the cases in regards to atropine administration (50.4%). We observed a significant increase of hypertension (73.9%, p = 0.001) after atropine administration, without effect on heart rate. Conclusions: The management of anaesthesia for ECT is specific and follows a predefined protocol in our institution. Adherence to our protocol was poor. Adverse events are frequent and significant association between the administration of atropine and the incidence of hypertension as well as poor protocol adherence implies reconsideration of our anaesthesia protocol for electroconvulsive therapy and better quality control of the clinical practice.

Estimation of glomerular filtration rate in hospitalised patients: are we overestimating renal function?

QUESTIONS UNDER STUDY AND PRINCIPLES: Estimating glomerular filtration rate (GFR) in hospitalised patients with chronic kidney disease (CKD) is important for drug prescription but it remains a difficult task. The purpose of this study was to investigate the reliability of selected algorithms based on serum creatinine, cystatin C and beta-trace protein to estimate GFR and the potential added advantage of measuring muscle mass by bioimpedance. In a prospective unselected group of patients hospitalised in a general internal medicine ward with CKD, GFR was evaluated using inulin clearance as the gold standard and the algorithms of Cockcroft, MDRD, Larsson (cystatin C), White (beta-trace) and MacDonald (creatinine and muscle mass by bioimpedance). 69 patients were included in the study. Median age (interquartile range) was 80 years (73-83); weight 74.7 kg (67.0-85.6), appendicular lean mass 19.1 kg (14.9-22.3), serum creatinine 126 μmol/l (100-149), cystatin C 1.45 mg/l (1.19-1.90), beta-trace protein 1.17 mg/l (0.99-1.53) and GFR measured by inulin 30.9 ml/min (22.0-43.3). The errors in the estimation of GFR and the area under the ROC curves (95% confidence interval) relative to inulin were respectively: Cockcroft 14.3 ml/min (5.55-23.2) and 0.68 (0.55-0.81), MDRD 16.3 ml/min (6.4-27.5) and 0.76 (0.64-0.87), Larsson 12.8 ml/min (4.50-25.3) and 0.82 (0.72-0.92), White 17.6 ml/min (11.5-31.5) and 0.75 (0.63-0.87), MacDonald 32.2 ml/min (13.9-45.4) and 0.65 (0.52-0.78). Currently used algorithms overestimate GFR in hospitalised patients with CKD. As a consequence eGFR targeted prescriptions of renal-cleared drugs, might expose patients to overdosing. The best results were obtained with the Larsson algorithm. The determination of muscle mass by bioimpedance did not provide significant contributions.