Cost-effectiveness of primary prevention of coronary heart disease through risk factor intervention in 60-year-old men from the county of Stockholm--a stochastic model of exercise and dietary advice

BACKGROUND: Recent screenings show a high prevalence of cardiovascular risk factors in the county of Stockholm. Primary prevention may be a way to lower the risk burden of coronary heart disease, but we must establish that preventive programs are cost-effective. METHODS: Through the use of a stochastic Markov model, which predicts reduction in coronary heart disease events based on risk factor reductions, this study evaluates the results of a previous controlled trial in middle-aged men comparing dietary advice, exercise, and the combination of both applied to an observed cohort of 60-year-old men in the county of Stockholm. RESULTS: The model predicts lower costs and higher effectiveness for dietary advice compared to the alternatives. Assuming a declining effect of the intervention, dietary advice saves 0.0228 life-years compared to no intervention. If no decline is assumed, the corresponding figure is 0.0997 life-years. From the societal perspective, the added costs are 2,892 Swedish Kronor (SEK) and 14,106 SEK for the two modeling assumptions, resulting in a cost-effectiveness of 127,065 SEK per life-year gained (LYG) and 141,555 SEK/LYG. These figures are below what is generally thought of as cost-effective. CONCLUSION: Based on the model, dietary advice appears to be the most cost-effective of the studied interventions.     

Effects of ejaculation by penile vibratory stimulation on bladder capacity in men with spinal cord lesions

PURPOSE: We examined the effects of ejaculation by penile vibratory stimulation on bladder capacity in men with spinal cord lesions. MATERIAL AND METHODS: Included in our study were 14 men with spinal cord lesions from C4 to T7 with detrusor hyperreflexia. Cystometry was performed before and immediately after ejaculation by penile vibratory stimulation to establish baseline conditions and repeated after 1 month of ejaculation by penile vibratory stimulation every third day. The third cystometry study was done after 1 month of ejaculation by penile vibratory stimulation every third day at home to determine any long-term effects of treatment. This third cystometry was performed 72 hours after the last ejaculation to exclude any acute effects of ejaculation by penile vibratory stimulation on detrusor hyperreflexia. In addition, 1 to 3 days later ejaculation was induced by penile vibratory stimulation and immediately followed by cystometry to examine whether it was possible to achieve an acute effect as well as a potential long-term effect. RESULTS: Baseline urodynamic investigations revealed bladder hyperreflexia and external sphincter dyssynergia in all individuals. There was no statistically significant difference in bladder capacity at leak point before and immediately after ejaculation by penile vibratory stimulation. However, after 4 weeks of frequent penile vibratory stimulation treatment bladder capacity at leak point increased significantly from a median of 190 ml. (range 17 to 700) at baseline to 293 (range 30 to 700) (Wilcoxon signed rank test p = 0.03). Furthermore, there was a trend toward decreased intravesical pressure during the filling phase. CONCLUSIONS: Ejaculation by penile vibratory stimulation was associated with a significant increase in bladder capacity at leak point after 4 weeks of frequent treatment. This finding may have implications in the management of incontinence in men with spinal cord lesions.     

Training-induced changes in neural function

Adaptive changes can occur in the nervous system in response to training. Electromyography studies have indicated adaptation mechanisms that may contribute to an increased efferent neuronal outflow with training, including increases in maximal firing frequency, increased excitability and decreased presynaptic inhibition of spinal motor neurons, and downregulation of inhibitory pathways.     

Secular trends in acute myocardial infarction in relation to physical activity in the general Danish population

Secular trends in AMI rates were analyzed in relation to physical activity levels. The population attributable risk of physical inactivity was calculated. Participants were randomly selected subjects from a suburb of Copenhagen, Denmark, screened during the years 1964-1991. Occupational physical activity and in leisure time were assessed 1964, 1974, 1976, 1982, 1987 and 1991 by self-administered questionnaire along with smoking habits and alcohol consumption. Blood pressure, weight, height and serum lipids were measured according to WHO-standards. Mortality data were obtained from death certificates, from hospital records or autopsies. Acute myocardial infarctions (AMI) 1964-1994 were included. 13.925 men and women aged 30, 40, 50 and 60 years, were drawn as random samples from a background population of 300.000 inhabitants. A cohort born in 1914 was examined in 1964 and 1974, a cohort born in 1936, was examined in 1976 and 1987; Monica (Monitoring trends and determinants in cardiovascular diseases) I cohort were examined in 1982 and 1987; MONICA II in 1986, and MONICA III in 1991. Mean physical activity level at leisure adjusted for age and sex increased over time (P < 0001). 25% of the men were sedentary, and more women reported a sedentary lifestyle than men. The overall trend was from 1964 to 1992 a decline in physical activity at work (P < 0001) in both gender and all age groups. The difference in AMI incidence rates between leisure time physical activity (LTPA) levels increased over time. No change was found in AMI rates comparing sedentary in different time periods. A remarkable decrease over time in the AMI incidence rate was found in physically active during leisure time. Population attributable risk (PAR) exceeded 40% in both genders in the late 1980s. In conclusion the difference in AMI rates between LTPA subgroups has increased over time. The low AMI rates observed among the most physically active reveal a substantial potential for the prevention of AMI through physical activity. A population attributable risk of more than 40% for physical inactivity suggests a potential for primary prevention through increased physical activity.     

Decreased cerebrospinal fluid acetylcholinesterase in patients with subcortical ischemic vascular dementia

The main objective was to investigate the acetylcholinesterase E (AChE) activity in the cerebrospinal fluid (CSF) of patients with three common dementia disorders. We also wanted to investigate the influence of apolipoprotein E (ApoE) epsilon4 allele possession and CSF-tau level on the CSF-AChE activity in these patients. The study included 17 consecutive patients with subcortical vascular dementia (SVD), 39 with Alzheimer's disease (AD), 14 with frontotemporal dementia (FTD) and 12 controls. CSF was obtained by lumbar puncture and CSF-AChE activity was measured by an enzyme antigen immunoassay. CSF-AchE activity was significantly decreased compared to controls only in the SVD group (p = 0.010). The CSF-tau level was increased in the AD group compared to the control (p < 0.01) and FTD groups (p < 0.05). No influence of ApoE epsilon4 allele possession on CSF-AChE activity was found. It is suggested that abnormal CSF-AChE activity in patients with SVD reflects a disturbance in the cholinergic system.     

Meniscectomy leads to an early increase in subchondral bone plate thickness in the rabbit knee

We evaluated morphological changes in the tibial bone after meniscectomy in a rabbit model. 15 rabbits subjected to a medial meniscectomy in the right knee and a sham-operation in the left. Histomorphometric parameters were evaluated in the subchondral bone plate and the underlying trabecular bone, 13, 25 and 40 weeks after surgery. 5 rabbits were used as unoperated controls. Meniscectomized knees had a thicker subchondral bone plate than sham-operated contralateral ones in 13 of the 15 rabbits (p = 0.01), but the trabecular bone showed no morphological differences. The meniscectomized knees of these rabbits developed mild osteoarthrosis, described elsewhere, which may have been partly due to a change in the mechanical properties of the thickened subchondral bone plate. Our findings suggest that the first bony response after meniscectomy occurs in the subchondral bone plate rather than in the trabecular bone.     

Effects of immediate switch from cyclosporine microemulsion to tacrolimus at first acute rejection in renal allograft recipients

BACKGROUND: A number of institutions have reported favorable results in renal transplant patients after conversion from cyclosporine (CsA) to tacrolimus at the time of acute rejection, but no prospective, controlled study has been performed to date. Here, we report the first randomized study comparing patients whose therapy was changed at a first episode of acute rejection to tacrolimus with those who were maintained on CsA microemulsion (ME). METHODS: This 3-month, prospective, open, multicenter, parallel-group study was conducted at 15 centers in seven European countries. In total, 119 renal graft recipients experiencing a first biopsy-proven acute rejection episode while receiving CsA-ME were randomized (1:1) to start tacrolimus-based therapy (n=61) or to continue CsA-ME-based therapy (n=58). RESULTS: Baseline characteristics were comparable for both groups. The initial rejection episode responded to steroid treatment in 93.4% (tacrolimus) and 63.8% (CsA-ME) (P=0.001), respectively. In patients at risk, the incidence of recurrent rejection events within 3 months was significantly lower with tacrolimus therapy (5/57, 8.8%) compared with CsA-ME therapy (15/44, 34.1%) (P=0.002). Patient and graft survival were similar in both study groups 3 months after randomization. The most frequently reported adverse events were increased serum creatinine (29.5% vs. 22.4%), hypertension (24.6% vs. 22.4%), and urinary tract infection (18.0% vs. 20.7%) for tacrolimus versus CsA-ME. Tremor was more common in tacrolimus treated-patients (17.4% vs. 2.1%, P=0.011). CONCLUSIONS: Early conversion to tacrolimus therapy benefited the resolution of acute rejection episodes and significantly reduced the risk of recurrent rejection compared with continuation of CsA-ME.     

C2 monitoring in maintenance renal transplant recipients: is it worthwhile?

Presently, there is little knowledge regarding cyclosporine (CsA) concentration at 2 hr post-dose (C2) monitoring in maintenance patients. This study evaluates the actual C2 range in stable renal transplant recipients (who underwent transplantation >12 months ago). In addition, we investigated whether underexposure or overexposure to CsA (assessed by C2) affects graft function (as measured by serum [S]-creatinine). All renal transplant recipients in Norway receiving CsA were asked to participate; 1447 fulfilled the criteria. Valid C2 and CsA trough concentration (C0) measurements were performed in 1032 renal transplant recipients (71%) monitored by C0. Target C0 level was 75 to 125 mumol/L. CsA levels were measured using a Cloned Enzyme Donor Immunoassay method, and all analyses were performed in the same laboratory (overall mean [+/-standard deviation] CsA C0=112+/-31 mug/L, CsA C2=697+/-211 mug/L [range 81-1580 mug/L], CsA dose [mg/day]=208+/-61, CsA dose [mg/kg/day]=2.8+/-1.1, and S-creatinine=141+/-58 mumol/L). A univariate analysis of variance showed that patients with C2 levels between 700 and 800 mug/L (n=203, S-creatinine=136+/-49 mumol/L) had significantly lower S-creatinine levels compared with patients with C2 levels greater than 950 mug/L (n=94, S-creatinine=152+/-56 mumol/L) (P<0.02). The same was true for patients with C2 levels less than 450 mug/L (n=95, S-creatinine 141+/-72 mumol/L) (P<0.05) when compared with patients with C2 levels greater than 950 mug/L. There was no significant difference in S-creatinine between patients in the low and intermediate C2 group; 666 patients had C0 levels in the therapeutic range (75-125 mumol/L). A linear regression showed a significant relation between S-creatinine and C2 for these patients (P=0.03). The corresponding relation between S-creatinine and C0 was nonsignificant (P=0.3). Monitoring of C2 in maintenance patients is a valuable tool to detect overexposure to CsA. Until results from prospective studies are available, we recommend C0 in the therapeutic range and reduction in CsA in overexposed patients, aiming at a C2 value between 700 and 800 mug/L.     

Genetic counselling for cancer and risk perception

The main aim was to investigate risk perception and psychological distress in individuals attending genetic counselling. A consecutive series of 86 individuals with a diagnosis and/or family history of breast, ovarian or colorectal cancer was included. Risk assessments were performed before and immediately after genetic counselling and at a one-year follow-up. Psychological distress was assessed 1 week before, and 6 weeks, 6 months and 1 year after genetic counselling. The number of individuals who correctly-estimated the general risk in the population increased significantly from 35%, before to 82% after counselling (p < 0.001). One year later, data on general risk estimates showed a significant reduction of the number of correct estimations to 51%, compared with directly after the counselling (p < 0.005). In total, 54% estimated their own lifetime risk correctly after the counselling, compared with 17% before (p < 0.001) (those with a cancer diagnosis estimated the risk of their children developing cancer). One year later, the number of correct estimations had dropped to 28%. Before the counselling, the majority of the participants overestimated both the general risk and their own/children's risk. The participants experienced moderate levels of psychological distress before the counselling and a decrease of anxiety afterwards (p < 0.02). However, half of the participants reported moderate or high distress. There were no differences in psychological distress between those who estimated their risk/ children's risk as low, moderate or high or between those who over-, under- or correctly estimated their own/children's risk. Further investigations are needed to develop and adjust the risk information provided to the individual in order to avoid misunderstanding, especially as this information is going to be revealed to family members Counselling support should be offered to those individuals who experience psychological distress.