Jorma Lahtela

Cholesterol-Lowering Drugs and Prostate Cancer Risk: A Population-based Case-Control Study

Background: Previous studies have shown that statin use may reduce prostate cancer risk. In the current study, we evaluated the association between serum cholesterol–lowering medication use and prostate cancer risk at the population level. Materials and Methods: All newly diagnosed prostate cancer cases in Finland during 1995 to 2002 and matched controls (24,723 case control pairs) were identified from the Finnish Cancer Registry and the Population Register Center, respectively. Detailed information on cholesterol-lowering drug purchases during the study period was obtained from the prescription database of the Social Insurance Institution of Finland. Results: After adjustment for potential confounders, having ever-use of any statin was associated with marginally elevated overall prostate cancer risk [odds ratio (OR), 1.07; 95% confidence interval (95% CI), 1.00-1.16]. However, none of the statins was associated with the overall prostate cancer risk when analyzed separately. On the other hand, the risk of advanced prostate cancer was decreased among users of atorvastatin, lovastatin, and simvastatin (OR 0.61, 95% CI 0.37-0.98; OR 0.61, 95% CI 0.43-0.85; and OR 0.78, 95% CI 0.61-1.01, respectively). The risk was not affected among users of other cholesterol drug groups. Conclusions: Our large population-based study showed no evidence for reduced overall prostate cancer risk among users of cholesterol-lowering drugs, whereas the risk of advanced cancer was decreased among statin users. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2226–32)

Self-reported non-severe hypoglycaemic events in Europe.

Hypoglycaemia presents a barrier to optimum diabetes management but data are limited on the frequency of hypoglycaemia incidents outside of clinical trials. The present study investigated the rates of self‐reported non‐severe hypoglycaemic events, hypoglycaemia awareness and physician discussion of events in people with Type 1 diabetes mellitus or insulin‐treated Type 2 diabetes mellitus.

Antidiabetic Medication and Prostate Cancer Risk: A Population-based Case-Control Study

Decreased risk of prostate cancer in diabetic men has been reported. The authors evaluated the association between antidiabetic medication use and prostate cancer at the population level. All incident prostate cancer cases in Finland during 1995-2002 were identified from the Finnish Cancer Registry. Matched controls were provided by the Population Register Center (24,723 case-control pairs). Information on medication use was obtained from a comprehensive prescription database. Multivariable-adjusted odds ratios were computed by using conditional logistic regression. The authors found that prostate cancer risk was decreased for antidiabetic medication users (odds ratio = 0.87, 95% confidence interval: 0.82, 0.92). The decrease was observed for most drug groups. The odds ratio decreased in a dose-dependent fashion by quantity of use. Duration of antidiabetic treatment was inversely associated with overall prostate cancer risk and risk of advanced cancer. Similar risk reduction for users of different antidiabetic drugs suggests that diabetes, instead of the medication itself, is behind the association. This finding is unlikely to be secondary because of differential uptake of the prostate-specific antigen test or different prostate-specific antigen levels between medication users and nonusers; prevalence of testing in Finland is low. Dose and time dependency of the relation probably indicates that duration of diabetes is negatively associated with risk.

Statins and prostate cancer prevention: where we are now, and future directions

Statins are cholesterol-lowering drugs that are widely used to prevent and treat atherosclerotic cardiovascular disease. Recent research from both in vitro and in vivo studies suggests that there is an association between the use of statins and a reduction in the incidence of and mortality from prostate cancer. Several mechanisms of action that might bring about these beneficial effects of statins have been proposed, most of which include direct effects of statins on intracellular signaling. In this Review we discuss the current knowledge on the use of statins to prevent prostate cancer. We will also look at future directions for clinical research on this topic.

Analysis of cardiovascular responses to passive head‐up tilt using continuous pulse wave analysis and impedance cardiography

Objective. To non‐invasively measure central haemodynamics, arterial stiffness, cardiac function and vascular resistance, with the subject in the supine position and during head‐up tilt, in order to examine the haemodynamic changes associated with alterations in the augmentation index, and to investigate repeatability and reproducibility of the measurement protocol. Material and methods. Thirty‐three healthy volunteers (21–51 years) were investigated using continuous pulse wave analysis from the radial artery with a tonometric sensor, whole‐body impedance cardiography and plethysmographic blood pressure (BP) recordings from the fingers. The measurements were performed with the subject supine and during passive head‐up tilt, and repeated during the same session and on four separate days. Results. During the head‐up tilt, diastolic BP (5.2±0.6 %), heart rate (27.6±1.9 %) and vascular resistance (12.5±1.7 %) increased (all p<0.05), while systolic BP (−3.2±0.6 %), aortic pulse pressure (−23.3±1.4 %), augmentation index (−11.6±0.7 %), aortic reflection time (−7.0±1.0 %), ejection duration (−21.4±0.7 %), stroke volume (−26.1±1.2 %) and cardiac output (−5.0±1.5 %) decreased (all p<0.05). Augmentation index at rest correlated with aortic systolic BP (r = 0.423), aortic reflection time (r = −0.647), pulse wave velocity (r = 0.287) and age (r = 0.480). The change in augmentation index during head‐up tilt correlated with the change in aortic systolic BP (r = 0.469), aortic pulse pressure (r = 0.606), ejection duration (r = 0.374) and heart rate (r = −0.445). According to Bland‐Altman and repeatability index analyses, repeatability and reproducibility of the measurements were good during the same session and on separate days. Conclusions. Combined pulse wave analysis and impedance cardiography with the subject in the supine position and during head‐up tilt is a repeatable and reproducible method for comprehensive investigation of the cardiovascular function.

Assessment of causes of death in a prostate cancer screening trial

Accurate assessment of the causes of death is crucial for a conclusive evaluation of the ongoing prostate cancer screening trials. Here, we report the validity of the official causes of death as compared with an independent expert review in the Finnish prostate cancer screening trial. Because nearly 80,000 men were involved, death‐cause evaluation was restricted to men diagnosed for prostate cancer. Medical charts were retrieved and the cause of death was assigned by an expert review panel for all deaths among men with prostate cancer during the study period, 1996–2003. The panel decision was compared with both death certificates and the official causes of death as assigned by Statistics Finland. Of a total of 315 deaths, the review panel attributed 127 (41%) to prostate cancer and 184 (59%) to other causes, the corresponding figures in death certificates being 124 (40%) and 187 (60%). Four cases were excluded because of insufficient information. The death‐certificate data were in agreement with the panels assessment in 305 out of 311 cases (overall agreement 97.7%, κ = 0.95). The overall agreement between the official causes of death and the panels decision was 97.4% (304/311, κ = 0.95). The sensitivity of the certificates in identifying prostate cancer deaths was 96.1% (panel as golden standard). Correspondingly, specificity was 98.9%. The official causes of death thus provide an accurate means for evaluating disease‐specific mortality in a large population‐based prostate‐cancer screening trial in Finland.

Effects of patient-reported non-severe hypoglycemia on healthcare resource use, work-time loss, and wellbeing in insulin-treated patients with diabetes in seven European countries.

Abstract Purpose: Hypoglycemia is a frequent side effect induced by insulin treatment of type 1 (T1DM) and type 2 diabetes (T2DM). Limited data exist on the associated healthcare resource use and patient impact of hypoglycemia, particularly at a country-specific level. This study investigated the effects of self-reported non-severe hypoglycemic events (NSHE) on use of healthcare resources and patient wellbeing. Methods: Patients with T1DM or insulin-treated T2DM diabetes from seven European countries were invited to complete four weekly questionnaires. Data were collected on patient demographics, NSHE occurrence in the last 7 days, hypoglycemia-related resource use, and patient impact. NSHE were defined as events with hypoglycemia symptoms, with or without blood glucose measurement, or low blood glucose measurement without symptoms, which the patient could manage without third-party assistance. Results: Three thousand, nine hundred and fifty-nine respondents completed at least one wave of the survey, with 57% completing all four questionnaires; 3827 respondents were used for data analyses. Overall, 2.3% and 8.9% of NSHE in patients with T1DM and T2DM, respectively, resulted in healthcare professional contact. Across countries, there was a mean increase in blood glucose test use of 3.0 tests in the week following a NSHE. Among respondents who were employed (48%), loss of work-time after the last hypoglycemic event was reported for 9.7% of NSHE. Overall, 10.2% (daytime) and 8.0% (nocturnal) NSHE led to work-time loss, with a mean loss of 84.3 (daytime) and 169.6 (nocturnal) minutes among patients reporting work-time loss. Additionally, patients reported feeling tired, irritable, and having negative feelings following hypoglycemia. Limitations: Direct comparisons between studies must be interpreted with caution because of different definitions of hypoglycemia severity, duration of the studies, and methods of data collection. Conclusions: NSHE were associated with use of extra healthcare resources and work-time loss in all countries studied, suggesting that NSHE have considerable impact on patients/society.

The Effect of Zoledronic Acid on the Clinical Resolution of Charcot Neuroarthropathy: A pilot randomized controlled trial

OBJECTIVE To investigate the clinical efficacy of zoledronic acid in patients with diabetes and acute Charcot neuroarthropathy. RESEARCH DESIGN AND METHODS Thirty-nine consecutive patients were randomly assigned to placebo or three intravenous infusions of 4 mg zoledronic acid. The primary outcome was clinical resolution of acute Charcot neuroarthropathy determined by total immobilization time (casting plus orthosis). RESULTS At baseline, there was no significant difference between the randomly assigned groups with respect to Charcot disease activity or other baseline values. In the zoledronic acid group, the median time for total immobilization was 27 weeks (range 10–62), and in the placebo group it was 20 weeks (20–52) (P = 0.02). CONCLUSIONS Zoledronic acid had no beneficial effect on the clinical resolution of acute Charcot neuroarthropathy in terms of total immobilization time. It is possible that it may prolong the time to clinical resolution of Charcot neuroarthropathy.

Serum N‐terminal atrial natriuretic peptide in adult patients late after surgical repair of atrial septal defect

The purpose of surgical closure of atrial septal defect (ASD) is to relieve the cardiovascular system from a haemodynamic burden. Excessive amounts of atrial peptides are released in congestive heart failure, valvular diseases and congenital heart diseases.

The Finnish trial of prostate cancer screening: where are we now?

P. FINNE*†, U.-H. STENMAN*, L. MÄÄTTÄNEN‡, T. MÄKINEN§, T.L.J. TAMMELA§, P. MARTIKAINEN¶, M. RUUTU**, M. ALA-OPAS**, J. ARO**, P.J. KARHUNEN††, J. LAHTELA‡‡, P. RISSANEN†, H. JUUSELA§§, M. HAKAMA†‡ and A. AUVINEN† *Department of Clinical Chemistry, University of Helsinki, Helsinki, †School of Public Health and ††Department of Forensic Medicine and Research Unit of Clinical Chemistry, University of Tampere, ‡Finnish Cancer Registry, Helsinki, §Division of Urology, ¶Department of Pathology, Centre for Laboratory Medicine, and ‡‡Department of Internal Medicine, Tampere University Hospital, Tampere, and **Departments of Urology, and §§Surgery, Jorvi Hospital, Helsinki University Central Hospital, Helsinki, Finland