Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke. Meta-analysis of randomized trials.

OBJECTIVE: To estimate the relative risk reduction of the clinical outcomes (coronary events, strokes, cardiovascular, non-cardiovascular and all-cause mortality) associated with statin therapy in primary and secondary prevention. DATA SOURCES: A literature search of the Medline and Cohrane databases for articles published from 1985 to July 2002 was performed. The data on systematic reviews and preliminary reports were also included in this study. Primary and secondary prevention trials and regression trials were eligible. DATA EXTRACTION AND STATISTICAL METHOD: Data were extracted by 2 authors according to the defined inclusion criteria. Disagreements were resolved by consensus or by a third reviewer. Testing for heterogeneity was applied and on the basis of these results a fixed effect model or a random effect model was used for calculation of relative risk values (RR) and 95% confidence intervals (95% CI). Sensitivity analysis tested the impact of the individual study--duration of study, type of statin therapy and study size. The number of patients needed to treat was calculated as an absolute measure of clinical effectiveness of statin therapy when appropriate. RESULTS: Data from 15 trials with 63,410 participants and mean duration of treatment of 3.6 years, were included in this overview. Tests for heterogeneity showed that the variability between study estimates is sufficiently small to assume that they are estimating the same underlying treatment effect. Statin therapy was associated with a 22% reduction in total cholesterol, 29% reduction in LDL cholesterol, 12% reduction in triglycerides and 6% increase in HDL cholesterol. Overall (primary and secondary studies) statin therapy significantly reduces relative risk of coronary events (RR, 0.73, 95% CI, 0.68, 0.77, *p < 0.0001), relative risk of cardiovascular disease mortality (RR, 0.78, 95% CI, 0.73, 0.84, *p < 0.0001), relative risk of non-fatal stroke (RR, 0.74, 95% CI, 0.67, 0.82, *p < 0.0001), relative risk of total (fatal and non-fatal) stroke (RR, 0.77, 95% CI, 0.70, 0.84, *p < 0.001) and relative risk of all-cause death (RR, 0.85, 95% CI, 0.81, 0.89, *p < 0.0001). There was a slight and insignificant reduction of relative risk in non-cardiovascular mortality (RR, 0.94, 95% CI, 0.86, 1.03, p = 0.1677) and fatal strokes (RR, 0.86, 95% CI, 0.70, 1.07, p = 0.1912). Sensitivity analysis showed the robustness of our results for all outcomes. The results were not altered if an individual study was removed from meta-analysis. CONCLUSIONS: This overview indicates that statin treatment reduces the relative risk of occurrence of coronary events, cardiovascular disease mortality, non-fatal strokes and all-cause mortality. While secondary prevention with statins provides considerable improvement of cardiovascular morbidity/mortality, primary prevention with statins provides only small and clinically hardly relevant improvement of cardiovascular morbidity/mortality.

Inventory of regulations and analysis techniques for trace elements in some water supply companies in eastern and western Europe.

With the ultimate objective in contributing to the improvement of the quality control of drinking water and to facilitate the checking of its compliance with the respective regulations, an inventory of analytical techniques used in water supply companies in Eastern and Western European countries is presented. The existing regulations for drinking water and bottled mineral water quality with respect to trace elements in these countries are compared to regulations of the World Health Organisation. The data obtained can be useful for further harmonisation of the respective regulations in Europe.

Therapy of opportunistic infections.

Opportunistic infections are becoming really or apparently more frequent because of improved diagnostic techniques, increased age of the people in the developed world, better medical therapy, and higher number of patients living with transplanted organs and on immunosuppressive and glucocorticoid therapy, and also because of AIDS pandemic. Prevention of bacterial, fungal and viral infections includes classical preventive measures, surveillance, and education of patients and medical personnel. Vaccination is important especially to prevent viral diseases and also some bacterial ones. Routine antibiotic prophylaxis decreases some surgical infections. Meticulous follow-up of immunocompromised patients and specific anti-infective therapy saves the patients' lives in non-fatal diseases and prolongs the life in AIDS patients.

Subcutaneous erythropoietin in the treatment of renal anaemia.

Erythropoietin was applied subcutaneously to 49 patients, 41 have been treated by hemodialysis, 3 by continuous ambulatory peritoneal-dialysis, 5 had chronic progressive renal failure. Mean initial dose of erythropoietin was 139.4 U/kg/week and maintenance dose 115.9 U/kg/week. In 43% of patients serum ferritin was decreasing during treatment, and in 20% it was low before the commencing of the treatment. During erythropoietin therapy vitamin B12 was decreasing in 22% of the patients, and the substitution was necessary in 18%. Only in 1 patient it was necessary to substitute also folic acid. There were no nonresponders among erythropoietin treated patients. Elevation of blood pressure was observed in half of the patients, hypertensive encephalopathy in 1, and thrombosis of arterio-venous fistula in 3.

Inhibition of complement activation with EDTA in vivo during sham hemodialysis.

To check whether in vivo EDTA prevents complement activation resulting from blood contact with the dialyzer membrane, sham hemodialysis (HD) was performed in seven healthy volunteers using Cuprophan hollow-fiber dialyzers. Blood samples were drawn from the arterial and venous blood lines of the dialyzer before and after EDTA was infused into the arterial line. Venous line plasma C3a concentrations before EDTA infusion were significantly higher than after EDTA. Also, venous line plasma C3a concentrations before and after EDTA infusion were significantly higher than in the arterial line. These results indicate that complement activation can be attenuated by EDTA during sham HD. Technical improvements in the procedure may permit complete inhibition of complement activation.

Urodynamic modeling of norfloxacin pharmacokinetics by means of computer simulation.

Urodynamic model was developed which, in conjunction with a compartmental pharmacokinetic model, was used for study of factors influencing drug concentrations in urine: urine flow rate, residual bladder urine, maximal bladder urine, stage of renal failure, and elimination kinetics of drugs. Norfloxacin (NOR) was used as a model drug, although the model haw general applicability for all urinary antiseptics. Pharmacokinetic data were obtained from a clinical study in which norfloxacin was administered orally as a single 400mg dose to four subjects with installed urine catheters. Sample of blood, bladder and catheter urine were collected and concentrations of NOR measured by a HPCL method. Modeling was performed on analog--hybrid computer EAI 580. Besides the fitting of model response to obtained in vivo data, simulations of expected clinical situations were performed in which the interplay of above mentioned factors was studied in terms of urine concentrations profiles. NOR treatment with 400mg b.i.d. secured sufficient urine concentrations in most studied cases. This approach should be applied for corresponding study of other urinary antiseptics, especially those with less favourable urinary levels.

Beta 2-microglobulin elimination characteristics during hemofiltration with acrylonitrile and polysulfone membrane hemofilters.

Elimination characteristics of beta 2-microglobulin (BMG) during hemofiltration (HF) with acrylonitrile (AN69) and polysulfone (PS) hemofilters were investigated in a prospective clinical investigation. Seven chronic uremics on regular HF were treated for 4 weeks, three times a week, with AN69 hemofilters. The study was then repeated with PS hemofilters. There were no significant differences in the patients' body weight, the ultrafiltrate volume per session, and the duration of each HF session between both treatments. At the start of HF, arterial plasma concentration of BMG was (for AN69) 33.5 +/- 4.0 mg/L (mean +/- SD) and (for PS) 35.8 +/- 6.5 mg/L (NS); at the end of HF it was (for AN69) 11.0 +/- 1.8 mg/L and (for PS) 17.5 +/- 4.2 mg/L (p less than 0.001). The amount of BMG in total ultrafiltrate was (for AN69) 179.3 +/- 22.6 mg and (for PS) 140.6 +/- 26.8 mg (p less than 0.02). With AN69 hemofilter, maximum BMG plasma clearance and sieving coefficient were 51.0 +/- 9.5 mL/min and 0.42 +/- 0.04 at 60 minutes. With PS hemofilter, maximum BMG plasma clearance and sieving coefficient were 37.4 +/- 5.7 mL/min and 0.27 +/- 0.03 at 15 minutes. Twenty-two percents of BMG entering the AN69 hemofilter at 15 minutes were adsorbed on the membrane (p less than 0.001). BMG elimination with the AN69 hemofilter was more efficient than with the PS hemofilter. Long-term studies will be necessary to demonstrate whether this difference is of any clinical significance.

Anaphylatoxins C3a and C5a adsorption on acrylonitrile membrane of hollow-fiber and plate dialyzer--an in vivo study.

We studied the adsorption of anaphylatoxins C3a and C5a on acrylonitrile (AN69) hollow-fiber (AN69HF) and plate (AN69P) dialyzers in 8 patients during 4-hour hemodialyses (HD). Blood passed first through a cuprophan dialyzer and then through AN69 dialyzers that were not in contact with dialysis fluid. Plasma C3a and C5a were measured in samples taken from the afferent and efferent blood lines of the acrylonitrile dialyzers at 15, 60 and 240 min. Plasma C3a concentrations decreased significantly in blood that had passed through AN69 dialyzers. This decrease, indicating membrane adsorption, was maximal (by 65% in AN69HF and by 59% in AN69P) at 15 min and minimal (by 53% in AN69HF and by 18% in AN69P) at 240 min. The decrease in plasma C5a concentrations was smaller and significant throughout HD only with AN69HF. The amount of C3a adsorbed was at least 45,000 micrograms in AN69HF and 18,000 micrograms in AN69P. These findings demonstrate that acrylonitrile dialyzers adsorb more C3a and C5a than they produce. This membrane adsorption may explain why the increase of plasma C3a and C5a is inhibited during HD.

Computer simulation of ciprofloxacin pharmacokinetics in patients on CAPD.

Continuous ambulatory peritoneal dialysis (CAPD) has become an accepted alternative to chronic hemodialysis in the treatment of end-stage renal disease. The method utilizes the diffusion of drugs from the blood through the peritoneal membrane to the peritoneal cavity if administered intravenously (IV) and perorally (PO) and in the opposite direction if applied intraperitoneally (IP). The present work uses an open, two-compartment pharmacokinetic model reversibly linked with the compartment representing the peritoneal cavity and an analog-hybrid computer to simulate drug levels in sampled and unsampled compartments under conditions of various routes of administration (IV, IP and sequential IV, IP and PO) and different clinical status (presence and absence of peritonitis). The drug chosen for simulation was ciprofloxacin (CIP), a new synthetic antibacterial agent of the 4-quinolone group. Eight patients were included in the study, and CIP concentrations in plasma and dialysate were obtained by HPLC analysis to assess the reliability of the model and the efficiency of the sequential dosing scheme. CIP plasma and dialysate levels were adequate for the majority of microbes causing CAPD peritonitis. The proposed regimen was efficient in 85% of cases.

[Kidney transplantation in the treatment of patients with end-stage renal failure]. / Transplantacija ledvic kot nadomestno zdravljenje bolnikov s koncno ledvicno odpovedjo.

Renal transplantation has become an acceptable mode of therapy for patients with end-stage renal failure since the early 1960s. Retrospective study was done to analyze clinical results od 126 patients who received either living related or cadaveric kidney. The cumulative graft survival rate was 90% one year and 80% four years after living related kidney transplantation. The corresponding patient survival rate was 96% one year and 94% four years after transplantation. There were no significant differences in graft and patient survival regarding mode of immunosuppressive therapy. In cadaveric kidney transplantation graft survival after one year was 78% and patient survival ranged at 98%. Our results are comparable to those of other centers and we think renal transplantation is adequate therapy for most patients with end-stage renal disease.