[Mediterranean or low-fat diets to reduce cardiovascular risk?]. / Mediterrane Ernährung oder fettarme Diät zur Modifikation Kardiovaskulärer Risikofaktoren bei Übergewicht?

This meta-analysis of randomized controlled trials comparing the effects of Mediterranean to low-fat diets in overweight/obese individuals for the modification of cardiovascular risk factors demonstrates the superiority of Mediterranean over low-fat diets in improving control of most cardiovascular risk factors after a follow-up of 2 years. Although the incremental effects of Mediterranean diets on individual cardiovascular risk factors was modest, the consistent benefit over a broad range of established cardiovascular risk factors may result in a reduction of cardiovascular complications.

Volume-controlled vs no/short-term drainage after axillary lymph node dissection in breast cancer surgery: a meta-analysis.

It is unknown whether there are any clinically relevant differences between volume-controlled (<30-50 ml/24h across trials) vs no/short-term drainage after axillary lymph node dissection in breast cancer surgery on outcomes such as seroma formation, wound infection or length of hospital stay. Randomised controlled trials comparing volume-controlled drainage vs no or short-term drainage after axillary lymph node dissection in breast cancer surgery were identified systematically using Pubmed, EMBASE and The Cochrane library. Trial data were reviewed and extracted independently by two reviewers in a standardised unblinded manner. Six randomised controlled trials which included a total of 561 patients fulfilled our inclusion criteria. Patients randomised to volume-controlled drainage were less likely to develop clinically relevant seromas compared to patients randomised to no/short-term drainage. There was, however, no difference in wound infections between patients treated with volume-controlled drainage and patients with no or short-term drainage. Patients randomised to volume-controlled drainage stayed significantly longer in hospital than patients randomised to no/short-term drainage. Based on available evidence, clinically relevant seromas occur more frequently in patients treated with no/short-term drainage. However, no/short-term drainage after axillary lymph node dissection does not lead to an increase in wound infections and is associated with shorter hospital stay.

Primary stenting versus primary balloon angioplasty for treating acute myocardial infarction.

BACKGROUND: Balloon angioplasty following myocardial infarction (MI) reduces death, non-fatal MI and stroke compared to thrombolytic reperfusion. However up to 50% of patients experience restenosis and 3% to 5% recurrent myocardial infarction. Therefore, primary stenting may offer additional benefits compared to balloon angioplasty in patients with acute myocardial infarction. OBJECTIVES: To examine whether primary stenting compared to primary balloon angioplasty reduces clinical outcomes in patients with acute myocardial infarction. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Pascal, Index medicus and The Cochrane Controlled Trials Register (The Cochrane Library) from 1979 to March 2002. SELECTION CRITERIA: Randomised controlled trials of primary stenting or balloon angioplasty prior to the invasive procedure; intervention in native coronary arteries within 24 hours after onset of symptoms of myocardial infarction; report of death or reinfarction; and follow-up of at least 1 month. Trials were excluded when randomisation occurred after an invasive procedure and if they exclusively included patients with cardiogenic shock. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected and extracted data from identified trials. Outcomes included mortality, reinfarction, coronary artery bypass grafting, target vessel revascularization, need for vascular repair or blood transfusion. Peto odds ratios were calculated. To explore the stability of the overall treatment effect various sensitivity analyses were performed. MAIN RESULTS: We included nine trials of 4433 participants. Odds ratios for mortality after stenting compared to balloon angioplasty at 30 days, 6 and 12 months were 1.16 (95% CI 0.78 to 1.73), 1.27 (95% CI 0.89 to 1.83), and 1.06 (95% CI 0.77 to 1.45). At 30 days, 6 and 12 months odds ratios for reinfarction after stenting compared to balloon angioplasty were 0.52 (95% CI 0.31 to 0.87), 0.67 (95% CI 0.45 to 1.00), and 0.67 (95% CI 0.45-0.98) and odds ratio for target vessel revascularization after stenting compared to balloon angioplasty were 0.45 (95%CI 0.34 to 0.60), 0.42 (95% CI 0.35 to 0.51), and 0.47 (95% CI 0.38 to 0.57). The odds ratio for post-interventional bleeding complications after stenting compared to balloon angioplasty was 1.34 (95% CI 0.95 to 1.88; test of heterogeneity p > 0.1). AUTHORS' CONCLUSIONS: There is no evidence to suggest that primary stenting reduces mortality when compared to balloon angioplasty. Stenting seems to be associated with a reduced risk of reinfarction and target vessel revascularization, but potential confounding due to unbalanced post-interventional antithrombotic/anticoagulant therapies can not be ruled out on basis of this review.

Demographics and prevalent risk factors of chronic subdural haematoma: results of a large single-center cohort study.

Chronic subdural haematoma (CSDH) is a typical disease in elderly patients and encountered frequently in neurosurgical practice. With an increasing number of elderly people in the general population, there is a need to investigate risk factors (age, falls, anticoagulant or antithrombotic therapy) which could be pertinent to the development of this disease. We reviewed 354 patients undergoing surgery for CSDH over a period of 7 years (1996-2002), the occurrence being equally distributed over these years. CSDH occurred more often in elderly (> or = 65 years) than in younger people (69 vs 31%), and in men than in women (64 vs 36%). Falls were reported in 77% of patients. There was a trend towards a higher risk of falls in the elderly. Antithrombotic or anticoagulant therapy was present in 41% of patients, 32% of them having had falls. Overall postoperative mortality was 0% and overall recurrence rate 13.6%. CSDH in the elderly population, especially in men, is frequently associated with falls and anticoagulation or antithrombotic therapy. The indication for these medications, especially in elderly patients at risk for falls, should be carefully evaluated and controlled.

Balloon angioplasty versus medical therapy for hypertensive patients with renal artery obstruction.

BACKGROUND: Atherosclerotic renal artery stenosis is the most common cause of secondary hypertension. Balloon angioplasty is widely used for the treatment of hypertensive patients with renal artery stenosis. OBJECTIVES: The objective of this systematic review was to compare the effectiveness of balloon angioplasty (with and without stenting) with medical therapy on blood pressure control, renal function, frequency of renovascular complications, and side effects in hypertensive patients with atherosclerotic renal artery stenosis. SEARCH STRATEGY: The reviewers performed a search of MEDLINE from 1966 to December 2002, EMBASE from 1980 to 2002, Science Citation Index from 1990 to 2002, the Cochrane Central Register of Controlled Trials and personal files to identify randomised controlled trials comparing balloon angioplasty with medical therapy in hypertensive patients with renal artery stenosis. In addition, reference lists of papers resulting from this search were hand-searched, and authors of published trials were contacted to enquire if they were aware of any eligible unpublished trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing balloon angioplasty with medical therapy in hypertensive patients with haemodynamically significant renal artery stenosis (greater than 50 per cent reduction in luminal diameter and minimal follow-up of six months). DATA COLLECTION AND ANALYSIS: Two investigators independently extracted data on trial design, characteristics of trial participants, types of interventions, and outcome measures. The quality of the available data precluded a formal meta-analysis to assess the effect on blood pressure, renal function, and number and defined daily doses of antihypertensive drugs. Peto's odds ratios and corresponding 95% confidence intervals (CI) were calculated for dichotomous outcomes such as the presence or absence of patent vessels and renovascular complications. MAIN RESULTS: Three randomised controlled trials involving 210 patients met the inclusion criteria. In unselected patients there was a consistent, but statistically non significant trend towards lower blood pressure in the balloon angioplasty group. Patients treated with balloon angioplasty required less antihypertensive drugs in two of three trials, and were more likely to have patent renal arteries after 12 months (OR 4.2, 95% CI 1.8 to 9.8). There were no differences in renal function. There were significantly fewer cardiovascular and renovascular complications in patients treated with angioplasty (OR 0.32, 95% CI 0.15 to 0.70, test for heterogeneity p > 0.1). REVIEWER'S CONCLUSIONS: Available data are insufficient to conclude that balloon angioplasty is superior to medical therapy in lowering blood pressure of patients with renal artery stenosis in whom blood pressure can be controlled with medical therapy. In patients with hypertension refractory to medical therapy, there is some weak evidence that balloon angioplasty lowers blood pressure more effectively than medical therapy. Balloon angioplasty appears to be safe and leads to fewer cardiovascular and renovascular complications. There is a need for randomised controlled trials comparing the effect of balloon angioplasty and medical therapy on the preservation of renal function in the long term.

A case-management program of medium intensity does not improve cardiovascular risk factor control in coronary artery disease patients: the Heartcare I trial.

BACKGROUND: Case-management programs for secondary prevention of coronary artery disease that utilize extensive resources can reduce cardiovascular risk factors, but less intensive approaches have failed to show benefits. This randomized trial evaluated whether a medium intensity case-management program improves risk factor control in patients with coronary artery disease. METHODS: We assigned 201 consecutive patients hospitalized for acute coronary events in the intensive care unit of University Hospital, Basel, Switzerland, to either a risk factor case-management program (n = 99) or care as usual (n = 102) using the patients' primary care physicians as the unit of randomization (cluster randomization). The case-management program consisted of an hour of counseling by a clinician during hospitalization and two short reminders by phone and mail 3 and 6 months later. Treatment decisions were left to patients and their primary care physicians. RESULTS: After 9 and 18 months of follow-up, there were no significant differences in lipid values, blood pressure control, fasting blood glucose, body-mass index, or number of smokers between the two groups. However, significantly more patients in the intervention group than in the care as usual group achieved target cholesterol values after 18 months (48% versus 27%, P = 0.002 and remained significant after Bonferroni-Holms correction) but not after 9 months of follow-up (31% versus 27%, P >0.2). CONCLUSION: This hospital-based case-management and outreach program, limited to counseling by a clinician, did not substantially improve cardiovascular risk factor control among patients hospitalized for coronary events.

Systematic, immediate in-hospital initiation of lipid-lowering drugs during acute coronary events improves lipid control.

Background: Patients who have had a coronary heart attack often go completely untreated for hypercholesterolemia. We investigated whether immediate initiation of lipid-lowering drugs during hospitalization for acute coronary events increases the proportion of correctly treated patients compared to referred treatment as recommended by current guidelines. Methods: This prospective, multicenter study randomized 57 hypercholesterolemic patients hospitalized for acute coronary events to immediate in-hospital initiation or to referred initiation of lipid-lowering drugs by primary care physicians 3 months after unsuccessful nutritional intervention. Results: After 6 months, 53 patients were available for follow-up. More patients in the immediate initiation group (26/30 patients, 87%) were treated with lipid-lowering drugs than in the referred initiation-group (13/23 patients, 57%, P=0.03). Twenty-seven patients (87%) in the immediate initiation group versus 17 patients (65%) in the referred initiation group had a 10% or greater decrease in total cholesterol or a 15% or greater decrease in LDL-cholesterol (P=0.18). Although statistically not significant, there was a trend to improved lipid values in the immediate initiation group compared to the referred initiation group (TC, -21.1 vs. -13.8% (P=0.08); LDL-C, -28.2 vs. -18.9% (P=0.13); HDL-C, +10.8 vs. +5% (P=0.44); TC/HDL-C ratio, -24.7 vs. -15.1% (P=0.22)), and the LDL-C/HDL-C ratio was -34.1 vs. -19.1% (P=0.04, P=NS after Bonferroni correction). Conclusion: The immediate initiation of lipid-lowering drugs in hypercholesterolemic patients hospitalized for acute coronary events increases the rate of correctly treated patients and has the potential to improve lipid control.

Comparison of self-reported home blood pressure measurements with automatically stored values and ambulatory blood pressure.

AIMS: To evaluate accuracy of patient-reported home blood pressure measurements (HBPM) when compared to real HBPM and their agreement with 12-h daytime ambulatory blood pressure monitoring (ABPM). MAJOR FINDINGS: Self-reported HBPM were compared to stored values of a fully automated, oscillometric blood pressure monitor with integrated memory device and 12-h daytime ambulatory monitoring in 54 patients. In most patients (n = 46, 85%) mean reported systolic or diastolic versus real HBPM differed by no more than 4 mmHg. In eight mostly uneducated patients (15%, 95% confidence interval, CI, 7-27%) means of reported and real HBPM differed by more than 4 mmHg (range 5-28 mmHg for systolic and 0-11 mmHg for diastolic blood pressure). Systolic agreement between self-reported HBPM and 12-h daytime ABPM was better for patients reporting > or = 80% than for patients reporting < 80% of measurements correctly (mean systolic difference 0 +/- 19 versus 5 +/- 14 mmHg, respectively), whereas the opposite was true concerning agreement of diastolic blood pressure values (mean diastolic difference -6 +/- 10 and -1 +/- 9 mmHg, respectively). CONCLUSION: Inadequate conclusions due to poor reporting accuracy of HBPM are possible, especially in less educated patients. Thus, ABPM or automatically stored HBPM may be preferable to self-reported HBPM in these patients.

[What is the evidence with regard to the effectiveness of orlistat?]. / Wie steht es um die Evidenz bezüglich der Wirksamkeit von Orlistat?

BACKGROUND: Obesity is worldwide one of today's most important medical and public health problems. Orlistat (Xenical) is a relatively new drug in the pharmacological treatment of obesity which partially blocks fat absorption. The following article analyses the available evidence of orlistat's effectiveness in the treatment of obese patients. METHODS: Three randomised controlled trials investigating the effect of orlistat in the treatment of obesity were identified by systematic Medline search. The internal and external validity of these studies was assessed using systematic criteria. RESULTS: All three studies consistently demonstrate a treatment benefit of orlistat compared to placebo. Patients treated with orlistat lost an average of 3.4 kg more than patients taking placebo while on a hypocaloric diet. Simultaneously, control of cardiovascular risk factors improved independently of the observed weight loss. Up to 40% of all patients experienced gastrointestinal side effects which were generally well tolerated. The studies prove that treatment with orlistat can result in a moderate weight reduction. However, the results of the studies cannot be easily generalised to obese patients in a primary care setting, due to limitations concerning the studies' internal and external validity. CONCLUSIONS: Based on these studies orlistat is an efficient pharmacological treatment for obesity in patients adhering to a hypocaloric diet. Studies demonstrating orlistat's effectiveness in a primary care setting are so far lacking. From a public health perspective there is a need for a randomised controlled trial showing not only orlistat's effectiveness on surrogate markers in a primary care setting but, ideally, a reduction in obesity-related mortality and morbidity.

Histopathological differences between temporary and permanent threshold shift.

The structural changes associated with noise-induced temporary threshold shift (TTS) were compared to the damage associated with permanent threshold shift (PTS). A within-animal paradigm involving survival-fixation was used to minimize problems with data interpretation from interanimal variability in response to noise. Auditory brainstem response thresholds for clicks and tone pips were determined pre- and 1-2 h post-exposure in 11 chinchillas. The animals were exposed for 24 h to an octave band of noise with a center frequency of 4 kHz and a sound pressure level of 86 dB. Three animals (0/0-day) had both cochleas terminal-fixed 2-3 h post-exposure. Two animals (27/27-day) had threshold shifts determined every other day for 1 week, every week thereafter, and underwent terminal-fixation of both cochleas 27 days after exposure. Six animals (0/n-day) had threshold shifts determined in both ears upon removal from the noise; their left cochlea was then survival-fixed 2-3 h post-exposure. Threshold shifts were determined in their right ear every 2-3 days until their hearing either returned to pre-exposure values or stabilized at a reduced level at which time their right cochlea was terminal-fixed (4-13 days post-exposure). All cochleas were prepared as plastic-embedded flat preparations. Missing hair cells were counted and supporting cells and nerve fibers were evaluated throughout the organ of Corti using phase-contrast microscopy. Post-exposure, all animals had moderate TTSs in their left and right ears which averaged 43 dB for 4-12 kHz. In the 0/0-day animals, the only abnormality which correlated with TTS was a buckling of the pillar bodies. In the 0/n-day animals, their left cochlea (survival-fixed 2-3 h post-exposure) had outer hair cell (OHC) stereocilia which were not embedded in the tectorial membrane in the region of the TTS whereas OHC stereocilia were embedded in the tectorial membrane throughout the cochleas of non-noise-exposed, survival-fixed controls. Three of six right cochleas (terminal-fixed 4-13 days post-exposure) from the 0/n-day animals developed a PTS and two of these cochleas had focal losses of inner and outer hair cells and afferent nerve fibers at the corresponding frequency location. The other cochlea with PTS had buckled pillars in the corresponding frequency region. These results suggest that with moderate levels of noise exposure, buckling of the supporting cells results in an uncoupling of the OHC stereocilia from the tectorial membrane which results in a TTS. The mechanisms resulting in TTS appear to be distinct from those that produce permanent hair cell damage and a PTS.

Survival-fixation of the cochlea: a technique for following time-dependent degeneration and repair in noise-exposed chinchillas.

To minimize problems with data interpretation due to interanimal variation in susceptibility to noise, we developed a survival-fixation paradigm which involves fixing one cochlea of an experimental chinchilla at one post-exposure time and fixing the second cochlea as much as 14-24 days later. This paradigm is analytically effective because there is a high correlation in the magnitude and pattern of damage in the left and right cochleas of binaurally exposed animals. Thus, each experimental animal provides two snapshots in the degeneration and repair continua in which it can be certain that both cochleas sustained equivalent amounts of damage during the exposure. Using this technique, the time course of degeneration of different structures and cells in the organ of Corti can be determined and primary damage can be distinguished from secondary effects. The present paper discusses the issues which had to be addressed to develop this technique and provides preliminary results from chinchillas exposed to a traumatic noise.

Aspects of the molecular structure and dynamics of neuropeptide Y.

Human neuropeptide Y (hNPY) and the Q34-->P34 mutant (P34-hNPY) have been characterized by CD spectroscopy. hNPY self-associates in aqueous solution with a dimerization constant in the micromolar range. The self-association correlates with an increase in secondary-structure content which was studied as a function of concentration, temperature and pH. The effects of temperature were measured in water (5-84 degrees C) and in ethanediol/water (2 : 1) (-90 degrees to +90 degrees C). A single-residue mutation, Q34-->P34, affects the pH, thermal and self-association properties of NPY. The CD results are correlated with photochemically induced dynamic nuclear polarization NMR experiments which show that the tyrosines at the interface between two monomer units present limited accessibility to a photoreactive dye. An equilibrium state is described, involving a PP-fold monomer form and a handshake dimer form, that accommodates the physicochemical properties of NPY.

[Lipid lowering therapy: new pathophysiologic aspects and clinical implications]. / Lipidsenkung: neue pathophysiologische Aspekte und klinische Implikationen.

Lipid-lowering therapy reduces cardiovascular morbidity and mortality. Although atherosclerotic plaques regress under lipid-lowering therapy, only minor changes in arteriosclerotic plaques are angiographically detectable. These changes cannot fully explain all the benefits of lipid-lowering therapy. Additional factors independent of macroscopically detectable alterations in plaque size may contribute to the clinical effects of lipid-lowering therapy. Qualitative changes in the composition of atherosclerotic plaques may reduce the risk of subsequent plaque rupture. Furthermore, hypercholesterolemia is associated with endothelial dysfunction, i.e., impaired endothelium-mediated vasodilation, induction of adhesion molecules, and altered expression of growth factors. Lipid lowering seems to reverse endothelial dysfunction. Also, lipid-lowering therapy may reduce peripheral arterial resistance and hyperinsulinemia, and may improve erythrocyte deformability. These effects of lipid-lowering therapy may contribute to the clinical benefits. In particular, the concept of endothelial dysfunction as a first, reversible manifestation of target organ damage deserves further attention in the diagnosis and therapy of cardiovascular disease.