Search

Background: Historically, there has been a general resistance to treating onychomycosis on the basis that such treatments were protracted and of uncertain outcome. However, modern treatments act more promptly and reliably., Objectives: To carry out a meta-analysis to evaluate the efficacy and safety of terbinafine in comparison with placebo, itraconazole and griseofulvin., Methods: The analysis used data from published trials, supplemented where necessary by reference to the original trial reports., Results: Three trials were included in which terbinafine was compared with placebo. From four trials comparing terbinafine with itraconazole, a statistically significant advantage in favour of terbinafine was observed for negative culture and microscopy at the end of the trials. Furthermore, both patients and physicians reported terbinafine to be better tolerated than itraconazole. From two trials comparing terbinafine with griseofulvin, a significantly higher rate of negative microscopy and culture was observed with terbinafine., Conclusions: A significant advantage in favour of treatment with terbinafine was observed.

Background: The objective of this study was to determine the efficacy of low protein diets in delaying the need to start maintenance dialysis based on an analysis of published literature., Methods: The search strategy involved a Medline and Embase search from January 1966 through to June 1999, congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, International Society of Nephrology since 1987) and direct contacts with investigators. The selection criteria included randomized trials comparing two different levels of protein intake in adult patients suffering from moderate to severe renal failure, followed for at least 1 year. Patients with diabetic nephropathy were excluded. Seven trials were selected from 40 studies since 1975. A total of 1494 patients were analysed: 753 had received reduced protein intake and 741 a higher protein intake. The numbers of 'renal deaths' (defined as the need for starting dialysis, the death of a patient or kidney transplant during the trial) were collected., Results: 242 renal deaths were recorded, 101 in the low protein diet and 141 in the higher protein diet group, giving an odds ratio of 0.61 with a 95% confidence interval of 0.46 to 0.83 (P=0.006)., Conclusion: Reducing protein intake in patients with chronic renal failure reduces the occurrence of renal death by about 40% as compared with larger or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.

Objectives: To compare the components of the time delay involved in pre-hospital and hospital thrombolytic therapy in patients presenting with suspected acute myocardial infarction., Material and Methods: From October 1988 to January 1992 a total of 198 mobile emergency units in 15 European countries and Canada randomized 5469 patients to receive either pre-hospital thrombolytic treatment, followed by placebo in hospital (pre-hospital group), or pre-hospital (hospital group) in the European Myocardial Infarction Project trial. We performed a post hoc analysis of these data to correlate components of the interval between symptom onset and treatment with baseline patient characteristics., Results: The delay between onset of symptoms and calling for an ambulance was significantly longer for female patients (P = 0.0001), older patients (> 65 years old; P = 0.0001), those who had experienced pain within the previous 24 h (P = 0.0001), and those with pulmonary oedema (P = 0.04). This delay was significantly shorter in patients with previous myocardial infarction (P = 0.02), those with ventricular fibrillation (P = 0.0001), and those in shock (P = 0.0001). The delay between the two injections was significantly longer for older patients (> 65 years old; P = 0.02), those with previous myocardial infarction (P = 0.03), and those in shock (P = 0.003)., Conclusions: Action undertaken to reduce delays between symptom onset and treatment should focus on modifiable factors such as patients who are likely to be late callers i.e. women and those over 65 years of age.

Osteoporosis is the main cause of spine and hip fractures. Morbidity, mortality, and costs arising from hip fractures have been well documented. Thyroid hormones (TH) are widely prescribed, mainly in the elderly. Some studies (but not all) found a deleterious effect of suppressive TH therapy on bone mass. These conflicting data raised a controversy as to the safety of current prescribing and follow-up habits, which, in turn, raised major health-care issues. To look for a detrimental effect on bone of TH therapy, we performed a meta-analysis (by pooling standardized differences, using a fixed effect model) of all published controlled cross-sectional studies (41, including about 1250 patients) concerning the impact of TH therapy on bone mineral density (BMD). Studies with women receiving estrogen therapy were excluded a priori, as were studies with a high percentage of patients with postoperative hypoparathyroidism, when no separate data were available. We decided to stratify the data according to anatomical site, menopausal status, and suppressive or replacement TH therapy, resulting in 25 meta-analysis on 138 homogeneous subsets of data. The main sources of heterogensity between studies that we could identify were replacement or suppressive TH therapy, menopausal status, site (lumbar spine, femoral neck, Ward's triangle, greater trochanter, midshaft and distal radius, with various percentages of cortical bone), and history of hyperthyroidism, which has recently been found to impair bone mass in a large epidemiological survey. To improve homogeneity, we excluded a posteriori 102 patients from 3 studies, who had a past history of hyperthyroidism and separate BMD data, thus allowing assessment of the TH effect in almost all 25 subset meta-analyses. However, controls were usually not matched with cases for many factors influencing bone mass, such as body weight, age at menarche and at menopause, calcium dietary intake, smoking habits, alcohol intake, exercise, etc. For lumbar spine and hip (as for all other sites), suppressive TH therapy was associated with significant bone loss in postmenopausal women (but not in premenopausal women), whereas, conversely, replacement therapy was associated with bone loss in premenopausal women (spine and hip), but not in postmenopausal women. The detrimental effect of TH appeared more marked on cortical bone than on trabecular bone. Only a large long term prospective placebo-controlled trial of TH therapy (e.g. in benign nodules) evaluating BMD (and ideally fracture rate) would provide further insight into these issues.

Reperfusion-induced ventricular fibrillation has been demonstrated in animal models of myocardial ischaemia, but no evidence exists for this in humans. The European Myocardial Infarction Project compared the efficacy and safety of pre-hospital thrombolytic therapy with that of hospital therapy. The objective of this study was to investigate the occurrence of reperfusion-induced ventricular fibrillation in acute myocardial infarction patients following thrombolytic therapy. In a double-blind multicentre trial, eligible patients were randomized to receive anistreplase at home followed by placebo in the hospital (A/P group), or placebo followed by anistreplase (P/A group). The occurrence of ventricular fibrillation, and other adverse events were recorded on specific study forms and could be attributed to defined time intervals. The incidence of ventricular fibrillation in the A/P group was significantly higher following the pre-hospital injection than in the P/A group (2.5% vs 1.6%; P = 0.021); the situation was reversed following the hospital injection (3.6% vs 5.3%; P = 0.002). No relationship was found between this excess of ventricular fibrillation and the patients' condition, with the exception of the site of the infarct. These results suggest the existence of reperfusion-induced ventricular fibrillation in patients developing myocardial infarction who receive thrombolytic treatment.

We examined the influence of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality in patients with heart failure of both ischaemic or non-ischaemic origin. Eleven, randomized, placebo-controlled trials of ACE inhibitors involving 1266 patients were selected. The follow-up period varied from 3 to 6 months. Four different ACE inhibitors were used in the 11 clinical trials. A total of 679 patients presented with an ischaemic heart failure and 587 with a non-ischaemic heart failure. Meta-analysis, performed for both subgroups, showed that mortality was significantly decreased in the ischaemic subgroup only (ischaemic group: odds ratio 0.45; 95% confidence interval 0.28 to 0.71; non-ischaemic subgroup: odds ratio 0.7; 95% confidence interval 0.4 to 1.5). Although the two odds ratio are not significantly different, further randomized, placebo-controlled trials with ACE inhibitors are required in order to determine more precisely the benefit/risk ratio in patients with non-ischaemic heart failure.

A total of 1290 patients were enrolled in a randomized multicentre double blind study in order to investigate the use of two doses of a new low molecular weight heparin, Logiparin, in the prevention of deep vein thrombosis (DVT) in general surgery. Patients who were included had no contraindication to heparin therapy and had at least one of the recognized risk factors for DVT. Patients were randomized to receive unfractionated heparin (UH) 5000 units b.d., Logiparin 2500 units daily or Logiparin 3500 units daily. Each treatment was given subcutaneously 2 h before surgery and continued for 7-10 days. Daily 125I-labelled fibrinogen uptake tests (FUTs) were performed from day 2 to day 7 to detect DVT, and phleboangiography was used to confirm the diagnosis. The wound was examined on a daily basis to check for haematoma formation, and all patients were followed up for 1 month after operation. All three treatment arms were well matched for age, sex, weight, diagnosis and type of operation performed. The three major inclusion criteria in the trial were malignancy, age over 60 years and a history of varicose veins. Positive FUTs (UH = 4.2 per cent, Logiparin 2500 units daily = 7.9 per cent, Logiparin 3500 units daily = 3.7 per cent) and positive angiograms (UH = 3.0 per cent, Logiparin 2500 units daily = 5.6 per cent, Logiparin 3500 units daily = 2.3 per cent) were significantly more common in the Logiparin 2500 units daily group than in the UH and Logiparin 3500 units daily groups. The rates of major complications (severe haemorrhage, death, pulmonary embolism, reintervention) were similar in the three groups.

In 378 placebo patients enrolled in the European Infarction Study (EIS), a secondary prevention study after acute myocardial infarction, 24-h baseline Holter monitoring was done 14 to 31 days after MI, and the relationship of electrical (ventricular arrhythmias) and mechanical (clinical signs of ventricular dysfunction) risk factors was analysed on the basis of mortality during the subsequent 2 years of follow-up. There was a rather low overall 2-year mortality rate of 6.9%. Consecutive arrhythmias (ventricular pairs and runs of ventricular premature beats) and left-ventricular dysfunction alone were associated with a low mortality of 4.0% and 3.6%, respectively. However, the combination of both defined a high-risk group characterized by a 2-year mortality rate of 16.7%. Additionally, the risk of dying was dependent on the frequency of consecutive arrhythmias: 22.2% of the patients with greater than 10 ventricular pairs per day died during the follow-up period in contrast to 9.9% of those with only 1-10 ventricular pairs per day. Thus, only the combination of electrical and mechanical risk factors, and especially the frequency of consecutive VPB, is helpful in identifying a subgroup of postMI patients with poor clinical outcome. An intervention study should restrict itself to this risk population only.

A cohort of thirty-five patients with angina pectoris were followed-up for six months with placebo as the only anti-anginal treatment apart from short-acting nitroglycerin. Only patients with at least five attacks per week were entered into the study. Prior to the study, their average number of attacks per week was 10.3(+/- 0.9) and their average nitroglycerin tablet consumption per week was 10.6(+/- 1.2). After admission into the study, the individual dosage of placebo could be blindly titrated during the first eight weeks. Once an adequate dosage was found, it was continued for 6 months. The primary end-point was predefined success or failure of the placebo treatment. Failure was assessed on the lack of improvement, occurrence of 'side-effects', or need for other anti-anginal treatment. In 27 patients, the placebo treatment was said to be a success (95% confidence limits of the percentage of success: 60-90%). No severe cardiac event occurred (confidence limits: 0-10%). Six patients developed 'side-effects'. The number of attacks per week decreased by 48% (P less than 0.0001) during the titration period (8 weeks) and by 77% during the whole 6 months. Exercise test improved, however, less markedly.

Synthetic human pancreatic tumor GH-releasing hormone (hpGRH 1-44-NH2) was given by iv bolus injection to 10 normal men at doses of 75, 150, 300, and 600 micrograms. At all doses the plasma GH responses were similar in an individual subject. Among subjects, however, the responses were significantly different, with peak GH concentrations ranging between 9.0 micrograms/liter and 54.9 micrograms/liter. The GH released in response to GRH was bioactive in the Nb2 lymphoma cell multiplication assay. The circulating GH 30 and 60 min after GRH was detected in 3 molecular forms corresponding to little, big, and big-big GH. These forms averaged 50%, 30%, and 20% of the total immunoreactive GH, respectively. The mean rise of plasma somatomedin-C, from 1.86 U/ml to 2.21 U/ml 24 h after GRH, was not statistically significant. A small but statistically significant GRH dose-dependent rise in plasma PRL (mean PRL concentrations 10 min after 600 micrograms GRH, 11.13 micrograms/liter occurred consistently after GRH injection. The evidence that the GH released by GRH is bioactive supports the potential use of GRH for therapeutic applications.

In this collaborative study involving 27 European medical centers, the plasma GH response to a single iv bolus dose of 2 micrograms/kg BW synthetic GHRH-(1-44)NH2 was determined in 574 children with growth failure of various etiologies. Analysis of the plasma GH response to GHRH was performed in 394 validated prepubertal children; these children were subdivided into 3 groups according to the degree of GH deficiency assessed within 6 months by conventional provocative tests (insulin, arginine, etc.): normal GH status (n = 210), partial GH deficiency (n = 73), or severe GH deficiency (n = 111). The mean peak GH values (+/- 2 SEM) after GHRH treatment in the three groups were 45.8 +/- 4.8, 29.2 +/- 6.3, and 16.8 +/- 3.1 microU/mL, respectively, and were greater than those after the conventional tests. The GH responses were consistent with the degree of GH deficiency based on the responses to the conventional tests. In addition, the areas under the GH response curves in the three groups were significantly different (P less than 0.0001). Among children with severe idiopathic GH deficiency 77% had a peak plasma GH level after GHRH above 10.0 microU/mL and 39% had a peak GH above 20.0 microU/mL. In these children, a single GHRH injection provides information on both their GH secretory capacity and the putative supresellar etiology of their GH deficiency, and may be of potential therapeutic value.

This study was undertaken to investigate whether sub-grouping post myocardial infarction (MI) patients with various risks of death was possible. Data on 6900 consecutive patients with clinical symptoms of acute MI were collected prospectively within 48 h of their admission. Vital status at one year was obtained for all but 264 (3.8%). A total of 476 (7.2%) patients died within the first 7 days. Correlation of baseline historical, demographic, biological and ECG variables with total mortality was first investigated with univariate analysis. Fifty-three secondary risk factors (SRF) were identified, based on: (1) a P value for comparison between dead and alive lower than 0.02; (2) a minimum number of 100 subjects in each cell of the four-fold table. Based on this set of SRFs, two approaches were used to investigate the distribution of patients still alive at 8 days regarding the one-year mortality risk, and to assign them in three sub-groups of equal size of increasing risk of death at one year. One approach consisted in merely distributing patients by the number of SRFs; the other consisted in distributing patients according to an individual expected risk computed with a logistic regression. Both approaches gave consistent findings. One third of the patients with the lowest risk of death within 12 months had an individual risk between 0% and 8%; the average mortality was 5-6% which represented 10.7% of the total number of deaths. The third with the highest individual risks had an individual risk ranging from 17-19% to 100%, with an average mortality of 35-37%; they accounted for 66-67% of the total number of deaths.(ABSTRACT TRUNCATED AT 250 WORDS)