[Clinical and microbiological characteristics of severe infections caused by group A streptococci]. / Klinická a mikrobiologická charakteristika závazných infekcii sposobených streptokokmi skupiny A.

AIM OF THE STUDY: Analysis of data on the occurrence of severe infections caused by group A streptococci, emm typing of the isolated strains, and survey of resistance to the selected antibiotics. MATERIAL AND METHODS: In 2012 and 2013, 43 S. pyogenes strains were isolated from severe infections. The isolates were most often recovered from wounds and abscesses (36 patients), followed by blood culture (5 patients), sputum (1 patient), and autopsy samples (1 patient). Antimicrobial susceptibility to selected antibiotics ( penicillin, erythromycin, clindamycin, spiramycin, and tetracycline) was tested by the disk-diffusion method and the minimal inhibitory concentrations (MICs) were determined. RESULTS: In 2012 and 2013, an increase in severe streptococcal infections was observed, with 27 and 16 cases reported, respectively. Resistance to macrolides was detected in 18.5% and 12.5% of isolates, respectively, and resistance to tetracycline in 25.9% and 20% of isolates, respectively. The isolated S. pyogenes strains were most often assigned to emm type 1. Risk factors for streptococcal infection were analyzed, with injury being most often identified as a risk factor- in seven and two patients, respectively. The patients were most frequently treated by beta-lactam antibiotics (penicillin and ampicillin). In 2012, two cases were fatal. CONCLUSION: This study reports cases of invasive group A streptococcal (GAS) infection as seen in clinical practice. An increased occurrence of S. pyogenes was observed in the hospital, with the isolates exhibiting elevated resistance to erythromycin and tetracycline. It is necessary to monitor the trends of antimicrobial resistance and the distribution of emm types among group A streptococcal isolates. Cooperation of the laboratory and clinical professionals in the prevention and therapy of streptococcal infections, invasive in particular, is crucial for risk reduction.

Aerosol vaccination induces robust protective immunity to homologous and heterologous influenza infection in mice.

Live-attenuated influenza vaccine (LAIV) delivered by large droplet intranasal spray is efficacious against infection. However, many of the large droplets are trapped in the external nares and do not reach the target nasal airway tissues. Smaller droplets might provide better distribution yielding similar protection with lower doses. We evaluated 20 and 30 µm aerosol delivery of influenza virus in mice. A 15s aerosol exposure optimally protected against homologous and heterologous influenza infection and induced a robust immune response. These results demonstrate the feasibility of nasal vaccination using aerosolized particles, providing a strategy to improve vaccine efficacy and delivery.

[Gastroenteropatic neuroendocrine tumors: multidisciplinary approach in therapy]. / Multidiscipliniárny prístup k liecbe gastroenteropankreatických neuroendokrinných tumorov.

INTRODUCTION: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are classified on the basis of hormonal activity of tumor cells to functional and non-functional tumors. Therapy of well differentiated NETs includes surgical procedures, debulking of tumor mass, biotherapy and peptid receptor radionuclid therapy. AIM OF THE STUDY: Analysis of therapeutic modalities in group of patients with well differentiated GEP-NETs. RESULTS: In time period from 1. 1. 2005 to 1. 1. 2010 we followed up 50 pts (19 men/31 women) with well differentiated GEP neuroendocrine tumors. Primary localisation was: stomach--6 times, pancreas--9 times, duodenum--1 times, jejunum-- 4 times, appendix--3 times, ileum--23 times, rectum--4 times. Metastatic disease was affirmed in time of diagnosis in 36 patients. Carcinoid syndroma had 20 pts, 4 pts with pancreatic tumor had functional tumors (2 times overproduction of calcitonine, 1 times of gastrin, 1 times of insuline). Surgical treatment was performed in 40 pts--resection of primary tumor and debulking of metastases, in 5 pts with pancreatic tumor resection was not possible due to invasion to sorrounding tissue and vessels. Biological treatment with long acting somatostatin analogues was indicated in 20 pts with carcinoid syndroma and in 4 pts with functional pancreatic tumors. In 5 pts with non resectable neuroendocrine carcinoma of pancreas peptid radionuclide receptor therapy (PRRT) was indicated: in 4 of them with 90Ytrium-DOTA-octreotid and in 1 patient with MIBG. In all pts a reduction of tumor volume was noticed. Biotherapy with somatostatin analogues reduced symptoms of hormonal activities and brought on stabilisation of disease in most of patients. In period of follow up 5 patients died. CONCLUSION: Complex therapy in patients with well differentiated neuroendocrine tumors markedly contributes to prolongation of survival of patients and also to enhancement quality of their life.

Combination therapy with amlodipine/valsartan in essential hypertension: a 52-week, randomised, open-label, extension study.

BACKGROUND: A majority of hypertensive patients require > or = 2 agents to achieve target blood pressure (BP). METHODS: This 52-week, multicentre, open-label, randomised extension trial to a previously reported double-blind, placebo-controlled study evaluated the safety and efficacy of amlodipine/valsartan (Aml/Val) combination. Patients who successfully completed the core study without serious drug-related adverse events (AEs) and mean sitting systolic BP (MSSBP)/mean sitting diastolic BP (MSDBP) < or = 150/95 mmHg were eligible to enter the extension and be treated with Aml/Val 2.5/80 or 5/80 mg. After 4 weeks of treatment, patients underwent force-titration to receive 5/160 mg (low dose) or 10/160 mg (high dose) for 48 weeks. Addition of hydrochlorothiazide (HCTZ) 12.5 mg was permitted if BP was > or = 140/90 mmHg at Week 8 or later. Patients could be down-titrated to the prior lower combination dose with or without HCTZ if an intolerable AE occurred. Safety evaluations included monitoring of AEs. Efficacy variables were change from baseline in MSDBP (primary) and MSSBP (secondary). RESULTS: Of 1246 patients randomised, 1075 (86.3%) completed the extension study. At week 52 end-point, change in MSSBP/MSDBP from core study baseline was -22.1/-17.2 mmHg for low-dose regimen and -22.8/-18.1 mmHg for high-dose regimen. For both regimens, reductions in BP were sustained over 52 weeks and mean BP maintained below approximately 135/85 mmHg at all visits. Frequent AEs in the low- and high-dose regimens were peripheral oedema (9.7% and 17.1% respectively), nasopharyngitis (8.1% and 7.2%), and dizziness (5.2% and 7.0%). Incidence of serious AEs was 3.7% with low dose and 4.1% with high dose. CONCLUSION: The combination of Aml/Val with the optional addition of HCTZ produced clinically significant and persistent reductions in BP over 52 weeks with a favourable tolerability profile.

Efficacy of combined local mechanical vibrations, continuous passive motion and thermotherapy in the management of osteoarthritis of the knee.

OBJECTIVES: We evaluated the efficacy of combined mechanical vibrations, continuous passive motion (CPM) and heat on the severity of pain in management of osteoarthritis of the knee (OA-K). METHODS: In this controlled, double crossover study, 71 OA-K patients were randomized in Phase 1 to receive 4 weeks active treatment consisting of two 20-min sessions per day (34 patients, Group AB) or treatment with a sham device (37 patients, Group BA). This was followed by a 2-week washout period (Phase 2). In Phase 3, patients crossed over so that Group AB was treated with the sham device and Group BA received active treatment for an additional 4 weeks. Patient assessments of pain (visual analog scale, VAS) and Western Ontario and McMaster Universities (WOMAC) OA index were performed at baseline and at study weeks 2, 4, 6, and 10. Net treatment effects were estimated by comparing outcomes between active and sham treatment study phases. RESULTS: Treatment benefits were noted for both of the trial's two pre-specified primary endpoints, VAS and WOMAC. VAS was reduced at all follow-up time points for patients receiving active treatment compared to sham treatment with a net treatment effect of 14.4+/-4.1 mm (P=0.001). Similarly, the WOMAC score was reduced significantly with active treatment at all measured points with a net effect of 8.8+/-1.9 points (P<0.001). The secondary endpoints, range of motion (ROM) and treatment satisfaction, also improved with active vs sham treatment. CONCLUSION: Four weeks treatment with combined CPM, vibration and local heating significantly decreases pain, improves ROM and the quality of life in patients with OA-K (ClinicalTrials.gov registration number: NCT00858416).

Hemosuccus pancreaticus.

In this study, authors describe a rare case of a 40-year old patient with a history of chronic pancreatitis due to ethanol abuse, repeatedly hospitalized for intermittent bleeding into gastrointestinal tract (GIT). The sources of bleeding were pseudoaneurysms of the peripancreatic arteries (gastroduodenal artery, right hepatic artery) bleeding into GIT via pancreatic duct. This type of bleeding is referred as hemosuccus pancreaticus and belongs to a rare form of bleeding into upper GIT. Development of each pseudoaneurysm was monitored with a 6 month time interval. The diagnosis was established using endoscope, Doppler ultrasound and CT angiography. During the therapeutic process, while stopping bleeding, two different radiological interventions were used. In pseudoaneurysm of gastroduodenal artery, hemostasis was achieved using selective transcatheter arterial embolization (TAE) with steel coils. In the second intervention, a stent was inserted into vascular lesion. In the discussion, authors review the problems of hemosuccus pancreaticus, epidemiology, symptoms, diagnostic and possible therapeutic approaches (Fig. 3, Ref. 31). Full Text (Free, PDF) www.bmj.sk.

ATM haplotypes and breast cancer risk in Jewish high-risk women.

While genetic factors clearly play a role in conferring breast cancer risk, the contribution of ATM gene mutations to breast cancer is still unsettled. To shed light on this issue, ATM haplotypes were constructed using eight SNPs spanning the ATM gene region (142 kb) in ethnically diverse non-Ashkenazi Jewish controls (n=118) and high-risk (n=142) women. Of the 28 haplotypes noted, four were encountered in frequencies of 5% or more and accounted for 85% of all haplotypes. Subsequently, ATM haplotyping of high-risk, non-Ashkenazi Jews was performed on 66 women with breast cancer and 76 asymptomatic. One SNP (rs228589) was significantly more prevalent among breast cancer cases compared with controls (P=4 x 10(-9)), and one discriminative ATM haplotype was significantly more prevalent among breast cancer cases (33.3%) compared with controls (3.8%), (P< or =10(-10)). There was no significant difference in the SNP and haplotype distribution between asymptomatic high-risk and symptomatic women as a function of disease status. We conclude that a specific ATM SNP and a specific haplotype are associated with increased breast cancer risk in high-risk non-Ashkenazi Jews.

Sex-related difference in regression of left ventricular hypertrophy with antihypertensive treatment: the LIFE study.

While left ventricular (LV) structure and function differ between hypertensive women and men, it remains unclear whether sex affects regression of LV hypertrophy with antihypertensive treatment. We analysed paired echocardiograms in 500 men and 347 women enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study at baseline and after 12 months of antihypertensive treatment with either losartan or atenolol. At enrollment, 177 women and 242 men were randomized to losartan-based treatment and 161 women and 247 men were randomized to atenolol-based treatment (sex difference=NS). After 12 months of antihypertensive treatment, blood pressure was lowered similarly in women (152/83 from 174/97 mmHg) and men (149/85 from 173/99 mmHg; both P<0.001, sex difference=NS), without significant change in body weight in either sex. Cardiac output and pulse pressure/stroke volume were equivalently reduced in both sexes (-0.2 vs -0.1 l/min and both -0.20 mmHg/ml/m(2), respectively; both P=NS). Absolute LV mass change after 12 months of antihypertensive treatment was greater in men than in women (-30 vs -24 g, P=0.01). However, after adjusting for baseline LV mass and randomized study treatment, LV mass reduction was greater in women than in men (-33 vs -23 g, P=0.001). LV mass regression was greater in women, by 8.0+/-2.8 g, after adjusting for baseline LV mass and randomized study treatment. After consideration of baseline LV mass and randomized study treatment, antihypertensive treatment regressed LV hypertrophy more in women. Further studies are needed to identify the mechanisms and prognostic implications of this sex-related difference.

The contribution of roots and shoots to whole plant nitrate reduction in fast- and slow-growing grass species.

The hypothesis was tested that slow-growing grass species perform a greater proportion of total plant NO3- reduction in their roots than do fast-growing grasses. Eight grass species were selected that differed in maximum relative growth rate (RGR) and net NO3- uptake rate (NNUR). Plants were grown with free access to nutrients in hydroponics under controlled-environment conditions. The site of in vivo NO3- reduction was assessed by combining in vivo NO3- reductase activity (NRA) assays with biomass allocation data, and by analysing the NO3- to amino acid ratio of xylem sap. In vivo NRA of roots and shoots increased significantly with increasing NNUR and RGR. The proportion of total plant NO3- reduction that occurs in roots was found to be independent of RGR and NNUR, with the shoot being the predominant site of NO3- reduction in all species. The theoretical maximum proportion of whole plant nitrogen assimilation that could take place in the roots was calculated using information on root respiration rates, RGR, NNUR, and specific respiratory costs associated with growth, maintenance and ion uptake. The calculated maximum proportion that the roots can contribute to total plant NO3- reduction was 0.37 and 0.23 for the fast-growing Dactylis glomerata L. and the slow-growing Festuca ovina L., respectively. These results indicate that slow-growing grass species perform a similar proportion of total plant NO3- reduction in their roots to that exhibited by fast-growing grasses. Shoots appear to be the predominant site of whole plant NO3- reduction in both fast- and slow-growing grasses when plants are grown with free access to nutrients.

Impact of coronary artery disease on left ventricular systolic function and geometry in hypertensive patients with left ventricular hypertrophy (the LIFE study).

Hypertensive patients with left ventricular (LV) hypertrophy have a higher incidence of cardiovascular events than those without it. We hypothesized that a close relation exists between clinical evidence of coronary artery disease (CAD) and alterations in LV structure and function that contribute to their higher risk. Echocardiograms were recorded in 963 hypertensive patients (mean age 66 +/- 7 years, 41% women) with electrocardiographic LV hypertrophy, and divided into 149 with and 814 without clinical (prior myocardial infarction or angina pectoris) or electrocardiographic (Minnesota codes 1.1, 1.2) evidence of CAD. Patients with CAD had larger LV internal dimensions (5.5 +/- 0.6 vs 5.2 +/- 0.5 cm), increased LV mass (136 +/- 31 vs 122 +/- 24 g/m(2), and 62.4 +/- 19.4 vs 55.5 +/- 12.1 g/m(2.7)), lower ejection fraction (58 +/- 10% vs 62 +/- 8%), higher circumferential end-systolic wall stress (cESS) (198 +/- 59 vs 181 +/- 47 kdynes/cm(2), all p <0.001), and higher total peripheral resistances (2,088 +/- 628 vs 1,963 +/- 553 dynes x s x m(2)/cm(3), p = 0.02). Although eccentric LV hypertrophy predominated, the CAD group had a greater prevalence of this geometric pattern than the non-CAD group (56% vs 47%, p <0.02). An index of myocardial oxygen demand per beat--the LV mass x cESS x ejection time--was 20% higher in patients with CAD. In conclusion, clinical evidence of CAD in hypertensive patients with electrocardiographic evidence of LV hypertrophy identifies subjects with structural and functional abnormalities at high risk for cardiovascular events. LV mass. cESS. ejection time, a noninvasive index that parallels myocardial oxygen demand per beat, is especially high in hypertensive patients with CAD.

Efficacy and short-term safety of a new ACAT inhibitor, avasimibe, on lipids, lipoproteins, and apolipoproteins, in patients with combined hyperlipidemia.

Although acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors have been shown to reduce lipid levels in several animal models, the safety and lipid modifying activity of any single agent in this class has not been demonstrated in humans. The safety and efficacy of avasimibe (CI-1011), a new, unique, wholly synthetic ACAT inhibitor, was evaluated in the treatment of 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia (low levels of high-density lipoprotein cholesterol [HDL-C]). Following an 8-week placebo and dietary-controlled baseline period, patients were randomly assigned to double-blind treatment with placebo, 50, 125, 250, or 500 mg avasimibe administered as capsules once daily for 8 weeks. At all evaluated doses, avasimibe treatment resulted in prompt and significant reductions (P<0.05) in plasma levels of total triglycerides (TG) and very low-density lipoprotein cholesterol (VLDL-C) with mean reductions of up to 23% and 30% respectively, apparently independent of dose. No statistically significant changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C or apolipoprotein (apo) B were detected. ApoAI levels were also unchanged on all doses of avasimibe apart from the 500 mg dosage, which was associated with a significant decrease in plasma apoAI. The relevance of this latter finding in only one dosage group is not known. All doses of avasimibe were well tolerated with no resulting significant abnormalities of biochemical, hematological, or clinical parameters.

Prognostic implications of the compensatory nature of left ventricular mass in arterial hypertension.

OBJECTIVE: To test whether inappropriate echocardiographic left ventricular (LV) mass (i.e. higher than predicted by individual body size, sex and cardiac load [delta%LVM]) is associated with an increased rate of cardiovascular events, and whether values of LV mass lower than appropriate confer protection. DESIGN: Prospective, longitudinal. SETTING: Institutional, hospital outpatient clinic. PATIENTS: A total of 294 hypertensive patients, 84 with inappropriate and 21 with low LV mass (lower than appropriate). MAIN OUTCOME MEASURES: Cardiovascular fatal and non-fatal events. RESULTS: Baseline delta%LVM was higher in patients with follow-up total (n = 50) or fatal (n = 14) events than in event-free survivors (all P < 0.0001) and predicted events independently of age and systolic pressure (all P < 0.0001). Although the performance was not better than with use of more traditional definition of LV hypertrophy, delta%LVM remained a predictor even in the subgroup of 126 patients (32 total events, 13 deaths) with clear-cut LV hypertrophy (P < 0.009). Patients with low LV mass exhibited supranormal LV chamber and midwall function, slightly higher heart rate and higher cardiac index (all P< 0.01). These patients had the same rate of events as those with appropriate LV mass. CONCLUSIONS: In hypertensive patients, increase in LV mass beyond values required to compensate cardiac workload at a given body size and sex predicts cardiovascular risk independently of age and blood pressure, in the whole population as well as in the subset of patients with LV hypertrophy. Hypertensive patients with levels of LV mass lower than needed to compensate cardiac workload exhibit hyperdynamic circulatory status and the same risk pattern as patients with higher values of LV mass, possibly due to activation of the sympathetic system.

Relation of left ventricular geometry and function to systemic hemodynamics in hypertension: the LIFE Study. Losartan Intervention For Endpoint Reduction in Hypertension Study.

OBJECTIVES: To clarify the relations of systemic hemodynamics to left ventricular (LV) geometric patterns in patients with moderate hypertension and target organ damage. BACKGROUND: LV geometry stratifies risk in hypertension, but relations of LV geometry to systemic hemodynamic patterns in moderately severe hypertension have not been fully elucidated. DESIGN: Cross-sectional case-control study. SETTING: Baseline findings in the echocardiographic substudy of the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE) and in a normotensive reference group. PATIENTS/PARTICIPANTS: Nine hundred and sixty-four patients with Stage I-II hypertension and LV hypertrophy by Cornell voltage duration criteria ((SV3 + RaVL [+ 6 mm in women]) x QRS > 2440 mm x ms) or modified Sokolow- Lyon voltage criteria (SV1 + RV5/RV6 > 38 mm), and 366 apparently normal adults. INTERVENTIONS: None. METHODS: Two-dimensional and Doppler echocardiograms were used to classify hypertensive patients into groups with normal geometry, concentric remodelling and concentric and eccentric hypertrophy, and to measure stroke volume (SV), cardiac output, peripheral resistance and pulse pressure/SV as a measure of arterial stiffness. Comparisons were adjusted for covariates by general linear model with the Sidak post-hoc test RESULTS: Mean SV was higher in patients with eccentric hypertrophy (83 ml/beat) and lower with concentric remodeling (68 ml/beat) than in normal adults (73 ml/ beat). Cardiac output was highest in patients with eccentric LV hypertrophy and lower with concentric remodeling than eccentric hypertrophy; mean pressure and peripheral resistance were equally high in all hypertensive subgroups, whereas pulse pressure/SV was most elevated (by a mean of 47% versus reference subjects) with concentric remodeling and least so (mean + 15%) with eccentric hypertrophy. In multivariate analysis (Multiple R + 0.68), LV mass was independently related to higher systolic pressure, older age, SV, male gender and body mass index (all P< 0.001). Relative wall thickness was independently related (Multiple R + 0.50) to older age, higher systolic pressure, lower SV (all P< 0.001) and higher body mass index (P + 0.007). SV and cardiac output were lower in patients with low stress-corrected midwall shortening. CONCLUSION: In patients with moderate hypertension and ECG LV hypertrophy, the levels of SV and pulse pressure/ SV, are associated with, and may be stimuli to different LV geometric phenotypes.

Pharmacokinetics of intraperitoneal piperacillin/tazobactam in patients on peritoneal dialysis with and without pseudomonas peritonitis.

OBJECTIVE: The objective of this study was to assess the pharmacokinetics of intraperitoneal (IP) administration of the antibiotic combination piperacillin/tazobactam (PIP/TAZ) to patients on chronic ambulatory peritoneal dialysis (CAPD) with and without pseudomonas peritonitis. DESIGN: Open-labeled study. SETTING: The study was carried out in the CAPD unit of Assaf Harofeh Medical Center, Zerifin, Israel. PATIENTS AND METHODS: Six patients participated in the study, 4 had pseudomonas peritonitis, all were given an IP loading dose of 4 g/0.5 g PIP/TAZ. Twenty-four hours after the initial dose, a maintenance dose of 0.5 g/0.0625 g PIP/TAZ was administered with each dialysate exchange for a period of 1 week. The patients without peritonitis received only the loading dose. High performance liquid chromatography was used to determine the concentrations of PIPITAZ in plasma obtained at 0, 30, 60, 90, 120, 360, 480, 600, 720, and 1440 minutes after administration. Samples of the dialysate fluid for determination of PIP/TAZ concentration were collected at 6,10,14, 24, and 72, 120, and 168 hours. RESULTS: After the loading dose, the highest plasma PIP concentration (Cmax) was 51.6 t 21.25 Lig/mL and appeared at 1.5 = 0.45 hours (t,,a). During the maintenance period plasma PIP concentration was 5.2 t 4.75 Lg/mL. Tazobactam was detected in the plasma of 1 patient only. The concentration of TAZ in the dialysate fluid during the maintenance period was 2.3 t 0.5 ig/mL. CONCLUSIONS: Piperacillin administered IP at 4 g reached plasma concentrations comparable to intravenous administration and considered therapeutic (above the MIC90 for Pseudomonas aeruginosa) in CAPD patients with or without peritonitis. The maintenance dose, however, should be augmented. Tazobactam could not be detected in the plasma of most patients and the therapeutic implications of IP administration of TAZ cannot be directly correlated to intravenous administration.

Conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm: the effect of no treatment and high-dose amiodarone. A randomized, placebo-controlled study.

BACKGROUND: Spontaneous conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm occurs commonly and is not affected by low-dose amiodarone treatment. METHODS: In a randomized, placebo-controlled trial of 100 patients with paroxysmal atrial fibrillation of recent onset (<48 h) we compared the effects of treatment with continuous intravenous amiodarone 125 mg per hour (total 3 g) and intravenous placebo. Patients in the placebo group who did not convert to normal sinus rhythm within 24 h were started on amiodarone therapy. RESULTS: Conversion to normal sinus rhythm occurred within 24 h in 32 of 50 patients (64%) in the placebo group, most of whom converted within 8 h. Lower conversion rates were observed in patients with hypertension, ischaemic heart disease or congestive heart failure and in patients with echocardiographic findings of left atrial diameter above 45 mm, ejection fraction below 45% or significant mitral regurgitation. However, in most patients these clinical or echocardiographic risk factors of decreases in conversion rate were not present. In such patients the spontaneous conversion rate was approximately 90%. The conversion rate during 24 h of treatment in the amiodarone group was 92% (P=0.0017, compared to the placebo group). In this group, the conversion rate was largely unaffected by baseline characteristics. Of the 18 patients who did not convert with placebo, 15 (85%) converted after being crossed over to amiodarone. All patients not responding to high-dose amiodarone were in chronic atrial fibrillation within 1 month. In patients still in atrial fibrillation after 8 h of treatment, the pulse rate decreased significantly more in the amiodarone as compared to the placebo group (83+/-15 vs 114+/-20 beats. min(-1), P=0.0014). CONCLUSION: The spontaneous conversion of recent onset paroxysmal atrial fibrillation is high and approaches 90% in specific clinical and echocardiographically defined subgroups. Intravenous high-dose amiodarone safely facilitates conversion of paroxysmal atrial fibrillation. However, such treatment should be reserved for patients with unfavourable risk factor profiles, not converting during 8 h of observation or requiring rate control.

Stroke volume/pulse pressure ratio and cardiovascular risk in arterial hypertension.

Ratio of stroke volume (SV, M-mode echocardiography) to pulse pressure (PP) has been proposed as an estimate of total arterial compliance and has been shown to be related to body size, age, and heart rate in normal adults. SV/PP was estimated in 294 hypertensive patients (98 women) as a raw value by use of SV/body surface area (SVi) and by the ratio of SV/PP to the value predicted by a previously developed equation (%SV/PP). At baseline, the 50 patients who had cardiovascular events over the following 10 years exhibited higher PP and lower SV/PP, SVi/PP, and %SV/PP (all P<0.008) than patients without events. Crude risk of follow-up total and fatal cardiovascular events increased with increasing level of PP and decreasing SV/PP, SVi/PP, and %SV/PP (all P<0.002). In multivariate logistic regression models with continuous covariates, the risk of total cardiovascular events was independently related to increasing age (P<0.0001) and left ventricular (LV) mass index (P<0.003) and decreasing values of %SV/PP (P<0.006) but not to increasing systolic, pulse, or mean blood pressure or gender. Similar although less strong results were obtained with the use of SVi/PP (P<0.02), whereas SV/PP did not enter the model as an independent predictor. Risk of cardiovascular death was only predicted by age and LV mass index. The %SV/PP was also an independent predictor of total cardiovascular events in Cox proportional hazards analysis (exp[b]: 2.49, P<0.001) independent of age (exp[b]: 1.05, P<0.003) and LV mass index (exp[b]: 1.02, P<0.0003), whereas no effect was detected for height. Thus, in patients with arterial hypertension, a reduced ratio of M-mode echocardiographic SV/PP as a percentage of the value predicted by demographic variables is a predictor of cardiovascular morbid events independent of age and LV mass index.

Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin.

OBJECTIVES: This study compared the efficacy and safety of atorvastatin, fluvastatin, lovastatin, and simvastatin in patients with documented atherosclerosis treated to U.S. National Cholesterol Education Program (NCEP) recommended low-density-lipoprotein (LDL) cholesterol concentration (< or = 100 mg/dl [2.59 mmol/liter]). BACKGROUND: For patients with advanced atherosclerosis, NCEP recommends lipid-lowering drug therapy if LDL cholesterol remains > or = 130 mg/dl (3.36 mmol/liter). METHODS: A total of 318 men or women with documented atherosclerosis and LDL cholesterol > or = 130 mg/dl (3.36 mmol/liter) and < or = 250 mg/dl (6.5 mmol/liter), and triglycerides < or = 400 mg/dl (4.5 mmol/liter) participated in this 54-week, multicenter, open-label, randomized, parallel-group, active-controlled, treat-to-target study. Patients were titrated at 12-week intervals until the LDL cholesterol goal was reached. Number of patients reaching target LDL cholesterol levels and dose to reach target were evaluated. RESULTS: At the starting doses, atorvastatin 10 mg produced significantly greater decreases (p < 0.05) in plasma LDL cholesterol than the other treatments. Subsequently, the percentage of patients reaching goal at the starting dose was 32% for atorvastatin, 1% for fluvastatin, 10% for lovastatin and 22% for simvastatin. Atorvastatin-treated patients required a lower median dose than other treatments. Median doses at week 54 with the last available visit carried forward were atorvastatin 20 mg/day, fluvastatin 40 mg/day + colestipol 20 g/day, lovastatin 80 mg/day, simvastatin 40 mg/day. CONCLUSIONS: A significantly greater number (p < 0.05) of patients with confirmed atherosclerosis treated with atorvastatin reached the target LDL cholesterol concentration at the starting dose than patients treated with fluvastatin or lovastatin, and significantly fewer (p < 0.05) patients treated with atorvastatin required combination therapy with colestipol to achieve target LDL cholesterol concentrations than all other statins tested.

The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin.

OBJECTIVE: Recognising the importance of treating hyperlipidaemia, the National Cholesterol Education Program (NCEP) has established widely accepted treatment goals for low density lipoprotein cholesterol (LDL-C). Medications used most commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The relative resource utilisation and cost associated with the use of reductase inhibitors of different LDL-C lowering efficacy are unknown, but are major health and economic concerns. The objective of this study was to determine the mean total cost of care to reach NCEP goals with various reductase inhibitors. DESIGN: In a randomised, 54-week, 30-centre controlled trial we compared resources used and costs associated with treating patients to achieve NCEP goals using 4 reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin. PATIENTS AND PARTICIPANTS: The trial studied 662 patients; 318 had known atherosclerotic disease. INTERVENTIONS: Reductase inhibitor therapy was initiated at recommended starting doses and increased according to NCEP guidelines and package insert information. For patients who did not reach the goal at the highest recommended dose of each reductase inhibitor, the resin colestipol was added. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with atorvastatin, compared-with other reductase inhibitors, were more likely to reach NCEP goals during treatment (p < 0.05), required fewer office visits (p < 0.001) and less adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95% confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471, 95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for patients with or without known atherosclerotic disease. CONCLUSIONS: In patients requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved significantly more often using fewer resources with atorvastatin compared with simvastatin, lovastatin or fluvastatin.