Functional and prognostic implications of left ventricular contractile reserve in patients with asymptomatic severe mitral regurgitation

Objective: To evaluate contractile reserve (CR) determined by exercise echocardiography in predicting clinical outcome and left ventricular (LV) function in asymptomatic severe mitral regurgitation (MR). Design: Cohort study. Setting: Regional cardiac centre. Patients and outcome measures: LV volumes and ejection fraction (EF) were measured at rest and after stress in 71 patients with isolated MR. During follow up (mean (SD) 3 (1) years), EF and functional capacity were serially assessed and cardiac events ( cardiac death, heart failure, and new atrial fibrillation) were documented. Results: CR was present in 45 patients (CR+) and absent in 26 patients (CR-). Age, resting LV dimensions, EF, and MR severity were similar in both groups. Mitral surgery was performed in 19 of 45 (42%) CR+ patients and 22 of 26 (85%) CR2 patients. In patients undergoing surgery, CR was an independent predictor of follow up EF (p = 0.006) and postoperative LV dysfunction (EF < 50%) persisted in five patients, all in the CR2 group. Event-free survival was lower in surgically treated patients without CR (p = 0.03). In medically treated patients, follow up EF was preserved in those with intact CR but progressively deteriorated in patients without CR, in whom functional capacity also deteriorated. Conclusions: Evaluation of CR by exercise echocardiography may be useful for risk stratification and may help to optimise the timing of surgery in asymptomatic severe MR.

Chronic inflammatory demyelinating polyneuropathy and respiratory failure

Neuromuscular respiratory failure is not considered to be a clinical feature of chronic inflammatory demyelinating polyneuropathy (CIDP). We present 4 patients with CIDP who required respiratory assistance and mechanical ventilation. Two patients needed emergent intubation and one patient lapsed in a stupor from hypercapnia. Respiratory failure in CIDP should be considered exceptional, but more formal studies in CIDP may be needed to assess its prevalence.

CHARMed - the effects of candesartan in heart failure

The Candesartan in Heart failure: Assessment of Reduction in Mortality and mortality (CHARM) programme has already shown that candesartan is an effective alternative to angiotensin-converting enzyme (ACE) inhibitors (CHARM-Alternative), that additional benefits can be achieved by adding candesartan to ACE inhibitors (CHARM-Added), and that in patients with a preserved cardiac output there are reduced hospital admissions (CHARM-Preserved). Further recent analysis of the CHARM programme has shown that of the cardiovascular deaths, the benefit of candesartan was due to a reduction in sudden death and progressive heart failure, and that these reductions were observed in the -Alternative and -Added but not -Preserved components. Combination of the CHAR M-Alternative and -Added trials confirmed this reduction of cardiovascular deaths, and also demonstrated that candesartan reduced hospital admissions. There were also improvements in the New York Heart Association functional class of heart failure in the -Alternative and -Added, but not -Preserved, components of CHARM. The benefits of candesartan in heart failure are maintained in the presence of an ACE inhibitor and P-blocker. So far, all of the findings with candesartan in the CHARM programme have been favourable/CHARMed, although the beneficial effects in patients with a preserved cardiac output are limited.

Australian and New Zealand practice in intensive care (ANZPIC II): Predictors of physician confidence to diagnose pneumonia and determine illness severity in ventilated patients

The manner in which elements of clinical history, physical examination and investigations influence subjectively assessed illness severity and outcome prediction is poorly understood. This study investigates the relationship between clinician and objectively assessed illness severity and the factors influencing clinician's diagnostic confidence and illness severity rating for ventilated patients with suspected pneumonia in the intensive care unit (ICU). A prospective study of fourteen ICUs included all ventilated admissions with a clinical diagnosis of pneumonia. Data collection included pneumonia type - community-acquired (CAP), hospital-acquired (HAP) and ventilator-associated (VAP), clinician determined illness severity (CDIS), diagnostic methods, clinical diagnostic confidence (CDC), microbiological isolates and antibiotic use. For 476 episodes of pneumonia (48% CAP, 24% HAP, 28% VAP), CDC was greatest for CAP (64% CAP, 50% HAP and 49% VAP, P < 0.01) or when pneumonia was considered life-threatening (84% high CDC, 13% medium CDC and 3% low CDC, P < 0.001). Life-threatening pneumonia was predicted by worsening gas exchange (OR 4.8, CI 95% 2.3-10.2, P < 0.001), clinical signs of consolidation (OR 2.0, CI 95% 1.2-3.2, P < 0.01) and the Sepsis-Related Organ Failure Assessment (SOFA) Score (OR 1.1, CI 95% 1.1-1.2, P < 0.001). Diagnostic confidence increased with CDIS (OR 163, CI 95% 8.4-31.4, P < 0.001), definite pathogen isolation (OR 3.3, CI 95% 2.0-5.6) and clinical signs of consolidation (OR 2.1, CI 95% 1.3-3.3, P = 0.001). Although the CDIS, SOFA Score and the Simplified Acute Physiologic Score (SAPS II) were all associated with mortality, the SAPS II Score was the best predictor of mortality (P = 0.02). Diagnostic confidence for pneumonia is moderate but increases with more classical presentations. A small set of clinical parameters influence subjective assessment. Objective assessment using SAPS II Scoring is a better predictor of mortality.

Effects of aldosterone on forearm vasculature in treated chronic heart failure

The nongenomic effects of aldosterone in disease states associated with endothelial dysfunction may differ from those in healthy subjects. The effects of locally infused aldosterone on the forearm blood flow and volume were studied in optimally treated patients with chronic heart failure (CHF). At baseline and after incremental intrabrachial aldosterone, forearm blood flow was assessed using conventional strain gouge plethysmography, and forearm venous volume was assessed by radionuclide plethysmography. Constriction of the resistance vasculature of the forearm without significant effect on forearm venous capacitance was demonstrated in response to aldosterone in patients treated for CHF. (C) 2005 by Excerpta Medica Inc.

Disease risk and mortality prediction in intensive care patients with pneumonia. Australian and New Zealand practice in intensive care (ANZPIC II)

This study of ventilated patients investigated pneumonia risk factors and outcome predictors in 476 episodes of pneumonia (48% community-acquired pneumonia, 24% hospital-acquired pneumonia, 28% ventilator-associated pneumonia) using a prospective survey in 14 intensive care units within Australia and New Zealand. For community acquired pneumonia, mortality increased with immunosuppression (OR 5.32, CI 95% 1.58-17.99, P < 0. 01), clinical signs of consolidation (OR 2.43, CI 95% 1.09-5.44, P = 0. 03) and Sepsis-Related Organ Failure Assessment (SOFA) scores (OR 1.19, CI 95% 1.08-1.30, P < 0. 001) but improved if appropriate antibiotic changes were made within three days of intensive care unit admission (OR 0.42, CI 95% 0.20-0.86, P = 0.02). For hospital-acquired pneumonia, immunosuppression (OR 6.98, CI 95% 1.16-42.2, P = 0.03) and non-metastatic cancer (OR 3.78, CI 95% 1.20-11.93, P = 0.02) were the principal mortality predictors. Alcoholism (OR 7.80, CI 95% 1.20-1750, P < 0.001), high SOFA scores (OR 1.44, CI 95% 1.20-1.75, P = 0.001) and the isolation of high risk organisms including Pseudomonas aeruginosa, Acinetobacter spp, Stenotrophomonas spp and methicillin resistant Staphylococcus aureus (OR 4.79, CI 95% 1.43-16.03, P = 0.01), were associated with increased mortality in ventilator-associated pneumonia. The use of non-invasive ventilation was independently protective against mortality for patients with community-acquired and hospital-acquired pneumonia (OR 0.35, CI 95% 0.18-0.68, P = 0.002). Mortality was similar for patients requiting both invasive and non-invasive ventilation and non-invasive ventilation alone (21% compared with 20% respectively, P = 0.56). Pneumonia risks and mortality predictors in Australian and New Zealand ICUs vary with pneumonia type. A history of alcoholism is a major risk factor for mortality in ventilator-associated pneumonia, greater in magnitude than the mortality effect of immunosuppression in hospital-acquired pneumonia or community-acquired pneumonia. Non-invasive ventilation is associated with reduced ICU mortality. Clinical signs of consolidation worsen, while rationalising antibiotic therapy within three days of ICU admission improves mortality for community-acquired pneumonia patients.

Effects of a nurse-led, clinic and home-based intervention on recurrent hospital use in chronic heart failure

Background: Few studies have examined the potential benefits of specialist nurse-led programs of care involving home and clinic-based follow-up to optimise the post-discharge management of chronic heart failure (CHF). Objective: To determine the effectiveness of a hybrid program of clinic plus home-based intervention (C+HBI) in reducing recurrent hospitalisation in CHF patients. Methods: CHF patients with evidence of left ventricular systolic dysfunction admitted to two hospitals in Northern England were assigned to a C+HBI lasting 6 months post-discharge (n=58) or to usual, post-discharge care (UC: n=48) via a cluster randomization protocol. The co-primary endpoints were death or unplanned readmission (event-free survival) and rate of recurrent, all-cause readmission within 6 months of hospital discharge. Results: During study follow-up, more UC patients had an unplanned readmission for any cause (44% vs. 22%: P=0.0191 OR 1.95 95% CI 1.10-3.48) whilst 7 (15%) versus 5 (9%) UC and C+HBI patients, respectively, died (P=NS). Overall, 15 (26%) C+HBI versus 21 (44%) UC patients experienced a primary endpoint. C+HBI was associated with a non-significant, 45% reduction in the risk of death or readmission when adjusting for potential confounders (RR 0.55, 95% CI 0.28-1.08: P=0.08). Overall, C+HBI patients accumulated significantly fewer unplanned readmissions (15 vs. 45: P

Financial aspects of heart failure programs of care

As suggested by studies that have examined the economic burden imposed by heart failure and, more specifically where the greatest expenditure occurs, the key to cost-effectively minimising the impact of a sustained heart failure epidemic is to minimise recurrent hospital use-even at the expense of increasing levels of community-based care and prescribed pharmacotherapy [Mark DB. Economics of treating heart failure. Am J Cardiol 1997;80:33H-38H; Weintraub WS, Cole J, Tooley JF. Cost and cost-effectiveness studies in heart failure research. Am Heart J 2002;143:565-76]. This paper examines the potential cost-benefits of applying specialist heart failure programs of care and the range of financial issues that need to be considered when establishing a formal heart failure service. (C) 2005 European Society of Cardiology. Published by Elsevier B.V.

Carvedilol reduces the costs of medical care in severe heart failure: An economic analysis of the COPERNICUS study applied to the United Kingdom

Background: The aim of this study was to determine the effects of carvedilol on the costs related to the treatment of severe chronic heart failure (CHF). Methods: Costs for the treatment for heart failure within the National Health Service (NHS) in the United Kingdom (UK) were applied to resource utilisation data prospectively collected in all patients randomized into the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study. Unit-specific, per them (hospital bed day) costs were used to calculate expenditures due to hospitalizations. We also included costs of carvedilol treatment, general practitioner surgery/office visits, hospital out-patient clinic visits and nursing home care based on estimates derived from validated patterns of clinical practice in the UK. Results: The estimated cost of carvedilol therapy and related ambulatory care for the 1156 patients assigned to active treatment was 530,771 pound (44.89 pound per patient/month of follow-up). However, patients assigned to carvedilol were hospitalised less often and accumulated fewer and less expensive days of admission. Consequently, the total estimated cost of hospital care was 3.49 pound million in the carvedilol group compared with 4.24 pound million for the 1133 patients in the placebo arm. The cost of post-discharge care was also less in the carvedilol than in the placebo group (479,200 pound vs. 548,300) pound. Overall, the cost per patient treated in the carvedilol group was 3948 pound compared to 4279 pound in the placebo group. This equated to a cost of 385.98 pound vs. 434.18 pound, respectively, per patient/month of follow-up: an 11.1% reduction in health care costs in favour of carvedilol. Conclusions: These findings suggest that not only can carvedilol treatment increase survival and reduce hospital admissions in patients with severe CHF but that it can also cut costs in the process.

Baseline serum lipids and renal function in chronic kidney disease patients entering the LORD trial

Objective: Previous studies investigating associations between serum lipids and renal disease have generally not taken into account dietary intake or physical activity - both known to influence circulating lipids. Furthermore, inclusion of patients on HMG-CoA reductase inhibitors may also have influenced findings due to the pleiotropic effect of this medication. Therefore, the aim of this study is to determine the relationships between serum lipids and renal function in a group of patients not taking lipid-lowering medication and taking into account dietary intake and physical activity. Methods: Data from 100 patients enrolled in the Lipid Lowering and Onset of Renal Disease (LORD) trial were used in this study. Patients were included with serum creatinine > 120 mu mol/l, and excluded if they were taking lipid-lowering medication. Unadjusted and adjusted relationships were determined between fasting serum lipid concentrations (total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol/HDL ratio) and measures of renal function (estimated glomerular filtration rate (eGFR), creatinine clearance and serum creatinine) and urinary protein excretion. Results: Significant (p < 0.05) negative unadjusted relationships were found between lipids (total cholesterol, LDL and HDL cholesterol) and serum creatinine. In support of these findings, logarithmically-transformed lipids (total cholesterol, LDL and HDL cholesterol) were significantly associated with eGFR and creatinine clearance although the effects were of a smaller magnitude. Adjustment for dietary saturated fat intake and physical activity did not substantially change these effects. Conclusion: These data do not support the premise that lipids are associated with renal dysfunction in patients with normocholesterolemia.

Development of a semimechanistic model to describe the pharmacokinetics of gentamicin in patients receiving Hemodialysis

The aim of this study was to ascertain the most suitable dosing schedule for gentamicin in patients receiving hemodialysis. We developed a model to describe the concentrationtime course of gentamicin in patients receiving hemodialysis. Using the model, an optimal dosing schedule was evaluated. Various dosing regimens were compared in their ability to achieve maximum concentration (C-max, >= 8 mg/L) and area under the concentration time-curve (AUC >= 70 mg(.)h/L and <= 120 mg(.)h/L per 24 hours). The model was evaluated by comparing model predictions against real data collected retrospectively. Simulations from the model confirmed the benefits of predialysis dosing. The mean optimal dose was 230 mg administered immediately before dialysis. The model was found to have good predictive performance when simulated data were compared to data observed in real patients. In summary, a model was developed that describes gentamicin pharmacokinetics in patients receiving hemodialysis. Predialysis dosing provided a superior pharmacokinetic profile than did postdialysis dosing.

Is mortality from heart failure increasing in Australia? An analysis of official data on mortality for 1997-2003

Objective To assess whether trends in mortality from heart failure(HF) in Australia are due to a change in awareness of the condition or real changes in its epidemiology. Methods We carried out a retrospective analysis of official data on national mortality data between 1997 and 2003. A death was attributed to HF if the death certificate mentioned HF as either the underlying cause of death (UCD) or among the contributory factors. Findings From a total of 907 242 deaths, heart failure was coded as the UCD for 29 341 (3.2%) and was mentioned anywhere on the death certificate in 135 268 (14.9%). Between 1997 and 2003, there were decreases in the absolute numbers of deaths and in the age-specific and age-standardized mortality rates for HF either as UCD or mentioned anywhere for both sexes. HF was mentioned for 24.6% and 17.8% of deaths attributed to ischaemic heart disease and circulatory disease, respectively, and these proportions remained unchanged over the period of study. In addition, HF as UCD accounted for 8.3% of deaths attributed to circulatory disease and this did not change materially from 1997 to 2003. Conclusion The decline in mortality from HF measured as either number of deaths or rate probably reflects a real change in the epidemiology of HF. Population-based studies are required to determine accurately the contributions of changes in incidence, survival and demographic factors to the evolving epidemiology of HF.

Low mannose-binding lectin function is associated with sepsis in adult patients

Mannose-binding lectin (MBL) is an innate immune system pattern recognition molecule that kills a wide range of pathogens via the lectin complement pathway. MBL deficiency is associated with severe infection but the best measure of this deficiency is undecided. We investigated the influence of MBL functional deficiency on the development of sepsis in 195 adult patients, 166 of whom had bloodstream infection and 35 had pneumonia. Results were compared with 236 blood donor controls. MBL function (C4b deposition) and levels were measured by enzyme-linked immunosorbent assay. Using receiver-operator characteristics of MBL function in healthy controls, we identified a level of < 0.2 U mu L-1 as a highly discriminative marker of low MBL2 genotypes. Median MBL function was lower in sepsis patients (0.18 U mu L-1) than in controls (0.48 U mu L-1, P < 0.001). MBL functional deficiency was more common in sepsis patients than controls (P < 0.001). MBL functional deficient patients had significantly higher sequential organ failure assessment (SOFA) scores and higher MBL function and levels were found in patients with SOFA scores predictive of good outcome. Deficiency of MBL function appears to be associated with bloodstream infection and the development of septic shock. High MBL levels may be protective against severe sepsis. © 2006 Federation of European Microbiological Societies Published by Blackwell Publishing Ltd. All rights reserved.

Prolonged effects of a home-based intervention in patients with chronic illness

Background: Data on the long-term benefits of nonspecific disease management programs are limited. We performed a long-term follow-up of a previously published randomized trial. Methods: We compared all-cause mortality and recurrent hospitalization during median follow-up of 7.5 years in a heterogeneous cohort of patients with chronic illness initially exposed to a multidisciplinary, homebased intervention (HBI) (n = 260) or to usual postdischarge care (n = 268). Results: During follow-up, HBI had no impact on all-cause mortality (relative risk, 1.04; 95% confidence interval, 0.80-1.35) or event-free survival from death or unplanned hospitalization (relative risk, 1.03; 95% confidence interval, 0.86-1.24). Initial analysis suggested that HBI had only a marginal impact in reducing unplanned hospitalization, with 677 readmissions vs 824 for the usual care group (mean +/- SD rate, 0.72 +/- 0.96 vs 0.84 +/- 1.20 readmissions/patient per year; P = .08). When accounting for increased hospital activity in HBI patients with chronic obstructive pulmonary disease during follow-up for 2 years, post hoc analyses showed that HBI reduced readmissions by 14% within 2 years in patients without this condition (mean +/- SD rate, 0.54 +/- 0.72 vs 0.63 +/- 0.88 readmission/patient per year; P =. 04) and by 21% in all surviving patients within 3 to 8 years (mean +/- SD rate, 0.64 +/- 1.26 vs 0.81 +/- 1.61 readmissions/ patient per year; P =. 03). Overall, recurrent hospital costs were significantly lower ( 14%) in the HBI group (mean +/- SD, $ 823 +/- $ 1642 vs $ 960 +/- $ 1376 per patient per year; P =. 045). Conclusion: This unique study suggests that a nonspecific HBI provides long-term cost benefits in a range of chronic illnesses, except for chronic obstructive pulmonary disease.