Depression as an independent prognostic factor for all-cause mortality after a hospital admission for worsening heart failure.

BACKGROUND: Depression is associated with increased mortality amongst patients with chronic heart failure (HF). Whether depression is an independent predictor of outcome in patients admitted for worsening of HF is unclear. METHODS: OPERA-HF is an observational study enrolling patients hospitalized with worsening HF. Depression was assessed by the Hospital Anxiety and Depression Scale (HADS-D) questionnaire. Comorbidity was assessed by the Charlson Comorbidity Index (CCI). Kaplan-Meier and Cox regression analyses were used to estimate the association between depression and all-cause mortality. RESULTS: Of 242 patients who completed the HADS-D questionnaire, 153, 54 and 35 patients had no (score 0-7), mild (score 8-10) or moderate-to-severe (score 11-21) depression, respectively. During follow-up, 35 patients died, with a median time follow-up of 360days amongst survivors (interquartile range, IQR 217-574days). In univariable analysis, moderate-to-severe depression was associated with an increased risk of death (HR: 4.9; 95% CI: 2.3 to 10.2; P<0.001) compared to no depression. Moderate-to-severe depression also predicted all-cause mortality after controlling for age, CCI score, NYHA class IV, NT-proBNP and treatment with mineralocorticoid receptor antagonist, beta-blocker and diuretics (HR: 3.0; 95% CI: 1.3 to 7.0; P<0.05). CONCLUSIONS: Depression is strongly associated with an adverse outcome in the year following discharge after an admission to hospital for worsening HF. The association is only partly explained by the severity of HF or comorbidity. Further research is required to demonstrate whether recognition and treatment of depression improves patient outcomes.

Derivation and validation of a simple clinical risk-model in heart failure based on 6 minute walk test performance and NT-proBNP status--do we need specificity for sex and beta-blockers?

BACKGROUND: It is unclear whether risk prediction strategies in chronic heart failure (CHF) need to be specific for sex or beta-blockers. We examined this problem and developed and validated the consequent risk models based on 6-minute-walk-test and NT-proBNP. METHODS: The derivation cohort comprised 636 German patients with systolic dysfunction. They were validated against 676 British patients with similar aetiology. ROC-curves for 1-year mortality identified cut-off values separately for specificity (none, sex, beta-blocker, both). Patients were grouped according to number of cut-offs met (group I/II/III - 0/1/2 cut-offs). RESULTS: Widest separation between groups was achieved with sex- and beta-blocker-specific cut offs. In the derivation population, 1-year mortality was 0%, 8%, 31% for group I, II and III, respectively. In the validation population, 1-year rates in the three risk groups were 2%, 7%, 14%, respectively, after application of the same cut-offs. CONCLUSION: Risk stratification for CHF should perhaps take sex and beta-blocker usage into account. We derived and independently validated relevant risk models based on 6-minute-walk-tests and NT-proBNP. Specifying sex and use of beta-blockers identified three distinct sub-groups with widely differing prognosis. In clinical practice, it may be appropriate to tailor the intensity of follow-up and/or the treatment strategy according to the risk-group.

Intelligent model-based advisory system for the management of ventilated intensive care patients. Part II: Advisory system design and evaluation.

The optimisation of ventilatory support is a crucial issue for the management of respiratory failure in critically ill patients, aiming at improving gas exchange while preventing ventilator-induced dysfunction of the respiratory system. Clinicians often rely on their knowledge/experience and regular observation of the patient's response for adjusting the level of respiratory support. Using a similar data-driven decision-making methodology, an adaptive model-based advisory system has been designed for the clinical monitoring and management of mechanically ventilated patients. The hybrid blood gas patient model SOPAVent developed in Part I of this paper and validated against clinical data for a range of patients lung abnormalities is embedded into the advisory system to predict continuously and non-invasively the patient's respiratory response to changes in the ventilator settings. The choice of appropriate ventilator settings involves finding a balance among a selection of fundamentally competing therapeutic decisions. The design approach used here is based on a goal-directed multi-objective optimisation strategy to determine the optimal ventilator settings that effectively restore gas exchange and promote improved patient's clinical conditions. As an initial step to its clinical validation, the advisory system's closed-loop stability and performance have been assessed in a series of simulations scenarios reconstructed from real ICU patients data. The results show that the designed advisory system can generate good ventilator-setting advice under patient state changes and competing ventilator management targets.

Intelligent model-based advisory system for the management of ventilated intensive care patients: Hybrid blood gas patient model.

Arterial blood gas (ABG) analyses are essential for assessing the acid-base status and guiding the adjustment of mechanical ventilation in critically ill patients. Conventional ABG sampling requires repeated arterial punctures or the insertion of an arterial catheter causing pain, haemorrhage and thrombosis to the patients. Less invasive and non-invasive blood gas analysers, with a technology still in transition, have offered some promise in the recent years. SOPAVent (Simulation of Patients under Artificial Ventilation) is a five compartment blood gas model which captures the basic features of respiratory physiology and gas exchange in the human lungs. It uses ventilator settings and routinely monitored physiological parameters as inputs to produce steady-state estimates of the patient's ABG. This paper overviews the original SOPAVent model and presents an improved data-driven hybrid model that is patient-specific and gives continuous and totally non-invasive ABG predictions. The model has been comprehensively tested in simulations and validated using recorded measurements of ABG and ventilator parameters from ICU patients.

A randomised, controlled study of rate versus rhythm control in patients with chronic atrial fibrillation and heart failure: (CAFE-II Study).

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) often coexist. The aim was to investigate whether restoring sinus rhythm (SR) could improve cardiac function, symptoms, exercise capacity and quality of life (QoL) in patients with chronic heart failure. METHODS: Patients with HF and persistent AF receiving guideline-recommended treatments, including anticoagulants, were eligible for the study. Patients were randomised to either rhythm (treated with amiodarone for at least 3 months prior to attempting biphasic external cardioversion and continued amiodarone long-term if SR was restored) or rate control. Anticoagulants were continued throughout the study regardless of rhythm, unless contraindications developed. Both groups were treated with beta blockers and/or digoxin to reduce the heart rate to <80 bpm at rest and <110 bpm after walking. Symptoms, walk distance (6-minute corridor walk test, 6MWT), QoL and cardiac function were assessed at baseline and 1 year. RESULTS: 61 patients with HF and persistent AF (median duration 14 months (IQR 5 to 32)) were randomly assigned to a rate or rhythm control strategy. Of patients assigned to rhythm control (n = 30), 66% were in SR at 1 year, and 90% of those assigned to rate control (n = 31) achieved the heart rate target. At 1 year, NYHA class (p = 0.424) and 6MWT distance (p = 0.342) were similar between groups but patients assigned to rhythm control had improved LV function (p = 0.014), NT-proBNP concentration (p = 0.046) and QoL (p = 0.019) compared with those assigned to rate control. Greatest improvement was seen in patients in whom SR was maintained. CONCLUSION: Restoring SR in patients with AF and heart failure may improve QoL and LV function when compared with a strategy of rate control.

Elevated glycated haemoglobin is a strong predictor of mortality in patients with left ventricular systolic dysfunction who are not receiving treatment for diabetes mellitus.

BACKGROUND: Glycated haemoglobin (HbA1c) is an indicator of average blood glucose concentrations over the preceding 3 months, is simpler to perform than either a fasting glucose or glucose tolerance test and is associated with a worse prognosis in some clinical settings. However, its relationship to survival in patients with suspected heart failure has not been studied. METHODS: Patients referred to a community-based heart failure clinic with suspected heart failure had a comprehensive assessment including the measurement of HbA1c. For this analysis, patients with DM or who started diabetic medication in the subsequent 12 months, which might influence HbA1c, were excluded. FINDINGS: Of 970 non-diabetic patients referred between 2001 and 2004, the median age was 72 years (range 25 to 96 years), 56% were men, 45% had left ventricular ejection fraction (LVEF) 6% (upper reference limit). Among patients with LVEF 6.7% (n = 68) compared with those with HbA1c 45% (HR 1.44, p = 0.36 after adjustment). INTERPRETATION: The abrupt increase in mortality with HbA1c may make it a useful risk stratification tool in non-diabetic patients with LVEF

The prognostic value of individual NT-proBNP values in chronic heart failure does not change with advancing age.

BACKGROUND: It is unclear whether age-related increases in N-terminal pro-brain natriuretic peptide (NT-proBNP) represent a normal physiological process-possibly affecting the prognostic power-of NT-proBNP-or reflect age-related subclinical pathological changes. OBJECTIVE: To determine the effect of age on the short-term prognostic value of NT-proBNP in patients with chronic heart failure (CHF). DESIGN: Prospective observational study with inclusion and matching of consecutive patients aged >65 years (mean (SD) 73.1 (6.0) years) to patients <65 years (53.7 (8.6) years) with respect to NT-proBNP, New York Heart Association stage, sex and aetiology of CHF (final n = 443). SETTING: University hospital outpatient departments in the UK and Germany. PATIENTS: Chronic stable heart failure due to systolic left ventricular dysfunction. INTERVENTION: None. OUTCOME MEASURE: All-cause mortality. RESULTS: In both age groups, NT-proBNP was a significant univariate predictor of mortality, and independent of age, sex and other established risk markers. The prognostic information given by NT-proBNP was comparable between the two groups, as reflected by the 1-year mortality of 9% in both groups. The prognostic accuracy of NT-proBNP as judged by the area under the receiver operating characteristics curve for the prediction of 1-year mortality was comparable for elderly and younger patients (0.67 vs 0.71; p = 0.09). CONCLUSION: NT-proBNP reflects disease severity in elderly and younger patients alike. In patients with chronic stable heart failure, the NT-proBNP value carries the same 1-year prognostic information regardless of the age of the patient.

Relating mean blood glucose and glucose variability to the risk of multiple episodes of hypoglycaemia in type 1 diabetes.

AIMS/HYPOTHESIS: The main disadvantage of intensive treatment in the Diabetes Control and Complications Trial (DCCT) was an increased risk of hypoglycaemia that was not explained by the difference in HbA(1c) values alone. This study re-analysed DCCT data to establish whether mean blood glucose (MBG) and/or glucose variability add to the predictive value of HbA(1c) for hypoglycaemia risk in type 1 diabetes. METHODS: The times to first and subsequent severe hypoglycaemic events were compared with MBG, HbA(1c) and within-day SD of blood glucose using Cox regression after adjusting for other known risk factors for hypoglycaemia. RESULTS: On its own, the incidence of time to first hypoglycaemic event increased 1.05-fold for each 1 mmol/l decrease in MBG and 1.07-fold for every 1 mmol/l increase in glucose SD. MBG and SD of blood glucose also both added to the ability of HbA(1c) to predict repeated hypoglycaemic events: after adjusting for HbA(1c), a 1 mmol/l increase in SD was associated with a 1.09-fold increased risk of a first event, increasing to a 1.12-fold risk of a fifth event. A 1 mmol/l fall in MBG added a constant 1.02-1.03-fold risk of repeated events. Daytime events were predicted more accurately than nocturnal episodes. CONCLUSIONS/INTERPRETATION: This study has established that HbA(1c), MBG and glucose variability measurements each have an independent role in determining an individual's risk of hypoglycaemia in type 1 diabetes. All three aspects of glycaemic assessment should thus be considered in patients in whom hypoglycaemia is a real or potential problem.

Prognostic value of systolic mitral annular velocity measured with Doppler tissue imaging in patients with chronic heart failure caused by left ventricular systolic dysfunction.

OBJECTIVE: To assess the prognostic value of various conventional and novel echocardiographic indices in patients with chronic heart failure (CHF) caused by left ventricular (LV) systolic dysfunction. METHODS: 185 patients with a mean (SD) age of 67 (11) years with CHF and LV ejection fraction < 45% despite optimal pharmacological treatment were prospectively enrolled. The patients underwent two dimensional echocardiography with tissue harmonic imaging to assess global LV systolic function and obtain volumetric data. Transmitral flow was assessed with conventional pulse wave Doppler. Systolic (Sm), early, and late diastolic mitral annular velocities were measured with the use of colour coded Doppler tissue imaging. RESULTS: During a median follow up of 32 months (range 24-38 months in survivors), 34 patients died and one underwent heart transplantation. Sm velocity (hazard ratio (HR) 0.648, 95% confidence interval (CI) 0.463 to 0.907, p = 0.011), diastolic arterial pressure (HR 0.965, 95% CI 0.938 to 0.993, p = 0.015), serum creatinine (HR 1.006, 95% CI 1.001 to 1.011, p = 0.023), LV ejection fraction (HR 0.945, 95% CI 0.899 to 0.992, p = 0.024), age (HR 1.035, 95% CI 1.000 to 1.071, p = 0.052), LV end systolic volume index (HR 1.009, 95% CI 0.999 to 1.019, p = 0.067), and restrictive pattern of transmitral flow (HR 0.543, 95% CI 0.278 to 1.061, p = 0.074) predicted the outcome of death or transplantation on univariate analysis. On multivariate analysis, only Sm velocity (HR 0.648, 95% CI 0.460 to 0.912, p = 0.013) and diastolic arterial pressure (HR 0.966, 95% CI 0.938 to 0.994, p = 0.016) emerged as independent predictors of outcome. CONCLUSIONS: In patients with CHF and LV systolic dysfunction despite optimal pharmacological treatment, the strongest independent echocardiographic predictor of prognosis was Sm velocity measured with quantitative colour coded Doppler tissue imaging.

Predicting peak oxygen uptake from 6-min walk test performance in male patients with left ventricular systolic dysfunction.

BACKGROUND: In patients with left ventricular systolic dysfunction (LVSD), peak oxygen uptake (pVO2) has strong predictive power for mortality, and can be used to guide management. However, many patients cannot tolerate standard test protocols. The 6-min walk test (6-MWT) is often used to estimate functional capacity due to its simplicity, cost effectiveness and familiarity to patients with LVSD. The relationship between 6-MWT performance and pVO2 is not certain, but if closely related could allow substitution of an expensive and cumbersome test for a cheaper and more familiar one. METHODS AND RESULTS: 120 male patients with LVSD (LVEF <40%; (mean+/-S.D.) age 68+/-13 years; BMI 28+/-5) performed, in random order, a maximal incremental treadmill exercise test with metabolic gas exchange measurements to derive peak oxygen consumption (pVO2 = 19.8+/-5.8 mL.kg(-1).min(-1)), and a standardised 6-MWT (308+/-142 m; r = 0.44; P = 0.00001). In multivariate models including demographic data, resting blood pressure and heart rate, spirometry, routine blood samples, and walk distance, five variables were independently predictive of peak oxygen consumption. pVO2 = 11.92 + (1.48 x FEV1 (L)) + (1.12 x haemoglobin (g dl(-1))) + (0.016 x distance walked (m)) - (0.33 x BMI) - (0.11 x age (years)). This equation accounted for 48% of the variation in pVO2. CONCLUSIONS: Using these five simple variables, peak oxygen consumption can be estimated with moderate accuracy. In clinical practice, however, when an estimate of peak oxygen consumption is required, incremental exercise testing with metabolic gas exchange measurements cannot be avoided in male patients with LVSD. Further work is needed to assess the relation between estimated pVO2 and outcome.

A randomised, single-blind, single-centre clinical trial to evaluate comparative clinical efficacy of shampoos containing ciclopirox olamine (1.5%) and salicylic acid (3%), or ketoconazole (2%, Nizoral) for the treatment of dandruff/seborrhoeic dermatitis.

BACKGROUND: The association between seborrhoeic dermatitis and dandruff and the yeast Malassezia furfur is well recognized. Symptoms include scalp itchiness and scaling. Due to its antimycotic activity, ciclopirox olamine is established as an effective treatment for these scalp conditions. Salicylic acid has keratolytic properties and aids in the removal of scales. OBJECTIVE: To compare the therapeutic efficacy of a shampoo containing 1.5% ciclopirox olamine and 3% salicylic acid (CPO/SA) with Nizoral (2.0% ketoconazole shampoo) in a study involving 154 subjects with dandruff - 70 of whom also had seborrhoeic dermatitis of the scalp. Nizoral is currently a registered treatment for dandruff and seborrhoeic dermatitis. METHODS: The shampoos were used three times week for 4 weeks, with 2-week washout and follow-up periods. Clinical and self-assessments were made throughout treatment and after follow-up (day 43). Within and between-treatment assessments of signs and symptoms were analysed. RESULTS: In the two groups, seborrhoeic dermatitis and dandruff improved significantly throughout treatment, with lower clinical and self-assessment scores at both the end of treatment (day 29) and follow-up (day 43). Only the subjects treated with CPO/SA shampoo showed a significant reduction in the itching of seborrhoeic dermatitis at these times. CONCLUSION: The study demonstrated that both CPO/SA and Nizoral were safe and effective in the treatment of dandruff and seborrhoeic dermatitis.

Association of life events and psychological distress in family caregivers of dementia patients.

Relationships between life events and psychological distress were investigated for 197 dementia caregivers and 218 non-caregivers. Participants indicated which events on the Louisville Older Persons Events Scale they had experienced over the past six months. Life events were then classified as associated or unassociated with care-giving using differences in incidence rates between caregivers and non-caregivers. Primary care-giving stressors and associated life events were most predictive of psychological distress among caregivers. Among non-caregivers, unassociated negative life events were the strongest predictors of depression and life satisfaction. Implications for the assessment of life events and caregiver interventions are discussed.

Latent growth models of the longitudinal effects of dementia caregiving: a comparison of African American and White family caregivers.

Self-report measures of depression, physical health symptoms, and life satisfaction were collected over a 2-year period from 197 family caregivers of dementia patients and 218 noncaregivers (controls). Latent growth models were used to compare changes across time for African American and White caregivers, with gender, age, and socioeconomic status serving as covariates. Results indicated that White caregivers sustained higher levels of elevated depression and decreasing life satisfaction over time compared with African American caregivers. Both groups of caregivers reported increases in physical symptoms over time. These results indicate worsening difficulties over time for many White caregivers. African American caregivers show more resilience on measures of depression and life satisfaction but are still vulnerable to increases in physical symptoms over time. Implications for additional research and clinical intervention are discussed.

A double-blind investigation of the potential systemic absorption of isotretinoin, when combined with chemical sunscreens, following topical application to patients with widespread acne of the face and trunk.

This study assessed the systemic absorption of isotretinoin and its metabolites, during a 4-week application of a cream containing 0.1% isotretinoin and chemical sunscreens, compared with a 4% benzoyl peroxide cream, in patients with acne on the face and trunk. Blood was drawn at weeks 0, 1, 2, 3 and 4 and at 96 h post-treatment. Plasma levels of isotretinoin (13-cis-retinoic acid) and tretinoin (all-trans-retinoic acid) were quantified by liquid chromatography with tandem mass spectrometry and the presence of their combined 4-oxo metabolites were monitored from the peak area ratios observed. The isotretinoin group showed no statistically or clinically significant increases in plasma retinoid levels and mean levels did not exceed +/-2 SD of the mean pre-treatment values, indicating that endogenous levels were not being exceeded. No significant differences were detected between the isotretinoin group and the 4% benzoyl peroxide group. These findings indicated that retinoid absorption from a cream containing 0.1% isotretinoin and chemical sunscreens was clinically insignificant, when applied to patients with widespread acne.

End of life care and reactions to death in African-American and white family caregivers of relatives with Alzheimer's disease.

Family caregivers for relatives with Alzheimer's Disease (AD) often experience significant stress-related problems in mental and physical health. Patients with AD often survive for protracted periods of time, placing an extensive burden of care on the caregiver prior to the patient's death. The present study addresses ethnic differences in the experience of AD caregivers around the time of their loved one's death, including life-sustaining treatment decisions and reactions to death. The results showed that, in our sample, more patients died in their homes than has been reported for deaths in the United States. African-American and White caregivers differed substantially in their reports of end of life care and subjective reactions to the death. Compared with White caregivers, African-American caregivers were less likely to make a decision to withhold treatment at the time of death, less likely to have their relative die in a nursing home, and reported less acceptance of the relative's death and greater perceived loss. Results suggest that death after AD caregiving deserves further study, and that ethnic differences in end of life care and bereavement may be of particular importance.

Relation of useful field of view and other screening tests to on-road driving performance.

The purpose of this study was to examine the value of a clinical driving assessment battery in predicting performance on an on-road driving test. 43 participants referred to the Bryn Mawr Rehab Adapted Driving Program for evaluation of driving ability underwent an evaluation consisting of a predriver screening and an on road driving test. The predriver screening included a vision screening, a reaction rime task, a split-attention task, the Hooper Visual Organization Test, verbal and symbolic sign recognition, and assessment of Useful Field of View. Logistic regression analyses were applied to identify which predriver screening variables could be used to predict outcome on the on road driving test (pass/fail); UFOV was that best single predictor. The addition of screening tests beyond UFOV alone did not increase predictive validity. These findings suggest that UFOV may serve as an indicator of the need for further driving assessment.

Longitudinal course of behavioral problems during Alzheimer's disease: linear versus curvilinear patterns of decline.

BACKGROUND: Patients with Alzheimer's Disease (AD) are commonly assumed to experience a linear decline in behavioral functioning that parallels progressive cognitive decline. However, some researchers have suggested that specific behavioral problems either decline at different rates or improve in late dementia. METHODS: The present analyses examined 150 AD patients at an initial assessment, 61 of whom were also evaluated annually on two additional occasions. Measures of cognitive impairment and behavioral problems were obtained. RESULTS: Cross-sectional results indicated curvilinear associations between dementia severity and certain behavioral problems (forgetful behaviors, and emotional and impulsive behaviors). Longitudinal analyses further indicated trends for curvilinear rates of behavioral disturbance across time, with some problem areas showing improvement as AD progresses through the most severe stages. CONCLUSIONS: Even though Alzheimer's disease is a progressive dementia characterized by increasing cognitive deterioration, it appears to be inaccurate to expect behavioral functioning to show the same linear decline across time.

A placebo-controlled clinical trial to compare a gel containing a combination of isotretinoin (0.05%) and erythromycin (2%) with gels containing isotretinoin (0.05%) or erythromycin (2%) alone in the topical treatment of acne vulgaris.

PURPOSE: To compare the clinical benefit of isotretinoin (0.05%) and erythromycin (2%) gels alone and in combination (Isotrexintrade mark) in acne patients. PROCEDURE: The study was a randomised placebo-controlled trial in acne patients who should benefit from topical therapy. RESULTS: All treatment groups except placebo produced a time-related reduction in lesion counts, with the combined therapy producing the largest mean decrease. Between-group comparisons showed several significant differences. CONCLUSION: Isotrexin was significantly better than placebo at all time points for inflamed and total lesions, and was better than isotretinoin at week 4. Side-effects were minimal.