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Temporal relationships of ventilatory failure, pump failure, and diaphragm fatigue.

The time course of ventilatory failure, pump failure, and diaphragm peripheral fatigue was determined during the application of external inspiratory resistive loads (IRL) in anesthetized rabbits. Pump failure is defined as the inability of the diaphragm to sustain the expected force under IRL. To assess contractile fatigue, transdiaphragmatic pressures (Pdi) generated by bilateral phrenic nerve stimulation at 75 Hz (Pdi-75) and 20 Hz (Pdi-20) were measured. The amplitude of evoked diaphragm electromyographic (EMG) signals was measured to assess neurotransmission failure. The rate of rise of spontaneous diaphragm EMG was used as an index of respiratory drive. Ventilation was evaluated together with arterial blood gases. During IRL the rate of rise of spontaneous diaphragm EMG increased, and there was a progressive hypercapnic acidosis and hypoxemia, indicating ventilatory failure. In contrast, Pdi-75 and Pdi-20 were stable until the time of respiratory arrest (apnea), when they decreased by 34 and 45%, respectively. The amplitude of evoked diaphragm EMG signals remained unchanged throughout the IRL and decreased only slightly at the time of apnea. We conclude that IRL induces progressive ventilatory failure long before any contractile fatigue of the diaphragm or pump failure occurs. This suggests that ventilatory failure is due to central fatigue, whereas pump failure (apnea) is attributable to multiple factors.

Airway Resistance↗

The shame of failure: examining the link between fear of failure and shame.

The present research was designed to examine hypotheses derived from the proposition that shame is the core of fear of failure. Study 1 was conducted in a naturalistic setting and demonstrated that individuals high in fear of failure reported greater shame upon a perceived failure experience than those low in fear of failure. These findings were obtained controlling for other negative emotions. Study 2 was conducted in a controlled laboratory setting and demonstrated that high fear of failure individuals reported greater shame, overgeneralization, and closeness to their mother (controlling for baseline levels of these variables) than those low in fear of failure. Those high in fear of failure also reported that they would be less likely to tell their mother and father about their failure experience and would be more likely to tell their mother and father about their success experience. The implications of these findings for acquiring a deeper understanding of fear of failure are discussed.

Achievement↗

Failure to practice evidence-based medicine: why do physicians not treat patients with heart failure with angiotensin-converting enzyme inhibitors?

The proportion of heart failure patients treated with an angiotensin-converting enzyme (ACE) inhibitor has increased over time, however, these drugs continue to be underutilized in this syndrome. There are a number of possible explanations for the failure of physicians to prescribe these agents optimally: (1) failure to recognize that heart failure is an important public health problem worthy of treatment; (2) failure to appreciate fully the magnitude of the clinical benefit of ACE inhibitors in heart failure; (3) failure to understand that the clinical benefits of ACE inhibitors fully justify the cost of these drugs; (4) concern that the adverse effects of ACE inhibitors outweigh their clinical benefits; (5) belief that the benefits observed in clinical trials do not translate into clinical practice. In reality, heart failure is a very common, extremely disabling, costly and deadly disorder. ACE inhibitors substantially reduce the morbidity and mortality related to heart failure, do this cost effectively and with a favourable risk-benefit ratio. Despite these facts, many patients are still denied ACE inhibitor therapy. An improved educational effort and clear and practical guidelines are essential if the uptake of ACE inhibitors is to increase.

Angiotensin-Converting Enzyme Inhibitors↗

Cumulative effect of complete left bundle-branch block and chronic atrial fibrillation on 1-year mortality and hospitalization in patients with congestive heart failure. A report from the Italian network on congestive heart failure (in-CHF database).

BACKGROUND: Many clinical variables have been proposed as prognostic factors in patients with congestive heart failure. Among these, complete left bundle-branch block and atrial fibrillation are known to impair significantly left ventricular performance in patients with congestive heart failure. However, their combined effect on mortality has been poorly investigated. The aim of this study was to determine whether left bundle-branch block associated with atrial fibrillation had an independent, cumulative effect on mortality for congestive heart failure. METHODS AND RESULTS: We analysed the Italian Network on congestive heart failure (IN-CHF) Registry that was established by the Italian Association of Hospital Cardiologists in 1995. One-year follow-up data were available for 5517 patients. Complete left bundle-branch block and atrial fibrillation were associated in 185 (3.3%) patients. In this population the cause of congestive heart failure was dilated cardiomyopathy (38.4%), ischaemic heart disease (35.1%), hypertensive heart disease (17.3%), and other aetiologies (9.2%). This combination of electrical defects was associated with an increased 1-year mortality from any cause (hazard ratio, HR: 1.88; 95% CI 1.37-2.57) and sudden death (HR: 1.89; 95% CI 1.17-3.03) and 1-year hospitalization rate (HR: 1.83; 95% CI 1.26-2.67). CONCLUSIONS: In patients with congestive heart failure, the contemporary presence of left bundle-branch block and atrial fibrillation was associated with a significant increase in mortality. This synergistic effect remained significant after adjusting for clinical variables usually associated with advanced heart failure. We can conclude that this combination of electrical disturbances identifies a congestive heart failure specific population with a high risk of mortality.

Adolescent↗

Prognostic implications of hyperlactatemia, multiple organ failure, and systemic inflammatory response syndrome in patients with acetaminophen-induced acute liver failure.

OBJECTIVE: Hyperlactatemia has been suggested as a prognostic marker in acetaminophen-induced fulminant hepatic failure, and a modification of the King's College Hospital criteria to incorporate arterial lactate measurements has recently been proposed. The aims of the present study were to further evaluate arterial lactate as a prognostic marker in acetaminophen-induced fulminant hepatic failure and to analyze its relationship to known causes of hyperlactatemia such as multiple organ failure and inflammation. DESIGN: Data were collected early after admission and again at the time of onset of grade 3-4 hepatic encephalopathy from acetaminophen-induced fulminant hepatic failure. Multiple organ failure and inflammatory response were assessed by the sequential organ failure assessment (SOFA) score and manifestation of the severe inflammatory response syndrome (SIRS), respectively. SETTING: A specialized liver intensive care unit at a tertiary liver center. PATIENTS: One hundred and one consecutive patients with acetaminophen-induced fulminant hepatic failure and grade 3-4 hepatic encephalopathy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial lactate was higher in nonsurvivors than in survivors both early after admission (9.8 +/- 6.5 mmol/L vs. 5.2 +/- 4.2 mmol/L, p = .00004) and at the time of onset of hepatic encephalopathy (6.9 +/- 5.6 mmol/L vs. 3.2 +/- 2.0 mmol/L, p < .00001). At both time points, arterial lactate significantly correlated with SOFA score and the number of SIRS components fulfilled. Applying the lactate modification of the King's College Hospital criteria increased their sensitivity but reduced their specificity to <50%. CONCLUSIONS: The study confirmed arterial lactate as a prognostic marker in acetaminophen-induced fulminant hepatic failure. Arterial lactate correlated with SOFA score and with the number of SIRS components fulfilled. The lactate modification of the King's College Hospital criteria showed no obvious advantages over the existing selection criteria.

Acetaminophen↗

Fulminant hepatic failure secondary to congestive heart failure.

An elderly female with an acute episode of congestive heart failure, unaccompanied by any periods of hypotension, developed fulminant hepatic failure with an accompanying coagulopathy. Attempts to establish an etiology for her acute hepatic insufficiency, other than cardiac failure, proved negative. Fulminant hepatic failure as a consequence of congestive heart failure, without prolonged periods of hypotension preceding alteration in hepatic function, has not heretofore been described. Liver function is adversely effected in congestive heart failure. Hepatic ammonia clearance is impaired in cardiac failure and may be diminished to the point of resulting in hepatic encephalopathy. Coagulopathy is a frequent concomitant of fulminant hepatic failure. Establishing a clear etiology for a coagulopathy in the face of concomitant liver disease is difficult, thus making any therapeutic intervention fraught with peril.

Aged↗

Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. The Quinapril Heart Failure Trial Investigators.

OBJECTIVES: This study was performed to assess the efficacy, safety and clinical consequences of abrupt cessation of quinapril therapy in a placebo-controlled, randomized, double-blind withdrawal trial. BACKGROUND: Angiotensin-converting enzyme inhibitor therapy has assumed a pivotal role in the treatment of chronic heart failure. Quinapril hydrochloride, a nonsulfydryl angiotensin-converting enzyme inhibitor, has shown beneficial clinical effects in previous studies. METHODS: After > or = 10 weeks of single-blind quinapril therapy, 224 patients with New York Heart Association class II or III heart failure were randomized in double-blind fashion to continue quinapril (n = 114) or to receive placebo (n = 110) for 16 weeks. Changes in treadmill exercise time, New York Heart Association functional class, quality of life and symptoms of heart failure were assessed. RESULTS: Patients withdrawn to placebo had a significant deterioration in exercise tolerance (median change -16 s with placebo vs. +3 s with quinapril, p = 0.015). New York Heart Association functional class (p = 0.004) and quality of life were improved and signs and symptoms of congestive heart failure were lessened in those remaining on quinapril therapy compared with those receiving placebo. During double-blind treatment, 18 patients were withdrawn from the placebo group because of worsening heart failure compared with 5 patients withdrawn from quinapril treatment (p < 0.001). Rather than a precipitous deterioration of clinical status or early incidence of adverse events, withdrawal from quinapril was associated with steady worsening of heart failure, beginning 4 to 6 weeks after randomization to placebo. CONCLUSIONS: Quinapril is effective and safe for maintaining clinical stability in patients with moderate congestive heart failure. Withdrawal of quinapril from patients with heart failure results in a slow progressive decline in clinical status.

Aged↗

Hospital cost effect of a heart failure disease management program: the Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) trial.

BACKGROUND: Determine the effect on hospitalization cost of a heart failure disease management (HFDM) program delivered within a diverse provider network as demonstrated in the SPAN-CHF randomized controlled trial. METHODS: The SPAN-CHF trial was a prospective randomized assessment of the effectiveness of HFDM delivered for 90 days across a diverse provider network in a heterogeneous population of 200 patients. Baseline clinical and demographic data were obtained on each patient, mortality was monitored, and hospitalizations were tracked for 90 days. Cost estimates for each hospitalization were based on a subsample of patients seen at Tufts-New England Medical Center for whom hospitalization costs were calculated. Heart failure disease management program costs were estimated using a programmatic budget model. Hospital utilization and cost data were combined to estimate medical costs for intervention and control groups. RESULTS: Heart failure disease management had a favorable effect on heart failure hospitalization, which was partially offset by noncardiac hospitalizations. The relative odds of at least one all-cause hospitalization during the intervention period trended less for the intervention group compared with the control group (0.76 [95% CI 0.38-1.51]). The point estimate of the differential hospitalization cost between control and intervention groups was a reduction in cost of $375 per patient. The net effect including the costs of the program was an increase of $488 per patient for the intervention group compared with the control group. The program would have been cost saving if HFDM costs had been 24% lower. CONCLUSION: The HFDM intervention, administered over 90 days to patients hospitalized for heart failure, succeeded in reducing the rate of heart failure hospitalizations, although this effect was partially offset by an increase in non-heart failure hospitalizations. The resulting modest reduction in all-cause hospitalization costs was exceeded by the cost of the intervention. Thus, although the reduction in heart failure may be interpreted as an improvement in health status, it could not be considered cost saving.

Cardiac Output, Low↗

Rationale and design of a randomized trial to assess the effects of beta-blocker in diastolic heart failure; Japanese Diastolic Heart Failure Study (J-DHF).

BACKGROUND: Heart failure consists of two phenotypes: systolic heart failure and diastolic heart failure (DHF). A growing body of evidence demonstrated benefits of beta-blocker, angiotensin-converting enzyme inhibitor, and angiotensin II receptor blocker in systolic heart failure; however, evidence leading to therapeutic strategy of DHF is lacking. METHODS AND RESULTS: The Japanese Diastolic Heart Failure Study (J-DHF) is a multicenter, prospective, randomized trial designed to assess effects of beta-blocker in patients with DHF. A total of 800 patients (400 patients in each group) will be enrolled. The primary outcome is a composite of cardiovascular death and unplanned admission to hospital for congestive heart failure. Other outcomes include all-cause mortality, worsening of the symptoms of heart failure, or a need for modification of the treatment for heart failure. Serial assessment of echocardiographic and neurohumoral parameters and cost analysis of the treatment regimen will be conducted. The follow-up period is a minimum of 2 years. CONCLUSION: This study will provide important evidences for the treatment of DHF.

Adrenergic beta-Antagonists↗

Nurse-led heart failure clinics improve survival and self-care behaviour in patients with heart failure: results from a prospective, randomised trial.

AIM: The aim of this trial was to prospectively evaluate the effect of follow-up at a nurse-led heart failure clinic on mortality, morbidity and self-care behaviour for patients hospitalised due to heart failure for 12 months after discharge. METHODS: A total of 106 patients were randomly assigned to either follow-up at a nurse-led heart failure clinic or to usual care. The nurse-led heart failure clinic was staffed by specially educated and experienced cardiac nurses, delegated the responsibility for making protocol-led changes in medications. The first follow-up visit was 2-3 weeks after discharge. During the visit the nurse evaluated the heart failure status and the treatment, gave education about heart failure and social support to the patient and his family. RESULTS: There were fewer patients with events (death or admission) after 12 months in the intervention group compared to the control group (29 vs 40, p=0.03) and fewer deaths after 12 months (7 vs 20, p=0.005). The intervention group had fewer admissions (33 vs 56, p=0.047) and days in hospital (350 vs 592, p=0.045) during the first 3 months. After 12 months the intervention was associated with a 55% decrease in admissions/patient/month (0.18 vs 0.40, p=0.06) and fewer days in hospital/patient/month (1.4 vs 3.9, p=0.02). The intervention group had significantly higher self-care scores at 3 and 12 months compared to the control group (p=0.02 and p=0.01). CONCLUSIONS: Follow up after hospitalisation at a nurse-led heart failure clinic can improve survival and self-care behaviour in patients with heart failure as well as reduce the number of events, readmissions and days in hospital.

Aged↗

Influence of carvedilol on hospitalizations in heart failure: incidence, resource utilization and costs. U.S. Carvedilol Heart Failure Study Group.

BACKGROUND: Carvedilol reduces disease progression in heart failure, but to our knowledge, its effects on hospitalizations and costs have not been evaluated. OBJECTIVES: We examined the effects on hospitalization frequency and costs in the U.S. Carvedilol Heart Failure Trials Program. This program consisted of four concurrent, multicenter, double-blind, placebo-controlled studies involving 1,094 patients with New York Heart Association class II to IV heart failure, which treated patients with placebo or carvedilol for up to 15 months (median, 6.5 months). METHODS: Detailed resource utilization data were collected for all hospitalizations occurring between randomization and the end of follow-up. In-patient care costs were estimated based on observed levels of resource use. RESULTS: Compared with placebo, carvedilol reduced the risk of hospitalization for any reason by 29% (p = 0.009), cardiovascular hospitalizations by 28% (p = 0.034) and heart failure hospitalizations by 38% (p = 0.041). Carvedilol also decreased the mean number of hospitalizations per patient (for cardiovascular reasons 30% [p = 0.02], for heart failure 53% [p = 0.03]). Among hospitalized patients, carvedilol reduced severity of illness during hospital admission, as reflected by shorter length of stay and less frequent use of intensive care. For heart failure hospital admissions, carvedilol decreased mean length of stay by 37% (p = 0.03) and mean number of intensive care unit/coronary care unit days by 83% (p = 0.001), with similar effects on cardiovascular admissions. As a result, estimated inpatient care costs with carvedilol were 57% lower for cardiovascular admissions (p = 0.016) and 81% lower for heart failure admissions (p = 0.022). CONCLUSIONS: Carvedilol added to angiotensin-converting enzyme inhibition reduces hospitalization risk as well as severity of illness and resource utilization during admission in patients with chronic heart failure.

Adrenergic beta-Antagonists↗

Renal failure in the ICU: comparison of the impact of acute renal failure and end-stage renal disease on ICU outcomes.

BACKGROUND: Acute renal failure (ARF) is associated with a persistent high mortality in critically ill patients in intensive care units (ICUs). Most studies to date have focused on patients with established, intrinsic ARF or relatively severe ARF due to multiple factors. None have examined outcomes of dialysis-dependent chronic renal failure [end-stage renal disease (ESRD)] patients in the ICU. We examined the incidence and outcomes of ARF in the ICU using a standard definition and compared these to outcomes of ICU patients with either ESRD or no renal failure. We sought to determine the impact of renal dysfunction and/or loss of organ function on outcome. METHODS: We prospectively scored 1530 admissions to eight ICUs over a 10-month period for illness severity at ICU admission using the Acute Physiological and Chronic Health Evaluation (APACHE III) evaluation tool. Patients were defined as having ARF based on the definition of Hou et al (Am J Med 74:243-248,1983) designed to detect significant measurable declines in renal function based on serum creatinine. ESRD patients were identified as being chronically dialysis-dependent prior to ICU admission and the remainder had no renal failure. Clinical characteristics at ICU admission and ICU and hospital outcomes were compared between the three groups. RESULTS: We identified 254 cases of ARF, 57 cases of ESRD and 1219 cases of no renal failure for an incidence of ARF of 17%. Roughly half the ARF patients had ARF at ICU admission and the remainder developed ARF during their ICU stay. Only 11% of ARF patients required dialysis support. ARF patients had significantly higher acute illness severity scores than those with no renal failure, whereas patients with ESRD had intermediate severity scores. ICU mortality was 23% for patients with ARF, 11% for those with ESRD, and 5% for those with no renal failure. There was no difference in outcome between patients who had ARF at ICU admission and those who developed ARF in the ICU. Patients with ARF severe enough to require dialysis had a mortality of 57%. APACHE III predicted outcome very well in patients with no renal failure and patients with ARF at the time of scoring but underpredicted mortality in those who developed ARF after ICU admission and overestimated mortality in patients with ESRD. CONCLUSIONS: ARF is common in ICU patients and has a persistent negative impact on outcomes, although the majority of ARF is not severe enough to require dialysis support. The mortality of patients with ARF from all causes is almost exactly similar to that noted using the same criteria two decades ago. More profound ARF requiring dialysis continues to have an even greater mortality. Nevertheless, acute declines in renal function are associated with a mortality that is not well explained simply by loss of organ function. The majority of ARF patients who did not require dialysis still had a considerably higher mortality than the ESRD patients, all of whom required dialysis; while ARF patients who did require dialysis had a much higher morality than ESRD patients. APACHE III performs well and captures the mortality of patients with ARF at the time of scoring. Development of ARF after scoring has a profound effect on standardized mortality. We were unable to identify a unique mortality associated with ARF, but the presence of measurable renal insufficiency continues to be a sensitive marker for poor outcome.

APACHE↗

Reshaping our perception of the typical hospitalized heart failure patient: a gender analysis of data from the ADHERE Heart Failure Registry.

Heart failure studies have suggested important differences between women and men both in heart failure etiology and in survival. Clinical trials and long-standing perceptions of the typical heart failure patient have related far more to men than to women, while more women than men in the United States may be hospitalized with heart failure. The goal of this study was to analyze ADHERE Registry data, the largest database of acute decompensated heart failure (ADHF) patient hospitalizations available, to gain insight into the effect of gender on medical history, clinical characteristics, and discharge counseling. This preliminary study analyzed the 85,617 ADHF hospitalizations in the ADHERE Registry as of October 2003, with 44,340 (52%) women and 41,276 (48%) men included. Women were significantly older (mean age 74.6 +/- 13.7 years) than men (mean age 70.2 +/- 13.9 years, P < .0001). Women were more likely to have a history of hypertension (75% vs. 69%, P < .0001) and a systolic blood pressure > 140 mm Hg (56% vs. 44%, P < .0001). History of coronary artery disease was more common in men (64% vs. 51%, P < .0001). Other risk factors for atherosclerosis, including smoking (17% vs. 10%, P < .0001) and hyperlipidemia (37% vs. 32%, P < .0001), were also more common in men. Men had a significantly lower mean left ventricular ejection fraction (32.9%, N = 30,831) than women (42.1%, N = 29,744); 51% of women had preserved left ventricular function (EF > 40%) compared to only 28% of men (P < 0.0001). At discharge, adherence to 3 of the 4 JCAHO standardized measures of quality of care far heart failure patients were documented more frequently for men than for women. A significantly smaller proportion of women received discharge instructions on management of diet, weight, and medications (30.1% vs. 32.8%); received or were scheduled for assessment of left ventricular function (81.5% vs. 85.6%); or were discharged with an angiotensin converting enzyme inhibitor prescription if appropriate (72.6% vs. 73.9%). Real-world data from the ADHERE Registry may lead to better recognition of the signs and symptoms of heart failure in women, increase the proportion of women who are correctly diagnosed, and may help to support gender-specific considerations in heart failure guidelines.

Aged↗

Renal failure in acute liver failure.

Renal failure develops in approximately 55% of all patients referred to specialized centres with acute liver failure. The renal failure may be secondary to the liver failure itself (and is termed the hepatorenal syndrome) or the renal failure may be a secondary insult that directly affects both liver and kidney alike (for example paracetamol overdose). The pathogenesis of the hepatorenal syndrome involves the development of a hyperdynamic circulation, with a lowering of renal perfusion pressure, the activation of the sympathetic nervous system, which renders the kidneys more susceptible to modest decreases in perfusion pressure, and increased synthesis of a variety of vasoactive mediators. These mediators can cause renal vasoconstriction, but more importantly they can also decrease the glomerular capillary ultrafiltration coefficient (Kf), thus causing a decline of glomerular filtration rate over and above that caused by renal vasoconstriction alone. The treatment of the renal failure in acute liver failure involves the optimization of renal haemodynamics and haemofiltration. Renal failure will always recover when there is recovery of liver function, and in the absence of a spontaneous hepatic recovery, liver transplantation will reverse the hepatorenal syndrome.

Acute Kidney Injury↗

Elevated serum immunoreactive inhibin levels in peripubertal boys with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure (CSPCRF).

OBJECTIVE: Boys with chronic renal failure have delayed progress through puberty and have raised gonadotrophin and low testosterone levels indicative of disturbed hypothalamo-pituitary-testicular function. Most studies into the mechanisms underlying the dysfunction have concentrated on the LH-Leydig cell interaction. However, it is now possible to probe the FSH-Sertoli cell axis by measuring plasma immunoreactive inhibin, which is a marker of Sertoli cell function. This study investigated the FSH-Sertoli cell (immunoreactive inhibin) axis in boys with chronic renal failure on conservative and dialysis treatment as they progressed through puberty. The effect of renal transplantation in chronic renal failure was also investigated. DESIGN: Blood was drawn at 15-minute intervals between 2000 and 0700 h from 51 boys with chronic renal failure at various stages of puberty. The samples were divided into two pools, corresponding to the hormone secretion in the first and second part of the night. Single blood samples were drawn from a group of normal boys between 0800 and 1000 h. PATIENTS: A total of 37 normal boys and 51 boys with chronic renal failure were examined immediately before and during puberty. Of a total of 80 pulse profiles taken in chronic renal failure, 36 were from transplanted and 44 from non-transplanted uraemic subjects. MEASUREMENTS: Immunoreactive inhibin, FSH and testosterone were measured using standard radioimmunoassays. The subjects were pooled into pubertal stages I, II/III and IV/V for analysis of hormone data. RESULTS: Early morning levels of immunoreactive inhibin like molecules (i-Inh) rose steadily with pubertal progression for all subject groups, those for boys with chronic renal failure being significantly elevated over normal boys from pubertal stage II/III onwards. Uraemic boys had higher levels than those who had been transplanted at all pubertal stages (P < 0.05). Early morning levels of FSH were significantly higher in uraemic patients with pubertal stages IV/V compared to our normal boys. There were no differences in i-Inh levels in plasma pooled from the samples taken between 2000 and 0115 h and 0130 and 0700 h for either treatment group at any stage of puberty. Testosterone levels rose in the second part of the profile from pubertal stages II/III onwards for both treatment groups. The proportional increase of testosterone was lower by mid puberty in uraemic than in transplanted children (percentage increases of 92 +/- 29 and 569 +/- 190 respectively, mean +/- SEM). i-Inh failed to correlate with FSH at any Tanner stage or for any subject group. CONCLUSION: Peripubertal boys with chronic renal failure have highly elevated serum immunoreactive inhibin and FSH levels which are partially reduced by renal transplantation. There was no evidence of any relationship between i-Inh and FSH secretion in either normal boys or in uraemic or transplanted boys with the exception of a positive correlation in late pubertal patients after transplantation. Finally, despite problems associated with the current immunoassay for inhibin, this assay may still prove to be a useful marker of Sertoli cell function in testicular pathology.

Adolescent↗

Acute heart failure and acute renal failure in Kawasaki disease.

Acute renal failure and acute heart failure are rare in Kawasaki disease. We experienced two patients with Kawasaki disease who presented acute renal failure and acute heart failure. These two patients gave us an important insight into the understanding of water balance and fluid therapy in Kawasaki disease. One patients showed acute prerenal failure due to fluid exudation from the intravascular to the extravascular space, and subsequent acute heart failure. The other patient showed acute heart failure caused by fluid infusion for the treatment of dehydration. It is suggested that acute renal failure could be caused by a fluid shift from the intravascular to the extravascular space in Kawasaki disease. It is also demonstrated that the reserve of cardiac function could be decreased in patients with Kawasaki disease due to myocarditis even with normal echocardiography and chest X-rays.

Acute Disease↗

Comparison of pioglitazone with other antidiabetic drugs for associated incidence of liver failure: no evidence of increased risk of liver failure with pioglitazone.

AIM: The aim of this study was to assess the incidence of liver failure in association with antidiabetic treatment using pioglitazone vs. other oral antidiabetic medications. METHODS: The study was a retrospective analysis of claim data from the PharMetrics Patient-Centric Database that had over 1.12 million enrollees with type 2 diabetes. All patients, > or =18 years of age with type 2 diabetes, who had initiated treatment either with a thiazolidinedione (pioglitazone and rosiglitazone), sulfonylurea or metformin were identified and matched on the basis of propensity scores, which served as a proxy for severity of disease. The primary measure of interest was the incidence of liver failure or hepatitis post-index date. In addition to unadjusted comparisons, Cox proportional hazard models were employed to estimate the risk of developing liver failure or hepatitis. RESULTS: There was no significant difference in the 1- and 2-year incidence rates of liver failure or hepatitis (primary and secondary diagnoses) between the pioglitazone monotherapy group and the respective comparator groups. In Cox proportional hazard models controlling for age, pre-index total healthcare costs, Charlson comorbidity index, procedures and a hospitalization or Emergency room (ER) visit for pre-index hyperglycaemia, and pioglitazone were not associated with an increased risk of liver failure or hepatitis, compared to all other defined groups. Furthermore, no primary or secondary diagnosis of liver failure was reported in the pioglitazone group during the follow-up period. CONCLUSIONS: Results of retrospective data analysis demonstrate no evidence of increased risk of liver failure or hepatitis for patients initiating therapy on pioglitazone, compared to other oral antidiabetic agents. Pioglitazone therapy was not associated with an increased risk of liver failure at 2 years relative to other oral antidiabetic therapies.

Administration, Oral↗

[Prognostic significance of diabetes in a heart failure population: one year mortality and heart failure related hospital admission].

BACKGROUND AND OBJECTIVE: The relationship between diabetes mellitus and heart failure is not fully established. The aim of the study was to assess the prevalence of diabetes and its prognostic significance, considering mortality and the need of hospital admission due to heart failure during the first year of follow-up, in an outpatient population with heart failure attended in a specialized Unit. PATIENTS AND METHOD: We studied 362 patients -73% men; mean age (standard deviation) 65.3 (10.9) years-. Mean ejection fraction was 32.2% (12.7%). Patients were in New York Heart Association functional class I (5%), II (47%), III (43%) and IV (5%). RESULTS: One-hundred forty-three out of 362 patients were diabetic (39.5%). Thirty patients (8%) died and 70 (19%) needed to be hospitalized due to heart failure during the first year of follow-up. One year mortality was 5% in non-diabetic patients and 13.3% in diabetic patients (p = 0.005). 13.2% of non-diabetic patients suffered at least one episode of heart failure needing hospital admission, whereas 28.7% of diabetic patients needed to be hospitalized at least once (p < 0.001). In the multivariate regression analysis, diabetes remained statistically associated both with mortality and with the need of heart failure related hospital admission. CONCLUSIONS: Diabetes significantly correlated with a higher one year mortality as well as with a greater need of hospital admission due to heart failure. Prevalence of diabetes in a general population with heart failure was high.

Aged↗