High- and intermediate-risk susceptibility variants in melanoma families from the Mediterranean area: A multicentre cohort from the MelaNostrum Consortium.

BACKGROUND: Most of large epidemiological studies on melanoma susceptibility have been conducted on fair skinned individuals (US, Australia and Northern Europe), while Southern European populations, characterized by high UV exposure and dark-skinned individuals, are underrepresented. OBJECTIVES: We report a comprehensive pooled analysis of established high- and intermediate-penetrance genetic variants and clinical characteristics of Mediterranean melanoma families from the MelaNostrum Consortium. METHODS: Pooled epidemiological, clinical and genetic (CDKN2A, CDK4, ACD, BAP1, POT1, TERT, and TERF2IP and MC1R genes) retrospective data of melanoma families, collected within the MelaNostrum Consortium in Greece, Italy and Spain, were analysed. Univariate methods and multivariate logistic regression models were used to evaluate the association of variants with characteristics of families and of affected and unaffected family members. Subgroup analysis was performed for each country. RESULTS: We included 839 families (1365 affected members and 2123 unaffected individuals). Pathogenic/likely pathogenic CDKN2A variants were identified in 13.8% of families. The strongest predictors of melanoma were ≥2 multiple primary melanoma cases (OR 8.1; 95% CI 3.3-19.7), >3 affected members (OR 2.6; 95% CI 1.3-5.2) and occurrence of pancreatic cancer (OR 4.8; 95% CI 2.4-9.4) in the family (AUC 0.76, 95% CI 0.71-0.82). We observed low frequency variants in POT1 (3.8%), TERF2IP (2.5%), ACD (0.8%) and BAP1 (0.3%). MC1R common variants (≥2 variants and ≥2 RHC variants) were associated with melanoma risk (OR 1.4; 95% CI 1.0-2.0 and OR 4.3; 95% CI 1.2-14.6, respectively). CONCLUSIONS: Variants in known high-penetrance genes explain nearly 20% of melanoma familial aggregation in Mediterranean areas. CDKN2A melanoma predictors were identified with potential clinical relevance for cancer risk assessment.

Toxicity and physiological effect of quercetin on generalist herbivore, Spodoptera litura Fab. and a non-target earthworm Eisenia fetida Savigny.

A novel flavonoid, quercetin, was isolated from the medicinal plant Euphorbia hirta L. through chromatography techniques including: TLC, Column chromatography, NMR and then screened for toxicity to larvae of Spodoptera litura Fab. Bioassays were used to analyze pupal weight, survival rate, fecundity, egg hatchability, population growth index, Nutritional index and histopathology of treated larvae at a range of E. hirta extract concentrations. Results of toxicity assays demonstrated that, 6 ppm of quercetin caused 94.6% mortality of second, 91.8% of third, 88% of fourth, and 85.2% of fifth instars respectively. The lethal concentrations (LC50 and LC90) was calculated as 10.88 and 69.91 ppm for fourth instar larvae. The changes in consumption ratio and approximate digestibility produced a reduction in growth rates. Histopathology examinations revealed that the cell organelles were severely infected. Analyses of earthworm toxicity effects resulted in significantly lower rates compared to synthetic insecticides (chloropyrifos and cypermethrin). These results suggests that the botanical compound (quercetin), could have a part as a new biorational product which provides an ecofriendly alternative. Validation of the potential of quercetin, still needs to be demonstrated under field conditions, where formulation will be important in maintaining the activity.

Target and non-target toxicity of botanical insecticide derived from Couroupita guianensis L. flower against generalist herbivore, Spodoptera litura Fab. and an earthworm, Eisenia foetida Savigny.

Botanical insecticides may provide alternatives to synthetic insecticides for controlling Spodoptera litura (F.) and they are target specific, biodegradable, and harmless to mammals. Eight natural chemical compounds with larvicidal activity were identified from fraction F6 of C. guianensis flower extract. Probit analysis of 95% confidence level exposed an LC50 of 223ppm against S. litura third instar larvae. The growth and development of S. litura was affected in sub-lethal concentrations of fraction F6 (50, 100, 150 and 200ppm) compared to controls. Similarly nutritional indices values decreased significantly compared to controls. Fraction F6 also damaged the gut epithelial layer and brush border membrane (BBM). This study also resolved the effects of toxicity to non-target earthworm treated with fraction F6 and chemical pesticides (monotrophos and cypermethrin) and the results showed that fraction F6 had no harmful effect on E. fetida. Further, fraction F6 was eluted and sub fractions F6c (50ppm) showed high mortality against S. litura third instar larvae. Octacosane from fraction F6c was established and confirmed using IR spectrum and HPLC. The time of retention of fraction F6c was confirmed with the octacosane standard. Fraction F6 of C. guianensis extract caused dose-dependent mortality towards S. litura. Octacosane in fraction F6c was establish to be the prominent chemical compound associated with causing mortality but other compounds present in the fraction F6 were shown to be associated with changes in development of S. litura at low dosages. S. litura at low dosage. Therefore, these findings suggest that octacosane may be one of the major insecticidal compounds affecting S. litura survival.

Formic and Acetic Acids in Degradation Products of Plant Volatiles Elicit Olfactory and Behavioral Responses from an Insect Vector.

Volatile phytochemicals play a role in orientation by phytophagous insects. We studied antennal and behavioral responses of the Asian citrus psyllid, Diaphorina citri, vector of the citrus greening disease pathogen. Little or no response to citrus leaf volatiles was detected by electroantennography. Glass cartridges prepared with ß-ocimene or citral produced no response initially but became stimulatory after several days. Both compounds degraded completely in air to a number of smaller molecules. Two peaks elicited large antennal responses and were identified as acetic and formic acids. Probing by D. citri of a wax substrate containing odorants was significantly increased by a blend of formic and acetic acids compared with either compound separately or blends containing ß-ocimene and/or citral. Response surface modeling based on a 4-component mixture design and a 2-component mixture-amount design predicted an optimal probing response on wax substrate containing a blend of formic and acetic acids. Our study suggests that formic and acetic acids play a role in host selection by D. citri and perhaps by phytophagous insects in general even when parent compounds from which they are derived are not active. These results have implications for the investigation of arthropod olfaction and may lead to elaboration of attract-and-kill formulations to reduce nontarget effects of chemical control in agriculture.

Identification and synthesis of a male-produced pheromone for the neotropical root weevil Diaprepes abbreviatus.

An unsaturated hydroxy-ester pheromone was isolated from the headspace and feces of male Diaprepes abbreviatus, identified, and synthesized. The pheromone, methyl (E)-3-(2-hydroxyethyl)-4-methyl-2-pentenoate, was discovered by gas chromatography-coupled electroantennogram detection (GC-EAD), and identified by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). The synthesis yielded an 86:14 mixture of methyl (E)-3-(2-hydroxyethyl)-4-methyl-2-pentenoate (active) and methyl (Z)-3-(2-hydroxyethyl)-4-methyl-2-pentenoate (inactive), along with a lactone breakdown product. The activity of the synthetic E-isomer was confirmed by GC-EAD, GC-MS, NMR, and bioassays. No antennal response was observed to the Z-isomer or the lactone. In a two-choice olfactometer bioassay, female D. abbreviatus moved upwind towards the synthetic pheromone or natural pheromone more often compared with clean air. Males showed no clear preference for the synthetic pheromone. This pheromone, alone or in combination with plant volatiles, may play a role in the location of males by female D. abbreviatus.

Cardiotoxicity in signal transduction therapeutics: erbB2 antibodies and the heart.

Cardiotoxicity is a common and potentially devastating side effect of antineoplastic drug therapy. This empiric observation is seen as paradoxical given that the cardiomyocyte is considered to be a terminally differentiated cell. Despite the fact that these cells do not divide after birth, adult cardiomyocytes may become "innocent bystander" targets of anticancer drugs designed to interfere with cell signaling pathways in rapidly proliferating cells. In breast cancer clinical trials, treatment with the erbB2 receptor antibody trastuzumab combined with anthracyclines has been associated with an increased risk for the development of cardiac pump failure. Trastuzumab/anthracycline cardiomyopathy may be the first clinically significant cardiotoxicity to emerge from signal transduction therapeutics. The erbB2 receptor tyrosine kinase is known to have a critical role in cardiac development. In addition, erbB2 is thought to participate in an important pathway for growth, repair, and survival of adult cardiomyocytes as part of a signaling network that involves neuregulins and the neuregulin receptor erbB4. However, erbB2 levels in the adult heart are low when compared with the levels found in erbB2-overexpressing breast cancer cells that are the intended targets of trastuzumab therapy. Thus, trastuzumab-associated cardiotoxicity must be explained by some alternative mechanism. After confirming that trastuzumab is capable of inducing tyrosine phosphorylation of the human cardiomyocyte erbB2 protein, a novel system for culturing human myocardium was developed in our laboratory. We used this system to study the effects of trastuzumab on human cardiomyocytes in vitro and observed trastuzumab-induced structural and functional changes in human cardiomyocytes that were at least partially reversible with the addition of recombinant neuregulins. The results obtained in these experiments support a direct action of trastuzumab on human cardiomyocytes. In addition, these data provide insight regarding potential molecular mechanisms. Most importantly, these data draw attention to the inherent risk of cardiotoxicity associated with a newly emerging class of antineoplastic drugs that interfere with signal transduction pathways.

A 9-year, single-institution, retrospective review of death rate and prognostic factors in adult respiratory distress syndrome.

OBJECTIVE: To evaluate, at a single institution, the adult respiratory distress syndrome (ARDS) death rate in critically ill ventilated surgical/trauma patients and to identify the factors predicting death in these patients. SUMMARY BACKGROUND DATA: The prognostic features affecting mortality at the onset of ARDS have not been clearly defined. Defining rare characteristics would be valuable because it would allow for better stratification of patients in clinical trials and more appropriate utilization of constrained resources in ICU environments. METHODS: A retrospective analysis of 980 ventilated surgical and trauma intensive care unit patients from January 1990 to December 1998 was performed at Rhode Island Hospital. One hundred eleven adult intensive care unit patients with ARDS were identified using the criteria of Lung Injury Score more than 2.50 and the definition from the American-European Consensus Conference. Slightly more than half were trauma patients, 57% were men, and the median age was 59 years. The overall death rate was 52%. Patients were segregated by admission date to the intensive care unit (before or after January 1, 1995). Severity of illness was measured by the Revised Trauma Score for trauma patients and the Acute Physiology and Chronic Health Evaluation III for surgical patients. The Multiple Organ Dysfunction Score was determined on the day of onset of ARDS for all patients. Other recorded variables were age, sex, intensive care unit length of stay, length and mode of ventilation, presence or absence of tracheostomy, ventilation variables of peak and mean airway pressures, lung injury scores, elective versus emergency surgery, and presence or absence of pneumonia. RESULTS: There was a significant decrease in the ARDS death rate from the period 1990 to 1994 to the period 1995 to 1998. The major reason for the decline was a reduction in the posttraumatic ARDS death rate. Lung-protective ventilation strategies were used more frequently in the second period than in the first, and the death rate was significantly decreased in trauma patients in the second period when lung-protective ventilation modes were used. Predictors of death at the onset of ARDS were advanced age, Multiple Organ Dysfunction Score of 8 or more, and Lung Injury Score of 2.76 or more. CONCLUSION: In this single-institution series, the death rate from ARDS declined from 1990 to 1998, primarily in posttraumatic patients, and the decrease is related to the use of lung-protective ventilation strategies. Based on this patient population, the authors developed a statistical model to evaluate important prognostic indicators (advanced age, organ system and pulmonary dysfunction measurements) at the onset of ARDS.

Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors.

BACKGROUND: Among patients with heart failure, there is controversy about whether there are clinical features and laboratory tests that can differentiate patients who have low ejection fractions from those with normal ejection fractions. The usefulness of angiotensin-converting enzyme (ACE) inhibitors among heart failure patients who have normal left ventricular ejection fractions is also not known. METHODS: From a registry of 2,906 unselected consecutive patients with heart failure who were admitted to 10 acute-care community hospitals during 1995 and 1997, we identified 1291 who had a quantitative measurement of their left ventricular ejection fraction. Patients were separated into three groups based on ejection fraction: < or =0.39 (n = 741, 57%), 0.40 to 0.49 (n = 238, 18%), and > or =0.50 (n = 312, 24%). In-hospital mortality, prescription of ACE inhibitors at discharge, subsequent rehospitalization, quality of life, and survival were measured; survivors were observed for at least 6 months after hospitalization. RESULTS: The mean (+/- SD) age of the sample was 75+/-11 years; the majority (55%) of patients were women. In multivariate models, age >75 years, female sex, weight >72.7 kg, and a valvular etiology for heart failure were associated with an increased probability of having an ejection fraction > or =0.50; a prior history of heart failure, an ischemic or idiopathic cause of heart failure, and radiographic cardiomegaly were associated with a lower probability of having an ejection fraction > or =0.50. Total mortality was lower in patients with an ejection fraction > or =0.50 than in those with an ejection fraction < or =0.39 (odds ratio [OR] = 0.69, 95% confidence interval [CI 0.49 to 0.98, P = 0.04). Among hospital survivors with an ejection fraction of 0.40 to 0.49, the 65% who were prescribed ACE inhibitors at discharge had better mean adjusted quality-of-life scores (7.0 versus 6.2, P = 0.02), and lower adjusted mortality (OR = 0.34, 95% CI: 0.17 to 0.70, P = 0.01) during follow-up than those who were not prescribed ACE inhibitors. Among hospital survivors with an ejection fraction > or =0.50, the 45% who were prescribed ACE inhibitors at discharge had better (lower) adjusted New York Heart Association (NYHA) functional class (2.1 versus 2.4, P = 0.04) although there was no significant improvement in survival. CONCLUSIONS: Among patients treated for heart failure in community hospitals, 42% of those whose ejection fraction was measured had a relatively normal systolic function (ejection fraction > or 0.40). The clinical characteristics and mortality of these patients differed from those in patients with low ejection fractions. Among the patients with ejection fractions > or =0.40, the prescription of ACE inhibitors at discharge was associated favorable effects.

The results of a randomized trial of a quality improvement intervention in the care of patients with heart failure. The MISCHF Study Investigators.

PURPOSE: Quality improvement and disease management programs for heart failure have improved quality of care and patient outcomes at large tertiary care hospitals. The purpose of this study was to measure the effects of a regional, multihospital, collaborative quality improvement intervention on care and outcomes in heart failure in community hospitals. PATIENTS AND METHODS: This randomized controlled study included 10 acute care community hospitals in upstate New York. After a baseline period, 5 hospitals were randomly assigned to receive a multifaceted quality improvement intervention (n = 762 patients during the baseline period; n = 840 patients postintervention), while 5 were assigned to a "usual care" control (n = 640 patients during the baseline period; n = 664 patients postintervention). Quality of care was determined using explicit criteria by reviewing the charts of consecutive patients hospitalized with the primary diagnosis of heart failure during the baseline period and again in the postintervention period. Clinical outcomes included hospital length of stay and charges, in-hospital and 6-month mortality, hospital readmission, and quality of life measured after discharge. RESULTS: Patients had similar characteristics in the baseline and postintervention phases in the intervention and control groups. Using hospital-level analyses, the intervention had mixed effects on 5 quality-of-care markers that were not statistically significant. The mean of the average length of stay among hospitals decreased from 8.0 to 6.2 days in the intervention group, with a smaller decline in mean length of stay in the control group (7.7 to 7.0 days). The net effects of the intervention were nonsignificant changes in length of stay of -1.1 days (95% confidence interval [CI]: -2.9 to 0.7 days, P = 0.18) and in hospital charges of -$817 (95% CI: -$2560 to $926, P = 0.31). There were small and nonsignificant effects on mortality, hospital readmission, and quality of life. CONCLUSIONS: The incremental effect of regional collaboration among peer community hospitals toward the goal of quality improvement was small and limited to a slightly, but not significantly, shorter length of stay.

Effects of fluconazole administration in critically ill patients: analysis of bacterial and fungal resistance.

HYPOTHESIS: The administration of fluconazole in intensive care unit (ICU) patients leads to the emergence of bacterial and fungal resistance. DESIGN: Retrospective analysis of 2 patient cohorts: (1) critically ill patients treated in surgical, trauma, and medical ICUs between June 1997 and January 1999 who did and did not receive fluconazole; and (2) ICU patients with fungal infections and sensitivity testing results from June 1994 to December 1998. SETTING: University-affiliated tertiary care hospital. PATIENTS: The first cohort included 99 ICU patients with documented microorganism culture(s) who were treated with (n = 50) or without (n = 49) fluconazole; the second cohort included 38 patients with Candida species infection, identification, and antifungal susceptibility testing. RESULTS: Mortality (40% vs 20%; P = .03) and hospital length of stay (33.8 vs 25.6 days; P = .04) were higher in the patients treated with fluconazole compared with patients not treated with fluconazole. The ICU length of stay was also higher in patients treated with fluconazole (23.7 vs 15.1 days; P = .009). An increase in bacterial resistance occurred in patients after fluconazole treatment as opposed to bacterial resistance of patients who were treated for bacterial microorganism(s) without fluconazole (16% vs 4%; P = .049). Comparison of patient populations with Candida species identification before and after December 1997 showed an increase in Candida species resistance to fluconazole (11% vs 36%; P = .16), respectively. Fungal strains were dominated by a combination of Candida albicans and Candida glabrata in both populations (60% [before 1998] vs 82% [after 1998]), with an emergence of Candida non-albicans species tolerant to fluconazole. The amount of fluconazole administered and the number of patients receiving fluconazole treatment in the ICUs has also increased when comparing both periods. CONCLUSIONS: Comparison of critically ill patient populations with and without fluconazole treatment found increased mortality and longer hospital and ICU lengths of stay in the fluconazole-treated group. This group also had higher bacterial pathogen resistance to antibiotics after fluconazole administration compared with bacterial resistance of patients without fluconazole treatment. Our results warrant concern regarding worsening bacterial infections, increased mortality, and an increase in Candida resistance to fluconazole from increased use in ICU patients, with a shift in yeast infection that is more difficult to treat.

Angiotensin-converting enzyme inhibitor use in older patients with heart failure and renal dysfunction.

OBJECTIVE: To examine the relationship between angiotensin-converting enzyme (ACE) inhibitor use and clinical outcomes among recently hospitalized patients with congestive heart failure (CHF) and coexisting renal insufficiency. DESIGN: A prospective cohort study. SETTING: Ten community hospitals in upstate New York. PARTICIPANTS: A total of 1076 hospital survivors identified from a consecutive series of CHF inpatients. MEASUREMENTS: Patients were followed prospectively for 6 months after hospital discharge to track mortality, hospital readmission, and quality of life. Clinical outcomes were stratified by ACE inhibitor use among those with renal dysfunction, defined as serum creatinine > or = 2.0 mg/dL, and among the remaining patients, whose serum creatinine was < or = 1.9. RESULTS: ACE inhibitor use was lower among 187 patients with renal dysfunction than among 889 patients with preserved function (41 vs 69%, P < .001). Age and sex were among the significant determinants of drug use in both groups. After adjustment for covariables, ACE inhibitor use among those with abnormal renal function was not associated with a lower risk for death or readmission, or better quality of life. By comparison, ACE inhibition conferred meaningful clinical benefit among those whose creatinine was < or = 1.9 mg/dL. CONCLUSION: Convincing evidence of clinical benefit from ACE inhibitor use is not readily detectable among a sample of 187 unselected older patients with CHF and moderate or severe renal insufficiency. Further studies to identify subsets of this group who might benefit are warranted.

Clinical outcomes in heart failure: report from a community hospital-based registry.

PURPOSE: Most of the recent information on the prognosis of patients with heart failure has come from large clinical trials or tertiary care centers. This study reports current information from a community hospital-based heart failure registry. SUBJECTS AND METHODS: We compiled data from 2,906 unselected consecutive patients with heart failure who were admitted to 10 acute care community hospitals in New York State between 1995 and 1997. Patients were followed prospectively for 6 months after hospital discharge or until their death. RESULTS: The mean (+/- SI)) age of the sample was 76 +/- 11 years. The majority of the patients were women (56%) and most were white (95%). Hospital length of stay averaged 7.4 +/- 7.6 days; hospital charges averaged $7,460 +/- $6,114. Mortality during the index admission was 5%. Among the 2,508 patients for whom mortality or follow-up data were available, an additional 411 died during follow-up, for a cumulative 6-month mortality of 23%. Progressive pump failure was the predominant cause of death in the hospital and after discharge. Although mean functional class (on a 1 to 4 scale) improved from 3.4 +/- 0.7 at hospital admission to 2.3 +/- 0.9 at 1 month after discharge, 43% of patients had at least one hospital readmission during follow-up and 25% had at least one recurrent admission for heart failure. The mean time from index discharge to first rehospitalization was 60 +/- 56 days. In all, 55% of patients (1,370 of 2,508) were rehospitalized or died during the study period. CONCLUSIONS: Despite advances in the management of heart failure, patients recently hospitalized for this disorder remain at high risk of death, hospital readmission, and poor clinical outcome. Discovery or implementation of new or existing methods of prevention and treatment remain a high priority.

Noninvasive assessment of transplant-associated arteriosclerosis.

BACKGROUND: Transplant-associated arteriosclerosis is the major limitation to long-term survival in the cardiac transplant recipient, and annual surveillance angiography is used in many centers to monitor its progression. Noninvasive methods would be preferable because angiography is invasive, costly, and insensitive; however, the reliability of such methods has been questioned. METHODS: All publications relating to the assessment of the cardiac allograft by noninvasive testing were identified through MEDLINE and a review of references from the published literature on transplant-associated arteriosclerosis. RESULTS: Resting and stress ECG, radionuclide scintigraphy, echocardiography, and positron emission tomography have all been used in cardiac transplant recipients with variable results. Most techniques are insensitive, but this limitation may be improved with pharmacologic stress imaging like dobutamine echocardiography. Although insensitive, some methods have good specificity (i.e., radionuclide scintigraphy). The noninvasive measurement of absolute coronary blood flow is promising as a specific and sensitive technique but is limited by availability and cost. CONCLUSIONS: In general, noninvasive techniques to assess transplant-associated coronary arteriosclerosis are limited by variable sensitivity and specificity. However, certain methods, such as dobutamine echocardiography and radionuclide scintigraphy, can provide important adjunctive physiologic information to angiography. Such techniques can therefore help to guide the care and treatment of the cardiac transplant recipient with allograft coronary arteriosclerosis.

Association between diuretic use, clinical response, and death in acute heart failure.

Because the impact of diuretic use on mortality in acute congestive heart failure (CHF) is not known, we examined the association between drug use, fluid balance, and death among 1,150 patients hospitalized for evaluation and treatment of CHF. After adjusting for other relevant intergroup differences, we observed that less net weight loss and a greater number of intravenous drug doses retained significant predictive value for death, suggesting that more frequent diuretic dosing or diuretic resistance may be related to mortality in acute CHF.

Use of angiotensin-converting enzyme inhibitors in heart failure with preserved left ventricular systolic function.

This study was conducted to provide evidence of an association between angiotensin-converting enzyme (ACE) inhibitor use and clinical outcomes among patients with congestive heart failure (CHF) and preserved left ventricular (LV) systolic function who are treated in the community setting, and to compare the magnitude and direction of these associations among the subset with preserved function to the subset with LV contractile dysfunction. Seven hundred sixty-three hospital survivors who had measurement of systolic function were identified from among a series of consecutive patients with CHF admitted to 10 community hospitals. They were prospectively followed-up for 6 months after discharge to track death, hospital readmission, and quality of life. Outcomes were stratified by ACE inhibitor use among those with preserved systolic function, defined as an LV ejection fraction (EF) > or = 40% or qualitatively normal contractility, and among those with systolic dysfunction, defined as an EF < or = 39% or qualitatively abnormal contractility. ACE inhibitor prescription rates were higher among the 413 patients with LV contractile dysfunction than among the 350 with preserved function (77% vs 54%, p < 0.0001). Drug-treated and untreated patients were similar in many ways, although lower serum creatinine levels, lower EF, and a higher prevelance of high blood pressure characterized those receiving ACE inhibitors. After adjusting for these and other covariables, ACE inhibitor use among the group with normal function was associated with a trend for a lower risk of death and delayed time to hospital readmission but not absolute rates of rehospitalization. By comparison, ACE inhibition among those with impaired systolic function was associated with trends for lower risk of death and rehospitalization. These data suggest that ACE inhibition may be of benefit when CHF occurs in the context of preserved or normal LV systolic function. Large, multicenter, prospective randomized trials to better test this hypothesis are warranted.

Predictors and determinants of hospital length of stay in congestive heart failure in ten community hospitals.

BACKGROUND: Little is known about the actual determinants of hospital length of stay (LOS) among patients admitted with congestive heart failure (CHF), in spite of its economic impact. To increase understanding of these factors, we examined the demographic, clinical, laboratory, and treatment characteristics of patients hospitalized with decompensated CHF. METHODS: The charts of consecutive patients admitted to 10 acute care community hospitals during 1995 were reviewed. The relationship between LOS and more than 140 patient-specific variables were examined. First, patient characteristics identifiable within the first 24 hours of hospitalization were examined for their relationship with LOS. Then, variables indicative of the processes of care and response to treatment were studied. Finally, administrative data were added to yield the final model for LOS. RESULTS: During the study period 1402 patients were admitted to the participating centers. The patients were predominantly elderly with moderately severe or severe CHF. With stepwise multiple linear regression, 5% of the variation in LOS could be explained by baseline characteristics alone (r = 0.22, p < 0.0001). When treatment and response variables were added to this model, 15% of the variation in LOS could be explained (r = 0.39, p < 0.0001). When administrative data were added, the final model explained 31% of the variation in LOS (r = 0.56, p < 0.0001). CONCLUSIONS: We conclude that LOS among patients hospitalized with decompensated CHF is partially related to patient demographics, severity of illness, management modalities, response to treatment, and administrative data. However, significant residual variation in LOS exists, which cannot be explained by these factors. These observations may be of value in the design and implementation of initiatives aimed at reducing resource utilization and improving quality of care in CHF.

The relationship between hospital length of stay and rate of death in heart failure.

OBJECTIVE: To study the relationship between length of stay (LOS) and the rate of death among patients hospitalized with congestive heart failure (CHF). DESIGN: A retrospective, observational study. SETTING: Fifteen acute care community hospitals in upstate New York. PATIENTS: Three thousand nine hundred fourteen patients whose principal billing diagnosis was diagnosis-related group number 127 (CHF and shock). OUTCOME MEASURES: Mean total LOS and hospital death rate. VARIABLES: Mean number of nonacute care hospital days per patient, mean number of acute care days (acute LOS) per patient, cases per hospital, hospital bed capacity, and the presence of a cardiac catheterization laboratory, cardiac surgical services, or a medical residency training program. An index of severity of illness and a severity-weighted expected LOS were calculated for each patient as well. RESULTS: Significant variability in mean total LOS (7.6 to 12.7 days), mean acute LOS (7.1 to 10.3 days), and death rates (4.3 to 12.0%) was noted among the centers. Minimal variation in mean expected LOS (5.2 to 6.1 days) and mean severity score (2.8 to 3.3) was observed. Mean total LOS (r = 0.14, p = 0.61) and acute LOS (r = 0.11, p = 0.69) were not related significantly to death rate for the 15 centers. When the hospitals were separated into tertiles based on rank order of total LOS and acute LOS, no differences among the subgroups were noted in the number of cases per hospital, deaths per hospital, death rates, expected LOS, and severity scores, Interhospital variation in total LOS was partially explained by the care of patients who did not require acute hospitalization. CONCLUSIONS: Significant interhospital variation exists in LOS and death rates for patients admitted with CHF; these two measures are not related to each another. This variability in outcome cannot be explained by severity of illness case-mix alone; significant variation in the processes and effectiveness of patient care may exist.

Does QI work? The Management to Improve Survival in Congestive Heart Failure (MISCHF) study.

BACKGROUND: In an ongoing study, a randomized, controlled trial is being conducted on the effects of a collaborative quality improvement program on practice patterns and patient outcomes regarding congestive heart failure (CHF) in community hospitals in upstate New York. CHF is associated with severe morbidity and mortality, with annual rates of death exceeding 50% among patients with the most severe disease. PHASE I: Phase I of the study was designed to model the processes of care and outcomes, develop valid disease-specific risk adjustment techniques, and target areas for quality improvement (QI) intervention. Beginning April 1, 1995, and ending December 31, 1995, baseline data were collected during hospitalization and for six months postdischarge for all 1,402 consecutive patients assigned diagnosis-related groups (DRGs) 127 and 124. Preliminary analyses revealed high rates of hospital readmission (46%) and postdischarge death (18%), with significant interhospital variation. QI INITIATIVES: Initiatives include educational programs on CHF, feedback of Phase I data to clinicians and administrators, design and implementation of a clinical care pathway, improvement of the emergency department (prehospital) phase of CHF management, and improvement in patient education and discharge planning. SUMMARY AND CONCLUSIONS: The study suggests that community hospitals, many without extensive experience in clinical investigation, can voluntarily collaborate to design and implement a timely QI initiative that is evidence based, clinically relevant, and scientifically sound. Preliminary results have led to better understanding of the processes of care and determinants of outcome for patients with heart failure. Phase II of the study should yield insights into the providers' response to a locally derived intervention and the effects of such a program on patient outcomes.