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.

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.

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.

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.

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.

Technetium-99m isonitrile myocardial uptake at rest. I. Relation to severity of coronary artery stenosis.

To determine the potential of planar technetium-99m methoxybutyl isonitrile myocardial imaging as a method of detecting totally occluded or severely stenosed coronary arteries, the regional distribution of technetium-99m isonitrile at rest was compared with the coronary anatomy in 38 patients with prior myocardial infarction who underwent coronary arteriography. Left ventricular technetium-99m isonitrile tracer uptake at rest was assessed in the three major coronary vascular territories. When qualitative rest technetium-99m isonitrile uptake was markedly reduced or absent (grade 0), there was a 91% probability of finding a totally occluded or severely stenosed coronary artery. When qualitative tracer uptake was reduced (grade 1) or normal (grade 2), it excluded all territories supplied by a totally occluded vessel with poor collateral flow. Quantitative technetium-99m isonitrile uptake (mean +/- 1 standard deviation) in territories supplied by an occluded coronary artery with poor collateral flow (42 +/- 21%) was lower than in territories supplied by a vessel with less than 50% stenosis (87 +/- 10%) and 50 to 99% stenosis (74 +/- 19%) (p less than 0.001). Furthermore, technetium-99m isonitrile uptake in areas supplied by an occluded coronary artery with good collateral flow (61 +/- 23%) was lower than in areas supplied by a vessel with less than 50% stenosis (87 +/- 10%) (p less than 0.001). Because rest technetium-99m isonitrile imaging detects coronary occlusion with poor collateral flow, this method may be useful in assessing patients with acute myocardial infarction.

Technetium-99m isonitrile myocardial uptake at rest. II. Relation to clinical markers of potential viability.

To determine the utility of rest-injected technetium-99m methoxybutyl isonitrile (Tc-99m isonitrile) uptake as a marker of myocardial viability, the regional uptake of this agent was compared with regional wall motion by equilibrium gated blood pool scan in 26 patients with previous myocardial infarction and with postrevascularization uptake in 8 patients after coronary bypass surgery. Rest left ventricular Tc-99m isonitrile uptake was assessed qualitatively in three coronary vascular territories as grade 0 (markedly reduced) to grade 2 (normal), and quantitatively by circumferential profile analysis. Wall motion was scored qualitatively in corresponding vascular territories as normal, hypokinetic or akinetic/dyskinetic. There was an overall relation between qualitative Tc-99m isonitrile uptake and wall motion. Abnormal wall motion occurred in 74% of vascular territories with perfusion grade 0, in 61% of those with grade 1 and in 30% of those with grade 2; however, 26% of territories with grade 0 uptake had normal wall motion. In the territories visually assigned perfusion grade 0, quantitative isonitrile uptake (mean value +/- SD) was higher when corresponding wall motion was normal or hypokinetic (62 +/- 15%) than when akinesia was detected by gated blood pool scan (39 +/- 16%, p less than 0.02). Qualitative Tc-99m isonitrile uptake improved after coronary bypass surgery in 12 of 13 territories with reduced uptake preoperatively; this included all 5 territories with a preoperative Tc-99m isonitrile score of 0. Quantitative uptake in these regions increased from 55 +/- 18% to 73 +/- 21% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

Evaluation of ventricular function in patients with coronary artery disease.

The recent expansion of interventional cardiovascular technologies has stimulated a concomitant expansion of noninvasive cardiac studies, both to assist in diagnosis and to evaluate treatment outcomes. Radionuclide ventricular function studies provide a reliable, reproducible means to quantify global left ventricular systolic performance, a critical determinant of prognosis in patients with cardiovascular disease. In addition, the ability to evaluate regional left ventricular wall motion and to assess ventricular performance during exercise have secured a fundamental role for such studies in the screening and treatment of patients with coronary artery disease. Radionuclide techniques have been extended to the evaluation of left ventricular relaxation/filling events, left ventricular systolic/diastolic function in the ambulatory setting, and with appropriate technical modifications, to the assessment of right ventricular performance at rest and with exercise. As a complement to radionuclide perfusion studies, cardiac blood-pool imaging allows for thorough noninvasive description of cardiac physiology and function in both normal subjects and in patients with a broad range of cardiovascular diseases.

Demonstration of viable, stunned myocardium with technetium-99m-sestamibi.

Delayed improvement of left ventricular contractile function in the setting of acute ischemia followed by reperfusion ("stunned myocardium") has been observed in a number of clinical scenarios, and may have important clinical implications. At present, there are no widely accepted techniques available to demonstrate its presence. We report a case in which a rest 99mTc-sestamibi scan performed 12 hr after thrombolytic therapy in the setting of acute myocardial infarction demonstrated viable myocardium in a region that was akinetic by contrast ventriculography. After surgical revascularization, follow-up 99mTc-sestamibi images showed normal perfusion and radionuclide ventriculography demonstrated normal left ventricular function. Demonstration of preserved 99mTc-sestamibi myocardial uptake in the infarct zone despite an extensive region of akinesis by contrast ventriculography predicted the recovery of left ventricular function after revascularization in this case. This suggests that perfusion imaging with 99mTc-sestamibi early after myocardial reperfusion can detect stunned myocardium and thus facilitate the decision-making process regarding management of such patients.

Myocardial perfusion scintigraphy: effect on diagnostic and clinical management algorithms.

UNLABELLED: Research has demonstrated that myocardial perfusion imaging increases the sensitivity and specificity of stress electrocardiography. However, the additional effect of the perfusion component of a stress study on clinical management algorithms remains poorly defined. METHODS: We prospectively assessed the decision-making process in 518 patients, from 191 clinicians, undergoing stress myocardial perfusion imaging in our departments. Each clinician was asked, by telephone interview, to define the probability of reversible myocardial ischemia and their management plan (i.e., no antianginal treatment, medical therapy or an invasive intervention) in three stages: pretest, after the stress data was made available and after completion of the perfusion study. RESULTS: The results of the stress data alone influenced the estimate of the probability of reversible ischemia in 149 of 518 patients, and management strategy in 50 of 518 patients. The data from the perfusion component in isolation changed probability of reversible disease in 219 of 518 patients and altered clinical management in 77 of 518 patients. Of 103 patients in whom an invasive procedure was planned after the stress data, the availability of the perfusion data led to deferral of catheterization in 48 cases (46.6%). Conversely, of the 415 patients triaged to a noninvasive plan after stress data, only 29 (7.0%) were changed to an invasive strategy. Of note, only 2.3% of women changed from a conservative strategy as a consequence of the perfusion data, compared to 9.1% of men. CONCLUSION: The perfusion component of a stress study has a significant effect on both estimation of clinical probability and the definition of patient management strategy. Myocardial perfusion imaging reduced the number of catheterizations in patients initially triaged to an invasive management strategy. Conversely, the effect of stress and perfusion data in patients triaged to conservative management on clinical grounds, especially women, remains less well defined.

Cardiac blood-pool imaging. II: Applications in noncoronary heart disease.

The role of radionuclide ventriculography in the initial evaluation, periodic assessment, and therapeutic follow-up of patients with valvular disease, hypertensive heart disease, lung disease, and cardiomyopathy is discussed.

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.

Patterns of angiotensin-converting enzyme inhibitor use in congestive heart failure in two community hospitals.

Because they provide relief of symptoms and reduce mortality, angiotensin-converting enzyme (ACE) inhibitors have become a highly recommended part of the pharmacologic treatment of patients with congestive heart failure (CHF). Although clinical trials suggest that 80% to 90% of patients with CHF tolerate ACE inhibitors, recent surveys reveal that for fewer than this number of patients are actually receiving these drugs. The reasons for this discrepancy are not known. To better understand physician-prescribing behavior, the current study examined the demographic, clinical, laboratory, and medical care characteristics of patients treated and not treated with ACE inhibitors during hospitalization for decompensated CHF. The charts of a consecutive series of patients admitted to 2 acute care hospitals during 1992 (n = 424) were reviewed and comparisons made between those receiving and not receiving ACE inhibitors at the time of hospital admission and hospital discharge. In addition, measures of in-hospital and postdischarge outcome were compared between the groups. The results revealed significant differences in certain demographic variables (e.g., patient age), clinical measures (e.g., left ventricular ejection fraction and serum creatinine), management issues (e.g., documentation of left ventricular function and documentation of etiology of CHF), and treatment strategies (e.g., ancillary drug use). Few differences were noted in measures of severity of CHF (e.g., New York Heart Association functional class and serum sodium level). Death rates were significantly higher for those not receiving ACE inhibitors. Patterns that emerged that could explain under-prescription ACE inhibitors included older age, worse renal function, left ventricular diastolic dysfunction, use of alternate vasodilators, and overall less intense medical management. Programs to educate care providers regarding the proper use of ACE inhibitors in CHF are recommended.

Comparison of thallium redistribution with rest "reinjection" imaging for the detection of viable myocardium.

To determine the incidence of incomplete redistribution on conventional delayed thallium images, 41 patients with persistent perfusion defects on myocardial images recorded 3 to 4 hours after thallium injection during exercise were studied. At the conclusion of their delayed images the patients were reinjected at rest with approximately 1 mCi of thallium-201 and a third set of images was recorded. The images were presented at random in pairs (initial:delayed, initial:reinjection) to 2 experienced observers for qualitative scoring of 9 segments/patient. Of the 360 segments analyzed, concordance between the delayed and reinjected images occurred in 307 (85%). Of 141 segments that demonstrated a persistent perfusion abnormality on 3- to 4-hour delayed images, 44 (31%) were reassigned to a redistribution score after reinjection. In 9 patients, reinjection images provided the only evidence of ischemia from the scintigraphic data. In 13 of 14 vascular territories that demonstrated redistribution after reinjection, intact perfusion (either anterograde or via collaterals) was detected at coronary angiography. These data suggest that rest reinjection imaging may provide a means of detecting viable myocardium in segments that demonstrate a fixed perfusion abnormality on conventional 3- to 4-hour delayed thallium images.

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.