Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery.

BACKGROUND: The failure rate of medical therapy in severe ulcerative colitis is high. A risk index, to aid the identification of patients of not responding at an early stage to intravenous corticosteroid therapy, would be useful to facilitate second-line treatment or surgery. METHODS: We recruited 167 consecutive patients with severe ulcerative colitis between January 1995 and March 2002; and employed multiple logistic regression to analyse parameters within the first 3 days of medical therapy. We applied statistical modelling to formulate a risk score according to the likelihood of medical failure. RESULTS: Sixty-seven (40%) patients failed to respond to medical therapy. Multiple logistic regression analysis identified mean stool frequency and colonic dilatation within the first 3 days and hypoalbuminaemia as independent predictors of outcome (P < 0.001, 0.001 and 0.002 respectively). A numerical risk score was formulated based on these variables. Patients with scores of 0-1, 2-3 and > or =4 had a medical therapy failure rate of 11%, 43% and 85% respectively. Receiver-operator characteristic analysis of this score yielded area under curve of 0.88, with a sensitivity of 85% and specificity of 75% using score > or =4 in predicting non-response. CONCLUSION: This risk score allows the early identification of patients with severe ulcerative colitis who would be suitable for second-line medical therapy or surgery.

Genetics of inflammatory bowel disease: scientific and clinical implications.

Considerable progress has been made in the last decade in studies of the genetics of the inflammatory bowel diseases, Crohn's disease and ulcerative colitis. Epidemiological data, notably concordance rates in twin pairs and sibling pairs, have provided strong evidence for the importance of the genetic contribution, particularly in Crohn's disease. These observations provided the catalyst for laboratory-based studies of the molecular genetics of Crohn's disease and ulcerative colitis around the world. The complementary strategies of genome-wide scanning and candidate gene-directed studies have led to the identification of a number of genetic markers which appear to predict disease susceptibility and behaviour. The identification of the IBD1 gene on chromosome 16 as NOD-2 is unquestionably an important scientific discovery. Although many issues with respect to gene function and expression remain to be resolved there is great optimism that important clinical applications will directly result.

Jaundice caused by a clinically undetectable T-cell lymphoma infiltrating the sphincter of Oddi.

Malignant lymphoma rarely presents with jaundice. We describe a patient who had a unique etiology for painless jaundice, dilated ducts, and a normal ampulla of Vater. A Whipple's procedure was performed for the suspicion of pancreatic cancer, and initial pathological review detected only mild focal chronic pancreatitis. Seven months later, the patient developed ascites, retroperitoneal mass, and splenomegaly caused by a T-cell lymphoma. Reevaluation of the Whipple's specimen revealed previously unrecognized microscopic infiltration and fibrosis of the sphincter of Oddi by atypical T-lymphocytes. Obstructive jaundice caused by a clinically undetectable primary duodenal T-cell lymphoma has not been previously reported and is contrasted with other causes of jaundice associated with malignant lymphoma and ampullary lesions.

Asian Indian women: knowledge, attitudes and behaviors toward breast cancer early detection.

Education programs have been developed to promote adherence to recommended breast cancer screening guidelines. Few studies have assessed the degree to which ethnic subgroups are perceiving and acting on the proffered information. Such assessment is vital to the creation of efficient public health interventions. This paper describes the reported breast cancer knowledge, attitudes, and screening behaviors of 194 American Asian Indian women. While monthly breast self exam adherence was low, only 40.7%, 61.3% of women 40 and older, and 70% of women 50 and older, reported having had a mammogram within the past 12 months. These rates for annual mammography screening are high relative to many other ethnic groups. While the results are encouraging, the respondents may not be representative of all Asian Indian women. The majority of these women reported that their breast cancer knowledge is inadequate. They were willing to be called upon to share with others any knowledge they gained. There is a clear opportunity for public health nurses to provide Asian Indian women with a more comprehensive understanding of breast health and disease. Those women can then share their health knowledge with other women within their ethnic group.

Self-reported differences between cardiologists and heart failure specialists in the management of chronic heart failure.

BACKGROUND: Heart failure (HF) is responsible for considerable mortality morbidity rates and resource utilization. Recently, several studies have reported improved outcomes when patients are managed by special HF clinics, but it is uncertain whether this improvement reflects differences in physician practices or other aspects of the operation of these clinics. OBJECTIVES: This study was designed to identify differences in HF management practices between general cardiologists and cardiologists specializing in the treatment of patients with HF. METHODS: A survey examining diagnostic and treatment practices in patients with HF was sent to a sample of cardiologists derived from the American Medical Association Masterfile and to HF specialists who were members of the Society of Transplant Cardiologists or principal investigators in HF trials. Responses were examined in relation to guidelines issued by the Agency for Health care Policy and Research released 9 months previously. RESULTS: In general both groups practice in conformity with published guidelines. However, there were important differences between the practice patterns of general cardiologists and HF specialists. For instance, in patients being evaluated for the first time, cardiologists reported using a chest radiograph to assist in the diagnosis more than did HF specialists (47% vs 12%), whereas HF specialists were more likely to use an echocardiogram (73% vs 48%). Both groups were likely to evaluate their patients for ischemia and possible revascularization, even in patients not having angina. However, HF specialists tended to use coronary angiography as the initial diagnostic test, whereas cardiologists were more likely to use stress testing. HF specialists more often used angiotensin-converting enzyme inhibitors as part of their initial therapy in patients with mild to moderate HF (94% vs 86%) and during maintenance therapy (91% vs 80%). Also, HF specialists were more likely than cardiologists to titrate angiotensin-converting enzyme inhibitors to higher doses (75% vs 35%), even in the presence of renal dysfunction. CONCLUSION: Cardiologists and HF specialists generally manage their patients in conformity with guidelines. However, in many areas, such as angiotensin-converting enzyme inhibitor use, HF specialists do so more aggressively. These approaches may, in part, explain the success of the HF clinic model and raise the possibility that some portion of the HF population may be more optimally managed by cardiologists with a special interest in and additional training or experience with this condition.

Prevention of hospitalizations for heart failure with an interactive home monitoring program.

Congestive heart failure is the most common cause of hospitalization for the older population. A previous study demonstrated that rehospitalizations, undertaken by 30% to 50% of elderly patients, can be prevented with intensive multidisciplinary intervention. A pilot study was designed to determine whether a less intensive program with patient education materials, automated reminders for medication compliance, self-monitoring of daily weights and vital signs, and facilitated telephone communication with a nurse-monitor could reduce hospitalizations and whether this benefit could be extended to younger outpatients. Twenty-seven male patients (mean age 62 years) with New York Heart Association class II to IV congestive heart failure caused by dilated cardiomyopathy underwent follow-up with an independent service, which provided the primary cardiologist with information concerning changes in vital signs or symptoms. The number of hospitalizations and hospital days during the mean value of 8.5 months in the program was compared patient by patient with the number during the equivalent period before entrance in the program. The number of hospitalizations for cardiovascular diagnoses and hospital days was reduced from 0.6 to 0.2 (p = 0.09) per patient year of follow-up and 7.8 to 0.7 days per patient per year (p < 0.05). Hospitalizations for all causes fell from 0.8 to 0.4 per patient per year (p = not significant) and 9.5 to 0.8 days per patient per year (p < 0.05). The greatest absolute and relative benefit was observed among patients with more severe congestive heart failure. The most frequent indication for intervention was an increase in weight, which was managed with adjustment of diuretic dosages. This preliminary experience suggests that close telephone monitoring by personnel from an independent service can prevent hospitalizations for heart failure among both recently discharged patients and ambulatory outpatients and among both elderly and middle-aged persons.

Differences between primary care physicians and cardiologists in management of congestive heart failure: relation to practice guidelines.

OBJECTIVES: This study was designed to characterize physician practices in the management of congestive heart failure (CHF) and to determine whether these practices vary by specialty and how they relate to guideline recommendations. BACKGROUND: Congestive heart failure is responsible for considerable mortality, morbidity and health care resource utilization. Although there have been important advances in the diagnostic evaluation and treatment of CHF, little information is available on physician practices in this area. METHODS: We surveyed physicians concerning their management of patients with CHF. The results were analyzed in multivariate models to determine the relation of diagnostic and treatment approaches to physician specialty, time since training, board certification and volume of patients with CHF. Surveys were sent to a sample of 2,250 family and general practitioners (FP/GPs), internists and cardiologists. Responses were examined in relation to guidelines issued by the Agency for Health Care Policy and Research that had been released 9 months previously. RESULTS: Significant differences were found between physician groups with regard to each of the major guideline recommendations. For example, routine evaluation of left ventricular function, a point of emphasis in the guideline, is performed by 87% of cardiologists, but by only 77% of internists and 63% of FP/GPs (p < 0.001 between groups). Angiotensin-converting enzyme inhibitors were used by cardiologists, internists and FP/GPs in 80%, 71% and 60% of patients with mild to moderate CHF, respectively (p < 0.001 between groups). Larger differences were reported in the prescribed dosages of these drugs and their use in patients with renal dysfunction. CONCLUSIONS: Cardiologists report practices more in conformity with published guidelines for CHF than do internists and FP/GPs. Because of the large numbers of patients with CHF and their substantial mortality, morbidity and cost of care, these differences may have a major impact on outcomes and health care costs.

Importance of assessing changes in ventricular response to atrial fibrillation during evaluation of new heart failure therapies: experience from trials of flosequinan.

This study evaluated the effects of flosequinan on ventricular rate in patients with congestive heart failure and atrial fibrillation to determine whether this agent has a facilitatory effect on atrioventricular conduction and whether such an effect may be deleterious. Flosequinan is known to have a dose-dependent positive chronotropic effect on the sinus node, but its effect on atrioventricular conduction has not been evaluated. An excessive increase in ventricular rate during the treatment of heart failure could raise a safety concern and counterbalance beneficial responses. Data were analyzed from 338 patients participating in three similarly designed placebo-controlled exercise trials with flosequinan who also underwent ambulatory electrocardiographic monitoring. The effects of two doses of flosequinan on supine, standing, ambulatory, and exercise heart rates and on exercise capacity in patients in sinus rhythm and atrial fibrillation were compared. Flosequinan increased heart rate in a dose-dependent manner, in patients both with sinus rhythm and atrial fibrillation. A 100 mg once daily dose produced significant increases, in both rhythms, ranging from 6 to 11 beats/min, in supine and standing heart rate, ambulatory heart rate, and exercise heart rate. With a dose of 75 mg twice daily, heart rates under these conditions increased by >20 beats/min in flosequinan-treated patients in atrial fibrillation, a change significantly greater than that observed with placebo or flosequinan, 100 mg once daily and also more than in patients in sinus rhythm treated with the same dose. These results indicate that flosequinan facilitates atrioventricular nodal conduction, increasing the ventricular response in atrial fibrillation, especially at higher dosages. This finding could result from a direct drug action, such as phosphodiesterese inhibition, or reflex sympathetic activation. This response is of sufficient magnitude potentially to impair left ventricular function and interfere with clinical benefit. The effect of heart-failure drugs on ventricular responses in atrial fibrillation should be examined to provide insight into potential mechanisms of both action and safety in this common patient group.

Future approaches to pharmacologic therapy for congestive heart failure.

There have been tremendous advances in our understanding of the pathophysiology of congestive heart failure, and this has led to improvements in its treatment. Nonetheless, the prevalence of congestive heart failure and the associated mortality and morbidity continue to increase. Hence, there remains a need for additional therapeutic approaches that will complement current management with diuretics, angiotensin-converting enzyme inhibitors, other vasodilators, and digoxin. This article reviews a number of potential avenues that are currently being evaluated or remain targets for future investigation. Given our current understanding of the mechanisms of progression of left ventricular dysfunction, therapies that limit neurohormonal activation or interfere with its consequences and those that improve the balance between myocardial energy requirements and supply appear to be the most promising. Agents that improve hemodynamics without altering the underlying pathophysiology may produce short-term symptomatic improvement but have limited potential to alter the natural history of congestive heart failure. Positive inotropic therapies probably fall into this category, but most of these also appear to accelerate progression and increase mortality. In the long-term, specific interventions that reverse changes at the cellular and molecular level offer the greatest promise.

Effect of polymers on dissolution from drug suspensions.

The effect of three viscosity grades of methylcellulose on the dissolution-dialysis rate of nitrofurantoin suspensions was investigated using a cell designed to provide a large surface area for dialysis. Apparent dialytic rate constants of drug dispersions and solutions were measured in 0.1 N HC1 and in pH 7.4 buffer. Samples containing methylcellulose had lower rates of dialysis, with the lowest rate being observed for samples in which the polymer was used as the suspending agent. The reduced rate of dialysis of the drug suspension containing methylcellulose is thought to be due to complexation of the drug in solution with the polymer as well as formation of microscopic regions of high viscosity surrounding the undissolved drug particles leading to a reduction in the dissolution rate of the drug. An empirical relationship was obtained to enable the estimation of the effective drug concentration in the dissolution chamber for drug dispersions. The method is based on utilizing dialysis rate data of drug solutions. This relationship could be used for comparing suspension formulations in terms of the amount of drug available for dialysis.