Severity of acute hepatitis and its outcome in patients with dengue fever in a tertiary care hospital Karachi, Pakistan (South Asia).

BACKGROUND: Liver injury due to dengue viral infection is not uncommon. Acute liver injury is a severe complicating factor in dengue, predisposing to life-threatening hemorrhage, Disseminated Intravascular Coagulation (DIC) and encephalopathy. Therefore we sought to determine the frequency of hepatitis in dengue infection and to compare the outcome (length of stay, in hospital mortality, complications) between patients of Dengue who have mild/moderate (ALT 23-300 IU/L) v/s severe acute hepatitis (ALT > 300 IU/L). METHODS: A Cohort study of inpatients with dengue viral infection done at Aga Khan University Hospital Karachi. All patients (> or = 14 yrs age) admitted with diagnosis of Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS) were included. Chi square test was used to compare categorical variables and fischer exact test where applicable. Survival analysis (Cox regression and log rank) for primary outcome was done. Student t test was used to compare continuous variables. A p value of less than or equal to 0.05 was taken as significant. RESULTS: Six hundred and ninety nine patients were enrolled, including 87% (605) patients with DF and 13% (94) patients with DHF or DSS. Liver functions tests showed median ALT of 88.50 IU/L; IQR 43.25-188 IU/L, median AST of 174 IU/L; IQR 87-371.5 IU/L and median T.Bil of 0.8 mg/dl; IQR 0.6-1.3 mg/dl. Seventy one percent (496) had mild to moderate hepatitis and 15% (103) had severe hepatitis. Mean length of stay (LOS) in patients with mild/moderate hepatitis was 3.63 days v.s 4.3 days in those with severe hepatitis (P value 0.002). Overall mortality was 33.3% (n = 6) in mild/moderate hepatitis vs 66.7% (n = 12) in severe hepatitis group (p value < 0.001). Cox regression analysis also showed significantly higher mortality in severe hepatitis group (H.R (4.91; 95% CI 1.74-13.87 and P value 0.003) and in DHF/DSS (5.43; CI 1.86-15.84 and P value 0.002). There was a significant difference for the complications like Bleeding (P value < 0.001), Acute Renal failure (ARF) (P value 0.002), Acalculus cholecystitis (P value 0.04) and encephalopathy (P value 0.02) in mild/moderate and Severe hepatitis groups respectively. CONCLUSION: Severe hepatitis (SGPT>300IU) in Dengue is associated with prolonged LOS, mortality, bleeding and RF.

Culture and quality care perceptions in a Pakistani hospital.

PURPOSE: Organizational culture is a determinant for quality improvement. This paper aims to assess organizational culture in a hospital setting, understand its relationship with perceptions about quality of care and identify areas for improvement. DESIGN/METHODOLOGY/APPROACH: The paper is based on a cross-sectional survey in a large clinical department that used two validated questionnaires. The first contained 20 items addressing perceptions of cultural typology (64 respondents). The second one assessed staff views on quality improvement implementation (48 faculty) in three domains: leadership, information and analysis and human resource utilization (employee satisfaction). FINDINGS: All four cultural types received scoring, from a mean of 17.5 (group), 13.7 (developmental), 31.2 (rational) to 37.2 (hierarchical). The latter was the dominant cultural type. Group (participatory) and developmental (open) culture types had significant positive correlation with optimistic perceptions about leadership (r = 0.48 and 0.55 respectively, p < 0.00). Hierarchical (bureaucratic) culture was significantly negatively correlated with domains; leadership (r = -0.61,p < 0.00), information and analysis (-0.50, p < 0.00) and employee satisfaction (r = -0.55, p < 0.00). Responses reveal a need for leadership to better utilize suggestions for improving quality of care, strengthening the process of information analysis and encouraging reward and recognition for employees. RESEARCH LIMITATIONS/IMPLICATIONS: It is likely that, by adopting a participatory and open culture, staff views about organizational leadership will improve and employee satisfaction will be enhanced. This finding has implications for quality care implementation in other hospital settings. ORIGINALITY/VALUE: The paper bridges an important gap in the literature by addressing the relationship between culture and quality care perceptions in a Pakistani hospital. As such a new and informative perspective is added.

An open study to assess the safety and efficacy of Heprovac-B vaccine 10 mcg-dose for adults.

Heprovac B is a novel recombinant vaccine. There are many vaccines available in Pakistani market but Heprovac B claims to be immunogenic even at 10 meg dose. Aim of the study is to determine whether using 10 meg of Heprovac B vaccine is safe and effective in producing sufficient immunity in Pakistani population. One hundred and twenty five subjects, who fulfilled the Inclusion criteria, were enrolled for the study. Heprovac B was administered in a three-dose regimen given at 0, 1 and 6 months and adverse events were recorded. Immunogenicity was tested by measuring hepatitis B surface antibody one month after each dose received. One month after the 3rd dose 98.7% of the subjects were found to be seroprotected with geometric mean titer of 488.83 mIU/1 after the third dose. Heprovac B, vaccine was well tolerated with minimal reported adverse events. It is safe and 10 mcg is immunogenic in producing antibodies in Pakistani population against Hepatitis B virus.

Use of Everolimus After Multivisceral Transplantation: A Report of Two Cases.

Inhibitors of mechanistic target of rapamycin are used in solid organ transplant procedures to avoid calcineurin inhibitor complications, including nephrotoxicity and malignancy. We present 2 cases of multivisceral transplantation for neuroendocrine tumor (NET) for which everolimus was implemented for its potential to prevent NET recurrence as well as preserve renal function. The first case was complicated by NET recurrence in the liver before initiation of everolimus. After initiation of everolimus, the patient developed a ventral hernia and elevated aminotransferase levels with nonspecific biopsy findings. The second case was complicated by cytomegalovirus infection with elevated everolimus trough levels as well as acute cellular rejection. Everolimus was reinitiated in both cases in addition to decreasing the dosage of tacrolimus, and there were no further complications. Everolimus was beneficial in stabilizing renal function in both patients and has the theoretical potential to prevent recurrence of NET.

A Case Report of Acute Cellular Rejection Following Intestinal Transplantation Managed With Adalimumab.

There is a higher incidence of acute cellular rejection (ACR) in small bowel transplantation (SBT) compared with transplantation of other solid organs. Although there are reports on the use of infliximab to successfully treat ACR refractory to other treatments, there are no reports, to our knowledge, regarding the use of adalimumab. We present a case of a female patient with a history of Crohn's disease who underwent an isolated SBT and developed an episode of severe ACR. She was initially treated with methylprednisolone, thymoglobulin, basiliximab, and a dosage adjustment of tacrolimus. Results of repeat endoscopies and biopsies revealed no significant improvement. The patient initiated treatment with adalimumab every 2 weeks for a total of 6 months, in addition to maintenance treatment with prednisone and tacrolimus. Subsequent evaluations showed gradual improvement to normal mucosa and villi without ulceration. A regimen that incorporates adalimumab can thus be used to treat ACR after intestinal transplantation. Larger multicenter studies are needed to show the full efficacy of this therapeutic regimen.

Multicenter Evaluation of Current Knowledge of Intestinal Transplantation and Rehabilitation Among Trainee Physicians.

BACKGROUND: The management of intestinal failure has evolved dramatically over the last 2 decades. In addition, improved management of patients requiring parenteral nutrition-associated liver disease is creating a paradigm shift in both intestinal failure management and in the evolving indications for intestinal transplantation. OBJECTIVES: We conducted an evaluation measuring current awareness among house officers (HO) regarding nutritional and transplant principles in the management of intestinal disease. Our goal was to use board-style questions with a single correct response to measure current knowledge level between HO. METHODS: A survey was distributed to HO via email to measure knowledge regarding 3 areas: principles of intestinal failure (PI), medical management of intestinal disease (MI), and transplantation for intestinal disease (TI). This was evaluated at 3 busy nontransplant centers (NTC) and a tertiary care intestine transplant center (TC). Statistical analysis was conducted using the independent samples t test and multiple linear regression analysis. RESULTS: Surveys were distributed to a total of 1068 HO; 208 (19.47%) responded. We received 139 responses (67%) from NTC and 69 (33%) from TC. 82% were postgraduate year (PGY) 1-3 and 18% were PGY 4-7. Of the respondents, 27% correctly answered questions regarding PI, 40% about MI, and 21% on TI. HO in NTC demonstrated more knowledge regarding PI than those in TC (P = .000). There was, otherwise, no difference between PGY 1-3 and PGY 4-7 (P > .05). CONCLUSIONS: This evaluation demonstrates potential deficiencies in the basic understanding of issues surrounding intestinal disease that can be used for implementation of an educational program regarding intestinal disease and transplantation.

Brief histories of medical physics in Asia-Oceania.

The history of medical physics in Asia-Oceania goes back to the late nineteenth century when X-ray imaging was introduced, although medical physicists were not appointed until much later. Medical physics developed very quickly in some countries, but in others the socio-economic situation as such prevented it being established for many years. In others, the political situation and war has impeded its development. In many countries their medical physics history has not been well recorded and there is a danger that it will be lost to future generations. In this paper, brief histories of the development of medical physics in most countries in Asia-Oceania are presented by a large number of authors to serve as a record. The histories are necessarily brief; otherwise the paper would quickly turn into a book of hundreds of pages. The emphasis in each history as recorded here varies as the focus and culture of the countries as well as the length of their histories varies considerably.

Hemodynamic effects of a new type III phosphodiesterase inhibitor (CI-914) for congestive heart failure.

Hemodynamic response after intravenous and oral administration of a new phosphodiesterase inhibitor, CI-914, was studied in 13 patients with severe congestive heart failure. Comparable significant increases in cardiac index of 26% (p less than 0.01) and 19% (p less than 0.02) after intravenous and oral administration were observed. Systemic vascular resistance, right atrial and pulmonary artery wedge pressure decreased significantly after intravenous drug administration. Although similar changes occurred after oral administration, they were not statistically significant. Peak CI-914 plasma concentration occurred 2.3 +/- 2.2 hours after oral drug administration and exhibited measurable hemodynamic effects for up to 10 to 12 hours. Seven of the 13 patients received long-term oral CI-914 for as long as 12 weeks and exhibited an improvement in New York Heart Association functional class and exercise capacity. Five patients died with progressive heart failure, 1 patient died suddenly and 1 died of sepsis. The drug was well tolerated and appears to have potential as a cardiotonic agent.

Hemodynamic, pharmacokinetic and clinical response to CI-930 in congestive heart failure due to ischemic or dilated cardiomyopathy.

CI-930, a new type III phosphodiesterase inhibitor, was evaluated for treatment of refractory congestive heart failure. The hemodynamic, pharmacokinetic and clinical response to the drug was determined in 10 patients. At the peak plasma concentration after intravenous CI-930, cardiac index increased from 2.0 to 2.7 liters/min/m2 (p less than 0.002), pulmonary artery wedge pressure decreased from 26 to 17 mm Hg (p less than 0.001) and systemic vascular resistance decreased from 1,999 to 1,471 dynes cm-5 (p less than 0.05). Heart rate and blood pressure did not change significantly. Similar changes were observed with oral CI-930. Peak CI-930 plasma concentration occurred 1.2 +/- 0.8 hours after oral administration. Beneficial hemodynamic effects were sustained 12 to 18 hours after the oral dose. The sustained hemodynamic effects observed after oral administration appear to be related to an active metabolite of CI-930 that has prolonged duration of action and slow washout. The drug was well tolerated and has potential for treatment of congestive heart failure.

Effects of cigarette smoking and propranolol in survivors of acute myocardial infarction.

The effect of propranolol on mortality and reinfarction after acute myocardial infarction (AMI) in cigarette smokers and nonsmokers was studied in the Beta Blocker Heart Attack Trial. Cigarette smokers (n = 2,332) were 5 years younger than nonsmokers and had a lower incidence of diabetes mellitus, systemic hypertension, previous AMI and cardiomegaly. Among cigarette smokers, the placebo group had a higher total mortality rate than the propranolol group (11.0 vs 7.4%, p less than 0.0008) and more sudden cardiac deaths (7.1 vs 4.6%, p less than 0.009). In nonsmokers the placebo group had a mortality (7.9 vs 7.1%, p greater than 0.64) similar to the propranolol group. After baseline adjustment, cigarette smokers were estimated to have 1.6 times the risk of dying as compared to nonsmokers (p less than 0.0007). Adjusting for baseline differences, both treatment with propranolol and nonsmoking were predictors of survival. No detectable nonsmoking/propranolol interaction could be identified. In survivors of AMI a beneficial effect of propranolol is observed for cigarette smokers. Nevertheless, cigarette smoking continues to be a risk factor for mortality after AMI even for those receiving propranolol.

Circadian variation in platelet function in healthy volunteers.

Circadian variation in hemostatic factors may contribute to a higher frequency of cardiac events observed in the morning and with activity. Diurnal changes in these factors were investigated by measuring in vitro platelet aggregability in response to epinephrine and adenosine diphosphate together with beta-thromboglobulin and platelet factor 4 as indexes of in vivo platelet activation. Activation of coagulation was measured by thrombin-antithrombin III complexes and D-Dimers. Tests were performed in 9 normal healthy subjects. Circadian changes occurred in beta-thromboglobulin (p less than 0.05) and platelet factor 4 (p less than 0.06). Plasma levels of beta-thromboglobulin and platelet factor 4 were lowest with patients supine and resting at 7 and 8 A.M., and increased with activity, with peak levels achieved at 3 P.M. (p less than 0.01). Thrombin-antithrombin III complexes (p = 0.44), D-Dimer (p = 0.36) and in vitro platelet aggregability to adenosine diphosphate (p = 0.20) did not show diurnal variation. There was a trend toward circadian variation in vitro platelet aggregability to epinephrine, but these changes did not achieve statistical significance (p = 0.16). Circadian changes of in vivo release of beta-thromboglobulin and platelet factor 4 correlated to patient activity and not to the morning peaks in ischemic events. These data indicate that changes in platelet function and not in coagulation have a diurnal occurrence.

Efficacy of propranolol therapy after acute myocardial infarction related to coronary arterial anatomy and left ventricular function.

The effect of the beta-adrenergic blocking agent propranolol on morbidity and mortality risk after acute myocardial infarction was studied relative to coronary anatomy and left ventricular (LV) ejection fraction in a subset of 406 patients participating in a randomized study of 3,837 patients in the Beta Blocker Heart Attack Trial (BHAT). Median follow-up for this subset of patients was 28 months. The mortality rate was 2% (2 of 100) in patients with 2- and 3-vessel coronary artery disease taking propranolol and 10% (12 of 126) in those taking placebo (p less than 0.02). In patients with 2- and 3-vessel coronary artery disease with decreased LV function (defined as ejection fraction less than 50%), no patient taking propranolol died, whereas 17% (7 of 42) taking placebo died (p less than 0.04). The salutary effect of propranolol on mortality in the larger BHAT after acute myocardial infarction also was evident in this population studied in regard to their coronary and LV anatomy and function.

Usefulness of exercise echocardiography in predicting cardiac events in an outpatient population.

The prognostic value of exercise echocardiography in an outpatient population is not well defined. A total of 1,020 consecutive patients referred for exercise echocardiography in an ambulatory care setting were studied by reviewing their medical records and exercise echocardiographic data. Of these, 71 (7%) were excluded due to technically inadequate tests, leaving 949 patients who were included in the analysis. A positive exercise echocardiogram (EE) was defined as an appearance of a new wall motion abnormality or worsening of a baseline abnormality. Cardiac events, defined as myocardial infarction, coronary angioplasty, coronary bypass surgery, and death, were documented during a 12-month follow-up period. Cardiac events occurred in 17% of patients (26 of 152) with a positive exercise echocardiogram (EE) and in 2.5% (20 of 797) with a negative EE (p <0.001). The incidence of myocardial infarction (2.6% vs 0.4%, p <0.02), coronary angioplasty (7% vs 1%, p <0.001), and coronary bypass surgery (9% vs 1%, p <0.001) were higher in patients with a positive versus a negative EE. There was 1 death in the positive study group and none in the negative group. Significant independent variables (p <0.05) that predicted cardiac events included a positive exercise electrocardiogram, history of coronary angioplasty, nonspecific ST-T changes on the baseline electrocardiogram, double product <25,000, men, chest pain on exercise test, and a positive exercise electrocardiogram. On a stepwise logistic regression model, exercise echocardiography emerged as an independent predictor of future cardiac events in an outpatient population. This predictive value was enhanced in the presence of a positive exercise electrocardiogram compared with a negative exercise electrocardiogram (24.2% vs 7.9%, p <0.03). Our study suggests that exercise echocardiography is an independent predictor of future cardiac events in an outpatient population.

Medical therapy after acute myocardial infarction.

Several therapeutic agents have been tested for secondary prevention after acute myocardial infarction. Each patient presents a clinical challenge and gives the physician an opportunity to use the tests and therapy most likely to benefit the clinical course. The presence of other associated medical conditions, the type of myocardial infarction, the presence or absence of accompanying ischemia, left ventricular dysfunction, intracardiac thrombus, or ventricular arrhythmias dictate the choices that are to be made. It is apparent from this review that no single class of agents can be considered a cure, although beta-adrenergic blocking agents come the closest to this role. Analysis of these drugs helps individualize drug therapy and provides a physiologic probe to understanding the pathophysiologic processes that characterize the period after myocardial infarction. To address the impact of developing technology and drug availability on the practice and cost of medical care, the American College of Cardiology and the American Heart Association have developed guidelines for the management of patients with myocardial infarction. The clinical trial remains the best test for the assessment of therapeutic choices and can also expand our knowledge of the natural history of the disease process. Nevertheless, the issue of appropriate therapy is ever-changing, affected by the explosion of new technology and the continued investigation into the pathophysiology of coronary artery disease.

Ball-valve thrombus obstructing a bioprosthetic mitral valve.

We present a patient with a large, left atrial ball valve thrombus that was intermittently obstructing a bioprosthetic mitral valve. The diagnosis was confirmed by transesophageal two-dimensional echocardiogram. The transthoracic study initially had failed to demonstrate the true ball valve nature of the thrombus and instead, suggested two separate mass lesions, one in the left atrium and one in the bioprosthetic mitral valve.

Transesophageal echocardiographic findings in patients with orthotopic heart transplantation.

This study was performed to determine the diagnostic value of TEE in recipients of orthotopic heart transplantation. Findings on TEE were compared with those of TTE in 30 patients with orthotopic heart transplantation. Transesophageal echocardiography identified left atrial appendage and flow across the interatrial septum ... findings not detected by TTE. In addition, pronounced bulging of the interatrial septum was seen in six patients by TEE and not by TTE. Spontaneous echo contrast (smoke) in the atria was detected by TEE in 14 patients and by TTE in one patient. Abnormal geometry of the atria and donor-recipient atrial anastomosis was identified in all patients by TEE and TTE. Our findings suggest that TEE should be selectively utilized in the operating room, in patients with suspected atrial thrombi, and in those with clinically significant right ventricular volume overload to assess integrity of interatrial anastomosis.

Factors influencing platelet serotonin uptake in essential hypertension.

In a study of the mechanism(s) of platelet serotonin uptake alteration in essential hypertension, a total of 90 blood samples were analysed for platelet count and platelet serotonin uptake. These included 20 blood samples each of hypertensives, controls before and after cross-incubation experiments and 10 samples of hypertensives after control of blood pressure. It was observed that serotonin uptake was markedly reduced in hypertensive platelets. Diminished serotonin uptake in essential hypertension correlated directly with diastolic and mean arterial blood pressure and inversely with plasma total cholesterol values. In cross-incubation experiments using control platelets and hypertensive plasma, there was a significant reduction in platelet serotonin uptake (303.06 +/- 86.28 cpm/10(8) vs. 204.26 +/- 66.45 cpm/10(8); P less than 0.001), whereas hypertensive platelets when incubated with control plasma, showed increased serotonin uptake (233.50 +/- 75.19 cpm/10(8) vs. 312.64 +/- 79.54 cpm/10(8); P less than 0.01). Upon control of blood pressure, the platelet serotonin uptake improved significantly (205.45 +/- 70.0 cpm/10(8) vs. 266.77 +/- 61.68 cpm/10(8); P less than 0.05-0.01). From these results, it appears that reduced platelet serotonin uptake in essential hypertension is a reversible phenomenon probably governed by the presence of plasma factor(s) and/or altered platelet-membrane function.

Temporary transvenous cardiac pacing.

Temporary cardiac pacing in the critical care setting can be a lifesaving intervention in a number of clinical situations. A variety of catheter types and pulse generators are available. Insertion techniques include the use of fluoroscopic imaging, intracavitary ECG monitoring, and blind advancement with surface ECG monitoring. This article focuses on the indications, equipment, techniques, complications, and troubleshooting of temporary transvenous cardiac pacemakers.

Racial differences in patients with heart failure.

BACKGROUND AND HYPOTHESIS: Limited data exist regarding racial differences in heart failure. The objective of this prospective study was to document racial differences in the baseline demographics and patterns of health care utilization and outcomes in patients with heart failure. METHODS: The data on 163 consecutive patients (113 black, 50 white) admitted with a diagnosis of heart failure confirmed by pulmonary congestion on chest x-ray were prospectively evaluated. Patient demographics, physical examination findings at admission, comorbid conditions, and medications at admission and discharge were analyzed. Follow-up was performed to document visits to the physician's office after discharge and readmission rate during a 6-month time period. RESULTS: Compared with whites, blacks were younger in age (mean age 63.8 +/- 13.7 years vs. 70.8 +/- 13.1, p = 0.003), and had a higher prevalence of hypertension (86 vs. 66%, p = 0.004), left ventricular hypertrophy (24 vs. 8%, p = 0.02), ejection fraction < 40% (64 vs. 43%, p = 0.03), and readmission rate (33 vs. 18%, p = 0.05). Whites had a higher prevalence of atrial fibrillation (42 vs. 21%, p = 0.006) and more frequently followed up with their cardiologists as outpatients (58 vs. 39%, p = 0.04). CONCLUSION: Significant racial differences exist in patients with heart failure with regard to age, incidence, etiologic factors, left ventricular hypertrophy, left ventricular function, and clinical follow-up. It is important to consider these racial differences in the evaluation and management of patients with heart failure.