Impact of direct acting antivirals on occurrence and recurrence of hepatocellular carcinoma: Biologically plausible or an epiphenomenon?

Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection (HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introduction of the new direct acting antivirals (DAAs) has revolutionized the management of HCV worldwide, with high rates of sustained virologic response in patients who could not have tolerated the previous interferon based treatments. However, recently there have been reports raising caution about the long term effects of DAAs, particularly a possible increased risk of HCC. Therefore this review explores the current molecular studies as well as clinical data that investigate the impact of DAAs on occurrence and recurrence of HCC

The discrepancy between admission and discharge diagnoses: Underlying factors and potential clinical outcomes in a low socioeconomic country

Objective: The discrepancy between admission and discharge diagnosis can lead to possible adverse patient outcomes. There are gaps in integrated studies, and less is understood about its characteristics and effects. Therefore, this study was conducted to determine the frequency, characteristics, and outcomes of diagnostic discrepancies at admission and discharge.Design and data sources: This retrospective study reviewed the admitting and discharge diagnoses of adult patients admitted at Aga Khan University Hospital (AKUH), Internal Medicine Department between October 2018 and February 2019. The frequency and outcomes of discrepancies in patient diagnoses were noted among Emergency Department (ED) physician versus admitting physician, admitting physician versus discharge physician, and ED physician versus discharge physician for the full match, partial match, and mismatch diagnoses. The studied outcomes included interdepartmental transfer, Intensive Care Unit (ICU) transfer, in-hospital mortality, readmission within 30 days, and the length of stay. For simplicity, we only analyzed the factors for the discrepancy among ED physicians and discharge physicians.Results: Out of 537 admissions, there were 25.3-27.2% admissions with full match diagnoses while 18.6-19.4% and 45.3-47.9% had mismatch and partial match diagnoses respectively. The discrepancy resulted in an increased number of interdepartmental transfers (5-5.8%), ICU transfers (5.6-8.7%), in-hospital mortality (8-11%), and readmissions within 30 days in ED (14.4%-16.7%). A statistically significant difference was observed for the ward\u27s length of stay with the most prolonged stay in partially matched diagnoses (6.3 ± 5.4 days). Among all the factors that were evaluated for the diagnostic discrepancy, older age, multi-morbidities, level of trainee clerking the patient, review by ED faculty, incomplete history, and delay in investigations at ED were associated with significant discrepant diagnoses.Conclusions: Diagnostic discrepancies are a relevant and significant healthcare problem. Fixed patient or physician characteristics do not readily predict diagnostic discrepancies. To reduce the diagnostic discrepancy, emphasis should be given to good history taking and thorough physical examination. Patients with older age and multi-morbidity should receive significant consideration

Irritable Bowel Syndrome and Psychiatric Disorders in Pakistan: A Case Control Study

Background. The psychiatric disorders like anxiety and depression could have a profound influence on onset, expression, and course of Irritable bowel syndrome (IBS). Aim. To estimate the frequency and strength of association of common mental disorders (CMDs) in patients with IBS and patients with other chronic diseases, that is, migraine and hypertension. Method. This was a case control study. Individuals aged 18–70 years diagnosed as IBS were enrolled as cases. The control groups consisted of patients without IBS but diagnosed to have a chronic disease, that is, migraine or HTN. Self-Reporting Questonnaire-20(SRQ-20) was used as a screening tool for the detection of CMD. Results. 82 patients were enrolled in each group. Mean SRQ score was significantly higher in IBS group than controls (9.9 ± 4.5 versus 4.9 ± 3.6, P < 0.001). CMDs were more frequent (67.1% versus 22%) and the odds of CMD were 7.24 times higher among IBS patients than controls (95% CI 3.6–14.5, P < 0.001). No difference was found in frequency of CMDs among various subtypes of IBS. Conclusion. We found that CMDs are more common and strongly associated with IBS as compared to other chronic diseases. Early screening for CMDs might be useful for an effective management of IBS

Consensus interferon plus ribavirin for Hepatitis C genotype 3 patients previously treated with pegylated interferon plus ribavirin

Background Not enough data are available about the effectiveness of consensus interferon (CIFN) among HCV genotype 3 patients who failed to respond to pegylated interferon and ribavirin. Objectives We aimed to assess the efficacy and safety of CIFN and ribavirin in non-responders and relapsers to pegylated interferon with ribavirin therapy. Patients and Methods This open-label investigator-initiated study included 44 patients who received CIFN 15 µg /day plus ribavirin 800-1200 mg daily. In patients with an early virological response (EVR), the dose of CIFN was reduced to 15 µg thrice a week for further 36 weeks. Patients with delayed virological response continued to receive daily CIFN plus ribavirin to complete 48 weeks. The patients were considered “non-responders” if there were less than 2 log reduction in HCV RNA at 12 weeks and detectable HCV RNA at 24 weeks. Results Twenty-four patients (55%) were non-responders and 20 patients were relapsers to the previous treatment with pegylated interferon plus ribavirin (mean age 43.6 ± 9.4 years, males 25 (57%)). Nine patients were clinically cirrhotic (Child A). End of treatment virological response was achieved in 19 (43.1%) patients and sustained virological response (SVR) occurred in 12 (27.3%). Out of these 12 patients, eight were non-responders and four were relapsers to the previous treatment. Advanced fibrosis or clinical cirrhosis was associated with low SVR. Adverse events were fever, myalgia, anorexia, depression, and weight loss. Two patients received granulocyte colony stimulating factor for transient neutropenia. Seven patients were given erythropoietin to improve hemoglobin, and six were treated for mild depression. Two patients developed portosystemic encephalopathy. Conclusions More than one-quarter of treatment-experienced patients with HCV genotype 3 achieved SVR after re-treatment with consensus interferon plus ribavirin

Hepatocellular carcinoma in Native South Asian Pakistani population; trends, clinico-pathological characteristics & differences in viral marker negative & viral-hepatocellular carcinoma

Background HCC is the fifth most common cancer globally. Our study was conducted to (1)investigate the trends and clinico-pathological characteristics of Hepatocellular carcinoma among native South Asian patients in Pakistan, (2)to estimate the prevalence as well as the trends of viral marker negative HCC and (3) to compare the clinico-pathological, radiological characteristics, applicability of treatment at diagnosis and prognostic factors among patients with both viral marker negative and viral marker positive-HCC being consulted at Aga Khan University Hospital(AKUH), Karachi, Pakistan. Method Patients ≥18 years, already diagnosed to have HCC and visiting AKUH during 1999–2009 were identified using ICD code 1550. The diagnosis of HCC was made in the presence of characteristic features of HCC on triple-phasic CT scan/MRI or with histological findings on biopsy. Results 645 patients were enrolled. Of these 546(84.7%) were viral-HCC and 99(15.3%) were viral marker negative HCC. Among viral-HCC group underlying etiology of cirrhosis was HCV in 67.9%, HBV in 21.8% and concomitant HBV with HCV or HDV in 10.3% cases. Majority (62.8%) patients had advanced HCC. Larger tumor size (p \u3c 0.001), shorter duration between diagnosis of cirrhosis and HCC (p 0.03), concomitant Diabetes Mellitus (p \u3c 0.001) were found significant factors associated with viral marker negative HCC. Conclusion The burden of hepatocellular carcinoma is rising among native South Asian Pakistani population and the viral marker negative HCC are not uncommon in our population. Viral marker negative HCC tend not to be under surveillance as compared to viral-HCC and are diagnosed mostly at advanced stage & when they became symptomatic

Applying a mixed-method approach to improve on-the-job learning and job satisfaction in a cohort of interns at a university hospital

Introduction: Job satisfaction is vital for the optimal functioning of medical practitioners. Herein, we report our experience of restructuring the internship program by identifying the gaps, developing, implementing strategies to overcome gaps and sharing the results of the pre-implementation and post-implementation audit, as an example for establishing a system for improving intern\u27s work-based learning and satisfaction in a university hospital setting.Methods: Using Kern\u27s six-step instructional model, a prospective mixed-method study was conducted at Aga Khan University Hospital. In phase 1 (2013) gaps were identified by evaluating various aspects of the internship program. Strategies were developed and implemented to overcome the identified gaps. In phase 2 (2014-2016) the impact of these developmental strategies was assessed.Results: A total of 65 interns, 30 residents, and 22 faculty members participated in phase I, while 71 interns participated in phase II. The reformation of orientation sessions, including practical exposure and content of sessions, opportunities to enhance hands-on experience and supervision in inpatient areas, operating rooms, supervision by fellows, supervision for hands-on procedures, career counseling, and mentorship, led to significant improvement in satisfaction. It was identified that the lack of hands-on opportunities can be overcome by surgical skills-based workshops. These reforms led to an overall rise in intern satisfaction (50% vs 75.4%, p=0.02).Conclusion: Periodic restructuring of an existing program helps to improve the work-based learning experience and overall satisfaction among interns. This not only maximizes learning but also eases interns into their postgraduate life and workload subsequently enabling them to become more competent and well-rounded health practitioners

Successful outcome of a pregnancy in a woman with advanced cirrhosis due to hepatitis B surface antigenemia, delta super-infection and hepatitis C co-infection: a case report

Pregnancy in women with advanced liver disease is rare. In this paper we described the case of a successful pregnancy in a young woman with advanced cirrhosis due to hepatitis B surface antigenemia, hepatitis delta super-infection and Hepatitis C co-infection. A brief review of the medical literature on pregnancy in women with cirrhosis is also presented

Prevalence and risk of hepatitis E virus infection in the HIV population of Nepal

Background: Infection with the hepatitis E virus (HEV) can cause acute hepatitis in endemic areas in immune-competent hosts, as well as chronic infection in immune-compromised subjects in non-endemic areas. Most studies assessing HEV infection in HIV-infected populations have been performed in developed countries that are usually affected by HEV genotype 3. The objective of this study is to measure the prevalence and risk of acquiring HEV among HIV-infected individuals in Nepal. Methods: We prospectively evaluated 459 Human Immunodeficiency Virus (HIV)-positive individuals from Nepal, an endemic country for HEV, for seroprevalence of HEV and assessed risk factors associated with HEV infection. All individuals were on antiretroviral therapy and healthy blood donors were used as controls. Results: We found a high prevalence of HEV IgG (39.4%) and HEV IgM (15.3%) in HIV-positive subjects when compared to healthy HIV-negative controls: 9.5% and 4.4%, respectively (OR: 6.17, 95% CI 4.42-8.61, p \u3c 0.001 and OR: 3.7, 95% CI 2.35-5.92, p \u3c 0.001, respectively). Individuals residing in the Kathmandu area showed a significantly higher HEV IgG seroprevalance compared to individuals residing outside of Kathmandu (76.8% vs 11.1%, OR: 30.33, 95% CI 18.02-51.04, p = 0.001). Mean CD4 counts, HIV viral load and presence of hepatitis B surface antigen correlated with higher HEV IgM rate, while presence of hepatitis C antibody correlated with higher rate of HEV IgG in serum. Overall, individuals with HEV IgM positivity had higher levels of alanine aminotransferase (ALT) than IgM negative subjects, suggesting active acute infection. However, no specific symptoms for hepatitis were identified. Conclusion: HIV-positive subjects living in Kathmandu are at higher risk of acquiring HEV infection as compared to the general population and to HIV-positive subjects living outside Kathmandu

Re-structuring university hospital’s internship program using kern’s six-step model of Instructional design

Abstract Background: Internship is a phase of training wherein a graduate learns in the context of practice, acquiring skills under supervision so that he/she may become capable of functioning independently. We are reporting the process of curriculum restructuring for strengthening the Internship Program at this university hospital. Methodology: We used Kerns’ six-step model to evaluate and restructure the internship curriculum. Step 01: Problem Identification & General need assessment- Thorough literature review revealed Internship as the crucial year of training that needs to be fashioned around the competencies required to make good doctor