Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine

BACKGROUND: Patients with HIV infection are at risk of co-infection with HBV, as the routes of transmission are shared and thus immunization with HBV vaccine could be protective in them. The aim of the present study was to assess the efficacy of recombinant vaccine in treatment-naive HIV positive patients and healthy controls, and to dissect out differences if any, in different limbs of immune response. METHODS: Forty HIV positive patients and 20 HIV negative controls, negative for HBsAg, HBsAbs and HBcAbs were vaccinated with three doses of 40μg and 20μg of vaccine respectively. Patients were divided into high CD4 and low CD4 group based on CD4+ lymphocytes of 200 and < 200/mm3 respectively. Group II consisted of healthy controls. Detection of phenotypic markers was done by flowcytometry. Cytokine estimation was done by sandwich ELISA. HBsAbs were estimated in serum by ELISA. RESULTS: After vaccination, CD(4)+, CD(8)+ and CD(3)+ cells increased significantly in all the groups. There was no increase in NK cell activity in patients with high CD(4)+ lymphocytes and only a marginal increase in patients with low CD(4)+ lymphocytes (170 to 293/mm3) whereas a marked increase was observed in controls (252 to 490/mm3). After vaccination, although an increase in memory cells was observed in HIV positive patients, yet HBsAb levels were significantly lower than controls (P < 0.05) indicating a functional defect of memory cells in HIV/AIDS patients. Basal IFN-γ levels were also significantly lower in HIV/AIDS patients (P < 0.01). Although the levels increased after vaccination, the peak level remained lower than in controls. HBsAb titers were much lower in HIV positive patients compared to controls. (High CD(4)+ group: 8834 mIU/ml, low CD(4)+ group: 462 mIU/ml Vs. Controls: 16,906 mIU/ml). IL-4 and IL-10 were low in patients. CONCLUSION: Despite a double dose in patients, IL-4 and IL-10, which regulate antibody response, were also lower in patients, and this together with low CD(4)+ counts and lack of T help, accounted for low HBsAb levels. Vaccination in patients with CD(4)+ lymphocytes < 50/mm(3) was ineffective. Thus early immunization is advocated in all HIV positive patients at a stage when they are still capable of mounting an adequate immune respons

A study of acceptability & feasibility of integrating humanities based study modules in undergraduate curriculum

Background & objectives: The field of medical education in our country remains deeply fragmented and polarised between the biomedical technical domains which are overrepresented and the humanitarian domains which are under-represented within the universe of medical pedagogy. To overcome this imbalance, we designed a module that integrates the two domains in a holistic biomedical and socio-cultural framework with the objective of providing unified field of learning experience to the undergraduate medical students attending rotatory clinical postings in a medical college in New Delhi, India. Methods: Undergraduate medical students of 6 th and 8 th semesters were enrolled in humanities based study module (HSM) on voluntary basis for a total duration of six months. During their compulsory rotatory medicine ward posting, they were introduced and exposed to learning bedside experience of HSM with various tools of art and literature in the form of poem, short narratives, paintings, sketches and group discussions to express their feelings about patients′ sufferings. Students′ feed-back was recorded through an anonymized questionnaire. Result: Of the 235 students, 223 (95%) enrolled themselves voluntarily and 94 per cent (210 of 223) of them completed the total six month duration of the study module. Seventy three per cent of the students found HSM effective in improving their affective motivational behavior, 82 per cent found it effective in motivating them to learn more about core medical subjects, and 85 per cent wanted its continuation as part of medical curriculum. Interpretation & conclusions: The positive response of the students towards the HSM was an indicator of the potential for integrating the module within the undergraduate medical curriculum

Utilisation of Health Technologies for Physical Health of People with Learning Disabilities: Point of Care Testing

The World Health Organisation defines health technologies as the “application of organized knowledge and skills in the form of devices, medicines, vaccines, procedures and systems developed to solve a health problem and improve quality of lives.” Innovative health technologies have immense potential to improve human health and well-being. However, their advent does not guarantee equitable health outcomes. Not all individuals have equal access to health technologies resulting in different health outcomes for those individuals. Barriers to adoption, implementation, access, research and design can lead to exclusion and perpetuate the health inequalities already experienced by vulnerable or marginalised groups, for example those with intellectual disabilities (ID). Point of care testing (POCT) is a health technology used to monitor physical health and has been available for almost a decade. POCT is reported to be minimally invasive, can be conducted in a wide range of settings, enables shorter time to clinical decision making, improved self-management of health conditions and patient empowerment. Despite the benefits of POCT, adoption, use, awareness and research of the use of this technology in people with ID to monitor physical health appears to be scant. This article will explore the application of POCT in this group of individuals for whom evidence informs us die up to 25 years earlier when compared to the general population, and physical health disease account for the overwhelming majority of premature deaths. This is a narrative review exploring the use of POCT for physical health of people with ID

Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression

Background & Aims: Chronic hepatitis C virus infection is associated with an increased prevalence of type 2 diabetes. We hypothesized that virus-induced insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C virus infection. Methods: In 260 hepatitis C virus-infected subjects, we examined the relationship between histological findings and anthropometric and biochemical data, including insulin resistance determined by the homeostasis model assessment (HOMA-IR). We also compared fasting serum insulin, C peptide, and HOMA-IR levels between the subset of 121 hepatitis C virus patients with stage 0 or 1 hepatic fibrosis and 137 healthy volunteers matched by sex, body mass index, and waist-hip ratio. Results: Hepatitis C virus-infected subjects with stage 0 or 1 hepatic fibrosis had higher levels of insulin, C peptide, and HOMA-IR (all P ≤ 0.01) compared with matched healthy controls. In the 250 hepatitis C virus patients (fibrosis stage 0 to 4), viral genotype and portal, but not lobular, inflammation were univariate predictors of HOMA-IR. By multiple linear regression analysis, independent predictors of HOMA-IR included body mass index (P < 0.1001), previous failed antiviral treatment (P < 0.001), portal inflammatory grade (P < 0.001), and genotype 3 status (P = 0.01). Genotype 3 had significantly lower HOMA-IR than other genotypes (which were comparable when adjusted for effects of the remaining independent predictors). HOMA-IR was an independent predictor for the degree of fibrosis (P < 0.001) and the rate of fibrosis progression (P = 0.03). Conclusions: Hepatitis C virus may induce insulin resistance irrespective of the severity of liver disease, and this effect seems to be genotype specific. Further, our findings support the hypothesis that insulin resistance may contribute to fibrotic progression in chronic hepatitis C virus infection

Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C

Data on the long-term outcome of nonalcoholic steatohepatitis (NASH)-associated cirrhosis are few, and most reports describe cases of cryptogenic cirrhosis associated with risk factors for NASH but without histologic definition. In this prospective cohort study, we describe the long-term morbidity and mortality of 23 patients with NASH-associated cirrhosis defined by strict clinicopathologic criteria. Outcomes were compared with 46 age-and gender-matched patients with cirrhosis from chronic hepatitis C virus (HCV) infection: 23 untreated and 23 nonresponders to antiviral therapy. During follow-up (mean, 84 months; median, 60 months; range, 5-177 months), 9 of the 23 NASH-associated cirrhosis cases developed liver-related morbidity (8 ascites and/or encephalopathy, 1 variceal bleeding). The probability of complication-free survival was 83%, 77%, and 48% at 1, 3, and 10 years, respectively, and the cumulative probability of overall survival was 95%, 90%, and 84% at 1, 3, and 10 years, respectively. Five deaths were from liver failure, 1 from a non-liver-related cause. By multivariate analysis, bilirubin (P = .02) and platelet (P = .04) were independent predictors of complication-free survival; bilirubin (P = .05) was the only predictor for overall survival. After controlling for these factors, there was no difference in complication-free or overall survival between the NASH-cirrhosis cohort and either group of HCV-cirrhosis. However, 8 cases of liver cancer occurred in the HCV-cirrhosis groups compared with none among NASH cases. In conclusion, liver failure is the main cause of morbidity and mortality in NASH-associated cirrhosis. The prognosis is either similar or less severe than HCV-cirrhosis, except that HCC appears less common

Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial

© 2015 The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected]. Background. In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal ß-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. Methods. In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. Results. We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P =. 06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. Conclusions. Combining an antistaphylococcal ß-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au)