Atul Kotwal

Monitoring of response to therapy with imatinib mesylate in Chronic Myeloid Leukemia in chronic phase (CML-CP)

BACKGROUND The BCR-ABL tyrosine kinase is a well validated therapeutic target in Chronic Myeloid Leukemia (CML). Imatinib mesylate (IM), a tyrosine kinase inhibitor is highly effective in the treatment of chronic phase CML. BCR - ABL transcripts have been well established as a molecular marker to document response to therapy in CML. Periodic monitoring of this marker helps in evolving therapeutic strategies with IM and also in diagnosing early relapse. This study was undertaken to monitor therapeutic response to IM in CML in chronic phase (CML-CP) by assessing BCR-ABL by real time quantitative PCR (RQ-PCR) techniques and to determine the effectiveness of the Indian generic IM. METHODS One hundred consecutive patients of CML in chronic phase (CML-CP) were treated with an Indian generic of IM. Eighty-five patients were evaluable at 12 months of therapy. At entry, diagnosis of CML-CP was confirmed by FISH and RQ-PCR. Response to therapy was monitored by assessing BCR-ABL levels by RQ-PCR at 6 and 12 months of therapy. Regular follow up of patients was done to evaluate the safety profile of IM used in these patients. RESULTS Complete hematological response (CHR) rates at 3, 6, 9 and 12 months were 92%, 94%, 100% and 100% respectively. The total molecular response at 12 months was 43.52% of which complete molecular response (CMR) was noted in 17.64% and major molecular response (MMR) was observed in 25.88%. A cumulative survival probability of 0.8 was observed. CONCLUSION The Indian generic molecule of IM is effective in the treatment of CML-CP. The cost of Indian generic molecule is less than Rs. 10,000 per month there by making this affordable for large number of CML-CP patients in India.

Seroprevalence of human parvovirus B19 in healthy blood donors

BACKGROUND Human parvovirus B19 is an emerging transfusion transmitted infection. Although parvovirus B19 infection is connected with severe complications in some recipients, donor screening is not yet mandatory. To reduce the risk of contamination, plasma-pool screening and exclusion of highly viraemic donations are recommended. In this study the prevalence of parvovirus B19 in healthy blood donors was detected by ELISA. METHODS A total of 1633 samples were screened for IgM and IgG antibodies against parvovirus B19 by ELISA. The initial 540 samples were screened for both IgM and IgG class antibodies and remaining 1093 samples were screened for only IgM class antibodies by ELISA. RESULTS Net prevalence of IgM antibodies to human parvovirus B19 in our study was 7.53% and prevalence of IgG antibodies was 27.96%. Dual positivity (IgG and IgM) was 2.40%. CONCLUSION The seroprevalence of human parvovirus B19 among blood donor population in our study is high, and poses an adverse transfusion risk especially in high-risk group of patients who have no detectable antibodies to B19. Studies with large sample size are needed to validate these results.

Effectiveness of homocysteine lowering vitamins in prevention of thrombotic tendency at high altitude area: A randomized field trial

INTRODUCTION A higher risk of thrombosis has been reported on prolonged stay at high altitude (HAA). Lowering of homocysteine (Hcy) has been found to reduce the risk of venous thrombosis. A randomized field trial was conducted with primary question whether Hcy lowering agents have any effect on the incidence of thrombosis at HAA amongst Indian soldiers as compared to existing interventions. METHODS All units freshly inducted to HAA were randomized into intervention (Vit B12 1000 microgram/day, B6 3mg/day & folic acid 5mg/day) and control arms, with a sample size of 12,000 person-years in each arm. RESULTS At the end of one year stay at HAA, Folate and B 12 levels decreased significantly in control arm. The levels of Hcy, fibrinogen and plasminogen activator inhibitor (PAI 1) were lower and nitric oxide higher in intervention arm as compared to control arm (p<0.05). At the end of 2years, 5 thrombotic episodes occurred in the intervention arm and 17 in control arm with RR of 0.29 (95% CI 0.11-0.80), attributable fraction % (AFe) 70.59%, Population attributable risk percent 54.55% and Protective Fraction 240%. CONCLUSION Intervention with B12 and folic acid is effective in reducing Hcy, PAI 1, fibrinogen levels and increasing NO levels at 1yr as compared to control arm and reducing the incidence of thrombosis at 2years of stay at HAA. Thus, vitamin B 12, B6 and folic acid intervention is safe and effective method of reducing morbidity and mortality caused by HAA induced coagulopathy.

Evaluation of Surrogate Markers for Prediction of CD4 Counts in People Living with Human Immunodeficiency Virus/ Acquired Immunodeficiency Syndrome

India is a developing country where resources are limited. HIV/ AIDS is an ominous public health problem faced by our population and the affordability of patients for 3-6 monthly monitoring of CD4 counts becomes difficult for most patients. The intent of the study was to identify parameters on complete blood counts that can predict a CD4 count of 1250/μL is predictive of a CD4 count <200/μL with a sensitivity and specificity of 87.3% and 70.0% respectively. In addition, a haemoglobin value <11.15g/dL is also a good predictor of the CD4 count <200/μL. The combination of both Hb <11.15g/dl and ALC counter <1250/μL was like a confirmatory test with a specificity of 92.2% and a NPV of 79.5%. Hemoglobin and absolute lymphocyte counts obtained on automated cell counter are robust, cost-effective and easily available methods to follow up PLHA patients and patients on ART. These can effectively predict the CD4 count <200/μL and are especially useful in a developing country where the cost of these tests is one-fifth of flow cytometry.

Predictors of first line antiretroviral therapy failure and burden of second line antiretroviral therapy

BACKGROUND As HIV steps into the third decade, there are more number of patients living on lifelong (antiretroviral therapy) ART and facing the threat of drug resistance with subsequent treatment failure. The aim of this study was to determine predictors of first-line ART failure with the objectives to estimate the burden of 2nd line ART. METHODS A retrospective 5-year cohort of HIV patients who were initiated on first line ART in 2008-09 was studied. Patients were followed from the time of ART initiation. Kaplan-Meier methods and Cox proportional hazards regression models were used to estimate probabilities and predictors of first line ART failure. RESULTS Of the total of 195 patients initiated on first line ART, 15 patients were switched to second line ART yielding 7.69% failure rate. During the 7178 person-years of follow-up, the incidence of first line ART failure was 2.09 per 1000 person-years. The Kaplan-Meier survival analysis gave a mean survival time of 55.6 months. BMI, CD4 count at ART initiation and presence of opportunistic infections were significant predictors of first line ART failure. The burden of second line ART patients by the end of 5 years of first line ART is expected to be 151 patients. CONCLUSION Though the first line ART failure is quite low in this study, we still need to be vigilant for lower BMI, low baseline CD4 count and occurrence of opportunistic infections to efficiently manage failures on first line ART.

Antimicrobial use and antimicrobial resistance in nosocomial pathogens at a tertiary care hospital in Pune

BACKGROUND Resistance to antimicrobial agents is emerging in wide variety of nosocomial and community acquired pathogens. Widespread and often inappropriate use of broad spectrum antimicrobial agents is recognized as a significant contributing factor to the development and spread of bacterial resistance. This study was conducted to gain insight into the prevalent antimicrobial prescribing practices, and antimicrobial resistance pattern in nosocomial pathogens at a tertiary care hospital in Pune, India. METHODS Series of one day cross sectional point prevalence surveys were carried out on four days between March and August 2014. All eligible in patients were included in the study. A structured data entry form was used to collect the data for each patient. Relevant samples were collected for microbiological examination from all the clinically identified hospital acquired infection cases. RESULTS 41.73% of the eligible patients (95% CI: 39.52-43.97) had been prescribed at least one antimicrobial during their stay in the hospital. Beta-lactams (38%) were the most prescribed antimicrobials, followed by Protein synthesis inhibitors (24%). Majority of the organisms isolated from Hospital acquired infection (HAI cases) were found to be resistant to the commonly used antimicrobials viz: Cefotaxime, Ceftriaxone, Amikacin, Gentamicin and Monobactams. CONCLUSION There is need to have regular antimicrobial susceptibility surveillance and dissemination of this information to the clinicians. In addition, emphasis on the rational use of antimicrobials, antimicrobial rotation and strict adherence to the standard treatment guidelines is very essential.

Profile of HIV patients on second line antiretroviral therapy: the Indian experience.

Background: The proportion of patients on second line in resource limited settings are estimated between 1-5%. The present study describes the profile and outcomes of Indian patients receiving second line ART. Methods: Information on HIV patients on second line ART was gathered. Socio demographic data, probable transmission route, baseline clinical parameters and comorbidities during therapy are studied along with first-line ART regimen initially introduced, its adherence and the reason for switch and components of the second-line ART regimen. Results: Out of the total 2174 HIV patients 53% were on first line ART and of these 51 patients on second line ART were studied. The average time of initiation of first line ART was 17.67 months with median of 2 months whereas switch to second line ART was in 53.75 months with median of 60 months. Almost 71% of the patients on second line ART had been diagnosed with HIV infection with low CD4 count of <200. However 54%, 67% and 58% patients show more than 50% rise in their CD4 count post switch to second line after 3, 6 and 12 months of treatment which is a substantial improvement. Twenty-five per cent of patients showed non adherence. Tenofovir based regimens had a slight advantage with lesser number of side effects being reported. Conclusion: Early diagnoses of infection, early initiation of ART and drug adherence are the cornerstones for success in managing HIV patients. Understanding the profile and drug resistance pattern is necessary for ensuring effective and long term survival.

Use of Kirkpatrick’s model for evaluation of reaction and learning of participant of national level workshop on linear regression

Workshop is a very useful learning method for increasing the understanding and knowledge of participant. Workshop is usually conducted among limited predecided participant. However the attendees may vary in their qualification and different knowledge of the subject, hence it throws a challenge to the organizer for taking every participant along. Like any other education process, the workshop needs to be evaluated. The evaluation is essential to generate empirical evidence whether the objectives of the workshop have been achieved. Also there is a increasing scrutiny to evaluate the academic programs for their stated objectives. 2

Pulmonary embolism in young natives of high altitude

Thrombotic events are relatively common in high altitude areas and known to occur in young soldiers working at high altitude without usual risk factors associated with thrombosis at sea-level. However, till now, cases with thrombotic events were reported only in lowlanders staying at high altitude. These two cases of pulmonary embolism demonstrate that thrombotic events can occur in highlanders after a prolonged stay at the extreme altitude.

High altitude pulmonary edema (HAPE) with pulmonary embolism

High altitude pulmonary edema (HAPE) is a life-threatening condition occurring at heights above 2500 meter mostly within 2-4 days of entry in high altitude. Postmortem studies showed evidence of thrombi in cases of HAPE suggesting possible role of thrombosis in the pathogenesis of HAPE. Here, we are presenting the two cases of HAPE with pulmonary embolism, and the possibility of pulmonary embolism should be considered in cases of HAPE with persistent radiographic opacities despite oxygen or descent.