Trends in oral anticoagulant use - A 10-year retrospective analysis from a general medicine department of a tertiary care hospital in south India.

Background: The prescribing practice of newer oral anticoagulants (NOACs) has not been adequately studied in the Indian scenario. Aims: We aimed to describe the prescribing practices of oral anticoagulants, the patient profile and medical comorbidities among patients admitted in a general medicine unit. Methods: In this retrospective study of the 2742 patients prescribed vitamin- K antagonists (VKAs), during the study period, 150 cases were randomly taken for analysis to match the 105 NOACs cases. Their demographic details, clinical characteristics and treatment details were analyzed. Results: More than 95% of anticoagulants prescribed were VKAs. The prescription of anticoagulants was more common in men (median age 63 years) for prescription of NOACs and 52 years for VKAs. Dabigatran (60.9%) and warfarin (81.3%) were the most prescribed drugs in their respective classes. The most common indication was for cardiovascular diseases with atrial fibrillation (32%). Diabetes and hypertension were the most common comorbidities in patients prescribed oral anticoagulants with a larger proportion of patients with heart failure being prescribed VKAs (P < 0.01). Patients in the NOACs group had a higher HAS-BLED high-risk score (33.3% vs. 17.3%; P = 0.002). Logistic regression analysis revealed that patients with co-morbidities of congestive heart failure were more likely to be prescribed VKAs while diabetics were more likely to receive NOACs. Conclusions: VKAs were the most prescribed anticoagulants; congestive heart failure, diabetes, and hypertension were the commonest comorbidities; and atrial fibrillation was the commonest indication. Patients with a high HAS-BLED score were prescribed NOACs more often.

Pilot randomized trial of nutritional supplementation in patients with tuberculosis and HIV-tuberculosis coinfection receiving directly observed short-course chemotherapy for tuberculosis.

OBJECTIVE: To investigate the effects of nutritional supplementation on the outcome and nutritional status of south Indian patients with tuberculosis (TB) with and without human immunodeficiency virus (HIV) coinfection on anti-tuberculous therapy. METHOD: Randomized controlled trial on the effect of a locally prepared cereal-lentil mixture providing 930 kcal and a multivitamin micronutrient supplement during anti-tuberculous therapy in 81 newly diagnosed TB alone and 22 TB-HIV-coinfected patients, among whom 51 received and 52 did not receive the supplement. The primary outcome evaluated at completion of TB therapy was outcome of TB treatment, as classified by the national programme. Secondary outcomes were body composition, compliance and condition on follow-up 1 year after cessation of TB therapy and supplementation. RESULTS: There was no significant difference in TB outcomes at the end of treatment, but HIV-TB coinfected individuals had four times greater odds of poor outcome than those with TB alone. Among patients with TB, 1/35 (2.9%) supplemented and 5/42(12%) of those not supplemented had poor outcomes, while among TB-HIV-coinfected individuals, 4/13 (31%) supplemented and 3/7 (42.8%) non-supplemented patients had poor outcomes at the end of treatment, and the differences were more marked after 1 year of follow-up. Although there was some trend of benefit for both TB alone and TB-HIV coinfection, the results were not statistically significant at the end of TB treatment, possibly because of limited sample size. CONCLUSION: Nutritional supplements in patients are a potentially feasible, low-cost intervention, which could impact patients with TB and TB-HIV. The public health importance of these diseases in resource-limited settings suggests the need for large, multi-centre randomized control trials on nutritional supplementation.

Evidence for lower CD4+ T cell and higher viral load in asymptomatic HIV-1 infected individuals of India: implications for therapy initiation.

PURPOSE: We have earlier documented that the south Indian population had lower CD4 counts. The aim of this study was to investigate a previous suggestion on a new CD4+ T cell cut off and association with HIV-1 RNA levels for decision on anti retroviral therapy in India (south). METHODS: We evaluated a new methodology i.e., artus real-time PCR and CD4+ T cell count by Guava EasyCD4 system. From 146 HIV infected individuals seen at a tertiary care centre, blood was collected for CD4+ T cell and HIV-1 RNA estimation. RESULTS: The receiver operating characteristic curve cut off value for the CD4 counts to distinguish between CDC clinical categories A and B was 243 cells/microL, and to distinguish B and C was 153 cells/microL. The RNA level that differentiated CDC A and B was 327473 RNA copies/mL, while for CDC B and C was 688543 copies/mL. There was a significant negative correlation (r = -0.55, P + T cell counts in HIV infected individuals. CONCLUSIONS: A majority with CD4 counts of 201-350 cells/microL in our population had higher viral load than the treatment threshold suggested by the International AIDS society and the above two methodologies are useful in monitoring HIV infections.

Genotypic resistance profile of HIV-1 protease gene: a preliminary report from Vellore, south India.

HIV-1 subtypes other than B are responsible for most new HIV infections worldwide; virus sequence data for drug resistance is described only from a limited number of non-B subtype HIV-1. This study is on mutations and polymorphisms of HIV-1 protease gene that can predict drug resistance in subtype C. The genotypic resistance assay was carried out on 38 HIV-1 strains with their plasma RNA and in nine, the proviral protease gene was sequenced. The treatment naïve strains showed minor resistance mutations, there were no major resistance mutations in the protease gene. We suggest the use of resistance testing to monitor individuals on therapy and also before initiation of therapy, gathering more sequence information for a data bank of Indian strains.

Acute abdomen: an unusual presentation of disseminated Penicillium marneffei infection.

Varied clinical presentations of Penicillium marneffei, an opportunistic pathogen in HIV disease has been rarely described in literature. We report a patient with advanced AIDS who presented to us with prolonged fever and had features of an acute abdomen. On radiologic imaging he had features of intestinal obstruction and mesenteric lymphadenitis. A diagnosis was made possible by endoscopic biopsies of the small bowel and bone marrow culture which grew P. Marneffei. He was treated with intravenous amphotericin for 2 weeks followed by oral itraconazole. This case is reported for its rarity and unusual presentation and to sensitise clinicians and microbiologists to consider this as an aetiology in patients with advanced HIV/AIDS who present with acute abdomen, more so in patients from a distinct geographic region--South-East Asia.

Pre-admission antibiotics for suspected cases of meningococcal disease.

BACKGROUND: Meningococcal disease begins suddenly and death can follow within hours. Pre-admission antibiotic therapy aims to prevent delay in starting therapy that occurs if bacterial confirmation is sought before instituting therapy. OBJECTIVES: To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo and of different pre-admission antibiotic regimens in decreasing mortality and morbidity in people suspected of meningococcal disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007, Issue 1), MEDLINE (1966 to February 2007) and EMBASE (1980 to February 2007). SELECTION CRITERIA: We selected randomised controlled trials (RCTs) or quasi-RCTs, of all people with suspected meningococcal infection. We compared antibiotic treatment versus placebo or no intervention, or different antibiotic treatments administered before admission to hospital or confirmation of the diagnosis. DATA COLLECTION AND ANALYSIS: Two author authors independently assessed quality and extracted data from included trials. We calculated the relative risk (RR) and 95% confidence interval (CI) for dichotomous data. As only one trial fulfilled inclusion criteria, data synthesis was not performed. MAIN RESULTS: No RCTs were found that compared pre-admission antibiotics versus no pre-admission antibiotics or placebo. One open-label RCT evaluated a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long acting (oily) chloramphenicol. Interventions did not differ significantly in mortality (RR 1.2, 95% CI 0.5 to 2.6; N = 510; 349 confirmed meningococcal meningitis; 26 deaths), nor in proportions of survivors who developed neurological sequelae (RR 1.2, 95% CI 0.6 to 2.2; N = 488; 36 with neurological sequelae), or that were classified as clinical failures (RR 0.8, 95% CI 0.4 to 1.8; N = 488, 25 clinical failures). No adverse effects of treatment were seen. No data were available for our secondary outcomes. AUTHORS' CONCLUSIONS: We found no reliable evidence to support or refute the use of pre-admission antibiotics for suspected cases of meningococcal disease. Evidence from one RCT-during an epidemic of meningococcal meningitis, indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective and safe in preventing mortality and morbidity. The choice between these antibiotics would be based on affordability, availability, and patterns of antibiotic resistance.Further RCTs comparing different pre-admission antibiotics, including penicillin, including participants with severe illness are ethically justifiable and are needed to provide reliable evidence to clinicians in differing clinical settings.

Usefulness of alternate prognostic serum and plasma markers for antiretroviral therapy for human immunodeficiency virus type 1 infection.

In developing countries, the usability of peripheral blood constituents that are low-cost alternatives to CD4-positive (CD4+) T-cell and human immunodeficiency virus type 1 (HIV-1) RNA estimation should be evaluated as prognostic markers. The aim of our study was to investigate the use of plasma levels of dehydroepiandrosterone sulfate (DHEAS), albumin, and C-reactive protein (CRP) as alternate prognostic markers for antiretroviral treatment (ART) response in place of HIV-1 load measurements. Paired blood samples were collected from 30 HIV-infected individuals before and after initiation of ART, 13 HIV-infected individuals before and after completion of antituberculosis therapy (ATT), and 10 HIV-infected individuals not on either ATT or ART. Because of the nonavailability of samples, the CRP estimation was done for samples from only 19, 9, and 8 individuals in groups 1, 2, and 3, respectively. The measurements of all three markers, i.e., DHEAS, albumin, and CRP, were carried out with commercial assays. The differences in the albumin levels before and after ART or ATT were significant (P < 0.05), while the differences in DHEAS and CRP levels were not significant (P > 0.05). When levels of DHEAS among the individuals who were followed up were analyzed, 13 (44.8%) in the ART group and 9 (69%) in the ATT group showed an increase following treatment. Prior to treatment of HIV-infected individuals, there was a significant positive correlation of CD4+ T-cell counts and a negative correlation of viral load with albumin and DHEAS levels (P < 0.01). Among the three plasma markers we tested, plasma albumin and, to some extent, DHEAS show promise as prognostic markers in monitoring HIV infection.

Screening for HIV infection by health professionals in India.

BACKGROUND: Stigma and discrimination, particularly in access to healthcare, remains a major problem for people Infected with HIV in most parts of India. METHODS: We did a multicentre study (n = 10) with a cross-sectional survey design using a standardized, interviewer-administered questionnaire. RESULTS: A total of 2200 healthcare providers participated. The knowledge, attitude and practice (KAP) related to HIV service delivery were very poor with a mean overall KAP score of only 49.7% (CI: 49.1-50.3). Only 5%, 5% and 1% of the participants scored more than 75% separately for the dimensions of knowledge, attitude and practice, respectively. Only 24.4% and 36.7% of responders knew that HIV screening was not recommended prior to surgery and pre-employment check-up. Many doctors (19.4%) had refused treatment to people living with HIV/AIDS (PLHA) at least some of the time and nearly half (47.2%) identified and labelled them; 23.9% isolated them in separate care areas and 13.3% postponed or changed treatment based on the patient's HIV status. Screening for HIV prior to elective surgery was done by 67% of providers. While 64.7% of responders were aware of the existence of national guidelines on and recommendations for HIV testing, only 38.4% had read the policy document. CONCLUSION: There is a growing need to provide care, support and treatment to a large number of PLHA. The capacity of healthcare providers must be urgently built up so as to improve their knowledge of and attitude to HIV to enable them to deliver evidence-based and compassionate care to PLHA in various healthcare settings.

One year trends in the gram-negative bacterial antibiotic susceptibility patterns in a medical intensive care unit in South India.

PURPOSE: To describe the changes in antibiotic susceptibility patterns of common intensive care unit pathogens with time from the medical intensive care unit of a tertiary care hospital. METHODS: A prospective observational study was conducted in the medical intensive care unit (MICU) of a 2100 bed tertiary care hospital in South India. All data regarding patient characteristics, disease characteristics, infective agents, identified along with their antibiotic sensitivity patterns and patient outcomes were prospectively recorded in MICU data base. Various bacterial pathogen antibiotic sensitivity patterns from August 2004 to May 2005 were prospectively documented. During this period 491 patients were admitted to the MICU. Data were analyzed using excel spreadsheets. RESULTS: Ceftazidime resistance reduced in Klebsiella spp. while cefotaxime resistance increased. In E. coli however, ceftazidime and cefotaxime resistance increased. Klebsiella resistance to cefotaxime and ceftazidime ranged from 25-50% and 14-91%, while E. coli resistance to these antibiotics ranged from 50-70% and 50 to 80% respectively. In Pseudomonas and the non-fermenting gram-negative bacteria (NFGNB) ceftazidime resistance decreased. Third generation cephalosporin resistance seemed to be reducing in the NFGNB, however, carbapenem resistance appeared to be increasing, possibly due to their increasing use. CONCLUSIONS: This study demonstrates the trend in antibiotic susceptibility pattern (AST) of common gram negative infections seen in intensive care units. It demonstrates the changes seen especially after a change in the protocol antibiotic. Changes in the AST patterns of Klebsiella, E. coli, Pseudomonas and non-fermenting gram negative bacteria were seen. The data on the changing antibiotic susceptibility trends we believe is an important pillar in our efforts at infection control especially in intensive care settings.

Leflunomide: a possible alternative for gangciclovir sensitive and resistant cytomegalovirus infections.

The search for newer more cost effective treatments for infectious diseases remains a challenge. Cytomegalovirus (CMV) infection, which is especially common in the immunosupressed, is an important challenge for treating physicians. Gangciclovir's cost is a major hurdle in developing countries. Leflunomide is cheaper and is easily given orally. It works by a novel mechanism inhibiting virion assembly. It also has immunosuppressive properties. It and has been shown to be effective in both gangciclovir sensitive as well as resistant cases of CMV infection. Given these considerations we believe that leflunomide is an exiting new drug for CMV infection. However, hepatotoxicity and teratogenicity are known side effects. The exact dose and duration of treatment for CMV infection, for secondary prophylaxis, and in situations of gangciclovir resistance need further study.

Predictors of mortality in mechanically ventilated patients.

OBJECTIVES: There are scarce data from India validating scoring systems used to predict outcome in patients requiring mechanical ventilation. This study prospectively compared the organ system failure (OSF), the acute physiology and chronic health evaluation (APACHE) II, and the APACHE III, scores on patients requiring mechanical ventilation in the medical intensive care unit, to predict outcome. METHODS: 200 consecutive patients requiring mechanical ventilation in a medical intensive care unit were recruited. OSF, APACHE II, and APCHE III scores were calculated at admission and daily for one week or until discharge in all patients. Other variables recorded include age, sex, diagnosis, oxygen therapy before ventilation, complications on ventilation, duration in hospital before ventilation, duration of ventilation, type of respiratory failure, alveolar arterial oxygen gradient, P/F ratio, use of tracheostomy, time on ventilator before tracheostomy, muscle relaxant used, fluid balance, inotrope support. Logistic regression analysis and area under the curve were computed to determine which variables independently predict outcome. RESULTS: Of the 200 patients, at discharge 143 patients (71.5%) had died. The factors that independently predicted outcome among these patients on mechanical ventilation were the type of respiratory failure (type I) OR = 2.7 (p = 0.02), the use of inotropes OR 2.4 (p = 0.04), and the APACHE II score OR = 1.8 (p = 0.008) for every five point increase in APACHE II score. CONCLUSIONS: Type 1 respiratory failure, the use of inotropes, and the APACHE II score measured at admission are significant independent predictors of mortality in the patients on mechanical ventilation.