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Biomedical subjects

V Sundararajan

Publications and source records attributed to V Sundararajan.

17 recordsLinked to original sources

Managed care.

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Australia↗

Heterologously expressed inner lipoyl domain of dihydrolipoyl acetyltransferase inhibits ATP-dependent inactivation of pyruvate dehydrogenase complex. Identification of important amino acid residues.

The activity of the pyruvate dehydrogenase multienzyme complex (PDC), which catalyses the oxidation of pyruvate to acetyl-CoA within the mitochondrion, is diminished in animal models of diabetes. Studies with purified PDC components have suggested that the kinases responsible for inactivating the decarboxylase catalytic subunits of the complex are most efficient in their regulatory role when they are bound to dihydrolipoyl acetyltransferase (E2) subunits, which form the structural core of the complex. We report that the addition of an exogenous E2 subdomain (inner lipoyl domain) to an intact PDC inhibits ATP-dependent inactivation of the complex. By combining molecular modelling, site-directed mutagenesis and biophysical characterizations, we have also identified two amino acid residues in this subdomain (Ile229 and Phe231) that largely determine the magnitude of this effect.

Acetyltransferases↗

Patterns and determinants of multiple provider use in patients with acute low back pain.

OBJECTIVE: To describe the patterns of provider use associated with an acute episode of nonspecific low back pain and their impact on cost. METHODS: The analysis is based on a prospective cohort study of patients with acute low back pain followed until they recovered completely or to 6 months. Patients were followed after an initial visit to one of four provider types: private primary care physician, chiropractor, orthopedic surgeon, or HMO primary care physician. Follow-up interviews were conducted at baseline, 2, 4, 8, 12, and 24 weeks; 1,580 (97%) of the participants completed the 6-month follow-up. MAIN RESULTS: Seventy-nine percent of patients saw only the initial provider who began their care for low back pain. Logistic regression revealed that duration of pain prior to initial visit, sciatica, higher Roland disability score, days to functional recovery, interval to complete recovery, referral by initial provider, disk attribution, satisfaction, and the type of index provider were significantly (p < .05) associated with seeking care from multiple provider types. Age, race, gender, and education were not significant. The adjusted proportions of multiple provider type use were 14% (95% confidence interval [CI] 11%, 17%) for the private primary care provider stratum; 19% (95% CI 16%, 23%) for the chiropractic stratum; 30% (95% CI 23%, 37%) for the orthopedic stratum; and 9% (95% CI 5%, 14%) for the HMO primary care physician stratum. Cost of seeing only the index provider was $439 (95% CI $404, $475), and cost of seeing multiple provider types was $1,137 (95% CI $1,064, $1,211) based on the adjusted model. CONCLUSIONS: Use of multiple provider types, is associated with several factors, one of which is the initial provider type. The cost of such use is significant.

Acute Disease↗

Controversies in new antibiotic therapy for ambulatory patients.

The care of the febrile neutropenic patient has undergone a shift in the last 10 years with the realization that neutropenic patients presenting with fever do not constitute a homogeneous group. Strategies of risk assessment have allowed the testing of novel therapies including outpatient treatment with oral and intravenous antibiotics, either in combination regimens or as monotherapy; the addition of growth factors to hasten the return of the absolute neutrophil count; and the possibility of self-initiation of antibiotics by cancer patients when they develop fever. The clinical trials data regarding these new approaches will be reviewed, and areas requiring further research will be discussed.

Ambulatory Care↗

Microbial profile of neonatal infection in Coimbatore.

In this study, 187 consecutive neonates suspected of having septicaemia were investigated for isolation of micro organisms. Two samples of blood were collected for isolation of aerobes and anaerobes. Cultures were positive in 75 (40%) cases. Aerobic bacteria were the major etiological agent, accounting for 93% of positives including the 8% cases showing polymicrobial etiology. Anaerobic bacteria and Candida species were isolated in 6.6% and 8% of positive cases respectively. Bacteroides fragilis (amongst anaerobic) and Staphylococcus aureus (amongst aerobic) were the predominant organisms isolated. Clinical presentations were not specifically different to distinguish aerobic from anaerobic bacteria. In the present study, 6.6% of bacteremias were due to anaerobes, hence possibility of some of the bactermias being due to anaerobes should be kept in mind while treating cases of neonatal septicaemia. For a complete microbial profile both aerobic and anaerobic cultures should be done.

Bacteroides fragilis↗

The quality of life associated with prophylactic treatments for women with BRCA1/2 mutations.

PURPOSE: This study was conducted to obtain and compare the preferences assigned to cancer states and prevention measures by women who had breast cancer, were at high risk for breast cancer, or had neither condition. PATIENTS AND METHODS: We administered a time trade-off questionnaire to 21 breast cancer patients, 28 women with a personal history of multiple breast biopsies or a family history of breast cancer, and 135 women without these conditions (the reference group). We stratified the reference group into two groups aged 20 to 32 years and 33 to 50 years, respectively. RESULTS: All four groups assigned higher preference to breast cancer than to ovarian cancer. Both reference groups preferred using a tamoxifen-like drug to having mastectomy or oophorectomy for cancer prevention; the high-risk and breast cancer groups did not. None of the four groups had a preference between prophylactic mastectomy and breast cancer. All the groups were willing to subtract more years from their life expectancy to protect offspring from genetic risk than to protect themselves. Reference group members in the 33- to 50-year age range had lower mean ratings than the breast cancer group for almost all the health states, and breast cancer patients were less willing than other respondents to trade time for health. Most of these differences were not statistically significant. The high-risk group was similar to the older reference group in time trade-off ratings. DISCUSSION: The time trade-off-based preferences of healthy women may be used to predict the treatment preferences of women with BRCA1/2 mutations. Obtaining healthy women's ratings of treatment outcomes may help health care policy makers envision the consequences of the difficult choices that high-risk women face.

Adult↗

Decision analysis of tamoxifen for the prevention of invasive breast cancer.

PURPOSE: The recent Breast Cancer Prevention Trial has shown that tamoxifen may prevent invasive breast cancer. We used a Markov model to estimate the long-term effects of chemoprevention with tamoxifen on survival, quality-adjusted survival, and health care costs. METHODS: We used a hypothetical cohort of women with breast-cancer risk similar to that of participants in the Breast Cancer Prevention Trial, and a computer-based decision analysis (Markov model and 500 Monte Carlo simulations) to model the outcomes of interest. Survival calculations were from Surveillance, Epidemiology, and End-Results (SEER) data; preference ratings from a time trade-off questionnaire administered to a group of average-risk women; and cost estimates from the Group Health Cooperative of Puget Sound and the Health Care Financing Administration. We obtained utility measures for quality-adjustment by administering a time trade-off questionnaire to a group of community-based women. RESULTS: Use of tamoxifen prolonged the average survival of cohort members by 69 days (95% probability interval [PI] 27 to 117) for those who started use at age 35 years; 40 days (95% PI 16 to 67) for those who started use at age 50 years; and 27 days (95% PI 14 to 40) for those who started use at age 60 years. Tamoxifen extended quality-adjusted survival by 38 days (95% PI 0.1 to 82) at age 35, 25 days (95% PI 0 to 50) at age 50, and 22 days (95% PI 5 to 39) days at age 60. Chemoprevention with tamoxifen cost $46,619 (95% PI $27,928 to $98,796) per life year life saved for women who started at age 35; for women over age 50, it cost more than $50,000 per life year saved. DISCUSSION: Tamoxifen use may improve long-term survival and quality-adjusted survival among women who are at increased risk of breast cancer, but this benefit diminishes with age. Tamoxifen is cost-effective in comparison with other cancer treatment strategies for younger women only.

Adult↗

Variations in the use of adjuvant chemotherapy for node-positive colon cancer in the elderly: a population-based study.

BACKGROUND: Since 1990, the recommended adjuvant therapy for patients with surgically resected node-positive colon cancer has been 5-fluorouracil (5-FU), usually in combination with leucovorin or levamisole. The purpose of this study is to assess the distribution of adjuvant 5-FU treatment in the elderly. METHODS: The Surveillance, Epidemiology and End Results-Medicare database provides population-based information on cancer patients, representing approximately 14% of the United States population, along with health care utilization data from Medicare claims files. We studied patients with node-positive colon cancer diagnosed between 1992 and 1996 who survived at least 120 days beyond diagnosis (N = 4998). RESULTS: About 50% of elderly patients received 5-FU within 4 months of diagnosis. The proportion of patients treated with 5-FU increased by about 10% from 1992 to 1996. In a multiple logistic regression model, 5-FU treatment was less likely to be given to older patients (compared with those aged 65-69 years, the odds ratio (OR) [95% CI] was 0.82 [0.67-1.00] for ages 70 to 74 years, 0.47 [0.39-0.57] for ages 75 to 79, 0.17 [0.13-0.20] for ages 80 to 84, and 0.04 [0.03-0.05] for ages 85 to 88 years. Non-Hispanic black patients were less likely to be treated than non-Hispanic white patients (OR 0.46 [0.36-0.59]); patients with more than three positive lymph nodes were more likely to be treated than those with three or less, and those with comorbid conditions were less likely to be treated than those without such conditions. CONCLUSIONS: Despite its proven efficacy in reducing colon cancer mortality, 5-FU-based chemotherapy is not widely used among apparently eligible patients over age 65. Efforts are needed to ensure that elderly and non-Hispanic black patients receive appropriate treatment.

Age Factors↗