Serum procalcitonin as a biomarker of bloodstream infection & focal bacterial infection in febrile patients.

Background & objectives: Bacteraemia is a serious form of infection in patients presenting with fever, thus, there is a necessity for a biomarker for rapid diagnosis of bacteraemia in such patients to make better therapeutic decisions. This study was conducted to measure the serum procalcitonin (PCT) levels at the time of initial presentation as a biomarker for identifying bacteraemia and as a predictor of mortality in patients admitted with acute fever. Methods: Four hundred and eighty patients, who presented with acute fever requiring admission to a tertiary care teaching hospital in south India, were prospectively studied. All patients were evaluated with a detailed history, physical examination, laboratory and imaging studies. Baseline serum PCT was measured for each patient within six hours of admission. Results: Among patients with single infectious cause (n=275), significantly higher median serum PCT levels were evident in bacteraemia compared to leptospirosis (P=0.002), dengue (P <0.001), scrub typhus (P <0.001) and evident focus of infection without bacteraemia (P=0.036). By receiver-operator characteristic curve analysis, at a cut-off value of >3.2 ng/ml, the sensitivity and specificity of serum PCT levels in predicting bacteraemia were 81.1 and 63.3 per cent, respectively. As per the worst-case scenario analysis, 91 (18.9%) patients had a poor outcome and these had significantly higher median serum PCT levels compared to survivors (n=389) [9.46 (2.03-44.4) vs. 1.23 (0.34-7.645); P <0.001]. At a cut-off value of >3.74 ng/ml, serum PCT levels at initial presentation predicted in-hospital mortality with a sensitivity and specificity of 67 and 67.5 per cent, respectively. Interpretation & conclusions: Our observations suggest that serum PCT level may be a useful biomarker for identifying bacteraemia as well as predicting mortality in patients with acute fever requiring admission to hospital.

A Randomized, Double Blind, Placebo Controlled, Crossover Study to Assess the Safety and Beneficial Effects of Cassia Tora Supplementation in Healthy Adults.

OBJECTIVE: The current clinical trial was aimed at evaluating the safety and beneficial effect of Cassia tora (C. tora) supplementation in healthy adults. DESIGN: A randomized, double blind, placebo controlled study with a crossover design was done on 60 healthy normal weight adults (age range: 20-55 yrs). The study consisted of 2 treatment phases of 24 weeks each with a washout period of 4 weeks between the phases. 30 subjects randomly allocated to the 'Placebo first' group and 30 to 'C. tora first' group and assigned to receive a dose of C. tora (330 mg) or matched placebo three times a day. Safety markers were measured at base line and at the end of both the treatment phases. Body mass index, blood pressure, fasting blood sugar, glycated hemoglobin, lipid profile and antioxidants were measured at baseline and at every three months interval. Repeated measures analysis was applied to assess the period and carryover effects of the drug over placebo on biochemistries. RESULTS: C. tora supplementation was well tolerated and no apparent changes were observed in safety markers. The net effect of C. tora in natural units over placebo was 0.83 [0.57, 1.09]- high density lipoprotein cholesterol; 27.63 [24.39, 30.88]- superoxide dismutase; 0.32 [0.28, 0.36]- catalase; 0.68 [0.56, 0.80]- glutathione peroxidase; 0.25 [0.22, 0.29]- glutathione s-transferase; 0.32 [0.29, 0.36]- glutathione and -1.08 [-1.63, -0.54]- low density lipoprotein cholesterol. CONCLUSION: The findings advocate that C. tora supplementation is safe and beneficial in elevating high density lipoprotein cholesterol and antioxidants and hence advised for consumption.

Study of the structure and functioning of referral mechanism of patients receiving treatment and records linkage under Revised National Tuberculosis Control Programme (RNTCP) of Government of India.

BACKGROUND: The reliable and successful performance of the Revised National Tuberculosis Control Programme (RNTCP) "referral mechanism" is profoundly important in the medical college scenario, and it is an important requirement of the programme to have feedback status report of the referred patients. METHODS: An observational study on tuberculosis (TB) patients referred from Directly Observed Treatment (DOT) Centre, Sri Venkateswara Institute of Medical Sciences (SVIMS) was conducted during the years 2010 to 2012 (n=622). Subjects referred to other TUs within the District but failed to report there within 45 days constituted "cases" and subjects, who obtained treatment from the TUs they were referred to "controls". The initial information or confirmation of registration for treatment status feedback were obtained from patient/Senior Treatment Supervisor (STS)/District Tuberculosis Centre (DTC) levels respectively both before using intervention (Phase I, year 2010) and after using intervention (Phase II, years 2011 and 2012) by sending day-to-day text messaging of referral details of patients to the STS and District Tuberculosis Officer (DTO). RESULTS: During Phase I, the distribution of subjects (n=242) in the ages ≤25, 26-50, and ≥51 years was similar in both the cases and control subjects (p=0.054). Further, there was no statistically significant difference in the median age of the cases and controls [34.5 (interquartile range, IQR 31-51) vs 39 (30-54); p=0.319]. There was no statistically significant difference in other parameters, such as gender distribution (p=0.9748); availability of phone numbers (p=0.9614); type of disease (p=0.8395); and type of case (p=0.0793). In Phase II, the effect of intervention on feedback related parameters showed statistically significant improvement in all the parameters such as initial feedback levels obtained within 15 days (p=0.0077); within 45 days (p<0.0001); above 45 days (p<0.0001); registration status confirmation within 45 days (p=0.0343); mismatch of feedback received by observer (p<0.0001); and telephone number of patients recorded (p<0.0001). CONCLUSION: Our findings suggest that text messaging reminders may be an important tool to achieve optimal feedback response in resource-limited settings.

Comparison of Disease Activity Score in 28 joints with ESR (DAS28), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) & Routine Assessment of Patient Index Data with 3 measures (RAPID3) for assessing disease activity in patients with rheumatoid arthritis at initial presentation.

BACKGROUND & OBJECTIVES: In patients with rheumatoid arthritis (RA), disease severity assessment is done using Disease Activity Score in 28 joints with ESR (DAS28). Computing DAS28 is time-consuming, requires laboratory testing and an online calculator. There is a need to validate rapid methods of disease severity assessment for routine daily use. This study was conducted to compare DAS28, Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) and Routine Assessment of Patient Index Data with 3 measures (RAPID3) to assess the disease activity in patients with RA. METHODS: We prospectively studied the utility of CDAI, HAQ-DI and RAPID3 scoring in 100 consecutive newly diagnosed, disease modifying antirheumatic drugs (DMARDs) naïve adult patients with RA seen during January 2013 and June 2014 at a tertiary care teaching hospital in south India. RESULTS: The mean age of the patients was 42.1±11.6 yr, there were 82 females. The median [interquartile range (IQR)] symptom duration was 6 (range 4-12) months. The median (IQR) DAS28, CDAI, HAQ-DI and RAPID3 scores at presentation were 7 (6-7), 36 (28-43), 2 (1-2) and 17 (13-19), respectively. A significant positive correlation was observed between DAS28 and CDAI (r=0.568; P<0.001); DAS28 and HAQ-DI (r=0.304; P=0.002) and DAS28 and RAPID3 (r=0.404; P<0.001). A 'slight-to-fair' agreement was observed in between DAS28 and CDAI (kappa-statistic=0.296). The agreement between DAS28 and HAQ-DI (kappa-statistic=0.007) and RAPID3 (kappa-statistic=0.072) was less robust. INTERPRETATION & CONCLUSIONS: In adult patients with RA, in the setting where illiteracy is high, CDAI emerged as the preferred choice for rapid assessment of severity of disease at the time of initial presentation.

Provider-initiated HIV testing & counselling in incident tuberculosis cases under National TB Programme conditions at a tertiary care teaching hospital in Tirupati, south India.

BACKGROUND & OBJECTIVES: : As sparse published data are available regarding burden of human immunodeficiency virus (HIV) infection in incident tuberculosis (TB) cases at tertiary care teaching hospitals under National TB Programme conditions from India, the present study was designed to assess the proportion of referred registered TB patients who had actually undergone HIV testing and HIV-seropositivity in these. METHODS: : This was a study of provider-initiated HIV testing and counselling in patients registered for the treatment under Revised National TB Control Programme (RNTCP) of Government of India at a tertiary care teaching hospital in Tirupati, south India, during 2012-2013. RESULTS: : Between January 2012 and June 2013, 610 adult patients registered under RNTCP who were referred to Integrated Counselling and Testing Centre for HIV testing, were prospectively studied. Of these, 458 patients (75%) [mean age: 38.6±16.3 yr; 295 (64.4%) males] underwent HIV testing; HIV-co-infection was present in 21 (4.6%) patients. A significantly higher proportion of HIV co-infection was evident in PTB compared with EPTB [13/179 (7.2%) vs 8/279 (2.8%); respectively, P=0.038] and in previously treated patients compared to new patients [6/51 (11.8%) vs 15/407 (3.7%); respectively, P=0.009]. INTERPRETATION & CONCLUSIONS: : The findings of this study showed that a higher proportion of TB patients underwent HIV testing (75%) compared to the national figure of 63 per cent in 2013-2014. HIV seropositivity (4.6%) in TB patients who underwent HIV testing was similar to the five per cent figure observed at national level during 2013-2014. The HIV status of 25 per cent of patients with incident TB still remained unknown, suggesting a need for better integration and co-ordination for effective management of HIV-TB co-infection.

Binary classification using multivariate receiver operating characteristic curve for continuous data.

The classification scenario needs handling of more than one biomarker. The main objective of the work is to propose a multivariate receiver operating characteristic (MROC) model which linearly combines the markers to classify them into one of the two groups and also to determine an optimal cut point. Simulation studies are conducted for four sets of mean vectors and covariance matrices and a real dataset is also used to demonstrate the proposed model. Linear and quadratic discriminant analysis has also been applied to the above datasets in order to explain the ease of the proposed model. Bootstrapped estimates of the parameters of the ROC curve are also estimated.

Effect of oral hypoglycaemic agents on bone metabolism in patients with type 2 diabetes mellitus & occurrence of osteoporosis.

BACKGROUND & OBJECTIVES: Type 2 diabetes mellitus (T2DM) is considered to be a protective factor against development of osteoporosis. But oral hypoglycaemic agents (OHA) are likely to increase the risk of osteoporosis. This study was carried out to evaluate the effect of various OHA on bone mineral density (BMD) in patients with T2DM. METHODS: Forty one patients (study group) with T2DM (mean age 51.9±5.5 yr; 31 females) receiving treatment with oral hypoglycaemic agents (OHA) [thiazolidinediones alone (n=14) or in combination with other OHA (n=27)] for a period of at least three consecutive years and 41 age- and gender-matched healthy controls (mean age 51.4±5.1 yr) were included in the study. A detailed clinical history was taken and all were subjected to physical examination and recording of anthropometric data. BMD was assessed for both patients and controls. RESULTS: The mean body mass index (kg/m [2] ) (26.5±4.90 vs 27.3 ±5.33) and median [inter-quartile range (IQR)] duration of menopause (yr) among women [6(2-12) vs 6(1-13)] were comparable between both groups. The bone mineral density (BMD; g/cm [2] ) at the level of neck of femur (NOF) (0.761±0.112 vs 0.762±0.110), lumbar spine antero-posterior view (LSAP) (0.849±0.127 vs 0.854±0.135); median Z-score NOF {0.100[(-0.850)-(0.550)] vs -0.200[(-0.800)-(0.600)]}, LSAP {-1.200[(-1.700)-(-0.200)] vs -1.300 [(-1.85)-(-0.400)]} were also similar in study and control groups. Presence of normal BMD (9/41 vs 8/41), osteopenia (16/41 vs 18/41) and osteoporosis (16/41 vs 15/41) were comparable between the study and control groups. No significant difference was observed in the BMD, T-scores and Z-scores at NOF and LSAP among T2DM patients treated with thiazolidinediones; those treated with other OHA and controls. INTERPRETATION & CONCLUSIONS: The present findings show that the use of OHA for a period of three years or more does not significantly affect the BMD in patients with T2DM.

Subclinical atherosclerosis in patients with rheumatoid arthritis by utilizing carotid intima-media thickness as a surrogate marker.

BACKGROUND & OBJECTIVES: Patients with rheumatoid arthritis (RA) are more prone for accelerated atherosclerosis and Asian Indians as an ethnic group are predisposed to a high risk of premature atherosclerosis. However, sparse data are available regarding the burden of atherosclerosis among asymptomatic adult patients with RA in south India. We studied the burden of asymptomatic atherosclerosis in adult south Indian patients with RA at Tirupati, Andhra Pradesh, India, utilizing carotid intima-media thickness (CIMT) as a surrogate marker. METHODS: Ultrasound examination of the carotids and CIMT measurement (mm) were carried out in 32 patients with RA, 32 age- and gender-matched normal controls, and 32 patients with atherosclerosis and angiographically proven coronary artery disease. The CIMT values in patients with CAD and normal controls were used to derive the appropriate cut-off value of CIMT for defining atherosclerosis that would be applicable for the ethnic population studied. RESULTS: Patients with RA had a higher mean CIMT (mm) compared with normal control subjects (0.598 ± 0.131 vs 0.501 ± 0.081; p0 = 0.001). Carotid plaque was found more frequently among the cases compared with normal controls [5/32 (15.6%) vs 0/32 (0%), p0 =0.020]. Using this cut-off value derived by the receiver operator characteristic curve method (≥ 0.57 mm; sensitivity 84.4; specificity 90.6%) and the 75 th percentile value among normal controls (≥ 0.55 mm) as surrogate markers, the presence of subclinical atherosclerosis was significantly more among asymptomatic patients with RA compared with normal controls [(59.3 vs 12.5%; p0 <0.001) and (62.5 vs 25%; P<0.001) respectively]. INTERPRETATION & CONCLUSIONS: Based on the present findings CIMT appears to be a useful surrogate marker for detecting subclinical atherosclerosis in adult Indian patients with RA.

Clinical profile of carcinoma stomach at a tertiary care hospital in south India.

Carcinoma of the stomach is an important cause of mortality due to cancer. Carcinoma of the stomach is common in the southern region of India. We conducted a retrospective study on the epidemiological, clinical and survival patterns among the patients with carcinoma of the stomach, attending our hospital from June 19, 1995 to 1st January 2003. All the patients had histopathological confirmation of malignancy. Patients with gastrooesophageal junction lesions were excluded. Surgery was performed with curative as well as palliative intent in suitable patients. Chemotherapy has been incorporated in to the combined modality treatment in our hospital since July 2000. Postoperative chemotherapy comprised commonly used intravenous chemotherapy regimens, while oral chemotherapy (etoposide) was given to patients with disease not amenable to surgery, and those having poor performance and nutritional status. Oral etoposide was given in a dose of 50 mg/day for 14 days, in a 28 day cycle. Quality of life was assessed in the oral chemotherapy group. Out of the 1749 cancer patients seen during the period, 151 had gastric malignancy (8.6%). The median age was 55 years (range 15-84 years). The male to female ratio was 4:1. Adenocarcinoma was found in 148 patients, 2 had stromal tumours and 1 had non-Hodgkin lymphoma. Stage disribution was as follows; stage 2-1 patient , stage 3a-25, stage3b-49, stage4-3 1, Metastatic-28. Staging was not completed in 17 patients. Eighty-nine patients underwent surgery. Fifty-nine patients (39%) did not have surgery. One patient underwent polypectomy. Curative gastrectomy was performed in 11 patients. Thirty-nine patients underwent palliative tumour resection. Palliative gastro-jejunostomy for relief of symptoms was performed in 26 patients and exploratory laparotomy alone was perforaied in 13. Thirty-eight patients received chemotherapy. Out of these, only 2 patients had prior complete resection of the tumour and 36 received palliative chemotherapy. Intravenous chemotherapy was given to 17 patients and oral chemotherapy to 19; All the patients who received oral etoposide did not experience any toxicity. Patients who received intravenous chemotherapy (n=17) had the following toxicities: grade 3 emesis in 4 (20%), discoloration of the skin and nails in 6(31%), alopecia in 8 (50%), grade 3 diarrhoea in 3 (15%) and neutropenic fever in 4 patients (20%). Median survival for the cohort was 10.4 months. Quality of life parameters, such as sleep, appetite, weight, pain, work and general sense of ill health showed improvement. In conclusion, 8.6% of all cancers at our hospital were due to cancer of stomach, in whom distal gastric tumor were more frequent and most were non-resectable. Median survival was 10.4 months. Oral etoposide was found to be safe, improved the quality of life and may play a role in the palliative management of advanced carcinoma of the stomach.