Mani Kalaivani

Prevalence and outcome of subclinical rheumatic heart disease in India: The RHEUMATIC (Rheumatic Heart Echo Utilisation and Monitoring Actuarial Trends in Indian Children) study

Objective To study the prevalence and medium term outcome of subclinical rheumatic heart disease (RHD) in India. Design Cross sectional echocardiographic screening study. Setting School children aged 5–15 years living in rural areas of north India. Patients A cross sectional echocardiographic screening study was carried out among 6270 randomly selected school children aged 5–15 years (10.8±2.6 years; 52.7% male). Of all the abnormal cases, 100 children (78%) were restudied at a mean follow-up of 15.4±6.6 months. Intervention Echocardiographic screening. Main outcome measure Echocardiography–Doppler criteria based prevalence of RHD. Results Clinical examination detected mitral regurgitation in five patients and the estimated prevalence of clinical RHD was 0.8/1000 school children. Echocardiography–Doppler diagnosed RHD in 128 cases, giving a prevalence of 20.4/1000 school children (95% CI 16.9 to 23.9/1000 children). On multivariate analysis, older age (OR 1.93, 95% CI 1.29 to 2.88; p=0.001), female sex (OR 1.84, 95% CI 1.25 to 2.72; p=0.002) and government funded school student, which is a surrogate measure of lower socioeconomic status (OR 1.55, 95% CI 1.02 to 2.34; p=0.039) were found to be independent predictors of RHD. On follow up, the severity of subclinical RHD was non-progressive in 68 children (68%) while it worsened in four (4%) and regressed in 28 children (28%). Conclusions The prevalence of RHD is several fold higher using echocardiographic screening compared with clinical examination. The prevalence is higher among girls and children of lower socioeconomic status. In the majority of cases, subclinical RHD appears to be non-progressive on medium term follow up. Routine echocardiographic screening may be indicated in populations at high risk of RHD.

Efficacy and Safety of Tacrolimus Versus Cyclosporine in Children With Steroid-Resistant Nephrotic Syndrome: A Randomized Controlled Trial

BACKGROUND To examine whether tacrolimus is more effective and safe than cyclosporine (CsA) in inducing remission in patients with steroid-resistant nephrotic syndrome (SRNS). STUDY DESIGN Randomized controlled trial, nonblind, parallel group. SETTINGS & PARTICIPANTS Tertiary-care hospital; 41 consecutive patients with idiopathic SRNS, estimated glomerular filtration rate greater than 60 mL/min/1.73 m(2), and histological characteristics showing minimal change disease, focal segmental glomerulosclerosis, or mesangioproliferative glomerulonephritis were randomly assigned to treatment with tacrolimus (n = 21) or CsA (n = 20). INTERVENTION Tacrolimus (0.1 to 0.2 mg/kg/d) or CsA (5 to 6 mg/kg/d) for 1 year; cotreatment with alternate-day prednisolone and enalapril. OUTCOMES Patients achieving complete remission (urinary protein-creatinine ratio < 0.2 g/g and serum albumin > or = 2.5 g/dL) or partial remission (urinary protein-creatinine ratio, 0.2 to 2 g/g, and serum albumin > or =2.5 g/dL) at 6 and 12 months; time to remission; proportion with relapses; side effects. RESULTS No patient was lost to follow-up. After 6 months of therapy, remission occurred in 18 (85.7%) and 16 patients (80%) treated with tacrolimus and CsA, respectively (relative risk [RR], 1.07; 95% confidence interval [CI], 0.81 to 1.41). Rates of remission at 12 months were also similar (RR, 1.14; 95% CI, 0.84 to 1.55). The proportion of patients who experienced relapse was significantly greater in those receiving CsA compared with tacrolimus (RR, 4.5; 95% CI, 1.1 to 18.2; P = 0.01). The decrease in blood cholesterol levels was greater with tacrolimus compared with CsA (difference in mean values, 45.1 mg/dL; 95% CI, 19.1 to 71.2). Persistent nephrotoxicity necessitating stoppage of medicine was seen in 4.7% and 10% patients, respectively. Cosmetic side effects (hypertrichosis and gum hypertrophy) were significantly more frequent in CsA-treated patients (P < 0.001). LIMITATIONS Single-center study, small sample size, and short duration of follow-up. CONCLUSIONS Tacrolimus or CsA in combination with low-dose steroids show similar efficacy in inducing remission in patients with SRNS. Therapy with tacrolimus is a promising alternative to CsA in view of the lower risk of relapses and lack of cosmetic side effects.

Myocardial injury in coronary artery bypass grafting: On-pump versus off-pump comparison by measuring high-sensitivity C-reactive protein, cardiac troponin I, heart-type fatty acid-binding protein, creatine kinase- MB, and myoglobin release

OBJECTIVES We sought to investigate the release pattern of different cardiac biomarkers (high-sensitivity C-reactive protein, cardiac troponin I, heart-type fatty acid-binding protein, creatine kinase-MB, and myoglobin) and to establish the diagnostic discrimination limits of each marker protein to evaluate perioperative myocardial injury in patients undergoing coronary artery bypass grafting with or without cardiopulmonary bypass. METHODS Fifty patients were randomly assigned to on-pump or off-pump coronary artery bypass grafting. All cardiac biomarkers were measured in serial venous blood samples drawn before heparinization in both groups and after aortic unclamping at 1, 2, 4, 8, 24, 48, and 72 hours in the on-pump group. In the off-pump group samples were taken after the last distal anastomosis and at same time intervals as in the on-pump group. RESULTS The total amount of heart-type fatty acid-binding protein, cardiac troponin I, and high-sensitivity C-reactive protein released was significantly higher in the on-pump group than in the off-pump group. Receiver operating characteristic curve analysis of cardiac biomarkers indicated cardiac troponin I and heart-type fatty acid-binding protein as the superior diagnostic discriminators of myocardial injury, with an optimal cutoff value of greater than 0.92 ng/mL (area under the curve, 0.95 [95% CI, 0.88-1.00]; sensitivity, 92%; specificity, 92%; likelihood ratio [+], 11.50) and greater than 6.8 ng/mL (area under the curve, 0.94 [95% CI, 0.88-1.00]; sensitivity, 88%; specificity, 88%; likelihood ratio [+], 7.33), respectively. Logistic regression analysis revealed that patients with increased cardiac troponin I levels of greater than 0.92 ng/mL and heart-type fatty acid-binding protein levels of greater than 6.8 ng/mL were at 132.25 (95% confidence interval, 17.14-1020.49) times and 53.77 (95% confidence interval, 9.76-296.12) times higher risk of myocardial injury after on-pump coronary artery bypass grafting. CONCLUSIONS Off-pump coronary artery bypass grafting provides better myocardial protection than on-pump coronary artery bypass grafting. Cardiac troponin I and heart-type fatty acid-binding protein, but not high-sensitivity C-reactive protein, served as superior diagnostic discriminators of perioperative myocardial damage after on-pump coronary artery bypass grafting.

Effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in vitamin D-deficient Asian Indians: a randomized, controlled trial

Context  Vitamin D deficiency is prevalent worldwide. Vitamin D supplementation has shown variable effect on skeletal muscle strength in the elderly with hypovitaminosis D. There is a paucity of similar data in young individuals.

Accelerated Infusion of Streptokinase for the Treatment of Left-Sided Prosthetic Valve Thrombosis A Randomized Controlled Trial

Background— No large prospective studies have evaluated the efficacy of fibrinolytic therapy for left-sided prosthetic valve thrombosis, yet it remains the first line of treatment in developing countries. Methods and Results— We performed a randomized controlled trial comparing an accelerated infusion with the conventional infusion of streptokinase in 120 patients with a first episode of left-sided prosthetic valve thrombosis. The primary outcome measure was the occurrence of a complete clinical response, defined as objectively documented complete restoration of valve function in the absence of major complications. The secondary outcome was a composite of death, major bleeding, embolic stroke, or non-central nervous system systemic embolism. Patients were recruited over a 2.5-year period at a single center in India. Complete clinical response occurred in 38 (64.4%) of 59 patients with the accelerated infusion compared with 32 (53.3%) of 60 with the conventional infusion (hazard ratio 1.6, 95% confidence interval 0.9 to 2.5, P=0.055). There was no significant difference in the occurrence of the composite secondary outcome (hazard ratio 1.4, 95% confidence interval 0.5 to 3.5, P=0.50) or major bleeding (hazard ratio 2.2, 95% confidence interval 0.6 to 7.7, P=0.24) with the accelerated infusion. The success rate with fibrinolytic therapy was low overall (59%) and very low in patients in New York Heart Association functional class III/IV (24%). Conclusions— The large number of patients recruited from a single center underscores the massive burden of prosthetic valve thrombosis in developing countries. Fibrinolytic therapy with streptokinase is less efficacious than previously believed. The accelerated streptokinase infusion is not better than the standard infusion for left-sided prosthetic valve thrombosis. Developing countries urgently need more effective strategies to prevent and treat prosthetic valve thrombosis.

Effects of add-on Melatonin administration on antioxidant enzymes in children with epilepsy taking carbamazepine monotherapy: A randomized, double-blind, placebo-controlled trial

Summary:  Purpose: Melatonin has been shown to exhibit antioxidant, antiexcitotoxic, and free radical–scavenging properties in various animal models. The study was designed to assess its effects on the blood levels of antioxidant enzymes in children with epilepsy receiving carbamazepine (CBZ).

Extending initial prednisolone treatment in a randomized control trial from 3 to 6 months did not significantly influence the course of illness in children with steroid-sensitive nephrotic syndrome

While studies show that prolonged initial prednisone therapy reduces the frequency of relapses in nephrotic syndrome, they lack power and have risk of bias. In order to examine the effect of prolonged therapy on frequency of relapses, we conducted a blinded, 1:1 randomized, placebo-controlled trial in 5 academic hospitals in India on 181 patients, 1-12 years old, with a first episode of steroid-sensitive nephrotic syndrome. Following 12 weeks of standard therapy, in random order, 92 patients received tapering prednisolone while 89 received matching-placebo on alternate days for the next 12 weeks. On intention-to-treat analyses, primary outcome of number of relapses at 1 year was 1.26 in the 6-month group and 1.54 in the 3-month group (difference -0.28; 95% confidence interval (CI) -0.75, 0.19). Relative relapse rate for 6- vs. 3-month therapy, adjusted for gender, age, and time to initial remission, was 0.70 (95% CI 0.47-1.10). Similar proportions of patients had sustained remission, frequent relapses, and adverse effects due to steroids. Adjusted hazard ratios for first relapse and frequent relapses with prolonged therapy were 0.57 (95% CI, 0.36-1.07) and 1.01 (95% CI, 0.61-1.67), respectively. Thus, extending initial prednisolone treatment from 3 to 6 months does not influence the course of illness in children with nephrotic syndrome. These findings have implications for guiding the duration of therapy of nephrotic syndrome.

Current perspectives of enteric fever: a hospital-based study from India

Abstract The last two decades have seen a change in the pattern of enteric fever with the emergence of multidrug-resistant strains (MDRS), particularly strains resistant to nalidixic acid. Aim: The aim of the study was to undertake a retrospective analysis of blood culture-confirmed cases of enteric fever diagnosed at Safdarjang Hospital, New Delhi, India from January 2001 to December 2003. Methods: The epidemiological details, clinical features, treatment outcome and antimicrobial resistance patterns were studied. Results: Of 377 blood culture-positive cases, 80.6% were Salmonella typhi and 19.4% Salmonella paratyphi A; 21.7% were children aged under 5 years and 6.1% were under 2 years. A significant decline in MDRS was observed, from 21.9% in 2001 to 12.4% in 2003 (p=0.04). There was a significant increase in nalidixic acid-resistant Salmonella (NARS) from 56.9% in 2001 to 88.9% in 2003 (p=0.0001). Complete resistance to ciprofloxacin (MIC>4 μg/ml) was detected in only two isolates, both Salmonella paratyphi A. Minimal inhibitory concentrations (MICs) of ciprofloxacin for NARS were increased (0.125–0.5 μg/ml) but were within National Committee for Clinical Laboratory Standards susceptibility ranges. NARS had a significantly longer fever defervescence time (7.7 vs 4.7 days, p<0.001) and hospital stay (12.1 vs 8.2 days, p<0.001), and higher rates of complications (55.5% vs 24.0%, p=0.014) and mortality than nalidixic acid-sensitive Salmonella (NASS). The rate of isolation of MDRS was higher in NARS than NASS (18.8% vs 7.3%, p=0.013). Conclusion: The high rate of occurrence of enteric fever in children <5 years and also of infections caused by Salmonella paratyphi A in India calls for critical re-assessment of vaccination strategy. Nalidixic acid resistance and rising MICs of fluoroquinolones in Salmonella spp pose a new global threat requiring debate on the optimum treatment of enteric fever.

Histopathologic changes in ascending aorta and risk factors related to histopathologic conditions and aortic dilatation in patients with tetralogy of Fallot.

OBJECTIVE The purposes of this study were to evaluate the histologic characteristics of the aortic wall and the risk factors related to histopathology and aortic dilatation in patients undergoing intracardiac repair of tetralogy of Fallot. METHODS Operatively excised full-thickness aortic wall tissue from 98 consecutive patients undergoing intracardiac repair of tetralogy of Fallot aged 6 months to 47 years (mean 104.5 +/- 102.8 months; median 72 months) were studied by light microscopy. The receiver operating characteristic curve analysis was done to quantify the diagnostic accuracy of loss of lamellar counts and multiple logistic regression models. RESULTS Twenty-five (25.5%) aortic tissue specimens were indicated as histologically normal and were used as normal controls. The incidence of elastic fragmentation, increased ground substance, medionecrosis, smooth muscle disarray, and fibrosis was 74.5%, 54%, 39.8%, 26.5%, and 57.1%, respectively. A lamellar count of less than 60 was associated with a sensitivity of 80% and a specificity of 87.67%. Area under the receiver operating characteristic curve indicated that 93.37% (standard error +/- 0.039) of the time the value of lamellar count was lower for the abnormal histopathology group than for the normal group (P < .001). The risk of aortic dilatation was 15.97 times higher in patients with histopathologically abnormal aorta. CONCLUSIONS The majority of aortic media of the ascending aorta in cyanotic tetralogy of Fallot indicates significant loss of lamellar units and pre-existing intrinsic aortopathy. The changes are present since infancy and are more pronounced in older patients subjected to long-standing cyanosis and volume overload and may account for or may coexist with the higher incidence of aortic dilatation encountered in these patients.

Gender differences in the utilisation of surgery for congenital heart disease in India

Background Corrective surgery for congenital heart disease may be life-saving, but its utilisation depends upon several social and economic factors. Girls with cardiac defects may not receive equitable care in India, but this has not been systematically studied. Methods In this prospective study, parents or guardians of 405 consecutive children aged up to 12 years (mean±SD age 3.43±3.44 years; 271 boys) who had been advised to undergo elective paediatric cardiac surgery were interviewed using a validated questionnaire. The status of the patients was reviewed after a year and the factors associated with non-compliance with treatment were analysed. In a qualitative sub-study the parents of 20 children who had not undergone surgery were interviewed. Qualitative data were analysed using an inductive analytical approach. Results Of the 405 patients studied, 44% (59/134) of girls had undergone surgery at 1 year compared with 70% (189/271) of boys (χ2=24.97; p<0.001). Independent predictors for non-compliance with surgery included female gender (OR 3.46, 95% CI −2.06 to 5.80; p<0.0001), lower socioeconomic classes (lower-middle: OR 18.62, 95% CI −2.14 to 161.8, p=0.008; upper-lower: OR 34.27, 95% CI −3.72 to 316.0, p=0.002) and higher cost of surgery (OR 1.92, 95% CI −1.06 to 3.47, p=0.03). In the in-depth interviews, apprehensions about future matrimonial prospects of girls and lack of social support emerged as the major factors responsible for delays in undergoing surgery. Conclusions Female gender is an important determinant of non-compliance with paediatric cardiac surgery. Deep-seated social factors underlie this gender bias.