Head to head comparison of adverse effects and efficacy between high dose deflazacort and high dose prednisolone in systemic lupus erythematosus: a prospective cohort study.

BACKGROUND: Deflazacort (DFZ), an oxazoline derivative of prednisolone (PDN), has a dose equivalence of 1.2:1 (mg) to PDN. No study to date has compared adverse effects and efficacy of high doses of DFZ as against high-dose PDN in systemic lupus erythematosus (SLE). OBJECTIVES: To compare adverse effects of high dose DFZ and PDN in SLE patients, especially in terms of cushingoid features and gain in body weight, 3 and 6 months after initiation of these agents. METHODS: In both the steroid arms, the following outcome parameters were assessed at 3 and 6 months: (a) cushingoid features by Cushing's Severity Index (CSI) (b) hirsutism by modified Ferriman Gallwey score (c) weight gain by difference (Δ, delta) of weight (in kilograms). RESULTS: Patients on PDN had 1.6 kg (3.2%) and 2 kg (5.1%) higher median weight gain as compared to those on DFZ at 3 and 6 months respectively ( p = 0.012 and 0.001). PDN caused 10% and 22.2% higher increment in median hirsutism scores as compared to DFZ at 3 months and 6 months follow-up, respectively ( p = 0.004 and 0.002). PDN caused 100% higher increase in median CSI scores than DFZ at 6 months ( p = 0.03). There was no significant difference by generalized estimation equation between the groups with respect to changes in SLEDAI, renal SLEDAI, anti-dsDNA titres and C3/C4 levels. There were two serious infections (requiring hospitalization/intravenous antibiotics) in the PDN group, while none in the DFZ group. CONCLUSION: Comparable intake and tapering of high dose DFZ and PDN in active SLE revealed 2-fold less weight gain, 2.5-fold less hirsutism and 1.5-fold lower cushingoid severity index as well as lower glycaemic elevation in the DFZ group as compared to PDN group. Both had similar efficacy.

Development and validation of limited sampling strategy equation for mycophenolate mofetil in children with systemic lupus erythematosus.

The aim of this study was to establish a limited sample strategy (LSS) to predict the mycophenolic acid (MPA) area under the curve (AUC)(0-12) in children with systemic lupus erythematosus (SLE). Three months after initiation of mycophenolate mofetil (MMF) 26 children with SLE presented for therapeutic drug monitoring of MPA. On the day of the test, 10 specimens were collected, analyzed, and MPA AUC(0-12) was calculated. Using step-wise regression analysis, LSS equations were developed. Using bootstrap validation, the predictive performance was calculated. The measured mean (standard deviation) for the trough concentration and AUC(0-12) were 2.55 (1.57) µg/ml and 62.6 (21.67) mg.h/L, respectively. The range of trough concentrations and AUC(0-12) were 0.7-5.54 µg/ml and 22.1-104.8 mg.h/L, respectively. The interindividual variability (%CV) for dose normalized AUC(0-12) and dose normalized Ctrough was 46.5% and 61.1%, respectively. The correlation between the concentrations at the different time points and MPA AUC(0-12) ranged from 0.05 (1.5 h) to 0.56 (4 h). Two LSS equations that included 4 or 5 time points up to 3 h were developed and validated. The 4 point LSS had a correlation (R2) of 0.88 and the 5 point LSS an R2 of 0.87. With respect to the 4 point and 5 point MPA LSS AUC(0-12), the bias was 1.92% and 1.96%, respectively, and the imprecision was 11.24% and 11.28%, respectively. A 4 point LSS which concludes within 3 h after the administration of the MMF dose was developed and validated, to determine the MPA AUC(0-12) in children with SLE.

Granulomatous hepatitis following open heart surgery with cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) initiates an inflammatory cascade, predisposing the patient to a number of infections. The stress of surgery and anaesthesia further expose the patient to a variety of non-infectious complications. We report a group of patients who developed granulomatous disease after open heart surgery. METHODS: We retrospectively analysed a subset of patients who developed a syndrome of fever, jaundice and hepatomegaly after open heart surgery. We recruited age- and sex-matched controls who underwent open heart surgery during the same period (July 2002-July 2004). Details of demographic profiles, diagnostic evaluation and drug treatment were noted and compared between the two groups using the SPSS software. RESULTS: Five patients were identified to have the specific syndrome of high grade intermittent fever with jaundice and hepatomegaly with investigations revealing an intrahepatic cholestasis. A detailed evaluation revealed granulomas in tissue specimens of the bone marrow and/or liver in these patients. An extensive evaluation for an alternative aetiological agent was non-contributory. CONCLUSION: We found granulomatous hepatitis in 5 patients following open heart surgery and they were given conventional antituberculous therapy to which they responded. It is possible that in these patients, tuberculosis was re-activated from a dormant focus due to a period of transient immunodeficiency caused by an extracorporeal circulation.

A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent.

BACKGROUND: Therapeutic drug monitoring for mycophenolic acid (MPA) is increasingly being advocated. The present therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC).However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this sampling period? AIM: To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. SETTINGS AND DESIGN: Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paired data. MATERIALS AND METHODS: Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept were evaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the time after transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the 12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factor applied. These two AUCs were then compared. STATISTICAL ANALYSIS: Linear regression, intra-class correlations (ICC) and a two-tailed paired t-test were applied to the data. RESULTS: Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2) were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. No bias was seen with a Bland Altman plot or by calculation. CONCLUSION: For patients on Cellcept with prednisolone +/- cyclosporine the 6-hour corrected is an accurate measure of the full 12-hour AUC.

Genital syndromes and syndromic management of vaginal discharge in a community setting.

The objective of the study was to determine the community prevalence of genital syndromes in women and evaluate the syndromic management of vaginal discharge in this setting. A representative sample for the state of Tamilnadu was chosen using probability proportional to size cluster technique. Thirty clusters were selected from three districts. Demographic, sexual behaviour, risk factors, clinical and laboratory data were collected from the selected population using a structured questionnaire. Direct smear examination for Trichomonas vaginalis, culture for Neisseria gonorrhoeae and Haemophilus ducreyi, serological tests for syphilis (RPR and TPHA), hepatitis B (Hbs Ag ELISA), IgM and IgG antibodies to HSV2 (Novum diagnostics, Germany) and PCR test for detection of C. trachomatis from urine were done. There were 1157 women in the selected population. On examination, vaginal discharge was the most common genital syndrome (38.4%). The sensitivity, specificity, positive and negative predictive value of vaginal discharge as a marker for STD in women was found to be 43.3%, 61.6%, 10.7% and 91.1%, respectively. We concluded that treatment on the basis of syndromic management would result in over-treatment of 90% of women with vaginal discharge.

Hereditary haemorrhagic telangiectasia with pulmonary arteriovenous malformations: a treatable cause of thromboembolic cerebral events.

Hereditary haemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is associated with mucocutaneous telangiectases and iron deficiency anaemia caused by epistaxis or blood loss from the gastrointestinal tract. We describe a 41-year-old Chinese man who presented with amaurosis fugax secondary to emboli from pulmonary arteriovenous malformations associated with HHT. He was diagnosed with the disorder in adolescence but follow-up in the outpatient setting was incomplete. Early screening and regular follow-up of patients with HHT are important to minimise the risk of development of serious sequelae, such as thromboembolic strokes and cerebral abscesses. Appropriate management demands a knowledge of the risks and benefits of asymptomatic screening and treatment in the rapidly-evolving evidence base for this disease.