Using first-contact serum ferritin to predict severe thrombocytopenia in dengue patients: determination and validation in independent cohorts.

BACKGROUND: Severe thrombocytopenia and associated haemorrhage are dreaded complications of dengue fever. The identification of a biomarker that can predict, or rule out, its subsequent development can help identify at-risk individuals. METHODS: 200 dengue patients were included - the first 100 in the deterministic cohort and the latter, the validation cohort. Serum ferritin levels were measured at first presentation. Platelets were monitored serially. Data from the first cohort was used to determine the optimal ferritin level to predict significant thrombocytopenia (<20,000/µL). This threshold was validated in the second cohort. RESULTS: In the deterministic cohort, a ferritin threshold of 593 ng/mL predicted severe thrombocytopenia with a sensitivity of 93.33%, negative predictive value of 98.18% and negative likelihood ratio (LR-) of 0.10. In the validation cohort, the sensitivity and negative predictive value of this threshold were both 100%. The power of the study (determined post-hoc) for each cohort was 98.4% and 86.4% respectively. CONCLUSION: First-contact ferritin consistently identified at-risk individuals. Individuals with ferritin levels below 593 ng/mL were unlikely to develop severe thrombocytopenia independent of clinical presentation.

A retrospective cohort study exploring diltiazem as a pharmaco-enhancer for tacrolimus, in a post-heart transplant setting.

BACKGROUND: A significant proportion of heart transplant-associated expenditure are attributable to immunosuppressants. Post-transplant hypertension adds to the pill burden and subsequent costs. In this study, we describe the effect of diltiazem-the antihypertensive and pharmaco-enhancer-on reducing the required oral dose of tacrolimus. METHODS: We included 17 recipients who had successfully undergone heart transplants but later developed post-transplant hypertension and were treated with diltiazem. Serum trough levels of the immunosuppressant tacrolimus were measured every 2 weeks. Required doses before and after the introduction of diltiazem were compared. Patients were assessed at each follow-up visit for any evidence of toxicity. Medication-related expenditure was estimated based on government-mandated standardized retail price. RESULTS: The power of the study was 98.92% at α = 0.05. The mean tacrolimus dose required prior to initiation of diltiazem was 5.85 ± 1.55 mg. After initiating diltiazem, the mean required doses reduced to 2.88 ± 1.24 mg (p < .0001). Relatively, the required doses reduced by 52.4 ± 10.9%-independently of age, sex, and dose of diltiazem. Medication-related monthly expenditure reduced by 50.3 ± 10.4%. No patient demonstrated evidence of toxicity. CONCLUSIONS: Concomitant use of diltiazem and tacrolimus can safely, effectively, and predictably reduce the required dose of tacrolimus and significantly reduce corresponding costs.

Low fixed-dose hydroxyurea in severely affected Indian children with sickle cell disease.

There is limited data on the efficacy of hydroxyurea (HU) in Indian sickle cell anemia patients who have severe manifestations despite high fetal hemoglobin (Hb F). Sixty sickle cell anemia children (5-18 years) with more than three episodes of vasoocclusive crises or blood transfusions per year were randomized to receive HU (n = 30) or placebo (n = 30) therapy. Fixed dose (10 mg/kg/day) of HU was administered for 18 months and the patients were followed-up monthly with clinical assessment and laboratory monitoring. In the HU group, hemoglobin (Hb) and Hb F levels increased significantly along with a significant decrease in the number of painful crises, blood transfusion requirements and hospitalizations compared to the placebo group. No major adverse events were observed in this study. In conclusion, low-fixed dose HU therapy was effective for the treatment of Indian sickle cell anemia children. However, there is a need for long-term studies to evaluate the efficacy and toxicity in a larger number of Indian sickle cell anemia patients.