Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study.

BACKGROUND: Worldwide, haemoglobin E ß-thalassaemia is the most common genotype of severe ß-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia. METHODS: In this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality. FINDINGS: 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2·51, 95% CI 1·16-5·43), patients with a history of serious infections (adjusted HR 8·49, 2·90-24·84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1·03, 1·01-1·06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4·5 g/dL (vs concentration >4·5 g/dL), serum ferritin concentration more than 1300 µg/L (vs concentration ≤1300 µg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival. INTERPRETATION: Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival. FUNDING: Wellcome Trust, Medical Research Council, US March of Dimes, Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal.

A nationwide survey of hospital-based thalassemia patients and standards of care and a preliminary assessment of the national prevention program in Sri Lanka.

OBJECTIVES: Our aim was to describe the numbers and distribution of patients with different types of thalassemia and to assess the standards of care in all thalassemia treatment centers throughout Sri Lanka and the success of the ongoing prevention programme. METHODS: This cross-sectional island-wide survey was conducted by two trained medical graduates, who visited each thalassemia center to collect data from every patient, using a standardized form. Data was collected through review of patient registers and clinical records. RESULTS: We collected data on 1774 patients from 23 centers. 1219 patients (68.7%) had homozygous ß-thalassemia, 360 patients (20.3%) had hemoglobin E ß-thalassemia, and 50 patients (2%) had sickle ß-thalassemia. There were unacceptably high serum ferritin levels in almost all centers. The annual number of births of patients with ß-thalassaemia varied between 45-55, with little evidence of reduction over 19 years. CONCLUSIONS: Central coordination of the treatment and ultimately prevention of thalassemia is urgently needed in Sri Lanka. Development of expert centers with designated staff with sufficient resources will improve the quality of care and is preferred to managing patients in multiple small units.

A study of the serum carotenoids of eight cases of hypercarotenemia in Sri Lanka.

Over-consumption of absorbable carotenoids causes hypercarotenemia. Although hypercarotenemia is detected in Sri Lanka, a detailed study on this condition has not been carried out previously. Two millilitres of venous blood was drawn from hypercarotenemic patients (n=8) and examined by high-performance liquid chromatography for carotenoids and vitamin A. A common high-performance liquid chromatographic pattern in serum was shown by six of the cases with beta-carotene (9.9-35.7 microg/dl), beta-cryptoxanthin and monohydroxy metabolites collectively (5.3-48.5 microg/dl), and six to eight metabolites of dihydroxy, trihydroxy and polyhydroxy metabolites (22.5-282.1 microg/dl). Vitamin A levels were within the normal range (32-61 microg/dl). However, two cases identified were abnormal. The first of these showed low beta-carotene (3.5 microg/dl) and no beta-cryptoxanthin and monohydroxy metabolites, but normal dihydroxy, trihydroxy and polyhydroxy metabolites (128.2 microg/dl). However, the vitamin A level was high (75.2 microg/dl). The other case showed high beta-carotene (212.3 microg/dl) and beta-cryptoxanthin (49.3 microg/dl) but no normal monohydroxy, dihydroxy, trihydroxy and polyhydroxy metabolites. Instead there was an atypical metabolite (343.9 microg/dl). According to the present study, excessive intake of boiled, homogenized carrot and ripe papaw is the main causative factor for hypercarotenemia. Over-consumption of carotenoids-rich plant foods may be complicated in the case of individuals having defects of either the control of the 15,15'-dioxygenase activity or metabolism of carotenoids.

Adverse drug reactions in children requiring hospital admission.

OBJECTIVE: To study the incidence of adverse drugs reactions (ADRs) in children admitted to Lady Ridgeway Hospital (LRH), Colombo. DESIGN: A prospective hospital based descriptive study. SETTING: Medical units of LRH, Colombo. METHODS: Information was collected by a hospital based investigator who visited the medical units at LRH from February to December 2002. The Naranjo algorithm was used to classify the information. REMARKS: During the 11 month study period, 63 admissions were due to ADRs, the commonest being secondary to administration of antibiotics. CONCLUSIONS: ADRs accounted for only 0.16% of admissions as compared to about 2% in North America. The commonest ADRs were due to antibiotics.