Klaas J. J Wierenga

Survival estimates for patients with homozygous sickle-cell disease in Jamaica: a clinic-based population study

BACKGROUND Information about life expectancy of patients with homozygous sickle-cell disease is needed for research and patient counselling. Our aim was to study two Jamaican populations, one clinic-based and one birth cohort and, by careful consideration of data quality and statistical analysis, to identify ways to increase the chances of obtaining valid and generalisable results. METHODS We investigated the survival experience of 3301 patients with homozygous sickle-cell disease attending the Jamaican sickle-cell clinic between Jan 1, 1987, and Dec 31, 1996. We applied and assessed a simulation technique for incorporating early life mortality using a birth cohort, and analysed the precision of this technique. Kaplan-Meier survival estimates are produced. FINDINGS 290 of the 3301 patients died. Median survival calculated with the excess mortality rate simulation data was 53 years (95% CI 49.3-57.0) for men and 58.5 (55.1-67.5) for women. INTERPRETATION Our simulation technique, with realistic assumptions based on empirical evidence, offers a new estimate of median survival for patients with homozygous sickle-cell disease. We present the precision of these survival estimates, which introduces an important level of uncertainty. The inherent biases of clinically ascertained populations of patients, and the assumptions underlying analysis techniques are crucial features of survival studies in sickle-cell disease, and can modify summary statistics substantially.

Glomerulonephritis after human parvovirus infection in homozygous sickle-cell disease

Glomerulonephritis with proteinuria of sufficient degree to manifest the nephrotic syndrome followed aplastic crises induced by human parvovirus (B19) in seven patients with homozygous sickle-cell disease, within 7 days in five patients and 6-7 weeks in two. Segmental proliferative glomerulonephritis was found in all four patients who underwent acute renal biopsies and focal segmental glomerulosclerosis was found in the fifth patient who had a biopsy 4 months later. One patient recovered completely, one died in chronic renal failure after 3 months, and the others had impaired creatinine clearance, four with continuing proteinuria.

Delayed adolescent growth in homozygous sickle cell disease.

Analysis of the growth abnormalities in sickle cell disease has been limited by the lack of longitudinal observations in individuals, and by an inability to quantitate the observed patterns. To investigate the timing and pattern of the adolescent growth spurt, longitudinal observations of height from the Jamaican cohort study were fitted to a mathematical model of growth (Preece-Baines model 1). The study included 44 children with homozygous sickle cell (SS) disease, 44 age and sex matched subjects with sickle cell haemoglobin C (SC) disease, and 44 age and sex matched controls with normal (AA) haemoglobin. Compared with AA controls, the onset of the adolescent growth spurt was delayed in SS disease by 1.4 years (95% confidence interval 0.8 to 2.0) with no significant sex difference. The age at peak height velocity was delayed by 1.6 years (0.9 to 2.3) in SS compared with AA subjects but the adolescent growth of SS children was otherwise normal and there was no difference in the attained height by age 17.9 years. The growth spurt was not delayed in SC disease. The age at menarche in girls with SS disease (mean (SD) 15.4 (1.3) years) was significantly later than girls with SC disease (13.7 (1.7) years) and those with AA haemoglobin (13.1 (1.3) years) but these genotype differences were no longer significant after controlling for the delay in the adolescent growth spurt. The normally coordinated but slightly delayed pattern of growth and normal adult heights suggests a good prognosis for adolescent growth delay in SS disease. Most children with SS disease can therefore be reassured on the outcome of retarded adolescent growth.

Significance of fever in Jamaican patients with homozygous sickle cell disease

OBJECTIVE To investigate the cause and outcome of high fever in Jamaican children with homozygous sickle cell disease. DESIGN Retrospective review of febrile episodes in a three year period (1 September 1993 to 31 August 1996). SETTING Sickle cell clinic, an outpatient clinic in Kingston run by the Medical Research Council Laboratories (Jamaica). PATIENTS Patients with homozygous sickle cell disease under 17 years of age presenting with an axillary temperature ⩾ 39.0°C (102.4°F). MAIN OUTCOME MEASURES Diagnosis, death. RESULTS There were 165 events in 144 patients (66 (45.8%) boys) with a median age of 6.1 years. Bacteraemia was found in 10 (6.1%) events (threeStreptococcus pneumoniae, twoHaemophilus influenzae type b, twoSalmonella sp, oneEscherichia coli, oneEnterobacter sp, and oneAcinetobacter sp), and urinary tract infections in four (2.4%). All cultures of cerebrospinal fluid were sterile. Acute chest syndrome occurred in 36 (21.8%) events. A painful crisis was associated with 45 (27.3%) events and was the only pathology identified in 20 events (12.1%). Hospital admission was necessary in 66 cases including all those with bacteraemia and 31 with acute chest syndrome. There were two deaths: a 5 year old boy with septic shock associated with H influenzaesepticaemia, and a 3 year old boy with the acute chest syndrome. CONCLUSIONS Painful crisis and acute chest syndrome were the most common complications associated with high fever, but other important associated features included bacteraemia and urinary tract infection. Enteric Gram negative organisms accounted for 50% of positive blood cultures.