Short- term impact of educational interventions on disease knowledge, illness perception and quality of life among Jamaican adolescents with sickle cell disease

OBJECTIVES: To assess the effect of educational interventions on disease knowledge, illness perception (IP) and quality of life (QOL) of adolescents with sickle cell disease (SCD) in Kingston, Jamaica. METHODS: A randomized controlled intervention study was conducted among 150 adolescents (ages 13-19 years) attending for routine visits. Baseline disease knowledge, IP and QOL were assessed prior to randomization to 3 groups (Group A: routine care; B: educational booklet; C: booklet + formal counselling) and all measures were repeated 3 months later. Changes in outcomes were analysed using random effects analysis of variance models. RESULTS: There were 76 girls and 74 boys (Mean age 16.1ñ1.9 years; 77% had homozygous SS disease), of whom 63.3% were reviewed at three months. Baseline knowledge was higher: with age (p value: 0.007) and in girls (p value: 0.024). Teen QOL was lower in girls (p value: 0.038) and lower in severe disease (p value< 0.001). Post-intervention knowledge scores were significantly higher within all 3 groups (increase of 1.68 in group A, 2.03 in B and 2.88 in C), but there was nil effect of interventions. There were no changes in QOL or IPs either. Adolescents who had higher knowledge scores had better understanding that their illness was long lasting (Coef: 0.22; p value: 0.008), and they perceived better personal control (Coef: 0.30; p value<0.001), as well as the effect of treatment (Coef: 0.12; p value: 0.01), in managing their illness. CONCLUSIONS: Participation in the study was associated with improved knowledge scores, but interventions per say appeared to have no effects.

Sickle Cell Disease and age at menarche in Jamaican girls: observations from a cohort study

AIMS: (1) To investigate the distribution of age at menarche in a representative sample of 99 patients with homozygous sickle cell disease (ss), 69 with sickle cell haemoglobin C (sc) disease, and 100 controls with a normal haemoglobin (AA) genotype followed in a cohort study from birth. (2) To explore the determinants of the age menarche. METHODS: Children ascertained in a new-born screening programme were followed prospectively from birth to age 18-26.5 years with regular assessments of height, weight, puberal stage, and haematological indices at the Sickle Cell Clinic of the University Hospital of the West Indies. RESULTS: All subjects have now reached menarche and the mean age in normal controls (13.0 years) was significantly earlier than in SC disease (13.5 years) or SS disease (15.4 years). Greater weight and earlier age at menarche was the only association significant across all genotypes although additional contributions occured from fetal haemoglobin and red cell count in SS disease. Alpha thalassaemia, which ameliorates many of the effects of SS disease, had no discernible effect on menarche. CONCLUSIONS: Mean age at menarche is delayed by 0.5 years in SC disease and by 2.4 years in SS disease. Weight appears to be the principle determinant of age at menarche. (AU)

Gallstones in sickle cell disease: observations from the Jamaican Cohort study

The prevalence, incidence, risk factors, clinical associations, and morbidity of gallstones were studied in 311 patients with homozygous sickle cell disease and 167 patients with sickle cell-hemoglobin C disease in a cohort study from birth. Gallstones developed in 96 patients with homozygous sickle cell disease and 18 patients with sickle cell-hemoglobin C disease; specific symptoms necessitating cholecystectomy occurred in only 7 patients with homozygous sickle cell disease.(AU)

Quality of life in children with sickle cell disease in Amsterdam area

OBJECTIVE: To determine the differences in quality of life between children with sickle cell disease and healthy immigrant children. DESIGN: Descriptive, comparative. METHOD: The quality of life of children with sickle cell disease between 5 and 15 years old being treated in the Emma Children's Hospital AMC in Amsterdam, the Netherlands, was assessed by using a questionnaire for parents (TNO-AZL Children's Quality of Life Questionnaire (TACQOL) parent form) if the child was between 8 and 15 years old. The study period was April-October 1998. The questionnaires were completed by 45 (parents of) patients. The results were compared with a healthy reference group of immigrant children. Statistical analysis was performed using the Student t-Test. RESULTS: Children with sickle cell disease as well as their parents scored signifcantly lower on the items general physical, motor and independent daily functioning and on occurrence of negative emotions. No significance was observed for the items cognitive functioning and school performance nor for social functioning or occurrence of positive emotions. CONCLUSIONS: In children, sickle cell disease leads to compromised physical and possibly also psychological wellbeing, as well as the experience of decreased independence in daily functioning, but not to compromised cognitive or social aspects of the quality of life. (AU)

Renal length in sickle cell disease: observation from a cohort study

Renal length has been measured by ultrasound in 237 subjects with homozygous sickle cell (SS) disease, 147 with sickle cell-hemoglobin C (SC) disease, and in 78 age-matched controls with a normal hemoglobin (AA) genotype. As expected, renal length increased with age in all genotypes but mean length was significantly greater in SS disease compared with SC disease (mean difference 4.3 mm after adjustment for height) and significantly greater in both genotypes than in AA controls (SS/AA difference 9.2 mm, SC/AA difference 5.0 mm after adjustment for height). Examination of relationship between renal length and some hematological indices (hemoglobin, fetal hemoglobin, reticulocyte counts, alpha thalassemia status) in SS or SC disease showed only a significant negative correlation with hemoglobin and positive correlation with reticulocyte count in SS disease. Further analysis suggested that the stronger relationship was between renal length and high reticulocyte count. The mechanism of renal enlargement is unknown although glomerular hypertrophy and increase renal blood volume are likely contributors.(AU)

Biliary sludge in sickle cell disease

Biliary sludge was observed in the gallbladder in 17 of 429 patients in a cohort study of sickle cell disease. Discrete gallstones later developed in 12 patients, but no stones developed in five patients; one patient with biliary sludge had no change in his condition for 5 years. None of the patients with biliary sludge had any symptoms referable to the biliary tract, and cholecystectomy has not been performed. The Jamaican experience suggests that biliary sludge may be treated conservatively, similar to our approach to asymptomatic gallstone. (AU)

Daily variability in resting levels of cardiovascular variable in normal subjects and those with homozygous sickle cell disease

Measurements were made of cardiovascular variables and oral temperature in 16 male subjects with homozygous sickle cell disease (SS) and in 17 matched controls (AA) at 10.00 a.m, 1.00 p.m and 4.00 p.m. All subjects were in a rested state throughout. At 10.00 a.m. mean arterial pressure was lower, while heart rate, total forearm blood flow and cutaneous red cell flux in the forearm were higher in SS than AA. Vascular resistance in total forearm and forearm skin, calculated by dividing arterial pressure by blood flow or red cell flux, were lower in SS but hand cutaneous red cell flux and vascular resistance were not significantly different in SS and AA. In both SS and AA, there were parallel increase over the three sessions, in mean arterial pressure (by approximately 12 and 10 percent respectively) forearm vascular resistance (by approximately 17 and 27 percent) and hand cutaneous vascular resistance and hand cutaneous resistance (by approximately 2240 and 350 percent) whereas forearm blood flow and hand cutaneous red cell flux fell. By contrast, forearm cutaneous resistance showed no change during the day in SS, but increased progressively in AA (by approximately 75 percent). These results indicate that, during the day, there is progressive vasconstriction in forearm muscle and hand skin in SS and AA and also in forearm skin of AA that contributes to a progressive rise in the resting level of mean arterial pressure. We suggest this daily variability should be considered in studies of cardiovascular function: within a given study they should be performed at the same time of day.(AU)

New classification of peripheral retinal vascular changes in sickle cell disease

The systemic complications of homozygous sickle cell disease (SS) are more severe than in sickle cell haemoglobin C (SC) disease, and yet visual loss due to proliferative retinopathy is more common in the latter. This anomaly is unexplained. It is believed that proliferative disease occurs in response to closure of the peripheral retinal vasculature, yet a systematic longitudinal survey of the peripheral retinal vascular bed has not been undertaken. In the Jamaica Sickle Cohort study all subjects are scheduled to receive annual ocular examination and fluorescein angiography. The results have now been analysed in subjects with SS and SC disease using a new classificaton system based on a comparison of the peripheral retinal vascular bed with that recorded in the cohort with normal haemoglobin (AA) genotype. The vascular patterns could be classified as qualitatively normal (type I) or abnormal (type II). An abnormal vascular pattern was identified more commonly with age, in a significantly larger proportion of subjects with SC than SS disease, and was associated with the development of proliferative disease. In order to establish the dynamics of change, the angiograms were analysed in the 18 subjects (24 eyes) who developed proliferative disease. It is shown that qualitatively normal vascular pattern may be retained despited loss of capillary bed and posterior displacement of the vascular border. A border which is qualitatively abnormal does not revert to normal, and once abnormal, continuous evolution may occur before development of proliferative lesions. The peripheral border of the retinal vasculature was too peripheral to photographed in 13 of the 24 eyes before it becoming qualitatively abnormal. It is concluded that a normal border, if posterior, results from gradual modification of the capillary bed and indicated low risk of proliferative disease. A qualitatively abnormal vascular border occurs as a radical alteration of retinal perfusion in subjects in whom little modification of the vascular bed occurred before the event, and signal risk of proliferative disease. This classification system is useful in identifying the likelihood of threat to vision in young Jamaicans with sickle cell disease, and the higher frequency of proliferative retinopathy in SC can be explained by the higher prevalence of a qualitatively abnormal peripheral retinal vasculture (AU)

Adolescent blood pressure in a cohort study of sickle cell disease

BACKGROUND: Previous studies on low blood pressure in patients with homozygous sickle cell (SS) disease have sought new hypothesis on the mechanism of low blood pressure but have not analyzed the role of known determinants such as weight. METHODS: Blood pressure has been measured by an automated oscillometric method in 220 patients with SS disease, 144 with sickle cell-hemoglobin C disease (both groups aged, 9.5 to 18.5 years) and 122 control subjects with a normal hemoglobin genotype (aged 16.0 to 18.5 years) participating in a cohort study from birth. RESULTS: Significant age-related increases in systolic and mean arterial pressure occurred in sickle cell-hemoglobin C disease but not in SS disease. Further analysis were confined to a subgroup of 51 patients with SS, 41 patients with sickle cell-hemoglobin C, and 97 subjects with normal hemoglobin, aged 16.0 to 18.5 years in whom simultaneous measurements of height, weight, arm circumference, and hematologic test results were also available. Crude analysis showed significantly lower systolic, diastolic, and mean arterial pressure in SS disease compared with control subjects with normal hemaglobin, but further analysis showed the systolic difference to be confined to males and all differences disapperared after ajustment for weight. No difference occurred in sickle cell-hemoglobin C disease. CONCLUSIONS: These results suggest that the lower blood pressure in SS disease is attributable to low weight and that no further mechanisms need be postulated (AU)

Is there an acute-phase response in steady-state sickle cell disease?

Metabolic and serum changes during steady-state homozygous sicle cell (SS) disease are consistent with an acute-phase response and raise the possibility that inflammation occurs in SS disease even during the steady state. To test this hypothesis, we measured concentrations of acute phase reactants in patients with SS disease, in patients with sickle cell haemoglobin C (SC) disease, and in normal (AA) control subjects. The concentrations of C-reactive protein and serum amyloid A were increased above 10 mg/L and 5mg/L, respectively (our definition of an acute-phase response) in 18 percent (26/143) of subjects with SS disease even when they were symptom free, in 17 percent (6/35) of subjects with SC disease, and in 1 percent (1/80) of AA controls (p<0.001). We suggest that subclinical vaso-occlusion may generate a covert inflammatory response and that the cytokine mediators of this response may contribute to the metabolic abnormalities and growth failure in sickle cell disease.(AU)

Testing for the random occurrence of sickle cell disease in a study of 100,000 Jamaican newborns

In a screening programme for sickle cell haemoglobinopathies at a maternity hospital in Kingston, Jamaica, 100,000 newborns were screened with the detection of 315 cases of SS disease, and 201 cases of SC disease. There was no upward or downward trend in the frequency of SS or SC births during the screening programme. The sequence numbers of the SS and SC births were analysed to examine whether these cases were randomly distributed among the 100,000 newborns. The occurence of SS births seems to accord well with the random model but there was an excess of very long intervals between SC births. (AU)

Nocturnal enuresis in sickle cell haemoglobinopathies

The prevalence of nocturnal enuresis (wet at least two nights a week) was investigated in children, aged 8, who were being followed up as part of a prospective cohort study. There were 175 children with homozygous sickle cell disease, 106 with sickle cell haemoglobin C disease, and 150 controls with a normal haemoglobin genotype. In homozygous sickle cell disease, 48 boys (52 percent) and 31 girls (38 percent) were enuretic, a significantly higher prevalence than in those with sickle cell haemoglobin C disease - five boys (10 percent) and 11 girls (20 percent) - or in normal children - 16 boys (22 percent) and 13 girls (17 percent). There was no significant difference between children with sickle cell haemoglobin C disease and the normal genotype. Boys with homozygous sickle cell disease were significantly more likely to be enuretic if they came from large families; there was a similar trend for girls with homozygous sickle cell disease, although it did not reach significance. Enuresis was more common in boys with homozygous sickle cell disease who had low concentrations of fetal haemoglobin and in girls with sickle cell haemoglobin C disease who had high mean corpuscular haemoglobin concentrations. Similar associations were not shown for girls with homozygous sickle cell disease or boys with sickle cell haemoglobin C disease. (AU)

Risk factors for proliferative sickle retinopathy

The prevalence, incidence, and risk factors associated with proliferative sickle retinopathy (PSR) were investigated in 786 patients with homozygous sickle cell (SS) disease and 533 patients with sickle cell hemo globin C (SC) disease. PSR was more common in SC disease, in which there was a significant predominance of males, and it increased with age in both genotypes. In SC disease the risk of developing PSR was highest between 15 and 24 years in males, between 20 and 39 years in females, and in SS disease between 25 and 39 years in both sexes. PSR tended to be bilateral, especially in SC disease. There was no evidence of familial clustering of PSR in SC siblings, and insufficient numbers of SS siblings were available to test for clustering. Haematological risk factors associated with PSR in SS disease were a high haemoglobin in males and a low fetal haemoglobin in both sexes and in SC disease, a high mean cell volume, and a low fetal haemoglobinin females. (AU)

Whole body protein turnover and resting metabolic rate in homozygous sickle cell disease

Whole body protein turnover and resting metabolic rate were measured in six adults with homozyguous sickle cell disease (genotype HbSS) and in six normal adults (genotype HbAA) of similar age. Turnover was measured with prime/intermittent oral doses of [15N]glycine over 18 h and resting energy expenditure was measured by indirect calorimetry. In HbSS, nitrogen flux (0.9 ñ 0.08 g day-1 kg-1), protein synthesis (6.0 ñ 0.5 g day-1 kg-1) and protein degradation (5.6 ñ 0.5 g day-1 kg-1) were significantly increased compared with HbAA nitrogen (flux 0.5 ñ 0.02g day-1 kg-1, protein synthesis 3.2 ñ 0.2 g day-1 kg-1 and protein degradation 2.8 ñ 0.2 g day-1 kg-1). Resting energy expenditure was significantly higher in HbSS compared with HbAA when expressed per unit of body weight (115 ñ 3 and 94 ñ 4 kj day-1 kg-1 respectively) or weight 0.75(317 ñ 6 and 269 ñ 8 kj day-1kg-0.75, respectively). The increase in protein turnover and energy expenditure suggest that patients with HbSS exist in a hypermetabolic state that requires greater dietary energy compared with HbAA. (AU)

Urea kinetics in sickle cell disease

When dietary nitrogen intake is adequate to satisfy the body's metabolic demand for nitrogen, adaptive mechanisms are involved whereby nitrogen losses are minimised. The most significant reduction in nitrogen loss is effected by reduced urea production and excretion and there is a concomitant increase in the proportion of urea hydrolysed and recycled in the body. This work was designed to explore the mechanisms by which nitrogen equilibrium is maintained in the whole body when the metabolic demands for nitrogen exceed the supply. Urea kinetics was measured in normal healthy controls (HbAA) and patients with homozygous sickle cell disease (HbSS). HbSS is characterised by an increased metabolic demand for nitrogen for erythropoesis, which is significantly higher than normal. Urea production (P), excretion (Eu), hydrolysis (T) and recycling (Pr) of hydrolysed urea to urea synthesis, were determined using isotopic urea(urea-30) orally or intravenously, and the two methods compared. The reliability of the methods was examined and demonstrated to be satisfactory. All aspects of urea metabolism were increased in HbSS compared with HbAA, except Eu which tended to be lower in HbSS. The proportion of urea hydrolysed in the colon was raised in HbSS, regardless of the route by which the isotope was given and the kinetics was measured. Individuals with sickle cell trait (HbAS), were also studied and exhibited rates of urea hydrolysis that were either similar to the HbAA values or raised to values corresponding to the HbSS. Urea nitrogen incorporated into haemoglobin in both the HbAA and HbSs. This finding confirmed the utilisation of endogenous urea nitrogen for protein synthesis in the body. The proportion of hydrolysed urea nitrogen is small (10 percent) compared to a larger pool of enteric nitrogen to which it contributes, suggesting that there may be a more significant contribution of enteric nitrogen metabolism to the nitrogen economy, than of hydrolysed urea alone. The possibility that glycine may be limited in HbSS has been indicated and warrants more detailed investigation. The metabolism of urea has been shown to be affected by depleting the body glycine pool and alternatively by glycine supplements. Results from this work support the idea that urea kinetics is modulated by dietary nitrogen intake (AU)

The cohort study of sickle cell disease - abstract

Most observations on sickle cell disease have been made on symptomatically selected hospital-based populations. As such, they represent a group of patients who are benign enough to have survived, but severe enough to have come to medical attention. Traditional medical descriptions have therefore emphasised only the severe end of what is now recognised to be a wide clinical spectrum. Documentation of this spectrum is important to an understanding of the natural history of the disease and to the determinants of severity. The cohort study was an attempt to define a large representative group of patients with sickle cell disease where there had been no element of symptomatic selection and to follow them prospectively. Between June 1973 and December 1981, 100,000 consecutive normal deliveries were screened at Victoria Jubilee Hospital, Kingston with the detection of 315 children with homozygous sickle cell (SS) disease. 201, with sickle cell-haemoglobin C (SC) disease, 33 with sickle cell cell-beta+ thalassaemia, and 14 with sickle cell-beta§ thalassaemia. Among the SS group, there have been 56 deaths, nearly 10 percent dying in the first year of life. Although symptoms are rare in the first six months of life because of high levels of HbF, the second 6 months of life is the highest risk period at any time in the life of the child, the mortality rate falling for each individual year subsequently. Thus, life-threatening complications occur in SS disease at an age when the underlying haemoglobinopathy may not be suspected. Principle causes of early mortality included acute chest syndrome, acute splenic sequestration and pneumococcal septicaemia. Since the frequency and outcome of these complications may be affected by prophylaxis or early intervention, it is essential that the diagnosis of the underlying haemoglobinopathy be made early. Neonatal diagnosis of sickle cell disease is simple and cost-effective and allows prophylaxis and education programmes to be instituted early (AU)

Haematological change in sickle cell-haemoglobin C disease and in sickle cell-beta thalassaemia: a cohort study from birth

The haematological changes in early years following neonatal diagnosis have been observed in representative groups of children with sickle cell-haemoglobin C (SC) disease, sickle cell-á+ thalassaemia, and in sickle cell-á Thalassaemia. Most haematological indices in SC disease were intermediate between previously published values in SS disease and in AA controls, generally being closer to values in normal children, Eceptions were microcytosis which may be genetically determined and a striking elevation of mean cell haemoglobin cocentration from age 2 months to 4 years. The combination of a raised MCHC and a lowered MCV is unusual and may be characteristic of SC disease. Features in sickle cell-á thalassaemaia generally differed accordingly to the type of á thalassaemia gene. Sickle cell-B degree thalassaemia had lower levels of haemoglobin, MCHC, red cell count, MCV, and higher reticulocytes, most differences being significant before 1 year. No differences between SB degree thalassaemia and Sá+ thalassaemia were apparent in HbF levels (which resembled those in SS disease) or in HbA2 levels (which exceeded those in SS disease by 1 year of age).(AU)