Academic performance in Jamaican children with sickle cell disease.

OBJECTIVE: Children with sickle cell disease (SCD) are at risk for neurocognitive deficits that can affect school performance, and psychosocial functioning. The aim of this study was to assess the academic performance of school-aged children with SCD in Jamaica compared to their school peers. METHOD: A cross-sectional survey of academic performance was done in a group of children 11 to 13 years of age, using a standardized state administered examination, the Grade Six Achievement Test (GSAT), covering 5 subjects. Scores were obtained from the Ministry of Education (MOE) for eligible children with SCD, as well as mean scores with standard deviation for unaffected classmates by gender. Socio-demographic and clinical data were obtained from our sickle cell clinic database and an interview administered questionnaire. RESULTS: Sixty-four children satisfied eligibility criteria. Children with SCD had lower percentage scores and significantly lower mean z-scores for 4 of 5 subjects (p < 0.05). Males had significantly lower mean z-scores compared with females. Thirty-seven children (57.8%) were classified as underperformers. Haemoglobin level was a significant predictor of subject score rank. CONCLUSION: Children with SCD in Jamaica perform worse in standardized school examinations than their class peers with boys being particularly vulnerable.

Edematous severe acute malnutrition is characterized by hypomethylation of DNA.

Edematous severe acute childhood malnutrition (edematous SAM or ESAM), which includes kwashiorkor, presents with more overt multi-organ dysfunction than non-edematous SAM (NESAM). Reduced concentrations and methyl-flux of methionine in 1-carbon metabolism have been reported in acute, but not recovered, ESAM, suggesting downstream DNA methylation changes could be relevant to differences in SAM pathogenesis. Here, we assess genome-wide DNA methylation in buccal cells of 309 SAM children using the 450 K microarray. Relative to NESAM, ESAM is characterized by multiple significantly hypomethylated loci, which is not observed among SAM-recovered adults. Gene expression and methylation show both positive and negative correlation, suggesting a complex transcriptional response to SAM. Hypomethylated loci link to disorders of nutrition and metabolism, including fatty liver and diabetes, and appear to be influenced by genetic variation. Our epigenetic findings provide a potential molecular link to reported aberrant 1-carbon metabolism in ESAM and support consideration of methyl-group supplementation in ESAM.

Use of a public park for physical activity in the Caribbean: evidence from a mixed methods study in Jamaica.

BACKGROUND: Small island Caribbean countries such as Jamaica are now facing an epidemic of obesity and decreased physical activity (PA) levels. Public parks have been shown to be important resources for PA that also provide psychological and social benefits associated with increased PA. There are no studies that document PA in parks in the Caribbean. METHODS: This study utilized a mixed method approach by using the System for Observing Play and Recreation in Communities (SOPARC) to obtain baseline data on park usage patterns in Emancipation Park, a large urban public park in Jamaica. In addition, in-depth interviews were conducted to gain additional insights on the park's use for PA. RESULTS: The park was used mostly by females, in the evenings and by persons 18-64 years old. Females had significantly lower mean energy expenditure (EE) than males (0.078 versus 0.080 kcal/kg/min, p < 0.05). In-depth interviews revealed that safety, a central location within a business district, aesthetic appeal, a walking track and individual health benefits were key reasons for persons engaging in PA at the park. CONCLUSIONS: This is the first study to describe the usage of a public park for PA in Jamaica. The study elicited aspects of park use for PA in a major urban park in Jamaica from different vantage points by using direct systematic observation augmented with a qualitative approach. It revealed important differential park use for PA by sex, age group and EE levels, and provided insights into factors that motivate and hinder park usage for PA. This can be used by policymakers in Jamaica to inform PA interventions to reduce obesity, provide baseline data for comparisons with other parks in developing countries and to advocate for well-designed public parks.

An Investigation of the Antioxidant Capacity in Extracts from Moringa oleifera Plants Grown in Jamaica.

Moringa oleifera trees grow well in Jamaica and their parts are popularly used locally for various purposes and ailments. Antioxidant activities in Moringa oleifera samples from different parts of the world have different ranges. This study was initiated to determine the antioxidant activity of Moringa oleifera grown in Jamaica. Dried and milled Moringa oleifera leaves were extracted with ethanol/water (4:1) followed by a series of liquid-liquid extractions. The antioxidant capacities of all fractions were tested using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. IC50 values (the amount of antioxidant needed to reduce 50% of DPPH) were then determined and values for the extracts ranged from 177 to 4458 µg/mL. Extracts prepared using polar solvents had significantly higher antioxidant capacities than others and may have clinical applications in any disease characterized by a chronic state of oxidative stress, such as sickle cell anemia. Further work will involve the assessment of these extracts in a sickle cell model of oxidative stress.

EXpanding Treatment for Existing Neurological Disease (EXTEND): An Open-Label Phase II Clinical Trial of Hydroxyurea Treatment in Sickle Cell Anemia.

BACKGROUND: Cerebral vasculopathy in sickle cell anemia (SCA) begins in childhood and features intracranial arterial stenosis with high risk of ischemic stroke. Stroke risk can be reduced by transcranial doppler (TCD) screening and chronic transfusion therapy; however, this approach is impractical in many developing countries. Accumulating evidence supports the use of hydroxyurea for the prevention and treatment of cerebrovascular disease in children with SCA. Recently we reported that hydroxyurea significantly reduced the conversion from conditional TCD velocities to abnormal velocities; whether hydroxyurea can be used for children with newly diagnosed severe cerebrovascular disease in place of starting transfusion therapy remains unknown. OBJECTIVE: The primary objective of the EXpanding Treatment for Existing Neurological Disease (EXTEND) trial is to investigate the effect of open label hydroxyurea on the maximum time-averaged mean velocity (TAMV) after 18 months of treatment compared to the pre-treatment value. Secondary objectives include the effects of hydroxyurea on serial TCD velocities, the incidence of neurological and non-neurological events, quality of life (QOL), body composition and metabolism, toxicity and treatment response, changes to brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), genetic and serologic markers of disease severity, and cognitive and pulmonary function. METHODS: This prospective Phase II trial will enroll children with SCA in Jamaica, between the ages of 2 and 17 years, with either conditional (170-199 cm/sec) or abnormal (≥ 200 cm/sec) TCD velocities. Oral hydroxyurea will be administered daily and escalated to the maximum tolerated dose (MTD). Participants will be seen in the Sickle Cell Unit (SCU) in Kingston, Jamaica monthly until achieving MTD, and then every 3 months. TCD will be performed every 6 months. RESULTS: Currently, 43 participants have been enrolled out of a projected 50. There was one withdrawal due to immigration, with no permanent screen failures. Of the 43 enrolled, 37 participants have initiated study treatment. CONCLUSIONS: This trial investigates the effects of hydroxyurea treatment at MTD in children with conditional or abnormal TCD velocities before transfusion therapy and may represent an important advance towards establishing a suitable non-transfusion protocol for stroke prevention in children with SCA. The trial outcomes will have profound significance in developing countries where the disease burden is highest. CLINICALTRIAL: ClinicalTrials.gov NCT02556099; https://clinicaltrials.gov/ct2/show/NCT02556099 (Archived by WebCite at http://www.webcitation.org/6k1yMAa9G).

Overactive bladder in adults with sickle cell disease.

AIMS: To characterize the prevalence and impact of nocturnal enuresis and overactive bladder (OAB) symptomatology in the adult sickle-cell disease (SCD) population. METHODS: We performed a single-center, cross-sectional study of adult SCD patients from October 2012 to February 2014, using the validated Pfizer OAB short form questionnaire and brief voiding history surveys. Patient responses and scores were compared to that of controls having normal or sickle cell trait hemoglobin genotypes. RESULTS: A group of 239 SCD patients (116 males, 123 females) were compared with 104 normal and 57 sickle cell trait patients. Seven of 239 (2.9%) SCD patients compared to none of the 161 patients without SCD (P = 0.04) reported current nocturnal enuresis. The median age of nocturnal enuresis cessation was higher in SCD patients (12.0, IQR 9.0-15.0 years) compared to that of both normal (7.5, IQR 6.0-9.8 years) and sickle cell trait (7.5, IQR 6.0-8.8 years) groups (P < 0.0001). Ninety-three of 239 (38.9%) SCD patients compared to 17 of 104 (16.3%) normal and 11 of 57 (19.3%) sickle cell trait had scores indicating OAB symptomatology (P < 0.0001). Patients with SCD had higher OAB symptom severity and lower health-related quality of life (HRQL) scores compared to the normal and sickle cell trait groups (P < 0.0001 and P < 0.0001, respectively). CONCLUSIONS: We demonstrate an elevated rate of nocturnal enuresis and OAB symptoms in the adult SCD population. An OAB phenotype may be an under-recognized complication of SCD irrespective of age. Neurourol. Urodynam. 35:642-646, 2016. © 2015 Wiley Periodicals, Inc.

A Retrospective Analysis of the Significance of Haemoglobin SS and SC in Disease Outcome in Patients With Sickle Cell Disease and Dengue Fever.

BACKGROUND: Little is known about the significance of haemoglobin genotype in dengue fever severity. This study was undertaken to determine the case fatality ratio and the impact of genotype in patients with sickle cell disease and confirmed dengue fever. METHODS: This retrospective analysis included 40 patients with confirmed dengue and sickle cell disease, during the study period (2010-2012). FINDINGS: There was a significantly higher case fatality ratio, 12.5% among patients with either haemoglobin SC disease or homozygous SS disease when compared to that of the general population 0.41% (p < 0.0001). The unadjusted odds of dying among those with haemoglobin SC disease compared with the group with homozygous SS disease was OR = 4.4 (95% CI 0.6 to 31.7). The predictors of mortality independent of sickle cell disease genotype were haemoglobin concentration at presentation OR = 0.57 (95% CI, 0.35 to 0.94) and the change in haemoglobin concentration from steady state OR = 0.59 (95% CI, 0.37 to 0.94). Adjusting for haemoglobin concentration at presentation increased the risk of death for the SC genotype relative to SS genotype OR = 13.4 (95% CI 1.1 to 160.3). INTERPRETATION: The risk of fatal dengue may be higher among patients with a relatively mild genotype (haemoglobin SC).

Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial.

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSß(0) -thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7-9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0-35%) in the hydroxyurea arm and 47% (95% CI = 6-81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (-15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities.

Impact of a Comprehensive Sickle Cell Center on Early Childhood Mortality in a Developing Country: The Jamaican Experience.

OBJECTIVE: To compare mortality in children <5 years of age with sickle cell disease (SCD) in Jamaica, a resource-limited country, diagnosed by newborn screening and managed in a comprehensive care facility, to that of the general population. STUDY DESIGN: The study was carried out at the Sickle Cell Unit in Kingston, Jamaica. We determined the status (dead/alive) at age 5 years in a cohort of 548 children with SCD diagnosed by newborn screening and managed at the Sickle Cell Unit during the period November 1995 to December 2009. The standardized mortality ratio was calculated using World Health Organization life tables for reference mortality. RESULTS: Eight deaths (1.5%) occurred in children <5 years of age during the study period. The mean age at death was 2.0 ± 1.5 years. The overall mortality incidence in children <5 years of age was 3.1 (95% CI 1.6, 6.2) per 1000 person-years with a standardized mortality ratio of 0.52 (95% CI 0.3, 1.0). CONCLUSIONS: Mortality in children <5 years of age with SCD diagnosed at birth and managed at a comprehensive care clinic in Jamaica is equivalent to that of the general population. Children with SCD, a highly vulnerable population, can be effectively managed, even in resource-limited environments.

Is testosterone deficiency a possible risk factor for priapism associated with sickle-cell disease?

PURPOSE: The purpose of this study was to determine the association of testosterone deficiency and priapism in adult men with sickle cell disease (SCD). METHODS: A cross-sectional study of 50 adult men with SCD (hemoglobin SS) was performed. All patients had early morning blood taken for total and free testosterone, FSH, LH, prolactin, lipid levels, LDH and hematological indices. Patients completed an interviewer-administered questionnaire regarding priapism frequency, duration and treatment. Testosterone deficiency was defined as a serum total testosterone<12 nmol/L (346 ng/dL). RESULTS: The mean age of the study population was 34.2±8.9 years. Priapism was noted in 24 (48%) patients and was most frequently seen in men between ages 18-25 years. Testosterone deficiency was observed in 11 of the 50 (22%) patients, particularly in 6 of 24 (25%) patients with histories of priapism. There was no difference in mean total testosterone levels in patients with and without a history of priapism (16.7±4.9 nmol/L and 15.4±5.9 nmol/L, respectively) (p=0.43). Similarly, there was no difference in serum LH and FSH levels based on history of priapism. CONCLUSION: Testosterone deficiency is prevalent in patients with SCD; however, we did not identify an association based on a history of priapism. Larger, prospectively gathered data are needed to define the priapism profile of SCD patients with testosterone deficiency.

Renal function in adult Jamaicans with homozygous sickle cell disease.

OBJECTIVES: As populations with sickle cell disease (SCD) live longer, it is likely that the burden of renal dysfunction will be an increasing challenge for patients. In this study, we aim to determine the prevalence of renal dysfunction and its possible predictors in persons with SCD. METHODS: Ninety-eight patients with the homozygous SCD (SS disease;55 females, 43 males; mean age 34 ± 2.3 years) in their steady state had measurements of glomerular filtration rate (GFR) using 99mTc-DTPA nuclear renal scan, serum creatinine, and urinary albumin: creatinine ratio. Other haematological and biochemical measurements and data on clinical events were completed for each individual. RESULTS: Chronic kidney disease (CKD) stages 3 and above was present in 6% of the study population, and 65.3% had albuminuria. Hyperfiltration occurred in 24.5% patients with two-thirds having albuminuria as well. Serum creatinine was an insensitive marker of renal dysfunction as started rising after measured GFR fell below 50 mls/min/1.73 m(2). Multiple regression modelling showed serum creatinine and height to be significantly associated with GFR. Serum creatinine was also significantly associated with albuminuria, and age was not a predictor in any of the models. There was no association with markers of haemolysis. CONCLUSION: We conclude that the burden of renal dysfunction is quite high in this young cohort with SS disease. Serum creatinine is a late and insensitive marker of worsening glomerular function, and screening for albuminuria could begin early in life. Longitudinal studies will continue to increase our understanding of pathophysiological mechanisms that lead to CKD in this specific population.

A double-blind, placebo-controlled phase II study of the efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease.

This placebo-controlled phase II study evaluated the pharmacodynamics, efficacy and safety of 2,2-dimethylbutyrate (HQK-1001), a fetal globin gene-inducing short-chain fatty acid derivative, administered orally at 15 mg/kg twice daily for 48 weeks in 76 subjects with sickle cell disease (SCD). The median age was 26 years (range: 12-55 years) and 37 subjects (49%) were treated previously with hydroxycarbamide. Sixty subjects (79%) had Hb SS and 16 (21%) had S/ß(0) thalassemia. The study was terminated after a planned interim analysis showed no significant increase in fetal hemoglobin (Hb F) and a trend for more pain crises in the HQK-1001 group. For 54 subjects with Week 24 data, the mean absolute increase in Hb F was 0.9% (95% confidence interval (CI): 0.1-1.6%) with HQK-1001 and 0.2% (95% CI: -0.7-1.1%) with placebo. Absolute increases in Hb F greater than 3% were noted in 9 of 38 subjects (24%) administered HQK-1001 and 1 of 38 subjects (3%) administered placebo. The mean changes in hemoglobin at Week 24 were comparable between the two groups. The mean annualized rate of pain crises was 3.5 with HQK-1001 and 1.7 with placebo. The most common adverse events in the HQK-1001 group, usually graded as mild or moderate, consisted of nausea, headache, vomiting, abdominal pain, and fatigue. Additional studies of HQK-1001 at this dose and schedule are not recommended in SCD. Intermittent HQK-1001 administration, rather than a daily regimen, may be better tolerated and more effective, as shown previously with arginine butyrate, and warrants further evaluation.

Risky behaviours of Jamaican adolescents with sickle cell disease.

OBJECTIVES: To describe the risky behaviours of Jamaican teens with sickle cell disease (SCD) and compare them to a national sample of Jamaican youth. METHODS: One hundred twenty two SCD adolescents, 15-19 years old, completed the standardized questionnaire used in the Jamaican Youth Risk and Resiliency Behaviour Survey (JYRRBS), which was a nationally representative survey of 1317 Jamaican youths. Information was obtained on socio-demographics, smoking, alcohol use, and sexual activity. Secondary data from the JYRRBS were extracted to measure the difference in risky behaviours between the groups. RESULTS: Almost 50% of SCD and 58% of national teens reported having had sexual intercourse. More SCD teens used alcohol (77.7% vs. 60.7%; P value = 0.001). Risky behaviours tended to coexist and living with a parent (odds ratio: 0.62, P value <0.01) and currently attending school (odds ratio: 0.43, P value <0.001) lowered the likelihood of having had sex. DISCUSSION: SCD teens engage in many risky behaviours and health care professionals should screen and counsel them at each visit.

Determining glomerular filtration rate in homozygous sickle cell disease: utility of serum creatinine based estimating equations.

BACKGROUND: Various estimating equations have been developed to estimate glomerular filtration rate (GFR) for use in clinical practice. However, the unique renal physiological and pathological processes that occur in sickle cell disease (SCD) may invalidate these estimates in this patient population. This study aims to compare GFR estimated using common existing GFR predictive equations to actual measured GFR in persons with homozygous SCD. If the existing equations perform poorly, we propose to develop a new estimating equation for use in persons with SCD. METHODS: 98 patients with the homozygous SS disease (55 females: 43 males; mean age 34±2.3 years) had serum measurements of creatinine, as well as had GFR measured using (99m)Tc-DTPA nuclear renal scan. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and the serum creatinine based CKD-EPI equations. The Bland-Altman limit of agreement method was used to determine agreement between measured and estimated GFR values. A SCD-specific estimating equation for GFR (JSCCS-GFR equation) was generated by means of multiple regression via backward elimination. RESULTS: The mean measured GFR±SD was 94.9±27.4 mls/min/1.73 m(2) BSA, with a range of 6.4-159.0 mls/min/1.73 m(2). The MDRD and CG equations both overestimated GFR, with the agreement worsening with higher GFR values. The serum creatinine based CKD-EPI equation performed relatively well, but with a systematic bias of about 45 mls/min. The new equation developed resulted in a better fit to our sickle cell disease data than the MDRD equation. CONCLUSION: Current estimating equations, other than the CKD-EPI equation, do not perform very accurately in persons with homozygous SS disease. A fairly accurate estimating equation, suitable for persons with GFR >60 mls/min/1.73 m(2) has been developed from our dataset and validated within a simulated dataset.

A dose-escalation phase IIa study of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell disease.

2,2-Dimethylbutyrate (HQK-1001), an orally-bioavailable promoter-targeted fetal globin gene-inducing agent, was evaluated in an open-label, randomized dose-escalation study in 52 subjects with hemoglobin SS or S/ß(0) thalassemia. HQK-1001 was administered daily for 26 weeks at 30 mg/kg (n = 15), 40 mg/kg (n = 18) and 50 mg/kg (n = 19), either alone (n = 21) or with hydroxyurea (n = 31). The most common drug-related adverse events were usually mild or moderate and reversible. Gastritis was graded as severe in three subjects at 40 mg/kg and was considered the dose-limiting toxicity. Subsequently all subjects were switched to the maximum tolerated dose of 30 mg/kg. Due to early discontinuations for blood transfusions, adverse events or non-compliance, only 25 subjects (48%) completed the study. Drug plasma concentrations were sustained above targeted levels at 30 mg/kg. Increases in fetal hemoglobin (Hb F) were observed in 42 subjects (80%), and 12 (23%) had increases ≥4%. The mean increase in Hb F was 2% [95% confidence interval (CI), 0.8-3.2%] in 21 subjects receiving HQK-1001 alone and 2.7% (95% CI, 1.7-3.8%) in 31 subjects receiving HQK-1001 plus hydroxyurea. Total hemoglobin increased by a mean of 0.65 g/dL (95% CI, 0.5-1.0 g/dL), and 13 subjects (25%) had increases ≥1 g/dL. Future studies are warranted to evaluate the therapeutic potential of HQK-1001 in sickle cell disease. .

Locus of control, depression and quality of life among persons with sickle cell disease in Jamaica.

This study explored how locus of control (LOC), depression and quality of life (QOL) interplay in patients with sickle cell disease. One hundred and forty-three sickle cell clinic patients with consecutive clinic consultations completed the Multidimensional Health Locus of Control and Short Factor 36 (SF-36) scales as well as the Beck Depression Inventory. Participants in this study had higher scores on the "chance", "other people" and "internal" domains of LOC than persons with a number of other chronic illnesses in a previous study. Hierarchical regression analyses showed that high scores on the "internal" domain of LOC were associated with better QOL and fewer symptoms of depression. Depressive symptoms were greater in persons with high scores on the "other people" LOC domain and in younger persons. These findings would suggest that it is possible that interventions which enhance internal LOC and discourage "other people" orientations might improve QOL and ameliorate depression among persons with sickle cell disease.

Excess risk of maternal death from sickle cell disease in Jamaica: 1998-2007.

BACKGROUND: Decreases in direct maternal deaths in Jamaica have been negated by growing indirect deaths. With sickle cell disease (SCD) a consistent underlying cause, we describe the epidemiology of maternal deaths in this population. METHODS: Demographic, service delivery and cause specific mortality rates were compared among women with (n = 42) and without SCD (n = 376), and between SCD women who died in 1998-2002 and 2003-7. RESULTS: Women with SCD had fewer viable pregnancies (p: 0.02) despite greater access to high risk antenatal care (p: 0.001), and more often died in an intensive care unit (p: 0.002). In the most recent period (2003-7) SCD women achieved more pregnancies (median 2 vs. 3; p: 0.009), made more antenatal visits (mean 3.3 vs. 7.3; p: 0.01) and were more often admitted antenatally (p:<0.0001). The maternal mortality ratio for SCD decedents was 7-11 times higher than the general population, with 41% of deaths attributable to their disorder. Cause specific mortality was higher for cardiovascular complications, gestational hypertension and haemorrhage. Respiratory failure was the leading immediate cause of death. CONCLUSIONS: Women with SCD experience a significant excess risk of dying in pregnancy and childbirth [MMR: (SCD) 719/100,000, (non SCD) 78/100,000]. MDG5 cannot be realised without improving care for women with SCD. Tertiary services (e.g. ventilator support) are needed at regional centres to improve outcomes in this and other high risk populations. Universal SCD screening in pregnancy in populations of African and Mediterranean descent is needed as are guidelines for managing SCD pregnancies and educating families with SCD.

Bone mineral density in Jamaican men on androgen deprivation therapy for prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) has been reported to reduce the bone mineral density (BMD) in men with prostate cancer (CaP). However, Afro-Caribbeans are under-represented in most studies. The aim was to determine the effect of androgen deprivation therapy (ADT) on the bone mineral density (BMD) of men with prostate cancer in Jamaica. METHODS: The study consisted of 346 Jamaican men, over 40 years of age: 133 ADT treated CaP cases (group 1), 43 hormone-naïve CaP controls (group 2) and 170 hormone naïve controls without CaP (group 3). Exclusion criteria included metastatic disease, bisphosphonate therapy or metabolic disease affecting BMD. BMD was measured with a calcaneal ultrasound and expressed in S.D. units relative to young adult men (T score), according to the World Health Organization definition. Patient weight, height and BMI were assessed. RESULTS: Mean ± sd, age of patients in group 1 (75± 7.4 yrs) was significantly greater than groups 2 and 3 (67 ± 8.1 yrs; 65±12.0 yrs). There was no significant difference in weight and BMI between the 3 groups. . The types of ADT (% of cases, median duration in months with IQR) included LHRH (Luteinizing hormone releasing hormone) analogues (28.6%, 17.9, IQR 20.4), oestrogens (9.8%, 60.5, IQR 45.6) anti-androgens (11.3%, 3.3, IQR 15.2) and orchiectomy (15.7%, 43.4, IQR 63.9). Unadjusted t score of group 1, mean ± sd, (-1.6± 1.5) was significantly less than group 2 (-0.9±1.1) and group 3 (-0.7±1.4), p <0.001. Ninety three (69.9%), 20 (45%) and 75 (42%) of patients in groups 1, 2 and 3 respectively were classified as either osteopenic or osteoporotic (p<0.001). Adjusting for age, there was a significant difference in t scores between groups 1 and 2 as well as between groups 1 and 3 (p<0.001). Compared with oestrogen therapy and adjusting for duration of therapy, the odds of low bone mineral density (osteopenia or osteoporosis) with LHRH analogue was 4.5 (95%CI, 14.3 to 3.4); with anti-androgens was 5.9 (95%CI, 32.7 to 5); with orchiectomy was 7.3 (95%CI, 30 to 5.8) and multiple drugs was 9.2 ((95%CI, 31 to 7.1). CONCLUSIONS: ADT is associated with lower BMD in Jamaican men on hormonal therapy for prostate cancer.

Impact of the National Health Fund policy on hormone treatment for prostate cancer in Jamaica.

OBJECTIVE: To compare the proportion of patients choosing surgical versus medical castration to treat prostate cancer, before and after the National Health Fund (NHF) of Jamaica began to subsidize hormone therapy. METHODS: A retrospective review was performed at the University Hospital of the West Indies (UHWI), Jamaica. The pathology database at UHWI was searched to identify patients who had prostate biopsies between January 2000 and December 2007. These were combined with records of biopsies at external institutions. Medical records of all patients with positive prostate biopsies were reviewed to determine if they had received androgen deprivation therapy (ADT). Patients were classified as having had surgical castration (bilateral orchiectomy) or medical castration. Chi-square statistics were used to determine the difference in proportions between those choosing medical versus surgical castration before and after March 2005, when the NHF began offering subsidies for ADT drugs. RESULTS: Of the 1,529 prostate biopsies performed during the study period, 680 (44.0%) cases of prostate cancer were diagnosed. Of these, 458 patients underwent ADT and had complete records available for analysis. The mean patient age was 72 years. During the entire study period, surgical castration was performed in 265 patients (58.0%) and medical castration in 193 (42.0%). A greater proportion of orchiectomies were performed before March 2005, rather than after (P < 0.001). Estrogens were the most common method of medical castration used before the NHF subsidy became available (62.0%); while luteinizing hormone-releasing hormone analogues (38.0%) and antiandrogens (36.5%) were most often chosen afterwards. CONCLUSIONS: Surgical castration was more common than medical castration before March 2005. After the NHF began to subsidize the cost of drugs for hormone therapy, medical castration was chosen more often. Increased access to drugs for hormone therapy has changed treatment patterns in Jamaica.