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1.
Ann Oncol ; 32(12): 1571-1581, 2021 12.
Article in English | MEDLINE | ID: mdl-34656740

ABSTRACT

BACKGROUND: Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis. PATIENTS AND METHODS: This global, phase III, open-label trial randomized (1 : 1) 5637 patients to adjuvant ET for ≥5 years ± abemaciclib for 2 years. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (≥20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. RESULTS: At the primary outcome analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P = 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR = 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR = 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile. CONCLUSION: Abemaciclib + ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.


Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Aminopyridines , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzimidazoles , Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Ki-67 Antigen , Neoplasm Recurrence, Local/drug therapy
2.
Lupus ; 25(14): 1597-1601, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27220348

ABSTRACT

INTRODUCTION: Tabalumab is a monoclonal antibody that neutralizes membrane and soluble B-cell activating factor. Two 52-week, randomized, double-blind, placebo controlled phase 3 trials evaluated the safety and efficacy of tabalumab in systemic lupus erythematosus. METHODS: Patients with moderate to severe active systemic lupus erythematosus (without severe active lupus nephritis) were randomly assigned 1:1:1 to receive tabalumab (120 mg subcutaneously every 2 or 4 weeks) or placebo for 52 weeks. Serum creatinine concentration, estimated glomerular filtration rate, urine protein/creatinine ratio, renal flares and renal adverse events were determined monthly. Data were analyzed for the intent-to-treat population and for intent-to-treat patients with baseline urine protein/creatinine ratio >20 mg/mmol (intent-to-treat plus urine protein/creatinine ratio). RESULTS: The trials enrolled 2262 patients. At baseline, demographics, systemic lupus erythematosus disease activity, serum creatinine concentration, estimated glomerular filtration rate and urine protein/creatinine ratio were similar among the treatment arms (with the exception of disease duration). In the intent-to-treat and intent-to-treat plus urine protein/creatinine ratio populations, there were no differences between the arms in the baseline-to-endpoint change in serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates. Tabalumab resulted in a significant B-cell reduction and decreased immunoglobulin G levels at both doses. CONCLUSIONS: Compared to placebo, tabalumab did not significantly affect the serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates over 1 year in intent-to-treat or intent-to-treat plus urine protein/creatinine ratio patients. There were no significant renal safety signals.ClinicalTrials.gov identifiers: NCT01205438 and NCT01196091 Lupus (2016) 25, 1597-1601.


Subject(s)
Antibodies, Monoclonal/administration & dosage , B-Lymphocytes/drug effects , Kidney/drug effects , Lupus Erythematosus, Systemic/drug therapy , Adult , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , B-Cell Activating Factor/antagonists & inhibitors , Creatinine/blood , Double-Blind Method , Drug Administration Schedule , Female , Humans , Immunoglobulin G/blood , Kidney Function Tests , Male , Middle Aged , Severity of Illness Index , Treatment Outcome , United States
3.
Pharmacopsychiatry ; 48(4-5): 164-9, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26091280

ABSTRACT

INTRODUCTION: Clozapine is the most effective treatment for treatment-resistant schizophrenia but its use is suboptimal. METHODS: Clozapine dispensing data from Queensland, Australia were extracted (2004-2013). The number of people dispensed clozapine each year and mean maintenance doses were calculated. The 18-week and 5-year cessation and treatment interruption rates were calculated using Kaplan-Meier analysis. RESULTS: Clozapine dispensings increased 36.4% (p<0.001) from 44 to 60 people per 100,000. This was estimated as 8.3% of people with schizophrenia and 33.3% of people with treatment resistant schizophrenia dispensed clozapine in 2013. Mean maintenance dose did not significantly change (364-399 mg) over 5 years of treatment. One in 7 (14.2%) people ceased within the first 3 weeks. 3-quarters (72.7%) reached maintenance therapy. The 5-year actuarial estimate of the proportion of people a) dispensed clozapine was 0.610 (S.E. 0.011) and b) with an interruption to treatment was 0.422 (S.E. 0.013). DISCUSSION: The number of patients being dispensed clozapine increased between 2004 and 2013 but clozapine is still underused. Increased use combined with continued monitoring for adverse effects will improve quality use of clozapine.


Subject(s)
Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Drug Utilization/statistics & numerical data , Schizophrenia/drug therapy , Antipsychotic Agents/administration & dosage , Clozapine/administration & dosage , Humans , Queensland
4.
Eur J Clin Nutr ; 67(9): 956-60, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23881006

ABSTRACT

BACKGROUND/OBJECTIVES: Bioelectrical impedance analysis (BIA) is used in population and clinical studies as a technique for estimating body composition. Because of significant under-representation in existing literature, we sought to develop and validate predictive equation(s) for BIA for studies in populations of African origin. SUBJECTS/METHODS: Among five cohorts of the Modeling the Epidemiologic Transition Study, height, weight, waist circumference and body composition, using isotope dilution, were measured in 362 adults, ages 25-45 with mean body mass indexes ranging from 24 to 32. BIA measures of resistance and reactance were measured using tetrapolar placement of electrodes and the same model of analyzer across sites (BIA 101Q, RJL Systems). Multiple linear regression analysis was used to develop equations for predicting fat-free mass (FFM), as measured by isotope dilution; covariates included sex, age, waist, reactance and height(2)/resistance, along with dummy variables for each site. Developed equations were then tested in a validation sample; FFM predicted by previously published equations were tested in the total sample. RESULTS: A site-combined equation and site-specific equations were developed. The mean differences between FFM (reference) and FFM predicted by the study-derived equations were between 0.4 and 0.6 kg (that is, 1% difference between the actual and predicted FFM), and the measured and predicted values were highly correlated. The site-combined equation performed slightly better than the site-specific equations and the previously published equations. CONCLUSIONS: Relatively small differences exist between BIA equations to estimate FFM, whether study-derived or published equations, although the site-combined equation performed slightly better than others. The study-derived equations provide an important tool for research in these understudied populations.


Subject(s)
Black People , Body Composition , Adult , Body Mass Index , Body Weight , Cohort Studies , Electric Impedance , Female , Ghana , Humans , Jamaica , Life Style , Linear Models , Longitudinal Studies , Male , Middle Aged , Motor Activity , Nutritional Status , Seychelles , South Africa , United States
5.
J Dev Orig Health Dis ; 4(4): 317-23, 2013 Aug.
Article in English | MEDLINE | ID: mdl-24993005

ABSTRACT

Low levels of serum adiponectin (i.e. hypoadiponectinaemia) are a marker of cardiometabolic risk in overweight children. It is not clear whether early-life factors may play a role in the development of hypoadiponectinaemia. We investigated whether antenatal factors and postnatal growth are associated with childhood adiponectin levels. This was an observational study in a birth cohort (Vulnerable Windows Cohort Study). Anthropometry was measured at birth, at 6 weeks, every 3 months up to 2 years and then every 6 months. Fasting glucose, insulin, lipids and adiponectin were measured at a mean age 11.5 years. Data on 323 children were analysed with age- and sex-adjusted multivariate analyses. The sizes of mother, placenta, fetus and newborn were not significantly associated with adiponectin levels. Current weight, body mass index (BMI), fat mass, waist circumference, glucose, insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)], triglycerides and systolic blood pressure were inversely related to adiponectin (P < 0.05). Faster growth in BMI during late infancy and childhood was associated with lower adiponectin levels (P < 0.05). After adjusting for current waist circumference, faster growth in BMI during early infancy was positively associated with adiponectin (P < 0.01). Faster growth in BMI during childhood was inversely associated (P < 0.001). These associations were similar after adjusting for HOMA-IR. We concluded that antenatal factors are not determinants of childhood adiponectin levels. Faster growth in BMI during infancy is associated with higher levels, whereas faster rates during childhood are associated with hypoadiponectinaemia. Hypoadiponectinaemia is a marker of a more adverse cardiometabolic profile in Afro-Caribbean children.

6.
J Hum Hypertens ; 26(5): 315-24, 2012 May.
Article in English | MEDLINE | ID: mdl-21593783

ABSTRACT

Habitual levels of dietary sodium and potassium are correlated with age-related increases in blood pressure (BP) and likely have a role in this phenomenon. Although extensive published evidence exists from randomized trials, relatively few large-scale community surveys with multiple 24-h urine collections have been reported. We obtained three 24-h samples from 2704 individuals from Nigeria, Jamaica and the United States to evaluate patterns of intake and within-person relationships with BP. The average (±s.d.) age and weight of the participants across all the three sites were 39.9±8.6 years and 76.1±21.2 kg, respectively, and 55% of the total participants were females. Sodium excretion increased across the East-West gradient (for example, 123.9±54.6, 134.1±48.8, 176.6±71.0 (±s.d.) mmol, Nigeria, Jamaica and US, respectively), whereas potassium was essentially unchanged (for example, 46.3±22.9, 40.7±16.1, 44.7±16.4 (±s.d.) mmol, respectively). In multivariate analyses both sodium (positively) and potassium (negatively) were strongly correlated with BP (P<0.001); quantitatively the association was stronger, and more consistent in each site individually, for potassium. The within-population day-to-day variation was also greater for sodium than for potassium. Among each population group, a significant correlation was observed between sodium and urine volume, supporting the prior finding of sodium as a determinant of fluid intake in free-living individuals. These data confirm the consistency with the possible role of dietary electrolytes as hypertension risk factors, reinforcing the relevance of potassium in these populations.


Subject(s)
Black People/statistics & numerical data , Blood Pressure , Hypertension/ethnology , Life Style/ethnology , Natriuresis , Potassium, Dietary/urine , Sodium Chloride, Dietary/urine , Adult , Black or African American/statistics & numerical data , Cultural Characteristics , Drinking/ethnology , Female , Humans , Hypertension/physiopathology , Hypertension/urine , Jamaica/epidemiology , Linear Models , Male , Middle Aged , Multivariate Analysis , Nigeria/epidemiology , Potassium, Dietary/adverse effects , Risk Assessment , Risk Factors , Sodium Chloride, Dietary/adverse effects , United States/epidemiology , Urodynamics
7.
Diabetes Obes Metab ; 13(8): 726-35, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21435142

ABSTRACT

AIM: To assess changes in insulin sensitivity in non-diabetic adults with schizophrenia or schizoaffective disorder treated with olanzapine or risperidone. METHODS: One hundred and thirty patients were randomly assigned to 12 weeks double-blind treatment with olanzapine or risperidone. Insulin sensitivity was measured using a two-step euglycaemic, hyperinsulinaemic clamp procedure. Whole-body adiposity was measured using dual-energy X-ray absorptiometry. The primary endpoint was the within-group change from baseline in insulin sensitivity normalized to fat-free mass (M(ffm) /I) during the clamp procedure's low-insulin phase, using an analysis of covariance model including the covariate weight change. RESULTS: Forty-one olanzapine-treated and 33 risperidone-treated patients completed baseline and endpoint clamp measurements. Mean M(ffm) /I during the low-insulin phase declined 9.0% (p = 0.226) in olanzapine-treated patients and 13.2% (p = 0.047) in risperidone-treated patients (between-group difference p = 0.354). During the high-insulin phase, M(ffm) /I declined 10.4% (p = 0.036) in olanzapine-treated patients and 2.1% (p = 0.698) in risperidone-treated patients (between-group difference p = 0.664). Changes in M(ffm) /I correlated inversely with changes in body weight and adiposity, which were generally higher in olanzapine-treated patients. Significant within-group increases in fasting glucose, but not haemoglobin A1c (HbA1c), were observed during olanzapine treatment. The fasting glucose change was not correlated with M(ffm) /I changes. CONCLUSIONS: Small, but statistically significant, decrements in insulin sensitivity were observed in olanzapine- and risperidone-treated patients at 1 of 2 insulin doses tested. Significant increases in fasting glucose and insulin and total fat mass were observed only in olanzapine-treated patients. Changes in insulin sensitivity correlated significantly with changes in weight or adiposity, but not with changes in glucose.


Subject(s)
Antipsychotic Agents/therapeutic use , Benzodiazepines/therapeutic use , Risperidone/therapeutic use , Schizophrenia/drug therapy , Absorptiometry, Photon , Adolescent , Adult , Aged , Antipsychotic Agents/adverse effects , Antipsychotic Agents/pharmacokinetics , Benzodiazepines/adverse effects , Benzodiazepines/pharmacokinetics , Blood Glucose/drug effects , Double-Blind Method , Female , Glucose Clamp Technique/methods , Glycated Hemoglobin , Humans , Insulin Resistance , Male , Middle Aged , Olanzapine , Risperidone/adverse effects , Risperidone/pharmacokinetics , Schizophrenia/blood , Schizophrenia/complications , Treatment Outcome , Young Adult
8.
Ann Trop Paediatr ; 31(1): 27-36, 2011.
Article in English | MEDLINE | ID: mdl-21262107

ABSTRACT

BACKGROUND: The causes of oedematous vs non-oedematous childhood malnutrition (OM vs NOM) remain elusive. It is possible that inherited differences in handling oxidant stressors are a contributing factor. AIMS: To test for associations between polymorphisms in five genes and (i) risk of OM, a case-control study, and (ii) percentage cytotoxicity in peripheral blood mononuclear cells (PBMCs) exposed to hydrogen peroxide (H(2)O(2)), an in vitro cell challenge study. METHODS: Participants had been admitted previously for treatment of OM (cases, n = 74) or NOM (controls, n = 50), or were an independent set of healthy pregnant women (n = 47) who donated peripheral blood mononuclear cells. We tested for associations between genetic variation and outcome using single markers or a bivariate score constructed by counting numbers of deleterious alleles for each of 15 possible pairs of markers. RESULTS: In the case-control study there were no significant single-marker associations with OM. We did find that higher bivariate scores were associated with OM for the pair of NAD(P)H:quinone oxidoreductase 1 and catalase (odds ratio 2·00, 95% CI 1·05-3·82). In the cell challenge experiments, there were no significant associations with percentage cytotoxicity. CONCLUSIONS: Variation in this small set of genes seems unlikely to have a large impact on either risk of OM or cytotoxicity after H(2)O(2) exposure. The use of larger sample sizes to test the effects of a much larger set of genetic variants will be required in order to determine whether genetic variation contributes to the risk of OM. Such studies have potential for improving our understanding of causal pathways in OM.


Subject(s)
Child Nutrition Disorders/enzymology , Child Nutrition Disorders/genetics , Leukocytes, Mononuclear/enzymology , Oxidative Stress , Case-Control Studies , Child , Child, Preschool , Edema/genetics , Edema/metabolism , Female , Genetic Predisposition to Disease , Genotype , Humans , Infant , Leukocytes, Mononuclear/metabolism , Pregnancy
9.
J Hum Hypertens ; 25(7): 457-64, 2011 Jul.
Article in English | MEDLINE | ID: mdl-20720573

ABSTRACT

We hypothesized that maternal size, fetal size and childhood growth are associated with childhood blood pressure, left ventricular mass (LVM) and arterial stiffness. The Vulnerable Windows Cohort is a longitudinal study of 569 mothers and their offspring. Anthropometry was measured on each child at birth, at 6 weeks, once in 3 months upto 2 years and then every 6 months. Blood pressure and body composition were assessed in 185 children (age 11.5 years) and echocardiography performed. LVM was not associated with maternal size after adjustment for child's weight. LVM was significantly associated with faster growth in childhood and with current weight, fat mass and lean mass. Systolic blood pressure was not related to maternal, fetal or newborn anthropometry, but was positively associated with infant and childhood growth, as well as current body size and fat mass. The pulse pressure/stroke volume ratio (an index of arterial stiffness) was inversely associated with maternal size, placental volume at 20 weeks, fetal size at 35 weeks and childhood growth even after adjustment for current weight. In conclusion, LVM in childhood is positively associated with maternal height, child's current size and rate of growth. Arterial stiffness is inversely related to maternal, fetal and placental size as well as growth throughout childhood.


Subject(s)
Black People , Body Size , Brachial Artery/physiology , Heart Ventricles/anatomy & histology , Adolescent , Adult , Anthropometry , Birth Weight , Blood Pressure/physiology , Child , Child Development , Cohort Studies , Echocardiography , Female , Fetal Development , Humans , Infant, Newborn , Jamaica , Longitudinal Studies , Male , Pregnancy , Prospective Studies , Stroke Volume , Young Adult
10.
Hum Genet ; 128(5): 557-61, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20839009

ABSTRACT

The relevance of loci associated with blood lipids recently identified in European populations in individuals of African ancestry is unknown. We tested association between lipid traits and 36 previously described single-nucleotide polymorphisms (SNPs) in 1,466 individuals of African ancestry from Spanish Town, Jamaica. For the same allele and effect direction as observed in individuals of European ancestry, SNPs at three loci (1p13, 2p21, and 19p13) showed statistically significant association (p < 0.05) with LDL, two loci (11q12 and 20q13) showed association with HDL cholesterol, and two loci (11q12 and 2p24) showed association with triglycerides. The most significant association was between a SNP at 1p13 and LDL cholesterol (p = 4.6 × 10(-8)). This SNP is in a linkage disequilibrium region containing four genes (CELSR2, PSRC1, MYBPHL, and SORT1) and was recently shown to relate to risk for myocardial infarction. Overall, the results of this study suggest that much of the genetic variation which influences blood lipids is shared across ethnic groups.


Subject(s)
Black People/genetics , Genetic Loci/genetics , Lipids/blood , Polymorphism, Single Nucleotide , White People/genetics , Adult , Aged , Female , Genetic Variation , Genome-Wide Association Study , Humans , Jamaica/ethnology , Male , Middle Aged , Sequence Analysis, DNA
11.
Eur J Clin Nutr ; 64(10): 1093-100, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20717127

ABSTRACT

BACKGROUND/OBJECTIVES: We hypothesized that maternal size during pregnancy and birth size are determinants of childhood physical activity energy expenditure (PAEE). Also, childhood PAEE is inversely related to adiposity and levels of cardiovascular risk factors. SUBJECTS/METHODS: The Vulnerable Windows Cohort Study is a longitudinal observational study of 569 Afro-Jamaican mothers recruited from the first trimester and their offspring. Anthropometry, bioelectrical impedance, PAEE (using the Actical monitor) and cardiovascular risk factors (blood pressure, fasting glucose, insulin and lipids) were measured in 124 boys and 160 girls at a mean age of 13.2 years. RESULTS: Boys had more fat-free mass (FFM) and expended more energy than girls (12.3±3.3 vs 9.6±2.8 kcal/kg/day; P<0.001). Maternal weight was associated with child's PAEE (r=0.29; P<0.001). PAEE was not significantly associated with birth weight. Maternal weight, after adjusting for child's age and sex, was positively associated with the child's FFM, fat mass and %fat (P-values 0.01). Age- and sex-adjusted PAEE was positively associated with FFM, fat mass and % fat (P-values <0.001), but not after adjusting for current weight. Age- and sex-adjusted PAEE was positively associated with triglycerides, insulin and systolic blood pressure (P-values <0.05), but not after adjusting for weight and height. PAEE was associated with fasting glucose after controlling for age, sex, weight and height (r=-0.12; P=0.02). CONCLUSIONS: Maternal size, but not birth weight, is a determinant of childhood PAEE. PAEE is not strongly associated with childhood body composition, but is inversely related to fasting glucose concentration.


Subject(s)
Energy Metabolism/physiology , Motor Activity/physiology , Overweight/epidemiology , Adiposity , Adolescent , Adult , Black People , Blood Glucose/analysis , Body Mass Index , Cardiovascular Diseases/epidemiology , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Jamaica/epidemiology , Longitudinal Studies , Male , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Metabolic Syndrome/prevention & control , Monitoring, Ambulatory , Overweight/blood , Overweight/prevention & control , Pregnancy , Risk Factors , Sex Characteristics , Young Adult
12.
West Indian Med J ; 59(3): 265-73, 2010 Jun.
Article in English | MEDLINE | ID: mdl-21291104

ABSTRACT

OBJECTIVE: To estimate the prevalence of the metabolic syndrome in Jamaican adults and to evaluate its association with socio-economic status (SES). METHODS: A cross-sectional analysis was performed using data from a cohort study of persons, 25-74 years old, living in St Catherine, Jamaica, and who were evaluated between 1993 and 2001. Participants completed an interviewer administered questionnaire and had blood pressure and anthropometric measurements performed by trained observers. Venous blood was collected for measurement of fasting glucose and lipids. The metabolic syndrome was defined using the International Diabetes Federation (IDF) and American Heart Association/National Heart Lung and Blood Institute (AHA/NHLBI) criteria. Income and education were used as markers of SES. RESULTS: Data from 1870 participants (717 males 1153 females) were analysed. Prevalence of the metabolic syndrome was 21.1% (95% CI 19.2, 22.9%) using IDF criteria and 18.4% (95% CI 16.6, 20.2%) using the AHA/NHLBI criteria. Prevalence was higher among females (27.6% [IDF], 23.0% [AHA]) compared to males (10.6% [IDF], 11.0% [AHA]). The prevalence of the metabolic syndrome increased with age. Compared to males with primary/lower education, those with secondary and tertiary education had higher odds of having the metabolic syndrome after adjusting for age; odds ratio 3.12 (1.54, 6.34) and 2.61 (1.33, 5.11) respectively. High income was also associated with increased odds of having the metabolic syndrome among males, OR = 6.0 (2.22, 16.19) adjusting for age-group. There were no significant associations among women. CONCLUSION: The metabolic syndrome is common in Jamaica. Clinicians should look for this syndrome in their patients and take steps to treat the abnormalities identified.


Subject(s)
Metabolic Syndrome/epidemiology , Adult , Cross-Sectional Studies , Educational Status , Female , Humans , Income , Jamaica/epidemiology , Logistic Models , Male , Prevalence , Socioeconomic Factors
13.
West Indian Med J ; 59(5): 486-93, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21473394

ABSTRACT

OBJECTIVES: To estimate the incidence of hypertension in people with and without prehypertension and determine the factors that predict progression to hypertension. METHODS: Data from a cohort of 25-74-year-old residents of Spanish Town, Jamaica, were analysed. All participants completed a structured questionnaire and had blood pressure (BP), anthropometric measurements and venous blood sampling performed by trained personnel. Blood Pressure was classified using the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-7) criteria. RESULTS: 708 persons who had the required data and were not hypertensive at baseline were included in this analysis. Mean follow-up time was 4.1 years; 28.7% of prehypertensive participants developed hypertension compared to 6.2% of normotensive participants. The unadjusted incidence rate ratio (IRR [95% CI]) for progression among prehypertensive compared to normotensive participants was 4.62 [2.96, 7.43]. Among males, the rate of progression to hypertension was significantly higher for those 45-64 years old and those who were current smokers. Among females, progression was higher for age groups 25-44 years, 45-64 years, those who were overweight (BMI > or =25), obese (BMI > or =30) and current smokers. In multivariate models, prehypertension, female gender overweight status and older age remained significantly associated with progression to hypertension among the combined prehypertensive and normotensive groups. IRR [95% CI] were: prehypertension, 3.45 [2.18-5.45]; female gender 1.81 [1.12, 2.94]; overweight, 1.87 [1.15, 2.94]; age 45-64 years, 1.73 [1.08, 2.76]; age > 65 years 2.39 [1.31, 4.34]. CONCLUSIONS: Prehypertension is associated with a three-fold increase in the incidence of hypertension. Higher BMI, age and female gender also independently predict the development of hypertension.


Subject(s)
Hypertension/epidemiology , Prehypertension/epidemiology , Adult , Aged , Cohort Studies , Disease Progression , Female , Humans , Hypertension/physiopathology , Incidence , Jamaica/epidemiology , Male , Middle Aged , Prehypertension/physiopathology , Risk Factors
14.
Purinergic Signal ; 4(2): 93-100, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18368517

ABSTRACT

An account is given of how a sensitive bioassay system for measurement of the neurotransmitter acetylcholine serendipitously led to the identification of adenosine triphosphate (ATP) released in vitro from active skeletal muscle. Subsequent application of the identification procedures to exercising human muscle in vivo, cardiac muscle cells in vitro, and human erythrocytes exposed to hypoxia gave rise to the general concept of ATP as a molecule that could influence cell function from the extracellular direction. Mechanisms of ATP release from cells in terms of "trigger" events such as mechanical distortion of the membrane, depolarization of the membrane, and exposure to hypoxia are discussed. Potential therapeutic uses of extracellular ATP in cancer therapy, radiation therapy, and a possible influence upon aging are discussed. Possible roles (distant and local) of extracellular ATP released from muscle during whole body exercise are discussed.

15.
Heart ; 94(9): 1171-4, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18070950

ABSTRACT

OBJECTIVES: A gradient of increased vascular risk with migration exists across the African diaspora. We investigated the hypothesis that differences in homocysteine/folic acid status contribute to this increased risk. DESIGN: Community cohort study of 73 Afro-Caribbeans in the United Kingdom and 151 matched Afro-Caribbeans in Jamaica with no conventional vascular risk factors. METHODS: Subjects were compared for baseline characteristics, vascular risk profile, homocysteine (tHcy), folate and B(12) concentrations. Endothelium-dependent vasodilatation was assessed by measuring the absolute change from baseline in the reflection index (RI) of the digital volume pulse during intravenous infusion of albuterol (5 microg/min, Delta RI(ALB)) and glyceryltrinitrate (GTN) (5 microg/min, Delta RI(GTN)). Carotid intima media thickness (CIMT) was measured ultrasonographically in the distal 1 cm of the common carotid artery. RESULTS: UK Afro-Caribbeans had higher tHcy (mean difference 2.3 (95% confidence interval 1.3 to 3.4) micromol/l) and lower folate (mean difference 3.2 (95% CI 1.8 to 4.7) microg/l) levels. Delta RI(ALB) was 5.1 (95% CI 2.5 to 7.6) percentage points lower and CIMT 0.124 (95% CI 0.075 to 0.173) mm greater in UK Afro-Caribbeans. Higher tHcy and lower folate concentrations correlated with impaired Delta RI(ALB) and increased CIMT. A 1 microg/l increase in folate concentration was associated with 0.3 (95% CI 0.1 to 0.5) percentage point increase in Delta RI(ALB) and 0.002 (95% CI 0.001 to 0.006) mm decrease in CIMT, independent of blood pressure, smoking and vascular risk profile. CONCLUSIONS: Lower folate concentrations in UK compared with West Indian African-Caribbeans may contribute to the higher stroke risk seen in UK African-Caribbean people.


Subject(s)
Black People , Homocysteine/blood , Vascular Diseases/ethnology , Adult , Biomarkers/blood , Cross-Sectional Studies , Emigration and Immigration , Female , Folic Acid/blood , Humans , Jamaica/ethnology , Male , Middle Aged , Plethysmography , Risk Factors , Statistics, Nonparametric , United Kingdom , Vascular Diseases/metabolism , Vascular Diseases/physiopathology
16.
West Indian Med J ; 57(4): 383-92, 2008 Sep.
Article in English | MEDLINE | ID: mdl-19566021

ABSTRACT

OBJECTIVE: Non-communicable Diseases (NCDs) are leading threats to health and well-being in the Caribbean. A study was undertaken in the latter part of 2005 to compute the economic burden of diabetes mellitus and hypertension within the Caribbean Community and Common Market (CARICOM). This report critiques the quality and availability of health information which can be used to facilitate cost burden analysis of diabetes mellitus and hypertension. METHODS: A form was developed and disseminated to obtain epidemiological and health service utilization data. Subsequent visits were made to seven CARICOM member countries to collect the data. RESULTS: The results revealed (i) a number of deficiencies in the reliability and validity of the data received, in particular, those needed to facilitate the analysis of cost-specific complications such as ischaemic heart disease, cerebrovascular disease, chronic renal failure, hypertensive and diabetic retinopathy and peripheral circulatory complications; (ii) data management systems in hospitals were not linked to facilitate generation of cost-effectiveness estimates and other information required to compare options for health investment; (iii) despite repeated attempts by regional governments to develop/strengthen Health Information Systems within the Caribbean, sustainability has been significantly hampered by human, material and financial resource constraints and ongoing monitoring and evaluation is generally poor. CONCLUSION: There are deficiencies in the quality and availability of health information to facilitate cost burden analysis of hypertension and diabetes mellitus in the Caribbean Strong commitment from CARICOM governments will be necessary to address these concerns if economic evaluations are to be undertaken more frequently as part of the effort to reduce the morbidity and mortality from these diseases.


Subject(s)
Diabetes Mellitus/economics , Health Care Costs , Hypertension/economics , Patient Education as Topic , Quality of Health Care , Access to Information , Caribbean Region/epidemiology , Cost-Benefit Analysis , Decision Support Systems, Clinical/economics , Decision Support Systems, Clinical/organization & administration , Decision Support Systems, Clinical/standards , Diabetes Mellitus/epidemiology , Hospital Information Systems/economics , Hospital Information Systems/organization & administration , Hospital Information Systems/standards , Humans , Hypertension/epidemiology , Prevalence , Reproducibility of Results
17.
West Indian med. j ; 56(5): 398-403, Oct. 2007. tab, graf
Article in English | LILACS | ID: lil-491691

ABSTRACT

OBJECTIVE: Populations in developing countries are particularly vulnerable to the development of obesity in the period of rapid transition to a more modernized lifestyle. We sought to determine the relationship between activity energy expenditure (AEE), adiposity and weight change in an adult population undergoing rapid socio-economic transition. METHODS: Total daily energy expenditure (TDEE) was measured using the doubly labelled water method, resting energy expenditure (REE) using indirect calorimetry and AEE calculated as the difference between TDEE and REE, in adults from a working class community in Spanish Town, Jamaica. During six years of follow-up, weight was measured between one and four times. Mixed effects regression modelling was used to test for association between components of the energy budget and weight change. RESULTS: Men (n = 17) weighed more but women (n = 18), had significantly more body fat, 38.5% vs 24.5%, respectively (p < 0.01). Men had higher levels of EE, particularly AEE after adjustment for body weight, 66.3 versus 46.4 kJ/kg.d for men and women, respectively (p < 0.001). At baseline, adjusted AEE was inversely associated with body fat in men and women, r = -0.46 and r = -0.48, respectively (p < 0.05). Mean rate of weight change was + 1.1 and + 1.2 kg/year for men and women, respectively. No component of EE, ie TDEE, REE or AEE, significantly predicted weight change in this small sample. CONCLUSIONS: These results suggest an important role for AEE in maintaining low levels of adiposity. The lack of association between EE and weight change, however, suggests populations in transition are at risk of obesity from environmental factors (eg dietary) other than simply declining physical activity levels.


OBJETIVO: Las poblaciones en los países en vía de desarrollo son particularmente vulnerables al desarrollo de la obesidad en el período de rápida transición a un estilo de vida más moderno. Buscamos determinar la relación entre el gasto energético por actividad (GEA), la adiposidad y el cambio de peso en una población adulta en proceso de rápida transición socio-económica. MÉTODOS: El gasto energético total diario (GETD) fue medido usando el método del agua doblemente marcada, gasto energético en reposo (GER) usando calorimetría indirecta y el GEA calculado como la diferencia entre GETD y GER, en adultos de una comunidad de clase obrera en Spanish Town, Jamaica. Durante seis años de seguimiento, el peso fue medido entre una y cuatro veces. Un modelo de regresión de efectos mixtos fue usado para probar la asociaciF3n entre los componentes del presupuesto de la energEDa y el cambio de peso. RESULTADOS: Los hombres (n = 17) pesaron más pero las mujeres (n = 18) teníEDan significativamente más grasa corporal, 38.5% frente a 24.5%, respectivamente (p < 0.01). Los hombres tenían niveles más altos de GE, particularmente GEA después del ajuste por peso corporal, 66.3 frente a 46.4 kJ/kg.d para los hombres y mujeres, respectivamente (p < 0.001). Al inicio, el GEA ajustado estaba inversamente asociado con la grasa del cuerpo en los hombres y mujeres, r = -0.46 y r = -0.48, respectivamente (p < 0.05). La tasa media de cambio de peso fue +1.1 y +1.2 kg/ano para los hombres y mujeres, respectivamente. Ningún componente de GE, es decir, GETD, GER o GEA, predijo significativamente el cambio de peso en esta muestra pequeña. CONCLUSIONES: Estos resultados sugieren un papel importante del GEA en cuanto a mantener niveles bajos de adiposidad. Sin embargo, la falta de asociación entre GE y cambio de peso, sugiere que las poblaciones en transición corren el riesgo de obesidad debido a factores ambientales (p.ej. dietéticos) distintos de la mera...


Subject(s)
Humans , Male , Female , Adult , Adiposity , Weight Gain , Obesity/epidemiology , Weight Loss , Motor Activity , Calorimetry , Nutritional Status , Sex Factors , Risk Factors , Jamaica/epidemiology , Environment , Pilot Projects , Body Mass Index
18.
Public Health Nutr ; 10(2): 122-30, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17261220

ABSTRACT

OBJECTIVES: To determine the relationship of diet to overweight and obesity among populations of African origin. DESIGN AND SETTING: Cross-sectional data were obtained from adults aged 25-74 years in rural Cameroon (n = 686), urban Cameroon (n = 975), Jamaica (n = 924) and Afro-Caribbeans in the UK (n = 257). Dietary data were collected using food-frequency questionnaires specifically designed for each site. Body mass index (BMI) was used as a measure of overweight. RESULTS: The expected gradient in the distribution of overweight across sites was seen in females (rural Cameroon, 9.5%; urban Cameroon, 47.1%; Jamaica, 63.8%; UK, 71.6%); however, among males overweight was less prevalent in Jamaica (22.0%) than urban Cameroon (36.3%). In developing countries increased risks of overweight (BMI > or = 25 kg m(-2) were influenced by higher energy (urban Cameroonian men) and protein (Jamaican women) intakes. No dietary variables were associated with obesity (BMI > or = 30 kg m(-2) in Cameroon or Jamaica. In the UK, energy intakes were inversely related with overweight whereas increased risks of being overweight were associated with higher protein (men) and fat (women) intakes. Similarly, whereas higher protein and fat intakes in UK men and women were associated with obesity, carbohydrate intakes were associated with decreased risks of obesity in men. CONCLUSIONS: Diet and overweight were associated in the UK but few dietary variables were related to overweight in Jamaica and the Cameroon. These findings suggest that associations between diet and overweight/obesity are not generalisable among populations.


Subject(s)
Diet , Energy Intake/physiology , Obesity/ethnology , Obesity/epidemiology , Adult , Africa/ethnology , Aged , Body Mass Index , Cameroon/epidemiology , Cross-Sectional Studies , Diet Surveys , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Female , Health Surveys , Humans , Jamaica/epidemiology , Male , Middle Aged , Sex Factors , Surveys and Questionnaires , United Kingdom/epidemiology
19.
West Indian Med J ; 56(5): 398-403, 2007 Oct.
Article in English | MEDLINE | ID: mdl-18303750

ABSTRACT

OBJECTIVE: Populations in developing countries are particularly vulnerable to the development of obesity in the period of rapid transition to a more modernized lifestyle. We sought to determine the relationship between activity energy expenditure (AEE), adiposity and weight change in an adult population undergoing rapid socio-economic transition. METHODS: Total daily energy expenditure (TDEE) was measured using the doubly labelled water method, resting energy expenditure (REE) using indirect calorimetry and AEE calculated as the difference between TDEE and REE, in adults from a working class community in Spanish Town, Jamaica. During six years of follow-up, weight was measured between one and four times. Mixed effects regression modelling was used to test for association between components of the energy budget and weight change. RESULTS: Men (n = 17) weighed more but women (n = 18), had significantly more body fat, 38.5% vs 24.5%, respectively (p < 0.01). Men had higher levels of EE, particularly AEE after adjustment for body weight, 66.3 versus 46.4 kJ/kg.d for men and women, respectively (p < 0.001). At baseline, adjusted AEE was inversely associated with body fat in men and women, r = -0.46 and r = -0.48, respectively (p < 0.05). Mean rate of weight change was + 1.1 and + 1.2 kg/year for men and women, respectively. No component of EE, ie TDEE, REE or AEE, significantly predicted weight change in this small sample. CONCLUSIONS: These results suggest an important role for AEE in maintaining low levels of adiposity. The lack of association between EE and weight change, however, suggests populations in transition are at risk of obesity from environmental factors (eg dietary) other than simply declining physical activity levels.


Subject(s)
Adiposity , Obesity/epidemiology , Weight Gain , Weight Loss , Adult , Body Mass Index , Calorimetry , Environment , Female , Humans , Jamaica/epidemiology , Male , Motor Activity , Nutritional Status , Pilot Projects , Risk Factors , Sex Factors
20.
West Indian Med J ; 55(3): 142-7, 2006 Jun.
Article in English | MEDLINE | ID: mdl-17087096

ABSTRACT

BACKGROUND: Asthma causes significant morbidity and mortality in the developing world. It is thus important to identify modifiable risk factors. OBJECTIVES: To undertake a cross-sectional study to determine the prevalence of skin test reactivity to aeroallergens in Jamaican children and adults and the relationship of the diagnosis of asthma to the pattern of skin test positivity. METHODS: One hundred and sixty subjects without the sickle cell gene (genotype AA), eighty adults and eighty children, were recruited. Skin testing to seven aeroallergens was undertaken (atopy being diagnosed if there were at least one positive reaction). Asthma status was determined by a questionnaire and/or medical records. RESULTS: Twenty-seven (34%) of the children and forty-one (51%) of the adults were skin test positive to at least one aeroallergen. The most common positive responses in both age groups were to Dermatophagoides farinae, Dermatophagoides pteronyssinus and cockroach mix-(German and American). All adult asthmatics with current symptoms reacted to cockroach allergen. CONCLUSIONS: Appropriate steps to reduce cockroaches and cockroach sensitization might positively impact on asthma morbidity in Jamaica.


Subject(s)
Allergens , Asthma/immunology , Hypersensitivity, Immediate/immunology , Skin Tests , Adolescent , Adult , Animals , Antigens, Dermatophagoides , Asthma/diagnosis , Asthma/physiopathology , Child , Cockroaches , Cross-Sectional Studies , Dermatophagoides farinae , Dermatophagoides pteronyssinus , Dust , Female , Humans , Hypersensitivity, Immediate/physiopathology , Jamaica , Male , Mites , Prevalence , Rhinitis , Surveys and Questionnaires
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