Pregnancy outcome in homozygous sickle cell disease: observations from the Jamaican Birth Cohort.

OBJECTIVE: To document pregnancy outcome in homozygous sickle cell (SS) disease and in age-matched controls with a normal haemoglobin genotype followed from birth for up to 45 years. METHODS: A total of 100 000 consecutive non-operative deliveries screened for sickle cell disease at the main Government maternity hospital in Kingston, Jamaica between 1973 and 1981 detected 311 (149 female) babies with SS disease who were matched by age and gender with 250 (129 female) controls with an AA haemoglobin phenotype. These individuals have been followed from birth with prospective assessment of menarche and detailed documentation of all pregnancies. RESULTS: There were 177 pregnancies in 71 SS patients and 226 pregnancies in 74 AA controls. Mothers with SS disease had more spontaneous abortions (adjusted relative risk [aRR] 3.2, 95% CI 1.6-6.1), fewer live births (aRR 0.7, 95% CI 0.6-0.9) and their offspring were more likely to have a gestational age <37 weeks (aRR 2.1, 95% CI 1.1-3.7) and low birthweight <2.5 kg (aRR 3.0, 95% CI 1.6-5.3). They were more prone to acute chest syndrome (aRR 13.7, 95% CI 4.1-45.5), urinary tract infection (aRR 12.8, 95% CI 1.3-125.9), pre-eclampsia/eclampsia (aRR 3.1, 95% CI 1.1-8.8), retained placenta (aRR 10.1, 95% CI 1.1-90.3), sepsis (Fisher's Exact test 0.04) and pregnancy-related deaths (Fisher's Exact test 0.02). Four of five deaths were attributable to acute chest syndrome. There was no genotypic difference in pregnancy-induced hypertension or postpartum haemorrhage. CONCLUSION: Pregnancy in SS disease carries risks for both mother and child. The variable characteristics of pregnancy-related deaths complicate their prevention. TWEETABLE ABSTRACT: Pregnancy in SS disease compared with controls showed increased abortions and stillbirths, fewer live births and maternal deaths in 7% patients.

Foot ulceration and its association with mortality in diabetes mellitus: a meta-analysis.

BACKGROUND: Diabetic foot ulcers portend an almost twofold increase in all-cause mortality compared with diabetes on its own. AIM: To investigate the association between diabetic foot ulcers and risk of death. METHODS: We performed a meta-analysis of all observational studies investigating the association between diabetic foot ulcers and all-cause mortality. Risk ratios and risk differences were pooled in a random-effects model. The I2 statistic was used to quantify heterogeneity between studies. RESULTS: Altogether, we identified 11 studies that reported 84 131 deaths from any cause in 446 916 participants with diabetes during a total of 643 499 person-years of follow-up. The crude event rate for all-cause mortality in individuals with diabetes who did not develop foot ulceration was 22% lower at 181.5 deaths (per 1000 person-years) than in those who developed foot ulcers (230.8 per 1000 person-years). Diabetic foot ulceration was associated with an increased risk of all-cause mortality (pooled relative risk 2.45, 95% CI 1.85-2.85). We did not observe any tangible differences in risk of all-cause mortality from diagnosis in studies reporting a mean duration of follow-up of ≤3 years (relative risk 2.43, 95% CI 2.27-2.61) or >3 years (relative risk 2.26, 95% CI 2.13-2.40) years. Funnel plot inspection revealed no significant publication bias among studies included in this meta-analysis. CONCLUSIONS: Our study shows an excess rate of all-cause mortality in people with diabetic foot ulceration when compared to those without foot ulceration. It is imperative that early interventions to prevent foot ulceration and modify cardiovascular disease risk factors are put in place to reduce excess mortality.

The spectrum of neuropsychiatric lupus in a Black Caribbean population: a report of the Barbados National Lupus Registry.

Objective The objective of this study was to examine neuropsychiatric lupus in a Black Caribbean population. Methods We reviewed Barbados National Lupus Registry patients with ≥4 American College of Rheumatology criteria and a diagnosis of neuropsychiatric lupus using the American College of Rheumatology 19 case definitions. Results From 366 patients with four or more American College of Rheumatology criteria for systemic lupus erythematosus, 55 (15%) had evidence of neuropsychiatric lupus. There were 51 females and four males (F:M = 13:1) with a median age of 31 years. A total of 76.4% had a single neuropsychiatric lupus complication and 23.6% had two or three complications occurring sequentially or concurrently. The top three complications were psychosis - 49.1% (95% CI 35.8, 62.5); ischaemic stroke - 32.7% (21.4, 46.5); and generalized tonic-clonic seizures - 12.7% (6.0, 24.8). Twelve of the American College of Rheumatology 19 neuropsychiatric syndromes were represented: 91.2% central; 8.8% peripheral. There were 521 observation years, and for 32 patients (58%) neuropsychiatric lupus was a presenting feature. For the remaining 23 (42%) the first neuropsychiatric lupus event came after systemic lupus erythematosus diagnosis - median time of two years. Of the 22 deaths, systemic lupus erythematosus nephritis caused almost half (45.5%) at a median age of 32. The prevalence of nephritis was lower in the neuropsychiatric lupus subgroup (25.5%) compared with the Barbados National Lupus Registry data (47%) ( P = 0.01). Ischaemic stroke caused 22.7% of deaths at a median age of 46 and was the main cause of chronic neurologic deficits amongst survivors. Conclusion Neuropsychiatric lupus was an early cause of morbidity in systemic lupus erythematosus with predominantly singular central nervous system complications, the most common of which was psychosis. Most deaths occurred at a young age, principally from systemic lupus erythematosus nephritis. Ischaemic stroke was the main neurologic cause of death and disability.

Systems Science for Caribbean Health: the development and piloting of a model for guiding policy on diabetes in the Caribbean.

BACKGROUND: Diabetes is highly prevalent in the Caribbean, associated with a high morbidity and mortality and is a recognised threat to economic and social development. Heads of Government in the Caribbean Community came together in 2007 and declared their commitment to reducing the burden of non-communicable diseases (NCDs), including diabetes, by calling for a multi-sectoral, systemic response. To facilitate the development of effective policies, policymakers are being engaged in the development and use of a system dynamics (SD) model of diabetes for Caribbean countries. METHODS: Previous work on a diabetes SD model from the United States of America (USA) is being adapted to a local context for three countries in the region using input from stakeholders, a review of existing qualitative and quantitative data, and collection of new qualitative data. Three country models will be developed using one-on-one stakeholder engagement and iterative revision. An inter-country model will also be developed following a model-building workshop. Models will be compared to each other and to the USA model. The inter-country model will be used to simulate policies identified as priorities by stakeholders and to develop targets for prevention and control. The model and model-building process will be evaluated by stakeholders and a manual developed for use in other high-burden developing regions. DISCUSSION: SD has been applied with success for health policy development in high-income country settings. The utility of SD in developing countries as an aid to policy decision-making related to NCDs has not been tested. This study represents the first of its kind.

A checklist that enhances the provision of education during insulin initiation simulation: a randomized controlled trial.

AIM: The study tested the hypothesis that doctors using an insulin information checklist during simulated insulin initiation would impart more information regarding insulin use. METHODS: A total of 128 simulations were conducted. Doctors (n = 64) were recruited from practitioners recently completing internship (n = 19) and those established in primary care (n = 45). Both groups of doctors were strata randomized to control (n = 32) and intervention groups (n = 32), so that each group contained equal numbers. Doctors in each group experienced two identical simulations of insulin initiation with an intervening period of 10 min. Doctors in the intervention arm were introduced to an insulin initiation checklist, which they reviewed independently and utilized in the second simulation. Trained assessors captured the provision of education in 21 predefined educational areas. Differences in the change of the total education provided between the first and second simulations were assessed using linear regression. RESULTS: The difference in the mean change of education provided between the first and second simulations within the 21 educational areas for the control and treatment groups was 9.7 [95% confidence interval (CI): 8.8-11.1, P < 0.001] - an increase of 46.2%. The difference for the 15 areas relevant to pen use was 7.3 (95% CI: 6.2-8.4, P < 0.001) - an increase of 51.6%. CONCLUSIONS: The checklist resulted in doctors providing significantly more education applicable to syringe and insulin pen routes of insulin administration during simulations. Further research is needed on the checklist's impact on healthcare professionals and patient outcomes in the clinical context. (Clinical Trials Registry No: NCT02266303).

Priapism in Homozygous Sickle Cell Disease: A 40-year Study of the Natural History.

OBJECTIVES: To describe the incidence, pattern, and outcome of priapism in homozygous sickle cell (SS) disease. METHODS: Regular review, for periods up to 40 years, was done of all 162 males with SS disease detected during the screening of 100 000 consecutive non-operative deliveries at the main government maternity hospital in Kingston, Jamaica, between June 1973 and December 1981. RESULTS: Priapism occurred in 52 (32.7%) patients overall, the incidence rising steeply in late adolescence to 32% by age 20 years and a cumulative incidence of nearly 60% of patients by age 40 years. Many cases were elicited only on direct questioning because of embarrassment and the lack of realization that priapism complicates SS disease. Initial events were recurrent stuttering episodes in 39 patients, a single short-term event in six patients and a major attack (more than six hours) in seven patients. Erectile function was preserved in almost all patients with simple stuttering or single events. Major attacks (> 6 hours) occurred in 17 patients, preceded by stuttering episodes in nine, by a single event in one, and occurring de novo in seven. In these, erectile function was unknown in five, deemed satisfactory in five (sometimes improving over three years), weak in three and impotence persisted in four (two with major attacks three and six months previously). CONCLUSION: A history of stuttering priapism should be routinely enquired and prophylactic measures used if attacks exceed once weekly. Major events generally result in short-term impotence, but the late recovery of erectile function cautions against the early insertion of penile prostheses.

The Chhattisgarh state screening programme for the sickle cell gene: a cost-effective approach to a public health problem.

In India, the Chhattisgarh State screening programme for sickle haemoglobin focuses on children aged 3-15 years and has screened over 1,050,440 subjects over the last 6 years. Commencing in the District around the capital Raipur, this programme has now completed screening in 7 of the 27 Districts of Chhattisgarh State. Screening is initially performed by solubility tests on fingerprick samples in the field and those with positive tests have venipunctures for haemoglobin electrophoresis. The frequency of the sickle cell trait was 9.64 % and of the SS phenotype 0.29 % with only two Districts in Hardy-Weinberg equilibrium, most Districts showing an excess of the SS 'phenotype' most readily explained by symptomatic selection. The estimated costs were US$0.28 (solubility tests alone) and US$0.60 (haemoglobin electrophoresis). Of the social groupings commonly used in India, the OBC's (other backward classes) had the highest frequencies of the sickle cell gene mutations, followed by the Scheduled Tribes and the Scheduled Castes. The objectives of the programme were the detection of sickle cell disease for prospective clinical management and of the sickle cell trait for purposes of genetic counselling. The former objective is being met for diagnosis although the success of referral to clinic services requires audit. The objective of genetic counselling is compromised by the failure of the screening test to detect other genes of potential clinical significance such as HbD Punjab and the beta thalassaemia trait. Despite these exceptions, the detection of HbS appears relatively robust and could be another condition factored into the traditions of partner selection amongst the underprivileged communities of this state. Overall, the Chhattisgarh programme seeks to address the daunting challenges of large populations carrying the sickle cell gene and maybe a useful model for elsewhere.

Newborn Screening for Sickle Cell Disease: Jamaican Experience.

OBJECTIVES: To review the history of newborn screening for sickle cell disease with especial reference to Jamaica. METHODS: A summary was done of the history, the development of associated laboratory technology and the implementation of newborn screening for sickle cell disease in Jamaica. RESULTS: Screening was initiated at Victoria Jubilee Hospital, Kingston from 1973-1981, reactivated in 1995 and extended to the University Hospital of the West Indies in 1997 and to Spanish Town Hospital in 1998. From August 2008, there was a progressive recruitment of 12 hospitals in the south and west of Jamaica which has raised the frequency of islandwide newborn coverage from 25% in 1973 to 81%. The results of this extended programme in southwest Jamaica are presented. Dried blood spots collected from the umbilical cord proved stable, cheap and efficient; mean sample collection rates were 98%, maternal contamination occurred in < 1% and caused diagnostic confusion in < 0.1%. By March 31, 2015, a total of 54 566 births have been screened, detecting 161 with homozygous sickle cell (SS) disease, 125 with sickle cell-haemoglobin C (SC) disease and 36 with sickle cell-beta thalassaemia. Of the 327 babies with clinically significant sickle cell syndromes, all except five who died within seven days of birth were confirmed by four to six weeks and recruited to local sickle cell clinics. CONCLUSION: Early detection of sickle cell disease and recruitment to clinics is known to reduce its morbidity and mortality. The methods currently detailed provide an effective and economic model of newborn screening which may be of value elsewhere.

The social determinants of diabetes and cardiovascular disease risk factors in Barbados: findings from the health of the nation study

OBJECTIVE: To describe the distribution of diabetes, hypertension and related behavioural and biological risk factors in adults in Barbados by sex, education and occupation. DESIGN AND METHODS: Multistage probability sampling was used to select a representative sample of the adult population (> 25 years). Participants were interviewed using standard questionnaires, underwent anthropometric and blood pressure measurements, and provided fasting blood for glucose and cholesterol measurements. Standard WHO Definitions were used. Data were weighted for sampling and non-response and age-adjusted for group comparisons. RESULTS: Study participation rate was 55%, with 764 women, 470 men. Prevalence of obesity was 33.8%, hypertension 40.6%, and diabetes 17.9%. Compared with women, men were less likely to be obese (prevalence ratio 0.53; 95%CI 0.42–0.67), diabetic (0.77; 0.61–0.98), or physically inactive (0.47; 0.39–0.57), but more likely to smoke tobacco (4.08; 2.48–6.69) and binge drink alcohol (4.53; 2.70–7.58). In women, higher educational level was significantly related to higher fruit and vegetable intake, more physical activity, less diabetes and less hypercholesterolaemia (p values: 0.01 – 0.04). In men, higher education was significantly related only to less smoking. Differences by occupational category were limited to smoking in men and hypercholesterolaemia in women. CONCLUSIONS: In this population, unlike in most high-income countries, sex appears to be a much stronger determinant of behavioural risk factors, and consequent obesity and diabetes, than education or occupation. These findings have major implications for meeting the commitments made in the 2011 Rio Political Declaration, to reduce health inequities.

Global estimates of diabetes prevalence for 2013 and projections for 2035.

INTRODUCTION: Diabetes is a serious and increasing global health burden and estimates of prevalence are essential for appropriate allocation of resources and monitoring of trends. METHODS: We conducted a literature search of studies reporting the age-specific prevalence for diabetes and used the Analytic Hierarchy Process to systematically select studies to generate estimates for 219 countries and territories. Estimates for countries without available source data were modelled from pooled estimates of countries that were similar in regard to geography, ethnicity, and economic development. Logistic regression was applied to generate smoothed age-specific prevalence estimates for adults 20-79 years which were then applied to population estimates for 2013 and 2035. RESULTS: A total of 744 data sources were considered and 174 included, representing 130 countries. In 2013, 382 million people had diabetes; this number is expected to rise to 592 million by 2035. Most people with diabetes live in low- and middle-income countries and these will experience the greatest increase in cases of diabetes over the next 22 years. CONCLUSION: The new estimates of diabetes in adults confirm the large burden of diabetes, especially in developing countries. Estimates will be updated annually including the most recent, high-quality data available.

Iron Deficiency among Jamaican Adolescents.

OBJECTIVES: To raise awareness of significant iron deficiency anaemia occurring in Jamaican secondary school students. METHODS: Haematological screening of students in the fifth and sixth forms of 14 secondary schools in the parishes of Manchester and Clarendon, Jamaica, was done. Samples were subject to haemoglobin electrophoresis, examination of haematological indices, and haemoglobin, alpha 2 (HbA2) levels where indicated. RESULTS: Of 13 172 students with normal haemoglobin (AA) genotype aged 15-19 years, haemoglobin levels below 10 g/dL occurred in 0.36% of males and in 3.79% females. These subjects had low mean red cell volumes, low mean cell haemoglobin and high red cell distribution width, characteristic of iron deficiency, which was confirmed by dramatic increases in haemoglobin level following iron supplementation. Most revealed classic symptoms, histories of poor diets and pica, which generally resolved on iron supplementation. CONCLUSIONS: Iron deficiency, even in the absence of anaemia, is known to limit physical and mental functions and may impair intellectual performance in these high school students. Significant anaemia could be detected by incorporating a blood test into the school medical assessments performed on entry to secondary schools. There is a need for simple oral iron medications to be available at health centres.

Homozygous sickle cell disease in Uganda and Jamaica a comparison of Bantu and Benin haplotypes / La anemia de células falciformes homocigóticas en Uganda y Jamaica comparación de haplotipos Bantú y Benin

OBJECTIVE: To compare the haematological and clinical features of homozygous sickle cell (SS) disease in Bantu and Benin haplotypes in a cross-sectional study of 115 Ugandan patients attending the Sickle Cell Clinic at Mulago Hospital, Kampala, Uganda, with 311 patients in the Jamaican Cohort Study. METHODS: This involved comparison of clinical features and haematology with special reference to genetic determinants of severity including fetal haemoglobin levels, beta-globin haplotype and alpha thalassaemia status. RESULTS: The Bantu haplotype accounted for 94% of HbS chromosomes in Ugandan patients and the Benin haplotype for 76% of HbS chromosomes in Jamaica. Ugandan patients were marginally more likely to have alpha thalassaemia, had similar total haemoglobin and fetal haemoglobin levels but had higher reticulocyte counts and total bilirubin levels consistent with greater haemolysis. Ugandan patients had less leg ulceration and priapism, but the mode of clinical presentation, prevalence of dactylitis, features of bone pain and degree of delay in sexual development, assessed by menarche, were similar in the groups. In Ugandan patients, a history of anaemic episodes was common but these were poorly documented. CONCLUSION: The haematological and clinical features of the Bantu haplotype in Uganda were broadly similar to the Benin haplotype in Jamaica except for less leg ulceration and priapism and possibly greater haemolysis among Ugandan subjects. Anaemic episodes in Uganda were treated empirically by transfusion often without a clear diagnosis; better documentation including reticulocyte counts and observations on spleen size is necessary to evolve appropriate models of care.

OBJETIVO: Comparar los rasgos clínicos de la anemia de células falciformes homocigóticas (SS) en los haplotipos Bantú y Benin en un estudio transversal de 115 pacientes ugandeses que asisten a la Clínica de la anemia de células falciformes en el Hospital de Mulago, Kampala, Uganda, con 311 pacientes en un estudio de cohorte jamaicano. MÉTODOS: El estudio conllevó la comparación de los rasgos clínicos y hematológicos con referencia especial a los determinantes genéticos de la severidad, incluyendo los niveles de la hemoglobina fetal, haplotipos del gen de la globina beta, y el estado de la alfa talasemia. RESULTADOS: El haplotipo Bantú dio cuenta del 94% de los cromosomas HbS en los pacientes ugandeses, en tanto que los haplotipos Benin dieron cuenta del 76% de los cromosomas de HbS en Jamaica. Los pacientes de Uganda presentaron una probabilidad marginalmente mayor de alfa talasemia, tenían niveles similares de hemoglobina total y hemoglobina fetal, pero en cambio presentaban conteos más altos de reticulocitos así como niveles mayores de bilirrubina total, en correspondencia con una mayor hemólisis. Los pacientes ugandeses presentaban menor ulceración de las piernas y priapismo, pero el modo de presentación clínica, la prevalencia de dactilitis, los rasgos de dolor óseo, y el grado de retraso en el desarrollo sexual, evaluado por la menarquia, fueron similares en todos los grupos. Los pacientes de Uganda se caracterizaron comúnmente por una historia de episodios de anemia, pobremente documentados. CONCLUSIÓN: Los rasgos clínicos y hematológicos del haplotipo Bantú en Uganda fueron considerablemente similares al haplotipo Benin en Jamaica, salvo por una menor presencia de ulceración de las piernas y priapismo, así como posiblemente mayor hemólisis entre los sujetos de Uganda. Los episodios de anemia en Uganda fueron tratados empíricamente mediante transfusión, a menudo sin un diagnóstico claro. Se necesita una mejor documentación - incluyendo conteos de reticulocitos - así como observaciones del tamaño del bazo, a fin de desarrollar modelos de cuidado apropiados.

Homozygous sickle cell disease in Uganda and Jamaica a comparison of Bantu and Benin haplotypes.

OBJECTIVE: To compare the haematological and clinical features of homozygous sickle cell (SS) disease in Bantu and Benin haplotypes in a cross-sectional study of 115 Ugandan patients attending the Sickle Cell Clinic at Mulago Hospital, Kampala, Uganda, with 311 patients in the Jamaican Cohort Study METHODS: This involved comparison of clinical features and haematology with special reference to genetic determinants of severity including fetal haemoglobin levels, beta-globin haplotype and alpha thalassaemia status. RESULTS: The Bantu haplotype accounted for 94% of HbS chromosomes in Ugandan patients and the Benin haplotype for 76% of HbS chromosomes in Jamaica. Ugandan patients were marginally more likely to have alpha thalassaemia, had similar total haemoglobin and fetal haemoglobin levels but had higher reticulocyte counts and total bilirubin levels consistent with greater haemolysis. Ugandan patients had less leg ulceration and priapism, but the mode of clinical presentation, prevalence of dactylitis, features of bone pain and degree of delay in sexual development, assessed by menarche, were similar in the groups. In Ugandan patients, a history of anaemic episodes was common but these were poorly documented. CONCLUSION: The haematological and clinical features of the Bantu haplotype in Uganda were broadly similar to the Benin haplotype in Jamaica except for less leg ulceration and priapism and possibly greater haemolysis among Ugandan subjects. Anaemic episodes in Uganda were treated empirically by transfusion often without a clear diagnosis; better documentation including reticulocyte counts and observations on spleen size is necessary to evolve appropriate models of care.

Pattern of pregnancy weight gain in homozygous sickle cell disease and effect on birth size.

OBJECTIVE: To assess pregnancy weight gain and newborn anthropometry in mothers with homozygous sickle cell (SS) disease and normal controls. METHODS: An eleven-year retrospective review at the University Hospital of the West Indies, Kingston, Jamaica, revealed 128 singleton deliveries in women with SS disease who were matched by maternal age and birth date with 128 controls with a normal AA phenotype. Restriction to those commencing antenatal care before 16 weeks gestation resulted in the final study group of 80 SS patients and 115 AA controls. Weight and height were measured at first antenatal visit and weight at 20, 25, 30, 35 and 38 weeks gestation. Longitudinal regression used mothers'weight as the outcome, genotype as a predictor and gestational age as a random effect. Regression analyses of maternal weight on childhood anthropometry were repeated in separate maternal genotypes. Neonatal indices included gestational age, birthweight, head circumference and crown-heel length. RESULTS: Mothers with SS disease had lower weight and body mass index at first antenatal clinic visit (p < 0.001). Total weight gain was 6.9 kg for SS women and 10.4 kg for AA controls (p < 0.001) and weekly weight gain 0.263 kg (95% CI 0.224, 0.301) and 0.396 kg (95% CI 0.364, 0.427) respectively. A significant relationship occurred between birthweight and maternal weight gain at 25-30 weeks gestation in AA controls but this relationship appears delayed in SS disease. CONCLUSION: Different patterns of maternal weight gain in SS mothers and normal controls may have significance for the lower birthweight in SS mothers.

A preliminary examination of the effects of genetic variants of redox enzymes on susceptibility to oedematous malnutrition and on percentage cytotoxicity in response to oxidative stress in vitro.

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.

Pattern of pregnancy weight gain in homozygous sickle cell disease and effect on birth size / Patrones de ganancia de peso gestacional y tamaño al nacer en los casos de anemia de células falciformes

OBJECTIVES: To assess pregnancy weight gain and newborn anthropometry in mothers with homozygous sickle cell (SS) disease and normal controls. METHODS: An eleven-year retrospective review at the University Hospital of the West Indies, Kingston, Jamaica, revealed 128 singleton deliveries in women with SS disease who were matched by maternal age and birth date with 128 controls with a normal AA phenotype. Restriction to those commencing antenatal care before 16 weeks gestation resulted in the final study group of 80 SS patients and 115 AA controls. Weight and height were measured at first antenatal visit and weight at 20, 25, 30, 35 and 38 weeks gestation. Longitudinal regression used mothers'weight as the outcome, genotype as a predictor and gestational age as a random effect. Regression analyses ofmaternal weight on childhood anthropometry were repeated in separate maternal genotypes. Neonatal indices included gestational age, birthweight, head circumference and crown-heel length. RESULTS: Mothers with SS disease had lower weight and body mass index at first antenatal clinic visit (p < 0.001). Total weight gain was 6.9 kg for SS women and 10.4 kg for AA controls (p < 0.001) and weekly weight gain 0.263 kg (95% CI 0.224, 0.301) and 0.396 kg (95% CI 0.364, 0.427) respectively. A significant relationship occurred between birthweight and maternal weight gain at 25-30 weeks gestation in AA controls but this relationship appears delayed in SS disease. CONCLUSION: Different patterns of maternal weight gain in SS mothers and normal controls may have significance for the lower birthweight in SS mothers.

OBJETIVO: Evaluar la ganancia de peso gestacional y la antropometría neonatal en madres con anemia de células falciformes (CF) homocigóticas y en controles normales. MÉTODO: Un examen retrospectivo de once años en el Hospital Universitario de West Indies West Indies, Kingston, Jamaica, reveló la ocurrencia de 128 partos únicos (e.d. de un solo bebé) en mujeres con la enfermedad de CF, que fueron comparadas sobre la base de la edad materna y la fecha de nacimiento, con 128 controles de fenotipo AA normal. A partir de restricciones a las gestantes que comenzaron el cuidado prenatal antes de las 16 semanas de gestación, se llegó finalmente al grupo de estudio de 80 pacientes con CF y 115 controles con AA. El peso y la altura se midieron en la primera visita prenatal, y el peso a las 20, 25, 30, 35 y 38 semanas de gestación. La regresión longitudinal usó el peso de las madres como resultado, el genotipo como predictor, y la edad gestacional como efecto aleatorio. Los análisis de la regresión de peso materno sobre la antropometría fueron repetidos en genotipos maternos separados. Los índices neonatales incluyeron la edad gestacional, el peso al nacer y la circunferencia cefálica. RESULTADOS: Las madres con la enfermedad de CF tenían más bajo peso e índice de masa corporal en la primera visita clínica prenatal (p < 0.001). La ganancia de peso total fue 6.9 kg para las mujeres con CF y 10.4 kg para los controles AA (p < 0.001) y la ganancia de peso semanal 0.263 kg (95% CI 0.224-0.301) y 0.396 kg (95% CI 0.364-0.427) respectivamente. Una relación significativa tuvo lugar entre el peso al nacer y la ganancia de peso materna en las semanas 25-30 de gestación en los controles AA, pero esta relación parece demorada en la enfermedad de CF. CONCLUSION: Los patrones diferentes de ganancia de peso materno en las madres con CF y los controles normales, pueden tener importancia significativa para las madres con CF.

Bacterial vaginosis in female facility workers in north-western Tanzania: prevalence and risk factors.

OBJECTIVES: To determine prevalence of, and risk factors for, bacterial vaginosis (BV) among herpes simplex virus (HSV) 2 seropositive Tanzanian women at enrollment into a randomised, placebo-controlled trial of HSV suppressive treatment. METHODS: 1305 HSV-2 seropositive women aged 16-35 years working in bars, guesthouses and similar facilities were interviewed, examined and tested for HIV, syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis, BV, candidiasis and trichomoniasis. Factors associated with BV were analysed using logistic regression to estimate odds ratios and 95% confidence intervals. RESULTS: BV prevalence was 62.9%; prevalence of Nugent score 9-10 was 16.1%. Independent risk factors for BV were work facility type, fewer dependents, increasing alcohol consumption, sex in the last week (adjusted OR 2.03; 95% CI 1.57 to 2.62), using cloths or cotton wool for menstrual hygiene, HIV (adjusted OR 1.41; 95% CI 1.09 to 1.83) and Trichomonas vaginalis infection. There was no association between BV and the frequency or method of vaginal cleansing. However, BV was less prevalent among women who reported inserting substances to dry the vagina for sex (adjusted OR 0.44; 95% CI 0.25 to 0.75). CONCLUSION: BV was extremely prevalent among our study population of HSV-2 positive female facility workers in North-western Tanzania. Although recent sex was associated with increased BV prevalence, vaginal drying was associated with lower BV prevalence. Further studies of the effects of specific practices on vaginal flora are warranted.

The changing face of homozygous sickle cell disease: 102 patients over 60 years.

Earlier reports on homozygous sickle cell (SS) disease have been biased by severely affected cases. The Jamaican clinic which seeks to avoid such bias has 102 patients surviving beyond 60 years. The objective of this study was to examine the features of elderly cases and assess factors determining survival and the behaviour of this disease with advancing age. A retrospective review of all cases and prospective assessment in survivors was conducted at The Sickle Cell Clinic at the University of the West Indies, Kingston, Jamaica previously operated by the MRC Laboratories. All patients with SS disease born prior to December 31, 1943 who would, by January 2004, have passed their 60th birthday were traced and their current status ascertained. The molecular and clinical features were assessed and observations on the clinical behaviour of the disease and of haematology and biochemistry are presented. Of the 102 patients, 58 had died, four had emigrated and 40 were alive, resident in Jamaica and aged 60-87 years. Survival was associated with female gender and higher foetal haemoglobin but not with alpha-thalassaemia or beta-globin haplotype. A tendency to familial clustering among elderly survivors did not reach statistical significance. Painful crises ameliorated with age and there was a benign course in pregnancy. Mean haemoglobin levels fell with age and were generally associated with rising creatinine levels indicating the importance of renal failure. Elderly survivors present some features of intrinsic mildness but also manifest age-related amelioration of painful crises and falling haemoglobin levels from progressive renal damage.

Anaesthetic morbidity at the University Hospital of the West Indies.

OBJECTIVE: There is little information on adverse anaesthetic outcomes from the Caribbean. The aim of this study was to investigate the occurrence of anaesthetic morbidity and mortality at the University Hospital of the West Indies (UHWI) and to identify possible risk factors. METHODS: All anaesthetic procedures at the UHWI were monitored for adverse events and patient outcomes for the 12-month period from March 2004 to February 2005. Possible risk factors for these adverse events were assessed using logistic regression. RESULTS: Of 3185 anaesthetic procedures, the incidence of intra-operative events was 201 per 1000 (95% CI 187, 215); 151 per 1000 being cardiovascular and 26 per 1000 respiratory. Others included excess blood loss and equipment failure, hyperglycaemia, nausea and vomiting. Patients with intraoperative complications were three times more likely to have complications during recovery (OR = 3.35; 95% CI 2.59, 4.33, p < 0.001). The incidence of complications among paediatric patients was 139 per 1000 (95% CI 104, 174) intra-operatively and 58 per 1000 (95% CI 34, 81) during recovery. Risk factors for developing complications (p < 0.05) included age > 50 years, ASA status > or = II, prolonged anaesthesia, high surgical risk, general or combined anaesthetic techniques, senior anaesthetist, intubated patients and co-morbidities. There were 14 operative mortalities, none of which was anaesthesia-related CONCLUSION: Anaesthetic complication rates at the UHWI are comparable to those in developed countries, except for higher paediatric complication rates and ICU admissions and lower rates of postoperative nausea and vomiting.