Pharmacological interventions for painful sickle cell vaso-occlusive crises in adults.

BACKGROUND: Sickle cell disease (SCD) is a group of inherited disorders of haemoglobin (Hb) structure in a person who has inherited two mutant globin genes (one from each parent), at least one of which is always the sickle mutation. It is estimated that between 5% and 7% of the world\u27s population are carriers of the mutant Hb gene, and SCD is the most commonly inherited blood disorder. SCD is characterized by distorted sickle-shaped red blood cells. Manifestations of the disease are attributed to either haemolysis (premature red cell destruction) or vaso-occlusion (obstruction of blood flow, the most common manifestation). Shortened lifespans are attributable to serious comorbidities associated with the disease, including renal failure, acute cholecystitis, pulmonary hypertension, aplastic crisis, pulmonary embolus, stroke, acute chest syndrome, and sepsis. Vaso-occlusion can lead to an acute, painful crisis (sickle cell crisis, vaso-occlusive crisis (VOC) or vaso-occlusive episode). Pain is most often reported in the joints, extremities, back or chest, but it can occur anywhere and can last for several days or weeks. The bone and muscle pain experienced during a sickle cell crisis is both acute and recurrent. Key pharmacological treatments for VOC include opioid analgesics, non-opioid analgesics, and combinations of drugs. Non-pharmacological approaches, such as relaxation, hypnosis, heat, ice and acupuncture, have been used in conjunction to rehydrating the patient and reduce the sickling process. OBJECTIVES: To assess the analgesic efficacy and adverse events of pharmacological interventions to treat acute painful sickle cell vaso-occlusive crises in adults, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, Embase via Ovid and LILACS, from inception to September 2019. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries. SELECTION CRITERIA: Randomized, controlled, double-blind trials of pharmacological interventions, of any dose and by any route, compared to placebo or any active comparator, for the treatment (not prevention) of painful sickle cell VOC in adults. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio (RR) and number needed to treat for one additional event, using standard methods. Our primary outcomes were participant-reported pain relief of 50%, or 30%, or greater; Patient Global Impression of Change (PGIC) very much improved, or much or very much improved. Our secondary outcomes included adverse events, serious adverse events, and withdrawals due to adverse events. We assessed GRADE and created three \u27Summary of findings\u27 tables. MAIN RESULTS: We included nine studies with data for 638 VOC events and 594 participants aged 17 to 42 years with SCD presenting to a hospital emergency department in a painful VOC. Three studies investigated a non-steroidal anti-inflammatory drug (NSAID) compared to placebo. One study compared an opioid with a placebo, two studies compared an opioid with an active comparator, two studies compared an anticoagulant with a placebo, and one study compared a combination of three drugs with a combination of four drugs. Risk of bias across the nine studies varied. Studies were primarily at an unclear risk of selection, performance, and detection bias. Studies were primarily at a high risk of bias for size with fewer than 50 participants per treatment arm; two studies had 50 to 199 participants per treatment arm (unclear risk). Non-steroidal anti-inflammatory drugs (NSAID) compared with placebo No data were reported regarding participant-reported pain relief of 50% or 30% or greater. The efficacy was uncertain regarding PGIC very much improved, and PGIC much or very much improved (no difference; 1 study, 21 participants; very low-quality evidence). Very low-quality, uncertain results suggested similar rates of adverse events across both the NSAIDs group (16/45 adverse events, 1/56 serious adverse events, and 1/56 withdrawal due to adverse events) and the placebo group (19/45 adverse events, 2/56 serious adverse events, and 1/56 withdrawal due to adverse events). Opioids compared with placebo No data were reported regarding participant-reported pain relief of 50% or 30%, PGIC, or adverse events (any adverse event, serious adverse events, and withdrawals due to adverse events). Opioids compared with active comparator No data were reported regarding participant-reported pain relief of 50% or 30% or greater. The results were uncertain regarding PGIC very much improved (33% of the opioids group versus 19% of the placebo group). No data were reported regarding PGIC much or very much improved. Very low-quality, uncertain results suggested similar rates of adverse events across both the opioids group (9/66 adverse events, and 0/66 serious adverse events) and the placebo group (7/64 adverse events, 0/66 serious adverse events). No data were reported regarding withdrawal due to adverse events. Quality of the evidence We downgraded the quality of the evidence by three levels to very low-quality because there are too few data to have confidence in results (e.g. too few participants per treatment arm). Where no data were reported for an outcome, we had no evidence to support or refute (quality of the evidence is unknown). AUTHORS\u27 CONCLUSIONS: This review identified only nine studies, with insufficient data for all pharmacological interventions for analysis. The available evidence is very uncertain regarding the efficacy or harm from pharmacological interventions used to treat pain related to sickle cell VOC in adults. This area could benefit most from more high quality, certain evidence, as well as the establishment of suitable registries which record interventions and outcomes for this group of people

Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population.

BACKGROUND: Both fasting plasma glucose (FPG) and HbA1c are recommended for the diagnosis of diabetes and prediabetes by the American Diabetes Association (ADA), and for diabetes by the World Health Organization. The ADA guidance is influential on clinical practice in many developing countries, including in the Caribbean and Latin America. We aimed to compare the prevalence and characteristics of individuals identified as having diabetes and prediabetes by FPG and HbA1c in a predominantly African ancestry Caribbean population. METHODS: A representative population-based sample of 1234 adults (≥25 years of age) resident in Barbados was recruited. Standard methods with appropriate quality control were used to collect data on height, weight, blood pressure, fasting lipids and history of diagnosed diabetes, and to measure fasting glucose and HbA1c. Those with previously diagnosed diabetes (n = 192) were excluded from the analyses. Diabetes was defined as: FPG ≥7.0 mmol/L or HbA1c ≥6.5%; prediabetes as: FPG ≥5.6 to <7mmol/L or HbA1c ≥5.7 to <6.5%. RESULTS: Complete data were available on 939 participants without previously diagnosed diabetes. The prevalence of undiagnosed diabetes was higher, but not significantly so, by HbA1c (4.9%, 95% CI 3.5, 6.8) vs FPG (3.5%, 2.4, 5.1). Overall 79 individuals had diabetes by either measure, but only 21 on both. The prevalence of prediabetes was higher by HbA1c compared to FPG: 41.7% (37.9, 45.6) vs 15.0% (12.8, 17.5). Overall 558 individuals had prediabetes by either measure, but only 107 on both. HbA1c, but not FPG, was significantly higher in women than men; and FPG, but not HbA1c, was significantly associated with raised triglycerides and low HDL cholesterol. CONCLUSION: The agreement between FPG and HbA1c defined hyperglycaemia is poor. In addition, there are some differences in the phenotype of those identified, and HbA1c gives a much higher prevalence of prediabetes. The routine use of HbA1c for screening and diagnosis in this population would have major implications for clinical and public health policies and resources. Given the lack of robust evidence, particularly for prediabetes, on whether intervention in the individuals identified would improve outcomes, this approach to screening and diagnosis cannot be currently recommended for this population

A cross-sectional study of physical activity and sedentary behaviours in a Caribbean population: combining objective and questionnaire data to guide future interventions

Abstract Background Current understanding of population physical activity (PA) levels and sedentary behaviour in developing countries is limited, and based primarily on self-report. We described PA levels using objective and self-report methods in a developing country population. Methods PA was assessed in a cross-sectional, representative sample of the population of Barbados (25–54 years), using a validated questionnaire (RPAQ) and individually calibrated combined heart rate and movement sensing monitors. The RPAQ collects information on recalled activity in 4 domains: home, work, transport, and leisure. Physical inactivity was defined according to World Health Organization (WHO) guidelines; sedentary lifestyle was defined as being sedentary for 8 h or more daily; PA overestimation was defined as perceiving activity to be sufficient, when classified as ‘inactive’ by objective measurement. Results According to objective estimates, 90.5 % (95 % CI: 83.3,94.7) of women and 58.9 % (48.4,68.7) of men did not accumulate sufficient activity to meet WHO minimum recommendations. Overall, 50.7 % (43.3,58.1) of the population was sedentary for 8 h or more each day, and 60.1 % (52.8,66.9) overestimated their activity levels. The prevalence of inactivity was underestimated by self-report in both genders by 28 percentage points (95 % CI: 18,38), but the accuracy of reporting differed by age group, education level, occupational grade, and overweight/obesity status. Low PA was greater in more socially privileged groups: higher educational level and higher occupational grade were both associated with less objectively measured PA and more sedentary time. Variation in domain-specific self-reported physical activity energy expenditure (PAEE) by educational attainment was observed: higher education level was associated with more leisure activity and less occupational activity. Occupational PA was the main driver of PAEE for women and men according to self-report, contributing 57 % (95 % CI: 52,61). The most popular leisure activities for both genders were walking and gardening. Conclusions The use of both objective and self-report methods to assess PA and sedentary behaviour provides important complementary information to guide public health programmes. Our results emphasize the urgent need to increase PA and reduce sedentary time in this developing country population. Women and those with higher social economic position are particularly at risk from low levels of physical activity

Ethnic and Gender Disparities in Premature Adult Mortality in Belize 2008-2010.

BACKGROUND: Data on disparities in mortality within low and middle income countries are limited, with little published data from the Caribbean or Central America. Our aim was to investigate disparities in overall and cause specific premature adult mortality in the multi-ethnic middle income country of Belize. METHODS: Mortality data from Belize 2008-2010 classified using the International Classification of Diseases 10 and the 2010 census stratified by age and ethnicity were used to calculate age, sex, and ethnic specific mortality rates for those 15-59 years, and life table analysis was used to estimate the probability of death between the ages of 15 and 59 (45q15). RESULTS: The probability of death among those aged 15 to 59 years was 18.1% (women 13.5%, men 22.7%). Creole and Garifuna ethnic groups have three times the 45q15 probability of death compared to Mayan and Mestizo groups (Creole 31.2%, Garifuna 31.1%, Mayan 10.2%, Mestizo 12.0%). This pattern of ethnic disparity existed in both sexes but was greater in men. The probability of death from injuries was 14.8% among Creole men, more than twice the rate of other ethnicities and peaks among young Creole men. These deaths are dominated by homicides and unspecified deaths involving firearms. CONCLUSIONS: Marked disparities in mortality between ethnic groups exist in this Central American/Caribbean country, from rates that are typical of high-income countries to those of low-income countries. The pattern of these extreme differences likely suggests that they reflect underlying social determinants rooted in the country's colonial past

Prostate Cancer Incidence and Mortality in Barbados, West Indies

We describe prostate cancer incidence and mortality in Barbados, West Indies. We ascertained all histologically confirmed cases of prostate cancer during the period July 2002 to December 2008 and reviewed each death registration citing prostate cancer over a 14-year period commencing January 1995. There were 1101 new cases for an incidence rate of 160.4 (95% Confidence Interval: 151.0–170.2) per 100,000 standardized to the US population. Comparable rates in African-American and White American men were 248.2 (95% CI: 246.0–250.5) and 158.0 (95% CI: 157.5–158.6) per 100,000, respectively. Prostate cancer mortality rates in Barbados ranged from 63.2 to 101.6 per 100,000, compared to 51.1 to 78.8 per 100,000 among African Americans. Prostate cancer risks are lower in Caribbean-origin populations than previously believed, while mortality rates appeared to be higher than reported in African-American men. Studies in Caribbean populations may assist understanding of disparities among African-origin populations with shared heredity

Comparison of the Systemic Lupus Erythematosus Activity Questionnaire and the Systemic Lupus Erythematosus Disease Activity Index in a Black Barbadian Population

In Barbados, use of the Systemic Lupus Erythematosus (SLE) Disease Activity Index (SLEDAI) is limited by the unavailability of serologic markers. The SLE Activity Questionnaire (SLAQ) excludes laboratory measurements and is therefore more accessible. Here, we investigate the agreement between the SLAQ, the SLEDAI, and the physician global assessment (PGA). A pilot of 32 participants completed the SLAQ and SLEDAI. The tools were compared (1) in their original format, (2) limited to common indices, and (3) limited to the same patient recall period. We compared the proportions of persons reporting disease activity and the concordance between calculated activity scores for SLAQ versus SLEDAI and for SLAQ versus PGA. Seventy-eight percent versus 59% of participants reported disease activity with the original SLEDAI versus SLAQ, respectively. The relationship was reversed to 22% versus 59% when the matched item tools were compared. Concordance was 0.62 (95% CI 0.42-0.81) between the original scores, 0.70 (0.57-0.83) when restricted by matched items, and 0.72 (0.59-0.84) when further restricted by recall period. Concordance between the SLAQ and PGA was 0.56 (0.32-0.80). Reversal of the disease activity percentage in the matched items comparison highlights the inadequacy of tools that exclude laboratory measurements and suggests that the subjective nature of SLAQ may contribute to over-reporting. Further work is needed to produce a robust disease activity tool apt for resourceconstrained environments

Anthropometric cut-offs to identify hyperglycemia in an Afro-Caribbean population: a cross-sectional population-based study from Barbados.

INTRODUCTION: Body mass index (BMI) and waist circumference (WC) cut-offs associated with hyperglycemia may differ by ethnicity. We investigated the optimal BMI and WC cut-offs for identifying hyperglycemia in the predominantly Afro-Caribbean population of Barbados. RESEARCH DESIGN AND METHODS: A cross-sectional study of 865 individuals aged ≥25 years without known diabetes or cardiovascular disease was conducted. Hyperglycemia was defined as fasting plasma glucose ≥5.6 mmol/L or hemoglobin A1c ≥5.7% (39 mmol/mol). The Youden index was used to identify the optimal cut-offs from the receiver operating characteristic (ROC) curves. Further ROC analysis and multivariable log binomial regression were used to compare standard and data-derived cut-offs. RESULTS: The prevalence of hyperglycemia was 58.9% (95% CI 54.7% to 63.0%). In women, optimal BMI and WC cut-offs (27 kg/m2 and 87 cm, respectively) performed similarly to standard cut-offs. In men, sensitivities of the optimal cut-offs of BMI ≥24 kg/m2 (72.0%) and WC ≥86 cm (74.0%) were higher than those for standard BMI and WC obesity cut-offs (30.0% and 25%-46%, respectively), although with lower specificity. Hyperglycemia was 70% higher in men above the data-derived WC cut-off (prevalence ratio 95% CI 1.2 to 2.3). CONCLUSIONS: While BMI and WC cut-offs in Afro-Caribbean women approximate international standards, our findings, consistent with other studies, suggest lowering cut-offs in men may be warranted to improve detection of hyperglycemia. Our findings do, however, require replication in a new data set.The project was supported by the Ministry of Health of the Government of Barbados. ANW is supported by the Fogarty International Center of the National Institutes of Health under Award Number K43TW010698. This paper describes the views of the authors and does not necessarily represent the official views of the National Institutes of Health (USA)

Sodium and potassium excretion in an adult Caribbean population of African descent with a high burden of cardiovascular disease

Abstract Background High sodium diets with inadequate potassium and high sodium-to-potassium ratios are a known determinant of hypertension and cardiovascular disease (CVD). The Caribbean island of Barbados has a high prevalence of hypertension and mortality from CVD. Our objectives were to estimate sodium and potassium excretion, to compare estimated levels with recommended intakes and to identify the main food sources of sodium in Barbadian adults. Methods A sub-sample (n = 364; 25–64 years) was randomly selected from the representative population-based Health of the Nation cross-sectional study (n = 1234), in 2012–13. A single 24-h urine sample was collected from each participant, following a strictly applied protocol designed to reject incomplete samples, for the measurement of sodium and potassium excretion (in mg), which were used as proxy estimates of dietary intake. In addition, sensitivity analyses based on estimated completeness of urine collection from urine creatinine values were undertaken. Multiple linear regression was used to examine differences in sodium and potassium excretion, and the sodium-to-potassium ratio, by age, sex and educational level. Two 24-h recalls were used to identify the main dietary sources of sodium. All analyses were weighted for the survey design. Results Mean sodium excretion was 2656 (2488–2824) mg/day, with 67% (62–73%) exceeding the World Health Organization (WHO) recommended limit of 2000 mg/d. Mean potassium excretion was 1469 (1395–1542) mg/d; < 0.5% met recommended minimum intake levels. Mean sodium-to-potassium ratio was 2.0 (1.9–2.1); not one participant had a ratio that met WHO recommendations. Higher potassium intake and lower sodium-to-potassium ratio were independently associated with age and tertiary education. Sensitivity analyses based on urine creatinine values did not notably alter these findings. Conclusions In this first nationally representative study with objective assessment of sodium and potassium excretion in a Caribbean population in over 20 years, levels of sodium intake were high, and potassium intake was low. Younger age and lower educational level were associated with the highest sodium-to-potassium ratios. These findings provide baseline values for planning future policy interventions for non-communicable disease prevention

Social determinants of depression and suicidal behaviour in the Caribbean: a systematic review.

BACKGROUND: Depressive disorder is the largest contributor to years lived with disability in the Caribbean, adding 948 per 100,000 in 2013. Depression is also a major risk factor for suicidal behaviour. Social inequalities influence the occurrence of depression, yet little is known about the social inequalities of this condition in the Caribbean. In support of the 2011 Rio Political Declaration on addressing health inequities, this article presents a systematic review of the role of social determinants on depression and its suicidal behaviours in the Caribbean. METHODS: Eight databases were searched for observational studies reporting associations between social determinants and depression frequency, severity, or outcomes. Based on the PROGRESS-plus checklist, we considered 9 social determinant groups (of 15 endpoints) for 6 depression endpoints, totalling 90 possible ways ('relationship groups') to explore the role of social determinants on depression. Studies with ≥50 participants conducted in Caribbean territories between 2004 and 2014 were eligible. The review was conducted according to STROBE and PRISMA guidelines. Results were planned as a narrative synthesis, with meta-analysis if possible. RESULTS: From 3951 citations, 55 articles from 45 studies were included. Most were classified as serious risk of bias. Fifty-seven relationship groups were reported by the 55 included articles, leaving 33 relationship groups (37%) without an evidence base. Most associations were reported for gender, age, residence, marital status, and education. Depression, its severity, and its outcomes were more common among females (except suicide which was more common among males), early and middle adolescents (among youth), and those with lower levels of education. Marriage emerged as both a risk and protective factor for depression score and prevalence, while several inequality relationships in Haiti were in contrast to typical trends. CONCLUSION: The risk of bias and few numbers of studies within relationship groups restricted the synthesis of Caribbean evidence on social inequalities of depression. Along with more research focusing on regional social inequalities, attempts at standardizing reporting guidelines for observational studies of inequality and studies examining depression is necessitated. This review offers as a benchmark to prioritize future research into the social determinants of depression frequency and outcomes in the Caribbean