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Sickle cell anaemia (SCA) is associated with macrovascular complications at relatively normal blood pressures. This has led to the development of the term ‘relative systemic hypertension’ (RSH). The electrocardiography (ECG) and echocardiography (ECHO) findings in these people has not been well highlighted. Patients with SCA in steady state were consecutively recruited. History, physical examination, ECG and ECHO information were obtained from all participants after informed consent was obtained. Eighty-three people were recruited in all- 15 of which had RSH, giving a prevalence of 18.1%. Those with RSH had higher packed cell volumes (PCV), smaller right atria area, lower tricuspid regurgitant velocities, lower incidence of early satiety, longer QTc and higher frequency of a history of vaso-occlusive crises. The indices of right and left ventricular function were normal in both groups. Right atrial area was the only significant determinant of RSH in this study. RSH is associated with higher PCV, longer QTc and smaller right atrial area in SCA patients. More studies to evaluate sympathetic output in SCA with RSH is required.

Introduction: Mammographic density is a strong predictor of breast cancer. Menopause has a significant effect on breast pattern and has been documented to have more important influence on the decline in mammographic densities than age. The aim of this study was to describe the breast parenchymal density patterns in postmenopausal women in Ibadan and correlate these with their socio-demographic and anthropometric characteristics. Methodology: This is a retrospective cross-sectional study of 196 postmenopausal women who had two screening views done on each breast in the Radiology Department of the University College Hospital Ibadan. Data was pulled from completed questionnaire by patient who had mammogram during the period under review. The report of the mammograms were matched with patients’ socio-demographic characteristics and entered into R statistical package for analysis. Results: The mean age of the women was 55.0±6.8 years while their mean age at menopause was 48.4±4.6 years. The combined BI-RADS 1 and 2 breast parenchymal patterns which are associated with low risk of breast cancer, were found in 82.1% of the women. The mean difference in age at first birth between women with BI-RADS 1 and 2 and BI-RADS 3 and 4 was statistically significant P=0.035. Body mass index, family and personal history of breast cancer also showed correlation with breast parenchymal pattern, though not statistically significant. Conclusion: The low prevalence of dense breast pattern in this study is consistent with previous findings of relatively lower prevalence of breast cancer in African women. The clustering of low mean age at birth of first child, low mean age at menopause and multi-parity, in association with the low mammographic density in majority of the women in this study further corroborates the relatively reduced risk of breast cancer in our studied population.

Left ventricular hypertrophy (LVH) is recognized as a cardiovascular risk factor and is a known consequence of sickle cell anemia (SCA). Abnormal left ventricular geometric patterns have been described but the determinants have not been well elucidated.Electrocardiography (ECG) and Echocardiography (ECHO) was done on subjects with SCA and hemoglobin A(HBA). Those with systemic hypertension were excluded. Voltages, durations, and intervals were measured as appropriate and recorded in a standard proforma. Analysis was made using a standard statistical software.Eighty four people with SCA and 91 with HBA were recruited as cases and controls respectively. Subjects with SCA have more abnormal LV geometric patterns than those with HBA(p=0.000). Eccentric LVH(p=0.000) was more in SCA subjects while concentric LVH(p=0.054) and concentric remodeling(p=0.319) were not. Forty-one and fifty-two subjects with SCA and HBA respectively did ECGs. . Subjects with eccentric LVH had lower hip circumference, higher left atrial diameter, right atrial area, higher sokolow-lyon voltage sum, stroke volume and cardiac output. The Sokolow-Lyon voltage criteria at the traditional cut off point was not different between those with and without eccentric LVH. However, Sokolow-Lyon voltage criteria at a cut-off of ≥4.7mV detected eccentric LVH with a sensitivity of 60% and specificity of 83.3%.While Sokolow-Lyon voltage sum, stroke volume, right atrial area, and left atrial diameter correlated positively, pulse rate and hip circumference correlated inversely with eccentric LVH. Sokolow Lyon voltage sum was the independent determinant of eccentric LVH in this study.Sickle cell anemia predisposes to abnormal LV geometric patterns, especially eccentric LVH. There may be a need to review the electrocardiographic cut off points for defining eccentric LVH in the SCA populace.

BACKGROUND: Iron deficiency anaemia (IDA) is a common finding among patients with chronic kidney disease (CKD) and a major contributor to the high morbidity, mortality and poor quality of life associated with the disease. Assessment of iron deficiency anaemia has become routine in the evaluation of patients with CKD and iron studies such as serum ferritin, total iron binding capacity and transferrin saturation are recommended as standard diagnostic work up. However, in Nigeria and other low and middle income countries (LMICs) where most patients pay out of pocket, only few patients could afford iron studies, in addition to other cost of care. It is therefore imperative to find and establish the utility of other relatively affordable markers of iron deficiency among patients in LMICs. In studies done within the general population, the percentage of hypochromic red blood cells (PHRC), RBC indices and reticulocyte haemoglobin concentration (CHr) have been shown to predict iron deficiency. However, the usefulness of these in CKD patients had not been established. Thus, we determined the utility of PHRC and RBC indices among patients with CKD. METHODS: this is a cross sectional survey of 157 participants with CKD and 157 apparently healthy controls. The patients with CKD were individuals receiving care at the renal unit of the University College Hospital, Ibadan. Clinical data were collected using standard care report forms and information obtained were demographic details, aetiologies of CKD, dialysis status, symptoms of iron deficiency anaemia, modalities of anaemia treatments and other medications. Blood samples were collected for iron studies, full blood count, red blood cell (RBC) indices, peripheral blood film for PHRC, plasma highly sensitive C- reactive protein, serum electrolytes, urea and creatinine. Data was analyzed using SPSS version 23. RESULTs: a total of 314 participants were enrolled in the study, half of them were patients with CKD while the remaining half were controls without CKD. The mean age for cases and controls were [a href=´#ref45.5±14.4 vs 46.1±15.5 years respectively´45.5±14.4 vs 46.1±15.5 years respectively/aa href=´#ref p = 0.72´ p = 0.72/a ] =a href=´#refwhile females were 57% vs 60.1%´while females were 57% vs 60.1% /a, a href=´#ref p = 0.06´ p 0.06/a]. The prevalence of IDA using iron studies [a href=´#ref67 (42.6%) vs 33 (21.0%)´67 (42.6%) vs 33 (21.0%)/a,a href=´#ref p = 0.01 p =0.01/a], RBC indices [a href=´#ref46 (29.3%) vs 25 (15.9%)´46 (29.3%) vs 25 (15.9%) /a,a href=´#ref p = 0.002´= p 0.002/a], and PHRC [a href=´#ref48 (30.5%) vs 32 (20.4%)´48 (30.5%) vs 32 (20.4%)/a, a href=´#ref p = 0.038´= p =0.038=/a]. The sensitivity and specificity of RBC indices and PHRC as surrogate markers of iron deficiency anaemia were [a href=´#ref73.8% ; 92.0%´73.8% ; 92.0% /a ] and [a href=´#ref80.0% ; 92.3%´=80.0% ; 92.3%/a,a href=´#ref´/a] respectively. CONCLUSION: this study confirmed that the 3 methods of diagnosis of iron deficiency anaemia vis-a-vis iron studies (Serum ferritin and TSAT), RBC indices and percentage hypochromic RBC, all demonstrated high prevalence of iron deficiency anaemia among patients with CKD. While RBC indices and percentage hypochromic RBC are reliable and highly specific surrogate markers of iron deficiency anaemia among individuals with CKD.

Introduction Among the risk factors for venous thromboembolism (VTE) are inheritance of the sickle cell gene and antiphospholipid syndrome. Antiphospholipid antibodies are elevated in sickle cell disease but there is little information on its levels in sickle cell trait. The prevalence of anticardiolipin antibodies and association with VTE is equally not known in the Nigerian population. Methods A case control study involving 50 consecutive patients with Doppler confirmed venous thromboembolism at the University College Hospital Ibadan and 50 apparently healthy individuals. Haemoglobin electrophoresis was carried out using cellulose acetate membrane. IgG and IgM anticardiolipin antibodies were assayed by ELISA. Results The mean age of the patients was 58.7±18.5years, range of 21-89 years, there were 21 males (42%). Majority of the patients (42 (84%)) had deep venous thrombosis while five (10%) patients presented with pulmonary embolism, one had both deep venous thrombosis and pulmonary embolism. A patient had portal vein thrombosis and another, an intracardiac clot. Sedentary lifestyles, hypertension and concomitant malignancy were the most prevalent risk factors (34% each) (figure I). Both sedentary lifestyle and cancer were significantly associated with VTE (p Conclusion The prevalence of sickle cell trait and anticardiolipin levels did not differ between VTE patients and healthy controls. Age, hypertension, sedentary lifestyle and malignancies were identified risk factors in our cohort of patients. Larger prospective studies may be helpful in determining the influence of sickle cell trait and antiphospholipid antibodies in venous thromboembolism. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background. Breast cancer is the leading cause of cancer-related mortality among women in Ghana. Data are limited on the predictors of poor outcomes in breast cancer patients in low-income countries; however, prolonged waiting time has been implicated. Among breast cancer patients who received treatment at Korle Bu Teaching Hospital, this study evaluated duration and factors that influenced waiting time from first presentation to start of definitive treatment. Method. We conducted a hospital-based retrospective study of 205 breast cancer patients starting definitive treatment at Korle Bu Teaching Hospital between May and December 2013. We used descriptive statistics to summarize patient characteristics. Mann–Whitney U and Kruskal–Wallis tests and Spearman rank correlation were performed to examine the patients, health system, and health worker factors associated with median waiting time. Poisson regression was used to examine the determinants of waiting time. Results. The mean age of the patients was 51.1 ± 11.8 years. The median waiting time was 5 weeks. The determinants of waiting time were level of education, age, income, marital status, ethnicity, disease stage, health insurance status, study sites, time interval between when biopsy was requested and when results were received and receipt of adequate information from health workers. Conclusion. A prolonged waiting time to treatment occurs for breast cancer patients in Ghana, particularly for older patients, those with minimal or no education, with lower income, single patients, those with late disease, those who are insured, and who did not receive adequate information from the health workers. Time to obtain biopsy reports should be shortened. Patients and providers need education on timely treatment to improve prognosis.

Poor outcomes for breast cancer in Ghana have been attributed to late presentation of symptoms at biomedical facilities. This study explored factors accounting for delays in initiation of breast cancer treatment at the Korle-Bu Teaching Hospital in Accra. Focus group discussions were conducted with 20 women with breast cancer. A theory-driven thematic analysis identified three multilevel factors influencing treatment seeking delays: (1) patient (e.g. misinterpretation of symptoms, fear), (2) healthcare provider (e.g. negative attitudes) and (3) health systems (e.g. shortage of medicines). Addressing treatment delays will require multilevel interventions, including culturally congruent education, psychosocial counselling/support and strengthening health systems.

More recent evidence however suggests the likelihood of four independent mutations of the sickle cell gene in different populations; three of which occurred in Africa. The trans-Atlantic slave trade accounted for the gene movement from Africa to the Caribbean and United States of America and lately migration has resulted in the introduction of the gene to the United Kingdom and other parts of Europe. The incidence of SCD in England (1:200 births) is increasing and the high prevalence is due to the high percentage of births to mothers of West African origin.

Alpha-thalassemia and the BCL11A rs1427407 T allele are commonly observed in sickle cell anemia (SCA) patients and are associated with reduced hemolysis and higher hemoglobin F levels, respectively. We investigated whether a high-risk genetic profile, defined as SCA patients who did not inherit either α-thalassemia or the BCL11A rs1427407 T allele, had stronger associations with clinical and laboratory variables than the individual genetic components in the University of Ibadan cohort (n=249). We then replicated our findings in SCA cohorts from the University of Illinois at Chicago (UIC)(n=260) and Walk-Treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy (Walk-PHaSST)(n=387). High-risk was associated with higher reticulocytes (15.0% vs. 7.8%, P=0.08) and stroke history (6% vs. 1%, P=0.02) than standard risk patients and these associations were more significant than the individual genetic components in the University of Ibadan cohort. These findings were replicated in high-risk patients from UIC and Walk-PHaSST for reticulocytes (UIC: 13.5% vs. 11.8%, P=0.03; Walk-PHaSST: 9.6% vs. 8.2%, P=0.0003) and stroke history (UIC: 32% vs. 22%, P=0.07; Walk-PHaSST: 14% vs. 7%, P=0.01). On combined analysis, high-risk had strong associations with increased markers of hemolysis (hemoglobin β= -0.29, 95%CI: -0.50 to -0.09; P=0.006; reticulocyte% β=2.29, 95%CI: 1.31 to 3.25; P=1x10-5) and stroke history (OR=2.0, 95%CI: 1.3 to 3.0; P=0.0002), but no association with frequent vaso-occlusive crises (≥3/year). A high-risk genetic profile is associated with increased hemolysis and stroke history in three independent cohorts. This profile may help identify patients to prioritize for hydroxyurea and for closer monitoring strategies for stroke.

Hepatitis B virus (HBV) co-infection with HIV is high among Nigerians. Some studies have suggested impaired CD4 recovery among coinfected patients compared to the HIV mono infected. This retrospective study of treatment-naive HIV infected patients was aimed at determining the trend of changes in CD4+ counts, HIV-RNA and renal and liver function tests in response to combined antiretroviral therapy (CART). A questionnaire was utilised to extract clinical and laboratory data of HBV co infected HIV/AIDS patients before treatment and at six, twelve and eighteen months of therapy with CART. Findings were compared to those of HIV mono infected. Relevant statistical instruments were used to analyse for comparisons of means of Log10 HIV viral load and CD4 count using SPSS package 15.0. All levels of sig-nificance were at 5 %. Two thousand five hundred and sixty two patients were analysed. Of these, 354(13.8%) were HBsAg positive. Majority (63.1%) were females. Most of the recruited patients were on combivir and nevirapine. The median CD4 count for the HBsAg negative was 104 cells/mm3 (IQR 34 – 171) and it was significantly higher than those of the positive (91 cells/mm3) (p < 0.05). ALT and AST were higher among HBsAg positives, while urea and creatinine levels were similar. The median change in CD4 count from baseline and during the course of therapy were similar in the two groups. Similarly, virological responses were not different in the two groups at the various time points. In con-clusion no significant difference in the rate of CD4 recovery and HIV-RNA decline in among coinfected and monoin-fected HIV patients at different stages of therapy.

Background. Despite a large body of evidence that hydroxyurea is effective for sickle cell anemia (SCA), utilization with the "maximum tolerated dose" regimen has been low.1 Hydroxyurea therapy for SCA increases hemoglobin F, reduces pain crises, acute chest syndrome and blood transfusions, and possibly increases survival.2 The increase in hemoglobin F with hydroxyurea is related to the plasma level achieved, which depends on the dose.3 Hydroxyurea is typically initiated at 15 mg/kg/day followed by dose escalations up to 35 mg/kg/day if tolerated - the "maximum tolerated dose" approach used in the seminal Multicenter Study of Hydroxyurea (MSH) in the 1990's.4 With this approach, neutropenia and thrombocytopenia are limitations to achieving maximal dose and frequent blood count monitoring is required.These considerations limit the use of hydroxyurea in areas of the world where frequent blood monitoring is not feasible, and they also cause primary care providers in the US to hesitate to prescribe the medication. Methods. We recently reported a trial of hydroxyurea (500 mg/day orally) in 48 adults with SCA in Ibadan, Nigeria - a "fixed low-dose" approach.5 In the present report, we compare hematologic responses in 38 per protocol patients from the Ibadan study (received at least five of the planned six 4-weekly supplies of hydroxyurea)5 to the responses in 152 patients in the MSH study.6 Results. Baseline hematologic values for the two studies are shown in Table 1. Over the first 12 to 14 weeks of hydroxyurea, responses in hemoglobin, mean corpuscular volume (MCV), and platelets were similar in the two studies (Figure 1). At end-of-study (24 weeks Ibadan and 104 weeks MSH) responses in hemoglobin F and complete blood count were similar, except that the decline in neutrophil count in the Ibadan cohort was significantly less than the decline in MSH after the Bonferroni correction for multiple comparisons (Table 1and Figure 2). At this time the median (range) dose of hydroxyurea per body weight was 10 (7-14) mg/kg per day in the 38 Ibadan patients versus 20 (2.5-35) mg/kg per day in the 119 patients who remained on hydroxyurea in the MSH study.6 We performed a review of the medical records in the Ibadan patients. There were seven acute non-infectious complications in the 38 patients while taking fixed low-dose hydroxyurea for 24 weeks (admission for pain or acute chest syndrome) versus 17 while being observed off hydroxyurea for 24 weeks (pain, acute chest syndrome, need for blood transfusion, heart failure or death) (Table 2). Incidence of infections was similar during 24 weeks of fixed low-dose hydroxyurea and during 24 weeks of observation off hydroxyurea (Table 2). Discussion. These findings suggest that a "fixed low-dose" regimen may have substantial clinical benefit. Such a regimen would have a low chance of inducing cytopenias, would be straightforward for primary care providers to prescribe and would be ideal to test in combination therapy regimens for SCA. It would also be cost-efficient and affordable, especially for patients in low and middle-income countries where access to health insurance is lacking. We propose that the clinical efficacy of "fixed low-dose" hydroxyurea for SCA should be investigated further. We believe that a randomized comparison of the efficacy and safety of the "fixed low-dose" and "maximum tolerated dose" regimens should be a high priority. References Stettler N, McKiernan CM, Melin CQ, Adejoro OO, Walczak NB. Proportion of adults with sickle cell anemia and pain crises receiving hydroxyurea. JAMA 2015;313:1671-2. Platt OS. Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med 2008;358:1362-9. Charache S, Dover GJ, Moore RD, et al. Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia. Blood 1992;79:2555-65. Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 1995;332:1317-22. Tayo BO, Akingbola TS, Saraf SL, et al. Fixed Low-Dose Hydroxyurea for the Treatment of Adults with Sickle Cell Anemia in Nigeria. Am J Hematol 2018. Charache S, Barton FB, Moore RD, et al. Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Medicine (Baltimore) 1996;75:300-26. Disclosures Hsu: Global Blood Therapeutics: Research Funding; Astra Zeneca: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ironwood: Research Funding; Emmi: Consultancy; Hilton Publishing: Consultancy; Gerson Lehman Group: Consultancy; Guidepoint: Consultancy.

BACKGROUND The severity of sickle cell anemia (SCA) has been associated with five specific haplotypes in the beta globin cluster, identifiable by distinct patterns of restriction fragment length polymorphism (RFLP). These RFLP-defined haplotypes, named according to the region where they were first discovered - Central Africa region (CAR), Benin, Senegal, Arabic-Indian, and Cameroon - suggested that the sickle cell mutation arose recently at least four independent times in Africa, each time on a different genetic background, and again in India - the Multi-centric Sickle Cell Model. The beta-globin locus, however, is prone to extensive structural rearrangements, and alongside observations of ancestral sequence haplotypes extending several hundreds of kilobases beyond the beta globin cluster, it has been suggested that there is more cis-variation in the beta-globin gene cluster than is evident from RFLP analyses, and current definitions of RFLP haplotypes may not accurately reflect the ancestral origin of the sickle mutation. This undescribed cis-variation is important to understanding inter-individual phenotype variation associated with the different haplotypes. To better define this variation, we have undertaken extended, long-range molecular haplotyping of the beta-globin cluster on differing RFLP haplotype backgrounds using real time single molecule sequencing (SMS). The SMS approach generates long, unbroken reads with uniform coverage, thereby allowing for detailed molecular phasing of RFLP haplotypes and identification of local structural variation that would otherwise be hidden within the complex repetitive elements of the beta-globin cluster. In so doing, we plan to evaluate the molecular evidence for a single origin for the sickle cell allele and identify potential cis-acting, disease-modifying, candidate variants within the beta globin cluster. METHODS DNA from 200 SCA patients from three countries in sub-Saharan Africa - Nigeria, Cameroon, and Kenya - were collected after informed consent. RFLP analysis revealed the majority of the patients to be homozygous for the Benin and CAR haplotypes, with a smaller sampling of Cameroon, Senegal, and Atypical haplotypes. From this group we selected 40 samples - representing the four main classical RFLP haplotypes in sub-Saharan Africa - were selected for SMS. PCR was used to tile barcoded amplicons across the cluster. SMS was performed on a Sequel machine (Pacific Biosciences). The resulting FASTQ sequences were de-multiplexed, read quality control filters were applied, and mapped to human reference genome Hg38, prior to annotation and calling of single nucleotide variants (SNV) and structural variants (SV). RESULTS Analyses have so far identified 227 insertions, 18 deletions, 7 duplications, 76 inversions and 13 translocations from long-read analyses of the initial 40 samples; the vast majority of these variants are not described in public variant databases. Atypical haplotypes demonstrated more translocation and duplication events than other haplotypes. Insertions ~48 kb upstream of the beta-globin locus control region and 1.3 kb upstream of gamma globin gene 2 (HBG2) were observed on 50% of Senegal and 45% of CAR haplotypes. Also, recurrent insertions ranging between 32bp and 1,184bp in length, 2.3 kb downstream of the beta globin gene (HBB), were seen on 50% of the Benin and 54% of the CAR haplotypes, but only once on Senegal haplotypes. CONCLUSIONS Our findings suggest there are more cis-SVs within the beta-globin gene cluster than previously described. Work to validate these SVs using orthogonal methods and complete similar analyses of SNVs is ongoing. Variation outside of the gene cluster will also be integrated with RFLP and within-cluster molecular haplotypes to investigate the ancestral origin of the mutation, and validated cis-acting variants will be used to identify markers associated with proxies of SCA disease modification. Disclosures No relevant conflicts of interest to declare.

Background: Sickle cell disease (SCD) is a hemoglobinopathy that characteristically gives rise to a number of complications triggered by hemolytic anemia and vaso-occlusion. The prevalence of the disease is highest in sub-Saharan Africa, with the highest being in Nigeria where it affects over 6 million people.In spite of its overwhelming burden in Nigeria and the serious complications that result as a consequence, there is little in terms of epidemiological data specific to Nigeria regarding morbidity and management of the disease. Treatment of SCD and its complications includes early screening, patient education, genetic counseling, prophylaxis in the form of penicillin, vaccinations, folate supplementation, and the appropriate use of hydroxyurea (HU). While the efficacies of these treatments have been well documented in the West, morbidity and mortality due to SCD is still a significant public health problem in Nigeria. Particularly, HU has proved to be an effective disease-modifying treatment in the West. Many believe HU to be under-prescribed in Nigeria,but there is conflicting evidence. This study sought to assess the use of disease-modifying and preventive treatments, as well as barriers to treatment of sickle cell disease patients in Ibadan, Nigeria. Methods: We surveyed 50 outpatients at the University College Hospital of Ibadan (UCH) about their past and current treatment of SCD. Patients above age 12 with a primary diagnosis of SCD of any genotype were included. IRB approval was obtained through the UCH Ethics Committee and the Dartmouth College Committee for Protection of Human Subjects. All surveys were done on paper, and were administered to participants non-literate in English through a trained interpreter. Responses were input into SurveyMonkey and Excel for descriptive statistical analysis. Results: Of the people that submitted survey responses, 54% were male and 45% were female. The majority of respondents (84%) indicated that they had the SS genotype, while 14% were of SC genotype and 2% were uncertain of their genotype. The majority of respondents were between the ages of 19-45, and the majority had completed a university degree or higher education. When asked about prevention of SCD crises, 73% of respondents indicated they plan to seek genetic counseling prior to having children. Eighty-two percent of respondents indicated that they have taken prophylactic anti-malarials, while fewer people indicated that they use mosquito nets regularly for prevention of malaria (62%). Complication rates arising from SCD are listed in Table 1. When asked about pharmacotherapy options for treatment of SCD, 96% of respondents had been prescribed folate, compared to the 14% and 46% of respondents who had been prescribed oral penicillin and HU therapies, respectively. Compliance of the above drugs was relatively high as well, as the percentage of people who indicated they have taken folate (90%), penicillin (14%), and HU (42%) correlated similarly with those who had been prescribed. While the rate of those who had taken HU seem relatively high, the majority of those who had taken HU were doing so through the clinical trials of the drug being held at UCH (69%), rather than through an outside prescriber (31%). Of the 22 respondents not taking HU, 5 (23%) indicated that they would like to be taking it but are not able to, compared to the 7% of people not on penicillin who would like to be taking it. The largest potential barriers to treatment were inability to get to a hospital or clinic when necessary (16%) and lack of information about treatment options (32%). Conclusions: The most common treatment for SCD was folate therapy, followed by HU. Many patients receiving HU were formerly or currently enrolled in the clinical trials being run at UCH, which may suggest that it is not commonly prescribed by their regular providers. Most patients had faced at least one complication from SCD, and feel that their biggest deficits in treatment of SCD stem from their inability to get to a clinic or hospital in the event of a complication, and lack of information of the breadth of options that exist for management. More investigation remains to be done about the reasons for decreased usage of HU therapy among providers in Nigeria, and the efficacy of this treatment among adult patients. Given the low utilization of HU in this region, more follow up studies should be done about barriers such as cost, compliance, and access. Disclosures No relevant conflicts of interest to declare.

Essential thrombocythemia (ET) is one of the classical clonal myeloproliferative neoplasms (MPNs) that constitute a clinical entity distinct from the other MPNs such as polycythemia vera and primary myelofibrosis despite the similarities in their molecular basis. The genetic basis of ET has been associated with the detection of the mutation of three mutually exclusive driver mutations, namely, Janus kinase 2 (JAK2), calreticulin, and myeloproliferative leukemia genes, making them important biomarkers in the diagnosis of ET. This condition is clinically characterized by thrombohemorrhagic complications and progression to myelofibrosis and acute myeloid leukemia. The reduction of the thrombotic complication and/or the associated hemorrhage constitutes the primary goal of the therapeutic practice for the management of ET. We report here seven cases of ET referred to the University College Hospital within a 3-year period (2014–2016). This case series describes the management practices and the therapeutic outcomes in the patients (using the resolution of the clinical presentations and decrease in platelet count). The report also highlights some of the challenges encountered in the management of ET in a resource-limited country like Nigeria.

A substantial proportion of patients with chronic kidney disease (CKD) develop iron deficiency anaemia (IDA). Despite the association of IDA with adverse cardiovascular outcomes, it remains underdiagnosed and poorly managed. Up to 70% of patients with CKD are anaemic at the time of initiating dialysis, while the predictors of IDA in these patients in our setting are unknown. This study aimed to determine the prevalence and risk factors for IDA in patients with CKD.This is a case-control study of 157 patients with CKD and 157 age and gender matched subjects without CKD. Information obtained from the participants were socio-demographic details, aetiology of CKD, medication history and features of IDA. All participants had serum ferritin, total iron binding capacity (TIBC), transferrin saturation (TSAT), highly sensitive C-reactive protein, serum creatinine and complete blood count determined.The median estimated glomerular rate (22.7 [3.4-59.5] vs. 110.2 [60.3-152.8] ml/min/1.73 mIDA is common among individuals with CKD while female gender and severity of CKD were factors that independently predicted IDA.

Introduction: The clinical and public health implications of the convergence of the human immunodeficiency virus (HIV) epidemic and chronic viral hepatitis in sub-Saharan Africa are poorly understood. This study was designed to determine the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV), and the impact of co-infection on baseline serum alanine transaminase (ALT), CD4 + T lymphocyte (CD4) count, and plasma HIV-RNA (viral load) in a cohort of HIV-infected Nigerians. Methods: A retrospective study was conducted, on eligible treatment-naive patients who presented between August 2004 and February 2007 to the University College Hospital (UCH), Ibadan, Nigeria. Demographic data and pre-treatment laboratory results (hepatitis B surface antigen (HBsAg), HCV antibodies (anti-HCV), ALT, CD4 count and viral load) were retrieved from the medical records. Fisher’s exact, two sample t-tests, and the Wilcoxon rank sum tests were used to compare groups. A logistic regression model was fitted to explore characteristics associated with co-infection status. Results: A total of 1779 HIV-infected patients (male: female ratio, 1:2) met inclusion criteria. HBsAg was present in 11.9%, antiHCV in 4.8% and both markers in 1%. HBsAg was more common among males than females (15.4% vs 10.1%, respectively p = 0.001) while anti-HCV was detected in a similar proportion of males and females (5.3% versus 4.6%, respectively p = 0.559). HIV-infected patients with anti-HCV alone had a lower mean baseline CD4 count compared to those without antiHCV or HBsAg (197 cells/mm 3 vs 247 cells/mm 3 , respectively p = 0.008). Serum ALT was higher among patients with HBsAg compared to those without HBsAg or anti-HCV (43 International Units (IU) vs. 39 IU, respectively p = 0.015). Male gender was associated with HBV co-infection on logistic regression (OR1.786; 95% CI, 1.306-2.443; p < 0.005). Conclusion: More HIV-infected females than males presented for care in this cohort. We identified a relatively high prevalence of HBV and HCV co-infection in general, and a higher rate of HBV co-infection among males than females. Pre-treatment CD4 count was significantly lower among those with HCV co-infection, while ALT was slightly higher among those with HBV co-infection. Triple infection with HIV, HBV and HCV was present in a small but significant proportion of patients. These findings underscore the importance of testing for HBV and HCV in all HIV-infected persons in our setting.

The objective of this review is to assess the effectiveness of intravenous calcium given during exchange blood transfusion (EBT) in neonates.More specifically, the objectives of the review are to determine whether:Neonatal hyperbilirubinaemia is an abnormally high level of bilirubin in the circulating blood, resulting in clinically visible icterus or jaundice. A serum bilirubin level above 5 mg per dL (86 μmol per L) is a frequently encountered problem worldwide and is a common reason for neonates to present to the emergency department.Unconjugated bilirubin is toxic to infants' brains when the concentration exceeds a certain level. An unconjugated serum bilirubin concentration at toxicity level is described as 'severe hyperbilirubinaemia'. The concentrations that define toxic level vary, depending on the gestational age of the neonates and fetal maturity.Severe hyperbilirubinaemia can cause encephalopathy if not promptly treated, with significant complications such as athetoid cerebral palsy, sensorineural hearing loss, paralysis of upward gaze, dental enamel dysplasia and death.Recent reports indicate that these conditions, though rare, are still occurring despite the availability of efficient methods for treatment of hyperbilirubinaemia and its prevention.These complications can be prevented if the level of bilirubin is reduced rapidly with exchange blood transfusion.Exchange blood transfusion (EBT) is the most rapid and effective method for lowering serum bilirubin concentrations, but it is rarely needed when intensive phototherapy is effective.In the presence of hemolytic disease, severe anaemia, or a rapid rise in the total serum bilirubin level (greater than 1 mg per dL per hour in less than six hours), EBT is the recommended treatment. EBT also removes partially hemolyzed and antibody-coated erythrocytes and which is then replaced with uncoated donor red blood cells. If intensive phototherapy fails to lower the bilirubin level, then EBT is always considered as the next line of treatment in any newborn with non-hemolytic jaundice.Complications of EBT can include hypocalcaemia, seizures and even death within 24 hours. The potential seriousness of these complications makes clinicians consider intensive phototherapy before EBT.However, the option of intensive phototherapy may not be feasible and could be quite ineffective in resource limited settings where the required facilities and electrical power supply are inadequate. Under these circumstances neonates with severe hyperbilirubinaemia will most likely be treated with EBT.Exchange transfusion of blood collected with acid-citrate-dextrose (ACD) containing bags may produce hypocalcaemia.To decrease the morbidity from chelation of divalent cations by citrate, routine administration of calcium gluconate during EBT was advocated,but tetany, convulsion and death may still occur when ACD blood is used.However, there are controversies about the effectiveness of intravenous calcium in reducing these calcium-related morbidities. A preliminary search for systematic reviews in MEDLINE, the Cochrane Library, Campbell Library and the Joanna Briggs Database of Systematic Reviews and Implementation Reports failed to identify any existing publications on this topic. As a result, this review will examine current quantitative evidence regarding the effectiveness of routine administration of intravenous calcium during EBT in the treatment of severe hyperbilirubinaemia, with specific aim to describe incidences of hypocalcaemia, seizures and deaths after such a transfusion.

There is a dearth of information on the reference values for haematological indices particularly according to the relevant trimesters of pregnant women in Nigeria. The objective of this study was to provide reference values for Nigerian pregnant women. The study took place at the Adeoyo Maternity Hospital and the University College Hospital, both in Ibadan. This descriptive study was carried out over a period of 8 months. Subjects were apparently healthy pregnant women that satisfied the inclusion and exclusion criteria. The mean values (and 95% confidence intervals, CI) of haematological indices were as follows -- First trimester: Haemoglobin (Hb) 112.44 (101.64 - 123.25) g/l, haematocrit (hct) 35 (32 - 38)%, WBC 5.488 (4.025 - 6.950) x 10(9)/l and platelet counts 227.56 (165.21 - 289.90) x 10(9)/l;Second trimester: Hb 100.39 (97.85 - 102.92) g/l, hct 29.3 (28.5 - 30.1)%, WBC 6.57 (6.19 - 6.95) x 10(9)/l, platelet count 229.56 (211.86 - 247.26); and the Third trimester: Hb 98.06 (96.12 - 100.00) g/l, hct 29.4 (28.7 - 29.9)%, WBC 6.92 (6.53 - 7.30), platelet count 186.52 (177.67 - 195.38) x 10(9)/l. These results were compared with those of 52 non-pregnant age matched women volunteers as controls whose mean haematological indices and 95% CI were: Hb 120.51 (116.61 - 124.41) g/l, hct 36 (25 - 48)%, WBC 5.28 (2.9 - 8.7) x 10(9), platelet count 330.87 (176 - 538) x 10(9)/l. The following haematological indices: WBC, platelet counts, RBC, PCT, and PDW, of women between the trimesters showed statistical significance (p value0.001 in each case). The WBC is inversely proportional to the PCT and the MCV in the pregnant women was slightly raised. In this study, pregnancy is characterised by lowest values of haemoglobin parameters in trimester three and there are statistically significant differences between the WBC, platelet counts, RBC, PCT, and PDW of women between the three trimesters.

Background: The vast majority of births with sickle cell anemia occur in Africa 1 and early-life mortality, generally before age five years, is as high as 90% 2,3. Hydroxyurea was approved for sickle cell anemia by the US FDA in 1998 but is not commonly used in Africa due to fear of toxicity, lack of awareness and limited availability. Hemoglobin F is a protective factor that decreases severity of sickle cell anemia, and hydroxyurea treatment leads to an increase in hemoglobin F. In the US, hydroxyurea is typically initiated at a dose of 15 mg/kg followed by dose escalations of up to 35 mg/kg if tolerated with a goal of maximal tolerated dose and maximal response in hemoglobin F. Neutropenia and thrombocytopenia are the usual limitations to achieving maximal dose. In the landmark Multicenter Study of Hydroxyurea, the clinical response to hydroxyurea correlated strongly with a reduction in the neutrophil count as well as an increase in the fetal hemoglobin concentration as reflected in percentage of F cells. A striking decrease in pain crises was observed in the first three months of therapy, before dose escalation and before maximal increase in hemoglobin F levels 4. Furthermore, hydroxyurea in the range of 10-15.9 mg/kg/day was reportedly effective in decreasing the frequency of pain episodes in children and adolescents in Oman 5, and hydroxyurea 10 mg/kg/day decreased pain episodes in children and adults with sickle cell anemia in India 6. From these perspectives, we reasoned that a fixed dose of hydroxyurea 10 mg/kg/day is reasonable to investigate in the African setting where the safety in relationship to the resources and infectious exposures is not known. Methods: We assigned 48 sickle cell anemia patients to hydroxyurea 500 mg/day for 24 weeks to determine safety and efficacy; 28 had high-risk disease based on hemoglobin F Results: The median (interquartile range) age was 25 (22-27) years and the median hydroxyurea dose 9.8 (9.1-10.4) mg/kg per day. The patients complied with treatment for a median of 20 (16-24) weeks. Four (8.3%) developed a pre-specified adverse outcome: clinical malaria (N=2), thrombocytopenia in combination with malaria (N=1), pulmonary tuberculosis (N=1). During therapy the median hemoglobin increased by 9.0 g/L, mean corpuscular volume by 11.2 fL and body weight by 3.0 kg while median white blood cells declined by 2600 per uL and platelets by 127,000 per uL (P Conclusion: Our results suggest that low, fixed-dose dose hydroxyurea for sickle cell anemia in Nigeria is associated with a low adverse outcome rate and with improvements in blood counts, hemoglobin F and body weight. The effects on vaso-occlusive episodes and on the risks of recrudescent tuberculosis and malaria-associated thrombocytopenia should be assessed in further studies. Acknowledgment: Supported by a grant from the Doris Duke Foundation. References 1. Williams TN, Obaro SK. Sickle cell disease and malaria morbidity: a tale with two tails. Trends Parasitol 2011;27:315-20. 2. Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Sickle cell disease in Africa: a neglected cause of early childhood mortality. Am J Prev Med 2011;41:S398-405. 3. Makani J, Cox SE, Soka D, et al. Mortality in sickle cell anemia in Africa: a prospective cohort study in Tanzania. PLoS One 2011;6:e14699. 4. Charache S, Barton FB, Moore RD, et al. Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Medicine (Baltimore) 1996;75:300-26. 5. Sharef SW, Al-Hajri M, Beshlawi I, et al. Optimizing Hydroxyurea use in children with sickle cell disease: low dose regimen is effective. Eur J Haematol 2013. 6. Patel DK, Mashon RS, Patel S, Das BS, Purohit P, Bishwal SC. Low dose hydroxyurea is effective in reducing the incidence of painful crisis and frequency of blood transfusion in sickle cell anemia patients from eastern India. Hemoglobin 2012;36:409-20. Disclosures Ezekekwu: American Society of Hematology: Other: The Visitor training program was sponsored by ASH. Hsu: AstraZeneca steering committee for HESTIA trial: Research Funding. Gordeuk: Emmaus Life Sciences: Consultancy.

Background Patients with sickle cell disease in the USA have been noted to have lower levels of vitamin D – measured as 25-hydroxyvitamin D (25(OH)D) – compared to controls. Average serum 25(OH)D levels are also substantially lower in African Americans than whites, while population distributions of 25(OH)D among Jamaicans of African descent and West Africans are the same as among USA whites. The purpose of this study was to examine whether adult patients with sickle cell disease living in tropical regions had reduced 25(OH)D relative to the general population. Methods We analyzed serum 25(OH)D in stored samples collected from studies in Jamaica and West Africa of adult patients with sickle cell disease and adult population controls. Results In samples of 20 Jamaicans and 50 West Africans with sickle cell disease mean values of 25(OH)D were 37% and 39% lower than controls, respectively. Metabolic abnormalities in the absorption and conversion pathways are possible causes for the consistent relative deficiency of 25(OH)D in sickle cell disease. Conclusions Low 25(OH)D levels in tropical Africa where the burden of sickle cell disease is highest, deserve further investigation, and a randomized trial is warranted to address efficacy of supplementation.

To identify factors that affect manifestations of sickle cell anemia we compared patients 11-30 years of age from University of Ibadan, Ibadan, Oyo, Nigeria (n = 214) and University of Illinois at Chicago, Chicago, IL, USA (n = 209). Paralleling findings in the general populations of the two countries, the Chicago patients were more often overweight or obese as defined by the Centers for Disease Control and Prevention (Atlanta, GA, USA) guidelines, and more often had elevated blood pressure (BP) as defined by the National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, USA guidelines. The Ibadan patients did not receive the pneumococcal vaccine or hydroxyurea (HU) therapy as frequently as the Chicago patients. Consistent with lower rates of elevated BP and increased body mass index (BMI), stroke history was less frequent in the Ibadan patients ≥18 years old. Furthermore, in combined analyses, systolic and diastolic BP directly correlated with BMI, and elevated weight status independently associated with history of stroke. Our findings are consistent with the possibility that higher values for BMI and BP in Chicago sickle cell anemia patients may contribute to an increased risk of stroke and highlights the need for measures to reduce these risk factors. On the other hand, lower pneumococcal vaccination and HU therapy rates in Ibadan patients highlights the need for more improved vaccination coverage and for studies to define the role of HU therapy in Africa.

Two common genetic modifiers, α-thalassemia and the BCL11A rs1427407 T allele, are observed in approximately one-third of patients with sickle cell anemia (SCA) and are associated with reduced hemolysis and higher hemoglobin F (HbF) levels, respectively. We investigated the laboratory and clinical effects of α-thalassemia and the BCL11A rs1427407 T allele in the University of Ibadan cohort of SCA patients and replicated our findings in two independent SCA cohorts, University of Illinois at Chicago (UIC) and Walk-Treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy (Walk-PHaSST). Alpha-thalassemia status was determined by PCR in all 3 cohorts while the BCL11A rs1427407 genotype was determined by PCR in the Ibadan and UIC cohorts and imputed in the Walk-PHaSST cohort. Comparisons according to genotype were performed using the linear trend test for continuous variables and Cochran's test of linear trend for categorical variables. Alpha-thalassemia was observed in 43% of 257 SCA patients from Ibadan and was associated with higher body mass index and lower white blood cell count (Table 1). The BCL11A rs1427407 T allele was observed in 46% of SCA patients from Ibadan and was associated with higher hemoglobin concentration. HbF levels by HPLC were available in 25 patients (12 with the BCL11A rs1427407 T allele) enrolled in a study of low-dose hydroxyurea; these levels were higher in patients with at least one rs1427407 T allele at baseline and progressively during therapy with hydroxyurea 10 mg/kg/day (repeated measures P=0.01). We defined a high risk genetic group as the absence of α-thalassemia in combination with absence of the BCL11A rs1427407 T allele. This high risk group was observed in 31% of SCA patients from the Ibadan cohort and was associated with a higher reticulocyte percentage (15.0% vs. 7.8%, P=0.08) and a higher prevalence for a history of stroke (6% vs. 1%, P=0.02). The association with stroke history persisted on logistic regression analysis after adjusting for age, gender, and hydroxyurea therapy (OR 9.4, 95%CI: 1.2-72.8; P=0.03). We then replicated the association of this high risk group with markers of hemolysis and with history of stroke in the UIC and Walk-PHaSST SCA cohorts. In the UIC cohort, the high risk group was observed in 34% (92/271) and was also associated with higher reticulocyte counts (13.5% vs. 11.9%, P=0.10) and higher prevalence for stroke history (33% vs. 22%; age, gender, HU-adjusted OR 1.7, 95%CI: 1.0-3.0; P=0.066). In the Walk-PHaSST cohort, this high risk profile was observed in 38% (149/394) and was associated with a higher reticulocyte percentage (9.7% vs. 8.4%, P=0.0005), lower hemoglobin concentration (8.4 vs. 8.8 g/dL; P=0.017), and higher prevalence for stroke history (15% vs. 6%; age, gender, HU-adjusted OR 2.6, 95%CI: 1.3-5.3; P=0.007). In conclusion, a high risk group of SCA patients, defined by the lack of the protective α-thalassemia and the BCL11A rs1427407 variants, is associated with a higher degree of hemolysis and a higher prevalence of stroke history on cross sectional analysis in three independent cohorts. This high-risk profile may help identify patients to prioritize for hydroxyurea therapy and for closer monitoring strategies for stroke. Disclosures Hsu: Sancilio: Research Funding; Astra Zeneca: Consultancy, Research Funding; Purdue Pharma: Research Funding; Gerson Lehman Group: Consultancy; Eli Lilly: Research Funding; Centers for Medicare and Medicaid Innovation: Research Funding; Hilton Publishing: Consultancy, Research Funding; Mast Therapeutics: Research Funding; EMMI Solutions: Consultancy; Pfizer: Consultancy, Research Funding.

The clinical and public health implications of the convergence of the human immunodeficiency virus (HIV) epidemic and chronic viral hepatitis in sub-Saharan Africa are poorly understood. This study was designed to determine the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV), and the impact of co-infection on baseline serum alanine transaminase (ALT), CD4+ T lymphocyte (CD4) count, and plasma HIV-RNA (viral load) in a cohort of HIV-infected Nigerians.A retrospective study was conducted, on eligible treatment-naive patients who presented between August 2004 and February 2007 to the University College Hospital (UCH), Ibadan, Nigeria. Demographic data and pre-treatment laboratory results (hepatitis B surface antigen (HBsAg), HCV antibodies (anti-HCV), ALT, CD4 count and viral load) were retrieved from the medical records. Fisher's exact, two sample t-tests, and the Wilcoxon rank sum tests were used to compare groups. A logistic regression model was fitted to explore characteristics associated with co-infection status.A total of 1779 HIV-infected patients (male: female ratio, 1:2) met inclusion criteria. HBsAg was present in 11.9%, anti-HCV in 4.8% and both markers in 1%. HBsAg was more common among males than females (15.4% vs 10.1%, respectively p = 0.001) while anti-HCV was detected in a similar proportion of males and females (5.3% versus 4.6%, respectively p = 0.559). HIV-infected patients with anti-HCV alone had a lower mean baseline CD4 count compared to those without anti-HCV or HBsAg (197 cells/mm3 vs 247 cells/mm3, respectively p = 0.008). Serum ALT was higher among patients with HBsAg compared to those without HBsAg or anti-HCV (43 International Units (IU) vs. 39 IU, respectively p = 0.015). Male gender was associated with HBV co-infection on logistic regression (OR1.786; 95% CI, 1.306-2.443; p0.005).More HIV-infected females than males presented for care in this cohort. We identified a relatively high prevalence of HBV and HCV co-infection in general, and a higher rate of HBV co-infection among males than females. Pre-treatment CD4 count was significantly lower among those with HCV co-infection, while ALT was slightly higher among those with HBV co-infection. Triple infection with HIV, HBV and HCV was present in a small but significant proportion of patients. These findings underscore the importance of testing for HBV and HCV in all HIV-infected persons in our setting.

Introduction: Chronic hemolysis occurs in sickle cell anemia as a result of recurrent sickling and other abnormalities of the red blood cells including eryptosis. Exuberant reticulocytosis is anticipated to partially compensate for the resultant anemia. Sickle cell anemia patients may also have aplastic crisis, bone marrow (BM) infarction and erythropoietin deficiency which could lead to reticulocytopenia despite the anemia. High degree of reticulocytosis among asymptomatic infants with sickle cell anemia has been associated with an increased risk of death or stroke during childhood. Assessment of BM function in sickle cell anemia is important due to potential complications associated with both under-activity and hyperactivity. This study aimed at evaluating the erythropoietic function of the BM in steady state sickle cell anemia using corrected reticulocyte counts. Methods: This study was carried out at the hematology clinic in the University College Hospital, Ibadan. HbSS patients in steady state were recruited from the hematology clinic. Local ethical committee approval was obtained and all participants gave written informed consent. Patients with M. tuberculosis, Hepatitis B, HIV and P. falciparum infection were excluded. Peripheral blood samples were analyzed using Sysmex Ki-X21 for complete blood count (CBC) and standard point of care for serum electrolytes and liver function tests. The glomerular filtration rates were calculated using the Cockcroft-Gault formula. Reticulocyte counts were determined manually using fresh samples from K2 EDTA bottles and methylene blue stain. Two drops of stain were mixed with two to four volumes of anticoagulated blood and incubated at 37ºC for 15 minutes. Afterwards, the cells were re-suspended and blood films were made. Corrected reticulocyte count and reticulocyte production index were calculated. Participants were categorized according to corrected reticulocyte counts of greater than or less than 2.5%. Univariate and multivariate analyses were performed to determine variables associated with corrected reticulocyte count Results: 92 HbSS patients were recruited with a mean (SD) age of 19.6 (5.8) years. There was no correlation between age and eGFR (p-value: 0.227). Median (range) reticulocyte count, corrected reticulocyte count and reticulocyte production index were 5.5 (0.5 - 29.9), 3.3 (0.1 - 17.1) and 1.7 (0.2 - 8.6) respectively. 40 (43.5%) patients had corrected reticulocyte count 2.5%. Those corrected reticulocyte count 2.5% (Table 1). CBC parameters were not different when compared between both groups. Results of multivariate logistic regression analysis carried out showed that only AST was independently linked with corrected reticulocyte count Table 1. Factors Associated with Low Reticulocyte Count Corrected count2.5% p-Value Age (Mean, SD) 21.4 (6.3) 18.4 (5.0) 0.013 Gender (N, %) Male 22 (55.0) 28 (53.8) 0.912 Female 18 (45.0) 24 (46.2) Height (Mean, SD) 1.6 (0.1) 1.5 (0.1) 0.041 BMI (Mean, SD) 18.7 (3.1) 18.7 (3.0) 0.753 GFR (Mean, SD) 64.3 (37.7) 66.4 (29.3) 0.453 Bilirubin (Mean, SD) 1.7 (1.1) 1.9 (2.6) 0.674 AST (Mean, SD) 22.5 (13.5) 14.5 (6.6) 0.006 ALT (Mean, SD) 13.4 (7.7) 14.4 (11.1) 0.876 Table 2. Independent Predictors of Corrected Reticulocyte Count Conclusion: Despite corrected reticulocyte count Disclosures No relevant conflicts of interest to declare.

The effect of association-dissociation on the sulphydryl reactivity of human hemoglobin A is reported. The reactivity of CysF9(93)beta towards the sulphydryl reagent, 5,5'-dithiobis(2-nitrobenzoate), is higher at lower concentrations of hemoglobin at all pH values. This is because hemoglobin dimers have higher sulphydryl reactivity than tetramers and it is known that the proportion of dimers increases as the hemoglobin concentration decreases. This study takes advantage of this observation to determine the tetramer-dimer dissociation constant, K(4,2), of hemoglobin A and subsequently the proton uptake and the proton release during this process. The concentration dependence profiles of the apparent second-order rate constants, k(app), show that (between 2 and 20 microM heme) k(app) decreases with increasing hemoglobin concentration. Above 30 M heme k(app) remains fairly constant for all hemoglobin derivatives (oxy, carbonmonoxy and aquomethemoglobin) used. The pH dependence of the negative logarithm of tetramer-dimer dissociation constant, pK(4,2), for oxy- (and for carbonmonoxy-) hemoglobin exhibits a biphasic character with a maximum near pH 7.4 (and 6.6). For aquomethemoglobin, pK(4,20 decreases with increasing pH. The tetramer-dimer dissociation of human oxyhemoglobin A at an ionic strength of 200 mM uptakes 0.87 +/- 0.09 mole of protons between pH 6.2 to 7.4 phase and releases 0.84 0.09 mole of protons between pH 7.4 and 9.0 phase. Under a similar condition carbonmonoxyhemoglobin uptakes 0.54 +/- 0.05 mole of protons between pH 5.8 and 6.6 phase and releases 0.48 +/- 0.05 mole of protons between pH 6.6 and 9.0 phase. Aquomethemoglobin has only a single phase, it releases 0.39 +/- 0.05 mole of protons during tetramer-dimer dissociation.

Hodgkin's disease and non-Hodgkin's lymphomas are interrelated disorders which have been reported to occur either simultaneously or sequentially in the same patient. We report here the development of nodular sclerosing type Hodgkin's disease in a patient two decades after successful treatment for Burkitt's lymphoma with cyclophosphomide and abdominal resection (AR). While the onset of symptoms after treatment for Burkitt's lymphoma was seven years definitive diagnosis of Hodgkin's disease was only made 22 years after the initial diagnosis of Burkitt's lymphoma. The recurrent and solitary nature of the lymphadenopathy and the fact that it was initially reported as reactive hyperplasia is typical of nodular lymphocyte predominant Hodgkin's disease. We believe that there was a transitory period of the malignancy as nodular lymphocyte predominant klodgkin's disease.

Sickle cell anemia (SCA) is among the most common monogenetic diseases worldwide and environmental and genetic factors are thought to contribute to variations in clinical presentation. We conducted a study to compare clinical and laboratory features between 214 SCA patients from the University of Ibadan, Nigeria and 200 SCA patients from the University of Illinois at Chicago, U.S. between the ages of 11 and 30 years old. Laboratory and clinical data were collected from clinic visits and comparisons between the two cohorts were adjusted for age, gender, and hydroxyurea use. SCA patients from Nigeria had lower median body weight, height, body mass index, systolic blood pressure, mean arterial pressure and pulse pressure (Table 1). Proportions of hydroxyurea use and vaccinations for streptococcus pneumoniae and influenza A were lower in SCA patients from Nigeria. Hematological indices showed that SCA patients from Nigeria had lower median values for hemoglobin F (HbF) percent, hemoglobin concentration and mean corpuscular volume but platelet and white blood cell counts were not significantly different compared to SCA patients from the U.S. In the white blood cell differential, lower granulocyte counts and higher lymphocyte and monocyte counts were observed in SCA patients from Nigeria. The proportion of patients with a history of ≥ 3 vaso-occlusive pain episodes requiring medical attention per year were similar between the Nigerian and U.S. cohorts but the proportions with histories of stroke, acute chest syndrome and > 5 lifetime transfusions were lower in the Nigerian versus U.S. cohort. On logistic regression analysis, male gender was independently associated with vaso-occlusive crises ≥ 3 per year in the Nigerian cohort (OR 1.9, 95% CI 1.1 – 3.4, p=0.04) and lower HbF concentration was associated with this pain category in the U.S. cohort (Hb F 1% decrement OR 1.1, 95% CI 1.0 – 1.1, p=0.02). A higher white blood cell count was independently associated with stroke history in both the Nigerian and U.S. cohorts (Nigeria: OR 1.1, 95% CI 1.0 - 1.3, p=0.03; US: OR 1.2, 95% CI 1.1 – 1.3, p=0.003). Additionally, a lower HbF concentration was independently associated with stroke history in the Nigerian cohort (Hb F 1% decrement OR 2.5, 95% CI 0.2 – 0.9, p=0.03). The lower height and low proportions of vaccination among the Nigerian SCA patients point to the need for improved nutrition and vaccination strategies, and the low utilization of hydroxyurea therapy highlights the need to investigate the appropriateness of this agent in the African context. On the other hand, the higher values for BMI and blood pressure in the UIC compared to Nigerian SCA patients parallel similar findings in non-sickle cell cohorts and raises the possibility that life-style factors may contribute to the higher rate of stroke in the UIC cohort. Whether the lower rate of complications in general in the Nigerian SCA patients reflects higher early mortality versus favorable genetic or environmental factors deserves further investigation. In summary, our study found both differences and similarities between patients with SCA from Nigeria and the U.S. and a better understanding of the genetic and environmental contributions may help guide future therapies for SCA in both settings. Disclosures: No relevant conflicts of interest to declare.

Background Mammography has been used in developed countries with considerable success but very little is known about this imaging modality in low resource settings. This study examined the level of awareness of mammography and determined factors influencing the level of awareness. Methods We conducted a hospital based cross sectional study to investigate the level of awareness of mammography among 818 randomly selected women attending the General Outpatient clinics (GOP) of the University College Hospital (UCH), Ibadan, Nigeria. Independent predictors of level of awareness of mammography were identified using multiple logistic regression analysis. Results The proportion of women who ever heard of mammography was 5%, and they demonstrated poor knowledge of the procedure. Those with primary or secondary levels of education were about three times less likely to be aware of mammography when compared with those with tertiary level of education (OR = 0.3, 95% CI, 0.12 – 0.73). Also, participation in community breast cancer prevention activities (OR = 3.4, 95% CI, 1.39 – 8.36), and previous clinical breast examination (OR = 2.34, 95% CI, 1.10 – 4.96) independently predicted mammography awareness. Newspapers and magazines appeared to be the most important sources of information about mammography screening. Conclusion The level of awareness of mammography is poor among women attending outpatient clinics in the studied population. Interventions promoting awareness of this screening procedure should give particular attention to the illiterate and older women while clinicians performing breast examinations should utilize the opportunity to inform women about the mammography procedure. Promotion of educational articles on breast cancer and its screening methods via media remains vital for the literate.