A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease

Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11·4%) and deferoxamine (11·1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease

Is renal medullary carcinoma the seventh nephropathy in sickle cell disease? A multi-center Nigerian survey

Introduction: Previous studies had enlisted renal medullary carcinoma (RMC) as the seventh nephropathy in sickle cell disease (SCD). Clinical experience has contradicted this claim and this study is targeted at refuting or supporting this assumption.Objective: To estimate the prevalence of RMC and describe other renal complications in SCD.Materials and methods: 14 physicians (haematologists and urologists) in 11 tertiary institutions across the country were collated from patients’ case notes and hospital SCD registers.Results: Of the 3,596 registered sickle patients, 2 (0.056%) had been diagnosed with RMC over a ten year period, thereby giving an estimated prevalence rate of 5.6 per 100,000. The most common renal complication reported by the attending physicians was chronic kidney disease (CKD). The frequency of routine renal screening for SCD patients varied widely between centres – most were done at diagnosis, annually or bi-annually.Conclusion: The ten year prevalence of RMC in Nigerian SCD patients was determined to be 5.6 (estimated incidence of 0.56). RMC is not more common in SCD patients and therefore cannot be regarded as a “Seventh Sickle nephropathy”. Most of the managing physicians reported that the commonest nephropathy observed in their SCD patients was chronic kidney disease.Keywords: Renal medullary carcinoma, seventh nephropathy, sickle cell disease, Nigerian surve

Is renal medullary carcinoma the seventh nephropathy in sickle cell disease? A multi-center Nigerian survey.

Introduction: Previous studies had enlisted renal medullary carcinoma (RMC) as the seventh nephropathy in sickle cell disease (SCD). Clinical experience has contradicted this claim and this study is targeted at refuting or supporting this assumption. Objective: To estimate the prevalence of RMC and describe other renal complications in SCD. Materials and methods: 14 physicians (haematologists and urologists) in 11 tertiary institutions across the country were collated from patients\u2019 case notes and hospital SCD registers. Results: Of the 3,596 registered sickle patients, 2 (0.056%) had been diagnosed with RMC over a ten year period, thereby giving an estimated prevalence rate of 5.6 per 100,000. The most common renal complication reported by the attending physicians was chronic kidney disease (CKD). The frequency of routine renal screening for SCD patients varied widely between centres \u2013 most were done at diagnosis, annually or bi-annually. Conclusion: The ten year prevalence of RMC in Nigerian SCD patients was determined to be 5.6 (estimated incidence of 0.56). RMC is not more common in SCD patients and therefore cannot be regarded as a \u201cSeventh Sickle nephropathy\u201d. Most of the managing physicians reported that the commonest nephropathy observed in their SCD patients was chronic kidney disease

Steady state haemoglobin level increases with the proportion of erythrocyte membrane n-3 fatty acids in sickle cell anaemia

Previous studies indicate that perturbation of erythrocyte and/or plasma lipids occurs in homozygous sickle cell disease (SCD), and treatment with n-3 fatty acids (FA) is beneficial to affected individuals (Tomer et al, Thromb Haemost 2001; 966–974). Phosphatidylserine has a role in sickle erythrocyte-endothelial adhesion, which contributes to vessel occlusion in SCD (Setty et al, Blood 2002; 1564–1571). Considering that n-3 and n-6 FA are essential structural and functional components of the red cell membrane, the objective of this study was to find out if abnormalities of these FA affect the degree of anaemia in SCD. We recruited 43 HbSS patients and 43 racially-matched, healthy, HbAA controls living in the same environment; analysed the fatty acid composition of erythrocyte membrane choline (CPG), serine (SPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SPM); and sought for relationship between steady-state Hb level in SCD and the proportion of n-3 FA in the red cell membrane. HbSS individuals had high levels of adrenic and docosapentanoic acids in CPG, EPG, SPG (p<0.001), and SPM (p<0.05). Arachidonic acid (AA) was increased in CPG (p<0.001) and EPG (p<0.005) of the patients. In contrast, linoleic acid (LA) was low in patients' CPG, EPG, SPG and SPM (p<0.001). Both LA and AA were reduced in plasma CPG, triglycerides and cholesterol esters of SCD patients. There was significant positive correlation between steady-state Hb level and n-3 FA content of erythrocytes: docosahexaenoic (DHA, p<0.01, r = 0.63) and eicosapentanoic (EPA) acids in red cell CPG, and EPA in EPG (p<0.05, r = 0.60); figs. 1&2. The observed high AA with low DHA/EPA levels favour red cell adherence to vascular endothelium and vaso-occlusion. The data suggest that in SCD: synthesis of AA and/or membrane uptake of LA and AA may be abnormal; increased proportions of erythrocyte membrane DHA and EPA confer some resistance to haemolysis

Blood mononuclear cells and platelets have abnormal fatty acid composition in homozygous sickle cell disease

Leukocyte adhesion to vascular endothelium contributes to vaso-occlusion and widespread organ damage in sickle cell disease (SCD). Previously, we found high expression of the adhesion molecules αMβ2 integrin and L-selectin in HbSS individuals with severe disease. The n-6 and n-3 polyunsaturated fatty acids (FA) are vital structural and functional components of cell and sub-cellular membranes. They modulate cell adhesion, inflammation, aggregation and vascular tone. We investigated the FA composition of mononuclear cells (MNC) and platelets of HbSS patients in steady-state (n = 28); and racially matched, healthy HbAA controls (n = 13). MNC phospholipids of the patients had low levels of docosahexanoic acid (DHA, p<0.01), n-3 metabolites (p<0.05) and total n-3 polyunsaturated FA (p<0.05); table 1. In contrast, arachidonic (AA, p<0.005), AA:DHA ratio (p<0.005, fig 1) and total n-6 metabolites (p<0.05) were increased in the patients. Similarly, platelets from HbSS patients had low levels of eicosapentanoic acid (EPA, p<0.05), and raised AA (p<0.05) in choline phosphoglycerides (CPG); with reduced linoleic acid (LA, p<0.005) and DHA (p<0.05) in ethanolamine phosphoglycerides. Platelet CPG had lower DHA levels in HbSS individuals with complications of SCD compared to those who had no complications (p<0.05, fig.2). Reduced EPA and DHA relative to AA favours the production of aggregatory and pro-inflmmatory eicosanoids that activate leukocytes and platelets. This may lead to enhanced inflammation, leukocyte adhesion, platelet aggregation and vaso-occlusion in SCD. Table 1: Fatty Acid Composition of MNC Total Phospholipids in HbSS Patients and HbAA Controls Fatty Acids HbSS Patients HbAA Controls 24:0 0.71 [0.30]*** 1.3 [0.4] saturates ∑ 38.2 [3.6] 39.1 [1.7] 16:1 0.69 [0.45] 0.56 [0.11] 18:1 14.4 [1.8]* 12.9 [1.9] 24:1 1.2 [0.3] 1.1 [0.4] ∑monoenes 16.2 [2.1]** 14.3 [1.4] 18:2n-6 6.1 [0.9] 7.0 [1.4] 18:3n-6 0.11 [0.04]* 0.23 [0.17] 20:2n-6 0.56 [0.18]** 0.83 [0.32] 20:3n-6 (DHGLA) 1.2 [0.2]* 1.4 [0.2] 20:4n-6 20.2 [1.7]*** 18.1 [1.8] 22:4n-6 1.7 [0.4] 1.6 [0.4] 22:5n-6 0.3 [0.21] 0.24 [0.14] n-6 metabolites ∑ 24.1 [1.9]* 22.6 [1.7] n-6 ∑ 30.2 [2.0] 29.7 [2.2] 20:5n-3 (EPA) 0.43 [0.16] 0.61 [0.35] 22:6n-3 (DHA) 1.9 [0.4]** 2.5 [0.6] ∑n-3metabolites 4.3 [0.9]* 4.8 [0.4] n-3 ∑ 4.5 [0.9]* 5.0 [0.4] DHGLA:AA ratio 0.06 [0.01]**** 0.08 [0.01] AA:EPA ratio 52.4 [20.9] 38.6 [18.4] Values are Means [SD}. *p<0.05, **p<0.01, ***p<0.005, ****p<0.00

Abstract D034: Patient and provider concordance and trust in providers among West African Immigrants: Findings from the CaPTC Familial Cohort Study

Background Healthcare disparities among racial and ethnic groups have been well documented across all aspects of clinical healthcare, and disparities in attainment of preventive services are particularly prevalent. African immigrants may be particularly susceptible to factors that contribute to healthcare disparities but little is known about this population. The purpose of this study was to assess patient-provider concordance and trust of health care providers among West African immigrants in the US. In addition, we explored the relationship between these variables and the prostate cancer (CaP) screening behavior of participants. Methods Data collection was part of a global study of prostate cancer in West African men. A study questionnaire was used to collect data from West African male immigrants in the US between the ages of 35 and 70 years. Survey scales for this study included country of birth, years since immigration, patient– provider concordance, trust of healthcare provider, attitude and cues towards CaP screening (PSA and DRE), and CaP screening history. Results There were 38 African immigrants from Cameroon, Nigeria, Sierra Leone, and Ghana. Participants’ average age was 46.2 years and they had spent an average of 13.9 years in the US. Most of the participants (over 60%) stated that they had no preference in regards to their provider race, ethnicity or gender. Over 70% indicated that their physician was of different ethnicity and race while 50% indicated that their physician was of a different gender. Furthermore, most respondents noted that they trusted their physicians with health decisions. However, 61% and 68% of participants did not complete PSA or DRE testing, respectively. Most stated that they did not discuss the advantages or disadvantages of prostate cancer screening with their physicians, noting they mostly received cues to getting tested from reading information, radio, and/or TV. Conclusion Although health disparities can be explained by socioeconomic status such as lack of insurance and various other observable impediments to accessing health care, others barriers persist. It is important to explore other contributing factors such as patient-physician relationships. This study suggests that patient-provider concordance may not be a priority. Emphasis should be placed on encouraging physician-initiated discussion on CaP screening. Unfortunately, current physician guidelines do not stress CaP screening and fail to account for the documented increased risk and early onset of CaP in Black Men