Knowledge of Pharmacogenetics among Healthcare Professionals and Faculty Members of Health Training Institutions in Ghana

Background: Pharmacogenetics has a potential for optimizing drug response and identifying risk of toxicity for patients. Pharmacogenetics knowledge of healthcare professionals and the unmet need for pharmacogenetics education in health training institutions are some of the challenges of integrating pharmacogenetics into routine medical practice.Aim: To assess pharmacogenetics knowledge among healthcare professionals and faculty members of health training institutions in Ghana.Method: Semi-structured questionnaires were used to interview healthcare professionals from selected public and private hospitals. Faculty members from health training institutions were also interviewed.Results: The respondents were Medical doctors 42 (46.7%), Pharmacists 29 (32.2%) and Nurses 19 (21.1%). Healthcare professionals rated their knowledge of Pharmacogenetics as Excellent 5 (5.6%), Very Good 10 (11.2%), Good 53 (60%) and Poor 19 (21.4%). Thirty-two faculty members from health training institutions were also interviewed. Faculty members rated their knowledge of pharmacogenetics as Excellent 2 (6.3%), Very Good 3 (9.4%), Good 9 (28.1%), Fair 12 (37.5%) and Poor 6 (18.8%). Thirty seven percent (12) of these faculty members said pharmacogenetics was not part of their institutions’ curriculum, 7 (22%) did not know if pharmacogenetics was part of their curriculum and only 13 (40.6%) said it was part of their curriculum.Conclusion: Few healthcare professionals and faculty members of training institutions are aware of the discipline of pharmacogenetics. There is the need for continuous professional education on pharmacogenetics and development of competency standards for all healthcare professionals in Ghana.Keywords: Pharmacogenetics; Faculty, Curriculum, Education, Ghanaia

Sickle cell disease: reappraisal of the role of foetal haemoglobin levels in the frequency of vaso-occlusive crisis

Background: Foetal haemoglobin has been implicated in the modulation of sickle cell crisis. Its level is generally inversely proportional to the severity of sickle cell disease (SCD) for a given sickle cell phenotypes. The main aim of therapy for vaso-occlusive crisis (VOC), which is the hallmark of SCD, is to reduce the chances of sickling through the prevention of polymerization of HbS. One way of preventing this polymerization is by increasing foetal haemoglobin levels.Objectives: To determine the relationship between HbF levels and the frequency of crisis in SCD patients in Ghana.Method: A longitudinal retrospective survey covering a period of 30 months was carried out on adult SCD patients at the Sickle Cell Clinic of the Korle-Bu Teaching Hospital.Results: Eighty-three adults aged 15 to 65 years made up of 40 males and 43 femalea were studied. Analysis of variance (ANOVA) gave significant results in Hb and HbF levels. Higher HbF levels were positively related to less frequent crisis and were significantly high in SCD patients than in controls. HbF effects on the clinical manifestations on SCD were variable.Conclusion: Threshold values of HbF play a role in reducing the frequency of vaso-occlusive crisis in SCD patients and this finding contributes to the body of available literature on SCD severity. However our work does not give the apparent threshold level of helpful HBF Level in SCD.Keywords: Haemoglobin F, Frequency of crisis, sickle cell disease

Hematological parameters in Ghanaian sickle cell disease patients

Charles Antwi-Boasiako,1 Ivy Ekem,2 Mubarak Abdul-Rahman,3 Frederika Sey,4 Alfred Doku,5 Bartholomew Dzudzor,6 Gifty B Dankwah,1 Kate Hagar Otu,7 John Ahenkorah,8 Robert Aryee1 1Department of Physiology, School of Biomedical and Allied Health Sciences, University of Ghana, Accra, Ghana; 2Department of Haematology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana; 3Department of Pathology, School of Biomedical and Allied Health Sciences, University of Ghana, Accra, Ghana; 4Sickle Cell Clinic, Korle-Bu Teaching Hospital, Accra, Ghana; 5Department of Internal Medicine, School of Medicine and Dentistry, University of Ghana, Accra, Ghana; 6Department of Medical Biochemistry, School of Biomedical and Allied Health Sciences, University of Ghana, Accra, Ghana; 7Department of Nursing and Midwifery, Greenhills School of Health Sciences, Accra, Ghana; 8Department of Anatomy, School of Biomedical and Allied Health Sciences, University of Ghana, Accra, Ghana Background: Effective treatment and management of sickle cell disease (SCD) has been a challenge in Africa over the years. Hematological parameters are very useful profiles in the effective management of the disease. However, there is scarcity of studies on the hematological parameters of SCD in Ghana. This study aimed at determining hematological parameters among SCD patients with vaso-occlusion, those in the steady state as well as healthy controls at a teaching hospital in Ghana. Methodology: This was a cross-sectional study involving a total of 628 subjects, including 148 HbAA controls, 208 HbSS patients in steady state, 82 HbSC patients in steady state, 156 HbSS patients in vaso-occlusive crises (VOC), and 34 HbSC patients in VOC. Venous blood sample was collected from all study participants. A full blood count was done within 2 hours of collection, and hemoglobin (Hb) concentration, packed cell volume, red blood cell (RBC) concentration, mean corpuscular Hb, mean cell volume, mean corpuscular Hb concentration, and white blood cells (WBC) and platelet (PLT) counts were recorded. Results: WBC and PLT counts were significantly higher in both female and male patients with SCD, compared with their healthy counterparts (P<0.05). The level of WBC was, however, significantly higher in patients with HbSS VOC among the SCD patients (P<0.001). Levels of Hb, RBC, and hematocrit were significantly higher in the controls (P<0.001). There was no significant difference in mean cell Hb among male patients with SCD (P=0.274) and female patients with SCD (P=0.5410). Conclusion: The SCD patients had lower Hb and RBC than the controls; however, higher PLT and WBC are noted in various status of SCD, possibly reflecting spleen effect in these patients. Further studies are needed to confirm these findings. Keywords: sickle cell disease, hematological parameters, full blood count, anemia, Ghan

Levels of Soluble Endothelium Adhesion Molecules and Complications among Sickle Cell Disease Patients in Ghana

Background: Soluble adhesion molecules are involved in the gathering and joining of inflammatory cells to vascular endothelium. Therefore, they serve as potential markers of endothelial dysfunction in vascular diseases including sickle cell disease (SCD). In Ghana, there are scarcely any report on the levels of adhesion molecules among SCD patients. The current study aimed to determine plasma levels of ICAM-1, VCAM-1 and E-Selectin as markers of endothelial dysfunction in SCD patients in steady state, complications and controls. Methodology: This was a cross-sectional study involving 60 HbAA controls, 46 HbSS steady state, 57 HbSS VOC, 18 HbSC VOC, 21 HbSS with leg ulcer and 11 HbSS with priapism. Blood samples were collected from all the study subjects (n = 213) and processed into plasma. The plasma levels of VCAM-1, ICAM-1 and E-Selectin concentrations of SCD patients and controls were measured using a double sandwich ELISA technique. Demographic information was also collected from the study subjects. Results: Levels of all soluble proteins (ICAM-1, VCAM-1 and E-Selectin) were significantly higher in HbSS steady-state patients compared to non-SCD controls (p < 0.001). Generally, SCD patients with complications had relatively higher levels of the soluble proteins compared to those in the steady-state. Of the SCD patients with complications, those with vaso-occlusion crisis (HbSS VOC) had relatively higher levels of ICAM-1, VCAM-1 and E-Selectin at (62.42 ng/mL ± 26.09), (634.99 ng/mL ± 324.31) and (236.77 ng/mL ± 114.40) respectively; Conclusion: Although levels of adhesion molecules were high in all the SCD patients with complications, those with vaso-occlusive crisis had higher levels. This might reflect an ongoing endothelial dysfunction in these patients. SCD patients with vaso-occlusive crisis presents with a more severe pathophysiology condition

Correlation Between Soluble Endothelial Adhesion Molecules and Nitric Oxide Metabolites in Sickle Cell Disease.

Nitric Oxide (NO) and soluble adhesion molecules are promising biomarkers, which predict endothelial dysfunction in sickle cell disease (SCD). Several studies have investigated the relationship between NO (as well as its metabolites) and endothelial adhesion molecules in SCD. However, these studies were done mainly in the developed world, and it is difficult to extrapolate the findings to SCD populations in other geographical regions such as Africa due to significant disparities in the results. The aim of the current study was to determine the correlation between levels of nitric oxide metabolites (NOx) and adhesion molecules in SCD patients in a tertiary hospital in Ghana. A case control cross-sectional study involving 100 SCD (made up of HbSS and HbSC patients) and 60 healthy controls was conducted. Concentrations of NOx and soluble endothelial adhesion molecules (ICAM-1, VCAM-1 and E-selectin) were measured in all the study participants (n = 160) by the Griess reagent system and enzyme-linked immunosorbent assay (ELISA). Correlation analysis was performed to determine a possible link between the variables. Levels of soluble adhesion molecules were higher in the HbSS patients. Correlation of NOx with ICAM-1 almost approached significance (r = 0.565, p = 0.058) in the HbSS patients. There were no correlations between NOx and E-selectin in both HbSS and HbSC patients. There were no significant correlations between NOx and VCAM-1 in all the study participants (p > 0.05). Of the soluble adhesion molecules, ICAM-1 showed a significant positive correlation with VCAM-1 in the HbSC patients. There were no significant differences between the adhesion molecules and the age of participants in the various study groups. Whether or not a significant correlation exists between NOx and soluble adhesion molecules may not depend on the sickle cell genotype. The expression of adhesion molecules may not depend on age

Contrasting Hygiene-Related Gastrointestinal Infections and Stress-Related Diseases at a Primary Health Care Facility within a Sub-Saharan African City: Before and during the COVID-19 Pandemic

Background: With the advent of the COVID-19 pandemic caused by SARS-CoV-2, protocols such as social distancing and upscaling of hygiene practices were implemented to limit the spread of the disease. Meanwhile, along with COVID-19 came stress due to restrictions on movement, trade and transport, and closure of schools, among others. Aim: This study compared the prevalence of hygiene-related gastrointestinal infections and stress-related diseases before (March 2019–February 2020) and during (March 2020–February 2021) the COVID-19 pandemic. Methodology: This was a retrospective single-center review of deidentified patient data from the Korle Bu Polyclinic, Accra, Ghana. Results: Comparing the pre-COVID-19 era to the COVID-19 era, there was a statistically nonsignificant change in the number of cases and prevalence of gastroenteritis and enteric fever (p = 0.084 and 0.081, respectively), although for gastroenteritis, the prevalence was higher for the pre-COVID-19 era compared to during COVID-19 by 1.8 per 1000 cases, while that of enteric fever was higher during the COVID-19 era compared to the pre-COVID-19 era by 1.0 per 1000 cases. Of the stress-related diseases, statistically significant increases in the prevalence of anxiety disorders (p = 0.028), insomnia (p = 0.001), and headache (p = 0.010), were noted, with 2.3, 5.5, and 2.4 per 1000 cases, respectively. There were more female cases than male cases recorded for depression (p = 0.001), headache (p = 0.010), and hypertension (p = 0.001) during the pandemic, and these were statistically significant. Conclusion: During the pandemic, a significant increase in the prevalence of stress-related diseases was observed. However, a statistically nonsignificant change was recorded for gastrointestinal infections, with females reporting more of these disorders. Consequently, it is important to strengthen the capacity for managing stress-related conditions alongside diseases that cause pandemics when they arise

Elevated Proangiogenic Markers are Associated with Vascular Complications within Ghanaian Sickle Cell Disease Patients

Sickle cell disease (SCD) is an inherited blood disorder that can result in vasculopathy and end organ damage. Angiogenesis has been implicated as a key contributing factor to vascular mediated tissue injury in SCD. The relative plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) greatly influence angiogenesis. Dysregulation of these growth factors, leading to a pro-angiogenic state in SCD patients, has been documented in the developed world but there is very little data in Africa. There is the need, therefore, for studies in Ghanaian SCD patients. The aim of this study was to assess plasma levels of Ang-1, Ang-2, and VEGF in homozygous (HbSS) SCD patients with or without complications and healthy controls (HbAA) in Ghana. The study was a case-control study involving 544 participants: 396 HbSS SCD patients and 148 HbAA healthy controls. The study was conducted at the Center for Clinical Genetics (Sickle Cell Clinic) and Accra Area Blood Centre for National Blood transfusion at the Korle-Bu Teaching Hospital, Accra, Ghana. The plasma levels of Ang-1, Ang-2, and VEGF of study participants were measured with a double sandwich enzyme-linked immunosorbent assay (ELISA) technique. Complete blood count (CBC) was measured with an autoanalyser. The mean plasma Ang-1, Ang-2, and VEGF were significantly higher in HbSS SCD patients with or without complications than healthy controls (p < 0.001). The Ang-2/Ang-1 ratio was significantly lower in the controls than the HbSS patients (p < 0.001). The Ang-2/Ang-1 ratio was higher in the HbSS patients with leg ulcers as compared with patients with other complications and healthy controls (p < 0.001). There were higher leucocyte counts in HbSS patients than healthy controls. Overall, there was elevated plasma levels of Ang-1, Ang-2, and VEGF in SCD patients. The higher Ang-2/Ang-1 plasma levels in patients with leg ulcers suggests a possible ongoing angiogenesis and response to inflammatory stimuli. The study provides a first report on plasma levels of angiopoietin-1, angiopoietin-2, and vascular endothelial growth factors in homozygous sickle cell disease patients in Ghana

Perspective: Food Environment Research Priorities for Africa-Lessons from the Africa Food Environment Research Network.

Over the last 2 decades, many African countries have undergone dietary and nutrition transitions fueled by globalization, rapid urbanization, and development. These changes have altered African food environments and, subsequently, dietary behaviors, including food acquisition and consumption. Dietary patterns associated with the nutrition transition have contributed to Africa&#8217;s complex burden of malnutrition-obesity and other diet-related noncommunicable diseases (DR-NCDs)-along with persistent food insecurity and undernutrition. Available evidence links unhealthy or obesogenic food environments (including those that market and offer energy-dense, nutrient-poor foods and beverages) with suboptimal diets and associated adverse health outcomes. Elsewhere, governments have responded with policies to improve food environments. However, in Africa, the necessary research and policy action have received insufficient attention. Contextual evidence to motivate, enable, and create supportive food environments in Africa for better population health is urgently needed. In November 2020, the Measurement, Evaluation, Accountability, and Leadership Support for Noncommunicable Diseases Prevention Project (MEALS4NCDs) convened the first Africa Food Environment Research Network Meeting (FERN2020). This 3-d virtual meeting brought researchers from around the world to deliberate on future directions and research priorities related to improving food environments and nutrition across the African continent. The stakeholders shared experiences, best practices, challenges, and opportunities for improving the healthfulness of food environments and related policies in low- and middle-income countries. In this article, we summarize the proceedings and research priorities identified in the meeting to advance the food environment research agenda in Africa, and thus contribute to the promotion of healthier food environments to prevent DR-NCDs, and other forms of&nbsp;malnutrition.</p

ABL fusion oncogene transformation and inhibitor sensitivity are mediated by the cellular regulator RIN1

ABL gene translocations create constitutively active tyrosine kinases that are causative in chronic myeloid leukemia, acute lymphocytic leukemia and other hematopoietic malignancies. Consistent retention of ABL SH3/SH2 autoinhibitory domains, however, suggests that these leukemogenic tyrosine kinase fusion proteins remain subject to regulation. We resolve this paradox, demonstrating that BCR-ABL1 kinase activity is regulated by RIN1, an ABL SH3/SH2 binding protein. BCR-ABL1 activity was increased by RIN1 overexpression and decreased by RIN1 silencing. Moreover, Rin1(−/−) bone marrow cells were not transformed by BCR-ABL1, ETV6-ABL1 or BCR-ABL1(T315I), a patient-derived drug-resistant mutant, as judged by growth factor independence. Rescue by ectopic RIN1 verified a cell autonomous mechanism of collaboration with BCR-ABL1 during transformation. Sensitivity to the ABL kinase inhibitor imatinib was increased by RIN1 silencing, consistent with RIN1 stabilization of an activated BCR-ABL1 conformation having reduced drug affinity. The dependence on activation by RIN1 to unleash full catalytic and cell transformation potential reveals a previously unknown vulnerability that could be exploited for treatment of leukemic cases driven by ABL translocations. The findings suggest that RIN1 targeting could be efficacious for imatinib-resistant disease and might complement ABL kinase inhibitors in first-line therapy