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Summary: HbSC disease is a common form of sickle cell disease with significant morbidity and early mortality. Whether hydroxyurea is beneficial for HbSC disease is unknown. Prospective Identification of Variables as Outcomes for Treatment (PIVOT, Trial ID PACTR202108893981080) is a double‐blind, randomised, placebo‐controlled phase II trial of hydroxyurea for people with HbSC, age 5–50 years, in Ghana. After screening, participants were randomised to placebo (standard of care) or hydroxyurea. The primary outcome is the cumulative incidence of haematological toxicities during 12 months of blinded treatment; secondary outcomes include multiple laboratory and clinical assessments. Between April 2022 and June 2023, 112 children and 102 adults were randomised, including 44% females and average age 21.6 ± 14.5 years. Participants had substantial morbidity including previous hospitalisations (93%), vaso‐occlusive events (86%), malaria (79%), often received transfusions (20%), with baseline haemoglobin 11.0 ± 1.2 g/dL and foetal haemoglobin 1.8% ± 1.5%. The spleen was palpable in six children and one adult, and ultrasonographic volumes were collected. Proliferative sickle retinopathy was common (30% children, 75% adults), but proteinuria was less common (3% children, 8% adults). Whole blood viscosity, ektacytometry, point‐of‐sickling, transcranial Doppler, near‐infrared spectrometry (NIRS), 6‐minute walk, and quality of life were also measured. Now fully enrolled, PIVOT will document the safety and potential benefits of hydroxyurea on clinical and laboratory outcomes in HbSC disease. [ABSTRACT FROM AUTHOR]

Introduction Materials and Methods Results Conclusion In sub‐Saharan Africa (SSA), an adequate supply of safe blood for transfusion is a major developmental challenge. In Ghana, deferral from blood donation for anemia accounts for nearly half of the ineligible blood donors. We conducted a longitudinal two‐arm parallel‐group non‐inferiority trial to test if iron supplementation among blood donors with iron deficiency (ID) or anemia could increase their hemoglobin levels to near those without ID or anemia.A structured questionnaire was used to collect participants' sociodemographic and medical information after written informed consent was obtained. Blood samples were analyzed for full blood count (FBC), serum ferritin, malaria rapid test, and a peripheral blood smear. The primary outcome was hemoglobin level after 4 months comparing anemic donors who received iron supplementation to the standard of care participants, nonanemic donors who did not receive iron supplementation. All donors received nutritional counseling.Adherence to low‐dose iron supplementation three times a week was poor. Hemoglobin levels in the iron supplementation arm were not close enough to those in the control group after 4 months of iron supplementation to declare non‐inferiority. However, non‐inferiority was met when the 4 month hemoglobin comparison was restricted to female donors.After 4 months of iron supplementation, hemoglobin levels in the iron supplementation group did not sufficiently match those in the control group to declare non‐inferiority. Data from this pilot trial informed and shaped the design of a larger randomized control type 1 pragmatic effectiveness implementation hybrid trial which is currently ongoing. [ABSTRACT FROM AUTHOR]

Background: Worldwide, about 20-25 million people are affected by sickle cell disease (SCD), with 60% of patients living in sub-Saharan Africa. Despite recent therapeutic advancements resulting in improved life expectancy among SCD patients, the prevalence of high-risk human papillomavirus (hr-HPV) and cervical lesions have not been studied in women with SCD. We determined the prevalence of hr-HPV and cervical lesions among women with SCD and recommended strategies for reducing cervical cancer incidence in this cohort. Methods: Through the mPharma 10,000 Women Initiative, women with SCD attending routine visits at the Ghana Institute of Clinical Genetics SCD clinic were screened by trained nurses. Screening was performed via concurrent MA-6000 hr-HPV DNA testing and enhanced visual assessment (EVA) mobile colposcopy from mobileODT. Results: Among 168 participants screened (mean age, 43.0 years), the overall prevalence rates of hr-HPV infection and cervical lesions were 28.6% (95% CI, 21.7-35.4) and 3.6% (95% CI, 0.8-6.4), respectively. The hr-HPV prevalence rates stratified by haemoglobin genotype were 29.4% (95% CI, 19.7-39.1) and 28.6% (95% CI, 18.5-38.7) for genotypes SS and SC, respectively. None of the five women with the SF genotype tested hr-HPV positive, and the only patient with Sbthal genotype tested hr-HPV positive. Two women were EVA 'positive' but hr-HPV negative, whereas four were EVA positive and hr-HPV positive. Exploratory analysis revealed no significant associations between hr-HPV positivity and age, education level, marital status or parity. Conclusion: In the absence of a comprehensive national cervical screening programme aimed at including women with SCD as a special population, cervical cancer may increase in frequency among SCD patients. Thus, there is a need to build capacity and expand the scope of screening services for women with SCD. [ABSTRACT FROM AUTHOR]

Malaria affects a significant portion of the global population, with 247 million cases in 2021, primarily in Africa. However, certain hemoglobinopathies, such as sickle cell trait (SCT), have been linked to lower mortality rates in malaria patients. Hemoglobin (Hb) mutations, including HbS and HbC, can cause sickle cell disease (SCD) when both alleles are inherited (HbSS and HbSC). In SCT, one allele is inherited and paired with a normal allele (HbAS, HbAC). The high prevalence of these alleles in Africa may be attributed to their protective effect against malaria. Biomarkers are crucial for SCD and malaria diagnosis and prognosis. Studies indicate that miRNAs, specifically miR-451a and let-7i-5p, are differentially expressed in HbSS and HbAS compared to controls. Our research examined the levels of exosomal miR-451a and let-7i-5p in red blood cells (RBCs) and infected red blood cells (iRBCs) from multiple sickle Hb genotypes and their impact on parasite growth. We assessed exosomal miR-451a and let-7i-5p levels in vitro in RBC and iRBC supernatants. Exosomal miRNAs exhibited distinct expression patterns in iRBCs from individuals with different sickle Hb genotypes. Additionally, we discovered a correlation between let-7i-5p levels and trophozoite count. Exosomal miR-451a and let-7i-5p could modulate SCD and malaria severity and serve as potential biomarkers for malaria vaccines and therapies. [ABSTRACT FROM AUTHOR]

Background: The supply of blood in many low‐ and middle‐income nations in Sub‐Saharan Africa (SSA) does not meet the patient care needs. Lack and delay of blood transfusion cause harm to patients and slow the rate of progress in other parts of the health system. Recognizing the power of implementation science, the BLOODSAFE Program was initiated which supports three SSA research study teams and one data coordinating center (DCC) with the goal to improve access to safe blood transfusion in SSA. Study Design and Methods: The study team in Ghana is focusing on studying and decreasing iron deficiency in blood donors and evaluating social engagement of blood donors through different approaches. The study team in Kenya is building a "vein to vein" workflow model to elucidate and devise strategies to overcome barriers to blood donation and improve infrastructural components of blood product production and use. The Malawi team is studying the infectious disease ramifications of blood donation as well as blood donor retention strategies aimed at blood donors who commence their donation career in secondary schools. Results and Discussion: Together the project teams and the DCC work as a consortium to support each other through a shared study protocol that will study donor motivations, outcomes, and adverse events across all three countries. The BLOODSAFE Program has the potential to lead to generalizable improvement approaches for increasing access to safe blood in SSA as well as mentoring and building the research capacity and careers of many investigators. [ABSTRACT FROM AUTHOR]

Summary: Ageing in sickle cell disease (SCD) is associated with a myriad of end‐organ complications, including cerebrovascular damage and cognitive impairment (CI). Although CI is very common in SCD, little is known about cognitive functioning and how it changes with age. This study examines cognitive patterns of 63 adults with SCD and 60 non‐SCD, age‐ and education‐matched controls in Ghana. Of those adults with SCD, 34 completed the neuropsychological battery at baseline and again seven years later. In cross‐sectional data, adults with SCD performed worse than controls in all cognitive test domains (p < 0.01 for all). The seven‐year follow‐up data showed that the group exhibited a significant decline in visuospatial abilities (ranging from Cohen's d = 1.40 to 2.38), and to a lesser extent, in processing speed and executive functioning. Exploratory analyses showed a significant time‐by‐education interaction, indicating that education may be protective from decline in cognitive performance. These findings have implications for clinical practice. Early neuropsychological surveillance coupled with early assessment and remedial programmes will provide avenues for enhancing the quality of life of adults living with SCD in Ghana. [ABSTRACT FROM AUTHOR]

Polycythaemia vera (PV) is a rare myeloproliferative neoplasm characterized primarily by erythrocytosis and an increased risk of thrombosis. We report a case of PV in a 60-year-old female with diabetes mellitus (DM) and a past history of recurrent abdominal pain and documented oesophageal varices who was followed up for 2 years as a case of non-cirrhotic portal hypertension of unknown cause. PV was only diagnosed after persistent complaints of vasomotor symptoms and better scrutiny of full blood count results. [ABSTRACT FROM AUTHOR]

In 2018, 228 million cases and 405,000 malaria-associated deaths were reported worldwide with a majority being in Africa. A wide range of factors, including parasitemia, host immunity, inflammatory responses to infection, and host hemoglobin genotype, mediate the severity of malaria. Among the hemoglobinopathies, hemoglobin S (HbS) is caused by a single amino acid substitution of Glutamic Acid replaced by Valine at the sixth position of the beta-globin chain (E6V). Hemoglobin C (HbC) on the other hand, involves a single amino acid substitution of Glutamic Acid by a Lysine (E6K), which has received the most attention. These substitutions alter the stability of Hb leading to wide-ranging hematological disorders. The homozygous state of hemoglobin S (HbSS) results in sickle cell anemia (SCA) whereas the heterozygous state (HbAS) results in sickle cell trait (SCT). Both mutations are reported to mediate the reduction in the severity and fatality of Plasmodium falciparum malaria. The mechanism underlying this protection is poorly understood. Since both malaria and sickle cell disease (SCD) are associated with the destruction of erythrocytes and widespread systemic inflammation, identifying which inflammatory factor(s) mediate susceptibility of individuals with different hemoglobin genotypes to Plasmodium infection could result in the discovery of new predictive markers and interventions against malaria or SCD severity. We hypothesized that hemoglobin genotypes modulate the inflammatory response to Plasmodium infection. We conducted a cross-sectional study in Ghana, West Africa, between 2014 and 2019 to ascertain the relationships between blood inflammatory cytokines, Plasmodium infection, and hemoglobin genotype. A total of 923 volunteers were enrolled in the study. A total of 74, age and sex-matched subjects were identified with various genotypes including HbAS, HbAC, HbSS, HbSC, HbCC, or HbAA. Complete blood counts and serum inflammatory cytokine expression levels were assessed. The results indicate that differential expression of CXCL10, TNF-α, CCL2, IL-8, and IL-6 were tightly linked to hemoglobin genotype and severity of Plasmodium infection and that these cytokine levels may be predictive for susceptibility to severe malaria or SCD severity. [ABSTRACT FROM AUTHOR]

We report a case of a young Ghanaian male who developed Bleomycin Induced Pneumonitis (BIP) after being treated for Hodgkin's Lymphoma. Pulmonary toxicity is the most feared complication of bleomycin therapy despite its effectiveness in achieving cure in patients with Hodgkin's lymphoma and germ cell tumors. BIP has a significant mortality rate if detected late and a high index of suspicion is required in all patients on bleomycin-based therapies with sudden onset of respiratory symptoms. [ABSTRACT FROM AUTHOR]

Background: In Ghana, diagnostic laboratories rely on reference intervals (RIs) provided by manufacturers of laboratory analyzers which may not be appropriate. This study aimed to establish RIs for hematological parameters in adult Ghanaian population. Methods: This cross‐sectional study recruited 501 apparently healthy adults from two major urban areas in Ghana based on the protocol by IFCC Committee for Reference Intervals and Decision Limits. Whole blood was tested for complete blood count (CBC) by Sysmex XN‐1000 analyzer, sera were tested for iron and ferritin by Beckman‐Coulter/AU480, for transferrin, vitamin‐B12, and folate was measured by Centaur‐XP/Siemen. Partitioning of reference values by sex and age was guided by "effect size" of between‐subgroup differences defined as standard deviation ratio (SDR) based on ANOVA. RIs were derived using parametric method with application of latent abnormal values exclusion method (LAVE), a multifaceted method of detecting subjects with abnormal results in related parameters. Results: Using SDR ≥ 0.4 as a threshold, RIs were partitioned by sex for platelet, erythrocyte parameters except mean corpuscular constants, and iron markers. Application of LAVE had prominent effect on RIs for majority of erythrocyte and iron parameters. Global comparison of Ghanaian RIs revealed lower‐side shift of RIs for leukocyte and neutrophil counts, female hemoglobin and male platelet count, especially compared to non‐African countries. Conclusion: The LAVE effect on many hematological RIs indicates the need for deliberate secondary exclusion for proper derivation of RIs. Obvious differences in Ghanaian RIs compared to other countries underscore the importance of country‐specific RIs for improved clinical decision‐making. [ABSTRACT FROM AUTHOR]

Sickle Cell Anaemia (SCA) is associated with a hypercoagulable state resulting in a predisposition to venous thromboembolism. With improvements in the quality of care, more patients with SCA survive into adulthood with an associated increase in the frequency of end-organ damage and chronic complications such as chronic leg ulcers (CLUs). These ulcers rarely occur in the first decade of life and are recurrent, painful, and slow-to-heal. This study tested the hypothesis that coagulation is enhanced in SCA patients with CLU. 145 participants (50 SCA with CLU, 50 SCA without CLU, and 45 with haemoglobin AA) were assessed to determine their coagulation profile using selected tests of coagulation. The SCA with the CLU group had the lowest mean haemoglobin (Hb) concentration. SCA patients with and without CLUs had elevated mean platelet counts, shorter mean aPTT, and marginally prolonged mean PT compared to HbAA patients. SCA with CLUs patients had a significantly shortened aPTT than those without CLUs (p = 0.035) and HbAA (p = 0.009). There were significant differences in the mean PT between SCA with CLUs patients and HbAA (p = 0.017); SCA without CLU and HbAA (p = 0.014). SCA with and without CLUs patients had higher mean D-dimer levels compared to HbAA. There was a negative correlation between Hb concentration and duration of CLU (r = -0.331, p = 0.021). In conclusion, our study demonstrates a heightened hypercoagulability in SCA patients with CLUs. We did not test for platelet activation, and it is not clear what role, if any, the enhanced hypercoagulability plays in the pathogenesis of CLUs in SCA. It will be useful to ascertain if antiplatelet agents or/and anticoagulants quicken the healing of CLUs in SCA patients. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoids (steroids) play a key role in the management of multiple medical conditions including haematological disorders. This study looked at the prevalence of steroid induced dysglycaemia in patients with haematological disorders receiving steroids as part of their treatment with the view of modifying its use and selection of patients where necessary. Methods: A retrospective review of haematology patients on treatment regimens including steroids. Information extracted included, demographic characteristics, clinical information such as age, gender, haematological disorder, type of steroid, daily and cumulative dose of steroid, duration of therapy, family history of diabetes and alcohol use. Results: The case records of 351 haematology patients were reviewed. However, eight patients with dysglycaemia before therapy were excluded. The median age of patients was 51.0 ± 26.0(IQR: Interquartile Range) years, with an age range of 13 to 87 years, and a female: male ratio of 1.2: 1 (p= 0.778). The prevalence of Steroid-Induced Dysglycaemia (SID) was 3.79% with a mean diagnosis interval of 8.8 + 2.1 months. Overall, 245 (71.4%) patients were on continuous steroids. Among the 13 patients who developed SID, 11 (84.6%) were on continuous steroids. In the majority of the patients (97.1%) there was no family history of diabetes in a first degree relative. Significant differences were found between patients with normoglycaemia and those with dysglycaemia with respect to age (p=0.049) and duration of steroid therapy (p=0.024). Conclusion: The prevalence of steroid-induced dysglycaemia is relatively low among Ghanaian patients with haematological disorders on steroid based chemotherapy. [ABSTRACT FROM AUTHOR]

Background. Abnormalities in lung function tests have been shown to commonly occur in a majority of patients with sickle cell disease (SCD) even at steady state. The prevalence and pattern of these lung function abnormalities have been described in other populations but this is unknown among our sickle cell cohort. There is generally little information available on risk factors associated with the lung function abnormalities and its relevance in patient care. Method. This was an analytical cross-sectional study involving 76 clinically stable, hydroxyurea-naive adult Hb-SS participants and 76 nonsickle cell disease (non-SCD) controls. A structured questionnaire was used to obtain sociodemographic data and clinical history of the participants. Investigations performed included spirometry, pulse oximetry, tricuspid regurgitant jet velocity (TRV) measurements via echocardiogram, complete blood counts, free plasma haemoglobin, serum urea, and creatinine. Results. Weight, BMI, mean FVC, and FEV1% predicted values were comparatively lower among the Hb-SS patients (p < 0.001). Abnormal spirometry outcome occurred in 70.4% of Hb-SS patients, predominantly restrictive defects (p < 0.001), and showed no significant association with steady-state Hb, WBC count, free plasma haemoglobin, frequency of sickling crisis, chronic leg ulcers, and TRV measurements (p > 0.05). The mean oxygen saturation was comparatively lower among Hb-SS patients (p < 0.001). Conclusion. Measured lung volumes were significantly lower in Hb-SS patients when compared to non-SCD controls and this difference was not influenced by anthropometric variance. Lung function abnormalities, particularly restrictive defects, are prevalent in Hb-SS patients but showed no significant association with recognized markers of disease severity. [ABSTRACT FROM AUTHOR]

Background: Africans have an increased risk for multiple myeloma (MM) compared to other races. Reports from Africa are few and involve small cohorts, but suggest significant epidemiological and clinical differences from Caucasian patients. Objective: This report describes the clinic-pathological features of MM patients in Ghana at diagnosis, and the factors affecting their survival. Methods: A retrospective review of 169 MM cases diagnosed in a Ghanaian tertiary hospital from 2002-2016. Results: Median age was 58 years, with 29% ≤50 years. One-third presented >12 months after onset of symptoms, which included bone pain (96%), anaemia (67%), weight loss (55%) and fractures (44%). Myeloma-related tissue impairment included hypercalcaemia (36%), renal impairment (33%), severe anaemia (52%) and osteolytic lesions (76%); 51.3% of patients were diagnosed in ISS Stage III. Median survival was 33 months; 1-year and 5-year overall survival were 51.6% and 15.5%, respectively. Neither the age at diagnosis nor the duration of symptoms prior to diagnosis correlated with prognosis. Median survival improved with early ISS stage, haemoglobin >8g/dL, plasmacytosis <20%, and normal creatinine and calcium levels. Conclusion: Early onset and late stage presentation are common at diagnosis of MM patients in Ghana, but do not affect survival. Studies into genetic associations are recommended. [ABSTRACT FROM AUTHOR]

In Africa, sickle cell disease (SCD) is a major public health problem with over 200,000 babies born per year. In Ghana, approximately 15,000 (2%) of Ghanaian newborns are diagnosed with SCD annually. A retrospective review of medical records of all SCD patients aged 13 years and above, who presented to the sickle cell clinic at Ghana Institute of Clinical Genetics (GICG), Korle-Bu, from 1st January 2013 to 31st December 2014, was carried out, using a data abstraction instrument to document their phenotypes, demographics, attendance/clinic visits, pattern of attendance, and common complications seen. During the period under review 5,451 patients were seen at the GICG, with 20,788 clinic visits. The phenotypes were HbSS (55.7%) and HbSC (39.6%) with other sickle cell phenotypes (4.7%). Out of the 20,788 clinic visits, outpatient visits were 15,802 (76%), and urgent care visits were 4,986 (24%), out of which 128 (2.6%) patients were admitted to the Teaching Hospital for further management of their acute complications. There were 904 patient referrals (out of 5,451 patients) for specialist care; the 3 specialties that had the most referrals were Obstetrics and Gynaecology (168 patients), Orthopaedics (150 patients), and Ophthalmology (143 patients). In 2014, complications seen at KBTH included 53 patients with avascular necrosis (AVN) and 61 patients with chronic leg ulcers. Our centre has a large number of patients living with sickle cell disease. From our experience, early recognition and referral of sickle cell related complications can reduce morbidity and mortality associated with this disease. A multidisciplinary approach to care of SCD patients is therefore important. [ABSTRACT FROM AUTHOR]

Background: Scarce studies have addressed hematological differences of malaria in urban and rural regions.Methods: Full or complete blood cell counts from 46 and 75 individuals (age range from < 1 to 92 years) with uncomplicated malaria infection living in urban (Accra) and rural (Dodowa) Ghana, respectively, were assessed. Sickle cell trait and patients were excluded from the study.Results: Between overall groups, patients from Accra had significantly lower parasite count (p < 0.0001) and granulocyte number (p = 0.026). Children in Accra had a significantly lower parasitemia (p = 0.0013), hemoglobin (p = 0.0254), platelet count (p = 0.0148) and red blood cell levels (p = 0.0080) when compared with the children of Dodowa. In adults, mean cell hemoglobin (p = 0.0086) and parasite count (p < 0.0001) were significantly higher in Dodowa.Conclusion: These results indicate that children living in urban setting may experience a greater anemic effect to malaria as compared with those living in a rural setting. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) occurs when two alleles of mutated hemoglobin (HbS or HbC) are inherited (HbSS and HbSC) rather than one (HbAS or HbAC), which indicates a person carries the sickle cell trait. The high prevalence of these two alleles in Africa have been associated with reduced malaria susceptibility. Recent in vitro research has been shown that microRNAs (miRNAs) miR-451a and let-7i-5p are differentially expressed in HbSS erythrocytes compared to healthy controls (HbAA) and are overexpressed in Plasmodium-infected malaria erythrocytes. However, these miRNAs have not been fully examined in the plasma of people with different sickle hemoglobin genotypes. Plasma circulating miRNAs are commonly encapsulated in extracellular vesicles, such as exosomes, and are thought to play a role in disease development. Circulating exosomal miR-451a and let-7i-5p were quantified from individuals with various hemoglobin genotypes (HbAA, HbAS, HbAC, HbSS, HbSC, and HbCC) with (+) and without (−) malaria. The results showed a higher level of exosomal let-7i-5p and miR-451a in HbSS-. Exosomal let-7i-5p and miR-451a levels were lower in HbSS+ compared to other genotypes. Based on the area under the curve (AUC) of the Receiver Operating Characteristics (ROCs), both exosomal miRNAs may be useful disease biomarkers for SCD with malaria. Finally, miR-451a and let-7i-5p modulate genes involved in inflammation, making them potential biomarkers of pathogenesis for both diseases. [ABSTRACT FROM AUTHOR]