Browsing by Author "Segbefia, C."

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Age of first pain crisis and associated complications in the CASiRe international sickle cell disease cohort
(Blood Cells, Molecules and Diseases, 2021) Tartaglione, I.; Strunk, C.; Antwi-Boasiako, C.; Andemariam, B.; Colombatti, R.; Asare, E.V.; Piccone, C.M.; Manwani, D.; Boruchov, D.; Tavernier, F.; Farooq, F.; Akatue, S.; Oteng, B.; Urbonya, R.; Wilson, S.; Owda, A.; Bamfo, R.; Boatemaa, G.D.; Rao, Sudha; Zempsky, W.; Sey, F.; Inusa, B.P.D.; Perrotta, Silverio; Segbefia, C.; Campbell, A.D.
Pain is a hallmark of Sickle Cell Disease (SCD) affecting patients throughout their life; the first pain crisis may occur at any age and is often the first presentation of the disease. Universal newborn screening identifies children with SCD at birth, significantly improving morbidity and mortality. Without early screening, diagnosis is generally made after disease manifestations appear. The Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaborative group evaluating the clinical severity of subjects with SCD using a validated questionnaire and medical chart review, standardized across 4 countries (United States, United Kingdom, Italy and Ghana). We investigated the age of first pain crisis in 555 sickle cell subjects, 344 adults and 211 children. Median age of the first crisis in the whole group was 4 years old, 5 years old among adults and 2 years old among children. Patients from the United States generally reported the first crisis earlier than Ghanaians. Experiencing the first pain crisis early in life correlated with the genotype and disease severity. Early recognition of the first pain crisis could be useful to guide counseling and management of the disease.
An Analysis of Racial and Ethnic Backgrounds Within the CASiRe International Cohort of Sickle Cell Disease Patients: Implications for Disease Phenotype and Clinical Research
(Journal of Racial and Ethnic Health Disparities, 2020-04-16) Boatemaa, G.D.; Campbell, A.D.; Colombatti, R.; Andemariam, B.; Strunk, C.; Tartaglione, I.; Piccone, C.M.; Manwani, D.; Asare, E.V.; Boruchov, D.; Farooq, F.; Urbonya, R.; Perrotta, S.; Sainati, L.; Rivers, A.; Rao, S.; Zempsky, W.; Sey, F.; Segbefia, C.; Inusa, B.; Antwi-Boasiako, C.
Millions are affected by sickle cell disease (SCD) worldwide with the greatest burden in sub-Saharan Africa. While its origin lies historically within the malaria belt, ongoing changes in migration patterns have shifted the burden of disease resulting in a global public health concern. We created the Consortium for the Advancement of Sickle Cell Research (CASiRe) to understand the different phenotypes of SCD across 4 countries (USA, UK, Italy, and Ghana). Here, we report the multi-generational ethnic and racial background of 877 SCD patients recruited in Ghana (n = 365, 41.6%), the USA (n = 254, 29%), Italy (n = 81, 9.2%), and the UK (n = 177, 20.2%). West Africa (including Benin Gulf) (N = 556, 63.4%) was the most common geographic region of origin, followed by North America (N = 184, 21%), Caribbean (N = 51, 5.8%), Europe (N = 27, 3.1%), Central Africa (N = 24, 2.7%), and West Africa (excluding Benin Gulf) (N = 21, 2.4%). SCD patients in Europe were primarily West African (73%), European (10%), Caribbean (8%), and Central African (8%). In the USA, patients were largely African American (71%), Caribbean (13%), or West African (10%). Most subjects identified themselves as Black or African American; the European cohort had the largest group of Caucasian SCD patients (8%), including 21% of the Italian patients. This is the first report of a comprehensive analysis of ethnicity within an international, transcontinental group of SCD patients. The diverse ethnic backgrounds observed in our cohort raises the possibility that genetic and environmental heterogeneity within each SCD population subgroup can affect the clinical phenotype and research outcomes.
Association Between Selected Single Nucleotide Polymorphisms in Globin and Related Genes and Response to Hydroxyurea Therapy in Ghanaian Children with Sickle Cell Disease
(Pharmacogenomics and Personalized Medicine, 2022) Manu, G.P.; Segbefia, C.; N’guessan, B.B.; Coffie, S.A.; Adjei, G.O.
Background: Sickle cell disease (SCD) is a group of genetic disorders affecting the structure and function of haemoglobin. Hydroxyurea (HU) stimulates fetal haemoglobin (HbF) and reduces sickle erythrocyte-endothelial cell interaction. However, the degree of HbF response to HU varies, with HbF expression-associated single nucleotide polymorphisms (SNPs) in quantitative trait loci (QTL) been implicated. We investigated the relationship between four SNPs (rs11886868, rs6706648, rs7606173 and 158C/T Xmn1) in two QTL (B-cell lymphoma 11A (BCL11A) and Xmn1) and HbF levels in children with SCD in Accra, Ghana. Methods: A total of 110 children with SCD in steady-state, comprising 64 and 46 SCD children treated with HU (HU+) or with no history of HU therapy (HU-), respectively, were recruited. HbF levels were measured in peripheral blood by alkali denaturation and SNPs were genotyped using polymerase chain reaction and restriction fragment length polymorphism. Results: The presence of SNPs (rs11886868, rs6706648, rs7606173 and −158C/T Xmn1) was identified. Observed heterozygosity and homozygosity for the derived alleles were 45.7%, 82.6%, 21.7% and 39.1% in rs11886868, rs6706648, rs7606173 and −158C/T Xmn1 polymorphisms, respectively, for the HU+ population. Observed frequencies of the minor alleles were 0.204, 0.477, 0.171 and 0.190 for rs11886868, rs6706648, rs7606173 and −158C/T Xmn1 polymorphisms, respectively. The three BCL11A SNPs in the HU+ population showed homozygous individuals for rs11886868 (CC), rs6706648 (CC) and heterozygous or homozygous mutant individuals for rs7606173 (CG/GG) having higher HbF values. The combined effect of the SNPs was associated with variance in HbF levels in the HU+ population. The BCL11A SNP, rs6706648 was strongly associated with HbF levels and the C allele frequency, with significantly elevated HbF levels. Conclusion: An association between the various variants and combined effect of SNPs and HbF among children with SCD was found and confirms the known association between HU intake and increased HbF in SCD.
Clinical and laboratory characteristics of children with sickle cell disease on hydroxyurea treated with artemether-lumefantrine for acute uncomplicated malaria
(Frontiers in Public Health, 2023) Segbefia, C.; Amponsah, S.K.; Afrane, A.K.A.; et al.
Introduction: Limited information exists on any interactions between hydroxyurea (HU) and antimalarials in sickle cell disease (SCD). We evaluated changes in clinical and laboratory parameters among children with SCD on HU therapy treated with artemether-lumefantrine (AL) for acute uncomplicated malaria (UM). Methods: A prospective, non-randomized, pilot study of 127 children with SCD (23, UM; 104, steady state) were recruited from three hospitals in Accra. UM participants were treated with standard doses of AL and followed up, on days 1, 2, 3, 7, 14, and 28. Venous blood was collected at baseline and follow-up days in participants with UM for determination of malaria parasitaemia, full blood count, reticulocytes, and clinical chemistry. Further, Plasmodium falciparum identification of rapid diagnostic test (RDT) positive samples was done using nested polymerase chain reaction (PCR). Results: Among SCD participants with UM, admission temperature, neutrophils, alanine-aminotransferase, gamma-glutamyl-transferase, and haemoglobin significantly differed between HU recipients (HU+) and steady state, while white blood cell, neutrophils, reticulocytes, bilirubin, urea, and temperature differed significantly between non-HU recipients (no-HU), and steady state. Mean parasitaemia (HU+, 2930.3 vs. no-HU, 1,060, p = 0.74) and adverse events (HU+, 13.9% vs. no-HU, 14.3%), were comparable (p = 0.94). Day 28 reticulocyte count was higher in the HU+ (0.24) (0.17 to 0.37) vs. no-HU, [0.15 (0.09 to 0.27), p = 0.022]. Significant differences in lymphocyte [HU+ 2.74 95% CI (−5.38 to 58.57) vs. no-HU −0.34 (−3.19 to 4.44), p = 0.024]; bilirubin [HU+, −4.44 (−16.36 to 20.74) vs. no-HU −18.37 (−108.79 to −7.16)]; and alanine aminotransferase, [HU+, −4.00 (−48.55 to 6.00) vs. no-HU, 7.00 (−22.00 to 22.00)] were observed during follow up Conclusion: Parasite clearance and adverse event occurrence were comparable between SCD children treated with AL irrespective of HU status. However, distinct patterns of changes in laboratory indices suggest the need for larger, more focused studies.
Diagnosis patterns of sickle cell disease in Ghana: a secondary analysis
(BMC Public Health, 2021) Sims, A.M.; Bonsu, K.O.; Urbonya, R.; Farooq, F.; Tavernier, F.; Yamamoto, M.; VanOmen, S.; Halford, B.; Gorodinsky, P.; Issaka, R.; Kpadenou, T.; Douglas, R.; Wilson, S.; Fu, C.; Canter, D.; Martin, D.; Novarra, A.; Graham, L.; Sey, F.; Antwi-Boasiako, C.; Segbefia, C.; Rodrigues, O.; Campbell, A.
Background: Despite having the highest prevalence of sickle cell disease (SCD) in the world, no country in Sub- Saharan Africa has a universal screening program for the disease. We sought to capture the diagnosis patterns of SCD (age at SCD diagnosis, method of SCD diagnosis, and age of first pain crisis) in Accra, Ghana. Methods: We administered an in-person, voluntary survey to parents of offspring with SCD between 2009 and 2013 in Accra as a part of a larger study and conducted a secondary data analysis to determine diagnosis patterns. This was conducted at a single site: a large academic medical center in the region. Univariate analyses were performed on diagnosis patterns; bivariate analyses were conducted to determine whether patterns differed by participant’s age (children: those < 18 years old whose parents completed a survey about them, compared to adults: those > = 18 years old whose parents completed a survey about them), or their disease severity based on SCD genotype. Pearson’s chi-squared were calculated. Results: Data was collected on 354 unique participants from parents. Few were diagnosed via SCD testing in the newborn period. Only 44% were diagnosed with SCD by age four; 46% had experienced a pain crisis by the same age. Most (66%) were diagnosed during pain crisis, either in acute (49%) or primary care (17%) settings. Children were diagnosed with SCD at an earlier age (74% by four years old); among the adults, parents reflected that 30% were diagnosed by four years old (p < 0.001). Half with severe forms of SCD were diagnosed by age four, compared to 31% with mild forms of the disease (p = 0.009). Conclusions: The lack of a robust newborn screening program for SCD in Accra, Ghana, leaves children at risk for disease complications and death. People in our sample were diagnosed with SCD in the acute care setting, and in their toddler or school-age years or thereafter, meaning they are likely being excluded from important preventive care. Understanding current SCD diagnosis patterns in the region can inform efforts to improve the timeliness of SCD diagnosis, and improve the mortality and morbidity caused by the disease in this high prevalence population.
Diagnosis patterns of sickle cell disease in Ghana: a secondary analysis
(BMC Public Health, 2021) Sims, A.M.; Bonsu, K.O.; Urbonya, R.; Farooq, F.; Tavernier, F.; Yamamoto, M.; VanOmen, S.; Halford, B.; Gorodinsky, P.; Issaka, R.; Kpadenou, T.; Douglas, R.; Wilson, S.; Fu, C.; Canter, D.; Martin, D.; Novarra, A.; Graham, L.; Sey, F.; Antwi-Boasiako, C.; Segbefia, C.; Rodrigues, O.; Campbell, A.
Background: Despite having the highest prevalence of sickle cell disease (SCD) in the world, no country in Sub Saharan Africa has a universal screening program for the disease. We sought to capture the diagnosis patterns of SCD (age at SCD diagnosis, method of SCD diagnosis, and age of first pain crisis) in Accra, Ghana. Methods: We administered an in-person, voluntary survey to parents of offspring with SCD between 2009 and 2013 in Accra as a part of a larger study and conducted a secondary data analysis to determine diagnosis patterns. This was conducted at a single site: a large academic medical center in the region. Univariate analyses were performed on diagnosis patterns; bivariate analyses were conducted to determine whether patterns differed by participant’s age (children: those < 18 years old whose parents completed a survey about them, compared to adults: those > = 18 years old whose parents completed a survey about them), or their disease severity based on SCD genotype. Pearson’s chi-squared were calculated. Results: Data was collected on 354 unique participants from parents. Few were diagnosed via SCD testing in the newborn period. Only 44% were diagnosed with SCD by age four; 46% had experienced a pain crisis by the same age. Most (66%) were diagnosed during pain crisis, either in acute (49%) or primary care (17%) settings. Children were diagnosed with SCD at an earlier age (74% by four years old); among the adults, parents reflected that 30% were diagnosed by four years old (p < 0.001). Half with severe forms of SCD were diagnosed by age four, compared to 31% with mild forms of the disease (p = 0.009). Conclusions: The lack of a robust newborn screening program for SCD in Accra, Ghana, leaves children at risk for disease complications and death. People in our sample were diagnosed with SCD in the acute care setting, and in their toddler or school-age years or thereafter, meaning they are likely being excluded from important preventive care. Understanding current SCD diagnosis patterns in the region can inform efforts to improve the timeliness of SCD diagnosis, and improve the mortality and morbidity caused by the disease in this high prevalence population.
Global geographic differences in healthcare utilization for sickle cell disease pain crises in the CASiRe cohort
(Blood Cells, Molecules and Diseases, 2021) Strunk, C.; Tartaglione, I.; Piccone, C.M.; Colombatti, R.; Andemariam, B.; Manwani, D.; Smith, A.; Haile, H.; Kim, E.; Wilson, S.; Asare, E.V.; Rivers, A.; Farooq, F.; Urbonya, R.; Boruchov, D.; Boatemaa, G.D.; Perrotta, S.; Ekem, I.; Sainati, L.; Rao, S.; Zempsky, W.; Sey, F.; Antwi-Boasiako, C.; Segbefia, C.; Inusa, B.; Campbell, A.D.
Background: Sickle cell disease (SCD) is characterized by frequent, unpredictable pain episodes and other vasoocclusive crises (VOCs) leading to significant healthcare utilization. VOC frequency is often an endpoint in clinical trials investigating novel therapies for this devastating disease. Procedure: The Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaboration investigating clinical severity in SCD using a validated questionnaire and medical chart review standardized across four countries (United States, United Kingdom, Italy and Ghana). Results: This study, focused on pain crisis incidence and healthcare utilization, included 868 patients, equally represented according to age and gender. HgbSS was the most common genotype. Patients from Ghana used the Emergency Room/Day Hospital for pain more frequently (annualized mean 2.01) than patients from other regions (annualized mean 1.56 U.S.; 1.09 U.K.; 0.02 Italy), while U.K. patients were hospitalized for pain more often (annualized mean: U.K. 2.98) than patients in other regions (annualized mean 1.98 U.S.; 1.18 Ghana; Italy 0.54). Italy's hospitalization rate for pain (annualized mean: 0.57) was nearly 20 times greater than its emergency room/day hospital only visits for pain (annualized mean: 0.03). When categorized by genotype and age, similar results were seen.
Multicentric Castleman’s Disease In A Ghanaian Adult
(Ghana medical journal, 2013-06) Dei-Adomakoh, Y.A.; Segbefia, C.; Ekem, I.; Taylor, A.
Castleman's disease is a rare cause of lymphoid hyperplasia that may result in localized symptoms or an aggressive, multisystem disorder that can mimic other diseases like lymphoma or tuberculosis. We describe a case of a 55-year-old Ghanaian male who was successfully diagnosed and managed for multicentric Castleman's disease with combination chemotherapy.
Multicentric Castleman's disease in a Ghanaian adult.
(Ghana medical journal, 2013-06) Dei-Adomakoh, Y.A.; Segbefia, C.; Ekem, I.; Taylor, A.
Castleman's disease is a rare cause of lymphoid hyperplasia that may result in localized symptoms or an aggressive, multisystem disorder that can mimic other diseases like lymphoma or tuberculosis. We describe a case of a 55-year-old Ghanaian male who was successfully diagnosed and managed for multicentric Castleman's disease with combination chemotherapy.
Pain Frequency and Health Care Utilization Patterns in Women with Sickle Cell Disease Experiencing Menstruation-Associated Pain Crises
(Journal of Women's Health, 2023) Segbefia, C.; Campbell, J.; Tartaglione, I.; et al.
Background: Pain crises in sickle cell disease (SCD) lead to high rates of health care utilization. Historically, women have reported higher pain burdens than men, with recent studies showing a temporal association between pain crisis and menstruation. However, health care utilization patterns of SCD women with menstruation associated pain crises have not been reported. We studied the frequency, severity, and health care utilization of menstruation-associated pain crises in SCD women. Materials and Methods: A multinational, cross-sectional cohort study of the SCD phenotype was executed using a validated questionnaire and medical chart review from the Consortium for the Advancement of Sickle Cell Research (CASiRe) cohort. Total number of pain crises, emergency room/day hospital visits, and hospitalizations were collected from a subcohort of 178 SCD women within the past 6 months and previous year. Results: Thirty-nine percent of women reported menstruation-associated pain crises in their lifetime. These women were significantly more likely to be hospitalized compared with those who did not (mean 1.70 vs. 0.67, p = 0.0005). Women reporting menstruation-associated pain crises in the past 6 months also experienced increased hospitalizations compared with those who did not (mean 1.71 vs. 0.75, p = 0.0016). Forty percent of women reported at least four menstruation-associated pain crises in the past 6 months. Conclusions: Nearly 40% of SCD women have menstruation-associated pain crises. Menstruation-associated pain crises are associated with high pain burden and increased rates of hospitalization. Strategies are needed to address health care disparities within gynecologic care in SCD.
A study of the geographic distribution and associated risk factors of leg ulcers within an international cohort of sickle cell disease patients: the CASiRe group analysis
(Annals of Hematology, 2020-05-06) Antwi-Boasiako, C.; Andemariam, B.; Colombatti, R.; Asare, E.V.; Strunk, C.; Piccone, C.M.; Manwani, D.; Boruchov, D.; Farooq, F.; Urbonya, R.; Wilson, S.; Boatemaa, G.D.; Perrotta, S.; Sainati, L.; Rivers, A.; Rao, S.; Zempsky, W.; Ekem, I.; Sey, F.; Segbefia, C.; Inusa, B.; Tartaglione, I.; Campbell, A.D.
Vasculopathy is a hallmark of sickle cell disease ultimately resulting in chronic end organ damage. Leg ulcer is one of its sequelae, occurring in ~ 5–10% of adult sickle cell patients. The majority of leg ulcer publications to date have emanated from single center cohort studies. As such, there are limited studies on the geographic distribution of leg ulcers and associated risk factors worldwide. The Consortium for the Advancement of Sickle Cell Research (CASiRe) was formed to improve the understanding of the different phenotypes of sickle cell disease patients living in different geographic locations around the world (USA, UK, Italy, Ghana). This cross-sectional cohort sub-study of 659 sickle cell patients aimed to determine the geographic distribution and risk factors associated with leg ulcers. The prevalence of leg ulcers was 10.3% and was associated with older age, SS genotype, male gender, and Ghanaian origin. In fact, the highest prevalence (18.6%) was observed in Ghana. Albuminuria, proteinuria, increased markers of hemolysis (lower hemoglobin, higher total bilirubin), lower oxygen saturation, and lower body mass index were also associated with leg ulceration. Overall, our study identified a predominance of leg ulcers within male hemoglobin SS patients living in sub-Saharan Africa with renal dysfunction and increased hemolysis.