CYP2J2∗7 Genotype Predicts Risk of Chemotherapy-Induced Hematologic Toxicity and Reduced Relative Dose Intensity in Ethiopian Breast Cancer Patients

Chemotherapy-induced hematologic toxicity is the primary reasons of dose reductions and/or delays, low relative dose intensity (RDI), and predicts anticancer response. We investigated the incidence and predictors of chemotherapy-induced hematologic toxicities and reduced RDI in Ethiopian breast cancer patients, and implication of pharmacogenetics variations. Breast cancer patients (n = 249) were enrolled prospectively to receive cyclophosphamide based chemotherapy. Hematological toxicity (neutropenia, anemia, and thrombocytopenia) were monitored throughout chemotherapy cycle. The primary and secondary outcomes were incidence of grade 3 or 4 toxicity and reduced RDI, respectively. CYP2B6∗6, CYP3A5∗3, CYP2C9 (∗2,∗3), CYP2C19 (∗2,∗3), CYP2J2∗7, POR∗28, and ABCB1 (rs3842) genotyping were done. Cox proportional hazard and logistic regression were used to estimate risk predictors of toxicity and reduced RDI, respectively. Majority (73.5%) of the patients were < 45 years of age. The incidence of grade 3 or 4 hematological toxicity was 51.0% (95% CI = 44.54–57.46%). Multivariate Cox proportional hazard regression indicated CYP2J2∗7 genotype [Hazard ratio (HR) = 1.82; 95% CI = 1.14–2.90], pretreatment grade 1 leukopenia (HR = 2.75; 95% CI = 1.47–5.15) or grade 1 or 2 neutropenia (HR = 2.75; 95% CI = 1.73–4.35) as significant predictors of hematologic toxicities. The odds of having hematologic toxicities was lower in CYP2C9∗2 or ∗3 carriers (p = 0.024). The prevalence of reduced RDI was 56.6% (95% CI = 50.3–62.9%). Higher risk of reduced RDI was associated with CYP2J2∗7 allele [Adjusted odds ratio (AOR) = 2.79; 95% CI = 1.21–6.46], BMI ≤ 18.4 kg/m2 (AOR = 5.98; 95% CI = 1.36–26.23), baseline grade 1 leukopenia (AOR = 6.09; 95% CI = 1.24–29.98), and baseline neutropenia (AOR = 3.37; 95% CI = 1.41–8.05). The odds of receiving reduced RDI was lower in patients with CYP2B6 ∗6/∗6 genotype (AOR = 0.19; 95% CI = 0.06–0.77). We report high incidence of chemotherapy-induced hematological toxicities causing larger proportion of patients to receive reduced RDI in Ethiopian breast cancer patients. Patients carrying CYP2J2∗7 allele and low baseline blood counts are at a higher risk for chemotherapy-induced hematologic toxicities and receiving reduced RDI, and may require prior support and close follow up during chemotherapy

Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021

Background Anaemia is a major health problem worldwide. Global estimates of anaemia burden are crucial for developing appropriate interventions to meet current international targets for disease mitigation. We describe the prevalence, years lived with disability, and trends of anaemia and its underlying causes in 204 countries and territories. Methods We estimated population-level distributions of haemoglobin concentration by age and sex for each location from 1990 to 2021. We then calculated anaemia burden by severity and associated years lived with disability (YLDs). With data on prevalence of the causes of anaemia and associated cause-specific shifts in haemoglobin concentrations, we modelled the proportion of anaemia attributed to 37 underlying causes for all locations, years, and demographics in the Global Burden of Disease Study 2021. Findings In 2021, the global prevalence of anaemia across all ages was 24·3% (95% uncertainty interval [UI] 23·9–24·7), corresponding to 1·92 billion (1·89–1·95) prevalent cases, compared with a prevalence of 28·2% (27·8–28·5) and 1·50 billion (1·48–1·52) prevalent cases in 1990. Large variations were observed in anaemia burden by age, sex, and geography, with children younger than 5 years, women, and countries in sub-Saharan Africa and south Asia being particularly affected. Anaemia caused 52·0 million (35·1–75·1) YLDs in 2021, and the YLD rate due to anaemia declined with increasing Socio-demographic Index. The most common causes of anaemia YLDs in 2021 were dietary iron deficiency (cause-specific anaemia YLD rate per 100 000 population: 422·4 [95% UI 286·1–612·9]), haemoglobinopathies and haemolytic anaemias (89·0 [58·2–123·7]), and other neglected tropical diseases (36·3 [24·4–52·8]), collectively accounting for 84·7% (84·1–85·2) of anaemia YLDs. Interpretation Anaemia remains a substantial global health challenge, with persistent disparities according to age, sex, and geography. Estimates of cause-specific anaemia burden can be used to design locally relevant health interventions aimed at improving anaemia management and prevention. Funding Bill & Melinda Gates Foundation

Maternal outcomes of magnesium sulphate and diazepam use in women with severe pre-eclampsia and eclampsia in Ethiopia

Background: Preferred anticonvulsant used to treat and prevent fits in eclampsia currently is magnesium sulphate. Clinical monitoring of tendon reflexes, respiration rate and measuring hourly urine output should be done to ensures safe administration of magnesium sulphateObjective: This study was conducted to evaluate maternal outcomes of magnesium sulphate and diazepam use in the management of severe pre-eclampsia and eclampsia in Jimma University Specialized Hospital.Methods: A retrospective hospital based cross-sectional comparative study was conducted using data collection format. Data was collected from the hospital delivery care register and patient chart records of all pregnant women who presented with the diagnosis of severe pre-eclampsia and eclampsia in two years and three months period from January, 2010 to April, 2012. Data analysis was done by SPSS version 16.0. A P-value of <0.05 was considered statistically significant in all tests.Results: A total of 357 patient charts, 217 from magnesium sulphate and 140 from diazepam treated pregnant women group, were reviewed and analyzed. Three pregnant women from the magnesium sulphate treated group and eleven pregnant women from diazepam treated group had at least one convulsion after taking the drug. Greater proportion of patients in the magnesium sulphate treated group had less than four days postpartum stay as compared to the diazepam treated patients (82.3% versus 66.2%). Seizure occurrence, duration of postpartum hospital stays and birth outcome had a statistically significant association with the type of anticonvulsant used.Conclusions: Magnesium sulphate is more effective than diazepam in the management of severe pre-eclamptic and eclamptic pregnant women in terms of seizure prevention, shortening postpartum hospital stay and reducing maternal morbidities

Genetic and non‐genetic factors influencing efavirenz population pharmacokinetics among human immunodeficiency virus‐1‐infected children in Ethiopia

Abstract Despite the potential for efavirenz (EFV) to be an effective alternative antiretroviral agent, its sources of wide inter‐ and intra‐individual pharmacokinetic (PK) variability are not well‐characterized in children. We investigated the effects of genetic and non‐genetic factors, including demographic, treatment duration, baseline clinical, and biochemical characteristics, on the PKs of EFV through population‐PK modeling. Antiretroviral therapy (ART) naïve HIV infected children, 3–16 years (n = 100), were enrolled in Ethiopia and received EFV‐based combination ART. EFV concentrations after the first dose and at steady‐state collected over a span of 1 year were modeled using population‐based methods. A one‐compartment model with first‐order absorption kinetics described the observed EFV data adequately. The CYP2B6*6 and ABCB1c.4036A>G genotypes were identified as major factors influencing EFV clearance. The typical estimates of oral clearance, volume of distribution, and absorption rate constant for typical 22 kg children with CYP2B6 *1/*1 and ABCB1c.4036G/G genotypes were 4.3 L/h, 124 L, and 0.776/h, respectively. Clearance was reduced by 28% and 72% in CYP2B6*1/*6 and CYP2B6*6/*6 genotypes, respectively. Compared to week 1, clearance was higher from weeks 8 and 12 in CYP2B6*1/*6 and CYP2B6*1/*1 genotypes, respectively. Simulations indicated that EFV 12‐h concentrations were comparable across weight bands, but more than 80% of subjects with CYP2B6*6/*6 had EFV concentrations greater than 4 μg/mL. EFV PK variability among children is partly explained by body weight, treatment duration, CYP2B6*6, and ABCB1 rs3842 genotypes. Therefore, in addition to body weight, pediatric dosing of EFV should consider pharmacogenetic variability, duration of therapy, and individual treatment outcomes

Clinicopathological Features and Survival of Patients with Hepatocellular Carcinoma in Ethiopia: A Multicenter Study

(1) Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers globally, killing over 700,000 people each year. Despite the rising incidence and mortality rates of HCC in Ethiopia, only few single-centered studies have been conducted; therefore, we aimed to explore the clinicopathological characteristics and survival of patients with HCC in multicenter settings. (2) Methods: We conducted a retrospective analysis of 369 patients with confirmed HCC diagnosed between 2016 and 2021. The survival of patients weas determined using the Kaplan–Meier method, and hazard ratios of the prognostic factors were estimated in Cox proportional hazard models. (3) Results: Majority patients were male (67%) and had a mean age of 52.0 ± 15.6 years. The majority of patients (87%) had a large tumor size (>5 cm) at diagnosis and presented with an advanced-stage condition. Cirrhosis (58%) and viral hepatitis (46.5%) were the main risk factors associated with HCC. The median overall survival was 141 days (95% CI: 117–165). Patients who took antivirals for HBV had a higher survival benefit compared to the untreated group (469 vs. 104 days; p < 0.001). The risk of death was 12 times higher in patients with Barcelona Clinic Liver Cancer-D (BCLC-D) terminal stage HCC compared to patients with an early stage (BCLC-A) HCC. The stage of HCC and treatment against HBV are the most significant survival predictors. (4) Conclusions: The overall survival of HCC patients in Ethiopia is poor. Cirrhosis and viral hepatitis are the primary risk factors linked with HCC. Patients who received antiviral therapy for HBV had a better survival outcome

Clinicopathological Features and Survival of Patients with Hepatocellular Carcinoma in Ethiopia: A Multicenter Study

(1) Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers globally, killing over 700,000 people each year. Despite the rising incidence and mortality rates of HCC in Ethiopia, only few single-centered studies have been conducted; therefore, we aimed to explore the clinicopathological characteristics and survival of patients with HCC in multicenter settings. (2) Methods: We conducted a retrospective analysis of 369 patients with confirmed HCC diagnosed between 2016 and 2021. The survival of patients weas determined using the Kaplan&ndash;Meier method, and hazard ratios of the prognostic factors were estimated in Cox proportional hazard models. (3) Results: Majority patients were male (67%) and had a mean age of 52.0 &plusmn; 15.6 years. The majority of patients (87%) had a large tumor size (&gt;5 cm) at diagnosis and presented with an advanced-stage condition. Cirrhosis (58%) and viral hepatitis (46.5%) were the main risk factors associated with HCC. The median overall survival was 141 days (95% CI: 117&ndash;165). Patients who took antivirals for HBV had a higher survival benefit compared to the untreated group (469 vs. 104 days; p &lt; 0.001). The risk of death was 12 times higher in patients with Barcelona Clinic Liver Cancer-D (BCLC-D) terminal stage HCC compared to patients with an early stage (BCLC-A) HCC. The stage of HCC and treatment against HBV are the most significant survival predictors. (4) Conclusions: The overall survival of HCC patients in Ethiopia is poor. Cirrhosis and viral hepatitis are the primary risk factors linked with HCC. Patients who received antiviral therapy for HBV had a better survival outcome

Vitamin D Status and Association of <i>VDR</i> Genetic Polymorphism to Risk of Breast Cancer in Ethiopia

Emerging evidence associates vitamin D deficiency and vitamin D receptor (VDR) genetic variations with risk for breast cancer. This study investigated the prevalence of vitamin D deficiency and its association with tumor characteristics and the implications of VDR genetic variations for risk of breast cancer in Ethiopia. This unmatched case&#8315;control study involved 392 female breast cancer patients and 193 controls. The plasma 25-hydroxyvitamin D (25(OH)D3) level was quantified in chemotherapy-na&#239;ve (N = 112) and tamoxifen-treated patients (N = 89). Genotyping for the VDR common variant alleles rs7975232 (ApaI), rs2228570 (FokI), and rs731236 (TaqI) was done. Eighty-six percent of the patients were vitamin D deficient (&lt;50 nmol/L). Chemotherapy-na&#239;ve breast cancer patients had a higher prevalence of vitamin D deficiency (91.9% vs. 78.3%) compared to the tamoxifen-treated group (p &lt; 0.001). The prevalence of severe vitamin D deficiency (&lt;25 nmol/L) was significantly higher in chemotherapy-na&#239;ve (41.1%) than tamoxifen-treated (11.2%) patients. Vitamin D deficiency was not significantly associated with tumor characteristics or VDR genotype. The rs2228570 GG genotype was associated with increased risk of breast cancer (OR = 1.44, 95% confidence interval = 1.01&#8722;2.06). Our result indicates that rs2228570 might be a moderate risk factor for breast cancer development in the Ethiopian population. The high prevalence of severe vitamin D deficiency in treatment-na&#239;ve breast cancer patients indicates the need for nutritional supplementation of vitamin D at the time of chemotherapy initiation

Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990–2021: findings from the Global Burden of Disease Study 2021

Background: Anaemia is a major health problem worldwide. Global estimates of anaemia burden are crucial for developing appropriate interventions to meet current international targets for disease mitigation. We describe the prevalence, years lived with disability, and trends of anaemia and its underlying causes in 204 countries and territories. Methods: We estimated population-level distributions of haemoglobin concentration by age and sex for each location from 1990 to 2021. We then calculated anaemia burden by severity and associated years lived with disability (YLDs). With data on prevalence of the causes of anaemia and associated cause-specific shifts in haemoglobin concentrations, we modelled the proportion of anaemia attributed to 37 underlying causes for all locations, years, and demographics in the Global Burden of Disease Study 2021. Findings: In 2021, the global prevalence of anaemia across all ages was 24·3% (95% uncertainty interval [UI] 23·9–24·7), corresponding to 1·92 billion (1·89–1·95) prevalent cases, compared with a prevalence of 28·2% (27·8–28·5) and 1·50 billion (1·48–1·52) prevalent cases in 1990. Large variations were observed in anaemia burden by age, sex, and geography, with children younger than 5 years, women, and countries in sub-Saharan Africa and south Asia being particularly affected. Anaemia caused 52·0 million (35·1–75·1) YLDs in 2021, and the YLD rate due to anaemia declined with increasing Socio-demographic Index. The most common causes of anaemia YLDs in 2021 were dietary iron deficiency (cause-specific anaemia YLD rate per 100 000 population: 422·4 [95% UI 286·1–612·9]), haemoglobinopathies and haemolytic anaemias (89·0 [58·2–123·7]), and other neglected tropical diseases (36·3 [24·4–52·8]), collectively accounting for 84·7% (84·1–85·2) of anaemia YLDs. Interpretation: Anaemia remains a substantial global health challenge, with persistent disparities according to age, sex, and geography. Estimates of cause-specific anaemia burden can be used to design locally relevant health interventions aimed at improving anaemia management and prevention. Funding: Bill & Melinda Gates Foundation