Determinants of Unsuccessful TB Treatment Outcomes Among Patients on Directly Observed Treatment Short Course in Jimma Town Health Facilities, Southwest Ethiopia: A Case-Control Study.

Background: Even though Ethiopia's Federal Ministry of Health has been implementing several programs aimed at reducing the burden of tuberculosis (TB), It does not demonstrate adequate progress. As a result, identifying the determinants of unsuccessful outcomes of directly observed treatment, short-course (DOTS) is critical. Purpose: This study aimed to assess the determinants of unsuccessful TB treatment outcomes among patients with DOTS in Jimma town, southwest Ethiopia. Patients and Methods: An unmatched case-control study using secondary data was conducted among 118 cases and 472 controls from April 1 to June 1, 2021. Cases were TB cases with unsuccessful treatment courses whereas controls were those of successful treatment. Data were collected using a standardized tool. Statistical analysis was done using SPSS version 23 software. A binary logistic regression model was used to identify the determinants. Results: We found that the determinants including age > 35 years (AOR=1.9, 95% CI: 1.14-3.2), lack of contact person (AOR= 27, 95% CI: 15.8-46.3), being HIV positive (AOR=7.3, 95% CI: 3.7-14.2)), and being malnourished (AOR=4.5, 95% CI: 1.5-12.9) were significantly associated with unsuccessful tuberculosis treatment outcome. Conclusion: In this study, advanced age, being HIV positive, lack of contact person, and being malnourished were determinant factors for unsuccessful TB treatment outcomes. Hence, careful monitoring, screening, and management of risk factors are recommended.

Sexual Coercion is Associated with HIV Risk Behavior Among Female Waiters in Jimma Town, Southwest Ethiopia.

Background: Female waiters are at higher risk of workplace violence including sexual coercion. Even though there are numerous studies on the prevalence of sexual coercion among students, nurses, adolescents, and young pregnant women, studies on the prevalence of sexual coercion among female waiters are limited. Furthermore, there is no evidence existed that show a relationship between sexual coercion and HIV risk behavior in Ethiopia. Purpose: The purpose of this study was to examine the relationship between sexual coercion and HIV risk behavior among female waiters in Jimma, southwest Ethiopia. Patients and Methods: We conducted a cross-sectional survey from 1st April to 30, 2018, among 420 female waiters of reproductive age working in the licensed food and drinking establishments in Jimma town. A structured interviewer-administered questionnaire was used to collect data. Statistical analysis was conducted with SPSS version 21 statistical software. A binary logistic regression model was used to determine the association between independent variables and outcome variables. Results: The lifetime prevalence of sexual coercion among female waiters was 71.4% (95% confidence interval: 67.1-76.8). More than two-thirds (71.6%) of female waiters engaged in HIV-related risk behaviors. Working in the bar (AOR 4.64, 95% CI: 2.15-10.0), being a substance user (AOR 3.37, 95% CI: 1.7-6.7), experiencing sexual coercion (AOR 7.6, 95% CI: 3.8-15.3) were significantly associated with HIV risk behaviors. Conclusion: A significant number of female waiters experienced sexual coercion and engaged in HIV-risk behaviors. Workplace, substance use, and sexual coercion were significantly associated with HIV risk behavior. As a result, establishments, town health offices, and other stakeholders should work together to safeguard female waiters from the burdens of sexual coercion, HIV risk behavior, and sexually transmitted infections.

Treatment outcomes among children admitted stabilization centers in Eastern Ethiopia: retrospective study.

Background: There is improved access to Sever Acute Malnutrition management in Ethiopia; however, studies have revealed an alarming rate of defaulters' poor recovery and deaths, emphasizing the importance of researching to identify major causes. As a result, the goal of this research is to identify treatment outcome determinants and associated factors in severely malnourished children aged 6-59 months admitted to public hospitals in Eastern Ethiopia's stabilization centers. Methods: This study used an institutional-based retrospective cohort study design with 712 children aged 6 to 59 months. Data was gathered using a Sever Acute Malnutrition registration logbook and patient charts. Participants were chosen at random from their respective healthcare facilities based on population proportion. Epi-data was entered and analyzed using STATA version 14. To identify associated factors, the Cox proportional hazard Ratio was calculated, and a p-value of 0.05 at the 95% confidence interval was considered statistically significant. Results: This study revealed that only 70.65% (95% CI = 67.19, 73.88) of the children were cured while 17.84% defaulted from the management and 5.90% died. Children who did not have tuberculosis (AHR = 1.58, 95%CI:1.04, 2.40), anemia (AHR = 1.31, 95% CI:1.03, 1.68), Kwash dermatosis (AHR = 1.41, 95%CI:1.04, 1.91), or on NG-tube (AHR = 1.71, 95%CI:1.41, 2.08) were more likely to be cured from SAM. Conclusion: This study discovered that the cure rate is extremely low and the defaulter rate is extremely high. As a result, intervention modalities that address the identified factor are strongly recommended to accelerate the rate of recovery in Eastern Ethiopia.

In vitro Antibacterial Activities of Selected Medicinal Plants Used by Traditional Healers for Treating Urinary Tract Infection in Haramaya District, Eastern Ethiopia.

Background: Despite the presence of antibacterial agents for urinary tract infection treatment, most of the uropathogenic bacteria reveal multi-drug resistance. Health and economic loss due to these represent a rising burden worldwide which necessitates serious action at regional, national and global levels. Thus, alternative approaches to overcome this problem by using bioactive compounds from traditional medicinal plants are required. This study was designed to evaluate the in-vitro antibacterial activity of Punica granatum fruit peels, Nigella sativa seeds, and Echinops kebericho used in the traditional treatment of urinary tract infections. Methods: An experimental study was employed to evaluate the in vitro antibacterial activity of methanol and ethanol crude extract of Punica granatum fruit peels, Nigella sativa seeds, and Echinops kebericho roots of six dilutions (25, 50, 100, 125, 250, and 500) mg/mL. Disc diffusion and macro broth dilution methods were used to determine antimicrobial activity test and minimum inhibitory concentration respectively against E. coli, P. aeruginosa, K. pneumoniae, P. mirabilis, and S. aureus bacterias. Results: Antibacterial activities of ethanol and methanol crude extract of Punica granatum fruit peels against E. coli ATCC25922, P. aeruginosa ATCC27853, S. aureus ATCC25923, K. pneumoniae UK5099 and P. mirabilis UK5999 had highest inhibition zones among tested plants. All tested bacteria were highly sensitive to Punica granatum extract. The second most active plant extract in inhibiting the growth of tested bacteria was Nigella sativa while Echinops kebericho showed the smallest efficacy against tested bacteria. The inhibition zone diameter produced by the methanol extract of each screened plant had higher inhibition zones than ethanol extract. Conclusion: The crude extracts of Punica granatum fruit peels, Nigella sativa seeds, and Echinops kebericho roots have promising antibacterial activity against tested uropathogenic bacteria.

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

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.

The genomic and bioclimatic characterization of Ethiopian barley (Hordeum vulgare L.) unveils challenges and opportunities to adapt to a changing climate.

The climate crisis is impacting agroecosystems and threatening food security of millions of smallholder farmers. Understanding the potential for current and future climatic adaptation of local crop agrobiodiversity may guide breeding efforts and support resilience of agriculture. Here, we combine a genomic and climatic characterization of a large collection of traditional barley varieties from Ethiopia, a staple for local smallholder farmers cropping in challenging environments. We find that the genomic diversity of barley landraces can be partially traced back to geographic and environmental diversity of the landscape. We employ a machine learning approach to model Ethiopian barley adaptation to current climate and to identify areas where its existing diversity may not be well adapted in future climate scenarios. We use this information to identify optimal trajectories of assisted migration compensating to detrimental effects of climate change, finding that Ethiopian barley diversity bears opportunities for adaptation to the climate crisis. We then characterize phenology traits in the collection in two common garden experiments in Ethiopia, using genome-wide association approaches to identify genomic loci associated with timing of flowering and maturity of the spike. We combine this information with genotype-environment associations finding that loci involved in flowering time may also explain environmental adaptation. Our data show that integrated genomic, climatic, and phenotypic characterizations of agrobiodiversity may provide breeding with actionable information to improve local adaptation in smallholder farming systems.

Data-driven, participatory characterization of farmer varieties discloses teff breeding potential under current and future climates.

In smallholder farming systems, traditional farmer varieties of neglected and underutilized species (NUS) support the livelihoods of millions of growers and consumers. NUS combine cultural and agronomic value with local adaptation, and transdisciplinary methods are needed to fully evaluate their breeding potential. Here, we assembled and characterized the genetic diversity of a representative collection of 366 Ethiopian teff (Eragrostis tef) farmer varieties and breeding materials, describing their phylogenetic relations and local adaptation on the Ethiopian landscape. We phenotyped the collection for its agronomic performance, involving local teff farmers in a participatory variety evaluation. Our analyses revealed environmental patterns of teff genetic diversity and allowed us to identify 10 genetic clusters associated with climate variation and with uneven spatial distribution. A genome-wide association study was used to identify loci and candidate genes related to phenology, yield, local adaptation, and farmers' appreciation. The estimated teff genomic offset under climate change scenarios highlighted an area around lake Tana where teff cropping may be most vulnerable to climate change. Our results show that transdisciplinary approaches may efficiently propel untapped NUS farmer varieties into modern breeding to foster more resilient and sustainable cropping systems.

Small farms support the livelihoods of about two billion people worldwide. Smallholder farmers often rely on local varieties of crops and use less irrigation and fertilizer than large producers. But smallholdings can be vulnerable to weather events and climate change. Data-driven research approaches may help to identify the needs of farmers, taking into account traditional knowledge and cultural practices to enhance the sustainability of certain crops. Teff is a cereal crop that plays a critical role in the culture and diets of Ethiopian communities. It is also a super food appreciated on international markets for its nutritional value. Rural smallholder farmers in Ethiopia rely on the crop for subsistence and income and make up the bulk of the country's agricultural system. Many grow local varieties with tremendous genetic diversity. Scientists, in collaboration with farmers, could tap that diversity to produce more productive or climate-resilient types of teff, both for national and international markets. Woldeyohannes, Iohannes et al. produced the first large-scale genetic, agronomic and climatic study of traditional teff varieties. In the experiments, Woldeyohannes and Iohannes et al. sequenced the genomes of 366 Ethiopian teff varieties and evaluated their agronomic value in common gardens. The team collaborated with 35 local farmers to understand their preference of varieties and traits. They then conducted a genome-wide association study to assess the crops' productivity and their adaptations to local growing conditions and farmer preferences. Genetic changes that speed up teff maturation and flowering time could meet small farmers' needs to secure teff harvest. Woldeyohannes, Iohannes et al. also identified a region in Ethiopia, where local teff varieties may struggle to adapt to climate change. Genetic modifications may help the crop to adapt to frequent droughts that may be a common characteristic of future climates. The experiments reveal the importance of incorporating traditional knowledge from smallholder farmers into data-driven crop improvement efforts considering genetics and climate science. This multidisciplinary approach may help to improve food security and protect local genetic diversity on small farms. It may also help to ensure that agricultural advances fairly and equitably benefit small farmers.

Magnitude of Depression and Associated Factors Among Patients on Tuberculosis Treatment at Public Health Facilities in Harari Regional State, Eastern Ethiopia: Multi-Center Cross-Sectional Study.

Background: Depression among tuberculosis patients remains a significant public health concern. Its burden and severity is increasing in low-income countries, especially in sub-Saharan Africa. Although it has negative impacts on quality of life, depression among tuberculosis patients is rarely studied in Ethiopia, particularly in the study area. Therefore, this study aimed to determine the magnitude of depression and associated factors among tuberculosis patients in Eastern Ethiopia. Methods: A facility-based cross-sectional study was conducted from April 15 to May 15, 2021, among 213 tuberculosis patients in public health facilities of the Harari Regional State, Eastern Ethiopia. Study participants were selected using a systematic sampling technique. Data were collected using interviewer-administered questionnaire. Depression was assessed using Patients Health Questionnaire-9 (PHQ-9). Epi-data and SPSS were used for data processing and analysis. Bi-variable and multivariable logistic regressions were employed to determine the effects of predictors on depression. Statistical significance was considered at a p-value <0.05. Results: The magnitude of depression among tuberculosis patients was 52.1% [95% CI (45.4, 58.8%)]. Patient's age of 25-34 years [AOR = 0.31, 95% CI (0.128, 0.75)], female sex [AOR = 5.04; 95% CI (2.18, 11.62)], intensive phase of tuberculosis treatment [AOR = 2.56; 95% CI (1.118, 5.876)], HIV-positive status [AOR = 7.143; 95% CI (1.55, 32.93)], smoking history [AOR = 9.08; 95% CI (3.35, 24.61)] and having poor social support [AOR = 4.13; 95% CI (1.29, 13.22)] were factors statistically associated with depression. Conclusion: In this study, the magnitude of depression was relatively high as more than half of the participants had depression. Advanced age, female sex, intensive phase of tuberculosis treatment, HIV-positive status, smoking history, and poor social support were identified as associated factors with depression. Therefore, this result calls all stakeholders to give duly emphasis on incorporating and integrating mental health support programs as routine practice in tuberculosis follow-up clinics, as screening, early detection and treatment, and training for all health care providers are very crucial in tackling depression among tuberculosis patients.

Stakeholders, Institutional Challenges and the Valuation of Wetland Ecosystem Services in South Sudan: The Case of Machar Marshes and Sudd Wetlands.

A number of wetland ecosystem-services valuation studies around the world have been carried out, however, most of these studies have focused on wetlands in developed countries and few have been conducted in Africa, particularly in South Sudan. Thus, this study is conducted to value ecosystem services and identify the role and interests of stakeholders of the Machar Marshes and the Sudd wetlands for sustainable wetland management in the Nile basin. Market price and benefit transfer approaches have been applied to value the wetlands biodiversity and ecosystem services, by adjusting for income and price differences. In addition to environmental valuation methods, we conducted stakeholder analysis. Accordingly, Machar Marshes wetland provides an estimated per annum economic value of $200 million, of which the provisioning services contributed about $61 million, regulating services $132 million, and biodiversity services $7.35 million considering the 2015 price as a base year. Similarly, the Sudd wetland provides an estimated per annum economic value of 2.3 billion, of which regulating is about $1.2 billion, biodiversity $857 million, provisioning $209 million, and transportation service $293,400. The findings show that the ecosystem services from the wetlands have benefits beyond the local communities. Thus, to maintain and ensure sustainable wetlands ecosystem services, stakeholders should play a significant role to implement alternative wetland development options through managing the existing institutional challenges. Ecosystem-services assessment and wetland development options suffer from weak institutional capacity due to prolonged conflicts and instability and physical inaccessibility to critical natural resources in the wetlands.

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.

Population Pharmacokinetic, Pharmacogenetic, and Pharmacodynamic Analysis of Cyclophosphamide in Ethiopian Breast Cancer Patients.

Cyclophosphamide (CPA) containing chemotherapy regimen is the standard of care for breast cancer treatment in sub-Saharan Africa. Wide inter-individual variations in pharmacokinetics (PK) of cyclophosphamide (CPA) influence the efficacy and toxicity of CPA containing chemotherapy. Data on the pharmacokinetics (PK) profile of CPA and its covariates among black African patients is lacking. We investigated population pharmacokinetic/pharmacogenetic/pharmacodynamic (PK-PG-PD) of CPA in Ethiopian breast cancer patients. During the first cycle of CPA-based chemotherapy, the population PK parameters for CPA were determined in 267 breast cancer patients. Absolute neutrophil count was recorded at baseline and day 20 post-CPA administration. A population PK and covariate model analysis was performed using non-linear mixed effects modeling. Semi-mechanistic and empiric drug response models were explored to describe the relationship between the area under concentration-time curve (AUC), and neutrophil toxicity. One compartment model better described CPA PK with population clearance and apparent volume of distribution (VD) of 5.41 L/h and 46.5 L, respectively. Inter-patient variability in CPA clearance was 54.5%. Patients carrying CYP3A5*3 or *6 alleles had lower elimination rate constant and longer half-life compared to wild type carriers. CYP2C9 *2 or *3 carriers were associated with increased clearance of CPA. Patients who received 500 mg/m2 based CPA regimen were associated with a 32.3% lower than average clearance and 37.1% lower than average VD compared to patients who received 600 mg/m2. A 0.1 m2 unit increase in body surface area (BSA) was associated with a 5.6% increment in VD. The mean VD (33.5 L) in underweight group (BMI < 18.5 kg/m2) was significantly lower compared to those of overweight (48.1 L) or obese patients (51.9 L) (p < 0.001). AUC of CPA was positively correlated with neutropenic toxicity. In conclusion, we report large between-patient variability in clearance of CPA. CYP3A5 and CYP2C9 genotypes, BSA, BMI, and CPA dosage regimen influence PK of CPA. Plasma CPA exposure positively predicts chemotherapy-associated neutropenic toxicity.

Trace elements geochemistry in high-incidence areas of liver-related diseases, northwestern Ethiopia.

This paper reports the results of trace elements geochemistry from Tigray national state, northwestern Ethiopia. The area is part of the Arabian-Nubian Shield, where the dominant exposure is low-grade metamorphic rocks and has a long history of liver-related diseases. The increase in the number of liver-related disease patients of the area has been an environmental health issue of national concern. The aim of the study is to determine the level of trace element concentrations and distributions in water and stream sediments of the area and identify the possible sources in relation to human health. Water, stream sediment and rocks samples (20 water, 20 stream sediments, and 6 rock samples) were collected in March 2011 and analyzed for major and trace element contents using ICP-MS, ICP-OES, ion Chromatography, and XRF methods. Bromine, aluminum, fluorine, arsenic, and nitrate values exceed the WHO maximum acceptable concentration (MAC) for drinking purpose. Bromine ranges from 0.11 to 1.48 mg/l show higher values in all samples, and fluorine ranges from 0.21 to 16.49 mg/l show higher values in 20% of the samples. Other trace elements are aluminum-30%, arsenic-10%, and nitrate (NO3)-10%, and they are examples of elements which have above MAC for drinking water. Selenium deficiency may be the other problematic element in the area for which its deficiency is associated with liver damage and heart muscle disorder. The concentration of cobalt and chromium exceeded world geochemical background value in average shale at most sample stations indicated that these stations were in potential risk.

CYP2D6 Genotype Predicts Plasma Concentrations of Tamoxifen Metabolites in Ethiopian Breast Cancer Patients.

Tamoxifen displays wide inter-individual variability (IIV) in its pharmacokinetics and treatment outcome. Data on tamoxifen pharmacokinetics and pharmacogenetics from black African breast cancer patient populations is lacking. We investigated the pharmacokinetic and pharmacogenetic profile of tamoxifen and its major active metabolite, endoxifen, in Ethiopian breast cancer patients. A total of 81 female breast cancer patients on adjuvant tamoxifen therapy were enrolled. Tamoxifen (Tam) and its major metabolites, N-desmethyltamoxifen (NDM), 4-hydroxy-tamoxifen (4-HT), and (Z)-endoxifen (E) were quantified using LC-MS/MS. Genotyping for CYP2D6, CYP2C9, CYP2C19, CYP3A5, POR, and ABCB1 and UGT2B15 and copy number variation for CYP2D6 were done. The proportion of patients with low endoxifen level (<5.9 ng/mL) was 35.8% (median concentration 7.94 ng/mL). The allele frequency of CYP2D6 gene deletion (*5) and duplication (*1×N or *2×N) was 4.3% and 14.8%, respectively. Twenty-six percent of the patients carried duplicated or multiplicated CYP2D6 gene. An increase in CYP2D6 activity score was associated with increased endoxifen concentration and MRE/NDM (p < 0.001). The IIV in endoxifen concentration and MRE/NDM was 74.6% and 59%, respectively. CYP2D6 diplotype explained 28.2% and 44% of the variability in absolute endoxifen concentration and MRE/NDM, respectively. The explanatory power of CYP2D6 diplotype was improved among ABCB1c.4036G carriers (43% and 65.2%, respectively for endoxifen concentration and MRE/NDM) compared to A/A genotype. CYP2C9, CYP2C19, and CYP3A5 genotypes had no significant influence on endoxifen concentration or MRE/NDM. In conclusion, we report a high rate of low endoxifen level as well as large IIV in tamoxifen and its metabolite concentrations. CYP2D6 is significant predictor of plasma endoxifen level in a gene-dose dependent manner.

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.

Vitamin D Status and Association of VDR 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⁻control study involved 392 female breast cancer patients and 193 controls. The plasma 25-hydroxyvitamin D (25(OH)D3) level was quantified in chemotherapy-naïve (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 (<50 nmol/L). Chemotherapy-naïve breast cancer patients had a higher prevalence of vitamin D deficiency (91.9% vs. 78.3%) compared to the tamoxifen-treated group (p < 0.001). The prevalence of severe vitamin D deficiency (<25 nmol/L) was significantly higher in chemotherapy-naïve (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 = 1.01-2.06). 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-naïve breast cancer patients indicates the need for nutritional supplementation of vitamin D at the time of chemotherapy initiation.

A phase I, open-label trial on the safety and immunogenicity of the adjuvanted tuberculosis subunit vaccine H1/IC31® in people living in a TB-endemic area.

BACKGROUND: H1/IC31® is a tuberculosis (TB) subunit vaccine candidate consisting of the fusion protein of Ag85B and ESAT-6 (H1) formulated with the IC31® adjuvant. Previous trials have reported on the H1/IC31® vaccine in M. tuberculosis (Mtb)-naïve, BCG-vaccinated and previously Mtb-infected individuals. In this trial, conducted between December 2008 and April 2010, the safety and immunogenicity of H1/IC31® was assessed in participants living in Ethiopia - a highly TB-endemic area. METHODS: Healthy male participants aged 18-25 years were recruited into four groups. Participants in group 1 (N = 12) and group 2 (N = 12) were Tuberculin Skin Test (TST) negative and QuantiFERON-TB Gold in-tube test (QFT) negative (Mtb-naïve groups), participants in group 3 (N = 3) were TST positive and QFT negative (BCG group), and participants in group 4 (N = 12) were both TST and QFT positive (Mtb-infected group). H1 vaccine alone (group 1) or H1 formulated with the adjuvant IC31® (groups 2, 3 and 4) was administered intramuscularly on day 0 and day 56. Safety and immunogenicity parameters were evaluated for up to 32 weeks after day 0. RESULTS: The H1/IC31®vaccine was safe and generally well tolerated. There was little difference among the four groups, with a tendency towards a higher incidence of adverse events in Mtb-infected compared to Mtb-naïve participants. Two serious adverse events were reported in the Mtb-infected group where a relationship to the vaccine could not be excluded. In both cases the participants recovered without sequelae within 72 h. Immunogenicity assays, evaluated in the 29 participants who received both vaccinations, showed a stronger response to TB antigens in the Mtb-naïve group vaccinated with the adjuvant. CONCLUSION: The trial confirmed the need for an adjuvant for the vaccine to be immunogenic and highlighted the importance of early phase testing of a novel TB vaccine candidate in TB-endemic areas. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT01049282. Retrospectively registered on 14 January 2010.

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 sulphate. OBJECTIVE: 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.

Maternal outcomes of magnesium sulphate and diazepam use in women with severe pre-eclampsia and eclampsia in Ethiopia / Resultados maternos del uso de sulfato de magnesio y diazepam en mujeres con pre-eclampsia grave en Etiopia

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 sulphate Objective: 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 treatedpregnant 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 (AU)

Antecedentes: El anticonvulsivante preferido para tratar y prevenir ataques en eclampsia es actualmente el sulfato de magnesio. Para garantizar una administración segura del sulfato de magnesio debería realizarse una monitorización clínica de los reflejos tendinales, velocidad de respiración y producción horaria de orina. Objetivo: Este estudio se realizó para evaluar los resultados maternos del uso de sulfato de magnesio y diazepam en el manejo de la pre-eclampsia y eclampsia graves en el Hospital especializado de la Universidad de Jimma. Métodos: Se realizó un estudio transversal retrospectivo mediante recogida de datos. Los datos se recogieron del registro de cuidados prestados en el hospital y de las historias clínicas de todas las embarazadas que presentaron diagnóstico de pre-eclampsia o eclampsia grave en los dos años y tres meses entre enero 2010 y abril 2012. El análisis se realizó con un SPSS versión 16.0. Se consideró significativo para todas las pruebas un p<0,05. Resultados: Se revisaron y analizaron un total de 357 historias clínicas de 217 pacientes tratados con sulfato de magnesio y 140 con diazepam. Tres embarazadas tratadas con sulfato de magnesio y 11 tratadas con diazepam habían tenido, al menos, una convulsión después de tomar el medicamento. La mayor proporción de pacientes tratadas con sulfato de magnesio tuvo menos de 4 días de estancia post-parto comparadas con las tratadas con diazepam (82,3% versus 66,2%). La aparición de convulsiones, la estancia hospitalaria post-parto y los resultados del parto tuvieron asociación estadísticamente significativa con el tipo de anticonvulsivante utilizado. Conclusiones: El sulfato de magnesio es más efectivo que el diazepam en el manejo de pre-eclampsia y eclampsia graves en términos de prevención de convulsiones, reducción de la estancia hospitalaria post-parto y reducción de las morbilidades maternas (AU)

Supplement Use Among Pregnant Women in Ethiopia: Prevalence and Predictors.

Purpose The purpose of this article was to assess the pattern of supplement use and associated factors among pregnant women in Ethiopia. Methods A facility-based cross-sectional study was conducted. A total of 339 pregnant women were included in the study, 63 (18.3%) and 23 (6.8%) of whom used at least 1 supplement during pregnancy and 2 to 4 weeks prior to pregnancy, respectively. Only 3 women were prescribed folic acid during pregnancy. The pregnant women were interviewed to collect supplements use and pregnancy-related information through a pretested semistructured questionnaire. Subsequent charts of prescribed supplements were reviewed using a pretested data collection format. Results The majority (76.4%) of the women claimed no awareness about the benefits of early supplementation. Supplement use was about 8 times higher among women with > 3 children (adjusted odds ratio, 7.85; 95% confidence interval, 1.69-36.28; P = .008) than among nulliparous women, and about 6 times higher among women in their second trimester (adjusted odds ratio, 6.26; 95% confidence interval, 1.91-20.55; P = .03) of pregnancy compared to those women in their first trimester. Conclusion Overall supplement use, particularly folic acid intake, was found to be negligible during the prenatal as well as antenatal periods. The majority of the women in the study lacked awareness about the benefits of supplementation and potential risks associated with the absence of folic acid during pregnancy. Information by the media and health care personnel given to childbearing women about the need to take folic acid to prevent neural tube defects seems to improve the intake of folic acid during the protective period.