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Abraha Hailu,1 Kibreab Gidey,1 Mohamedawel Mohamedniguss Ebrahim,2 Yonas Berhane,1 Teklay Gebrehaweria Baraki,1 Tesfay Hailemariam,1 Ataklti Negash,1 Habtamu Mesele,1 Tekleab Desta,1 Haylsh Tsegay,1 Mulubirhan Assefa,3 Alemayehu Bayray3 1Department of Internal Medicine, School of Medicine, Mekelle University-College of Health Sciences, Mekelle, Tigray, Ethiopia; 2Department of Biostatistics, School of Public Health, Mekelle University-College of Health Sciences, Mekelle, Tigray, Ethiopia; 3Department of Epidemiology, School of Public Health, Mekelle University-College of Health Sciences, Mekelle, Tigray, EthiopiaCorrespondence: Abraha Hailu, Department of Internal Medicine, Cardiology Unit, School of Medicine, Mekelle University-College of Health Sciences, Mekelle, Tigray, Ethiopia, Tel +251911413363, Email abrahahailu7@gmail.comBackground: Documentation of cardiovascular diseases (CVDs) including major contributors to hospitalization and their outcomes in sub-Saharan Africa and Ethiopia is important to prioritize further research, prevention and treatment strategies.Objective: This study aimed to describe the clinical profiles of CVD admissions, risk factors, and patient outcomes at Ayder Comprehensive Specialized Hospital (ACSH) in Tigray, Ethiopia.Methods: Data of patients with the diagnosis of CVD was collected prospectively from Nov. 1, 2017 – Oct. 31, 2018 for patients admitted to medical wards and ICU of ACSH. Socio-demographic profiles, final admission diagnosis, duration of hospital stay and outcomes of hospitalization were variables recorded using a data abstraction checklist. Diseases were categorized using the World Health Organization’s International Classification of Diseases (ICD)-10 coding system. Data was analyzed using SPSS version 26.Results: Of the 2084 admissions over 1 year period, 767 (36.5%) had CVDs. The mean age of the study population was 53.4 ± 19.4 years with 55% females. Leading CVD admissions were stroke (35%), Venous thromboembolism (17%), rheumatic heart disease (RHD) (16.2%), ischemic heart disease (IHD) (11.3%) and cardiomyopathy (CMP) (7.4%). Heart Failure (HF) was found in 300 (39.1%) patients with structural heart disease. The structural cardiac lesions in those with HF were RHD (36%), CMP (19%), IHD (18%) and Cor pulmonale (9%). The in-hospital mortality of all CVD admissions was 13.2%. Of the total 101 CVD deaths most were because of stroke (n=37, 36.6%) followed by IHD (18.8%). Hypertension was the most frequent risk factor (28.8%).Conclusion: This study shows stroke to be the most common form of CVD and RHD to be the main reason for HF among hospital admissions in Northern Ethiopia, ACSH. Hypertension is the leading reported risk factor and hence the need to give high priority to hypertension and RHD control programs.Keywords: cardiovascular disease, admissions, outcomes, sub-Saharan Africa, Ethiopia

Abay Atnafu,1 Liya Wassie,1 Melaku Tilahun,1,&ast; Selfu Girma,1 Yohannes Zenebe,2 Muluye Abebe Beyene,1 Ashenafi Alemu,1 Emnet Fisseha,1 Haymanot Agze,1 Tigist Desta,1 Kassu Desta,3,&ast; Kidist Bobosha1,&ast; 1Armauer Hansen Research Institute, Addis Ababa, Ethiopia; 2Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia; 3Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia&ast;These authors contributed equally to this workCorrespondence: Abay Atnafu, Tel +251912205822, Email ayatab.ayele7@gmail.comBackground: Extrapulmonary tuberculosis (EPTB), particularly tubercular lymphadenitis (TBLN), remains to pose a huge public health problem in Ethiopia. A significant number of TBLN patients who completed a full course anti-TB treatment regimen were reported to have enlarged lymph nodes and other TB-like clinical presentations. This could either be from a paradoxical reaction or microbiological relapse, possibly due to mono/multi-drug resistance.Objective: To investigate the rate of mono and multidrug resistance patterns of Mycobacterium tuberculosis as a cause of the observed treatment failures in clinically diagnosed and anti-TB treatment (newly or previously)-initiated LN patients.Methods: A cross-sectional study was conducted on 126 TBLN-suspected and previously treated patients between March and September 2022. Data were analyzed using SPSS (Version 26.0). Descriptive statistics were used to determine the frequency, percentage, sensitivity, specificity, and positive and negative predictive values. The level of agreement was determined using Cohen’s kappa and a Chi-square test was used to measure the association between risk factors and laboratory test outcomes. A P-value < 0.05 was considered statistically significant.Results: Mycobacterium tuberculosis was confirmed in 28.6% (N=36) of the 126 cases using BACTEC MGIT 960 culture detection method. Approximately, 13% (N=16) of the samples were collected from previously treated TBLN patients, of which 5/16 (31.3%) were multi-drug resistant, 7/16 were drug-sensitive and 4/16 were culture negative. To rule out other non-tuberculous agents, all samples were grown on blood and Mycosel agar plates, and no growth was detected.Conclusion: The emergence of drug resistant (DR) TB seems to not just be limited to pulmonary form but also to TBLN. In this study we observed a considerable number of microbiologically confirmed relapses among previously treated cases, possibly indicating the need for confirmation of drug resistance using rapid molecular methods or phenotypical methods during treatment follow up.Keywords: tubercular lymphadenitis, relapse, drug sensitivity testing, DST, FNA

Abraha Hailu,1 Kibreab Gidey,1 Mohamedawel Mohamedniguss Ebrahim,2 Yonas Berhane,1 Teklay Gebrehawaria,1 Tesfay Hailemariam,1 Atakelti Negash,1 Habtamu Mesele,1 Tekleab Desta,1 Haylsh Tsegay,1 Mulubirhan Assefa Alemayohu,3 Alemayehu Bayray3 1Department of Internal Medicine, School of Medicine, Mekelle University - College of Health Sciences, Mekelle, Tigray, Ethiopia; 2Department of Biostatistics, School of Public Health, Mekelle University - College of Health Sciences, Mekelle, Tigray, Ethiopia; 3Department of Epidemiology, School of Public Health, Mekelle University - College of Health Sciences, Mekelle, Tigray, EthiopiaCorrespondence: Abraha Hailu Weldegerima, Department of Internal Medicine, Cardiology Unit, Mekelle University College of Health Sciences, Mekelle, Tigray, Ethiopia, Tel +251-91-141-3363, Email abrahahailu7@gmail.comBackground: Previous works show that noncommunicable diseases (NCDs) are on the rise in developing nations, including Ethiopia, in the background of preexisting communicable diseases (CDs). Data on hospital admission in sub-Saharan Africa are scarce, particularly prospectively collected, and hence this study was done to close the gap in acquiring accurate diagnosis usually faced with retrospective data. We aimed to describe medical admission patterns, their outcomes and determinants at Ayder Comprehensive Specialized Hospital (ACSH) in Tigray, Ethiopia.Methods: Data were collected prospectively from November 1, 2017 to October 31, 2018 for all medical admissions. Sociodemographic profiles, final diagnosis, outcome of hospitalization, and complications were recorded using a data-abstraction checklist. Data were analyzed using SPSS 26.Results: There were 2084 medical admissions over 1 year. Median age was 45 years (IQR 31). A majority (1107, 53.1%) were male. The age-group 25– 34 years had the most admissions (19.0%). NCDs constituted 68.2% of admissions. According to the International Classification of Diseases, patients were admitted most frequently due to disease of the circulatory system (36.7%) followed by infectious or parasitic diseases (24.1%). Of NCDs, cardiovascular diseases contributed to 53.9%, followed by cancers (8.6%). Of CDs, HIV/AIDS contributed to 31.3%, followed by tuberculosis (22.8%). A total of 1375 (66%) were discharged improved, while 311 (14.9%) died. On multivariate analysis, the in-hospital mortality was significantly higher (18.7%) for CDs than NCDs (13.2%, AOR 1.8, 95% CI 1.4– 2.3; P< 0.001). Bed occupancy of ACSH medical wards and ICU was 54%.Conclusion: NCDs were leading causes of medical admissions in ACSH. The presence of CDs and the development of complications were associated with higher risk of death. Attention should be given by policy-makers to curb the higher morbidity from NCDs and mortality from CDs.Keywords: medical admissions, mortality, Ayder, Ethiopia

Temesgen Tsega Desta,1 Mulugeta Naizgi2 1Saint Paul Hospital Millennium Medical College, Addis Ababa, Ethiopia; 2Ayder Hospital, Mekelle University, Tigray, EthiopiaCorrespondence: Temesgen Tsega Desta Tel +251 911023103Email yafettemu@gmail.comBackground: Rheumatic fever continues to be a major public health problem in the developing world, being responsible for many morbidities and mortalities. Were it not for its serious effects on the cardiovascular system, and to some extent on the central nervous system, the disease might not have significant consequences. The central nervous system involvement is explained with Sydenham chorea in which case the patient manifests with purposeless and choreiform movements aggravated by stress. Apart from this movement disorder the patient will also demonstrate emotional liability and motor manifestations. It is seen more commonly in children and young adolescent girls. It usually manifests as an isolated phenomenon called pure chorea, without evidence of active rheumatic fever; the other rare form of which is a type of acute rheumatic fever.Clinical Description: This case report is about a nine-year-old female child presenting with two weeks of complaint of abnormal purposeless, non-rhythmic movement of extremities and the face, with failure to communicate. At presentation, she had non-pruritic skin lesions that had appeared a day prior to admission. The skin lesions were circular, red in color, and painless, involving the abdomen, and lower chest anteriorly, and extending to all extremities and the back. Two months previously she had a history of sore throat and treatment with unspecified P.O. medication. Antistreptolysin O (ASO) antibody was 430 Todd units/mL and the erythrocyte sedimentation rate was 58 mm/h. Echocardiography study revealed carditis (no evidence of chronicity) with moderate to severe MR, mild TR, no pulmonary hypertension, good biventricular function, and no pericardial effusion.Conclusion: In this case report, we would like to show the central nervous system manifestation of rheumatic fever called Sydenham chorea seen together with erythema marginatum and other features of rheumatic fever.Keywords: Sydenham chorea, erythema marginatum, rheumatic recurrence, antistreptolysin O antibody

Introduction: Tuberculous lymphadenitis (TBLN) is an infection of the lymph node caused by Mycobacterium tuberculosis. Histological diagnoses of presumptive patients are often accompanied by cytomorphological features. However, the sensitivities of these features are often precluded by the variable degrees of narrative similarities compared to other diagnostic modalities., Objective: The aim of this study was to investigate and compare the cytomorphological and clinical features of presumptive TBLN patients with bacteriological detection methods., Methods: A similar cohort of TBLN patients from our previous study who were enrolled prospectively from the ALERT Specialized Hospital, Addis Ababa, Ethiopia, was considered for this analysis. SPSS version 26 was used for data analysis. Descriptive analysis was conducted to characterize the study population using the independent variable and presented with frequency tables. The chi-square test was used to measure the association. A P-value of < 0.05 was considered statistically significant., Results: Using FNAC, 60/126 (47.6%) of the participants were reported to have features consistent with TB. Of the total FNAC-positive cases, many (30/60 and 27/60) showed pattern B (caseous necrosis only) and pattern C (epithelioid granuloma with caseous necrosis), respectively. Strong concordance was observed in Pattern A (abundant caseous necrosis with few epithelioid macrophages) followed by patterns B and C with GeneXpert and MGIT culture (P value < 0.001). Night sweats and alcohol intake were shown to correlate with positive cases as reported by FNAC (P value = 0.008 respectively), GeneXpert (P value = 0.02 & 0.001), and culture methods (P-value = < 0.001 & 0.002)., Conclusion: Cytomorphological features, particularly patterns A, B, and C, could be considered in the diagnosis of TBLN given their comparable outcomes with bacteriological detection methods. On another note, we recommend that due care and attention be given when treating TBLN patients based solely on clinical presentation, as these diagnostics may be prone to false results, leading to inappropriate administration of anti-TB drugs and other consequences., (© 2024. The Author(s).)

Background: With a neonatal mortality rate of 33 per 1,000 live births in 2019, Ethiopia is striving to attain the Sustainable Development Goal target of 12 deaths per 1,000 live births by 2030. A better understanding of the major causes of neonatal mortality is needed to effectively design and implement interventions to achieve this goal. Minimally Invasive Tissue Sampling (MITS), an alternative to conventional autopsy, requires fewer resources and through task-shifting of sample collection from pathologists to nurses, has the potential to support the expansion of pathology-based post-mortem examination and improve mortality data. This paper evaluates the accuracy and adequacy of MITS performed by nurses at a tertiary and general hospital and in the home of the deceased., Methods: Nurses in a tertiary and general hospital in Ethiopia were trained in MITS sample collection on neonatal deaths and stillbirths using standardized protocols. MITS sample collection was performed by both pathologists and nurses in the tertiary hospital and by nurses in the general hospital and home-setting. Agreement in the performance of MITS between pathologists and nurses was calculated for samples collected at the tertiary hospital. Samples collected by nurses in the general hospital and home-setting were evaluated for technical adequacy using preestablished criteria., Results: One hundred thirty-nine MITS were done: 125 in hospitals and 14 inside homes. There was a perfect or almost perfect agreement between the pathologists and the nurses in the tertiary hospital using Gwet's agreement interpretation criteria. The adequacy of MITS samples collected by nurses in the general hospital was more than 72% when compared to the preset criteria. The adequacy of the MITS sampling yield ranged from 87% to 91% on liveborn neonatal deaths and 76% for the liver, right and left lungs and 55% for brain tissues in stillbirths., Conclusions: This study demonstrated that task-shifting MITS sample collection to nurses can be achieved with comparable accuracy and adequacy as pathologists. Our study showed that with standardized training and supportive supervision MITS sample collection can be conducted by nurses in a tertiary, general hospital and, at the home of the deceased. Future studies should validate and expand on this work by evaluating task-shifting of MITS sample collection to nurses within community settings and with larger sample sizes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Muhe, Paganelli, Ayele, Desta, Mekasha, Demtse, Awoke, Elfu, Gebremariam, Tamrat, Jiffar, Zenabu, Sori, Parlberg, Worku and Nigussie.)

Purpose: Different biological characteristics, therapeutic responses, and disease-specific outcomes are associated with different molecular subtypes of breast cancer (BC). Although there have been different studies on BC in the Ethiopian capital city of Addis Ababa, there have been few studies in other parts of the nation, and none have evaluated biological characteristics in other locations in the context of the extensive ethnic and genetic diversity found in Ethiopia. This study was carried out to evaluate the distribution of immunohistochemistry (IHC) subtypes of BCs throughout four Ethiopian regions., Methods: A total of 227 formalin-fixed paraffin-embedded (FFPE) tissue blocks were collected from tertiary hospitals in four Ethiopian regions between 2015 and 2021. The IHC staining was performed for subtyping, ER, PR, HER2, and Ki-67 proliferation markers., Results: The mean age at diagnosis was 43.9 years. The percentage of ER and PR-negative tumors were 48.3% and 53.2%, respectively. The IHC subtypes showed the following distribution: 33.1% triple-negative breast cancer (TNBC), 27.6% luminal B, 25.2% luminal A, and 14.1% HER2 enriched. In multiple logistic regression analysis, grade III and HER2 positivity were associated with larger tumor size, and also originating from Jimma compared to Mekele., Conclusion: Patients with ER-negative, PR-negative, and TNBC were found in 48.3%, 53.2%, and 33.1% of cases, respectively, showing that half the patients could potentially benefit from endocrine treatment. A considerably high prevalence of TNBC was reported in our study, demanding additional research that includes genetic predisposition factors. Additionally, aggressive tumors were found in a high percentage of younger age groups, which must be considered when planning personalized treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Belachew, Desta, Gebremariam, Deneke, Ashenafi, Yeshi, Fenta, Alem, Alemu, Abafogi, Desta, Chanyalew, Beshah, Taylor, Bauer, Tsehay, Girma, Melka, Tessema, Kantelhardt and Howe.)

Background: Tibial shaft fractures are the most common long bone fractures requiring treatment. High-energy trauma often causes tibia bone injuries, causing severe complications and long-term disability due to inadequate soft tissue coverage. Tibial shaft fractures can be treated using casts, external fixators, plating, or intramedullary nails. Intramural nailing leads to faster union and reduced complications like malunion and shortening. However, patients often report subjective and objective difficulties after Surgical Instrument generation network (SIGN) nail fixation, affecting knee range of motion, quality of life, and sport activities. Tibial nails and plates are associated with increased knee pain, which negatively affects functional outcomes. No study has been conducted in a poor resource setting like Ethiopia. This study aims to assess functional outcomes of the knee and associated factors after intramedullary nailing of Tibial Diaphysial Fractures at AaBET hospital in Ethiopia., Methods: A retrospective health facility based cross-sectional study was conducted on functional outcomes of the knee and associated factors after intramedullary nailing of tibial diaphysial fractures done at AaBET hospital. A medical record review form and a structured questionnaire from patient chart and SIGN nail database collected data. The study was conducted on 151 patients registered on the SIGN nail database using a simple random sampling. Knee injury and Osteoarthritis Outcome Score (KOOS) was used to assess the knee functional outcome. Descriptive statistics such as frequency and percentage were used to summarize the results and binary logistic regression was used to describe the association between variables. P value < 0.05 was considered statistically significant association., Results: The study constituted 151 patients with tibial shaft fractures; 113(74.8%) males and 38(25.2%) females with a mean age of 31.4 years, with a standard deviation of [10.5]. The prevalence of patients with good knee functional outcomes was 87(57.6%), while 64(42.4%) patients had poor knee functional outcomes. Associated factors identified include sex, age, soft tissue status, postoperative infection postoperative physiotherapy and comminuted fracture pattern., Conclusion and Recommendation: This study determined the magnitude of knee functional outcomes revealed that more than half (57.6% ) of patients had good knee functional outcomes with identified factors increseaes odds of poor knee functional outcomes were sex, age, soft tissue injuries, post operative infection, postoperative physiotherapy and comminuted fracture patterns respectively. Therefore, Policymakers and health planners should closely monitor postoperative physiotherapy treatment courses among tibial shaft fractures treated with intramedullary nailing to increases good knee functional outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: The intramedullary nailing of long bone fractures is a major challenge for orthopedic surgeons, with increased risk of infection in third-world countries. Research gaps remain in Ethiopia, determining the magnitude of the problem. This study aimed to determine the prevalence and associated factors of infection after intramedullary nailing of long bone fractures in Ethiopia., Methods: This was a descriptive, cross-sectional, retrospective design study with a total census of 227 cases of long bone fractures treated with intramedullary Surgical Implant Generation Network nails at Addis Ababa Burn Emergency and Trauma Hospital from August 2015 to April 2017. Data were collected from 227 patients and descriptive analyses were done to summarize the study variables. Binary and multivariable logistic regression analyses were performed at a p value of 0.05 with a 95% confidence interval and adjusted odds ratio., Results: The mean age of patients was 32.9 years, with a male-to-female ratio of 3.5:1. Only 22 (9.3%) of the 227 patients with long bone fractures treated with intramedullary nails developed a surgical site infection, and 8 (3.4%) were developed deep (implant) infections requiring debridement. Road traffic injuries were the leading cause of trauma (60.9%), followed by falls from a height (22.7%). Debridement was done within 24 h for 52 (61.9%) and within 72 h for 69 (82.1%) patients with open fractures. Only 19 (22.4%) and 55 (64.7%) patients with open fractures and tibial long bone fractures received antibiotics within 3 h. Open fractures and tibial fractures had higher percentages of infection, 18.6% and 12.1%, respectively. Previous use of an external fixator (44.4%) and prolonged surgery (12.5%) were associated with higher proportions of infection., Conclusion: This study found that the prevalence of infections after intramedullary nailing of long bone fractures in Ethiopia was 44.4% after external fixation, compared to 6.4% after intramedullary nail was inserted directly. Proper control measures are needed to reduce morbidity and complications related to long fracture treatment, such as open fractures, tibial fractures, the use of an external fixator, delayed debridement and skin closure, and prolonged surgery developed surgical site infection rate., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: In Ethiopia, little is known about postoperative pain trajectories and possible predictive factors associated with them in patients undergoing surgery following traumatic fractures., Methods: This multi-center prospective observational cohort study included surgical candidates for traumatic fractures (n = 218). Worst pain intensity was measured with an 11-point numeric rating scale on the first 4 postoperative days and day of hospital discharge. Growth mixture modeling was used to identify subgroups of patients based on their pain trajectories, and logistic regression models to quantify associations between pain trajectories and demographic, clinical, psychological, and life style factors., Results: Two postoperative pain trajectory subgroups were identified: rapid pain relief (48% of included individuals) and consistently high pain (52% of included individuals). Sub-analysis stratified by cause of injury demonstrated that higher preoperative pain was an independent risk factor for consistently high postoperative pain regardless of the patient's injury type: traffic accident (OR = 1.48, 95% CI 1.23-1.79), machine/tool injury or conflict (OR = 1.58, 95% CI 1.11-2.26), or fall (OR = 1.47, 95% CI 1.08-1.99). Moreover, longer surgical time was a risk factor for consistently high postoperative pain among patients who had a fall-related injury (OR = 1.02, 95% CI 1.00-1.03). In contrast, among patients with a traffic-related injury, receiving a nerve block was a protective factor (OR = 0.19, 95% CI 0.04-0.87) compared with general anesthesia., Conclusion: Higher preoperative pain and longer surgical time were associated with a consistently high acute postoperative pain trajectory. Clinicians may use these potentially modifiable factors to identify patients at risk for consistently high pain during the early postoperative period., (© 2023. The Author(s).)

Objectives: To determine the outcome of tibial fractures treated with the SIGN FIN nail., Study Design: Retrospective case series study., Study Setting: Trauma center., Methods and Materials: We included 14 patients aged 18-51 years with 16 tibial fractures in this study. Patients were followed clinically and radiographically, and the minimum time followed was 6 months. Johner and Wruhs criteria with modification were used to assess the outcome., Result: There were 11 male (78.6%) and three female (21.4%) patients. The mean age was 32.44 ± 8.98 (range 18-51) years. The right-sided tibia was injured in six as compared with the left side in four, and four patients had bilateral injuries. Eight (50%) fractures were closed fractures, whereas the rest eight (50%) were open types of fractures. Among the latter, half (n = 4; 50%) fractures were Gustilo type II fractures, while three (37.5%) fractures were Gustilo type III fractures, and one (12.5%) patient had a Gustilo type I fracture. All patients had radiologic union. There were no infections or secondary surgery for any reason. Excellent, good, and fair results were achieved in 62.5%, 25%, and 12.5%, respectively. All patients were able to return to their preinjury activity except two patients., Conclusion: SIGN FIN nail is an option for treating tibial shaft fractures with good outcomes and few complications in selected fractures., Level of Evidence: Level IV., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Objective: This study aimed to assess the incidence and associated factors of acute postoperative pain after cesarean section within the first 24 h of postoperative period., Methods: An institutional-based prospective observational study was conducted on parturients who had undergone cesarean section in Gandhi Memorial Hospital from 1 December 2019 to 28 February 2020. A numerical rating scale was used to evaluate the incidence of acute postoperative pain. Patients having a pain score of >4 were considered having moderate-to-severe pain on numerical rating scale. Data were analyzed using SPSS version 20. Bivariable and multivariable logistic regression were used to assess the association of variables. A p value of less than 0.05 was taken as significant association with dependent variables., Result: In total, 290 parturients participated in the study with a response rate of 98%. Moderate-to-severe acute postoperative pain after cesarean section was 76.2% (95% confidence interval: 71%, 81%) in the first 24 h postoperatively. On multivariable analysis, previous cesarean section history (adjusted odds ratio: 2.80, 95% confidence interval: 1.40, 5.55; p  = 0.003), preoperative anxiety (adjusted odds ratio: 2.70, 95% confidence interval: 1.45, 5.05; p  = 0.003), transverse incision type (adjusted odds ratio: 3.35, 95% confidence interval: 1.67, 6.72; p  = 0.002), and incision length (adjusted odds ratio: 2.46, 95% confidence interval: 1.24, 4.85; p  = 0.009) were identified as risk factors for postoperative moderate-to-severe acute pain., Conclusion: The incidence of moderate-to-severe postoperative pain was high in the first 24-h postoperative period; this indicates that pain management after cesarean section was treated inadequately. History of previous cesarean section, preoperative anxiety, transverse incision, and incision length >10 cm were the factors of postoperative acute pain after cesarean section. Therefore, we suggest the study institution develop a protocol for pain management., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background & Aims: EDP-305 is an oral farnesoid X receptor (FXR) agonist under development for the treatment of non-alcoholic steatohepatitis (NASH). Herein, we aimed to assess the efficacy, safety and tolerability of EDP-305 in patients with fibrotic NASH., Methods: In this double-blind phase II study, patients with fibrotic NASH (without cirrhosis), diagnosed by historical biopsy or phenotypically, were randomized to EDP-305 1 mg, EDP-305 2.5 mg, or placebo, for 12 weeks. The primary endpoint was mean change in alanine aminotransferase (ALT) from baseline to Week 12, and the key secondary endpoint was mean change in liver fat content from baseline to Week 12., Results: Between January 2018 and July 2019, 134 patients were randomized and 132 were evaluated. At Week 12, the least squares mean reductions from baseline in ALT for patients receiving 2.5 mg EDP-305 and 1 mg EDP-305 were -27.9 U/L (95% CI 0.03 to 24.9; p = 0.049) and -21.7 U/L (-5.8 to 18.3: p = 0.304), respectively, compared to -15.4 U/L for those receiving placebo. Absolute liver fat reduction was -7.1% (2.0-7.5; p = 0.0009) with 2.5 mg EDP-305, -3.3% with EDP-305 1 mg, and -2.4% with placebo. The most common (≥5%) adverse events were pruritus, nausea, vomiting, diarrhea, headache, and dizziness. Pruritus occurred in 50.9%, 9.1%, and 4.2% of patients in the 2.5 mg, 1 mg, and placebo groups, respectively, and led to study drug discontinuation in 20.8% of patients in the 2.5 mg group and 1.8% in the 1 mg group., Conclusions: EDP-305 reduced ALT levels and liver fat content, providing support for a longer-term trial assessing histological endpoints in patients with NASH. CLINICALTRIALS., Gov Number: NCT03421431 LAY SUMMARY: Non-alcoholic fatty liver disease is a chronic hepatic disease that can progress to non-alcoholic steatohepatitis (NASH), which is associated with an increased risk of cirrhosis and liver cancer. Results from this phase II study support continued development of EDP-305, an oral farnesoid X receptor agonist, for the treatment of patients with NASH., Competing Interests: Conflict of interest KK received support from Enanta paid to his institution; grants or contracts from Intercept, Gilead, NGM, Madrigal, Pfizer, Enanta, Viking, Celgene, Terns, Corcept paid to his institution; speaker’s and teaching honoraria or consulting fees from Intercept, Gilead, and Inipharm; Stock or stock options from Inipharm. EL received research grants from 89Bio, Allergan Inc, Akero Therapeutics, Alnylam Pharmaceuticals, Astrazeneca, Axcella Health, Bristol-Myers Squibb, Boeringer Ingelheim, Celgene, Durect Corporation, Eli Lilly and Company, Enanta Pharmaceuticals, Enyo, Galmed Pharmaceuticals, Genfit, Gilead Sciences, Hanmi Pharmaceuticals, Intercept Pharmaceuticals, Laboratory for Advanced Medicine, Madrigal Pharmaceuticals, Merck, Metacrine, Novartis, Novo Nordisk, Poxel, Roche Pharmaceuticals, Terns Pharmaceuticals, Viking Therapeutics, Zydus. AS reports research grants from Enanta Pharmaceuticals, Genentech, Madrigal, Viking Therapeutics, NovoNordisk, Bristol-Myers Squibb, NorthSea Therapeutics, Galectin, NGM Therapeutics, Intercept, Hepion, Allergan, Ionis, and Boehringer Ingelheim, and stock options from Gilead. B N-T received grants or contracts from Allergan, BMS, Cirius, Enanta, Genfit, Gilead, HighTide, Intercept, Madrigal, NGM payed to Saint Louis University. Payments for DSMB or Advisory Board participation by Akero, Alimentiv, Allergan, Allysta, Alnylam, Amgen, Arrowhead, Axcella, Boehringer Ingelheim, BMS, Coherus, Cymabay, Durect, Enanta, Fortress, Genfit, Gilead, High Tide, HistoIndex, Innovo, Intercept, Ionis, LG Chem, Lipocine, Madrigal, Medimmune, Merck, Mirum, NGM, NovoNordisk, Novus Therapeutics, pH-Pharma, Sagimet, Target RWE, Theratechnologies, 89Bio. Stock or stock options in HepGene; Honoraria from American Diabetes Association, American Gastroenterological Associations, Canadian Association for the Study of the Liver, Clinical Care Options, Houston Methodist Hospital, NASH Summit, NASH-TAG. ME received support from Enanta Pharmaceuticals for this study; grants or contracts from AbbVie, Gilead, Genfit, Intercept, Assembly, Madrigal, and Novartis; consulting fees from AbbVie, Gilead, and Intercept; and honoraria from AbbVie. JD received support from Enanta Pharmaceuticals for this study. DD, TK, MR, and TD have nothing to disclose. BG, AA, and NA are employees and may be stockholders of Enanta Pharmaceuticals, Inc. VR has received consulting fees from Boehringer-Ingelheim, Novo-Nordisk, Galmed, Terns, Theratechnologies, Bristol-Myers-Squibb, Genfit, Madrigal, and NGM Bio. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Ethiopia endorsed the African regional measles elimination goal in 2012 and has been implementing measles elimination strategies. Administration of measles vaccine before the age of nine months decreases seroconversion. Ensuring administration of valid doses and monitoring vaccine effectiveness is crucial for achieving measles elimination. The objective of the study was to describe the magnitude of invalid measles dose administration and vaccine effectiveness in Ethiopia., Methods: we analysed the 2016 Ethiopian Demographic and Health Survey (EDHS) immunization coverage data for Ethiopia to determine the age at measles vaccine administration and proportion of measles age invalid doses administered. The national measles surveillance data for children with birthdates that match 12-23 months old children surveyed in the EDHS 2016, were analysed to determine the Proportion of Cases Vaccinated (PCV) with one dose of measles vaccine. We estimated the effectiveness of measles vaccine by using the proportion of measles cases vaccinated (PCV) from measles surveillance data and the measles vaccination coverage among children aged 12-23 months reported in the demographic health survey (DHS) done in 2016 (Percent of Population Vaccinated for measles, PPV). The screening method was used to estimate measles vaccine effectiveness at national level and for regions which reported more than 30 measles cases among children 9-23 months of age in the 2013-2015 period. The correlation between the median age of invalid doses administered, proportion of invalid doses and measles vaccine effectiveness was analysed., Results: at national level, the proportion of invalid measles dose administration was 27.6% for children aged 12-35 months surveyed in the 2016 DHS survey in Ethiopia. Among children reported in the measles case-based surveillance database with birthdates that match the children surveyed in the Ethiopian DHS 2016, the proportion of measles cases vaccinated with a single dose of measles vaccine in the 2013-2015 period was 22.7%. The vaccine effectiveness for single dose measles vaccination was estimated at 75.3%. The measles vaccine effectiveness was low for regions with high proportion of invalid dose administration and lower median age of invalid dose administration. The median age of measles dose administered before the age of nine months was significantly correlated with measles vaccine effectiveness (r=0.971, p=0.001) in the respective regions., Conclusion: the proportion of invalid measles dose administration is very high in Ethiopia and is associated with lower vaccine effectiveness. Further assessment should be carried out to understand the underlying root causes for invalid dose administration, focusing on areas with high proportion of invalid measles doses. The national program should devise strategies to promote timely vaccination as per the national schedule, and to revaccinate those vaccinated before 9 months of age. The ministry of health should also strengthen the platform for immunization in the 2 nd year life, to ensure high routine immunization coverage with two doses of measles vaccine to achieve the measles elimination goal in Ethiopia., Competing Interests: The authors declare no competing interests., (Copyright: Teklay Desta et al.)

The neocortex is disproportionately expanded in human compared with mouse 1,2 , both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth 3 . Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues. We demonstrate a strong correspondence between morphological, physiological and transcriptomic phenotypes of five human glutamatergic supragranular neuron types. These were enriched in but not restricted to layers, with one type varying continuously in all phenotypes across layers 2 and 3. The deep portion of layer 3 contained highly distinctive cell types, two of which express a neurofilament protein that labels long-range projection neurons in primates that are selectively depleted in Alzheimer's disease 4,5 . Together, these results demonstrate the explanatory power of transcriptomic cell-type classification, provide a structural underpinning for increased complexity of cortical function in humans, and implicate discrete transcriptomic neuron types as selectively vulnerable in disease., (© 2021. The Author(s).)

Bovine trypanosomosis remains an important livestock disease constraint, which is threatening livestock health and production, despite ongoing tsetse and trypanosomosis control efforts in Sadi Chanka district, Kellem Wollega zone, Oromia regional state, Ethiopia. A cross-sectional study was conducted in May 2018, to determine the prevalence of bovine trypanosomosis and distribution of the vectors of disease in Sadi Chanka district, Western Ethiopia. A total of 370 blood samples were collected from randomly selected local Horro and Abigar cattle breeds covering five villages of the district. The collected samples were examined using buffy coat microscopy and Giemsa-stained thin blood smear techniques. In this study, 12.4% (95% CI: 12.3-12.4) of the animals were found to be infected with trypanosomes. The study showed that 69.6% of trypanosome infections were caused by T. congolense followed by 26.1% T. vivax and 4.3% mixed T. congolense and T. vivax. In the present study, the association of bovine trypanosomosis was assessed in releation to body condition scores, sex, and age of cattle, and a significant association (P < 0.05) was observed between body condition scores. However, significant differences were not observed between sex and age categories (P > 0.05). The Mean Packed Cell Volume (PCV) of infected (21.6%) and non-infected (24.5%) groups of cattle had significant variation (P < 0.05). In an entomological survey, a total of 616 flies were trapped, of which 280 (45.5%) were Glossina and the remaining 336 (54.5%) were Stomoxys, Tabanus, and Haematopota. The apparent density of Glossina, Stomoxys, Tabanus, and Haematopota was 3.5, 3.1, 0.7 and 0.4 fly per trap per day, respectively. This study generated basic scientific data on the epidemiology of bovine trypanosomosis and its vectors in Sadi Chanka district, which can be used in planning the control of bovine trypanosomosis in the area., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Neurons are frequently classified into distinct types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 4,200 mouse visual cortical GABAergic interneurons and reconstructed the local morphologies of 517 of those neurons. We find that most transcriptomic types (t-types) occupy specific laminar positions within visual cortex, and, for most types, the cells mapping to a t-type exhibit consistent electrophysiological and morphological properties. These properties display both discrete and continuous variation among t-types. Through multimodal integrated analysis, we define 28 met-types that have congruent morphological, electrophysiological, and transcriptomic properties and robust mutual predictability. We identify layer-specific axon innervation pattern as a defining feature distinguishing different met-types. These met-types represent a unified definition of cortical GABAergic interneuron types, providing a systematic framework to capture existing knowledge and bridge future analyses across different modalities., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Back Ground: Tsetse-transmitted trypanosomosis much depends on the distribution and capacity of Glossina species responsible for transmission., Method: A cross-sectional study based on parasitological and entomological studies was conducted from October to June 2018 to determine the epidemiology, distribution, and magnitude of the vector, the disease and Analyze associated risk factors., Results: Based on implemented entomological study, Didessa river basin has a total apparent fly density of 5.33 Fly/Trap/Day (FTD); similarly, Glossina species accounted about 4.04 and 1.29 were other biting flies (Stomoxys and Tabanus). The composition of Glossina species identified in the study were 3335 (98.56%) Glossina tachinoides and 49 (1.44%) Glossina fuscipes. Comparatively higher and lower FTD found in altitude ranges from 1317 m above sea-level Bedele District (FTD = 5.19) and 1334 m above sea-level Boracha District (FTD = 1.88). Furthermore, from the total of n = 1517, local breeds of cattle examined for the infection of parasite and 82 cattle were found infected with an overall prevalence of 5.41%. The resulted overall prevalence was composed of Trypanosome congolense and Trypanosome vivax, 59 (3.89%) and 23 (1.52%), respectively. Among studied Districts; Goma, Limukosa, Limuseka, Bedele, Boracha, and Gechi prevalence of bovine trypanosomosis was 6.56%, 6.48%, 7.56%, 3.56%, 6.71%, and 1.60%, respectively. Based on parasitological study, statistically significant prevalence was demonstrated between Districts of Limuseka 7.56% and Gechi 1.60% with highest and lowest, respectively. During the early dry season, the prevalence of Trypanosome vivax 0.53% was significantly lower than that of late rainy season 0.99%; however, the higher number of Trypanosome congolense 2.44% resulted during the late rainy season. The study also demonstrated that trypanosomosis strongly causes anemia with mean pcv of infected cattle 20.93 ± 3.93 and non-infected cattle 26.74 ± 3.81 (Mean pcv ± SD) with 95% CI, Pr (T > t) = 0.0000. Moreover, trypanosomosis-related anemia was highly associated with T. congolense with mean pcv result of 18.80 ± 4.66 [mean pcv ± SD, Pr (T > t) = 0.0000] when compared with T. vivax 27.53 ± 4.47 (Mean pcv ± SD, Pr (T > t) = 0.6222)., Conclusion: Finally, the research demonstrated the new local demographic occurrence of G.f. fuscipes in the Didessa river basin which was not reported by other studies so far, therefore, the current finding invites further studies and investigations.

Uncertainty about the causes of neonatal deaths impedes achieving global health targets to reduce mortality. Complete diagnostic autopsy (CDA) is the gold standard to determine cause of death. However, it is often difficult to perform in high-burden, low-income settings. Validations of more feasible methods to determine cause of death are needed. This prospective, multi-center study in Ethiopia assessed the validity of the minimally invasive tissue sampling (MITS) approach to contribute to causes of death in preterm neonates compared to CDA. The MITS and CDA of 105 cases were reviewed. The MITS sampling success for lungs and liver was 100% and 84%, respectively. The kidney and brain had sampling successes of 58% each. MITS showed good agreement with CDA for the diagnosis of hyaline membrane disease (kappa = 0.78), and moderate to substantial agreement for pneumonia and pulmonary hemorrhage (kappa = 0.59 and 0.68, respectively). Even though CDA is the gold standard in identifying the cause of death, we believe that the MITS method can be a useful alternative method in supporting determination of cause of death in low-resource settings., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Neonatal deaths now account for 47% of all deaths in children younger than 5 years globally. More than a third of newborn deaths are due to preterm birth complications, which is the leading cause of death. Understanding the causes and factors contributing to neonatal deaths is needed to identify interventions that will reduce mortality. We aimed to establish the major causes of preterm mortality in preterm infants in the first 28 days of life in Ethiopia., Methods: We did a prospective, cross-sectional, observational study in five hospitals in Ethiopia. Study participants were preterm infants born in the study hospitals at younger than 37 gestational weeks. Infants whose gestational age could not be reliably estimated and those born as a result of induced abortion were excluded from the study. Data were collected on maternal and obstetric history, clinical maternal and neonatal conditions, and laboratory investigations. For neonates who died of those enrolled, consent was requested from parents for post-mortem examinations (both complete diagnostic autopsy and minimally invasive tissue sampling). An independent panel of experts established the primary and contributory causes of preterm mortality with available data., Findings: Between July 1, 2016, to May 31, 2018, 4919 preterm infants were enrolled in the study and 3852 were admitted to neonatal intensive care units. By 28 days of post-natal age, 1109 (29%) of those admitted to the neonatal intensive care unit died. Complete diagnostic autopsy was done in 441 (40%) and minimally invasive tissue sampling in 126 (11%) of the neonatal intensive care unit deaths. The main primary causes of death in the 1109 infants were established as respiratory distress syndrome (502 [45%]); sepsis, pneumonia and meningitis (combined as neonatal infections; 331 [30%]), and asphyxia (151 [14%]). Hypothermia was the most common contributory cause of preterm mortality (770 [69%]). The highest mortality occurred in infants younger than 28 weeks of gestation (89 [86%] of 104), followed by infants aged 28-31 weeks (512 [54%] of 952), 32-34 weeks (349 [18%] of 1975), and 35-36 weeks (159 [8%] of 1888)., Interpretation: Three conditions accounted for 89% of all deaths among preterm infants in Ethiopia. Scale-up interventions are needed to prevent or treat these conditions. Further research is required to develop effective and affordable interventions to prevent and treat the major causes of preterm death., Funding: Bill & Melinda Gates Foundation., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Understanding the diversity of cell types in the brain has been an enduring challenge and requires detailed characterization of individual neurons in multiple dimensions. To systematically profile morpho-electric properties of mammalian neurons, we established a single-cell characterization pipeline using standardized patch-clamp recordings in brain slices and biocytin-based neuronal reconstructions. We built a publicly accessible online database, the Allen Cell Types Database, to display these datasets. Intrinsic physiological properties were measured from 1,938 neurons from the adult laboratory mouse visual cortex, morphological properties were measured from 461 reconstructed neurons, and 452 neurons had both measurements available. Quantitative features were used to classify neurons into distinct types using unsupervised methods. We established a taxonomy of morphologically and electrophysiologically defined cell types for this region of the cortex, with 17 electrophysiological types, 38 morphological types and 46 morpho-electric types. There was good correspondence with previously defined transcriptomic cell types and subclasses using the same transgenic mouse lines.

Despite numerous international and national efforts, only 12 countries in the World Health Organization's African Region met the Millennium Development Goal #4 (MDG#4) to reduce under-five mortality by two-thirds by 2015. Given the variability across sub-Saharan Africa, a four-country study was undertaken to examine barriers and facilitators of child survival prior to 2015. Liberia and Zambia were chosen to represent countries making substantial progress towards MDG#4, while Kenya and Zimbabwe represented countries making less progress. Our individual case studies suggested that strong health governance and leadership (HGL) was a significant driver of the greater success in Liberia and Zambia compared with Kenya and Zimbabwe. To elucidate specific components of national HGL that may have substantially influenced the pace of reductions in child mortality, we conducted a cross-country analysis of national policies and strategies pertaining to maternal, neonatal and child health (MNCH) and qualitative interviews with individuals working in MNCH in each of the four study countries. The three aspects of HGL identified in this study which most consistently contributed to the different progress towards MDG#4 among the four study countries were (1) establishing child survival as a top national priority backed by a comprehensive policy and strategy framework and sufficient human, financial and material resources; (2) bringing together donors, strategic partners, health and non-health stakeholders and beneficiaries to collaborate in strategic planning, decision-making, resource-allocation and coordination of services; and (3) maintaining accountability through a 'monitor-review-act' approach to improve MNCH. Although child mortality in sub-Saharan Africa remains high, this comparative study suggests key health leadership and governance factors that can facilitate reduction of child mortality and may prove useful in tackling current Sustainable Development Goals., (© The Author(s) 2019. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Background and Aims: Remimazolam is an ultrashort-acting benzodiazepine., Methods: We performed a randomized double-blind comparison of remimazolam to placebo for outpatient colonoscopy. This study design was a requirement of the U.S. Food and Drug Administration. An additional group was randomized to open-label midazolam administered according to its package insert instructions (the randomization ratio for remimazolam:placebo:midazolam was 30:6:10). Study medications were administered under the supervision of the endoscopist, without any involvement of an anesthesia specialist. Patients were given 50 to 75 μg of fentanyl before receiving study medications. Patients who failed to achieve adequate sedation in any arm were rescued with midazolam dosed at the investigator's discretion. The primary endpoint was a composite that required 3 criteria be met: completion of the colonoscopy, no need for rescue medication, and ≤5 doses of remimazolam or placebo in any 15-minute interval (≤3 doses of midazolam in any 12-minute interval in the open-label midazolam arm)., Results: There were 461 randomized patients in 12 U.S. sites. The primary endpoint was met for remimazolam, placebo, and midazolam in 91.3%, 1.7%, and 25.2% of patients, respectively (P < .0001 for remimazolam vs placebo). Patients administered remimazolam received less fentanyl, had faster recovery of neuropsychiatric function, were ready for discharge earlier, and felt back to normal sooner than patients with both placebo and midazolam. Hypotension was less frequent with remimazolam, and hypoxia occurred in 1% of patients with remimazolam or midazolam. There were no treatment-emergent serious adverse events., Conclusion: Remimazolam can be administered safely under the supervision of endoscopists for outpatient colonoscopy, and it allows faster recovery of neuropsychiatric function compared with placebo (midazolam rescue) and midazolam. (Clinical trial registration number: NCT02290873.)., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the extent to which Integrated Management of Childhood Illness (IMCI) has been adopted and scaled up in countries., Setting: The 95 countries that participated in the survey are home to 82% of the global under-five population and account for 95% of the 5.9 million deaths that occurred among children less than 5 years of age in 2015; 93 of them are low-income and middle-income countries (LMICs)., Methods: We conducted a cross-sectional self-administered survey. Questionnaires and data analysis focused on (1) giving a general overview of current organisation and financing of IMCI at country level, (2) describing implementation of IMCI's three original components and (3) reporting on innovations, barriers and opportunities for expanding access to care for children. A single data file was created using all information collected. Analysis was performed using STATA V.11., Participants: In-country teams consisting of representatives of the ministry of health and country offices of WHO and Unicef., Results: Eighty-one per cent of countries reported that IMCI implementation encompassed all three components. Almost half (46%; 44 countries) reported implementation in 90% or more districts as well as all three components in place (full implementation). These full-implementer countries were 3.6 (95% CI 1.5 to 8.9) times more likely to achieve Millennium Development Goal 4 than other (not full implementer) countries. Despite these high reported implementation rates, the strategy is not reaching the children who need it most, as implementation is lowest in high mortality countries (39%; 7/18)., Conclusion: This survey provides a unique opportunity to better understand how implementation of IMCI has evolved in the 20 years since its inception. Results can be used to assist in formulating strategies, policies and activities to support improvements in the health and survival of children and to help achieve the health-related, post-2015 Sustainable Development Goals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Background: With nearly 15 million annual preterm births globally, preterm birth is the most common cause of neonatal death. Forty to 60 % of neonatal deaths are directly or indirectly associated with preterm mortality. As countries aim to meet the Sustainable Development Goals to reduce neonatal mortality, significant reductions in preterm mortality are needed. This study aims to identify the common causes of preterm illness and their contribution to preterm mortality in low-resource settings. This article will describe the methods used to undertake the study., Methods: This is a prospective, multi-centre, descriptive clinical study. Socio-demographic, obstetric, and maternal factors, and clinical and laboratory findings will be documented. The major causes of preterm mortality will be identified using clinical, laboratory, imaging, and autopsy methods and use the national Ethiopian guidelines on management of preterm infants including required investigations to reach final diagnoses. The study will document the clinical and management protocols followed in these settings. The approach consists of clinical examinations and monitoring, laboratory investigations, and determination of primary and contributory causes of mortality through both clinical means and by post-mortem examinations. An independent panel of experts will validate the primary and contributory causes of mortality. To obtain the estimated sample size of 5000 preterm births, the study will be undertaken in five hospitals in three regions of Ethiopia, which are geographically distributed across the country. All preterm infants who are either born or transferred to these hospitals will be eligible for the study. Three methods (last menstrual period, physical examination using the New Ballard Score, and ultrasound) will be used to determine gestational age. All clinical procedures will be conducted per hospital protocol and informed consent will be taken from parents or caretakers prior to their participation in the study as well as for autopsy if the infant dies., Discussion: This study will determine the major causes of death and illness among hospitalized preterm infants in a low-resource setting. The result will inform policy makers and implementers of areas that can be prioritized in order to contribute to a significant reduction in neonatal mortality.

Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor's molecular and cellular landscapes are complex, and their relationships to histologic features routinely used for diagnosis are unclear. We present the Ivy Glioblastoma Atlas, an anatomically based transcriptional atlas of human glioblastoma that aligns individual histologic features with genomic alterations and gene expression patterns, thus assigning molecular information to the most important morphologic hallmarks of the tumor. The atlas and its clinical and genomic database are freely accessible online data resources that will serve as a valuable platform for future investigations of glioblastoma pathogenesis, diagnosis, and treatment., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer's disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging.brain-map.org/). We confirm established associations between AD pathology and dementia, albeit with increased, presumably aging-related variability, and identify sets of co-expressed genes correlated with pathological tau and inflammation markers. Finally, we demonstrate a relationship between dementia and RNA quality, and find common gene signatures, highlighting the importance of properly controlling for RNA quality when studying dementia.

As of 2015, only 12 countries in the World Health Organization's AFRO region had met Millennium Development Goal #4 (MDG#4) to reduce under-five mortality by two-thirds by 2015. Given the variability across the African region, a four-country study was undertaken to examine barriers and facilitators of child survival prior to 2015. Kenya was one of the countries selected for an in-depth case study due to its insufficient progress in reducing under-five mortality, with only a 28% reduction between 1990 and 2013. This paper presents indicators, national documents, and qualitative data describing the factors that have both facilitated and hindered Kenya's efforts in reducing child mortality. Key barriers identified in the data were widespread socioeconomic and geographic inequities in access and utilization of maternal, neonatal, and child health (MNCH) care. To reduce these inequities, Kenya implemented three major policies/strategies during the study period: removal of user fees, the Kenya Essential Package for Health, and the Community Health Strategy. This paper uses qualitative data and a policy review to explore the early impacts of these efforts. The removal of user fees has been unevenly implemented as patients still face hidden expenses. The Kenya Essential Package for Health has enabled construction and/or expansion of healthcare facilities in many areas, but facilities struggle to provide Emergency Obstetric and Neonatal Care (EmONC), neonatal care, and many essential medicines and commodities. The Community Health Strategy appears to have had the most impact, improving referrals from the community and provision of immunizations, malaria prevention, and Prevention of Mother-to-Child Transmission of HIV. However, the Community Health Strategy is limited by resources and thus also unevenly implemented in many areas. Although insufficient progress was made pre-2015, with additional resources and further scale-up of new policies and strategies Kenya can make further progress in child survival.

Despite notable progress reducing global under-five mortality rates, insufficient progress in most sub-Saharan African nations has prevented the achievement of Millennium Development Goal four (MDG#4) to reduce under-five mortality by two-thirds between 1990 and 2015. Country-level assessments of factors underlying why some African countries have not been able to achieve MDG#4 have not been published. Zimbabwe was included in a four-country study examining barriers and facilitators of under-five survival between 2000 and 2013 due to its comparatively slow progress towards MDG#4. A review of national health policy and strategy documents and analysis of qualitative data identified Zimbabwe's critical shortage of health workers and diminished opportunities for professional training and education as an overarching challenge. Moreover, this insufficient health workforce severely limited the availability, quality, and utilization of life-saving health services for pregnant women and children during the study period. The impact of these challenges was most evident in Zimbabwe's persistently high neonatal mortality rate, and was likely compounded by policy gaps failing to authorize midwives to deliver life-saving interventions and to ensure health staff make home post-natal care visits soon after birth. Similarly, the lack of a national policy authorizing lower-level cadres of health workers to provide community-based treatment of pneumonia contributed to low coverage of this effective intervention and high child mortality. Zimbabwe has recently begun to address these challenges through comprehensive policies and strategies targeting improved recruitment and retention of experienced senior providers and by shifting responsibility of basic maternal, neonatal and child health services to lower-level cadres and community health workers that require less training, are geographically broadly distributed, and are more cost-effective, however the impact of these interventions could not be assessed within the scope and timeframe of the current study., (© The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey.

Background and Aims: This phase-2b study examined the safety and efficacy of an all-oral, interferon-free combination of the NS5A replication complex inhibitor daclatasvir (DCV), the NS3 protease inhibitor asunaprevir (ASV), and the nonnucleoside NS5B polymerase inhibitor beclabuvir (BCV) with or without ribavirin in patients with HCV genotype (GT) 1 infection., Methods: A total of 187 patients received 12 weeks of DCV 30 mg BID plus ASV 200 mg BID and BCV 150 mg BID (n = 86) or 75 mg BID with (n = 21) or without (n = 80) weight-based ribavirin BID. The primary endpoint was HCV RNA <25 IU/ml at post-treatment week 12 (SVR12)., Results: Overall, 90% of patients (169/187) in the combined treatment groups achieved SVR on or after post-treatment week 12. SVR rates were similar across subgroups (by mITT analysis), i.e. patients with cirrhosis (88%, 14/16), HCV GT-1a (90%, 137/155), and IL28B non-CC genotype (90%, 115/128). There were no drug-related serious AEs or grade 4 AEs. The most frequently reported AEs were headache, diarrhoea, fatigue and nausea. Addition of ribavirin to DCV+ASV+BCV was associated with decreased haemoglobin, compared with DCV+ASV+BCV alone. There were six grade 3/4 laboratory abnormalities noted, all unrelated to the study drugs. Viral breakthrough occurred in 2.5-4.8% of patients across groups and appeared unrelated to BCV dose or ribavirin inclusion., Conclusions: Results support phase 3 evaluation of a twice-daily, fixed-dose formulation of this DCV+ASV+BCV regimen with or without ribavirin in HCV GT-1-infected patients., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Every year, millions of babies are born and a large proportion of them are being admitted to hospital for various indications. This study was conducted to identify the general characteristics, disease spectrum and common causes of Neonatal morbidity and mortality at Gondar University Hospital, Neonatal Unit., Methods: Institution based prospective cross-sectional study was conducted at Gondar University Hospital (GUH), Neonatal Unit, from January 1(st) to March 31(st), 2014. The study included 325 newborns who were admitted to the unit during the study period. The neonates were followed up using structured checklist and neonatal parameters like Neonatal sex, place of delivery, address, length of stay, gestational age, diagnosis and discharge conditions were transcribed into an electronic database for all observations. The primary outcome measures were death and cause of death., Results: A total of 325 neonates were admitted during the study period. Of these, 75.1%, 23.1%, 1.2% and 0.6% were discharged improved, died, discharged with same condition and disappeared, respectively. Ten variables were found to have significant statistical associations with neonatal mortality after adjusting for demographic covariates: Prematurity (p < 0.001), Meningitis (p <0.001), Hemorrhagic Diseases (P <0.001), Hyaline Membrane Disease (P<0.001), Neonatal Sepsis (p <0.05), Meningitis (<0.05), Perinatal Asphyxia (p <0.05), Neonatal Seizure (p <0.05), Home delivery (p <0.05) and Meconium Aspiration (p <0.05)., Conclusion: Our study showed that the common causes of neonatal mortality are almost similar with the previous evidences (problems of prematurity, Asphyxia and Sepsis).

Objective: The World Health Organization (WHO) prospective surveys of acquired HIV drug resistance (HIVDR) evaluate HIVDR emerging after the first year of antiretroviral therapy (ART) and associated factors., Methods: Consecutive ART starters in 2009 were enrolled at 3 sentinel sites in Namibia. Genotyping was performed at start and after 12 months in patients with HIV viral load (VL) >1000 copies per mL. HIVDR outcomes were: HIVDR prevention (VL ≤1000 copies/mL), possible HIVDR (VL >1000 copies/mL without detectable HIVDR or loss to follow-up or ART stop), and HIVDR (VL >1000 copies/mL with detectable HIVDR). Adherence was assessed using medication possession ratio (MPR)., Results: Of 394 starters, at 12 months, 80% were on first-line ART, 1% died, 4% transferred out, 1% stopped ART, <1% switched to second-line, and 15% were lost to follow-up. Among patients on first-line, 77% had VL testing, and 94% achieved VL ≤1000 copies per mL. At baseline, 7% had HIVDR. After 12 months, among patients with VL testing, 5% had HIVDR. A majority of patients failing therapy had high-level resistance to nonnucleoside reverse transcriptase inhibitors but none to protease inhibitors. All sites achieved the WHO target of ≥70% HIVDR prevention. Factors associated with not achieving HIVDR prevention were: baseline resistance to nonnucleoside reverse transcriptase inhibitors [odds ratio (OR) 3.0, P = 0.023], WHO stage 3 or 4 at baseline (OR 2.0, P = 0.012), and MPR <75% (OR 4.9, P = 0.021)., Conclusions: Earlier ART initiation and removal of barriers to on-time drug pickups may help to prevent HIVDR. These data inform decisions at national and global levels on the effectiveness of first- and second-line regimens.

The neocortex contains diverse populations of excitatory neurons segregated by layer and further definable by their specific cortical and subcortical projection targets. The current study describes a systematic approach to identify molecular correlates of specific projection neuron classes in mouse primary somatosensory cortex (S1), using a combination of in situ hybridization (ISH) data mining, marker gene colocalization, and combined retrograde labeling with ISH for layer-specific marker genes. First, we identified a large set of genes with specificity for each cortical layer, and that display heterogeneous patterns within those layers. Using these genes as markers, we find extensive evidence for the covariation of gene expression and projection target specificity in layer 2/3, 5, and 6, with individual genes labeling neurons projecting to specific subsets of target structures. The combination of gene expression and target specificity imply a great diversity of projection neuron classes that is similar to or greater than that of GABAergic interneurons. The covariance of these 2 phenotypic modalities suggests that these classes are both discrete and genetically specified., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)