Cardiac Tuberculosis: A Case Series from Ethiopia, Italy, and Uganda and a Literature Review.

Extrapulmonary tuberculosis (TB) is estimated to account for up to 20% of active cases of TB disease, but its prevalence is difficult to ascertain because of the difficulty of diagnosis. Involvement of the heart is uncommon, with constrictive pericarditis being the most common cardiac manifestation. Diagnostic research for cardiac disease is frequently lacking, resulting in a high mortality rate. In addition to direct cardiac involvement, instances of cardiac events during antitubercular therapy are described. This case series describes five cases of TB affecting the heart (cardiac TB) from Italy and high-burden, low-income countries (Ethiopia and Uganda), including a case of Loeffler syndrome manifesting as myocarditis in a patient receiving antitubercular therapy. Our study emphasizes how cardiac TB, rare but important in high-burden areas, is a leading cause of pericardial effusion or pericarditis. Timely diagnosis and a comprehensive approach, including imaging and microbiological tools, are crucial. Implementing high-sensitivity methods and investigating alternative samples, such as detection of tuberculosis lipoarabinomannan or use of the GeneXpert assay with stool, is recommended in TB control programs.

Protocol for an evaluation of the initiation of an integrated longitudinal outpatient care model for severe chronic non-communicable diseases (PEN-Plus) at secondary care facilities (district hospitals) in 10 lower-income countries.

INTRODUCTION: The Package of Essential Noncommunicable Disease Interventions-Plus (PEN-Plus) is a strategy decentralising care for severe non-communicable diseases (NCDs) including type 1 diabetes, rheumatic heart disease and sickle cell disease, to increase access to care. In the PEN-Plus model, mid-level clinicians in intermediary facilities in low and lower middle income countries are trained to provide integrated care for conditions where services traditionally were only available at tertiary referral facilities. For the upcoming phase of activities, 18 first-level hospitals in 9 countries and 1 state in India were selected for PEN-Plus expansion and will treat a variety of severe NCDs. Over 3 years, the countries and state are expected to: (1) establish PEN-Plus clinics in one or two district hospitals, (2) support these clinics to mature into training sites in preparation for national or state-level scale-up, and (3) work with the national or state-level stakeholders to describe, measure and advocate for PEN-Plus to support development of a national operational plan for scale-up. METHODS AND ANALYSIS: Guided by Proctor outcomes for implementation research, we are conducting a mixed-method evaluation consisting of 10 components to understand outcomes in clinical implementation, training and policy development. Data will be collected through a mix of quantitative surveys, routine reporting, routine clinical data and qualitative interviews. ETHICS AND DISSEMINATION: This protocol has been considered exempt or covered by central and local institutional review boards. Findings will be disseminated throughout the project's course, including through quarterly M&E discussions, semiannual formative assessments, dashboard mapping of progress, quarterly newsletters, regular feedback loops with national stakeholders and publication in peer-reviewed journals.

Causes of maternal deaths in Sierra Leone from 2016 to 2019: analysis of districts' maternal death surveillance and response data.

INTRODUCTION: Sierra Leone is among the top countries with the highest maternal mortality rates. Although progress has been made in reducing maternal mortality, challenges remain, including limited access to skilled care and regional disparities in accessing quality care. This paper presents the first comprehensive analysis of the burden of different causes of maternal deaths reported in the Maternal Death Surveillance and Response (MDSR) system at the district level from 2016 to 2019. METHODS: The MDSR data are accessed from the Ministry of Health and Sanitation, and the secondary data analysis was done to determine the causes of maternal death in Sierra Leone. The proportions of each leading cause of maternal deaths were estimated by districts. A subgroup analysis of the selected causes of death was also performed. RESULTS: Overall, obstetric haemorrhage was the leading cause of maternal death (39.4%), followed by hypertensive disorders (15.8%) and pregnancy-related infections (10.1%). Within obstetric haemorrhage, postpartum haemorrhage was the leading cause in each district. The burden of death due to obstetric haemorrhage slightly increased over the study period, while hypertensive disorders showed a slightly decreasing trend. Disparities were found among districts for all causes of maternal death, but no clear geographical pattern emerged. Non-obstetric complications were reported in 11.5% of cases. CONCLUSION: The MDSR database provides an opportunity for shared learning and can be used to improve the quality of maternal health services. To improve the accuracy and availability of data, under-reporting must be addressed, and frontline community staff must be trained to accurately capture and report death events.

Active close contact investigation of tuberculosis through computer-aided detection and stool Xpert MTB/RIF among people living in Oromia Region, Ethiopia (CADOOL Study): protocol for a prospective, cross-sectional study.

INTRODUCTION: Pulmonary tuberculosis (TB) is an infectious disease with high incidence in low-income countries (LICs); it remains one of the infectious diseases with the highest mortality in the world, especially in LICs. It is crucial to recognise and diagnose TB as soon as possible, but microbiological tests on sputum are not always sensitive enough. New methods for an early diagnosis of TB are needed. In this study, we will investigate the role of two different tests to detect TB in Ethiopia (where the prevalence of TB is high): molecular search for TB in stool samples with Xpert assay and detection of pulmonary TB signs on chest X-rays with CAD4TB technology. METHODS AND ANALYSIS: A prospective diagnostic test accuracy study during TB active contact investigation will be conducted. In the referral hospital in Southwest Shoa Zone, Oromia Region, Ethiopia, patients with pulmonary TB and a sputum sample positive for Mycobacterium tuberculosis and household contacts of at least 4 years of age will be enrolled, with a target sample size of 231 patients. Trained staff will label household contacts as 'possible TB' cases or not according to their symptoms; when TB is possible, a stool Xpert and computer-aided detection on chest X-ray will be performed, alongside standard diagnostic methods, assessing the diagnostic accuracy of CAD4TB compared with Xpert MTB/RIF during TB contact investigation and the accuracy of stool Xpert compared with sputum Xpert. ETHICS AND DISSEMINATION: This study has been approved by the Oromia Health Bureau Research Ethics Committee (ref no BFO/MBTFH/1-16/100023). All information obtained will be kept confidential. Selected investigators will have access to data, while international partners will sign a dedicated data protection agreement. Eligible participants will receive brief information about the study before being asked to participate and they will provide written informed consent. Results will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05818059.

Adherence to WHO guidelines on severe pneumonia management in children and its impact on outcome: an observational study at Jinka General Hospital in Ethiopia.

Introduction: Poor adherence to guidelines during empirical antibiotic prescription in low-income countries could increase antimicrobial resistance without improving outcomes. Revised World Health Organization (WHO) guidelines published in 2014 on childhood (2-59 months) pneumonia re-defined the classification of severe pneumonia and changed the first-line treatment. The adherence to WHO guidelines in southern Ethiopia at the hospital level is unknown. We sought to determine the adherence to WHO guidelines on severe pneumonia first-line treatment in children in an Ethiopian referral hospital and assess the impact of non-adherence on patient outcomes. Methods: An observational study was conducted on all children (2-59 months) clinically diagnosed with severe pneumonia and admitted to the Pediatric Ward of Jinka Hospital from 1 June 2021 to 31 May 2022. Exclusion criteria included a known HIV infection, ongoing antibiotic treatment before the event not related to acute pneumonia, or any other severe bacterial infection, confirmed or suspected. Adherence to guidelines was defined as first-line treatment with ampicillin or benzylpenicillin and gentamicin at the recommended dose. We compared the patients treated adherently vs. non-adherently. For categorical variables, the chi-square or Fisher's exact test was used, while for continuous variables, the Mann-Whitney U-test was used. Multivariate logistic regression was used to evaluate the association between adherence and demographic and clinical characteristics. Results: During the observational period, 266 patients were registered as having severe pneumonia with an age between 2 and 59 months. After excluding 114 patients due to missing charts or other exclusion criteria, a total of 152 patients were included in the analysis. Of these, 78 (51%) were girls with a median age of 10 months (IQR 7-14). Overall, 75 (49%) patients received therapy according to the WHO guidelines. Compared to patients treated adherently to the guidelines, patients not treated adherently had similar outcomes [median length of stay of 3 (IQR 3-5) and 4 (IQR 3-6) days], median duration of oxygen therapy of 2 (IQR 1-3) for both the groups, and self-discharge rates of 5% and 6.5%, respectively). Conclusion: Adherence to the revised WHO guideline was limited and not associated with outcomes. Efforts should focus on reducing the gap between theory and practice.

Stool Xpert MTB/RIF as a possible diagnostic alternative to sputum in Africa: a systematic review and meta-analysis.

Introduction: Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries. Methods: Four investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool. Results: overall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1-74.7%) even if characterized by a high heterogeneity (I2=53.7%). Specificity was almost 100% (99%, 95%CI: 97-100%; I2 = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis. Conclusions: Our study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples.

Priority age targets for COVID-19 vaccination in Ethiopia under limited vaccine supply.

The worldwide inequitable access to vaccination claims for a re-assessment of policies that could minimize the COVID-19 burden in low-income countries. Nine months after the launch of the national vaccination program in March 2021, only 3.4% of the Ethiopian population received two doses of COVID-19 vaccine. We used a SARS-CoV-2 transmission model to estimate the level of immunity accrued before the launch of vaccination in the Southwest Shewa Zone (SWSZ) and to evaluate the impact of alternative age priority vaccination targets in a context of limited vaccine supply. The model was informed with available epidemiological evidence and detailed contact data collected across different geographical settings (urban, rural, or remote). We found that, during the first year of the pandemic, the mean proportion of critical cases occurred in SWSZ attributable to infectors under 30 years of age would range between 24.9 and 48.0%, depending on the geographical setting. During the Delta wave, the contribution of this age group in causing critical cases was estimated to increase on average to 66.7-70.6%. Our findings suggest that, when considering the vaccine product available at the time (ChAdOx1 nCoV-19; 65% efficacy against infection after 2 doses), prioritizing the elderly for vaccination remained the best strategy to minimize the disease burden caused by Delta, irrespectively of the number of available doses. Vaccination of all individuals aged ≥ 50 years would have averted 40 (95%PI: 18-60), 90 (95%PI: 61-111), and 62 (95%PI: 21-108) critical cases per 100,000 residents in urban, rural, and remote areas, respectively. Vaccination of all individuals aged ≥ 30 years would have averted an average of 86-152 critical cases per 100,000 individuals, depending on the setting considered. Despite infections among children and young adults likely caused 70% of critical cases during the Delta wave in SWSZ, most vulnerable ages should remain a key priority target for vaccination against COVID-19.

Directed self-assembly of a xenogeneic vascularized endocrine pancreas for type 1 diabetes.

Intrahepatic islet transplantation is the standard cell therapy for ß cell replacement. However, the shortage of organ donors and an unsatisfactory engraftment limit its application to a selected patients with type 1 diabetes. There is an urgent need to identify alternative strategies based on an unlimited source of insulin producing cells and innovative scaffolds to foster cell interaction and integration to orchestrate physiological endocrine function. We previously proposed the use of decellularized lung as a scaffold for ß cell replacement with the final goal of engineering a vascularized endocrine organ. Here, we prototyped this technology with the integration of neonatal porcine islet and healthy subject-derived blood outgrowth endothelial cells to engineer a xenogeneic vascularized endocrine pancreas. We validated ex vivo cell integration and function, its engraftment and performance in a preclinical model of diabetes. Results showed that this technology not only is able to foster neonatal pig islet maturation in vitro, but also to perform in vivo immediately upon transplantation and for over 18 weeks, compared to normal performance within 8 weeks in various state of the art preclinical models. Given the recent progress in donor pig genetic engineering, this technology may enable the assembly of immune-protected functional endocrine organs.

Epidemiological factors affecting outpatient department service utilization and hospitalization in patients with diabetes: A time-series analysis from an Ethiopian hospital between 2018 and 2021.

Background: The burden of diabetes-related deaths reached two million in 2019 globally. Accessibility to health care services and adherence to follow-up and therapy are key to improving outcomes for diabetic patients. We aimed to assess outpatient department (OPD) service utilization and diabetes-related hospitalizations over a period of 44 months. Methods: A retrospective cohort study was conducted on OPD visits and hospitalizations recorded between January 1, 2018, and August 31, 2021, at the St Luke Catholic Hospital (Ethiopia). All diabetic patients were included in the analysis. A linear regression model was used for univariate analysis of OPD visits and hospitalizations and their association with potential predictors. The autoregressive integrated moving average (ARIMA) method was applied to both the time series of OPD visits and hospitalizations. Potential predictors were sociodemographic factors, COVID-19 cases, mean monthly temperature and precipitations. Results: In the time series analysis, OPD visits increased over time (P < 0.01) while hospitalizations were stable. The time series model was ARIMA (0,1,1) for OPD visits and ARIMA (0,0,0) for hospitalizations. There were 1685 diabetes OPD patients (F = 732, 43%). Females had an average of 16% fewer OPD accesses per month (P < 0.01) and a lower number of hospitalizations per month (P = 0.03). There were 801 patients missing follow-up (48%). The time between follow-up increased with age (P < 0.01). OPD visits decreased differently by geographic area as COVID-19 cases increased (P < 0.01). There were 57 fewer forecast OPD visits per month on average using COVID-19 cases as ARIMA regressor. The odds ratio (OR) of new diagnosis at hospitalization was lower in patients with type 2 diabetes (OR = 0.26, 95% CI = 0.14-0.49, P = 0.02). Conclusions: Despite an increase in OPD visits for diabetic patients over the study period, the number of losses at follow-up and diagnoses at hospitalization remains high. Female sex, older age, and COVID-19 were associated with impaired OPD service accessibility. Primary health care should be implemented to achieve better health coverage and improve diabetes management.

Treating iPSC-Derived ß Cells with an Anti-CD30 Antibody-Drug Conjugate Eliminates the Risk of Teratoma Development upon Transplantation.

Insulin-producing cells derived from induced pluripotent stem cells (iPSCs) are promising candidates for ß cell replacement in type 1 diabetes. However, the risk of teratoma formation due to residual undifferentiated iPSCs contaminating the differentiated cells is still a critical concern for clinical application. Here, we hypothesized that pretreatment of iPSC-derived insulin-producing cells with an anti-CD30 antibody−drug conjugate could prevent in vivo teratoma formation by selectively killing residual undifferentiated cells. CD30 is expressed in all human iPSCs clones tested by flow cytometry (n = 7) but not in iPSC-derived ß cells (ißs). Concordantly, anti-CD30 treatment in vitro for 24 h induced a dose-dependent cell death (up to 90%) in human iPSCs while it did not kill ißs nor had an impact on iß identity and function, including capacity to secrete insulin in response to stimuli. In a model of teratoma assay associated with iß transplantation, the pretreatment of cells with anti-CD30 for 24 h before the implantation into NOD-SCID mice completely eliminated teratoma development (0/10 vs. 8/8, p < 0.01). These findings suggest that short-term in vitro treatment with clinical-grade anti-CD30, targeting residual undifferentiated cells, eliminates the tumorigenicity of iPSC-derived ß cells, potentially providing enhanced safety for iPSC-based ß cell replacement therapy in clinical scenarios.

Engineering of immune checkpoints B7-H3 and CD155 enhances immune compatibility of MHC-I-/- iPSCs for ß cell replacement.

Induced pluripotent stem cells (iPSCs) represent a source from which ß cells can be derived for diabetes replacement therapy. However, their application may be hindered by immune-mediated responses. Although abrogation of major histocompatibility complex class I (MHC-I) can address this issue, it may trigger natural killer (NK) cells through missing-self recognition mechanisms. By profiling the relevant NK-activating ligands on iPSCs during in vitro differentiation into pancreatic ß cells, we find that they express high levels of B7-H3 and CD155. Hypothesizing that such surface ligands could be involved in the amplification of NK-activating signals following missing-self, we generate MHC-I-deprived B7-H3-/-, CD155-/-, and B7-H3-/-/CD155-/- iPSCs. All engineered lines correctly differentiate into insulin-secreting ß cells and are protected from cell lysis mediated by CD16dim and CD16+ NK subpopulations both in vitro and in vivo in NSG mice. Our data support targeted disruption of NK-activating ligands to enhance the transplant compatibility of MHC-I-/- iPSC pancreatic derivatives.

Training on the Silverman and Andersen score improved how special care unit nurses assessed neonatal respiratory distress in a low-resource setting.

AIM: Identifying the severity of neonatal respiratory distress (RD) is essential, so that resources can be appropriately allocated. We assessed the ability of nurses to grade neonatal RD in a low-resource setting before and after they were trained to use a dedicated scoring tool. METHODS: The study was conducted in the Special Care Unit of St Luke Wolisso Hospital, Ethiopia. Ten nurses reviewed nine local video recordings and graded neonatal RD without a standardised method, which was current practice, and then after they were trained to use the Silverman and Andersen score. The data were analysed using the McNemar test and Cohen's kappa. RESULTS: Training increased the identification of mild RD from 63% to 93% (p = 0.008) and moderate RD from 40% to 73% (p = 0.03). Severe RD was 93% before and 90% after training (p = 0.99). Overall, the agreement improved from kappa 0.59 to 0.84, mainly by reducing the overestimation of milder degrees of RD. CONCLUSION: Being trained on how to use the Silverman and Andersen score improved the ability of nurses to identify mild and moderate neonatal RD. This improvement has the potential to optimise the use of equipment, staff and time.

An integrated hospital-district performance evaluation for communicable diseases in low-and middle-income countries: Evidence from a pilot in three sub-Saharan countries.

INTRODUCTION: The last two decades saw an extensive effort to design, develop and implement integrated and multidimensional healthcare evaluation systems in high-income countries. However, in low- and middle-income countries, few experiences of such systems implementation have been reported in the scientific literature. We developed and piloted an innovative evaluation tool to assess the performance of health services provision for communicable diseases in three sub-Saharan African countries. MATERIAL AND METHODS: A total of 42 indicators, 14 per each communicable disease care pathway, were developed. A sub-set of 23 indicators was included in the evaluation process. The communicable diseases care pathways were developed for Tuberculosis, Gastroenteritis, and HIV/AIDS, including indicators grouped in four care phases: prevention (or screening), diagnosis, treatment, and outcome. All indicators were calculated for the period 2017-2019, while performance evaluation was performed for the year 2019. The analysis involved four health districts and their relative hospitals in Ethiopia, Tanzania, and Uganda. RESULTS: Substantial variability was observed over time and across the four different districts. In the Tuberculosis pathway, the majority of indicators scored below the standards and below-average performance was mainly reported for prevention and diagnosis phases. Along the Gastroenteritis pathway, excellent performance was instead evaluated for most indicators and the highest scores were reported in prevention and treatment phases. The HIV/AIDS pathway indicators related to screening and outcome phases were below the average score, while good or excellent performance was registered within the treatment phase. CONCLUSIONS: The bottom-up approach and stakeholders' engagement increased local ownership of the process and the likelihood that findings will inform health services performance and quality of care. Despite the intrinsic limitations of data sources, this framework may contribute to promoting good governance, performance evaluation, outcomes measurement and accountability in settings characterised by multiple healthcare service providers.

Evaluating Healthcare Performance in Low- and Middle-Income Countries: A Pilot Study on Selected Settings in Ethiopia, Tanzania, and Uganda.

The literature reports some experiences regarding the design of integrated healthcare Performance Evaluation Systems (PES) applied in Low- and Middle-income Countries (LMIC). This study describes the design of an integrated and bottom-up PES aimed at evaluating healthcare services delivery in rural settings. The analysis involved four hospitals and their relative health districts in Ethiopia, Tanzania, and Uganda. The evaluation process was undertaken for those indicators that could be evaluated using the same reference standard. The evaluation scores were determined through the international standards identified in the literature or through benchmarking assessment. Both administrative and health data were extracted from the hospitals' registers and District Health Information Systems (DHIS) from 2017 to 2020. We defined 128 indicators: 88 were calculated at the hospital level and 40 at the health district level. The evaluation process was undertaken for 48 indicators. The evaluated indicators are represented using effective graphical tools. In settings characterised by multiple healthcare providers, this framework may contribute to achieving good governance through performance evaluation, benchmarking, and accountability. It may promote evidence-based decision-making in the planning and allocation of resources, thus ultimately fostering quality improvement processes and practices, both at the hospital and health district level.

COVID-19 in Solid Organ Transplant Recipient: Exploring Cumulative Incidence, Seroprevalence and Risk Factors for Disease Severity.

BACKGROUND: Solid organ transplant (SOT) recipients may be at increased risk for severe disease and mortality from COVID-19 because of immunosuppression and prolonged end-stage organ disease. As a transplant center serving a diverse patient population, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in our cohort of SOT recipients. METHODS: We prospectively included in this observational study SOT recipients with a functioning kidney (n = 201), pancreas ± kidney (n = 66) or islet transplant (n = 24), attending outpatient regular follow-up at the San Raffaele Hospital from February 2020 to April 2021. Antibodies to SARS-CoV-2 were tested in all patients by a luciferase immunoprecipitation system assay. RESULTS: Of the 291 SOT recipients, 30 (10.3%) tested positive for SARS-CoV-2 during the study period and prevalence was not different among different transplants. The SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR. As for the WHO COVID-19 severity classification, 19 (63.3%) SOT recipients were mild, nine (30%) were moderate, and two were critical and died yielding a crude mortality rate in our patient population of 6.7%. Kidney transplant (OR 12.9 (1.1-150) p = 0.041) was associated with an increased risk for moderate/critical disease, while statin therapy (OR 0.116 (0.015-0.926) p = 0.042) and pancreas/islet transplant (OR 0.077 (0.007-0.906) p = 0.041) were protective. CONCLUSIONS: The incidence of SARS-CoV-2 infection in SOT recipients may be higher than previously described. Due to the relative high crude mortality, symptomatic SOT recipients must be considered at high risk in case of SARS-CoV-2 infection.

Parents' Experience and Satisfaction in Neonatal Intensive Care Units in Ethiopia: A Multicenter Cross-Sectional Study Using an Adapted Version of EMPATHIC-N.

Background: In neonatal intensive care units (NICU) setting, parents' experience and satisfaction permit to evaluate clinical practice and improve the care of infants and parents. Little is known about this topic in low resource settings. The aim of this study was to (1) translate, adapt and validate the EMpowerment of PArents in THe Intensive Care-Neonatology (EMPHATIC-N) questionnaire in two languages in Ethiopia (2) explore parents' satisfaction with the care received in the NICUs in three hospitals; and, (3) explore socio-demographic characteristics and level of the NICU influence on the EMPATHIC-N domains. Methods: This was a cross-sectional multicenter study. Participants were recruited from three different NICUs in Ethiopia upon discharge. We reduced the original EMPATHIC-N instrument to 38 items, culturally adapted and validated it in two local languages. Confirmatory Factor Analysis (CFA) was applied to verify the factor structure of the questionnaire, investigating the relationship between items and the five latent domains. Single item scores and the aggregate scores of the domains were investigated across NICUs and in the sample overall. Differences in the distribution of the domain scores were tested according to socio-demographic participants' characteristics. The scores of four general questions about overall experience and satisfaction were investigated in relation to the participant's characteristics and NICU levels. Qualitative data were collected using four open-ended questions and a synthesis of results was provided. Results: Almost all the parents answered to the questionnaire (92%, n = 386). Questionnaire items on satisfaction on average scored more than four. The highest mean scores were obtained for Parental participation (median: 5.17; iqr: 4.67-5.62), while they were lower for Organization/Hospital environment (median: 4.67; iqr:4.33-5.17). Different levels of parent satisfaction were observed across the NICU levels showing a statistically higher satisfaction in level II NICU compared to the other levels. Education, place of residence and length of stay were associated with parental satisfaction and experience. Conclusion: This study validated two Ethiopian versions of the EMPATHIC-N questionnaire to assess parents' experience and satisfaction during their child's stay in the NICU. The differences found across the three levels of NICU suggest the need to further investigate the determinants of satisfaction.

The effectiveness of maternity waiting homes in reducing perinatal mortality: a case-control study in Ethiopia.

BACKGROUND: The 2030 Agenda for Sustainable Development aims to reduce neonatal mortality to at least 12 per 1000 live births. Most of the causes can be prevented or cured. Access to quality healthcare during pregnancy and labour is the key to reduce perinatal deaths, and maternity waiting homes (MWHs) may have an impact, especially for women who live far from the healthcare system. We conducted a case-control study to evaluate the effectiveness of MWH in reducing perinatal mortality in a secondary hospital in Ethiopia. METHODS: We did a nested case-control study from January 2014 through December 2017. The enrolled cases were mothers whose childbirth resulted in stillbirth or early neonatal death. The controls were mothers with an alive baby at 7 days or with an alive baby on discharge. We collected demographic, anamnestic, pregnancy-related and obstetric-related data. The effectiveness of the MWH on perinatal death was assessed by a logistic regression model, adjusted for all other variables investigated as potential confounders. We also did a sensitivity analysis to explore the role of twin pregnancies. RESULTS: We included 1175 cases and 2350 controls. The crude analysis showed a protective effect of the MWH towards perinatal mortality (OR=0.700; 95% CI: 0.505 to 0.972), even more protective after adjustment for confounders (adjusted OR (AOR)=0.452; 95% CI: 0.293 to 0.698). Sensitivity analyses showed a consistent result, even excluding twin pregnancies (AOR=0.550; 95% CI: 0.330 to 0.917). CONCLUSION: MWHs appear to reduce perinatal mortality by 55%. Our findings support the decision to invest in MWH to support pregnant women with higher quality and more comprehensive healthcare strategy, including quality antenatal care in peripheral primary care clinics, where risk factors can be recognised and women can be addressed for admission to MWH.

Modeling the interplay between demography, social contact patterns, and SARS-CoV-2 transmission in the South West Shewa Zone of Oromia Region, Ethiopia.

BACKGROUND: COVID-19 spread may have a dramatic impact in countries with vulnerable economies and limited availability of, and access to, healthcare resources and infrastructures. However, in sub-Saharan Africa, a low prevalence and mortality have been observed so far. METHODS: We collected data on individuals' social contacts in the South West Shewa Zone (SWSZ) of Ethiopia across geographical contexts characterized by heterogeneous population density, work and travel opportunities, and access to primary care. We assessed how socio-demographic factors and observed mixing patterns can influence the COVID-19 disease burden, by simulating SARS-CoV-2 transmission in remote settlements, rural villages, and urban neighborhoods, under school closure mandate. RESULTS: From national surveillance data, we estimated a net reproduction number of 1.62 (95% CI 1.55-1.70). We found that, at the end of an epidemic mitigated by school closure alone, 10-15% of the population residing in the SWSZ would have been symptomatic and 0.3-0.4% of the population would require mechanical ventilation and/or possibly result in a fatal outcome. Higher infection attack rates are expected in more urbanized areas, but the highest incidence of critical disease is expected in remote subsistence farming settlements. School closure contributed to reduce the reproduction number by 49% and the attack rate of infections by 28-34%. CONCLUSIONS: Our results suggest that the relatively low burden of COVID-19 in Ethiopia observed so far may depend on social mixing patterns, underlying demography, and the enacted school closures. Our findings highlight that socio-demographic factors can also determine marked heterogeneities across different geographical contexts within the same region, and they contribute to understand why sub-Saharan Africa is experiencing a relatively lower attack rate of severe cases compared to high-income countries.

Generation of ß Cells from iPSC of a MODY8 Patient with a Novel Mutation in the Carboxyl Ester Lipase (CEL) Gene.

CONTEXT: Maturity-onset diabetes of the young (MODY) 8 is a rare form of monogenic diabetes characterized by a mutation in CEL (carboxyl ester lipase) gene, which leads to exocrine pancreas dysfunction, followed by ß cell failure. Induced pluripotent stem cells can differentiate into functional ß cells. Thus, ß cells from MODY8 patients can be generated in vitro and used for disease modelling and cell replacement therapy. METHODS: A genetic study was performed in a patient suspected of monogenic diabetes. RESULTS: A novel heterozygous pathogenic variant in CEL (c.1818delC) was identified in the proband, allowing diagnosis of MODY8. Three MODY8-iPSC (induced pluripotent stem cell) clones were reprogrammed from skin fibroblasts of the patient, and their pluripotency and genomic stability confirmed. All 3 MODY8-iPSC differentiated into ß cells following developmental stages. MODY8-iPSC-derived ß cells were able to secrete insulin upon glucose dynamic perifusion. The CEL gene was not expressed in iPSCs nor during any steps of endocrine differentiation. CONCLUSION: iPSC lines from a MODY8 patient with a novel pathogenic variant in the CEL gene were generated; they are capable of differentiation into endocrine cells, and ß cell function is preserved in mutated cells. These results set the basis for in vitro modelling of the disease and potentially for autologous ß cell replacement.

Effectiveness of screening and treatment of children with severe acute malnutrition by community health workers in Simiyu region, Tanzania: a quasi-experimental pilot study.

Health system constraints hamper treatment of children with severe acute malnutrition (SAM) in Tanzania. This non-inferiority quasi-experimental study in Bariadi (intervention) and Maswa (control) districts assessed the effectiveness, coverage, and cost-effectiveness of SAM treatment by community health workers (CHWs) compared with outpatient therapeutic care (OTC). We included 154 and 210 children aged 6-59 months with SAM [mid-upper arm circumference (MUAC) < 11.5 cm] without medical complications in the control and intervention districts, respectively. The primary treatment outcome was cure (MUAC ≥ 12.5 cm). We performed costing analysis from the provider's perspective. The probability of cure was higher in the intervention group (90.5%) than in the control group (75.3%); risk ratio (RR) 1.17; 95% CI 1.05, 1.31 and risk difference (RD) 0.13; 95% CI 0.04, 0.23. SAM treatment coverage was higher in the intervention area (80.9%) than in the control area (41.7%). The cost per child treated was US$146.50 in the intervention group and US$161.62 in the control group and that per child cured was US$161.77 and US$215.49 in the intervention and control groups, respectively. The additional costs per an additional child treated and cured were US$134.40 and US$130.92, respectively. Compared with OTC, treatment of children with uncomplicated SAM by CHWs was effective, increased treatment coverage and was cost-effective.