Point prevalence of evidence-based antimicrobial use among hospitalized patients in sub-Saharan Africa: a systematic review and meta-analysis.

Excessive and improper use of antibiotics causes antimicrobial resistance which is a major threat to global health security. Hospitals in sub-Saharan Africa (SSA) has the highest prevalence of antibiotic use. This systematic review and meta-analysis aimed to determine the pooled point prevalence (PPP) of evidence-based antimicrobial use among hospitalized patients in SSA. Literature was retrieved from CINAHL, EMBASE, Google Scholar, PubMed, Scopus, and Web of Science databases. Meta-analysis was conducted using STATA version 17. Forest plots using the random-effect model were used to present the findings. The heterogeneity and publication bias were assessed using the I2 statistics and Egger's test. The protocol was registered in PROSPERO with code CRD42023404075. The review was conducted according to PRISMA guidelines. A total of 26, 272 study participants reported by twenty-eight studies published from 10 countries in SSA were included. The pooled point prevalence of antimicrobial use in SSA were 64%. The pooled estimate of hospital wards with the highest antibiotic use were intensive care unit (89%). The pooled prevalence of the most common clinical indication for antibiotic use were community acquired infection (41%). The pooled point prevalence of antimicrobial use among hospitalized patients were higher in SSA. Higher use of antibiotics was recorded in intensive care units. Community acquired infection were most common clinical case among hospitalized patients. Health systems in SSA must design innovative digital health interventions to optimize clinicians adhere to evidence-based prescribing guidelines and improve antimicrobial stewardship.

Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers.

Children with rare, relapsed or refractory cancers often face limited treatment options, and few predictive biomarkers are available that can enable personalized treatment recommendations. The implementation of functional precision medicine (FPM), which combines genomic profiling with drug sensitivity testing (DST) of patient-derived tumor cells, has potential to identify treatment options when standard-of-care is exhausted. The goal of this prospective observational study was to generate FPM data for pediatric patients with relapsed or refractory cancer. The primary objective was to determine the feasibility of returning FPM-based treatment recommendations in real time to the FPM tumor board (FPMTB) within a clinically actionable timeframe (<4 weeks). The secondary objective was to assess clinical outcomes from patients enrolled in the study. Twenty-five patients with relapsed or refractory solid and hematological cancers were enrolled; 21 patients underwent DST and 20 also completed genomic profiling. Median turnaround times for DST and genomics were within 10 days and 27 days, respectively. Treatment recommendations were made for 19 patients (76%), of whom 14 received therapeutic interventions. Six patients received subsequent FPM-guided treatments. Among these patients, five (83%) experienced a greater than 1.3-fold improvement in progression-free survival associated with their FPM-guided therapy relative to their previous therapy, and demonstrated a significant increase in progression-free survival and objective response rate compared to those of eight non-guided patients. The findings from our proof-of-principle study illustrate the potential for FPM to positively impact clinical care for pediatric and adolescent patients with relapsed or refractory cancers and warrant further validation in large prospective studies. ClinicalTrials.gov registration: NCT03860376 .

Factors Associated with Inappropriate Use of Antibiotics Among Animal Health Professionals in Selected Districts of Rwanda, 2021.

BACKGROUND: Antibiotic resistance is a global health concern. Humans can acquire antibiotic resistance through human-to-human transmission, from the environment, via the food chain, and through the contact with animals. The National Action Plan on antimicrobial resistance 2020-2024 highlights the prudent use of antibiotics in veterinary activities as the key element in keeping antibiotics effective. We determined the factors associated with misuse of antibiotics among animal health professionals in Rwanda. METHODS: This was a cross-sectional study that enrolled animal health field professionals from five districts, where stratified random sampling was used to select one district by each province of Rwanda. Structured questions were used during face-to-face interviews. The misuse of antibiotics was defined as the use of antibiotics for reasons other than treatment, the non-completion of required courses, or the use of a high dose (i.e., an overdose) of antibiotics. We collected socio-demographic data of respondents, as well as elementary knowledge and perceptions on veterinary antibiotics and antibiotic resistance. A backward stepwise logistic regression model was used to identify the factors that were predictive of the inappropriate use of antibiotics. RESULTS: There were 256 respondents to the survey. Of those, 198 were male and 58 were female. Almost three quarters of respondents (n = 174/256; 68%) reported the misuse of antibiotics at least once in the previous 12 months. The final logistic regression analysis identified the following factors to be predictive of antibiotics misuse: aged ≤ 24 years (aOR 0.92; 95% CI [0.88, 0.96]; p < 0.001); low trust in veterinary antibiotics available in the local market (aOR 8.45; 95% CI [4.18, 17.07]; p < 0.01), insufficient knowledge about basic understanding of antibiotics and antibiotic resistance (aOR 2.78; 95% CI [1.38, 5.58], p < 0.01) and not acquiring any continuing education (aOR 1.97; 95% CI [1.02, 4.19]; p = 0.04). CONCLUSIONS: This study identified inadequate perceptions of proper antibiotic use among animal health professionals. There is a need for continuous education on appropriate antibiotic use among animal health professionals to lessen the negative impact of antibiotic resistance on public health security.

Safety and pharmacokinetics of ONC201 (dordaviprone) administered two consecutive days per week in pediatric patients with H3 K27M-mutant glioma.

BACKGROUND: This study evaluated the safety and pharmacokinetics (PK) of oral ONC201 administered twice-weekly on consecutive days (D1D2) in pediatric patients with newly diagnosed DIPG and/or recurrent/refractory H3 K27M glioma. METHODS: This phase 1 dose-escalation and expansion study included pediatric patients with H3 K27M-mutant glioma and/or DIPG following ≥1 line of therapy (NCT03416530). ONC201 was administered D1D2 at 3 dose levels (DLs; -1, 1, and 2). The actual administered dose within DLs was dependent on weight. Safety was assessed in all DLs; PK analysis was conducted in DL2. Patients receiving once-weekly ONC201 (D1) served as a PK comparator. RESULTS: Twelve patients received D1D2 ONC201 (DL1, n = 3; DL1, n = 3; DL2, n = 6); no dose-limiting toxicities or grade ≥3 treatment-related adverse events occurred. PK analyses at DL2 (D1-250 mg, n = 3; D1-625 mg, n = 3; D1D2-250 mg, n = 2; D1D2-625 mg, n = 2) demonstrated variability in Cmax, AUC0-24, and AUC0-48, with comparable exposures across weight groups. No accumulation occurred with D1D2 dosing; the majority of ONC201 cleared before administration of the second dose. Cmax was variable between groups but did not appear to increase with D1D2 dosing. AUC0-48 was greater with D1D2 than once-weekly. CONCLUSIONS: ONC201 given D1D2 was well tolerated at all DLs and associated with greater AUC0-48.

Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis.

Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. Funding: ECDC.

Effectiveness of a fourth SARS-CoV-2 vaccine dose in previously infected individuals from Austria.

INTRODUCTION: Evidence is limited on the effectiveness of a fourth vaccine dose against coronavirus disease 2019 (COVID-19) in populations with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We estimated the risk of COVID-19 deaths and SARS-CoV-2 infections according to vaccination status in previously infected individuals in Austria. METHODS: This is a nationwide retrospective observational study. We calculated age and gender adjusted Cox proportional hazard ratios (HRs) of COVID-19 deaths (primary outcome) and SARS-CoV-2 infections (secondary outcome) from 1 November to 31 December 2022, primarily comparing individuals with four versus three vaccine doses. Relative vaccine effectiveness (rVE) was calculated as (1-HR) X 100. RESULTS: Among 3,986,312 previously infected individuals, 281,291 (7,1%) had four and 1,545,242 (38.8%) had three vaccinations at baseline. We recorded 69 COVID-19 deaths and 89,056 SARS-CoV-2 infections. rVE for four versus three vaccine doses was -24% (95% CI: -120 to 30) against COVID-19 deaths, and 17% (95% CI: 14-19) against SARS-CoV-2 infections. This latter effect rapidly diminished over time and infection risk with four vaccinations was higher compared to less vaccinated individuals during extended follow-up until June 2023. Adjusted HR (95% CI) for all-cause mortality for four versus three vaccinations was 0.79 (0.74-0.85). DISCUSSION: In previously infected individuals, a fourth vaccination was not associated with COVID-19 death risk, but with transiently reduced risk of SARS-CoV-2 infections and reversal of this effect in longer follow-up. All-cause mortality data suggest healthy vaccinee bias.

Adherence to evidence-based implementation of antimicrobial treatment guidelines among prescribers in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: Adherence to evidence-based standard treatment guidelines (STGs) enable healthcare providers to deliver consistently appropriate diagnosis and treatment. Irrational use of antimicrobials significantly contributes to antimicrobial resistance in sub-Saharan Africa (SSA).  The best available evidence is needed to guide healthcare providers on adherence to evidence-based implementation of STGs. This systematic review and meta-analysis aimed to determine the pooled prevalence of adherence to evidence-based implementation of antimicrobial treatment guidelines among prescribers in SSA. METHODS: The review followed the JBI methodology for systematic reviews of prevalence data. CINAHL, Embase, PubMed, Scopus, and Web of Science databases were searched with no language and publication year limitations. STATA version 17 were used for meta-analysis. The publication bias and heterogeneity were assessed using Egger's test and the I2 statistics. Heterogeneity and publication bias were validated using Duval and Tweedie's nonparametric trim and fill analysis using the random-effect analysis. The summary prevalence and the corresponding 95% confidence interval (CI) of healthcare professionals' compliance with evidence-based implementation of STG were estimated using random effect model. The review protocol has been registered with PROSPERO code CRD42023389011. The PRISMA flow diagram and checklist were used to report studies included, excluded and their corresponding section in the manuscript. RESULTS: Twenty-two studies with a total of 17,017 study participants from 14 countries in sub-Saharan Africa were included. The pooled prevalence of adherence to evidence-based implementation of antimicrobial treatment guidelines in SSA were 45%. The pooled prevalence of the most common clinical indications were respiratory tract (35%) and gastrointestinal infections (18%). Overall prescriptions per wards were inpatients (14,413) and outpatients (12,845). Only 391 prescribers accessed standard treatment guidelines during prescription of antimicrobials. CONCLUSIONS: Healthcare professionals' adherence to evidence-based implementation of STG for antimicrobial treatment were low in SSA. Healthcare systems in SSA must make concerted efforts to enhance prescribers access to STGs through optimization of mobile clinical decision support applications. Innovative, informative, and interactive strategies must be in place by the healthcare systems in SSA to empower healthcare providers to make evidence-based clinical decisions informed by the best available evidence and patient preferences, to ultimately improving patient outcomes and promoting appropriate antimicrobial use.

Bacterial profile and antimicrobial resistance patterns of infected diabetic foot ulcers in sub-Saharan Africa: a systematic review and meta-analysis.

The number of diabetic foot ulcer patients is substantially increasing, with the rapidly rising burden of diabetic mellitus in sub-Saharan Africa. The data on the regional prevalence of diabetic foot ulcer infecting bacteria and their antimicrobial resistance patterns is crucial for its proper management. This systematic review and meta-analysis determined the pooled prevalence of bacterial profiles and antimicrobial resistance patterns of infected diabetic foot ulcers in sub-Saharan Africa. A comprehensive search of the literature was performed on CINAHL, EMBASE, Google Scholar, PubMed, Scopus, and Web of Science databases. Critical appraisal was done using the Joanna Briggs Institute's tool for prevalence studies. A pooled statistical meta-analysis was conducted using STATA Version 17.0. The I2 statistics and Egger's test were used to assess the heterogeneity and publication bias. The pooled prevalence and the corresponding 95% confidence interval of bacterial profiles and their antimicrobial resistance patterns were estimated using a random effect model. Eleven studies with a total of 1174 study participants and 1701 bacteria isolates were included. The pooled prevalence of the most common bacterial isolates obtained from DFU were S. aureus (34.34%), E. coli (21.16%), and P. aeruginosa (20.98%). The highest pooled resistance pattern of S. aureus was towards Gentamicin (57.96%) and Ciprofloxacin (52.45%). E.coli and K. Pneumoniae showed more than a 50% resistance rate for the most common antibiotics tested. Both gram-positive and gram-negative bacteria were associated with diabetic foot ulcers in sub-Saharan Africa. Our findings are important for planning treatment with the appropriate antibiotics in the region. The high antimicrobial resistance prevalence rate indicates the need for context-specific effective strategies aimed at infection prevention and evidence-based alternative therapies.

Rhabdoid tumors in patients conceived following ART: is there an association?

STUDY QUESTION: In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART? SUMMARY ANSWER: We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with RT. WHAT IS KNOWN ALREADY: Anecdotal evidence suggests an association of ART with RT. STUDY DESIGN, SIZE, DURATION: This was a multi-institutional retrospective survey. Children with RT conceived by ART were identified in our EU-RHAB database (n = 11/311 children diagnosed between January 2010 and January 2018) and outside the EU-RHAB database (n = 3) from nine different countries. A population-representative German EU-RHAB control cohort of children with RTs conceived without ART (n = 211) (EU-RHAB control cohort) during the same time period was used as a control cohort for clinical, therapeutic, and survival analyses. The median follow-up time was 11.5 months (range 0-120 months) for children with RT_ART and 18.5 months (range 0-153 months) for the EU-RHAB control cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analyzed 14 children with RT_ART diagnosed from January 2010 to January 2018. We examined tumors and matching blood samples for SMARCB1 mutations and copy number alterations using FISH, multiplex ligation-dependent probe amplification, and DNA sequencing. DNA methylation profiling of tumor and/or blood samples was performed using DNA methylation arrays and compared to respective control cohorts of similar age (n = 53 tumors of children with RT conceived without ART, and n = 38 blood samples of children with no tumor born small for gestational age). MAIN RESULTS AND THE ROLE OF CHANCE: The median age at diagnosis of 14 individuals with RT_ART was 9 months (range 0-66 months), significantly lower than the median age of patients with RT (n = 211) in the EU-RHAB control cohort (16 months (range 0-253), P = 0.03). A significant female predominance was observed in the RT_ART cohort (M:F ratio: 2:12 versus 116:95 in EU-RHAB control cohort, P = 0.004). Eight of 14 RT_ART patients were diagnosed with atypical teratoid rhabdoid tumor, three with extracranial, extrarenal malignant rhabdoid tumor, one with rhabdoid tumor of the kidney and two with synchronous tumors. The location of primary tumors did not differ significantly in the EU-RHAB control cohort (P = 0.27). Six of 14 RT_ART patients presented with metastases at diagnosis. Metastatic stage was not significantly different from that within the EU-RHAB control cohort (6/14 vs 88/211, P = 1). The incidence of pathogenic germline variants was five of the 12 tested RT_ART patients and, thus, not significantly different from the EU-RHAB control cohort (5/12 versus 36/183 tested, P = 0.35). The 5-year overall survival (OS) and event free survival (EFS) rates of RT_ART patients were 42.9 ± 13.2% and 21.4 ± 11%, respectively, and thus comparable to the EU-RHAB control cohort (OS 41.1 ± 3.5% and EFS 32.1 ± 3.3). We did not find other clinical, therapeutic, outcome factors distinguishing patients with RT_ART from children with RTs conceived without ART (EU-RHAB control cohort). DNA methylation analyses of 10 tumors (atypical teratoid RT = 6, extracranial, extrarenal malignant RT = 4) and six blood samples from RT_ART patients showed neither evidence of a general DNA methylation difference nor underlying imprinting defects, respectively, when compared to a control group (n = 53 RT samples of patients without ART, P = 0.51, n = 38 blood samples of patients born small for gestational age, P = 0.1205). LIMITATIONS, REASONS FOR CAUTION: RTs are very rare malignancies and our results are based on a small number of children with RT_ART. WIDER IMPLICATIONS OF THE FINDINGS: This cohort of patients with RT_ART demonstrated a marked female predominance, and a rather low median age at diagnosis even for RTs. Other clinical, treatment, outcome, and molecular factors did not differ from those conceived without ART (EU-RHAB control cohort) or reported in other series, and there was no evidence for imprinting defects. Long-term survival is achievable even in cases with pathogenic germline variants, metastatic disease at diagnosis, or relapse. The female preponderance among RT_ART patients is not yet understood and needs to be evaluated, ideally in larger international series. STUDY FUNDING/COMPETING INTEREST(S): M.C.F. is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.10, by the 'Deutsche Forschungsgemeinschaft' DFG FR 1516/4-1 and by the Deutsche Krebshilfe 70113981. R.S. received grant support by Deutsche Krebshilfe 70114040 and for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. P.D.J. is supported by the Else-Kroener-Fresenius Stiftung and receives a Max-Eder scholarship from the Deutsche Krebshilfe. M.H. is supported by DFG (HA 3060/8-1) and IZKF Münster (Ha3/017/20). BB is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.05. We declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Testing the Impact of Phone Texting Reminders for Children's Immunization Appointments in Rural Cameroon: Protocol for a Nonrandomized Controlled Trial.

BACKGROUND: Globally, over 20 million children are unvaccinated and over 25 million missed their follow-up doses during the COVID-19 pandemic; thus, they face vaccine-preventable diseases and unnecessary deaths. This is especially the case for those with HIV or living in vulnerable settings. Using cell phones to send reminders to parents has been shown to improve vaccination rates. OBJECTIVE: We aim to determine whether implementation of an automated SMS reminder will improve child vaccination rates in a turbulent, semiurban/semirural setting in a low-income country. METHODS: This will be a nonrandomized controlled trial that will be conducted at Azire Integrated Health Centre, Bamenda, Cameroon. RESULTS: A total of 200 parents per study group (aged over 18 years) who are registered at the clinic at least one month prior to the study will be recruited. The intervention group will receive 2 reminders: 1 week and 2 days prior to the scheduled vaccination. For those who miss their appointments, a reminder will be sent 1 week after their missed appointment. The control group will receive the regular care provided at the clinic. Baseline information, clinical visit data, and vaccination records will be collected for both groups. Descriptive statistics will be used to summarize baseline characteristics between and within clusters and groups. The Fisher exact test will be used to compare parent-child units who return for follow-up visits (as a percentage) and children vaccinated as scheduled (as a percentage) between the study groups. Finally, we will compare how many members of both study groups return for 1 follow-up visit using Kaplan-Meier survival analysis. CONCLUSIONS: Due to limited effective child vaccination interventions in unstable settings, this study will be of high importance for suggesting a holistic approach to improve child vaccination and public health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47018.

Implementation of a Surveillance System for Severe Acute Respiratory Infections at a Tertiary Care Hospital in Austria: Protocol for a Retrospective Longitudinal Feasibility Study.

BACKGROUND: The risk of a large number of severe acute respiratory infection (SARI) cases emerging is a global concern. SARI can overwhelm the health care capacity and cause several deaths. Therefore, the Austrian Agency for Health and Food Safety will explore the feasibility of implementing an automatic electronically based SARI surveillance system at a tertiary care hospital in Austria as part of the hospital network, initiated by the European Centre for Disease Prevention and Control. OBJECTIVE: We aim to investigate the availability of routinely collected health record data pertaining to respiratory infections and the optimal approach to use such available data for systematic surveillance of SARI in a real-world setting, describe the characteristics of patients with SARI before and after the beginning of the COVID-19 pandemic, and investigate the feasibility of identifying the risk factors for a severe outcome (intensive care unit admission or death) in patients with SARI. METHODS: We will test the feasibility of a surveillance system, as part of a large European network, at a tertiary care hospital in the province of Lower Austria (called Regional Hospital Wiener Neustadt). It will be a cross-sectional study for the inventory of the electronic data records and implementation of automatic data retrieval for the period of January 2019 through the end of December 2022. The analysis will include an exploration of the database structure, descriptive analysis of the general characteristics of the patients with SARI, estimation of the SARI incidence rate, and assessment of the risk factors and different levels of severity of patients with SARI using logistic regression analysis. RESULTS: This will be the first study to assess the feasibility of SARI surveillance at a large 800-bed tertiary care hospital in Austria. It will provide a general overview of the potential for establishing a hospital-based surveillance system for SARI. In addition, if successful, the electronic surveillance will be able to improve the response to early warning signs of new SARI, which will better inform policy makers in strengthening the surveillance system. CONCLUSIONS: The findings will support the expansion of the SARI hospital-based surveillance system to other hospitals in Austria. This network will be of use to Austria in preparing for future pandemics. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/47547.

Lessons Learned from Sudan Ebola Virus Disease (SUDV) Preparedness in Rwanda: A Comprehensive Review and Way Forward.

BACKGROUND: Ebola Virus Disease (EVD) is a severe and often fatal illness that affects humans and has significant public health implications, including high mortality rates, strain on healthcare systems, and social and economic disruption. On 20 September 2022, Uganda declared an Ebola disease outbreak caused by the Sudan ebolavirus species. The neighboring countries of Uganda were classified by World Health Organization (WHO) as being at high risk of Sudan Ebola Virus Disease (SUDV) importation. The country of Rwanda implemented different sustainable strategies and activities to prepare and ensure a timely and effective response to SUDV outbreaks once it has arrived in the country. We aimed to highlight the sustainable strategies and activities implemented for SUDV preparedness and the subsequent lessons learnt in Rwanda. METHODS: This paper reviewed the documentation on activities implemented for SUDV preparedness, with a focus on lessons learned from different countries. The paper analyzed the common themes and highlighted the key components of EVD preparedness in Rwanda after declaration of SUDV outbreak in Uganda. RESULTS: The key components of SUDV preparedness include its readiness assessment in Rwanda, effective coordination, collaboration and leadership mechanisms, enhancing the early detection and surveillance system, effective risk communication and community engagement, capacity building of healthcare providers on case management and infection prevention and control (IPC), and continual preparedness. These components were essential to ensure timely and effective preparation and response to SUDV related outbreaks. CONCLUSION: A multi-sectoral approach involving all stakeholders was necessary to ensure timely and effective preparation and response. Continuous investment in preparedness, strengthening of health systems, and the review of preparedness components provided insights into the best practices for SUDV preparedness, which were essential to prevent future outbreaks and minimize their impact. This will inform other countries about the role of timely development of preparedness plans.

Effect of Non-pharmaceutical Interventions on COVID-19 in Rwanda: An Observational Study.

BACKGROUND: On 11 March 2020, COVID-19 was declared as a pandemic by the World Health Organization (WHO). The first case was identified in Rwanda on 24 March 2020. Three waves of COVID-19 outbreak have been observed since the identification of the first case in Rwanda. During the COVID-19 epidemic, the country of Rwanda has implemented many Non-Pharmaceutical Interventions (NPIs) that appear to be effective. However, a study was needed to investigate the effect of non-pharmaceutical interventions applied in Rwanda to guide ongoing and future responses to epidemics of this emerging disease across the World. METHODS: A quantitative observational study was conducted by conducting analysis of COVID-19 cases reported daily in Rwanda from 24 March 2020 to 21 November 2021. Data used were obtained from the official Twitter account of Ministry Health and the website of Rwanda Biomedical Center. Frequencies of COVID-19 cases and incidence rates were calculated, and to determine the effect of non-pharmaceutical interventions on changes in COVID-19 cases an interrupted time series analysis was used. RESULTS: Rwanda has experienced three waves of COVID-19 outbreak from March 2020 to November 2021. The major NPIs applied in Rwanda included lockdowns, movement restriction among districts and Kigali City, and curfews. Of 100,217 COVID-19 confirmed cases as of 21 November 2021, the majority were female 51,671 (52%) and 25,713 (26%) were in the age group of 30-39, and 1866 (1%) were imported cases. The case fatality rate was high among men (n = 724/48,546; 1.5%), age > 80 (n = 309/1866; 17%) and local cases (n = 1340/98,846; 1.4%). The interrupted time series analysis revealed that during the first wave NPIs decreased the number of COVID-19 cases by 64 cases per week. NPIs applied in the second wave decreased COVID-19 cases by 103 per week after implementation, while in the third wave after NPIs implementation, a significant decrease of 459 cases per week was observed. CONCLUSION: The early implementation of lockdown, restriction of movements and putting in place curfews may reduce the transmission of COVID-19 across the country. The NPIs implemented in Rwanda appear to be effectively containing the COVID-19 outbreak. Additionally, setting up the NPIs early is important to prevent further spread of the virus.

Prevalence of Group B Streptococcus maternal colonization, serotype distribution, and antimicrobial resistance in Sub-Saharan Africa: A systematic review and meta-analysis.

OBJECTIVE: Group B Streptococcus (GBS)-associated maternal, perinatal, and neonatal mortality and morbidity disproportionately affects Sub-Saharan Africa (SSA). This systematic review and meta-analysis aimed to address the estimated prevalence, antimicrobial susceptibility, and serotype distribution of GBS isolates in SSA. METHODS: This study was done according to PRISMA guidelines. MEDLINE/PubMed, CINAHL (EBSCO), Embase, SCOPUS, Web of Sciences databases, and Google Scholar were used to retrieve both published and unpublished articles. STATA software version 17 was used for data analysis. Forest plots using the random-effect model were used to present the findings. Heterogeneity was assessed using Cochrane chi-square (I2) statistics, while the Egger intercept was used to assess publication bias. RESULTS: Fifty-eight studies that fulfilled the eligibility criteria were included for meta-analysis. The pooled prevalence of maternal rectovaginal colonization and vertical transmission of GBS were 16.06, 95% CI [13.94, 18.30] and 43.31%, 95% CI [30.75, 56.32], respectively. The highest pooled proportion of antibiotic resistance to GBS was observed in gentamicin (45.58%, 95% CI [4.12%, 91.23]), followed by erythromycin, (25.11%, 95% CI [16.70, 34.49]). The lowest antibiotic resistance was observed in vancomycin (3.84%, 95% CI [0.48, 9.22]). Our findings indicate that serotypes Ia/Ib/II/ III/and V cover almost 88.6% of serotypes in SSA. CONCLUSIONS: The estimated high prevalence and resistance to different antibiotic classes observed in GBS isolates from SSA suggests the need for implementation of effective intervention efforts.

Children Immunization App (CIMA): A Non-randomized Controlled Trial Among Syrian Refugees in Zaatari Camp, Jordan.

Approximately 20 million children are not vaccinated, especially among refugees. There is a growing access to smartphones, among refugees, which can help in improving their vaccination. We assessed the impact of an app for the vaccination follow-up visit among refugees in Jordan. We developed an app and tested it through a non-randomized trial at the Zaatari refugees camp in Jordan. The study was conducted during March - December 2019 at three vaccination clinics inside the camp. The study included two study groups (intervention and control groups) for refugees living at the camp. The intervention group included parents who own an Android smartphone and have one newborn that require between one and four first vaccination doses and they accepted to participate in the study, during their regular visit to the vaccination clinics. The control group was for the usual care. We compared both study groups for returning back to one follow-up visit, using Kaplan-Meier survival analysis. We recruited 936 babies (n = 471; 50.3% in the intervention group, both study groups were similar at baseline). The majority of mothers were literate (94.2%) with a median age of 24. The majority of the babies had a vaccination card (n = 878, 94%). One quarter (26%) of mother-babies pairs of the intervention group came back within one week (versus 22% for control group); When it comes to lost-follow-up, 22% and 28% did not have a history of returning back (intervention and control groups respectively, p = 0.06) (Relative risk reduction: 19%). The Kaplan-Meier Survival Analysis showed a statistically significant progressive reduction in the duration of coming back late for the follow-up vaccine visit. We tested a vaccination app for the first time, in a refugee population setting. The app can be used as a reminder for parents to come back on time for their children's vaccine follow-up visits.

Access to support services for individuals who experience intimate partner violence during stressful life events (SLEs) in high-income countries: Protocol for a scoping review.

BACKGROUND: Women, gender minorities and their children are at heightened risk of intimate partner violence (IPV) following stressful life events (SLE). The increase in IPV during the global pandemic of the Novel Coronavirus (COVID-19) is recent evidence. Studies have linked IPV to poor health, resulting in lower mental, physical, sexual, and reproductive health outcomes. IPV has also been shown as a barrier to labour force participation, leading to negative socioeconomic outcomes (i.e., low or no employment). Formal and informal supports help individuals who experience IPV, but it is unclear if and how these are being accessed during SLEs such as environmental disasters, pandemics, and economic recessions. Accessibility to programs is an issue in normal times because of stigma, social norms, and lack of knowledge; this has been further amplified by situations where individuals who experience violence are isolated physically and emotionally, as well as face controlling behaviours by their perpetrators of violence. This scoping review will be used to conduct a comprehensive review of literature and address the research question: What is known in published literature about access to services by individuals who experience IPV during stressful life events in high-income countries? METHODS: The following electronic databases will be searched for relevant publications: MEDILINE (OVID), Embase (OVID), PsychINfo (OVID), CINAHL (EBSCO), Global Health (EBSCO), Gender Watch (ProQuest), Web of Science and Applied Social Sciences Index & Abstracts (ProQuest). Key terms and medical subject headings (MeSH) will be based on previous literature and consult with an expert librarian. The major concepts include 'stressful life events' AND intimate partner violence' AND 'access to services'. Google, Google Scholar, and the WHO website will be used to search for grey literature, books/chapters, and programme reports as well as references of relevant reviews. Studies will be screened and extracted by two reviewers and conflicts resolved through discussion or a third reviewer. Both quantitative and qualitative analysis of relevant data will outline key findings. DISCUSSION: The scoping review will provide synthesized and summarized findings on literature regarding access to informal and formal social supports by victims of IPV during SLEs (i.e., pandemics and natural/environmental disasters/emergencies, economic recessions) where possible, highlighting key barriers, facilitators and lessons learned. Findings have potential to inform programs, policies, and interventions on accessibility to necessary support and health services during disasters.

COVID-19 Case Management Outcomes Amongst Diabetes and Hypertensive Patients in the United Arab Emirates: A Prospective Study.

The global pandemic of the novel Coronavirus infection 2019 (COVID-19) challenged the care of comorbid patients. The risk imposed by COVID-19 on diabetes patients is multisystemic, exponential, and involves glucose dysregulation. The increased burden for diabetes patients infected with COVID-19 is substantial in countries with a high prevalence of diabetics, such as the United Arab Emirates (UAE). This study aims to explore the prevalence of diabetes, clinical characteristic, and outcomes of patients admitted for COVID-19 treatment with or without a concurrent preadmission diagnosis of diabetes. A prospective study was performed on 1199 adults admitted with confirmed COVID-19 from December 2020 to April 2021 to a single hospital in the UAE. The study compared the demographics, clinical characteristics, and outcomes in COVID-19-infected patients with diabetes to patients without diabetes. The study endpoints include the development of new-onset diabetes, admission to ICU, trends in the blood glucose levels, and death. A total of 1199 patients (390 with diabetes) were included in the study. A diabetes prevalence was detected among 9.8% of the study population. Among the diabetes group, 10.8% were morbidly obese, 65.4% had associated hypertension, and 18.9% had coronary artery disease. Diabetes patients showed higher rates of ICU admission (11.1% vs. 7.1%), NIV requirement (9.6% vs. 6.4%), and intubation (5.45% vs. 2%) compared to the non-diabetes group. Advanced age was a predictor of a worsening COVID-19 course, while diabetes (p < 0.050) and hypertension (p < 0.025) were significant predictors of death from COVID-19. Nearly three-fourths (284 (73.4%)) of the diabetic patients developed worsened hyperglycemia as compared to one-fifth (171 (20.9%)) of the nondiabetic patients. New-onset diabetes was detected in 9.8% of COVID-19 patients. COVID-19 severity is higher in the presence of diabetes and is associated with worsening hyperglycemia and poor clinical outcomes. Preexisting hypertension is a predictor of COVID-19 severity and death.

Diagnostic Study to Assess the Performance of a New Urinary Legionella Antigen Test-A National Study in Three Referral University Hospitals in Austria during 2014-2017.

BACKGROUND: We evaluated the performance of a rapid diagnostic antigen test (Coris) as an index test versus the urinary Antigen ELISA (Bartels) as the reference test. METHODS: Prospective diagnostic accuracy study (2014-2017) at three university hospitals in Austria. RESULTS: A total of 996 patients were included in the study. Legionellosis was diagnosed in 49/996 (4.9%) using the reference test. The sensitivity and specificity of the Coris test were 75.5% (95% CI 61.1-86.7%) and 100% (95%CI 99.6-100%), respectively. The PPV was 100% and when using the lower 95% CI limit of the estimate for sensitivity, the resulting PPV was 61.1%. The NPV was 98.7% and the accuracy was 98.8%. The index test showed a PPV > 97% during the period of summer and autumn (May through November) and ≥88% during winter (December through February). The NPV was >97% during all of the periods. The median of the monthly incidence in the general population was 0.1 per 100,000 (IQR 0.1; 0.3). CONCLUSION: The new rapid test gave a high level of diagnostic accuracy in a rapid fashion. The test can be applied at the bedside by non-laboratory staff.

Phase I dose escalation and expansion trial of single agent ONC201 in pediatric diffuse midline gliomas following radiotherapy.

Background: ONC201, a dopamine receptor D2 (DRD2) antagonist and caseinolytic protease P (ClpP) agonist, has induced durable tumor regressions in adults with recurrent H3 K27M-mutant glioma. We report results from the first phase I pediatric clinical trial of ONC201. Methods: This open-label, multi-center clinical trial (NCT03416530) of ONC201 for pediatric H3 K27M-mutant diffuse midline glioma (DMG) or diffuse intrinsic pontine glioma (DIPG) employed a dose-escalation and dose-expansion design. The primary endpoint was the recommended phase II dose (RP2D). A standard 3 + 3 dose escalation design was implemented. The target dose was the previously established adult RP2D (625 mg), scaled by body weight. Twenty-two pediatric patients with DMG/DIPG were treated following radiation; prior lines of systemic therapy in addition to radiation were permitted providing sufficient time had elapsed prior to study treatment. Results: The RP2D of orally administered ONC201 in this pediatric population was determined to be the adult RP2D (625 mg), scaled by body weight; no dose-limiting toxicities (DLT) occurred. The most frequent treatment-emergent Grade 1-2 AEs were headache, nausea, vomiting, dizziness and increase in alanine aminotransferase. Pharmacokinetics were determined following the first dose: T 1/2, 8.4 h; T max, 2.1 h; C max, 2.3 µg/mL; AUC0-tlast, 16.4 hµg/mL. Median duration of treatment was 20.6 weeks (range 5.1-129). Five (22.7%) patients, all of whom initiated ONC201 following radiation and prior to recurrence, were alive at 2 years from diagnosis. Conclusions: The adult 625 mg weekly RP2D of ONC201 scaled by body weight was well tolerated. Further investigation of ONC201 for DMG/DIPG is warranted.

"Because This Is an Evidence-Based Program": The Learning Experience of Croatia with the Lions Quest Skills for Adolescence, Implemented In-Person and Online.

Background: The Lions Quest Skills for Adolescence (LQSFA) is an evidence-based social and emotional learning program for school students. It is implemented as a teacher-led extracurricular activity for children aged 10-15 years. From 2019 to 2022, the United Nations Office on Drugs and Crime, in collaboration with Lions Clubs International Foundation, implemented the LQSFA in 41 schools in Croatia. Due to the COVID-19 lockdown measures, the intervention was adjusted into a hybrid modality (in-class and online). We evaluated the experience that the teachers had with the LQSFA in a hybrid modality. Methods: We used a focus-group discussion approach to evaluate the experience of five LQSFA teachers. Results: Three themes emerged: (1) the appreciation of evidence-based programs by the teachers, (2) the benefit of the LQSFA on the parents, and (3) the length of the online version of the questionnaire tool that was used to assess pre- and post-LQSFA experiences among students was too long. These results indicate that the LQSFA is undergoing a scaling on a national level in Croatia, even when implemented in a hybrid setting. Conclusions: Using an evidence-based program such as the LQSFA was rewarding for teachers, despite the challenges in the administrative adjustments regarding the online and in-person class teaching. LQSFA filled an important gap during COVID19-related stress.