Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project.

INTRODUCTION: To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS: Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS: Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION: This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

Antibiotic Treatment for Well-Appearing Infants Born at ≥35 Weeks' Gestation to Mothers with Chorioamnionitis Before and After Implementation of Neonatal Early-Onset Sepsis Calculator.

Purpose: Our quality improvement study aimed to determine whether application of a neonatal early-onset sepsis calculator (NSC) among well-appearing infants born at ≥35 weeks' gestation to mothers with chorioamnionitis decreases the number of lab evaluations (LEs) and antibiotic treatments (Abxs) without missing early-onset sepsis. Methods: We compared 2 years (January 1, 2019-January 3, 2021) of data from a historical-control group before implementation of the NSC to 1 year (January 4, 2021-December 31, 2021) of data from a calculator group after implementation of the NSC to evaluate whether LE and Abx decreased following implementation of the NSC on January 4, 2021. A P-value of <0.05 was considered statistically significant for the chi-squared test, Fisher's exact test, Student's t-test, and Mann-Whitney U test used for the analyses. Results: In the historical-control group, 94% of infants received LE and Abx. Retrospective application of the NSC in the historical-control group decreased LE from 94% to 21% and Abx from 94% to 13%. In the calculator group, 14% and 5% of infants received LE and Abx, respectively, and none of the blood culture was positive. Median time from birth to antibiotic initiation was significantly longer (14.5 vs 3.8 hours; P=0.0037) with no increase in median length of stay (2.3 vs 2.4 days; P=0.02) after NSC implementation. No significant difference in neonatal intensive care unit admission was identified between groups (4% vs 1%; P=0.15). Conclusions: There was a significant decrease in LE and Abx among well-appearing infants born at ≥35 weeks' gestation to mothers with chorioamnionitis after implementation of the NSC without missing early-onset sepsis. There was no increase in neonatal intensive care unit admission or length of hospital stay in infants who received antibiotics later after they appeared equivocal or clinically ill in the calculator group. Larger prospective studies that include follow ups are needed to confirm that early-onset sepsis is not missed.

Staphylococcus aureus Biofilm-Secreted Factors Cause Mucosal Damage, Mast Cell Infiltration, and Goblet Cell Hyperplasia in a Rat Rhinosinusitis Model.

Chronic rhinosinusitis (CRS) is an inflammatory condition of the sinonasal mucosa. Despite being a common health issue, the exact cause of CRS is yet to be understood. However, research suggests that Staphylococcus aureus, particularly in its biofilm form, is associated with the disease. This study aimed to investigate the impact of long-term exposure to secreted factors of Staphylococcus aureus biofilm (SABSFs), harvested from clinical isolates of non-CRS carrier and CRS patients, on the nasal mucosa in a rat model. Animals were randomised (n = 5/group) to receive daily intranasal instillations of 40 µL (200 µg/µL) SABSFs for 28 days or vehicle control. The sinonasal samples were analysed through histopathology and transcriptome profiling. The results showed that all three intervention groups displayed significant lymphocytic infiltration (p ≤ 0.05). However, only the SABSFs collected from the CRSwNP patient caused significant mucosal damage, mast cell infiltration, and goblet cell hyperplasia compared to the control. The transcriptomics results indicated that SABSFs significantly enriched multiple inflammatory pathways and showed distinct transcriptional expression differences between the control group and the SABSFs collected from CRS patients (p ≤ 0.05). Additionally, the SABSF challenges induced the expression of IgA and IgG but not IgE. This in vivo study indicates that long-term exposure to SABSFs leads to an inflammatory response in the nasal mucosa with increased severity for S. aureus isolated from a CRSwNP patient. Moreover, exposure to SABSFs does not induce local production of IgE.

Post implementation quarantine recommendations that support preparedness: A systematic review and quarantine implementation capability framework.

BACKGROUND: During COVID-19, countries utilised various quarantine systems to achieve specific outcomes. At different stages and durations, voluntary and mandatory quarantine occurred in homes, hotels and facilities based on local and national elimination strategies. Countries are incorporating quarantine lessons from COVID-19 into revising pandemic plans as part of the World Health Organization's Preparedness and Resilience for Emerging Threats (PRET) activities. This review aimed to amalgamate quarantine post implementation recommendations from a whole-of-system perspective. METHODS: This review utilised MEDLINE, Embase, CINAHL, APA, and PsycINFO. To capture all pandemics, no date restriction was applied. Recommendations were synthesised and inductively grouped into quarantine capability categories. This review was registered in PROSPERO (CRD42023420765). RESULTS: A total of 449 published articles were screened, with 51 articles included and 156 recommendations extracted. Recommendations were grouped into 15 quarantine capability categories, comprising governance, preparation, infection prevention and control, ventilation, compliance, data, information and technology, safety-quality-risk, communication, healthcare model, home quarantine, hotel quarantine, facility quarantine, workforce, and resident considerations. The capability categories were further consolidated into strategic, structural, and operational domains to support the whole-of-system perspective. CONCLUSION: The quarantine implementation capability framework generated provides comprehensive and deeper insights into the essential capabilities required for quarantine systems to support governments in PRET activities, including reviewing and revising pandemic plans and developing quarantine preparedness exercises.

Deferiprone-Gallium-Protoporphyrin Chitogel Decreases Pseudomonas aeruginosa Biofilm Infection without Impairing Wound Healing.

Pseudomonas aeruginosa is one of the most common pathogens encountered in clinical wound infections. Clinical studies have shown that P. aeruginosa infection results in a larger wound area, inhibiting healing, and a high prevalence of antimicrobial resistance. Hydroxypyridinone-derived iron chelator Deferiprone (Def) and heme analogue Gallium-Protoporphyrin (GaPP) in a chitosan-dextran hydrogel (Chitogel) have previously been demonstrated to be effective against PAO1 and clinical isolates of P. aeruginosa in vitro. Moreover, this combination of these two agents has been shown to improve sinus surgery outcomes by quickly reducing bleeding and preventing adhesions. In this study, the efficacy of Def-GaPP Chitogel was investigated in a P. aeruginosa biofilm-infected wound murine model over 6 days. Two concentrations of Def-GaPP Chitogel were investigated: Def-GaPP high dose (10 mM Def + 500 µg/mL GaPP) and Def-GaPP low dose (5 mM Def + 200 µg/mL GaPP). The high-dose Def-GaPP treatment reduced bacterial burden in vivo from day 2, without delaying wound closure. Additionally, Def-GaPP treatment decreased wound inflammation, as demonstrated by reduced neutrophil infiltration and increased anti-inflammatory M2 macrophage presence within the wound bed to drive wound healing progression. Def-GaPP Chitogel treatment shows promising potential in reducing P. aeruginosa cutaneous infection with positive effects observed in the progression of wound healing.

Rare Immune-Related Adverse Events (irAEs): Approach to Diagnosis and Management.

Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape across many solid organ malignancies and form part of routine clinical practice in many tumours. As indications for monotherapy, doublet therapy and combination approaches with chemotherapy and targeted agents expand, clinicians must be aware of the wide range of possible immune-related adverse events (irAEs). Common toxicities, including rash, colitis, hepatitis and pneumonitis are well described in the literature, and have established diagnostic and management algorithms. Rarer toxicities, often with an incidence of less than 1%, are less defined. These syndromes can be poorly recognised, may take on a fulminant course and do not have established or evidence-based diagnostic and management strategies. As such, patients may experience increased morbidity, mortality and poorer outcomes, related both to these irAEs as well as how the treatment of these may affect the management of their underlying malignancy. In this review, we aim to explore the incidence, potential biomarkers, pathogenesis, diagnostic work-up and clinical sequelae of a selection of uncommon irAEs, with a focus on myocarditis, neurological and haematologic syndromes. Further prospective research is required to accurately define the incidence and pathogenesis of these conditions, with the aim of increasing clinician awareness of rare irAEs and to assist with a more personalised and mechanism-based approach to these syndromes.

Demographic Characteristics of Unvaccinated Asymptomatic and Symptomatic SARS-CoV-2 Cases in Barwon South West, Victoria, Australia.

We investigated 328 SARS-CoV-2 cases in Barwon South West, Victoria, Australia, in the 2020 pre-vaccination period, comparing infections with symptoms to those that remained asymptomatic. De-identified self-reported data on case characteristics and symptom progression from three sequential questionnaires were examined. Multivariable logistic regression was used to model associations between demographic profiles and symptoms. Asymptomatic infections were more than three times as likely to be seen in ethnic minority groups than the Caucasian population after adjusting for gender and age [OR 3.2, 95% CI 1.5-6.7, p < 0.01] and were more common among cases of Asian background [OR 2.8, 95%CI 1.2-6.4]. Asymptomatic infections were also more common in youth and younger adults, but cases were approximately seven times more likely to be in seniors (≥65 years) compared with those 24 years of age or younger after adjusting for sex and ethnicity [OR 6.9, 95% CI 1.3-35.8]. The overrepresentation of ethnic minority groups among asymptomatic infections is suggestive of genetic haplotype variability by ethnic group, conferring greater cross-protection from other coronaviruses in the initial phase of the COVID-19 pandemic. Replication of this analysis in the post-vaccination era and reassessment of symptom expression according to ethnicity in a community with established vaccine and infection-induced immunity would determine whether this is a sustained association or one confined to the early stages of a pandemic in an immunologically naive population. These findings may, in part, reflect differences in testing patterns by ethnicity and true differences in disease expression, both of which are important to understand in order to inform transmission prevention strategies and tailored risk messaging according to ethnic background.

Forecasting pandemic quarantine in New Zealand and Australia: A scoping review of quarantine characteristics and capabilities within preparedness plans and pandemic exercise reports from 2002 to 2019.

BACKGROUND: This scoping review aims to identify and critically review quarantine preparedness in New Zealand and Australia pre-COVID-19 by categorising, comparing, and evaluating quarantine information contained within pandemic plans and exercises from both countries. METHODS: Parliamentary websites, including Archives New Zealand, ParlInfo and Google Scholar, were searched for publicly available plans and exercise reports from 2002 to 2019. Data were extracted from documents meeting the inclusion criteria and analysed using directive content analysis based on the Australian Disaster Preparedness Framework categories. This scoping review followed the Joanna Briggs Institute methodology for scoping reviews, which guided the data extraction, analysis, and presentation of results. RESULTS: A total of 16 documents mentioned quarantine and were included in this scoping review. The emphasis and level of detail regarding quarantine characteristics and capabilities varied between New Zealand's five documents (one plan and four exercise reports) and Australia's 11 documents (one Influenza pandemic plan, eight state plans and two exercise reports). New Zealand's plan forecasted the need for both voluntary quarantine at home and involuntary quarantine in facilities for incoming travellers, whilst the Australian Influenza pandemic plan and state plans primarily considered voluntary quarantine within private residences. Capability gaps identified during exercises were not consistently incorporated into revised plans. Some government documents containing information on quarantine may not be publicly available, limiting the available evidence for this review. CONCLUSION: This scoping review highlights the need to incorporate a range of possible quarantine options into plans and preparation activities to test and identify gaps in government and responsible agencies' capabilities. Pandemic preparedness will be strengthened by incorporating quarantine scale and duration variables into exercise scenarios.

Corrigendum: Corynebacterium accolens inhibits Staphylococcus aureus induced mucosal barrier disruption.

[This corrects the article DOI: 10.3389/fmicb.2022.984741.].

A cross-disciplinary view of current and emerging COVID-19 developments.

The emergency phase of the coronavirus disease 2019 (COVID-19) pandemic is over. Still, the work goes on in understanding the SARS-CoV-2 virus and its evolution, infection impacts - acute and long term - as well as therapeutics and the lessons for preventing and responding to future pandemics. Research into the long-term post-infection effects and therapeutic interventions also expands as the post-infection period lengthens. We provide an overview of the leading edge of COVID-19 research across clinical, epidemiological and social domains.

Pandemic policing and the construction of publics: an analysis of COVID-19 lockdowns in public housing.

COVID-19 responses have cast a spotlight on the uneven impacts of public health policy with particular populations or sites targeted for intervention. Perhaps the starkest example in Australia was the 'hard' lockdown of nine public housing complexes in inner-city Melbourne from 4 to 18 July 2020, where residents were fully confined to their homes. These complexes are home to diverse migrant communities and the lockdown drew public criticism for unfairly stigmatising ethnic minorities. This article draws on media articles published during the lockdown and the Victorian Ombudsman's subsequent investigation to explore the implications of broad, top-down public health measures for culturally and linguistically diverse (CALD) communities. Drawing on Lea's (2020) conceptualisation of policy ecology, we analyse the lockdown measures and community responses to explore the normative assumptions underpinning health policy mechanisms, constituting 'target populations' in narrow, exclusionary terms. We argue that the lockdown measures and use of police as compliance officers positioned tower residents as risky subjects in risky places. Tracing how such subject positions are produced, and resisted at the grassroots level, we highlight how policy instruments are not neutral interventions, but rather instantiate classed and racialised patterns of exclusion, reinforcing pervasive social inequalities in the name of public health.

Wound healing in endoscopic sinus surgery: Phase 1 clinical trial evaluating the role of Chitogel with adjuvants.

OBJECTIVES: This study aimed to determine the safety and efficacy of Chitogel, with and without Deferiprone (Def) and Gallium Protoporphyrin (GaPP), as a promoter of wound healing to improve surgical outcomes after endoscopic sinus susgery. DESIGN: A double-blinded, randomised control human clinical trial was conducted in patients undergoing ESS as a treatment for chronic rhinosinusitis. Participants underwent functional ESS or FESS with drill out as required and were randomised to receive test product Chitogel, Chitogel in combination with Def or Def-GaPP versus no packing (control). SETTING: Ostial stenosis and persistent inflammation are the main reasons for revision endoscopic sinus surgery (ESS). Post-operative (PO) dressings can improve PO wound healing and patient outcomes after ESS. PARTICIPANTS: Eighty two patients were included in this study with 79 patients completing the study with 40 undergoing full house FESS and 39 FESS plus frontal drillout. MAIN OUTCOME MEASURES: Patients were followed up at 2, 6 and 12 weeks PO, and outcome scores such as SNOT-22, VAS and LKS, pre and post-surgery (12 weeks) were compared. RESULTS: Seventy nine patients completed the study, there was a significant reduction in SNOT-22 score and improvement of VAS at 12 weeks in patients treated with Chitogel compared to control (p < .05). In those patients, the mean ostium area for the Chitogel and the Chitogel + Def + GaPP groups was higher across all three sinuses compared to the no-treatment control group, without statistical significance. Sphenoid sinus ostium was significantly more patent in patients treated with Chitogel compared to the control at the 12-week time point (p < .05). CONCLUSION: Chitogel as a PO dressing after ESS results in the best patient-reported symptom scores and objective measurements. The combination of Def and GaPP to Chitogel though proving safe, had no effect on the ostium patency or mucosal healing.

Antipsychotics and Medical Comorbidity: A Retrospective Study in an Urban Outpatient Psychiatry Clinic.

Patients with psychotic disorders have increased rates of medical comorbidities. In this cross-sectional study, we investigated the relationship between antipsychotics and medical comorbidities among patients with psychotic disorders in an urban psychiatry clinic in Atlanta, Georgia (n = 860). Each antipsychotic group was compared to a group of patients from the same sample who were not on any antipsychotic, and logistic regression models were constructed for each comorbidity. Ziprasidone was associated with diabetes (aOR 2.56, 95% CI 1.03-6.38) and obesity (aOR 3.19, 95% CI 1.37-7.41). Aripiprazole was associated with obesity (aOR 2.39, 95% CI 1.27-4.51). Clozapine was associated with GERD (aOR 3.59, 95% CI 1.11-11.61), movement disorders (aOR 4.44, 95% CI 1.02-19.32), and arrythmias (4.89, 95% CI 1.44-16.64). Two antipsychotics that are considered weight neutral, ziprasidone and aripiprazole, were associated with cardiometabolic comorbidities. This study suggests that research is warranted to study the association between antipsychotics, medical comorbidity, and psychotic symptom burden.

Impact of the COVID-19 pandemic on total, sex- and age-specific all-cause mortality in 20 countries worldwide during 2020: results from the C-MOR project.

BACKGROUND: To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. METHODS: Total, sex- and age-specific weekly all-cause mortality for 2015-2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015-2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. RESULTS: Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. CONCLUSIONS: This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies.

Protocol for a feasibility study of a cancer symptom awareness campaign to support the rapid diagnostic centre referral pathway in a socioeconomically deprived area: Targeted Intensive Community-based campaign To Optimise Cancer awareness (TIC-TOC).

INTRODUCTION: Rapid diagnostic centres (RDCs) are being implemented across the UK to accelerate the assessment of vague suspected cancer symptoms. Targeted behavioural interventions are needed to augment RDCs that serve socioeconomically deprived populations who are disproportionately affected by cancer, have lower cancer symptom awareness and are less likely to seek help for cancer symptoms. The aim of this study is to assess the feasibility and acceptability of delivering and evaluating a community-based vague cancer symptom awareness intervention in an area of high socioeconomic deprivation. METHODS AND ANALYSIS: Intervention materials and messages were coproduced with local stakeholders in Cwm Taf Morgannwg, Wales. Cancer champions will be trained to deliver intervention messages and distribute intervention materials using broadcast media (eg, local radio), printed media (eg, branded pharmacy bags, posters, leaflets), social media (eg, Facebook) and attending local community events. A cross-sectional questionnaire will include self-reported patient interval (time between noticing symptoms to contacting the general practitioner), cancer symptom recognition, cancer beliefs and barriers to presentation, awareness of campaign messages, healthcare resource use, generic quality of life and individual and area-level deprivation indicators. Consent rates and proportion of missing data for patient questionnaires (n=189) attending RDCs will be measured. Qualitative interviews and focus groups will assess intervention acceptability and barriers/facilitators to delivery. ETHICS AND DISSEMINATION: Ethical approval for this study was given by the London-West London & GTAC Research Ethics (21/LO/0402). This project will inform a potential future controlled study to assess intervention effectiveness in reducing the patient interval for vague cancer symptoms. The results will be critical to informing national policy and practice regarding behavioural interventions to support RDCs in highly deprived populations.

Corynebacterium accolens inhibits Staphylococcus aureus induced mucosal barrier disruption.

Background: Corynebacterium accolens (C. accolens) is a common nasal colonizer, whereas Staphylococcus aureus (S. aureus) is typically regarded a pathogenic organism in patients with chronic rhinosinusitis (CRS). This study aims to evaluate the interaction of the two bacteria in vitro. Methods: Clinical isolates of C. accolens and S. aureus from sinonasal swabs, as well as primary human nasal epithelial cells (HNECs) cultured from cellular brushings of both healthy and CRS patients were used for this study. The cell-free culture supernatants of all isolates grown alone and in co-cultures were tested for their effects on transepithelial electrical resistance (TER), FITC-Dextran permeability, lactate dehydrogenase (LDH), and IL-6 and IL-8 secretion of HNECs. Confocal scanning laser microscopy and immunofluorescence were also used to visualize the apical junctional complexes. C. accolens cell-free culture supernatants were also tested for antimicrobial activity and growth on planktonic and biofilm S. aureus growth. Results: The cell-free culture supernatants of 3\C. accolens strains (at 60% for S. aureus reference strain and 30% concentration for S. aureus clinical strains) inhibited the growth of both the planktonic S. aureus reference and clinical strains significantly. The C. accolens cell-free culture supernatants caused no change in the TER or FITC-Dextran permeability of the HNEC-ALI cultures, while the cell-free culture supernatants of S. aureus strains had a detrimental effect. Cell-free culture supernatants of C. accolens co-cultured with both the clinical and reference strains of S. aureus delayed the S. aureus-dependent mucosal barrier damage in a dose-dependent manner. Conclusion: Corynebacterium accolens cell-free culture supernatants appear to inhibit the growth of the S. aureus planktonic bacteria, and may reduce the mucosal barrier damage caused by S. aureus.

Proteomic examination of Cornus officinalis stimulated 1.1B4 human pancreatic cells reveals activation of autophagy and Keap1/Nrf2 pathway.

Type 1 diabetes (T1D) is an autoimmune disease initiated by genetic predisposition and environmental influences culminating in the immunologically mediated destruction of pancreatic ß-cells with eventual loss of insulin production. Although T1D can be accurately predicted via autoantibodies, therapies are lacking that can intercede autoimmunity and protect pancreatic ß-cells. There are no approved interventional modalities established for this purpose. One such potential source for clinical agents of this use is from the frequently utilized Cornus officinalis (CO) in the field of ethnopharmacology. Studies by our lab and others have demonstrated that CO has robust proliferative, metabolic, and cytokine protective effects on pancreatic ß-cells. To identify the molecular mechanism of the biological effects of CO, we performed a proteomic and phosphoproteomic analysis examining the cellular networks impacted by CO application on the 1.1B4 pancreatic ß-cell line. Our label-free mass spectrometry approach has demonstrated significant increased phosphorylation of the selective autophagy receptor of p62 (Sequestosome-1/SQSTM1/p62) and predicted activation of the antioxidant Kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor-erythroid factor 2-related factor 2 (Nrf2) pathway. Further validation by immunoblotting and immunofluorescence revealed markers of autophagy such as increased LC3-II and decreased total p62 along with nuclear localization of Nrf2. Both autophagy and the Keap1/Nrf2 pathways have been shown to be impaired in human and animal models of T1D and may serve as an excellent potential therapeutic target stimulated by CO.

Prevalence of chronic non-communicable diseases in Ethiopia: A systematic review and meta-analysis of evidence.

Background: Non-communicable diseases (NCDs) are a growing global health challenge disproportionately impacting low- and middle-income settings, including Ethiopia. Currently, the body of evidence describing the burden of NCDs is fragmented, inconsistent, health facility- or institution-based, and out-dated in Ethiopia. We conducted a systematic review of the literature and meta-analysis of the prevalence of NCDs in community settings in Ethiopia. Review methodology: Community-based quantitative studies published in English between January 1st, 2012, and June 30th, 2022, that reported on the prevalence of NCDs in Ethiopia were included. A systematic search of Medline, Embase, Scopus, CINAHL, and Global Health using pretested search terms related to NCDs was conducted, and data were extracted using a piloted data extraction proforma adapted from the Joanna Briggs Institute tool. Meta-analysis was performed using Stata 16. While the pooled prevalence of Diabetes Mellitus (DM) and undiagnosed (DM) was computed and presented using forest plots, then overall prevalence of NCDs and other various types of NCDs were narratively synthesized. I 2 was used to assess heterogeneity. Studies that did not fulfill the criteria (used similar tool to measure the types of NCDs) for meta-analysis were narratively synthesized. Results: Twenty-two studies met the inclusion criteria. Five studies measured the prevalence of NCDs (all NCDs together), ranging from 29 to 35% (prevalence estimates not pooled). The pooled prevalence of Diabetes Mellitus (DM) across ten studies was 5% (95% CI: 4-7%). Three studies each reported on the prevalence of undiagnosed DM (pooled prevalence 5%, 95% CI: 4-7%) and pre-DM (pooled prevalence 7%, 95% CI: 3-14%%). In a narrative analysis the prevalence of cardiovascular conditions ranged from 13.4 to 32.2% (n = 3 studies), cancer mortality ranged from 4 to 18% (n = 3 studies) and respiratory conditions ranged from 1 to 18% (n = 3 studies). Some studies have determined more than one NCDs and that is why the total number of studies are exceeding more than twenty studies. Conclusion and recommendations: Our analysis found that approximately one-third of Ethiopians have an NCD, with cardiovascular diseases the most common of all NCDs. The prevalence of respiratory conditions also appears high, but there are insufficient data for a pooled estimate. Whilst the prevalence of DM appears relatively low, there is evidence that the magnitude is increasing. Public health actions to address the high burden of cardiovascular and respiratory diseases, as well as the increasing magnitude of DM in Ethiopia, must be prioritized. Systematic review registration: PROSPERO [CRD42020196815].

Molecular Epidemiology of Penicillin-Susceptible Staphylococcus aureus Bacteremia in Australia and Reliability of Diagnostic Phenotypic Susceptibility Methods to Detect Penicillin Susceptibility.

BACKGROUND: Defined by the emergence of antibiotic resistant strains, Staphylococcus aureus is a priority bacterial species with high antibiotic resistance. However, a rise in the prevalence of penicillin-susceptible S. aureus (PSSA) bloodstream infections has recently been observed worldwide, including in Australia, where the proportion of methicillin-susceptible S. aureus causing bacteremia identified phenotypically as penicillin-susceptible has increased by over 35%, from 17.5% in 2013 to 23.7% in 2020. OBJECTIVES: To determine the population structure of PSSA causing community- and hospital-onset bacteremia in Australia and to evaluate routine phenotypic antimicrobial susceptibility methods to reliably confirm penicillin resistance on blaZ-positive S. aureus initially classified as penicillin-susceptible by the Vitek® 2 automated microbiology system. RESULTS: Whole genome sequencing on 470 PSSA collected in the 2020 Australian Group on Antimicrobial Resistance Australian Staphylococcus aureus Sepsis Outcome Programme identified 84 multilocus sequence types (STs), of which 79 (463 isolates) were grouped into 22 clonal complexes (CCs). The dominant CCs included CC5 (31.9%), CC97 (10.2%), CC45 (10.0%), CC15 (8.7%), and CC188 (4.9%). Many of the CCs had multiple STs and spa types and, based on the immune evasion cluster type, isolates within a CC could be classified into different strains harboring a range of virulence and resistance genes. Phylogenetic analyses of the isolates showed most CCs were represented by one clade. The blaZ gene was identified in 45 (9.6%) PSSA. Although multiclonal, approximately 50% of blaZ-positive PSSA were from CC15 and were found to be genetically distant from the blaZ-negative CC15 PSSA. The broth microdilution, Etest® and cefinase, performed poorly; however, when the appearance of the zone edge was considered; as per the EUCAST and CLSI criteria, disc diffusion detected 100% of blaZ-positive PSSA. CONCLUSIONS: In Australia, PSSA bacteremia is not caused by the expansion of a single clone. Approximately 10% of S. aureus classified as penicillin-susceptible by the Vitek® 2 harbored blaZ. Consequently, we recommend that confirmation of Vitek® 2 PSSA be performed using an alternative method, such as disc diffusion with careful interpretation of the zone edge.