Is timing and extended prophylaxis with antibiotics to prevent surgical-site infections still a concern across Africa? Findings and implications

Background and Objectives: Increasing inappropriate prescribing of antimicrobials increases antimicrobial resistance (AMR) - a growing concern across sub-Saharan Africa (SSA). A key area is healthcare-associated infections (HAIs) with their subsequent impact on morbidity, mortality and costs. Major issues include the timing and extended use of antibiotics to prevent surgical site infections (SSIs), with studies across SSA documenting concerns with these two issues, increasing adverse drug reactions, AMR and costs. Successful initiatives can improve future antibiotic use in low- and middle-income countries (LMICs), particularly in SSA. Consequently, a need to document the timing and duration of surgical antibiotic prophylaxis (SAP) among SSA countries together with potential ways forward. Methods: A narrative review of submitted and published studies among SSA countries coupled with studies across LMICs documenting successful approaches to improve SAP. Results: Inappropriate prescribing of antibiotics for SAP is common in SSA. In Botswana, a study showed only 15% of surgical patients received antibiotics pre-operatively, 58.3% post-surgery, and 26.8% were not prescribed any antibiotic. In Ethiopia, 62.2% of patients received SAP longer than one hour pre-operatively, and in Nigeria, between 57.6% and 83.5% of patients were not administered their first antibiotic dose within the 60-minute window. In Nigeria, 98.7% of patients in one study and all patients in another were given prophylaxis for more than one day with a mean of 8.7 days, and in Botswana extended prophylaxis was common in one study with a mean (SD) of 5 (2.6) days. In a point prevalence survey (PPS) in Botswana, extended prophylaxis was also common, i.e. 100% of tertiary- and primary hospitals, with similar high rates in Ethiopia (88.9%), Ghana (69% to 77%), Kenya (100% in neurotrauma patients) and Rwanda (92%). In recent PPS studies in Nigeria and South Africa, 76.2% and 73.2% patients respectively received SAP for longer than 24 hours. Multiple approaches have been used across LMICs to improve SAP, including educational initiatives and audits. Studies have shown such initiatives improve the timing and duration of antibiotic use and reduce costs. In one study, timing and appropriateness of antibiotics improved from 30.1% to 91.4%, prolonged duration reduced from 92.1% to 5.7% and mean antibiotic costs decreased eleven-fold. Other studies have also shown appreciable improvements. Conclusion: There are considerable concerns with the timing and duration of SAP across Africa. Multiple interventions, including effective guidelines, education and audit, can reverse this and provide future direction to reduce AMR and costs

Antibiotic use and stewardship indicators in the first- and 2 second-level hospitals in Zambia : findings and implications 3 for the future

There are increasing concerns with growing rates of antimicrobial resistance (AMR) across Africa including Zambia, enhanced by inappropriate utilization of antibiotics across the sectors. There is a need in hospitals to document current prescribing patterns via point prevalence surveys (PPS) alongside recognized indicators to improve future use. The findings can subsequently be used to develop and instigate appropriate antimicrobial stewardship programs (ASPs) to improve the quality of future antimicrobial prescribing across Zambia. This includes encouraging the pre-scribing of 'Access' over 'Watch' and 'Reserve’ antibiotics where pertinent. Methods: A PPS was undertaken using the WHO methodology among ten first- and second-level public hospitals across the ten provinces of Zambia. A sampling process was used to select the hospitals. Results: The prevalence of antibiotic use among the in-patients was 307/520 (59.0%), with a high rate of empiric prescribing of ceftriaxone at 36.1% of all antibiotics prescribed (193/534). The reason for antibiotic use was recorded in only 15.7% of occasions and directed treatment prescribed in only 3.0% of occasions. Compliance with national Standard Treatment Guidelines (STGs) was also low at only 27.0% of occasions. Conclusion: High empiric prescribing, limited documentation of the rationale behind antibiotic prescribing, high use of ‘Watch’ antibiotics, and limited compliance to STGs among surveyed hospitals require the urgent instigation of ASPs across Zambia to improve future prescribing

African countries are working together to enhance medicine use

Growing burden of infectious and NCDs across Africa, e.g. 70% of world’s HIV patients live in sub-Sahara Africa and 30 to 45% of adults have hypertension. This requires groups to collaborate. This is happening, e.g. SAHTAS, PharfA and MURIA. MURIA is researching antibiotic use, adherence to medicines and strengthening DTCs. This should continue to optimise medicine use and scarce resources. The socioeconomic burden of diseases is increasing in Africa. For instance in 2011, 70% of the world’s HIV population resided in sub-Sahara Africa. There are also growing rates of AMR, which necessitates newer more expensive antibiotics adding to costs. There is also a growing burden of NCDs, 3 out of 4 patients with hypertension currently live in LMICs, with prevalence rates up to 30% to 45% among adults in Africa. Alongside this, up to 70% of total healthcare expenditure is spent on medicines in LMICs; much of this out-of-pocket. Consequently, an urgent need to strengthen collaborative research to improve medicine use. Summary of groups working together in Africa including the Medicines Utilisation Research in Africa (MURIA) group. African Strategies for Health identifies and advocates best practices, as well as works with others to develop sustainable solutions. Pharmacology for Africa (PharfA) organises and promotes pharmacology on the African continent, including research in clinical pharmacology, alongside the IUPHAR sub-division. ISPOR Africa co-ordinates activities from the different African country chapters. SAHTAS is a scientific and professional society for all those who produce, use, or encounter HTA in Southern Africa, and WHO International and Regional groups are improving antibiotic drug utilisation capabilities in Africa. The MURIA group was established in 2015 [1]. Ongoing collaborative research includes (i) initiatives to optimise antibiotic use; (ii) methods to enhance adherence to anti-infective prescribing guidance, (iii) approaches to improve adherence to HIV and NCDs; (iv) researching current anti-hypertensive and anti-diabetes medicines utilisation patterns and knowledge; (v) approaches to enhance DTC activities, and (vi) strengthening medicine utilisation capabilities [2,3]. These activities have already strengthened research ties across Africa. A number of groups are already working across Africa to enhance appropriate medicine use, and should continue. Ongoing MURIA activities include antibiotic point-prevalence studies, ongoing research into infectious diseases, NCDs and DTCs including adherence as well as the third workshop and symposium in Namibia in 2017

Cognitive Profiles and Education of Female Cyber Defence Operators

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The Rat Genome Database (RGD): developments towards a phenome database

The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms

Awareness and acceptance of COVID-19 vaccines and associated factors among pharmacy students in Zambia

Background: Several vaccines have been developed and administered since coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020. In April 2021, the authorities in Zambia administered the first doses of the Oxford-AstraZeneca® COVID-19 vaccine. Objective: To assess the awareness and acceptance of COVID-19 vaccines and associated factors among pharmacy students in Zambia. Methods: A cross-sectional study among 326 undergraduate pharmacy students in Lusaka, Zambia, from February through to 25 April 2021. Data were analysed using Stata version 16.1. Multivariable logistic regression was used to determine factors influencing vaccine acceptance. Results: Of the 326 participants, 98.8% were aware of the COVID-19 vaccines, but only 24.5% would accept vaccination. Being of Christian faith was associated with reduced odds of awareness of the COVID-19 vaccine (aOR=0.01; 95% CI: 0.01-0.20). Compared to females, male respondents were 86% more likely to accept the vaccine if it was made available (aOR=1.86; 95% CI: 1.10-3.14). Unmarried compared to married respondents were 2.65 times as likely to accept vaccination (aOR=2.65; 95% CI: 1.06-6.63) whilst unemployed respondents were less likely to accept vaccination (aOR=0.32; 95% CI: 0.16-0.46). Barriers to the acceptability of the vaccine were possible side effects (78.5%) and scepticism about its effectiveness to prevent COVID-19 (10.2%). Conclusion: There was significant vaccine hesitancy toward COVID-19 vaccines among Zambian pharmacy students despite their awareness of the vaccines. Health authorities must work collaboratively with training institutions to mitigate vaccine hesitancy, especially with healthcare students being a key part of the future healthcare workforce overseeing disease prevention strategies

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Safe vs. Fair: A formidable trade-off in tackling climate change

Global warming requires a response characterized by forward-looking management of atmospheric carbon and respect for ethical principles. Both safety and fairness must be pursued, and there are severe trade-offs as these are intertwined by the limited headroom for additional atmospheric CO2 emissions. This paper provides a simple numerical mapping at the aggregated level of developed vs. developing countries in which safety and fairness are formulated in terms of cumulative emissions and cumulative per capita emissions respectively. It becomes evident that safety and fairness cannot be achieved simultaneously for strict definitions of both. The paper further posits potential global trading in future cumulative emissions budgets in a world where financial transactions compensate for physical emissions: the safe vs. fair tradeoff is less severe but remains formidable. Finally, we explore very large deployment of engineered carbon sinks and show that roughly 1,000 Gt CO2 of cumulative negative emissions over the century are required to have a significant effect, a remarkable scale of deployment. We also identify the unexplored issue of how such sinks might be treated in sub-global carbon accounting

Ongoing strategies to improve the management of upper respiratory tract infections and reduce inappropriate antibiotic use particularly among lower and middle-income countries: findings and implications for the future

Introduction: Antibiotics are indispensable to maintaining human health; however, their overuse has resulted in resistant organisms, increasing morbidity, mortality and costs. Increasing antimicrobial resistance (AMR) is a major public health threat, resulting in multiple campaigns across countries to improve appropriate antimicrobial use. This includes addressing the overuse of antimicrobials for self-limiting infections, such as upper respiratory tract infections (URTIs), particularly in lower- and middle-income countries (LMICs) where there is the greatest inappropriate use and where antibiotic utilization has increased the most in recent years. Consequently, there is a need to document current practices and successful initiatives in LMICs to improve future antimicrobial use. Methodology: Documentation of current epidemiology and management of URTIs, particularly in LMICs, as well as campaigns to improve future antimicrobial use and their influence where known. Results: Much concern remains regarding the prescribing and dispensing of antibiotics for URTIs among LMICs. This includes considerable self-purchasing, up to 100% of pharmacies in some LMICs. However, multiple activities are now ongoing to improve future use. These incorporate educational initiatives among all key stakeholder groups, as well as legislation and other activities to reduce self-purchasing as part of National Action Plans (NAPs). Further activities are still needed however. These include increased physician and pharmacist education, starting in medical and pharmacy schools; greater monitoring of prescribing and dispensing practices, including the development of pertinent quality indicators; and targeted patient information and health education campaigns. It is recognized that such activities are more challenging in LMICs given more limited resources and a lack of healthcare professionals. Conclusion: Initiatives will grow across LMICs to reduce inappropriate prescribing and dispensing of antimicrobials for URTIs as part of NAPs and other activities, and these will be monitored