COVID-19 surveillance in Democratic Republic of Congo, Nigeria, Senegal and Uganda: strengths, weaknesses and key Lessons.

INTRODUCTION: As part of efforts to rapidly identify and care for individuals with COVID-19, trace and quarantine contacts, and monitor disease trends over time, most African countries implemented interventions to strengthen their existing disease surveillance systems. This research describes the strengths, weaknesses and lessons learnt from the COVID-19 surveillance strategies implemented in four African countries to inform the enhancement of surveillance systems for future epidemics on the continent. METHODS: The four countries namely the Democratic Republic of Congo (DRC), Nigeria, Senegal, and Uganda, were selected based on their variability in COVID-19 response and representation of Francophone and Anglophone countries. A mixed-methods observational study was conducted including desk review and key informant interviews, to document best practices, gaps, and innovations in surveillance at the national, sub-national, health facilities, and community levels, and these learnings were synthesized across the countries. RESULTS: Surveillance approaches across countries included - case investigation, contact tracing, community-based, laboratory-based sentinel, serological, telephone hotlines, and genomic sequencing surveillance. As the COVID-19 pandemic progressed, the health systems moved from aggressive testing and contact tracing to detect virus and triage individual contacts into quarantine and confirmed cases, isolation and clinical care. Surveillance, including case definitions, changed from contact tracing of all contacts of confirmed cases to only symptomatic contacts and travelers. All countries reported inadequate staffing, staff capacity gaps and lack of full integration of data sources. All four countries under study improved data management and surveillance capacity by training health workers and increasing resources for laboratories, but the disease burden was under-detected. Decentralizing surveillance to enable swifter implementation of targeted public health measures at the subnational level was a challenge. There were also gaps in genomic and postmortem surveillance including community level sero-prevalence studies, as well as digital technologies to provide more timely and accurate surveillance data. CONCLUSION: All the four countries demonstrated a prompt public health surveillance response and adopted similar approaches to surveillance with some adaptations as the pandemic progresses. There is need for investments to enhance surveillance approaches and systems including decentralizing surveillance to the subnational and community levels, strengthening capabilities for genomic surveillance and use of digital technologies, among others. Investing in health worker capacity, ensuring data quality and availability and improving ability to transmit surveillance data between and across multiple levels of the health care system is also critical. Countries need to take immediate action in strengthening their surveillance systems to better prepare for the next major disease outbreak and pandemic.

Application of estimand framework in ICH E9 (R1) to safety evaluation.

Defining the right question of interest is important to a clinical study. ICH E9 (R1) introduces the framework of an estimand and its five attributes, which provide a basis for connecting different components of a study with its clinical questions. Most of the applications of the estimand framework focus on efficacy instead of safety assessment. In this paper, we expand the estimand framework into the safety evaluation and compare/contrast the similarity and differences between safety and efficacy estimand. Furthermore, we present and discuss applications of a safety estimand to oncology trials and pooled data analyses. At last, we also discuss the potential usage of safety estimand to handle the impacts of COVID-19 pandemic on safety assessment.

SARS-CoV-2 primary and breakthrough infections in patients with cancer: Implications for patient care.

Initial reports of SARS-CoV-2 caused COVID-19 suggested that patients with malignant diseases were at increased risk for infection and its severe consequences. In order to provide early United States population-based assessments of SARS-CoV-2 primary infections in unvaccinated patients with hematologic malignancies or cancer, and SARS-CoV-2 breakthrough infections in vaccinated patients with hematologic malignancies or cancer, we conducted retrospective studies using two, unique nationwide electronic health records (EHR) databases. Using these massive databases to provide highly statistically significant data, our studies demonstrated that, compared to patients without malignancies, risk for COVID-19 was increased in patients with all cancers and with all hematologic malignancies. Risks varied with specific types of malignancy. Patients with hematologic malignancies or cancer were at greatest risk for COVID-19 during the first year after diagnosis. Risk for infection was increased for patients 65 years and older, compared to younger patients and among Black patients compared to white patients. When patients with hematologic malignancies or cancer were vaccinated against SARS-CoV-2, their risk for breakthrough infections was decreased relative to primary infections but remained elevated relative to vaccinated patients without malignancies. Compared to vaccinated patients without malignancies, vaccinated patients with hematologic malignancy or cancer showed increased risk for infection at earlier post vaccination time points. As with primary infections, risk for breakthrough infections was greatest in patients during their first year of hematologic malignancy or cancer. There were no signs of racial disparities among vaccinated patients with hematologic malignancies or cancer. These results provide the population basis to understand the significance of subsequent immunologic studies showing relative defective and delayed immunoresponsiveness to SARS-CoV-2 vaccines among patients with hematologic malignancies and cancers. These studies further provide the basis for recommendations regarding COVID-19 vaccination, vigilance and maintaining mitigation strategies in patients with hematologic malignancies and cancers.

Interventions for Maintenance of Essential Health Service Delivery during the COVID-19 Response in Uganda, between March 2020 and April 2021.

INTRODUCTION: The COVID-19 pandemic overwhelmed health systems globally and affected the delivery of health services. We conducted a study in Uganda to describe the interventions adopted to maintain the delivery of other health services. METHODS: We reviewed documents and interviewed 21 key informants. Thematic analysis was conducted to identify themes using the World Health Organization health system building blocks as a guiding framework. RESULTS: Governance strategies included the establishment of coordination committees and the development and dissemination of guidelines. Infrastructure and commodity strategies included the review of drug supply plans and allowing emergency orders. Workforce strategies included the provision of infection prevention and control equipment, recruitment and provision of incentives. Service delivery modifications included the designation of facilities for COVID-19 management, patient self-management, dispensing drugs for longer periods and the leveraging community patient networks to distribute medicines. However, multi-month drug dispensing led to drug stock-outs while community drug distribution was associated with stigma. CONCLUSIONS: Health service maintenance during emergencies requires coordination to harness existing health system investments. The essential services continuity committee coordinated efforts to maintain services and should remain a critical element of emergency response. Self-management and leveraging patient networks should address stigma to support service continuity in similar settings and strengthen service delivery beyond the pandemic.

SARS-CoV-2 primary and breakthrough infections in patients with cancer: Implications for patient care

Initial reports of SARS-CoV-2 caused COVID-19 suggested that patients with malignant diseases were at increased risk for infection and its severe consequences. In order to provide early United States population-based assessments of SARS-CoV-2 primary infections in unvaccinated patients with hematologic malignancies or cancer, and SARS-CoV-2 breakthrough infections in vaccinated patients with hematologic malignancies or cancer, we conducted retrospective studies using two, unique nationwide electronic health records (EHR) databases. Using these massive databases to provide highly statistically significant data, our studies demonstrated that, compared to patients without malignancies, risk for COVID-19 was increased in patients with all cancers and with all hematologic malignancies. Risks varied with specific types of malignancy. Patients with hematologic malignancies or cancer were at greatest risk for COVID-19 during the first year after diagnosis. Risk for infection was increased for patients 65 years and older, compared to younger patients and among Black patients compared to white patients. When patients with hematologic malignancies or cancer were vaccinated against SARS-CoV-2, their risk for breakthrough infections was decreased relative to primary infections but remained elevated relative to vaccinated patients without malignancies. Compared to vaccinated patients without malignancies, vaccinated patients with hematologic malignancy or cancer showed increased risk for infection at earlier post vaccination time points. As with primary infections, risk for breakthrough infections was greatest in patients during their first year of hematologic malignancy or cancer. There were no signs of racial disparities among vaccinated patients with hematologic malignancies or cancer. These results provide the population basis to understand the significance of subsequent immunologic studies showing relative defective and delayed immunoresponsiveness to SARS-CoV-2 vaccines among patients with hematologic malignancies and cancers. These studies further provide the basis for recommendations regarding COVID-19 vaccination, vigilance and maintaining mitigation strategies in patients with hematologic malignancies and cancers.

A Free-Market Environmentalist Enquiry on Spain's Energy Transition along with Its Recent Increasing Electricity Prices.

This paper analyzes the Spanish energy transition's general situation and its increasing electricity prices in recent years from a free-market environmentalist (FME) approach. We hypothesize and argue that high taxes, high government subsidies, and government industrial access restrictions breach private property rights, hindering Spain's renewable energy (RE) development. Our paper discovers that Spain's state-interventionist policies have increased the cost of the energy and power industries, leading to electricity prices remaining relatively high before and after the outbreak of the COVID-19 pandemic. After reviewing the literature on the FME approach and Spain's case, a Box-Jenkins (ARIMA) model is used to clarify the economic performance of the Spanish electricity industry with a proposal for forecasting electricity prices. It is observed that Spain fails the EU and its national goal of providing an affordable energy price as a part of the green energy transition. Finally, free-market environmental solutions and policy reforms are proposed to facilitate Spain's energy transition.

Applying Kern's Six Steps to the Development of a Community-Engaged, Just-in-Time, Interdisciplinary COVID-19 Curriculum.

Universities and medical schools often work towards operationalizing their shared mission of facilitating community-engaged work independently. Based on their experience teaching the COVID-19 Elective course at Stanford University School of Medicine, the authors proposed a novel solution for universities and medical schools to achieve an interdisciplinary collaboration within a diverse student population by creating targeted, project-based, and community-engaged courses for addressing emergent health needs. In this article, the authors discuss their curriculum, which was created using Kern's six-step approach for curriculum development, to address emergent health needs related to the novel coronavirus pandemic. The curriculum provides an opportunity for universities and medical schools to advance community health, educate students across the medical and non-medical education continuum, and foster interdisciplinary cooperation.

Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Mortality in Vaccinated Patients With Cancer in the US Between December 2020 and November 2021.

Importance: Limited data have been presented to examine breakthrough SARS-CoV-2 infections, hospitalizations, and mortality in vaccinated patients with cancer in the US. Objectives: To examine the risk of breakthrough SARS-CoV-2 infection, hospitalizations, and mortality in vaccinated patients with cancer between December 2020 and November 2021. Design, Setting, and Participants: Retrospective cohort study of electronic health records (EHRs) of vaccinated patients from a multicenter and nationwide database in the US during the period of December 2020 through November 2021. The study population comprised patients who had documented evidence of vaccination (2 doses of Moderna or Pfizer-BioNTech or single dose of Janssen/Johnson & Johnson vaccines) in their EHRs from December 2020 to November 2021 and had no SARS-CoV-2 infection prior to vaccination. Exposures: The 12 most common cancers combined and separately; recent vs no recent encounter for cancer; and breakthrough SARS-CoV-2 infection. Main Outcomes and Measures: Time trends of incidence proportions of breakthrough SARS-CoV-2 infections from December 2020 to November 2021 in vaccinated patients with all cancer; cumulative risks of breakthrough infections in vaccinated patients for all cancer and 12 common cancer types; hazard ratios (HRs) and 95% CIs of breakthrough infections between propensity score-matched patients with vs without cancer and between propensity score-matched patients with cancer who had a recent medical encounter for cancer vs those who did not; overall risks, HRs, and 95% CIs of hospitalizations and mortality in patients with cancer who had breakthrough infections vs those who did not. Results: Among 45 253 vaccinated patients with cancer (mean [SD] age, 68.7 [12.4] years), 53.5% were female, 3.8% were Asian individuals, 15.4% were Black individuals, 4.9% were Hispanic individuals, and 74.1% were White individuals. Breakthrough SARS-CoV-2 infections in patients with cancer increased from December 2020 to November 2021 and reached 52.1 new cases per 1000 persons in November 2021. The cumulative risk of breakthrough infections in patients with all cancer was 13.6%, with highest risk for pancreatic (24.7%), liver (22.8%), lung (20.4%), and colorectal (17.5%) cancers, and lowest risk for thyroid (10.3%), endometrial (11.9%), and breast (11.9%) cancers, vs 4.9% in the noncancer population (P < .001). Patients with cancer had significantly increased risk for breakthrough infections vs patients without cancer (HR, 1.24; 95% CI, 1.19-1.29), with greatest risk for liver (HR, 1.78; 95% CI, 1.38-2.29), lung (HR, 1.73; 95% CI, 1.50-1.99), pancreatic (HR, 1.64; 95% CI, 1.24-2.18), and colorectal (HR, 1.53; 95% CI, 1.32-1.77) cancers and lowest risk for thyroid (HR, 1.07; 95% CI, 0.88-1.30) and skin (HR, 1.17; 95% CI, 0.99-1.38) cancers. Patients who had medical encounters for cancer within the past year had higher risk for breakthrough infections than those who did not (HR, 1.24; 95% CI, 1.18-1.31). Among patients with cancer, the overall risk for hospitalizations and mortality was 31.6% and 3.9%, respectively, in patients with breakthrough infections, vs 6.7% and 1.3% in those without breakthrough infections (HR for hospitalization: 13.48; 95% CI, 11.42-15.91; HR for mortality: 6.76; 95% CI, 4.97-9.20). Conclusions and Relevance: This cohort study showed significantly increased risks for breakthrough infection in vaccinated patients with cancer, especially those undergoing active cancer care, with marked heterogeneity among specific cancer types. Breakthrough infections in patients with cancer were associated with significant and substantial risks for hospitalizations and mortality.

Therapeutic plant landscape design of urban forest parks based on the five senses theory: A case study of Stanley Park in Canada

As an important part of urban development, urban forest parks (UFPs) are critical community resources for supporting physical activity of people of all ages, and are also crucial for connecting people to nature, specifically for mental health benefits. During the COVID-19 pandemic, urban parks have experienced exponential increases in the volume of users as people have sought ways to enjoy green spaces and their benefits safely. As the park environment provides a pleasant, healthy and comfortable atmosphere for people of all ages, UFPs have a vital impact on human health, which has been recognized and recognized by more and more people all over the world.. The five senses, seeing, hearing, touching, smelling, and tasting, are the most direct ways that humans perceive external information and assess experiences. Notably, Canada has a strong presence in and a long history of designing and conserving UFPs. Therefore, we used Stanley Park in Canada as a case study to analyze the therapeutic functions of and design methods for plant landscape in UFPs. We conducted an on-site survey of tourists to investigate their perception, level of satisfaction, possible inadequacies, and suggestions regarding potential therapeutic plants in Stanley Park. The results show that the high plant diversity in the park has created a functional therapeutic landscape that can be perceived by the five senses. The overall satisfaction level of visitors and their dependency on these therapeutic landscape components are high. The inadequacies are relatively simple vegetation structure and lack of wetland plants. The plant species in Stanley Park were categorized according to their sensory influences. Based on the survey results and the literature, we have provided feasible recommendations for the design and management of therapeutic landscapes in UFPs.

Polymersomes as Stable Nanocarriers for a Highly Immunogenic and Durable SARS-CoV-2 Spike Protein Subunit Vaccine.

Multiple successful vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to address the ongoing coronavirus disease 2019 (Covid-19) pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein coadministered with CpG adjuvant. To enhance the immunogenicity of our formulation, both antigen and adjuvant were encapsulated with our proprietary artificial cell membrane (ACM) polymersome technology. Structurally, ACM polymersomes are self-assembling nanoscale vesicles made up of an amphiphilic block copolymer comprising poly(butadiene)-b-poly(ethylene glycol) and a cationic lipid, 1,2-dioleoyl-3-trimethylammonium-propane. Functionally, ACM polymersomes serve as delivery vehicles that are efficiently taken up by dendritic cells (DC1 and DC2), which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing antibody titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of functional memory CD4+ and CD8+ T cells that produce T helper type 1 cytokines. This study is an important step toward the development of an efficacious vaccine in humans.

A Free-Market Environmentalist Transition toward Renewable Energy: The Cases of Germany, Denmark, and the United Kingdom

Renewable energy (RE) is one of the most popular public policy orientations worldwide. Compared to some other countries and continents, Europe has gained an early awareness of energy and environmental problems in general. At the theoretical level, free-market environmentalism indicates that based on the principle of private property rights, with fewer state interventionist and regulation policies, entrepreneurs, as the driving force of the market economy, can provide better services to meet the necessity of offering RE to protect the environment more effectively. Previous studies have revealed that Germany, Denmark, and the United Kingdom have made some progress in using the market to develop RE. However, this research did not analyze the three countries’ RE conditions from the perspective of free-market environmentalism. Based on our review of the principles of free-market environmentalism, this paper originally provides an empirical study of how Germany, Denmark, and the United Kingdom have partly conducted free-market-oriented policies to successfully achieve their policy goal of RE since the 1990s on a practical level. In particular, compared with Germany and Denmark, the UK has maintained a relatively low energy tax rate and opted for more pro-market measures since the Hayekian-Thatcherism free-market reform of 1979. The paper also discovers that Fredrich A. Hayek’s theories have strongly impacted its energy liberalization reform agenda since then. Low taxes on the energy industry and electricity have alleviated the burden on the electricity enterprises and consumers in the UK. Moreover, the empirical results above show that the energy enterprises play essential roles in providing better and more affordable RE for household and industrial users in the three sampled countries. Based on the above results, the paper also warns that state intervention policies such as taxation, state subsidies, and industrial access restrictions can impede these three countries’ RE targets. Additionally, our research provides reform agendas and policy suggestions to policymakers on the importance of implementing free-market environmentalism to provide more efficient RE in the post-COVID-19 era.

Next generation vaccine platform: polymersomes as stable nanocarriers for a highly immunogenic and durable SARS-CoV-2 spike protein subunit vaccine (preprint)

Multiple successful vaccines against SARS-CoV-2 are urgently needed to address the ongoing Covid-19 pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein co-administered with CpG adjuvant. To enhance the immunogenicity of our formulation, both antigen and adjuvant were encapsulated with our proprietary artificial cell membrane (ACM) polymersome technology. Structurally, ACM polymersomes are self-assembling nanoscale vesicles made up of an amphiphilic block copolymer comprising of polybutadiene-b-polyethylene glycol and a cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane. Functionally, ACM polymersomes serve as delivery vehicles that are efficiently taken up by dendritic cells, which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of memory CD4+ and CD8+ T cells that produce Th1 cytokines. This study is an important step towards the development of an efficacious vaccine in humans.

The Outcome and Implications of Public Precautionary Measures in Taiwan-Declining Respiratory Disease Cases in the COVID-19 Pandemic.

With the rapid development of the COVID-19 pandemic, countries are trying to cope with increasing medical demands, and, at the same time, to reduce the increase of infected numbers by implementing a number of public health measures, namely non-pharmaceutical interventions (NPIs). These public health measures can include social distancing, frequent handwashing, and personal protective equipment (PPE) at the personal level; at the community and the government level, these measures can range from canceling activities, avoiding mass gatherings, closing facilities, and, at the extreme, enacting national or provincial lockdowns. Rather than completely stopping the infectious disease, the major purpose of these NPIs in facing an emerging infectious disease is to reduce the contact rate within the population, and reduce the spread of the virus until the time a vaccine or reliable medications become available. The idea is to avoid a surge of patients with severe symptoms beyond the capacity of the hospitals' medical resources, which would lead to more mortality and morbidity. While many countries have experienced steep curves in new cases, some, including Hong Kong, Vietnam, South Korea, New Zealand, and Taiwan, seem to have controlled or even eliminated the infection locally. From its first case of COVID-19 on the 21 January until the 12 May, Taiwan had 440 cases, including just 55 local infections, and seven deaths in total, representing 1.85 cases per 100,000 population and a 1.5% death rate (based on the Worldometer 2020 statistics of Taiwan's population of 23.8 million). This paper presents evidence that spread prevention involving mass masking and universal hygiene at the early stage of the COVID-19 pandemic resulted in a 50% decline of infectious respiratory diseases, based on historical data during the influenza season in Taiwan. These outcomes provide potential support for the effectiveness of widely implementing public health precaution measures in controlling COVID-19 without a lockdown policy.

Rural and Remote Cardiology During the COVID-19 Pandemic: Cardiac Society of Australia and New Zealand (CSANZ) Consensus Statement.

THE CHALLENGES: Rural and remote Australians and New Zealanders have a higher rate of adverse outcomes due to acute myocardial infarction, driven by many factors. The prevalence of cardiovascular disease (CVD) is also higher in regional and remote populations, and people with known CVD have increased morbidity and mortality from coronavirus disease 2019 (COVID-19). In addition, COVID-19 is associated with serious cardiac manifestations, potentially placing additional demand on limited regional services at a time of diminished visiting metropolitan support with restricted travel. Inter-hospital transfer is currently challenging as receiving centres enact pandemic protocols, creating potential delays, and cardiovascular resources are diverted to increasing intensive care unit (ICU) and emergency department (ED) capacity. Regional and rural centres have limited staff resources, placing cardiac services at risk in the event of staff infection or quarantine during the pandemic. MAIN RECOMMENDATIONS: Health districts, cardiologists and government agencies need to minimise impacts on the already vulnerable cardiovascular health of regional and remote Australians and New Zealanders throughout the COVID-19 pandemic. Changes in management should include.