Planning for post-pandemic cancer care delivery: Recovery or opportunity for redesign?

The delivery of cancer care has never changed as rapidly and dramatically as we have seen with the coronavirus disease 2019 (COVID-19) pandemic. During the early phase of the pandemic, recommendations for the management of oncology patients issued by various professional societies and government agencies did not recognize the significant regional differences in the impact of the pandemic. California initially experienced lower than expected numbers of cases, and the health care system did not experience the same degree of the burden that had been the case in other parts of the country. In light of promising trends in COVID-19 infections and mortality in California, by late April 2020, discussions were initiated for a phased recovery of full-scale cancer services. However, by July 2020, a surge of cases was reported across the nation, including in California. In this review, the authors share the response and recovery planning experience of the University of California (UC) Cancer Consortium in an effort to provide guidance to oncology practices. The UC Cancer Consortium was established in 2017 to bring together 5 UC Comprehensive Cancer Centers: UC Davis Comprehensive Cancer Center, UC Los Angeles Jonsson Comprehensive Cancer Center, UC Irvine Chao Family Comprehensive Cancer Center, UC San Diego Moores Cancer Center, and the UC San Francisco Helen Diller Family Comprehensive Cancer Center. The interventions implemented in each of these cancer centers are highlighted, with a focus on opportunities for a redesign in care delivery models. The authors propose that their experiences gained during this pandemic will enhance pre-pandemic cancer care delivery.

Multimodeling approach to evaluating the efficacy of layering pharmaceutical and nonpharmaceutical interventions for influenza pandemics.

When an influenza pandemic emerges, temporary school closures and antiviral treatment may slow virus spread, reduce the overall disease burden, and provide time for vaccine development, distribution, and administration while keeping a larger portion of the general population infection free. The impact of such measures will depend on the transmissibility and severity of the virus and the timing and extent of their implementation. To provide robust assessments of layered pandemic intervention strategies, the Centers for Disease Control and Prevention (CDC) funded a network of academic groups to build a framework for the development and comparison of multiple pandemic influenza models. Research teams from Columbia University, Imperial College London/Princeton University, Northeastern University, the University of Texas at Austin/Yale University, and the University of Virginia independently modeled three prescribed sets of pandemic influenza scenarios developed collaboratively by the CDC and network members. Results provided by the groups were aggregated into a mean-based ensemble. The ensemble and most component models agreed on the ranking of the most and least effective intervention strategies by impact but not on the magnitude of those impacts. In the scenarios evaluated, vaccination alone, due to the time needed for development, approval, and deployment, would not be expected to substantially reduce the numbers of illnesses, hospitalizations, and deaths that would occur. Only strategies that included early implementation of school closure were found to substantially mitigate early spread and allow time for vaccines to be developed and administered, especially under a highly transmissible pandemic scenario.

Coupled models of genomic surveillance and evolving pandemics with applications for timely public health interventions.

Disease surveillance systems provide early warnings of disease outbreaks before they become public health emergencies. However, pandemics containment would be challenging due to the complex immunity landscape created by multiple variants. Genomic surveillance is critical for detecting novel variants with diverse characteristics and importation/emergence times. Yet, a systematic study incorporating genomic monitoring, situation assessment, and intervention strategies is lacking in the literature. We formulate an integrated computational modeling framework to study a realistic course of action based on sequencing, analysis, and response. We study the effects of the second variant's importation time, its infectiousness advantage and, its cross-infection on the novel variant's detection time, and the resulting intervention scenarios to contain epidemics driven by two-variants dynamics. Our results illustrate the limitation in the intervention's effectiveness due to the variants' competing dynamics and provide the following insights: i) There is a set of importation times that yields the worst detection time for the second variant, which depends on the first variant's basic reproductive number; ii) When the second variant is imported relatively early with respect to the first variant, the cross-infection level does not impact the detection time of the second variant. We found that depending on the target metric, the best outcomes are attained under different interventions' regimes. Our results emphasize the importance of sustained enforcement of Non-Pharmaceutical Interventions on preventing epidemic resurgence due to importation/emergence of novel variants. We also discuss how our methods can be used to study when a novel variant emerges within a population.

A Post-Pandemic Enigma: The Cardiovascular Impact of Post-Acute Sequelae of SARS-CoV-2.

COVID-19 has become the first modern-day pandemic of historic proportion, affecting >600 million individuals worldwide and causing >6.5 million deaths. While acute infection has had devastating consequences, postacute sequelae of SARS-CoV-2 infection appears to be a pandemic of its own, impacting up to one-third of survivors and often causing symptoms suggestive of cardiovascular phenomena. This review will highlight the suspected pathophysiology of postacute sequelae of SARS-CoV-2, its influence on the cardiovascular system, and potential treatment strategies.

Toll-Like Receptor 4-Dependent Platelet-Related Thrombosis in SARS-CoV-2 Infection.

BACKGROUND: SARS-CoV-2 is associated with an increased risk of venous and arterial thrombosis, but the underlying mechanism is still unclear. METHODS: We performed a cross-sectional analysis of platelet function in 25 SARS-CoV-2 and 10 healthy subjects by measuring Nox2 (NADPH oxidase 2)-derived oxidative stress and thromboxane B2, and investigated if administration of monoclonal antibodies against the S protein (Spike protein) of SARS-CoV-2 affects platelet activation. Furthermore, we investigated in vitro if the S protein of SARS-CoV-2 or plasma from SARS-CoV-2 enhanced platelet activation. RESULTS: Ex vivo studies showed enhanced platelet Nox2-derived oxidative stress and thromboxane B2 biosynthesis and under laminar flow platelet-dependent thrombus growth in SARS-CoV-2 compared with controls; both effects were lowered by Nox2 and TLR4 (Toll-like receptor 4) inhibitors. Two hours after administration of monoclonal antibodies, a significant inhibition of platelet activation was observed in patients with SARS-CoV-2 compared with untreated ones. In vitro study showed that S protein per se did not elicit platelet activation but amplified the platelet response to subthreshold concentrations of agonists and functionally interacted with platelet TLR4. A docking simulation analysis suggested that TLR4 binds to S protein via three receptor-binding domains; furthermore, immunoprecipitation and immunofluorescence showed S protein-TLR4 colocalization in platelets from SARS-CoV-2. Plasma from patients with SARS-CoV-2 enhanced platelet activation and Nox2-related oxidative stress, an effect blunted by TNF (tumor necrosis factor) α inhibitor; this effect was recapitulated by an in vitro study documenting that TNFα alone promoted platelet activation and amplified the platelet response to S protein via p47phox (phagocyte oxidase) upregulation. CONCLUSIONS: The study identifies 2 TLR4-dependent and independent pathways promoting platelet-dependent thrombus growth and suggests inhibition of TLR4. or p47phox as a tool to counteract thrombosis in SARS-CoV-2.

Integrating Veterinary Diagnostic Laboratories for Emergency Use Testing during Pandemics1.

The SARS-CoV-2 pandemic showed limitations in human outbreak testing. Veterinary diagnostic laboratories (VDLs) possess capabilities to bolster emergency test capacity. Surveys from 26 participating VDLs found human SARS-CoV-2 testing was mutually beneficial, including One Health benefits. VDLs indicated testing >3.8 million human samples during the pandemic, which included some challenges.

Lessons Learned from Cross-Systems Approach to COVID-19 Pandemic Response in Juvenile Justice System, Colorado, USA.

The global COVID-19 pandemic illustrates the importance of a close partnership between public health and juvenile justice systems when responding to communicable diseases. Many setting-specific obstacles must be navigated to respond effectively to limit disease transmission and negative health outcomes while maintaining necessary services for youth in confinement facilities. The response requires multidisciplinary expertise and collaboration to address unique considerations. Public health mitigation strategies must balance the risk for disease against the negative effects of restrictions. Key aspects of the COVID-19 response in the juvenile justice system of Colorado, USA, involved establishing robust communication and data reporting infrastructures, building a multidisciplinary response team, adapting existing infection prevention guidelines, and focusing on a whole-person health approach to infection prevention. We examine lessons learned and offer recommendations on pandemic emergency response planning and managing a statewide public health emergency in youth confinement settings that ensure ongoing readiness.

Progress with the Learning Health System 2.0: a rapid review of Learning Health Systems' responses to pandemics and climate change.

BACKGROUND: Pandemics and climate change each challenge health systems through increasing numbers and new types of patients. To adapt to these challenges, leading health systems have embraced a Learning Health System (LHS) approach, aiming to increase the efficiency with which data is translated into actionable knowledge. This rapid review sought to determine how these health systems have used LHS frameworks to both address the challenges posed by the COVID-19 pandemic and climate change, and to prepare for future disturbances, and thus transition towards the LHS2.0. METHODS: Three databases (Embase, Scopus, and PubMed) were searched for peer-reviewed literature published in English in the five years to March 2023. Publications were included if they described a real-world LHS's response to one or more of the following: the COVID-19 pandemic, future pandemics, current climate events, future climate change events. Data were extracted and thematically analyzed using the five dimensions of the Institute of Medicine/Zurynski-Braithwaite's LHS framework: Science and Informatics, Patient-Clinician Partnerships, Continuous Learning Culture, Incentives, and Structure and Governance. RESULTS: The search yielded 182 unique publications, four of which reported on LHSs and climate change. Backward citation tracking yielded 13 additional pandemic-related publications. None of the climate change-related papers met the inclusion criteria. Thirty-two publications were included after full-text review. Most were case studies (n = 12, 38%), narrative descriptions (n = 9, 28%) or empirical studies (n = 9, 28%). Science and Informatics (n = 31, 97%), Continuous Learning Culture (n = 26, 81%), Structure and Governance (n = 23, 72%) were the most frequently discussed LHS dimensions. Incentives (n = 21, 66%) and Patient-Clinician Partnerships (n = 18, 56%) received less attention. Twenty-nine papers (91%) discussed benefits or opportunities created by pandemics to furthering the development of an LHS, compared to 22 papers (69%) that discussed challenges. CONCLUSIONS: An LHS 2.0 approach appears well-suited to responding to the rapidly changing and uncertain conditions of a pandemic, and, by extension, to preparing health systems for the effects of climate change. LHSs that embrace a continuous learning culture can inform patient care, public policy, and public messaging, and those that wisely use IT systems for decision-making can more readily enact surveillance systems for future pandemics and climate change-related events. TRIAL REGISTRATION: PROSPERO pre-registration: CRD42023408896.

Identifying the panorama of potential pandemic pathogens and their key characteristics: a systematic scoping review.

The globe has recently seen several terrifying pandemics and outbreaks, underlining the ongoing danger presented by infectious microorganisms. This literature review aims to explore the wide range of infections that have the potential to lead to pandemics in the present and the future and pave the way to the conception of epidemic early warning systems. A systematic review was carried out to identify and compile data on infectious agents known to cause pandemics and those that pose future concerns. One hundred and fifteen articles were included in the review. They provided insights on 25 pathogens that could start or contribute to creating pandemic situations. Diagnostic procedures, clinical symptoms, and infection transmission routes were analyzed for each of these pathogens. Each infectious agent's potential is discussed, shedding light on the crucial aspects that render them potential threats to the future. This literature review provides insights for policymakers, healthcare professionals, and researchers in their quest to identify potential pandemic pathogens, and in their efforts to enhance pandemic preparedness through building early warning systems for continuous epidemiological monitoring.

Cerebrovascular Complications of COVID-19 and COVID-19 Vaccination.

The risk of stroke and cerebrovascular disease complicating infection with SARS-CoV-2 has been extensively reported since the onset of the pandemic. The striking efforts of many scientists in cooperation with regulators and governments worldwide have rapidly brought the development of a large landscape of vaccines against SARS-CoV-2. The novel DNA and mRNA vaccines have offered great flexibility in terms of antigen production and led to an unprecedented rapidity in effective and safe vaccine production. However, as mass vaccination has progressed, rare but catastrophic cases of thrombosis have occurred in association with thrombocytopenia and antibodies against PF4 (platelet factor 4). This catastrophic syndrome has been named vaccine-induced immune thrombotic thrombocytopenia. Rarely, ischemic stroke can be the symptom onset of vaccine-induced immune thrombotic thrombocytopenia or can complicate the course of the disease. In this review, we provide an overview of stroke and cerebrovascular disease as a complication of the SARS-CoV-2 infection and outline the main clinical and radiological characteristics of cerebrovascular complications of vaccinations, with a focus on vaccine-induced immune thrombotic thrombocytopenia. Based on the available data from the literature and from our experience, we propose a therapeutic protocol to manage this challenging condition. Finally, we highlight the overlapping pathophysiologic mechanisms of SARS-CoV-2 infection and vaccination leading to thrombosis.

Impact of COVID-19 on the time to counseling and treatment of prostate cancer.

PURPOSE: This study investigates how the COVID-19 pandemic (CP) impacted the timeline between initial diagnosis (ID) of prostate carcinoma and subsequent therapy consultation (TC) or radical prostatectomy (RP) due to the implementation of a "minimal contact concept," which postponed clinical examinations until the day of admission. METHODS: We analyzed patient data from a tertiary care center from 2018 to September 2021. The focus was on comparing the time intervals from ID to TC and from ID to RP before and during the CP. RESULTS: Of 12,255 patients, 6,073 (61.6%) were treated before and 3,791 (38.4%) during the CP. The median time from ID to TC reduced from 37 days (IQR: 21 - 58d) pre-CP to 32 days (IQR: 20 - 50d) during CP (p < 0.001). Similarly, the time from ID to RP decreased from 98 days (IQR: 70 - 141d) to 75 days (IQR: 55 - 108d; p < 0.001) during the CP. There was a significant decrease in low-risk tumor cases at ID (18.9% vs. 21.4%; p = 0.003) and post-RP (4% vs. 6.7%; p < 0.001) during the CP. CONCLUSION: Our findings suggest that the COVID-19 pandemic facilitated more timely treatment of prostate cancer, suggesting potential benefits for both low-risk and aggressive tumor management through expedited clinical procedures.

Country-specific determinants for COVID-19 case fatality rate and response strategies from a global perspective: an interpretable machine learning framework.

BACKGROUND: There are significant geographic inequities in COVID-19 case fatality rates (CFRs), and comprehensive understanding its country-level determinants in a global perspective is necessary. This study aims to quantify the country-specific risk of COVID-19 CFR and propose tailored response strategies, including vaccination strategies, in 156 countries. METHODS: Cross-temporal and cross-country variations in COVID-19 CFR was identified using extreme gradient boosting (XGBoost) including 35 factors from seven dimensions in 156 countries from 28 January, 2020 to 31 January, 2022. SHapley Additive exPlanations (SHAP) was used to further clarify the clustering of countries by the key factors driving CFR and the effect of concurrent risk factors for each country. Increases in vaccination rates was simulated to illustrate the reduction of CFR in different classes of countries. FINDINGS: Overall COVID-19 CFRs varied across countries from 28 Jan 2020 to 31 Jan 31 2022, ranging from 68 to 6373 per 100,000 population. During the COVID-19 pandemic, the determinants of CFRs first changed from health conditions to universal health coverage, and then to a multifactorial mixed effect dominated by vaccination. In the Omicron period, countries were divided into five classes according to risk determinants. Low vaccination-driven class (70 countries) mainly distributed in sub-Saharan Africa and Latin America, and include the majority of low-income countries (95.7%) with many concurrent risk factors. Aging-driven class (26 countries) mainly distributed in high-income European countries. High disease burden-driven class (32 countries) mainly distributed in Asia and North America. Low GDP-driven class (14 countries) are scattered across continents. Simulating a 5% increase in vaccination rate resulted in CFR reductions of 31.2% and 15.0% for the low vaccination-driven class and the high disease burden-driven class, respectively, with greater CFR reductions for countries with high overall risk (SHAP value > 0.1), but only 3.1% for the ageing-driven class. CONCLUSIONS: Evidence from this study suggests that geographic inequities in COVID-19 CFR is jointly determined by key and concurrent risks, and achieving a decreasing COVID-19 CFR requires more than increasing vaccination coverage, but rather targeted intervention strategies based on country-specific risks.

Dynamics of viral disease outbreaks: A hundred years (1918/19-2019/20) in retrospect - Loses, lessons and emerging issues.

Infectious diseases continue to be the leading cause of morbidity and mortality, and a formidable obstacle to the development and well-being of people worldwide. Viruses account for more than half of infectious disease outbreaks that have plagued the world. The past century (1918/19-2019/20) has witnessed some of the worst viral disease outbreaks the world has recorded, with overwhelming impact especially in low- and middle-income countries (LMIC). The frequency of viral disease outbreak appears to be increasing. Generally, although infectious diseases have afflicted the world for centuries and humankind has had opportunities to examine the nature of their emergence and mode of spread, almost every new outbreak poses a formidable challenge to humankind, beating the existing pandemic preparedness systems, if any, and causing significant losses. These underscore inadequacy in our understanding of the dynamics and preparedness against viral disease outbreaks that lead to epidemics and pandemics. Despite these challenges, the past 100 years of increasing frequencies of viral disease outbreaks have engendered significant improvements in response to epidemics and pandemics, and offered lessons to inform preparedness. Hence, the increasing frequency of emergence of viral outbreaks and the challenges these outbreaks pose to humankind, call for the continued search for effective ways to tackle viral disease outbreaks in real time. Through a PRISMA-based approach, this systematic review examines the outbreak of viral diseases in retrospect to decipher the outbreak patterns, losses inflicted on humanity and highlights lessons these offer for meaningful preparation against future viral disease outbreaks and pandemics.

How to protect long-term care facilities from pandemic-like events? - A systematic review on the effectiveness of non-pharmacological measures to prevent viral respiratory infections.

BACKGROUND: The SARS-CoV-2 pandemic underscored the need for pandemic preparedness, with respiratory-transmitted viruses considered as a substantial risk. In pandemics, long-term care facilities (LTCFs) are a high-risk setting with severe outbreaks and burden of disease. Non-pharmacological interventions (NPIs) constitute the primary defence mechanism when pharmacological interventions are not available. However, evidence on the effectiveness of NPIs implemented in LTCFs remains unclear. METHODS: We conducted a systematic review assessing the effectiveness of NPIs implemented in LTCFs to protect residents and staff from viral respiratory pathogens with pandemic potential. We searched Medline, Embase, CINAHL, and two COVID-19 registries in 09/2022. Screening and data extraction was conducted independently by two experienced researchers. We included randomized controlled trials and non-randomized observational studies of intervention effects. Quality appraisal was conducted using ROBINS-I and RoB2. Primary outcomes encompassed number of outbreaks, infections, hospitalizations, and deaths. We synthesized findings narratively, focusing on the direction of effect. Certainty of evidence (CoE) was assessed using GRADE. RESULTS: We analysed 13 observational studies and three (cluster) randomized controlled trials. All studies were conducted in high-income countries, all but three focused on SARS-CoV-2 with the rest focusing on influenza or upper-respiratory tract infections. The evidence indicates that a combination of different measures and hand hygiene interventions can be effective in protecting residents and staff from infection-related outcomes (moderate CoE). Self-confinement of staff with residents, compartmentalization of staff in the LTCF, and the routine testing of residents and/or staff in LTCFs, among others, may be effective (low CoE). Other measures, such as restricting shared spaces, serving meals in room, cohorting infected and non-infected residents may be effective (very low CoE). An evidence gap map highlights the lack of evidence on important interventions, encompassing visiting restrictions, pre-entry testing, and air filtration systems. CONCLUSIONS: Although CoE of interventions was low or very low for most outcomes, the implementation of NPIs identified as potentially effective in this review often constitutes the sole viable option, particularly prior to the availability of vaccinations. Our evidence-gap map underscores the imperative for further research on several interventions. These gaps need to be addressed to prepare LTCFs for future pandemics. TRIAL REGISTRATION: CRD42022344149.

Association depressive symptoms with memory function and social capital before and during COVID-19 in community-dwelling older adults in rural Japan: A retrospective study with a longitudinal data.

OBJECTIVES: This study aimed to investigate the impact of memory function and social capital on depressive symptoms during the COVID-19 pandemic among older adults in rural Japan. METHODS: A retrospective study with longitudinal data was conducted during COVID-19 from May 2021 to November 2021 (T2) in Kurogawa, Japan. The candidate population for this study was 145 with the following requirements: (1) older individuals aged 65 years or above who were registered in the Kurogawa study, and (2) those with previous data (from November 2016 to February 2020; T1 as pre-pandemic). Memory function was assessed using the Wechsler Memory Scale-Revised Logical Memory II delayed recall part A (LM II-DR). Depressive symptoms were assessed using the Japanese version of the 15-item Geriatric Depression Scale (GDS-15). Social capital was evaluated through civic participation, social cohesion, and reciprocity. Fear of the COVID-19 infection (FCV-19S) was evaluated. RESULTS: The final analysis included 96 participants (mean age = 81.0 years, SD = 4.8) Multivariate analysis for GDS-15 score by Mixed Model Repeated Measures (MMRM) revealed significant associations between LM II-DR (ß = -0.13, 95% CI: -0.21-0.05, p = 0.002) and FCV-19S during COVID-19 (ß = 0.08, 95% CI: 0.01-0.15, p = 0.02) with GDS-15 score. However, civic participation, social cohesion and reciprocity were not associated with GDS-15 score. CONCLUSIONS: Among older adults in rural Japan, memory function and fear of the COVID-19 infection were significantly associated with depressive symptoms in MMRM analysis. However, social capital was not associated with depressive symptoms. This highlights the need to address memory function and fear of the COVID-19 infection in interventions for older adults during crises like the COVID-19 pandemic.

Are thoughts and behaviours of individuals with schizophrenia more susceptible to being influenced during pandemic situations? A glimpse provided by the COVID-19 pandemic.

Individuals with psychotic disorders such as schizophrenia may be more vulnerable during pandemics, but research on this topic is limited. This study examined COVID-19 impact on a population affected by schizophrenia during the COVID-19 pandemic. Levels of psychological distress and COVID-19-related behaviours, from the COVID-related Thoughts and Behavioral Symptoms (Cov-Tabs) Scale, were compared between 107 patients with schizophrenia and 70 control participants. Participants with schizophrenia had significantly higher Cov-Tabs scores than non-clinical participants. These results suggest a higher vulnerability in this population, emphasising the need for targeted support and further assessment.

Health of singleton neonates in Switzerland through time and crises: a cross-sectional study at the population level, 2007-2022.

BACKGROUND: Being exposed to crises during pregnancy can affect maternal health through stress exposure, which can in return impact neonatal health. We investigated temporal trends in neonatal outcomes in Switzerland between 2007 and 2022 and their variations depending on exposure to the economic crisis of 2008, the flu pandemic of 2009, heatwaves (2015 and 2018) and the COVID-19 pandemic. METHODS: Using individual cross-sectional data encompassing all births occurring in Switzerland at the monthly level (2007-2022), we analysed changes in birth weight and in the rates of preterm birth (PTB) and stillbirth through time with generalized additive models. We assessed whether the intensity or length of crisis exposure was associated with variations in these outcomes. Furthermore, we explored effects of exposure depending on trimesters of pregnancy. RESULTS: Over 1.2 million singleton births were included in our analyses. While birth weight and the rate of stillbirth have remained stable since 2007, the rate of PTB has declined by one percentage point. Exposure to the crises led to different results, but effect sizes were overall small. Exposure to COVID-19, irrespective of the pregnancy trimester, was associated with a higher birth weight (+12 grams [95% confidence interval (CI) 5.5 to 17.9 grams]). Being exposed to COVID-19 during the last trimester was associated with an increased risk of stillbirth (odds ratio 1.24 [95%CI 1.02 to 1.50]). Exposure to the 2008 economic crisis during pregnancy was not associated with any changes in neonatal health outcomes, while heatwave effect was difficult to interpret. CONCLUSION: Overall, maternal and neonatal health demonstrated resilience to the economic crisis and to the COVID-19 pandemic in a high-income country like Switzerland. However, the effect of exposure to the COVID-19 pandemic is dual, and the negative impact of maternal infection on pregnancy is well-documented. Stress exposure and economic constraint may also have had adverse effects among the most vulnerable subgroups of Switzerland. To investigate better the impact of heatwave exposure on neonatal health, weekly or daily-level data is needed, instead of monthly-level data.

Which roads lead to access? A global landscape of six COVID-19 vaccine innovation models.

BACKGROUND: Unequal and inequitable access to Covid-19 vaccines in low- and middle-income countries (L&MICs) was a major political, ethical and public health failure in the pandemic. However, vaccine developers' practices were not monolithic, but rather, took diverse approaches to supplying different countries, with important implications for global access. RESULTS: Using data on R&D investments, regulatory approvals, manufacturing and purchase agreements, and vaccine deliveries, we identified six distinct innovation models that apply across the 14 COVID-19 vaccines with more international presence from 2020-2022. "Western Early Arrivers" Pfizer/BioNTech and Moderna supplied the largest volumes quickly and prioritized high-income countries (HICs) from registration to vaccine delivery. "Western Latecomers" Janssen and Novavax supplied intermediate volumes later, also prioritizing HICs but with a greater proportion to L&MICs. "Major Chinese Developers" Sinopharm and Sinovac supplied intermediate volumes early, primarily to middle-income countries (MICs). "Russian Developer" Gamaleya completed development early but ultimately supplied small volumes, primarily to middle-income countries (MICs). "Cosmopolitan Developer" Oxford/AstraZeneca supplied large volumes early to HICs and MICs at the lowest prices. Finally, "Small MIC Developers" CanSino, Bharat Biotech, Medigen, Finlay Institute and the Center for Genetic Engineering and Biotechnology (CGEB), exported relatively small volumes to a few MICs. Low-income countries (LICs) were not targeted by any developer, and received far fewer doses, later, than any other income group. Almost all developers received public funding and other forms of support, but we found little evidence that such support was leveraged to expand global access. CONCLUSIONS: Each of the six innovation models has different implications for which countries get access to which vaccines, how quickly, and at which prices. Each offers different strengths and weaknesses for achieving equitable access. Our findings also suggest that Western firms had the greatest capacity to develop and deliver vaccines quickly during the pandemic, but such capacity is rapidly becoming more globally distributed with MICs playing a significant role, especially in supplying other MICs. Given the critical role of public support in enabling pandemic vaccine development and supply, governments have both the capacity and responsibility to craft international rules that will make responses to future pandemics more equitable and effective.

The impact of the COVID-19 pandemic on 397 631 elective dental admissions among the under-25s in England: a retrospective study.

BACKGROUND: COVID-19 caused widespread disruptions to health services worldwide, including reductions in elective surgery. Tooth extractions are among the most common reasons for elective surgery among children and young people (CYP). It is unclear how COVID-19 affected elective dental surgeries in hospitals over multiple pandemic waves at a national level. METHODS: Elective dental tooth extraction admissions were selected using Hospital Episode Statistics. Admission trends for the first 14 pandemic months were compared with the previous five years and results were stratified by age (under-11s, 11-16s, 17-24s). RESULTS: The most socioeconomically deprived CYP comprised the largest proportion of elective dental tooth extraction admissions. In April 2020, admissions dropped by >95%. In absolute terms, the biggest reduction was in April (11-16s: -1339 admissions, 95% CI -1411 to -1267; 17-24s: -1600, -1678 to -1521) and May 2020 (under-11s: -2857, -2962 to -2752). Admissions differed by socioeconomic deprivation for the under-11s (P < 0.0001), driven by fewer admissions than expected by the most deprived and more by the most affluent during the pandemic. CONCLUSION: Elective tooth extractions dropped most in April 2020, remaining below pre-pandemic levels throughout the study. Despite being the most likely to be admitted, the most deprived under-11s had the largest reductions in admissions relative to other groups.

Protocol for a systematic review to understand the long-term mental-health effects of influenza pandemics in the pre-COVID-19 era.

AIMS: This protocol describes a forthcoming systematic review of the question: 'What are the long-term effects of historical influenza pandemics on mental health, resulting either from illness itself or the social or economic effects of pandemics and public health responses?' METHODS: We will review studies that investigate associations between influenza pandemics and long-term mental-health impacts. Following the PICO framework, populations (P) may include those with and without pre-existing mental-health symptoms or conditions. Intervention (I) is exposure to an influenza pandemic during the study period encompassing five pandemics (1889-2009). Comparators or controls (C) are not applicable. The review will address outcomes (O) of mental-health morbidity from direct infection and/or related circumstances, including, for example, receiving a disability pension, institutionalisation and/or death. RESULTS: Due to societal disruptions, illness and bereavement during pandemics, many people are likely to be affected in myriad ways. Therefore, investigation into mental-health consequences should not be restricted by risk group or diagnosis. To our knowledge, this protocol and forthcoming systematic review are the first to include studies for broad populations and multiple measures of mental-health morbidity. The historical perspective and comparison of pandemics with varying severity but assumed similar causative pathogens also enable insights into the consistency of long-term consequences across pandemics. CONCLUSIONS: Pandemics likely produce long-term mental-health impacts with relevance for social, health and economic planning. The systematic review based on this protocol will complement other evidence on pandemic impacts and help policymakers incorporate relevant interventions.