Project description:The coronavirus disease 2019 (COVID-19) pandemic has elicited a swift response by the scientific community to elucidate the pathogenesis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced lung injury and develop effective therapeutics. Clinical data indicate that severe COVID-19 most commonly manifests as viral pneumonia-induced acute respiratory distress syndrome (ARDS), a clinical entity mechanistically understood best in the context of influenza A virus-induced pneumonia. Similar to influenza, advanced age has emerged as the leading host risk factor for developing severe COVID-19. In this review we connect the current understanding of the SARS-CoV-2 replication cycle and host response to the clinical presentation of COVID-19, borrowing concepts from influenza A virus-induced ARDS pathogenesis and discussing how these ideas inform our evolving understanding of COVID-19-induced ARDS. We also consider important differences between COVID-19 and influenza, mainly the protean clinical presentation and associated lymphopenia of COVID-19, the contrasting role of interferon-γ in mediating the host immune response to these viruses, and the tropism for vascular endothelial cells of SARS-CoV-2, commenting on the potential limitations of influenza as a model for COVID-19. Finally, we explore hallmarks of ageing that could explain the association between advanced age and susceptibility to severe COVID-19.
Project description:Population screening for colorectal cancer (CRC) has recently commenced in the United Kingdom supported by the evidence of a number of randomised trials and pilot studies. Certain factors are known to influence screening cost-effectiveness (e.g. compliance), but it remains unclear whether an ageing population (i.e. demographic change) might also have an effect. The aim of this study was to simulate a population-based screening setting using a Markov model and assess the effect of increasing life expectancy on CRC screening cost-effectiveness. A Markov model was constructed that aimed, using a cohort simulation, to estimate the cost-effectiveness of CRC screening in an England and Wales population for two timescales: 2003 (early cohort) and 2033 (late cohort). Four model outcomes were calculated; screened and non-screened cohorts in 2003 and 2033. The screened cohort of men and women aged 60 years were offered biennial unhydrated faecal occult blood testing until the age of 69 years. Life expectancy was assumed to increase by 2.5 years per decade. There were 407 552 fewer people entering the model in the 2033 model due to a lower birth cohort, and population screening saw 30 345 fewer CRC-related deaths over the 50 years of the model. Screening the 2033 cohort cost pound 96 million with cost savings of pound 43 million in terms of detection and treatment and pound 28 million in palliative care costs. After 30 years of follow-up, the cost per life year saved was pound 1544. An identical screening programme in an early cohort (2003) saw a cost per life year saved of pound 1651. Population screening for CRC is costly but enables cost savings in certain areas and a considerable reduction in mortality from CRC. This Markov simulation suggests that the cost-effectiveness of population screening for CRC in the United Kingdom may actually be improved by rising life expectancies.
Project description:Due to COVID 19 (Corona virus disease)pandemic, majority of surgeries, including surgery for cancer patients got delayed across the globe. Surgeries were limited to emergency set up only. At our institute we tried to perform colorectal cancer surgeries through out the pandemic, albeit in less numbers, as we thought cancer in itself is an emergency setting. we are planning to analyse the prospectively managed database of this particular group of patients over a period of last six 6 months and look out at 30 day post operative morbidity and mortality. Besides we will try to analyse the implications of our decision to carry on with cancer surgeries in terms of number of health care workers who got infected while being involved in primary care of these patients.
Project description:AimThe purpose of this review is to discuss the current status of local and international efforts undergoing clinical trials aiming at developing a Coronavirus Disease-2019 (COVID-19) vaccine, and to highlight the anticipated challenges of this vaccine globally and in Saudi Arabia.Present findingsCOVID-19 vaccine development efforts started in early January 2020 when Chinese scientists shared the Coronavirus genomic sequence in public domain. Approximately 321 research groups initiated the search for a vaccine, out of which 41 have reached phase I/II trails and 11 reached phase-III clinical trials, including approved vaccines for early to limited use. Out of these projects are two labs in the Kingdom of Saudi Arabia still in early stages of development of a COVID-19 vaccine. Several vaccine attempts are being tested from traditional, attenuated virus methods, to new nucleic acid-based designs. However, no vaccine has yet completed clinical trials and reached public domain.In spite of the challenges faced during previous vaccine trials, researchers have found that Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 is structurally similar to the (SARS-CoV-1) and the Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), which caused epidemics in 2003 and 2012 respectively. Both SARS strains show identical affinity towards the type-II alveolar pneumocytes angiotensin converting enzyme-2 (ACE-2) receptor binding domains and therefore, similar pathogenicity. The race to develop the vaccine is predominantly for individuals at high risk of developing the infection, i.e. population groups who are most susceptible to experiencing fatal symptoms of the coronavirus. These include patients with comorbidities, above the age of 60 years and people at risk of contracting large viral loads, such as healthcare providers caring for critical admissions in in-patient wards, Intensive Care Units and Emergency Room settings.SummaryMany different vaccine strategies are under development throughout different stages of the research timeline; however, it is estimated that none will show favorable results before end of 2020. For any immunization or interventional prevention/therapy system to reach the public and patients at high risk, it needs to undergo multiple phase trials to ensure safety and effectiveness. In this scoping review we aim to map the literature on COVID-19 vaccines and provide recommendations related to gaps in research, applicability and expected challenges for implementation of nationwide vaccination in Saudi Arabia.
Project description:Covid-19 endangers lives, has disrupted normal life, changed the way medicine is practised and is likely to alter our world for the foreseeable future. Almost two years on since the presumptive first diagnosis of COVID-19 in China, more than two hundred and fifty million cases have been confirmed and more than five million people have died globally, with the figures rising daily. One of the most striking aspects of COVID-19 illness is the marked difference in individuals' experiences of the disease. Some, most often younger groups, are asymptomatic, whereas others become severely ill with acute respiratory distress syndrome (ARDS), pneumonia or proceed to fatal organ disease. The highest death rates are in the older and oldest age groups and in people with co-morbidities such as diabetes, heart disease and obesity. Three major questions seem important to consider. What do we understand about changes in the immune system that might contribute to the older person's risk of developing severe COVID-19? What factors contribute to the higher morbidity and mortality in older people with COVID-19? How could immunocompetence in the older and the frailest individuals and populations be supported and enhanced to give protection from serious COVID-19 illness?
Project description:The map presented in this brief note summarizes regional differences in population age structures between the NUTS-3 regions of Europe in the context of unequal age- and sex-specific death risks associated with the spread of the COVID-19 pandemic. Since older people are exposed to much higher death risks, older populations are expected to face much more difficult challenges coping with the pandemic. The urban/rural dimension turns out to be very important as the remote rural areas are also the oldest. In the map NUTS-3 regions of Europe are colored according to the deviation from European pooled estimate of the proportion of population at risk of death due to COVID-19. We assume that 5/6 of the populations get infected and experience age-specific infection-fatality ratios (IFRs) modelled by the Imperial College COVID-19 Response Team. We adjust IFRs by sex ratios of age-specific case-fatality ratios observed in the European countries that are included in the COVerAGE-DB. Thus, we effectively introduce a summary measure of population age structures focused on the most vulnerable to the pandemic. Such an estimate for the total European population is 1%. The map reflects the unequal population age structures rather than the precise figures on COVID-19 fatality. It is a case-if scenario that highlights the possible effect of the population age structures, a demographic perspective. This analysis clearly shows the contribution of regional differences in population age structures to the magnitude of the pandemic - other things equal, we expect to see a four-fold variation in average regional infection-fatality ratios across Europe due only to differences in the population structures.
Project description:Research summaryDespite growing national awareness that COVID-19 in jails and prisons constitutes a public health emergency in the United States, remarkably little attention has been paid to understanding how the virus affects people under community supervision. We used data from the National Survey on Drug Use and Health (NSDUH) to explore differences in the extent to which men under community supervision are vulnerable to COVID-19 and have access to care during the pandemic, relative to men who are not involved with the U.S. criminal legal system. Results from this study highlight the greater levels of risk for serious illness or death from COVID-19 and the disproportionate lack of health insurance among men under community supervision.Policy implicationsJurisdictions across the United States are currently relying on decarceration to contain the spread of COVID-19 in jails and prisons. Decarceration efforts alone, however, are insufficient for addressing the spread of COVID-19 among people involved with the U.S. criminal legal system. People released from jails and prisons or diverted from incarceration during the pandemic must be given the opportunity to receive the COVID-19 vaccination upon their transitions. Likewise, individuals under community supervision must be prioritized for immediate vaccination against COVID-19. People involved with the U.S. criminal legal system should also be eligible for emergency Medicaid during the COVID-19 crisis, and their health insurance coverage should remain available beyond the pandemic.
Project description:Research questionDiscontinuation of IVF cycles has been part of the radical transformation of healthcare provision to enable reallocation of staff and resources to deal with the COVID-19 pandemic. This study sought to estimate the impact of cessation of treatment on individual prognosis and US population live birth rates.DesignData from 271,438 ovarian stimulation UK IVF cycles was used to model the effect of age as a continuous, yet non-linear, function on cumulative live birth rate. This model was recalibrated to cumulative live birth rates reported for the 135,673 stimulation cycles undertaken in the USA in 2016, with live birth follow-up to October 2018. The effect of a 1-month, 3-month and 6-month shutdown in IVF treatment was calculated as the effect of the equivalent increase in a woman's age, stratified by age group.ResultsThe average reduction in cumulative live birth rate would be 0.3% (95% confidence interval [CI] 0.3-0.3), 0.8% (95% CI 0.8-0.8) and 1.6% (95% CI 1.6-1.6) for 1-month, 3-month and 6-month shutdowns. This corresponds to a reduction of 369 (95% CI 360-378), 1098 (95% CI 1071-1123) and 2166 (95% CI 2116-2216) live births in the cohort, respectively. Th e greatest contribution to this reduction was from older mothers.ConclusionsThe study demonstrated that the discontinuation of fertility treatment for even 1 month in the USA could result in 369 fewer women having a live birth, due to the increase in patients' age during the shutdown. As a result of reductions in cumulative live birth rate, more cycles may be required to overcome infertility at individual and population levels.
Project description:Background and objectiveIn the absence of characterization on pharmacokinetics and reference concentrations for hydroxychloroquine in COVID-19 patients, the dose and treatment duration for hydrochloroquine are currently empirical, mainly based on in vitro data, and may vary across national guidelines and clinical study protocols. The aim of this paper is to describe the pharmacokinetics of hydroxychloroquine in COVID-19 patients, considered to be a key step toward its dosing optimization.MethodsWe have developed a population pharmacokinetic model for hydroxychloroquine in COVID-19 patients using prospectively collected pharmacokinetic data from patients either enrolled in a clinical trial or treated with hydroxychloroquine as part of standard of care in two tertiary Belgian hospitals.ResultsThe final population pharmacokinetic model was a one-compartment model with first-order absorption and elimination. The estimated parameter values were 9.3/h, 860.8 L, and 15.7 L/h for the absorption rate constant, the central compartment volume, and the clearance, respectively. The bioavailability factor was fixed to 0.74 based on previously published models. Model validations by bootstraps, prediction corrected visual predictive checks, and normalized prediction distribution errors gave satisfactory results. Simulations were performed to compare the exposure obtained with alternative dosing regimens.ConclusionThe developed models provide useful insight for the dosing optimization of hydroxychloroquine in COVID-19 patients. The present results should be used in conjunction with exposure-efficacy and exposure-safety data to inform optimal dosing of hydroxychloroquine in COVID-19.