Determining the optimal strategy for reopening schools, the impact of test and trace interventions, and the risk of occurrence of a second COVID-19 epidemic wave in the UK: a modelling study

BACKGROUND: As lockdown measures to slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection begin to ease in the UK, it is important to assess the impact of any changes in policy, including school reopening and broader relaxation of physical distancing measures. We aimed to use an individual-based model to predict the impact of two possible strategies for reopening schools to all students in the UK from September, 2020, in combination with different assumptions about relaxation of physical distancing measures and the scale-up of testing. METHODS: In this modelling study, we used Covasim, a stochastic individual-based model for transmission of SARS-CoV-2, calibrated to the UK epidemic. The model describes individuals' contact networks stratified into household, school, workplace, and community layers, and uses demographic and epidemiological data from the UK. We simulated six different scenarios, representing the combination of two school reopening strategies (full time and a part-time rota system with 50% of students attending school on alternate weeks) and three testing scenarios (68% contact tracing with no scale-up in testing, 68% contact tracing with sufficient testing to avoid a second COVID-19 wave, and 40% contact tracing with sufficient testing to avoid a second COVID-19 wave). We estimated the number of new infections, cases, and deaths, as well as the effective reproduction number (R) under different strategies. In a sensitivity analysis to account for uncertainties within the stochastic simulation, we also simulated infectiousness of children and young adults aged younger than 20 years at 50% relative to older ages (20 years and older). FINDINGS: With increased levels of testing (between 59% and 87% of symptomatic people tested at some point during an active SARS-CoV-2 infection, depending on the scenario), and effective contact tracing and isolation, an epidemic rebound might be prevented. Assuming 68% of contacts could be traced, we estimate that 75% of individuals with symptomatic infection would need to be tested and positive cases isolated if schools return full-time in September, or 65% if a part-time rota system were used. If only 40% of contacts could be traced, these figures would increase to 87% and 75%, respectively. However, without these levels of testing and contact tracing, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a second wave that would peak in December, 2020, if schools open full-time in September, and in February, 2021, if a part-time rota system were adopted. In either case, the second wave would result in R rising above 1 and a resulting second wave of infections 2·0-2·3 times the size of the original COVID-19 wave. When infectiousness of children and young adults was varied from 100% to 50% of that of older ages, we still found that a comprehensive and effective test-trace-isolate strategy would be required to avoid a second COVID-19 wave. INTERPRETATION: To prevent a second COVID-19 wave, relaxation of physical distancing, including reopening of schools, in the UK must be accompanied by large-scale, population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of diagnosed individuals. FUNDING: None

In the interests of time: Improving HIV allocative efficiency modelling via optimal time-varying allocations

Introduction: International investment in the response to HIV and AIDS has plateaued and its future level is uncertain. With many countries committed to ending the epidemic, it is essential to allocate available resources efficiently over different response periods to maximize impact. The objective of this study is to propose a technique to determine the optimal allocation of funds over time across a set of HIV programmes to achieve desirable health outcomes. Methods: We developed a technique to determine the optimal time-varying allocation of funds (1) when the future annual HIV budget is pre-defined and (2) when the total budget over a period is pre-defined, but the year-on-year budget is to be optimally determined. We use this methodology with Optima, an HIV transmission model that uses non-linear relationships between programme spending and associated programmatic outcomes to quantify the expected epidemiological impact of spending.We apply these methods to data collected from Zambia to determine the optimal distribution of resources to fund the right programmes, for the right people, at the right time. Results and discussion: Considering realistic implementation and ethical constraints, we estimate that the optimal time-varying redistribution of the 2014 Zambian HIV budget between 2015 and 2025 will lead to a 7.6% (7.3% to 7.8%) decrease in cumulative new HIV infections compared with a baseline scenario where programme allocations remain at 2014 levels. This compares to a 5.1% (4.6% to 5.6%) reduction in new infections using an optimal allocation with constant programme spending that recommends unrealistic programmatic changes. Contrasting priorities for programme funding arise when assessing outcomes for a five-year funding period over 5-, 10- and 20-year time horizons. Conclusions: Countries increasingly face the need to do more with the resources available. The methodology presented here can aid decision-makers in planning as to when to expand or contract programmes and to which coverage levels to maximize impact

Maximizing the impact of malaria funding through allocative efficiency: using the right interventions in the right locations.

BACKGROUND: The high burden of malaria and limited funding means there is a necessity to maximize the allocative efficiency of malaria control programmes. Quantitative tools are urgently needed to guide budget allocation decisions. METHODS: A geospatial epidemic model was coupled with costing data and an optimization algorithm to estimate the optimal allocation of budgeted and projected funds across all malaria intervention approaches. Interventions included long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), intermittent presumptive treatment during pregnancy (IPTp), seasonal mass chemoprevention in children (SMC), larval source management (LSM), mass drug administration (MDA), and behavioural change communication (BCC). The model was applied to six geopolitical regions of Nigeria in isolation and also the nation as a whole to minimize incidence and malaria-attributable mortality. RESULTS: Allocative efficiency gains could avert approximately 84,000 deaths or 15.7 million cases of malaria in Nigeria over 5 years. With an additional US$300 million available, approximately 134,000 deaths or 37.3 million cases of malaria could be prevented over 5 years. Priority funding should go to LLINs, IPTp and BCC programmes, and SMC should be expanded in seasonal areas. To minimize mortality, treatment expansion is critical and prioritized over some LLIN funding, while to minimize incidence, LLIN funding remained a priority. For areas with lower rainfall, LSM is prioritized over IRS but MDA is not recommended unless all other programmes are established. CONCLUSIONS: Substantial reductions in malaria morbidity and mortality can be made by optimal targeting of investments to the right malaria interventions in the right areas

Optima Nutrition: an allocative efficiency tool to reduce childhood stunting by better targeting of nutrition-related interventions.

BACKGROUND: Child stunting due to chronic malnutrition is a major problem in low- and middle-income countries due, in part, to inadequate nutrition-related practices and insufficient access to services. Limited budgets for nutritional interventions mean that available resources must be targeted in the most cost-effective manner to have the greatest impact. Quantitative tools can help guide budget allocation decisions. METHODS: The Optima approach is an established framework to conduct resource allocation optimization analyses. We applied this approach to develop a new tool, 'Optima Nutrition', for conducting allocative efficiency analyses that address childhood stunting. At the core of the Optima approach is an epidemiological model for assessing the burden of disease; we use an adapted version of the Lives Saved Tool (LiST). Six nutritional interventions have been included in the first release of the tool: antenatal micronutrient supplementation, balanced energy-protein supplementation, exclusive breastfeeding promotion, promotion of improved infant and young child feeding (IYCF) practices, public provision of complementary foods, and vitamin A supplementation. To demonstrate the use of this tool, we applied it to evaluate the optimal allocation of resources in 7 districts in Bangladesh, using both publicly available data (such as through DHS) and data from a complementary costing study. RESULTS: Optima Nutrition can be used to estimate how to target resources to improve nutrition outcomes. Specifically, for the Bangladesh example, despite only limited nutrition-related funding available (an estimated $0.75 per person in need per year), even without any extra resources, better targeting of investments in nutrition programming could increase the cumulative number of children living without stunting by 1.3 million (an extra 5%) by 2030 compared to the current resource allocation. To minimize stunting, priority interventions should include promotion of improved IYCF practices as well as vitamin A supplementation. Once these programs are adequately funded, the public provision of complementary foods should be funded as the next priority. Programmatic efforts should give greatest emphasis to the regions of Dhaka and Chittagong, which have the greatest number of stunted children. CONCLUSIONS: A resource optimization tool can provide important guidance for targeting nutrition investments to achieve greater impact

Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and the agent-based model Covasim, in June 2021, to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. Using these estimates in Covasim (calibrated 1 September 2020 to 20 June 2021), in June 2021, we found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'

Evaluation of a web-based intervention to reduce antibiotic prescribing for LRTI in six European countries: quantitative process analysis of the GRACE/INTRO randomised controlled trial.

To reduce the spread of antibiotic resistance, there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI. This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries. The aim was to understand how the interventions were implemented and to examine effects of the interventions on general practitioners' (GPs') and patients' attitudes

Modelling the potential impact of mask use in schools and society on COVID-19 control in the UK.

As the UK reopened after the first wave of the COVID-19 epidemic, crucial questions emerged around the role for ongoing interventions, including test-trace-isolate (TTI) strategies and mandatory masks. Here we assess the importance of masks in secondary schools by evaluating their impact over September 1-October 23, 2020. We show that, assuming TTI levels from August 2020 and no fundamental changes in the virus's transmissibility, adoption of masks in secondary schools would have reduced the predicted size of a second wave, but preventing it would have required 68% or 46% of those with symptoms to seek testing (assuming masks' effective coverage 15% or 30% respectively). With masks in community settings but not secondary schools, the required testing rates increase to 76% and 57%

Concurrent use of prescription drugs and herbal medicinal products in older adults: A systematic review

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The use of herbal medicinal products (HMPs) is common among older adults. However, little is known about concurrent use with prescription drugs as well as the potential interactions associated with such combinations. Objective Identify and evaluate the literature on concurrent prescription and HMPs use among older adults to assess prevalence, patterns, potential interactions and factors associated with this use. Methods Systematic searches in MEDLINE, PsycINFO, EMBASE, CINAHL, AMED, Web of Science and Cochrane from inception to May 2017 for studies reporting concurrent use of prescription medicines with HMPs in adults (≥65 years). Quality was assessed using the Joanna Briggs Institute checklists. The Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) three stage approach to mixed method research was used to synthesise data. Results Twenty-two studies were included. A definition of HMPs or what was considered HMP was frequently missing. Prevalence of concurrent use by older adults varied widely between 5.3% and 88.3%. Prescription medicines most combined with HMPs were antihypertensive drugs, beta blockers, diuretics, antihyperlipidemic agents, anticoagulants, analgesics, antihistamines, antidiabetics, antidepressants and statins. The HMPs most frequently used were: ginkgo, garlic, ginseng, St John’s wort, Echinacea, saw palmetto, evening primrose oil and ginger. Potential risks of bleeding due to use of ginkgo, garlic or ginseng with aspirin or warfarin was the most reported herb-drug interaction. Some data suggests being female, a lower household income and less than high school education were associated with concurrent use. Conclusion Prevalence of concurrent prescription drugs and HMPs use among older adults is substantial and potential interactions have been reported. Knowledge of the extent and manner in which older adults combine prescription drugs will aid healthcare professionals can appropriately identify and manage patients at risk.Peer reviewedFinal Published versio

The influence of portfolio aims and structure on student attitudes towards portfolios as a learning tool: A Scoping Review

Background: Portfolios are widely used in undergraduate health professional education, however the majority of literature suggests that these are poorly received by students, in terms of being an effective learning tool. Objectives: to evaluate whether the aims/purpose or structure/level of standardisation/content of student portfolios influences their attitudes to and perceptions of its use as a learning tool. Major Findings: Aims/purpose and structure/level of standardisation/content of portfolios were analysed in relation to student responses in order to determine any relationship between these. The level of information provided in the studies was variable, making analysis difficult, however there appeared to be no clear link between any of these factors and student responses. The interplay of level of support and guidance, the time required for completion of the portfolio, and the role of assessment appear to have the greatest influence on student views. Conclusions: Considering the wide use of portfolios in health professional education, student support for these is limited, and further research is required to determine if alternative approaches to portfolio learning can positively influence student attitudes and perceptions

Tolerability and safety of novel half milliliter formulation of glatiramer acetate for subcutaneous injection: an open-label, multicenter, randomized comparative study

Daily glatiramer acetate (GA) 20 mg/1.0 mL is a first-line treatment for relapsing-remitting multiple sclerosis (RRMS). To reduce the occurrence of injection pain and local injection site reactions (LISRs), a reduced volume formulation of GA was developed. This study compared pain and LISRs after injecting the marketed and the novel formulations. RRMS patients currently injecting GA participated in this multicenter, randomized, crossover comparative study. All patients administered once-daily subcutaneous injections of GA 20 mg/1.0 mL (marketed formulation) or GA 20 mg/0.5 mL (reduced volume formulation) for 14 days. Patients were crossed-over to the alternate treatment for an additional 14 days. Using a Visual Analog Scale (VAS), patients recorded in daily diaries the severity of injection pain immediately and 5 min post-injection, and the presence and severity of LISRs (swelling, redness, itching, lump) within 5 min and 24 h post-injection. VAS pain scores were ranked significantly lower immediately and 5 min after GA 20 mg/0.5 mL injections (p < 0.0001). Although LISRs were rare for both preparations, the severity of reactions ranked significantly lower and fewer symptoms occurred within 5 min and 24 h of using the reduced volume formulation (p < 0.0001). GA injected subcutaneously in a reduced volume formulation is a more tolerable option