Impact of the COVID-19 pandemic on antimicrobial stewardship support for general practices in England: a qualitative interview study.

BACKGROUND: In England, Clinical Commissioning Group (CCG) (now replaced by Integrated Care Systems (ICS)) and Primary Care Network (PCN) professionals support primary care prescribers to optimise antimicrobial stewardship (AMS). AIM: To explore views and experiences of CCG/PCN staff in supporting AMS, and the impact of COVID-19 on this support. DESIGN AND SETTING: Qualitative interview study in primary care in England. METHOD: Semi-structured interviews-with staff from CCG/PCNs responsible for AMS-at two time-points, via telephone interviews. These were audio-recorded, transcribed, and analysed thematically. RESULTS: Twenty-seven interviews were conducted with 14 participants (nine CCG, five PCN) in Dec 2020/Jan 2021 and Feb/Mar 2021.We found that AMS support was 1) deprioritised- to keep general practice operational and deliver COVID-19 vaccines; 2) disrupted-as social distancing made it harder to build relationships, conduct routine AMS activities, and challenge prescribing decisions; and 3) adapted-with opportunities identified for greater use of technology and from changed patient/public perceptions of viruses and self-care. We also found that resources to support AMS were valued if they were both novel, to counter AMS 'fatigue', and sufficiently familiar to fit with existing/future AMS. CONCLUSION: AMS needs to be reprioritised in general practice in the post-pandemic era and within the new ICS in England. This should include interventions/strategies that combine novel elements with already familiar strategies to refresh prescribers' motivation and opportunity for AMS. Behaviour change interventions should be aimed at improving the culture and processes for how PCN pharmacists voice concerns about AMS to prescribers in general practice and take advantage of the changed patient/public perceptions of viruses and self-care.

The COVID-19 pandemic and health-related quality of life across 13 high- and low-middle-income countries: A cross-sectional analysis.

BACKGROUND: Most research on the Coronavirus Disease 2019 (COVID-19) health burden has focused on confirmed cases and deaths, rather than consequences for the general population's health-related quality of life (HRQoL). It is also important to consider HRQoL to better understand the potential multifaceted implications of the COVID-19 pandemic in various international contexts. This study aimed to assess the association between the COVID-19 pandemic and changes in HRQoL in 13 diverse countries. METHODS AND FINDINGS: Adults (18+ years) were surveyed online (24 November to 17 December 2020) in 13 countries spanning 6 continents. Our cross-sectional study used descriptive and regression-based analyses (age adjusted and stratified by gender) to assess the association between the pandemic and changes in the general population's HRQoL, measured by the EQ-5D-5L instrument and its domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and how overall health deterioration was associated with individual-level (socioeconomic, clinical, and experiences of COVID-19) and national-level (pandemic severity, government responsiveness, and effectiveness) factors. We also produced country-level quality-adjusted life years (QALYs) associated to COVID-19 pandemic-related morbidity. We found that overall health deteriorated, on average across countries, for more than one-third of the 15,480 participants, mostly in the anxiety/depression health domain, especially for younger people (<35 years old) and females/other gender. This translated overall into a 0.066 mean "loss" (95% CI: -0.075, -0.057; p-value < 0.001) in the EQ-5D-5L index, representing a reduction of 8% in overall HRQoL. QALYs lost associated with morbidity were 5 to 11 times greater than QALYs lost based on COVID-19 premature mortality. A limitation of the study is that participants were asked to complete the prepandemic health questionnaire retrospectively, meaning responses may be subject to recall bias. CONCLUSIONS: In this study, we observed that the COVID-19 pandemic was associated with a reduction in perceived HRQoL globally, especially with respect to the anxiety/depression health domain and among younger people. The COVID-19 health burden would therefore be substantially underestimated if based only on mortality. HRQoL measures are important to fully capture morbidity from the pandemic in the general population.

Antibiotic review kit for hospitals (ARK-Hospital): a stepped-wedge cluster-randomised controlled trial.

BACKGROUND: Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotic use. There is scarce evidence for how to support these decisions. We evaluated a multifaceted behaviour change intervention (ie, the antibiotic review kit) designed to reduce antibiotic use among adult acute general medical inpatients by increasing appropriate decisions to stop antibiotics at clinical review. METHODS: We performed a stepped-wedge, cluster (hospital)-randomised controlled trial using computer-generated sequence randomisation of eligible hospitals in seven calendar-time blocks in the UK. Hospitals were eligible for inclusion if they admitted adult non-elective general or medical inpatients, had a local representative to champion the intervention, and could provide the required study data. Hospital clusters were randomised to an implementation date occurring at 1-2 week intervals, and the date was concealed until 12 weeks before implementation, when local preparations were designed to start. The intervention effect was assessed using data from pseudonymised routine electronic health records, ward-level antibiotic dispensing, Clostridioides difficile tests, prescription audits, and an implementation process evaluation. Co-primary outcomes were monthly antibiotic defined daily doses per adult acute general medical admission (hospital-level, superiority) and all-cause mortality within 30 days of admission (patient level, non-inferiority margin of 5%). Outcomes were assessed in the modified intention-to-treat population (ie, excluding sites that withdrew before implementation). Intervention effects were assessed by use of interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed by use of meta-regression. This trial is completed and is registered with ISRCTN, ISRCTN12674243. FINDINGS: 58 hospital organisations expressed an interest in participating. Three pilot sites implemented the intervention between Sept 25 and Nov 20, 2017. 43 further sites were randomised to implement the intervention between Feb 12, 2018, and July 1, 2019, and seven sites withdrew before implementation. 39 sites were followed up for at least 14 months. Adjusted estimates showed reductions in total antibiotic defined daily doses per acute general medical admission (-4·8% per year, 95% CI -9·1 to -0·2) following the intervention. Among 7 160 421 acute general medical admissions, the ARK intervention was associated with an immediate change of -2·7% (95% CI -5·7 to 0·3) and sustained change of 3·0% (-0·1 to 6·2) in adjusted 30-day mortality. INTERPRETATION: The antibiotic review kit intervention resulted in sustained reductions in antibiotic use among adult acute general medical inpatients. The weak, inconsistent intervention effects on mortality are probably explained by the onset of the COVID-19 pandemic. Hospitals should use the antibiotic review kit to reduce antibiotic overuse. FUNDING: UK National Institute for Health and Care Research.

Malaysian public preferences and decision making for COVID-19 vaccination: A discrete choice experiment.

Background: Low vaccine uptake has the potential to seriously undermine COVID-19 vaccination programs, as very high coverage levels are likely to be needed for virus suppression to return life to normal. We aimed to determine the influence of vaccine attributes (including access costs) on COVID-19 vaccination preferences among the Malaysian public to improve national uptake. Methods: An online Discrete Choice Experiment (DCE) was conducted on a representative sample of 2028 Malaysians. Respondents were asked to make vaccination decisions in a series of hypothetical scenarios. A nested, mixed logit model was used to estimate the preferences for vaccination over vaccine refusal and for how those preferences varied between different sub-populations. The attributes were the risk of developing severe side effects of the vaccine, vaccine effectiveness, vaccine content, vaccination schedule, and distance from home to vaccination centre. Findings: Reported public uptake of COVID-19 vaccination was primarily influenced by the risk of developing severe side effects (b = -1·747, 95% CI = -2·269, -1·225), vaccine effectiveness (b = 3·061, 95% CI = 2·628, 3·494) and its Halal status (b = 3·722, 95% CI = 3·152, 4·292). Other factors such as appointment timing and travel distance to the vaccination centre also had an effect on vaccine uptake. There was substantial heterogeneity in preferences between different populations, particularly for age groups, ethnicity, regions, and underlying health conditions. Interpretation: Perceived effectiveness and side effects are likely to affect COVID-19 vaccine uptake in Malaysia. Halal content is critical to Malays' vaccination choices. Reducing the physical distance to vaccination centres, particularly in rural areas where uptake is lower, is likely to improve uptake. Funding: Ministry of Health Research Grant from the Malaysian government [NIH/800-3/2/1 Jld.7(46), grant reference no: 57377 and warrant no: 91000776].

The economic challenges of new drug development.

The COVID-19 pandemic has witnessed highly successful efforts to produce effective vaccines and treatments at an unprecedented pace. This perspective discusses factors that made this possible, from long-term investments in research infrastructure to major government interventions that absorbed much of the risk from research and development. We discuss key economic obstacles in the discovery of new drugs for infectious diseases, from novel antibiotics to diseases that primarily affect the poor. The world's collective experience of the pandemic may present an opportunity to reform traditional economic models of drug discovery to better address unmet needs. A tax-funded global institution could provide incentives for drug discovery based on their global health impact. International co-operation would be needed to agree and commit to adequate funding mechanisms, and the necessary political will would require strong public support. With the current heightened appreciation of the need for global health system resilience, there may be no better opportunity than now.

Impact of the COVID-19 Pandemic on Community Antibiotic Prescribing and Stewardship: A Qualitative Interview Study with General Practitioners in England.

The COVID-19 pandemic has had a profound impact on the delivery of primary care services. We aimed to identify general practitioners' (GPs') perceptions and experiences of how the COVID-19 pandemic influenced antibiotic prescribing and antimicrobial stewardship (AMS) in general practice in England. Twenty-four semi-structured interviews were conducted with 18 GPs at two time-points: autumn 2020 (14 interviews) and spring 2021 (10 interviews). Interviews were audio-recorded, transcribed and analysed thematically, taking a longitudinal approach. Participants reported a lower threshold for antibiotic prescribing (and fewer consultations) for respiratory infections and COVID-19 symptoms early in the pandemic, then returning to more usual (pre-pandemic) prescribing. They perceived the pandemic as having had less impact on antibiotic prescribing for urinary and skin infections. Participants perceived the changing ways of working and consulting (e.g., proportions of remote and in-person consultations) in addition to changing patient presentations and GP workloads as influencing the fluctuations in antibiotic prescribing. This was compounded by decreased engagement with, and priority of, AMS due to COVID-19-related urgent priorities. Re-engagement with AMS is needed, e.g., through reviving antibiotic prescribing feedback and targets/incentives. The pandemic disrupted, and required adaptations in, the usual ways of working and AMS. It is now important to identify opportunities, e.g., for re-organising ways of managing infections and AMS in the future.

Is There Broad-Based Support in High-Income Countries for COVID-19 Vaccine Donation? Evidence from Seven Countries.

BACKGROUND: Many high-income countries (HICs) have now vaccinated a substantial proportion of their population against COVID-19. Many low-income countries (LICs) may need to wait until at least 2022 before even the most vulnerable 20% of their populations are vaccinated. Beyond ethical considerations, some redistribution of doses would reduce the risk of the emergence and spread of new variants and benefit the economy, both globally and in donor countries. However, the willingness of HIC governments to donate vaccine doses is likely to depend on public support. While previous work has indicated strong average levels of public support in HIC for donation, little is known about how broad-based this support is. OBJECTIVE: To investigate the extent to which support for donation holds across both pre-specified and exploratory subgroups. METHODS: From 24 November-28 December 2020 we conducted an online survey of 8209 members of the general public in seven HIC (Australia, Canada, France, Italy, Spain, UK and USA). We conducted tests of proportions and used Bayesian ordinal logistic regression models to assess the extent of support for donation across population subgroups. RESULTS: We found broad-based support for donations in terms of age, gender, socio-economic status and political ideology. We found no strong evidence that support for donations was higher among those with greater income or a university education. Support for donation among those on the political right and centre was lower than on the left, but 51% (95% confidence interval 48-53%) of respondents who identified with the right supported some level of donation. Those in the more altruistic half of the sample (as captured by willingness to donate money to a good cause) were more likely to support donation than those who were not, but around half of the less altruistic group supported some level of donation. CONCLUSION: There is broad-based support for policymakers in HICs to donate some of their countries' COVID-19 vaccine doses for distribution to LICs.

Citizens from 13 countries share similar preferences for COVID-19 vaccine allocation priorities.

How does the public want a COVID-19 vaccine to be allocated? We conducted a conjoint experiment asking 15,536 adults in 13 countries to evaluate 248,576 profiles of potential vaccine recipients who varied randomly on five attributes. Our sample includes diverse countries from all continents. The results suggest that in addition to giving priority to health workers and to those at high risk, the public favors giving priority to a broad range of key workers and to those with lower income. These preferences are similar across respondents of different education levels, incomes, and political ideologies, as well as across most surveyed countries. The public favored COVID-19 vaccines being allocated solely via government programs but were highly polarized in some developed countries on whether taking a vaccine should be mandatory. There is a consensus among the public on many aspects of COVID-19 vaccination, which needs to be taken into account when developing and communicating rollout strategies.

Lessons from the pandemic on the value of research infrastructure.

The COVID-19 pandemic has shed a spotlight on the resilience of healthcare systems, and their ability to cope efficiently and effectively with unexpected crises. If we are to learn one economic lesson from the pandemic, arguably it is the perils of an overfocus on short-term allocative efficiency at the price of lack of capacity to deal with uncertain future challenges. In normal times, building spare capacity with 'option value' into health systems may seem inefficient, the costs potentially exceeding the benefits. Yet the fatal weakness of not doing so is that this can leave health systems highly constrained when dealing with unexpected, but ultimately inevitable, shocks-such as the COVID-19 pandemic. In this article, we argue that the pandemic has highlighted the potentially enormous option value of biomedical research infrastructure. We illustrate this with reference to COVID-19 response work supported by the United Kingdom National Institute for Health Research Oxford Biomedical Research Centre. As the world deals with the fallout from the most serious economic crisis since the Great Depression, pressure will soon come to review government expenditure, including research funding. Developing a framework to fully account for option value, and understanding the public appetite to pay for it, should allow us to be better prepared for the next emerging problem.

Preferences for Medical Consultations from Online Providers: Evidence from a Discrete Choice Experiment in the United Kingdom.

BACKGROUND: In the UK, consultations for prescription medicines are available via private providers such as online pharmacies. However, these providers may have lower thresholds for prescribing certain drugs. This is a particular concern for antibiotics, given the increasing burden of antimicrobial resistance. Public preferences for consultations with online providers are unknown, hence the impact of increased availability of online consultations on antibiotic use and population health is unclear. OBJECTIVE: To conduct a discrete choice experiment survey to understand UK public preferences for seeking online consultations, and the factors that influence these preferences, in the context of having symptoms for which antibiotics may be appropriate. METHODS: In a survey conducted between July and August 2018, general population respondents completed 16 questions in which they chose a primary care consultation via either their local medical centre or an online provider. Consultations were described in terms of five attributes, including cost and similarity to traditional 'face-to-face' appointments. Choices were modelled using regression analysis. RESULTS: Respondents (n = 734) placed a high value on having a consultation via their local medical centre rather than an online provider, and a low value on consultations by phone or video. However, respondents characterised as 'busy young professionals' showed a lower strength of preference for traditional consultations, with a higher concern for convenience. CONCLUSION: Before COVID-19, the UK public had limited appetite for consultations with online providers, or for consultations that were not face-to-face. Nevertheless, prescriptions from online providers should be monitored going forward, particularly for antibiotics, and in key patient groups.