Overcoming challenges in the economic evaluation of interventions to optimise antibiotic use.

Bacteria are becoming increasingly resistant to antibiotics, reducing our ability to treat infections and threatening to undermine modern health care. Optimising antibiotic use is a key element in tackling the problem. Traditional economic evaluation methods do not capture many of the benefits from improved antibiotic use and the potential impact on resistance. Not capturing these benefits is a major obstacle to optimising antibiotic use, as it fails to incentivise the development and use of interventions to optimise the use of antibiotics and preserve their effectiveness (stewardship interventions). Estimates of the benefits of improving antibiotic use involve considerable uncertainty as they depend on the evolution of resistance and associated health outcomes and costs. Here we discuss how economic evaluation methods might be adapted, in the face of such uncertainties. We propose a threshold-based approach that estimates the minimum resistance-related costs that would need to be averted by an intervention to make it cost-effective. If it is probable that without the intervention costs will exceed the threshold then the intervention should be deemed cost-effective.

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 comparative mortality of an elite group in the long run of history: an observational analysis of politicians from 11 countries.

This study aims to compare the mortality rate and life expectancy of politicians with those of the age and gender-matched general populations. This was an observational analysis of mortality rates of politicians (i.e. members of national parliaments with available data on dates of birth, death and election, gender, and life tables) in 11 developed countries. Politicians were followed from date of first election until either death or the last available year with life table data. Relative mortality differences were estimated using standardised mortality ratios (SMRs). Absolute inequalities were quantified as the difference in survival by deducting a population's remaining life expectancy from politicians' remaining life expectancy at age 45, estimated using Gompertz parametric proportional hazards models. We included 57,561 politicians (with follow-up ranging from 1816-2016 for France to 1949-2017 for Germany). In almost all countries politicians had similar rates of mortality to the general population in the early part of the twentieth century. Relative mortality and survival differences (favouring politicians) increased considerably over the course of the twentieth century, with recent SMRs ranging from 0.45 (95%CI 0.41-0.50) in Italy to 0.82 (95%CI 0.69-0.95) in New Zealand. The peak life expectancy gaps ranged from 4.4 (95% CI, 3.5-5.4) years in the Netherlands to 7.8 (95% CI, 7.2-8.4) years in the US. Our results show large relative and absolute inequalities favouring politicians in every country. In some countries, such as the US, relative inequalities are at the greatest level in over 150 years.

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.

Eliciting risk preferences that predict risky health behavior: A comparison of two approaches.

Information on attitudes to risk could increase understanding of and explain risky health behaviors. We investigate two approaches to eliciting risk preferences in the health domain, a novel "indirect" lottery elicitation approach with health states as outcomes and a "direct" approach where respondents are asked directly about their willingness to take risks. We compare the ability of the two approaches to predict health-related risky behaviors in a general adult population. We also investigate a potential framing effect in the indirect lottery elicitation approach. We find that risk preferences elicited using the direct approach can better predict health-related risky behavior than those elicited using the indirect approach. Moreover, a seemingly innocuous change to the framing of the lottery question results in significantly different risk preference estimates, and conflicting conclusions about the ability of the indicators to predict risky health behaviors.

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.

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.

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.

Public preferences for delayed or immediate antibiotic prescriptions in UK primary care: A choice experiment.

BACKGROUND: Delayed (or "backup") antibiotic prescription, where the patient is given a prescription but advised to delay initiating antibiotics, has been shown to be effective in reducing antibiotic use in primary care. However, this strategy is not widely used in the United Kingdom. This study aimed to identify factors influencing preferences among the UK public for delayed prescription, and understand their relative importance, to help increase appropriate use of this prescribing option. METHODS AND FINDINGS: We conducted an online choice experiment in 2 UK general population samples: adults and parents of children under 18 years. Respondents were presented with 12 scenarios in which they, or their child, might need antibiotics for a respiratory tract infection (RTI) and asked to choose either an immediate or a delayed prescription. Scenarios were described by 7 attributes. Data were collected between November 2018 and February 2019. Respondent preferences were modelled using mixed-effects logistic regression. The survey was completed by 802 adults and 801 parents (75% of those who opened the survey). The samples reflected the UK population in age, sex, ethnicity, and country of residence. The most important determinant of respondent choice was symptom severity, especially for cough-related symptoms. In the adult sample, the probability of choosing delayed prescription was 0.53 (95% confidence interval (CI) 0.50 to 0.56, p < 0.001) for a chesty cough and runny nose compared to 0.30 (0.28 to 0.33, p < 0.001) for a chesty cough with fever, 0.47 (0.44 to 0.50, p < 0.001) for sore throat with swollen glands, and 0.37 (0.34 to 0.39, p < 0.001) for sore throat, swollen glands, and fever. Respondents were less likely to choose delayed prescription with increasing duration of illness (odds ratio (OR) 0.94 (0.92 to 0.96, p < 0.001)). Probabilities of choosing delayed prescription were similar for parents considering treatment for a child (44% of choices versus 42% for adults, p = 0.04). However, parents differed from the adult sample in showing a more marked reduction in choice of the delayed prescription with increasing duration of illness (OR 0.83 (0.80 to 0.87) versus 0.94 (0.92 to 0.96) for adults, p for heterogeneity p < 0.001) and a smaller effect of disruption of usual activities (OR 0.96 (0.95 to 0.97) versus 0.93 (0.92 to 0.94) for adults, p for heterogeneity p < 0.001). Females were more likely to choose a delayed prescription than males for minor symptoms, particularly minor cough (probability 0.62 (0.58 to 0.66, p < 0.001) for females and 0.45 (0.41 to 0.48, p < 0.001) for males). Older people, those with a good understanding of antibiotics, and those who had not used antibiotics recently showed similar patterns of preferences. Study limitations include its hypothetical nature, which may not reflect real-life behaviour; the absence of a "no prescription" option; and the possibility that study respondents may not represent the views of population groups who are typically underrepresented in online surveys. CONCLUSIONS: This study found that delayed prescription appears to be an acceptable approach to reducing antibiotic consumption. Certain groups appear to be more amenable to delayed prescription, suggesting particular opportunities for increased use of this strategy. Prescribing choices for sore throat may need additional explanation to ensure patient acceptance, and parents in particular may benefit from reassurance about the usual duration of these illnesses.

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.

First estimates of inequality benchmark incomes for a range of countries.

It is known that virtually all inequality measures imply the existence of a 'benchmark income', above which adding incremental income increases inequality, and below which it decreases inequality. Benchmark incomes can be interpreted as social reference levels that identify the richest individual for whom it would be just to subsidize their income. Despite the intuitive appeal of benchmark incomes, there have been hardly any empirical applications to date. This paper provides the first estimates of benchmark incomes for a range of contrasting countries and different inequality measures. All benchmark incomes lie far above official national poverty lines. The results suggest that economic growth together with falling inequality need not necessarily be poverty reducing.

Awareness of Appropriate Antibiotic Use in Primary Care for Influenza-Like Illness: Evidence of Improvement from UK Population-Based Surveys.

Influenza-like illnesses (ILI) account for a significant portion of inappropriate antibiotic use. Patient expectations for antibiotics for ILI are likely to play a substantial role in 'unnecessary' antibiotic consumption. This study aimed to investigate trends in awareness of appropriate antibiotic use and antimicrobial resistance (AMR). Three sequential online surveys of independent representative samples of adults in the United Kingdom investigated expectations for, and consumption of, antibiotics for ILI (May/June 2015 (n = 2064); Oct/Nov 2016 (n = 4000); Mar 2017 (n = 4000)). Respondents were asked whether they thought antibiotics were effective for ILI and about their antibiotic use. Proportions and 95% confidence intervals (CI) were calculated for each question and interactions with respondent characteristics were tested using logistic regression. Over the three surveys, the proportion of respondents who believed antibiotics would "definitely/probably" help an ILI fell from 37% (95% CI 35-39%) to 28% (95% CI 26-29%). Those who would "definitely/probably" visit a doctor in this situation fell from 48% (95% CI 46-50%) to 36% (95% CI 34-37%), while those who would request antibiotics during a consultation fell from 39% (95% CI 37-41%) to 30% (95% CI 29-32%). The percentage of respondents who found the information we provided about AMR "new/surprising" fell from 34% (95% CI 32-36%) to 28% (95% CI 26-31%). Awareness improved more among black, Asian and minority ethnic (BAME) than white people, with little other evidence of differences in improvements between subgroups. Whilst a degree of selection bias is unavoidable in online survey samples, the results suggest that awareness of AMR and appropriate antibiotic use has recently significantly improved in the United Kingdom, according to a wide range of indicators.

Delayed Antibiotic Prescription by General Practitioners in the UK: A Stated-Choice Study.

Delayed antibiotic prescription in primary care has been shown to reduce antibiotic consumption, without increasing risk of complications, yet is not widely used in the UK. We sought to quantify the relative importance of factors affecting the decision to give a delayed prescription, using a stated-choice survey among UK general practitioners. Respondents were asked whether they would provide a delayed or immediate prescription in fifteen hypothetical consultations, described by eight attributes. They were also asked if they would prefer not to prescribe antibiotics. The most important determinants of choice between immediate and delayed prescription were symptoms, duration of illness, and the presence of multiple comorbidities. Respondents were more likely to choose a delayed prescription if the patient preferred not to have antibiotics, but consultation length had little effect. When given the option, respondents chose not to prescribe antibiotics in 51% of cases, with delayed prescription chosen in 21%. Clinical features remained important. Patient preference did not affect the decision to give no antibiotics. We suggest that broader dissemination of the clinical evidence supporting use of delayed prescription for specific presentations may help increase appropriate use. Establishing patient preferences regarding antibiotics may help to overcome concerns about patient acceptance. Increasing consultation length appears unlikely to affect the use of delayed prescription.

Why do hospital prescribers continue antibiotics when it is safe to stop? Results of a choice experiment survey.

BACKGROUND: Deciding whether to discontinue antibiotics at early review is a cornerstone of hospital antimicrobial stewardship practice worldwide. In England, this approach is described in government guidance ('Start Smart then Focus'). However, < 10% of hospital antibiotic prescriptions are discontinued at review, despite evidence that 20-30% could be discontinued safely. We aimed to quantify the relative importance of factors influencing prescriber decision-making at review. METHODS: We conducted an online choice experiment, a survey method to elicit preferences. Acute/general hospital prescribers in England were asked if they would continue or discontinue antibiotic treatment in 15 hypothetical scenarios. Scenarios were described according to six attributes, including patients' presenting symptoms and whether discontinuation would conflict with local prescribing guidelines. Respondents' choices were analysed using conditional logistic regression. RESULTS: One hundred respondents completed the survey. Respondents were more likely to continue antibiotics when discontinuation would 'strongly conflict' with local guidelines (average marginal effect (AME) on the probability of continuing + 0.194 (p < 0.001)), when presenting symptoms more clearly indicated antibiotics (AME of urinary tract infection symptoms + 0.173 (p < 0.001) versus unclear symptoms) and when patients had severe frailty/comorbidities (AME = + 0.101 (p < 0.001)). Respondents were less likely to continue antibiotics when under no external pressure to continue (AME = - 0.101 (p < 0.001)). Decisions were also influenced by the risks to patient health of continuing/discontinuing antibiotic treatment. CONCLUSIONS: Guidelines that conflict with antibiotic discontinuation (e.g. pre-specify fixed durations) may discourage safe discontinuation at review. In contrast, guidelines conditional on patient factors/treatment response could help hospital prescribers discontinue antibiotics if diagnostic information suggesting they are no longer needed is available.