Cost-utility analysis of molnupiravir plus usual care versus usual care alone as early treatment for community-based adults with COVID-19 and increased risk of adverse outcomes in the UK PANORAMIC trial.

BACKGROUND: The cost-effectiveness of molnupiravir, an oral antiviral for early treatment of SARS-CoV-2, has not been established in vaccinated populations. AIM: To evaluate the cost-effectiveness of molnupiravir relative to usual care alone among mainly vaccinated community-based people at higher risk of severe outcomes from COVID-19 over six months. DESIGN AND SETTING: Economic evaluation of the PANORAMIC trial in the UK. METHOD: A cost-utility analysis that adopted a UK National Health Service and personal social services perspective and a six-month time horizon was performed using PANORAMIC trial data. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity and subgroup analyses assessed the impacts of uncertainty and heterogeneity. Threshold analysis explored the price for molnupiravir consistent with likely reimbursement. RESULTS: In the base case analysis, molnupiravir had higher mean costs of £449 (95% confidence interval [CI] 445 to 453) and higher mean QALYs of 0.0055 (95% CI 0.004 to 0.007) than usual care (mean incremental cost per QALY of £81190). Sensitivity and subgroup analyses showed similar results, except those aged ≥75 years with a 55% probability of being cost-effective at a £30000 per QALY threshold. Molnupiravir would have to be priced around £147 per course to be cost-effective at a £15000 per QALY threshold. CONCLUSION: Molnupiravir at the current cost of £513 per course is unlikely to be cost-effective relative to usual care over a six-month time horizon among mainly vaccinated COVID-19 patients at increased risk of adverse outcomes, except those aged ≥75 years.

Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease.

INTRODUCTION: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. METHODS AND ANALYSIS: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid). ELIGIBILITY CRITERIA: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18-49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial. ETHICS AND DISSEMINATION: Ethical approval granted by South Central-Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN30448031; EudraCT number: 2021-005748-31.

Association Between Blood Pressure Control and Coronavirus Disease 2019 Outcomes in 45 418 Symptomatic Patients With Hypertension: An Observational Cohort Study.

Hypertension has been identified as a risk factor for coronavirus disease 2019 (COVID-19) and associated adverse outcomes. This study examined the association between preinfection blood pressure (BP) control and COVID-19 outcomes using data from 460 general practices in England. Eligible patients were adults with hypertension who were tested or diagnosed with COVID-19. BP control was defined by the most recent BP reading within 24 months of the index date (January 1, 2020). BP was defined as controlled (<130/80 mm Hg), raised (130/80-139/89 mm Hg), stage 1 uncontrolled (140/90-159/99 mm Hg), or stage 2 uncontrolled (≥160/100 mm Hg). The primary outcome was death within 28 days of COVID-19 diagnosis. Secondary outcomes were COVID-19 diagnosis and COVID-19-related hospital admission. Multivariable logistic regression was used to examine the association between BP control and outcomes. Of the 45 418 patients (mean age, 67 years; 44.7% male) included, 11 950 (26.3%) had controlled BP. These patients were older, had more comorbidities, and had been diagnosed with hypertension for longer. A total of 4277 patients (9.4%) were diagnosed with COVID-19 and 877 died within 28 days. Individuals with stage 1 uncontrolled BP had lower odds of COVID-19 death (odds ratio, 0.76 [95% CI, 0.62-0.92]) compared with patients with well-controlled BP. There was no association between BP control and COVID-19 diagnosis or hospitalization. These findings suggest BP control may be associated with worse COVID-19 outcomes, possibly due to these patients having more advanced atherosclerosis and target organ damage. Such patients may need to consider adhering to stricter social distancing, to limit the impact of COVID-19 as future waves of the pandemic occur.

Establishing a pharmacist-prescriber partnership in publicly funded primary healthcare clinics to optimise antibiotic prescribing in the Western Cape: An exploratory study.

BACKGROUND: Promoting evidence-based antibiotic prescribing through successful antimicrobial stewardship (AMS) programmes is critical to preserving the effectiveness of antibiotics for common infections in primary care. This requires a coordinated multidisciplinary effort. Such pharmacist-prescriber partnerships have been effective in high-income countries (HICs). Yet, evidence generated in such countries is not always applicable because of different social determinants of health. METHODS: A multidisciplinary workshop was conducted with pharmacists and clinicians (doctors, nurses) on community-based antibiotic stewardship, the purpose of which was to explore how and where such partnerships might work in publicly funded primary care clinics in the greater Cape Metro region. RESULTS: Participants perceived that promoting effective AMS was a priority for South African primary healthcare. However, it was clear that there are many hurdles to overcome working in settings that are relatively resource-poor. Prescribing guidelines needed to be harmonised. Participants felt that staff training on the principles of AMS should be mandatory. Research was urgently needed to better understand their community's understanding of antibiotic use and AMS, and to champion outreach projects in the community. CONCLUSION: Important stakeholder perspectives in the community were highlighted to promote a multidisciplinary approach to AMS initiatives in primary care. These will need to be addressed to optimise antibiotic prescribing in the community.

Introducing new point-of-care tests for common infections in publicly funded clinics in South Africa: a qualitative study with primary care clinicians.

Broad-spectrum antibiotics are routinely prescribed empirically in the resource-poor settings for suspected acute common infections, which drive antimicrobial resistance. Point-of-care testing (POCT) might increase the appropriateness of decisions about whether and which antibiotic to prescribe, but implementation will be most effective if clinician's perspectives are taken into account. OBJECTIVES: To explore the perceptions of South African primary care clinicians working in publicly funded clinics about: making antibiotic prescribing decisions for two common infection syndromes (acute cough, urinary tract infection); their experiences of existing POCTs; their perceptions of the barriers and opportunities for introducing (hypothetical) new POCTs. DESIGN, METHOD, PARTICIPANTS, SETTING: Qualitative semistructured interviews with 23 primary care clinicians (nurses and doctors) at publicly funded clinics in the Western Cape Metro district, South Africa. Data were analysed using thematic analysis. RESULTS: Clinicians reported that their antibiotic prescribing decisions were influenced by their clinical assessment, patient comorbidities, social factors (eg, access to care) and perceived patient expectations. Their experiences with currently available POCTs were largely positive, and they were optimistic about the potential for new POCTs to: support evidence-based prescribing decisions that might reduce unnecessary antibiotic prescriptions; reduce the need for further investigations; support effective communication with patients, especially when antibiotics were unlikely to be of benefit. Resources and workflow disruption were seen as the main barriers to uptake into routine care. CONCLUSIONS: Clinicians working in publicly funded clinics in the Western Cape Metro of South Africa saw POCTs as potentially useful for positively addressing both clinical and social drivers of the overprescribing of broad-spectrum antibiotics, but were concerned about the resource implications and disruption of existing patient workflows.

The use of chaperones in general practice: Is this just a 'Western' concept?

BACKGROUND: The literature about medical chaperones in primary care is limited to a handful of English-speaking countries. It remains largely unknown to what extent chaperones are offered (and used) outside the published literature. OBJECTIVE: The current study aimed to explore the attitudes and experiences of a group of general practitioners (GPs; family doctors) attending an international primary care conference regarding their use of medical chaperones. METHODS: Ninety international GPs completed a validated questionnaire, providing information on their current practice, availability and preferred choice of chaperone. Participants expressed their opinion on the importance of, and facilitators and barriers for chaperone use. RESULTS: Although most participants had knowledge of the term 'medical chaperone' (75%), those with a qualification from Europe (other than the UK) were less likely to offer a chaperone. Two-thirds of all participants would consider offering a chaperone and were more likely to work in the public sector (p = .04; Cramér's V = 0.27). A practice nurse was most commonly used as chaperone. Chaperone users ranked the 'medico-legal protection of doctors', 'doctors' professional practice' and 'protection of patients' as the most important factors for using a chaperone. Non-users reported 'personal choice of the doctor', 'confidentiality' and 'impact on the doctor-patient relationship' as the main areas influencing their decision not to use a chaperone. CONCLUSION: International doctors hold different views about the use (or not) of chaperones within their clinical practice and its effect on the doctor-patient consultation. Further research is needed to tease out the reasons for this.