C-reactive protein point-of-care testing in primary care-broader implementation needed to combat antimicrobial resistance.

This study presents the perspective of an international group of experts, providing an overview of existing models and policies and guidance to facilitate a proper and sustainable implementation of C-reactive protein point-of-care testing (CRP POCT) to support antibiotic prescribing decisions for respiratory tract infections (RTIs) with the aim to tackle antimicrobial resistance (AMR). AMR threatens to render life-saving antibiotics ineffective and is already costing millions of lives and billions of Euros worldwide. AMR is strongly correlated with the volume of antibiotics used. Most antibiotics are prescribed in primary care, mostly for RTIs, and are often unnecessary. CRP POCT is an available tool and has been proven to safely and cost-effectively reduce antibiotic prescribing for RTIs in primary care. Though established in a few European countries during several years, it has still not been implemented in many European countries. Due to the complexity of inappropriate antibiotic prescribing behavior, a multifaceted approach is necessary to enable sustainable change. The effect is maximized with clear guidance, advanced communication training for primary care physicians, and delayed antibiotic prescribing strategies. CRP POCT should be included in professional guidelines and implemented together with complementary strategies. Adequate reimbursement needs to be provided, and high-quality, and primary care-friendly POCT organization and performance must be enabled. Data gathering, sharing, and discussion as incentivization for proper behaviors should be enabled. Public awareness should be increased, and healthcare professionals' awareness and understanding should be ensured. Impactful use is achieved when all stakeholders join forces to facilitate proper implementation.

'Everyone has heard of it, but no one knows what it is': A qualitative study of patient understandings and experiences of herpes zoster.

BACKGROUND: Shingles (herpes zoster), caused by reactivation of the varicella-zoster virus, is usually diagnosed and managed in primary care. The lifetime risk of shingles in the general population is approximately 30%, and it can have a detrimental effect on quality of life. There has been little qualitative research about patient experience and understanding of shingles. DESIGN AND SETTING: Qualitative interviews with people recruited from primary care in England. METHOD: Qualitative semi-structured remote interviews were undertaken with 29 participants in a randomised controlled trial in primary care in England (ATHENA, ISRCTN14490832). Participants were aged >49 and were diagnosed within six days of shingles rash onset. Interviewees were sampled for diversity in terms of pain, intervention adherence, age, gender, and ethnicity. Data were analysed using reflexive thematic analysis. FINDINGS: Participants' understanding of shingles was limited, particularly pre-diagnosis. Television campaigns about the shingles vaccination programme helped some to recognise the rash. Shingles was understood as a disease with a variable prognosis, resulting in a sense of uncertainty about the significance when diagnosed. Participants reported a range of symptoms which impacted on everyday life. Some people thought their diagnosis was caused by poor mental health or challenging life circumstances, a perception sometimes reinforced by healthcare professionals. Many participants sought meaning in their diagnosis, reflecting upon, and sometimes changing, their life and circumstances. CONCLUSION: Primary care practitioners should be aware of the broad spectrum of patient knowledge, and the potential for better understanding to promote early attendance and treatment, to reduce the impact of shingles.

Cost-utility analysis of molnupiravir for high-risk, community-based adults with COVID-19: an economic evaluation of the 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 6 months. DESIGN AND SETTING: An economic evaluation of the PANORAMIC trial in the UK. METHOD: A cost-utility analysis that adopted a UK NHS and personal social services perspective and a 6-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 = 0.0044 to 0.0067) than usual care (mean incremental cost per QALY of £81 190). Sensitivity and subgroup analyses showed similar results, except for those aged ≥75 years, with a 55% probability of being cost-effective at a £30 000 per QALY threshold. Molnupiravir would have to be priced around £147 per course to be cost-effective at a £15 000 per QALY threshold. CONCLUSION: At the current cost of £513 per course, molnupiravir is unlikely to be cost-effective relative to usual care over a 6-month time horizon among mainly vaccinated patients with COVID-19 at increased risk of adverse outcomes, except those aged ≥75 years.

Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients.

Viral clearance, antibody response and the mutagenic effect of molnupiravir has not been elucidated in at-risk populations. Non-hospitalised participants within 5 days of SARS-CoV-2 symptoms randomised to receive molnupiravir (n = 253) or Usual Care (n = 324) were recruited to study viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1437 viral genomes. Molnupiravir accelerates viral load decline, but virus is detectable by Day 5 in most cases. At Day 14 (9 days post-treatment), molnupiravir is associated with significantly higher viral persistence and significantly lower anti-SARS-CoV-2 spike antibody titres compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment. Persistence of detectable viral RNA at Day 14 in the molnupiravir group is associated with higher transition mutations following treatment cessation. Viral viability at Day 14 is similar in both groups with post-molnupiravir treated samples cultured up to 9 days post cessation of treatment. The current 5-day molnupiravir course is too short. Longer courses should be tested to reduce the risk of potentially transmissible molnupiravir-mutated variants being generated. Trial registration: ISRCTN30448031.