Antimicrobial stewardship in human healthcare in Aotearoa New Zealand: urgent call for national leadership and co-ordinated efforts to preserve antimicrobial effectiveness

Within 30 years, the global number of deaths from AMR-associated infections is predicted to increase from ~700,000 to ~10 million people annually, if we do not act now.1 The Aotearoa New Zealand (NZ) response to the current COVID-19 pandemic has been lauded internationally-found-ed in science, responsive to expert advice, implemented with clear leadership and communication, and subject to ongoing critical evaluation and improvement. AMR-associated infections and related care (eg, time off work or school to travel to hospital for treatment) will disproportionately impact the most socioeconomically disadvantaged among us, those living in rural or remote settings, and Maori and Pacific populations who shoulder a greater infection and AMR burden and have increased reliance on antimicrobial therapy.6'7 One of the biggest drivers for AMR is antimicrobial use, which is high in human health in NZ compared with many developed countries.8'9 Most of our antimicrobial use (95%) is in the community9 and up to 50% may be inappropriate.2 The NZ community antibacterial consumption rate increased 49% between 2006 and 2014;in 2013, it exceeded that of 22 out of 29 European countries.8 A subsequent modest 14% decrease occurred across 2015 to 2018, mainly due to reductions in under 5 year olds,10 which is pleasing as antimicrobial use in childhood may create reservoirs of resistant pathogens impacting communities cross-generationally. In 2013, the Health Quality and Safety Commission (HQSC) published a scoping report that offered insight into what was needed to progress AMS in NZ.14 Key recommendations were to establish: * National leadership and coordination of AMS activities * National antimicrobial prescribing guidelines * Quality improvement tools and measures In the near decade that has followed this report, none of these recommendations have been achieved. The NCAMS should provide access to (and support use of) quality improvement tools (eg, auditing systems for between facility benchmarking), develop initiatives to improve antimicrobial use (including those involving consumers), monitor performance against quality markers, and establish clinical care standards with the oversight of NAMSEG.

Cardiovascular Disease Prevention During the COVID-19 Pandemic: Lessons Learned and Future Opportunities.

The coronavirus disease 2019 (COVID-19) pandemic has been the defining healthcare issue since its outbreak, consuming healthcare systems and disrupting all aspects of human life throughout 2020 and continuing through 2021. When reviewing cardiovascular disease (CVD) prevention throughout the COVID-19 pandemic, the first tendency may be to focus on the negative disruption. Months of quarantine, isolation, and missed healthcare visits or delayed care may have exacerbated the epidemic of CVD in the United States. Looking back, however, perhaps it wasn't a lost year as much as a health crisis that better prepared us for the battle to improve cardiovascular health. The pandemic brought new platforms for interacting with patients eager to engage, presenting a unique opportunity to reset how we approach preventive care. In this review, we discuss what the pandemic has taught us about caring for those vulnerable patients who were most afflicted-older adults, persons of color, and people facing adverse socioeconomic circumstances-and who continue to be impacted by CVD. We also identify opportunities for enhanced CVD prevention now boosted by the overnight adoption of telemedicine and other innovative cardiac care models. Lastly, we discuss how the COVID-19 pandemic has motivated physicians and patients alike to prioritize our health above all else, if only transiently, and how we can leverage this increased health awareness and investment into long-term, meaningful disease prevention.

Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial.

PURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.

The impacts of New Zealand's COVID-19 epidemic response on community antibiotic use and hospitalisation for pneumonia, peritonsillar abscess and rheumatic fever.

BACKGROUND: The rate of community antibiotic use in New Zealand (NZ) is high and some may be unnecessary. Non-pharmaceutical public health interventions (Alert Levels) were implemented in 2020 to reduce the spread of COVID-19 in NZ and were likely to have affected antibiotic prescribing. METHODS: We aimed to identify the impact of these public health interventions on community antibiotic dispensing. We also examined rates of hospitalisation with infectious diseases that could be influenced by changing community antibiotic use. A retrospective review of two national databases was undertaken. FINDINGS: 1.17 million people received 1.19 million prescriptions for antibiotics between 23/02/2020 and 18/07/2020. Antibiotic dispensing rates fell from 14 prescriptions per 1000 population per week during pre-Alert Level weeks to 9 prescriptions per 1000 population per week (a reduction of 36%) during the weeks of COVID Alert Level 3-4. Large reductions were seen with antibiotics predominantly used for respiratory- or urinary-tract infections. Hospital discharges with sentinel infections did not increase over this period; pneumonia discharges during Alert Level weeks were lower than in 2017-2019 (3 vs 6 discharges per 100,000 population). INTERPRETATION: A large reduction in community antibiotic dispensing was observed in NZ during the implementation of non-pharmaceutical public health interventions to eliminate COVID-19. Despite this marked reduction in antibiotic use, there was no increase in rates of hospitalisation for sentinel infections that community antibiotic use could prevent. These findings suggest that countries with high rates of antibiotic use could significantly reduce their use without an increase in morbidity. FUNDING: No financial support received.

COVID and Cardiovascular Disease: What We Know in 2021.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has been the cause of significant global morbidity and mortality. Here, we review the literature to date of the short-term and long-term consequences of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection on the heart. RECENT FINDINGS: Early case reports described a spectrum of cardiovascular manifestations of COVID-19, including myocarditis, stress cardiomyopathy, myocardial infarction, and arrhythmia. However, in most cases, myocardial injury in COVID-19 appears to be predominantly mediated by the severity of critical illness rather than direct injury to myocardium from viral particles. While cardiac magnetic resonance imaging remains a powerful tool for diagnosing acute myocarditis, it should be used judiciously in light of low baseline prevalence of myocarditis. Guiding an athletic patient through return to play (RTP) after COVID-19 infection is a challenging process. More recent data show RTP has been a safe endeavor using a screening protocol. "Long COVID" or post-acute sequelae of SARS-CoV-2 infection has also been described. The reported symptoms span a large breadth of cardiopulmonary and neurologic complaints including fatigue, palpitations, chest pain, breathlessness, brain fog, and dysautonomia including postural tachycardia syndrome (POTS). Management of POTS/dysautonomia primarily centers on education, exercise, and salt and fluid repletion. Our understanding of the impact of COVID-19 on the cardiovascular system is constantly evolving. As we enter a new age of survivorship, additional research is needed to catalogue the burden of persistent cardiopulmonary symptoms. Research is also needed to learn how acute management may alter the likelihood and prevalence of this chronic syndrome.

Tandem high-dose influenza vaccination is associated with more durable serologic immunity in patients with plasma cell dyscrasias.

Patients with plasma cell dyscrasias (PCDs) experience an increased burden of influenza, and current practice of single-dose annual influenza vaccination yields suboptimal protective immunity in these patients. Strategies to improve immunity to influenza in these patients are clearly needed. We performed a randomized, double-blind, placebo-controlled clinical trial comparing tandem Fluzone High-Dose influenza vaccination with standard-of-care influenza vaccination. Standard-of-care vaccination was single-dose age-based vaccination (standard dose, <65 years; high dose, ≥65 years), and patients in this arm received a saline placebo injection at 30 days. A total of 122 PCD patients were enrolled; 47 received single-dose standard-of-care vaccination, and 75 received 2 doses of Fluzone High-Dose vaccine. Rates of hemagglutinin inhibition (HAI) titer seroprotection against all 3 strains (H1N1, H3N2, and influenza B) were significantly higher for patients after tandem high-dose vaccination vs control (87.3% vs 63.2%; P = .003) and led to higher seroprotection at the end of flu season (60.0% vs 31.6%; P = .04). These data demonstrate that tandem high-dose influenza vaccination separated by 30 days leads to higher serologic HAI titer responses and more durable influenza-specific immunity in PCD patients. Similar vaccine strategies may also be essential to achieve protective immunity against other emerging pathogens such as novel coronavirus in these patients. This trial was registered at www.clinicaltrials.gov as #NCT02566265.

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).

Opportunities to improve cardiovascular health in the new American workplace.

Adult working-class Americans spend on average 50% of their workday awake time at their jobs. The vast majority of these jobs involve mostly physically inactive tasks and frequent exposure to unhealthy food options. Traditionally, the workplace has been a challenging environment for cardiovascular prevention, where cardiovascular guidelines have had limited implementation. Despite the impact that unhealthy lifestyles at the workplace may have on the cardiovascular health of U.S. workers, there is currently no policy in place aimed at improving this. In this review, we discuss recent evidence on the prevalence of physical inactivity among Americans, with a special focus on the time spent at the workplace; and the invaluable opportunity that workplace-based lifestyle interventions may represent for improving the prevention of cardiovascular disease. We describe the current regulatory context, the key stakeholders involved, and present specific, guideline-inspired initiatives to be considered by both Congress and employers to improve the "cardiovascular safety" of US jobs. Additionally, we discuss how the COVID-19 pandemic has forever altered the workplace, and what lessons can be taken from this experience and applied to cardiovascular disease prevention in the new American workplace. For many Americans, long sitting hours at their job represent a risk to their cardiovascular health. We discuss how a paradigm shift in how we approach cardiovascular health, from focusing on leisure time to also focusing on work time, may help curtail the epidemic of cardiovascular disease in this country.