The Impact of the COVID-19 Pandemic on Cardiac Procedure Wait List Mortality in Ontario, Canada.

BACKGROUND: The novel SARS-CoV-2 (COVID-19) pandemic has dramatically altered the delivery of healthcare services, resulting in significant referral pattern changes, delayed presentations, and procedural delays. Our objective was to determine the effect of the COVID-19 pandemic on all-cause mortality in patients awaiting commonly performed cardiac procedures. METHODS: Clinical and administrative data sets were linked to identify all adults referred for: (1) percutaneous coronary intervention; (2) coronary artery bypass grafting; (3) valve surgery; and (4) transcatheter aortic valve implantation, from January 2014 to September 2020 in Ontario, Canada. Piece-wise regression models were used to determine the effect of the COVID-19 pandemic on referrals and procedural volume. Multivariable Cox proportional hazards models were used to determine the effect of the pandemic on waitlist mortality for the 4 procedures. RESULTS: We included 584,341 patients who were first-time referrals for 1 of the 4 procedures, of whom 37,718 (6.4%) were referred during the pandemic. The pandemic period was associated with a significant decline in the number of referrals and procedures completed compared with the prepandemic period. Referral during the pandemic period was a significant predictor for increased all-cause mortality for the percutaneous coronary intervention (hazard ratio, 1.83; 95% confidence interval, 1.47-2.27) and coronary artery bypass grafting (hazard ratio, 1.96; 95% confidence interval, 1.28-3.01), but not for surgical valve or transcatheter aortic valve implantation referrals. Procedural wait times were shorter during the pandemic period compared with the prepandemic period. CONCLUSIONS: There was a significant decrease in referrals and procedures completed for cardiac procedures during the pandemic period. Referral during the pandemic was associated with increased all-cause mortality while awaiting coronary revascularization.

Prioritizing IVF treatment in the post-COVID 19 era: a predictive modelling study based on UK national data.

STUDY QUESTION: Can we use prediction modelling to estimate the impact of coronavirus disease 2019 (COVID 19) related delay in starting IVF or ICSI in different groups of women? SUMMARY ANSWER: Yes, using a combination of three different models we can predict the impact of delaying access to treatment by 6 and 12 months on the probability of conception leading to live birth in women of different age groups with different categories of infertility. WHAT IS KNOWN ALREADY: Increased age and duration of infertility can prejudice the chances of success following IVF, but couples with unexplained infertility have a chance of conceiving naturally without treatment whilst waiting for IVF. The worldwide suspension of IVF could lead to worse outcomes in couples awaiting treatment, but it is unclear to what extent this could affect individual couples based on age and cause of infertility. STUDY DESIGN, SIZE, DURATION: A population-based cohort study based on national data from all licensed clinics in the UK obtained from the Human Fertilisation and Embryology Authority Register. Linked data from 9589 women who underwent their first IVF or ICSI treatment in 2017 and consented to the use of their data for research were used to predict livebirth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three prediction models were used to estimate the chances of livebirth associated with immediate treatment versus a delay of 6 and 12 months in couples about to embark on IVF or ICSI. MAIN RESULTS AND THE ROLE OF CHANCE: We estimated that a 6-month delay would reduce IVF livebirths by 0.4%, 2.4%, 5.6%, 9.5% and 11.8% in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively, while corresponding values associated with a delay of 12 months were 0.9%, 4.9%, 11.9%, 18.8% and 22.4%, respectively. In women with known causes of infertility, worst case (best case) predicted chances of livebirth after a delay of 6 months followed by one complete IVF cycle in women aged <30, 30-35, 36-37, 38-39 and 40-42 years varied between 31.6% (35.0%), 29.0% (31.6%), 23.1% (25.2%), 17.2% (19.4%) and 10.3% (12.3%) for tubal infertility and 34.3% (39.2%), 31.6% (35.3%) 25.2% (28.5%) 18.3% (21.3%) and 11.3% (14.1%) for male factor infertility. The corresponding values in those treated immediately were 31.7%, 29.8%, 24.5%, 19.0% and 11.7% for tubal factor and 34.4%, 32.4%, 26.7%, 20.2% and 12.8% in male factor infertility. In women with unexplained infertility the predicted chances of livebirth after a delay of 6 months followed by one complete IVF cycle were 41.0%, 36.6%, 29.4%, 22.4% and 15.1% in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively, compared to 34.9%, 32.5%, 26.9%, 20.7% and 13.2% in similar groups of women treated without any delay. The additional waiting period, which provided more time for spontaneous conception, was predicted to increase the relative number of babies born by 17.5%, 12.6%, 9.1%, 8.4% and 13.8%, in women aged <30, 30-35, 36-37, 38-39 and 40-42 years, respectively. A 12-month delay showed a similar pattern in all subgroups. LIMITATIONS, REASONS FOR CAUTION: Major sources of uncertainty include the use of prediction models generated in different populations and the need for a number of assumptions. Although the models are validated and the bases for the assumptions are robust, it is impossible to eliminate the possibility of imprecision in our predictions. Therefore, our predicted live birth rates need to be validated in prospective studies to confirm their accuracy. WIDER IMPLICATIONS OF THE FINDINGS: A delay in starting IVF reduces success rates in all couples. For the first time, we have shown that while this results in fewer babies in older women and those with a known cause of infertility, it has a less detrimental effect on couples with unexplained infertility, some of whom conceive naturally whilst waiting for treatment. Post-COVID 19, clinics planning a phased return to normal clinical services should prioritize older women and those with a known cause of infertility. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this study. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy work for ObsEva, Merck, Merck KGaA, Guerbet and iGenomics. S.B. is Editor-in-Chief of Human Reproduction Open. None of the other authors declare any conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).

COVID-19 pandemic and STEMI: pathway activation and outcomes from the pan-London heart attack group.

OBJECTIVES: To understand the impact of COVID-19 on delivery and outcomes of primary percutaneous coronary intervention (PPCI). Furthermore, to compare clinical presentation and outcomes of patients with ST-segment elevation myocardial infarction (STEMI) with active COVID-19 against those without COVID-19. METHODS: We systematically analysed 348 STEMI cases presenting to the PPCI programme in London during the peak of the pandemic (1 March to 30 April 2020) and compared with 440 cases from the same period in 2019. Outcomes of interest included ambulance response times, timeliness of revascularisation, angiographic and procedural characteristics, and in-hospital clinical outcomes RESULTS: There was a 21% reduction in STEMI admissions and longer ambulance response times (87 (62-118) min in 2020 vs 75 (57-95) min in 2019, p<0.001), but that this was not associated with a delays in achieving revascularisation once in hospital (48 (34-65) min in 2020 vs 48 (35-70) min in 2019, p=0.35) or increased mortality (10.9% (38) in 2020 vs 8.6% (38) in 2019, p=0.28). 46 patients with active COVID-19 were more thrombotic and more likely to have intensive care unit admissions (32.6% (15) vs 9.3% (28), OR 5.74 (95%CI 2.24 to 9.89), p<0.001). They also had increased length of stay (4 (3-9) days vs 3 (2-4) days, p<0.001) and a higher mortality (21.7% (10) vs 9.3% (28), OR 2.72 (95% CI 1.25 to 5.82), p=0.012) compared with patients having PPCI without COVID-19. CONCLUSION: These findings suggest that PPCI pathways can be maintained during unprecedented healthcare emergencies but confirms the high mortality of STEMI in the context of concomitant COVID-19 infection characterised by a heightened state of thrombogenicity.

Cardiac procedural deferral during the coronavirus (COVID-19) pandemic.

We aimed to examine factors impacting variability in cardiac procedural deferral during the COVID-19 pandemic and assess cardiologists' perspectives regarding its implications. Unprecedented cardiac procedural deferral was implemented nationwide during the COVID-19 pandemic. A web-based survey was administered by Society for Cardiovascular Angiography and Interventions and the American College of Cardiology Interventional Council to cardiac catheterization laboratory (CCL) directors and interventional cardiologists across the United States during the COVID-19 pandemic. Among 414 total responses, 48 states and 360 unique cardiac catheterization laboratories were represented, with mean inpatient COVID-19 burden 16.4 ± 21.9%. There was a spectrum of deferral by procedure type, varying by both severity of COVID-19 burden and procedural urgency (p < .001). Percutaneous coronary intervention volumes dropped by 55% (p < .0001) and transcatheter aortic valve replacement volumes dropped by 64% (p = .004), with cardiologists reporting an increase in late presenting ST-elevation myocardial infarctions and deaths among patients waiting for transcatheter aortic valve replacement. Almost 1/3 of catheterization laboratories had at least one interventionalist testing positive for COVID-19. Salary reductions did not influence procedural deferral or speed of reinstituting normal volumes. Pandemic preparedness improved significantly over time, with the most pressing current problems focused on inadequate testing and staff health risks. During the COVID-19 pandemic, cardiac procedural deferrals were associated with procedural urgency and severity of hospital COVID-19 burden. Yet patients did not appear to be similarly influenced, with cardiologists reporting increases in late presenting ST-elevation myocardial infarctions independent of local COVID-19 burden. The safety and importance of seeking healthcare during this pandemic deserves emphasis.

Impact of the COVID-19 pandemic on hyperacute stroke treatment: experience from a comprehensive stroke centre in Singapore.

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to - 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI - 1.605 to 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.

Acute stroke care in a New York City comprehensive stroke center during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: The coronavirus disease-2019 (COVID-19) pandemic caused unprecedented demand and burden on emergency health care services in New York City. We aim to describe our experience providing acute stroke care at a comprehensive stroke center (CSC) and the impact of the pandemic on the quality of care for patients presenting with acute ischemic stroke (AIS). METHODS: We retrospectively analyzed data from a quality improvement registry of consecutive AIS patients at New York University Langone Health's CSC between 06/01/2019-05/15/2020. During the early stages of the pandemic, the acute stroke process was modified to incorporate COVID-19 screening, testing, and other precautionary measures. We compared stroke quality metrics including treatment times and discharge outcomes of AIS patients during the pandemic (03/012020-05/152020) compared with a historical pre-pandemic group (6/1/2019-2/29/2020). RESULTS: A total of 754 patients (pandemic-120; pre-pandemic-634) were admitted with a principal diagnosis of AIS; 198 (26.3%) received alteplase and/or mechanical thrombectomy. Despite longer median door to head CT times (16 vs 12 minutes; p = 0.05) and a trend towards longer door to groin puncture times (79.5 vs. 71 min, p = 0.06), the time to alteplase administration (36 vs 35 min; p = 0.83), door to reperfusion times (103 vs 97 min, p = 0.18) and defect-free care (95.2% vs 94.7%; p = 0.84) were similar in the pandemic and pre-pandemic groups. Successful recanalization rates (TICI≥2b) were also similar (82.6% vs. 86.7%, p = 0.48). After adjusting for stroke severity, age and a prior history of transient ischemic attack/stroke, pandemic patients had increased discharge mortality (adjusted OR 2.90 95% CI 1.77 - 7.17, p = 0.021) CONCLUSION: Despite unprecedented demands on emergency healthcare services, early multidisciplinary efforts to adapt the acute stroke treatment process resulted in keeping the stroke quality time metrics close to pre-pandemic levels. Future studies will be needed with a larger cohort comparing discharge and long-term outcomes between pre-pandemic and pandemic AIS patients.

Care of immunocompromised patients with head and neck cancer during the COVID-19 pandemic: Two challenging and informative clinical cases.

BACKGROUND AND METHODS: There is an added level of complexity in the management of head and neck cancer patients with underlying immunosuppressive disorders during the COVID-19 pandemic. Head and neck oncologists are tasked with balancing the dual risks of cancer progression in the setting of impaired tumor immunity and increased susceptibility to life-threatening complications from exposure to viral infection for patients and providers. Through two cases of immunocompromised patients with newly diagnosed head and neck malignancies, we aim to provide guidance to clinicians struggling with how to best counsel and manage this unique subset of patients under these difficult circumstances. RESULTS: After careful consideration of the options, we took different approaches in the care of these two patients. CONCLUSIONS: Ultimately, there is no uniform set of rules to apply to this heterogeneous group of immunocompromised patients. We provide some general principles to help guide patient management during the current pandemic.