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JMIR Public Health Surveill ; 8(2): e32426, 2022 02 21.
Article in English | MEDLINE | ID: covidwho-1702252


BACKGROUND: Early estimates of excess mortality are crucial for understanding the impact of COVID-19. However, there is a lag of several months in the reporting of vital statistics mortality data for many jurisdictions, including across Canada. In Ontario, a Canadian province, certification by a coroner is required before cremation can occur, creating real-time mortality data that encompasses the majority of deaths within the province. OBJECTIVE: This study aimed to validate the use of cremation data as a timely surveillance tool for all-cause mortality during a public health emergency in a jurisdiction with delays in vital statistics data. Specifically, this study aimed to validate this surveillance tool by determining the stability, timeliness, and robustness of its real-time estimation of all-cause mortality. METHODS: Cremation records from January 2020 until April 2021 were compared to the historical records from 2017 to 2019, grouped according to week, age, sex, and whether COVID-19 was the cause of death. Cremation data were compared to Ontario's provisional vital statistics mortality data released by Statistics Canada. The 2020 and 2021 records were then compared to previous years (2017-2019) to determine whether there was excess mortality within various age groups and whether deaths attributed to COVID-19 accounted for the entirety of the excess mortality. RESULTS: Between 2017 and 2019, cremations were performed for 67.4% (95% CI 67.3%-67.5%) of deaths. The proportion of cremated deaths remained stable throughout 2020, even within age and sex categories. Cremation records are 99% complete within 3 weeks of the date of death, which precedes the compilation of vital statistics data by several months. Consequently, during the first wave (from April to June 2020), cremation records detected a 16.9% increase (95% CI 14.6%-19.3%) in all-cause mortality, a finding that was confirmed several months later with cremation data. CONCLUSIONS: The percentage of Ontarians cremated and the completion of cremation data several months before vital statistics did not change meaningfully during the COVID-19 pandemic period, establishing that the pandemic did not significantly alter cremation practices. Cremation data can be used to accurately estimate all-cause mortality in near real-time, particularly when real-time mortality estimates are needed to inform policy decisions for public health measures. The accuracy of this excess mortality estimation was confirmed by comparing it with official vital statistics data. These findings demonstrate the utility of cremation data as a complementary data source for timely mortality information during public health emergencies.

COVID-19 , Cremation , Humans , Ontario/epidemiology , Pandemics , SARS-CoV-2
Lancet Reg Health Am ; 7: 100130, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1561710


BACKGROUND: The effects of the COVID-19 pandemic on non-natural manners of death in Ontario is not known. Understanding the indirect consequences of the pandemic and related public health measures (i.e. lockdown) fills a vital need to inform best practice in public health and guide policy decisions. METHODS: The Office of the Chief Coroner and the Ontario Forensic Pathology Service (OCC-OFPS) investigate sudden and unexpected deaths in the province of Ontario. The number of homicides, suicides, and accidental deaths (non-natural deaths=77,655) were extracted from the centralized Coroner's Information System database (total deaths=197,966), across four provincially defined stages of lockdown related to the COVID-19 pandemic (March 17 to December 31, 2020), and crude rates (per 100,000 people) were compared to the previous eleven years. FINDINGS: There was no major change to the rate of homicides during 2020 compared to 2009-2019 (RR 1⋅1, 95% CI 0⋅95-1⋅2; p=0⋅19; estimated annual effect=21 more deaths in 2020). The rate of suicides also did not show an overall major change in 2020 (RR 1⋅02, 95% CI 0⋅96-1⋅1; p=0⋅50; estimated annual effect=27 more deaths in 2020). However, during the first stage of lockdown (Stage 0), there was a decrease in the rate of suicides compared to all combinations of recent years from 2013 onwards (RRs 0⋅82-0⋅86, combined 95% CI 0⋅69-0⋅99; max p=0⋅039; estimated effect of 30 less deaths in Stage 0). There was an excess of over 1,500 accidental drug-related deaths that occurred during 2020 (RR 2⋅5, 95% CI 2⋅4-2⋅7; p<0⋅001). This finding held up to 'interrupted time series' robustness testing, indicating that 2020 had substantially more drug-related deaths, even when accounting for the linear increasing trend over time. Although motor vehicle collision associated fatalities appeared to decrease slightly in 2020 (RR 0⋅89, 95% CI 0⋅81-0⋅96; p=0⋅0039; estimated annual effect of 78 less deaths), we could not conclude any lockdown-associated effect, particularly when compared to 2019 (RR 0⋅26, 95% CI 0⋅75-1⋅1; p=0⋅26). INTERPRETATION: In Ontario, the short-term effects of the COVID-19 pandemic did not greatly increase homicide or suicide rates, nor decrease motor vehicle collision fatality rates; however, the longer-term impact of the pandemic remains to be elucidated and ongoing vigilance is warranted in the event that other trends emerge. Accidental drug-related fatalities substantially increased during all stages of the lockdown, marking an urgent need for consideration in policy. These results highlight the vital role of death investigation systems in providing high quality and timely data to inform public health recommendations.

Blood ; 136(Supplement 1):37-38, 2020.
Article in English | PMC | ID: covidwho-1338941


Introduction:Hypomethylating agents (HMAs) or DNA methyltransferase inhibitors (DNMTi) such as decitabine or azacitidine are established standard of care for the treatment of MDS and CMML. The oral bioavailability of these agents has been limited due to rapid degradation by cytidine deaminase (CDA) in the gut and liver, hence requiring intravenous infusion or subcutaneous injections daily for 5-7 days every month (m). This parenteral administration requirement adds significant burden to older cancer patients due to daily time commitment and travel to treatment centers. It also increases exposure to and infection risk with SARS-CoV-2 during the COVID-19 pandemic. Oral decitabine 35 mg/cedazuridine 100 mg (ASTX727) is an oral fixed dose combination drug of decitabine and the CDA inhibitor cedazuridine that have shown 99% (90% CI 93% to 106%) equivalent exposure to standard dose IV decitabine 20 mg/m2 in a randomized cross-over study (Garcia-Manero et al, ASH 2019). Here, we present the clinical efficacy and safety results of oral decitabine/cedazuridine from 133 patient study in MDS and CMML (ASTX727-02 ASCERTAIN study).Methods:We used a randomized cross over design where patients were randomized in the first 2 cycles 1:1 to either Sequence A: decitabine 35 mg/ cedazuridine 100 mg in Cycle 1 followed by IV decitabine at 20 mg/m2 in Cycle 2, or Sequence B: IV decitabine in Cycle 1 followed by oral decitabine/cedazuridine in Cycle 2 to do an intra-patient comparison of decitabine PK (primary PK endpoint: decitabine AUC equivalence over 5 days of dosing). Cycles were repeated every 28 days. All patients received oral decitabine/cedazuridine in all subsequent cycles from Cycle 3 onwards until disease progression or unacceptable toxicity. Patients were eligible as per the FDA-approved label of IV decitabine (MDS patients by FAB classification including CMML, or MDS IPSS Intermediate-1, 2 or high-risk patients). Clinical endpoints were best response as assessed by an independent expert panel according to International Working Group (IWG) 2006 response criteria, transfusion independence for at least 8 or 16 consecutive weeks, overall survival, and safety. Adverse events (AEs) were graded by Common Terminology Criteria for Adverse Events (CTCAE) v 4.03.Results:138 subjects were randomized, of whom 133 were treated on study. The median age was 71.0 years (range 44-88), 65% were male, 88% MDS and 12% CMML, 43% were either red blood cells (RBCs) or platelets transfusion-dependent at baseline, 25% had poor-risk cytogenetics, and 42% had baseline bone marrow blasts >5%. At the data cutoff for the response analysis, the median duration of follow up was 12.6 m (range 9.3 to 20.5 m) with median number of treatment cycles of 8 (range 1 to 18). Of the 133 treated patients the best response was complete response (CR) in 28 patients (21%;95% CI 15-29%), marrow (m)CR with hematological improvement (HI) in 20 patients (15%), mCR without HI in 23 patients (17.3%), and HI in 10 patients (7.5%) for an overall objective response (CR+mCR+HI) in 81 patients (61%;95% CI 52-69%). Median duration of CR was 7.5 m (range 1.6 to 17.5 m), and median time to CR was 4.3 m (range 2.1 to 15.2 m). Of the 133 treated patients 27 (20%) went on to receive allogeneic hematopoietic cell transplant. Of the 57 patients who were either RBCs or platelets transfusion-dependent at baseline, 30 (53%) became transfusion independent for both RBCs and platelets for at least 8 consecutive weeks, and 19 (33%) were both RBCs and platelets transfusion independent for at least 16 consecutive weeks. Median survival has not been reached. Most common Treatment-Emergent AEs of Grade ≥3 regardless of causality were neutropenia in 51.5%, thrombocytopenia in 50%, anemia in 40%, febrile neutropenia in 26%, leukopenia in 21%, pneumonia in 12%, and sepsis in 7% of patients treated with oral decitabine/cedazuridine (excluding the IV decitabine cycle).Summary/Conclusions: Efficacy and safety from oral decitabine 35 mg/ cedazuridine 100 mg daily for 5 days every 28 days are consist nt with clinical data from standard IV decitabine 20 mg/m2 daily for 5 days. Oral decitabine/cedazuridine is the only oral HMA with systemic exposure equivalent to its injectable drug. Further investigation of oral decitabine/cedazuridine in all-oral combination studies is warranted and underway.