Indirect Impact of COVID-19 Vaccination on Weekly Trends in Morbidity and Mortality Indicators in Brazil, 2020 to 2021

Background: With the outbreak of the COVID-19 pandemic, safe and efficacious vaccines were quickly developed and made available to reduce its morbidity and mortality. This study aimed to describe the trends and evaluate the association of COVID-19 vaccination with indicators of morbidity and mortality due to the disease in Brazil.Methods: This was an ecological study whose unit of analysis was the time elapsed between February 16th, 2020, from the introduction of COVID-19 in Brazil and July 17th, 2021, six months after the start of vaccination in the country. From secondary databases, indicators of morbidity and mortality (incidence of hospitalization, proportion of severe cases, lethality and mortality) and vaccine coverage (doses 1, 2 or single dose) per epidemiological week (EW) and age groups were calculated (18 to 59 years and 60 years or older). Indicators of morbimortality were compared in the pre-vaccination (EW 8/2020 to EW 2/2021) and vaccination (EW 3/2021 to EW 28/2021) periods, analyzing the trends estimated using the JointPoint model and their associations using the Poisson model.Results: For individuals aged 60 years and over, during the period of COVID-19 vaccination there was a weekly trend towards a reduction in the incidence of hospitalizations (PMSV: -4.7%), severity (PMSV: -0.3%, lethality (PMSV: -2.0%) and mortality (PMSV: -2.8%); the increase in COVID-19 vaccination coverage was inversely associated with the incidence of hospitalizations (IRR: 0.969), lethality (IRR: 0.993), and mortality (IRR: 0.981). For individuals aged 18 to 59 years of age, during the period of COVID-19 vaccination there was a weekly trend towards a reduction in the incidence of hospitalizations (PMSV: -2.6%) and lethality (PMSV: -2.0%), while there was an increase in mortality (PMSV: 3.8%); the increase in COVID-19 vaccination coverage was inversely associated with the incidence of hospitalizations (IRR: 0.975) and lethality (IRR: 0.939). Conversely, it was directly associated with mortality (IRR: 1.054).Conclusions: it was demonstrated that COVID-19 vaccination had an indirect impact in reducing the morbidity and mortality trend from the disease in Brazil, especially in the elderly population, in which vaccination was prioritized and achieved greater coverage, when compared to individuals aged 18 to 59 years.

Comparative Efficacy over time of the mRNA-1273 (Moderna) vaccine and the BNT162b2 (Pfizer-BioNTech) vaccine

Importance Real-world analysis of the incidence of SARS-CoV-2 infection post vaccination is important in determining the comparative efficacy of the available vaccines. Objective To study the incidence of SARS-CoV-2 infection in individuals fully vaccinated with either the BNT162b2 or the mRNA-1273 at 30-, 60-, and 90-days post vaccination Design Retrospective cohort study Setting Deidentified administrative claims for Medicare Advantage and commercially insured individuals in a research database. Participants Over 3.5 million fully-vaccinated individuals including 6,434 individuals with SARS-CoV-2 infection with a follow up period between 14 and 151 days after their second dose. Exposure Vaccination by either mRNA-1273 or BNT162b2. Main Outcome and Measures The rate of Covid-19 infection occurring at 30, 60, and 90 days at least 14 days after the second dose of either the mRNA-1273 vaccine or the BNT162b2 vaccine. Sub analyses included the incidence of hospitalization, ICU admission, and death/hospice transfer. Separate analysis was conducted for individuals ≥ age 65 and those without a prior diagnosis of Covid-19 and both yielded results similar to the general population. Results The mRNA-1273 vaccine provided slightly superior protection against SARS-CoV-2 infection compared to the BNT162b2 vaccine. In the full population, there were no significant differences in the risk of hospitalization, ICU admission, or death/hospice transfer. Conclusion Immunization with mRNA-1273, compared to BNT162b2, provided slightly more protection against SARS-CoV-2 infection that reached statistical significance at 90 days with a number needed to vaccinate of ≥292.There were no differences in vaccine efficacy for protection against hospitalization, ICU admission, or death/hospice transfer.

Safety and feasibility of outpatient high-dose cytarabine and intermediate-dose cytarabine for consolidation therapy in acute myeloid leukemia

Introduction The standard of care consolidation therapy for acute myeloid leukemia is high-dose cytarabine or intermediate-dose cytarabine, which are traditionally given inpatient. At Moffitt Cancer Center, we have moved the administration of high-dose cytarabine and intermediate-dose cytarabine to the outpatient setting through the inpatient/outpatient program. To facilitate outpatient administration, high-dose cytarabine and intermediate-dose cytarabine are given in a shorter interval of every 10 h instead of 12 h. The safety of a shorter duration interval of high-dose cytarabine and intermediate-dose cytarabine is unknown. This study aims to assess the safety and feasibility of administering high-dose cytarabine and intermediate-dose cytarabine consolidation therapy in the inpatient/outpatient setting. Methods This is a retrospective chart review to analyze acute myeloid leukemia patients treated with inpatient/outpatient high-dose cytarabine or intermediate-dose cytarabine consolidation therapy at Moffitt Cancer Center from January 1, 2015, through November 1, 2018. The primary objective was to determine the incidence of hospitalization during the inpatient/outpatient administration of high-dose cytarabine or intermediate-dose cytarabine. Results Two hundred fifty-three of 255 cycles of high-dose cytarabine/intermediate-dose cytarabine were delivered outpatient over the reviewed time period to 118 patients. No patients receiving outpatient high-dose cytarabine/intermediate-dose cytarabine consolidation required hospitalization during chemotherapy. Our incidence of hospitalization (24%) after chemotherapy is consistent with the reported literature. Through the inpatient/outpatient administration of high-dose cytarabine and intermediate-dose cytarabine, 1265 inpatient days were saved with an approximate revenue of $3,135,176 generated in our study period. Conclusion Inpatient/outpatient administration of high-dose cytarabine and intermediate-dose cytarabine is both safe and feasible. Moving high-dose cytarabine/intermediate-dose cytarabine administration to the outpatient setting resulted in significant additional revenue vs. inpatient administration.

Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children’s hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.

The Effects of Dapagliflozin in Patients With Heart Failure Complicated With Type 2 Diabetes: A Meta-Analysis of Placebo-Controlled Randomized Trials

BackgroundCardiovascular disease threatens the health and quality of life of individuals, particularly those with type II diabetes. Recently, some studies have reported the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the rates of hospitalization or urgent visits, resulting in IV therapy for heart failure in patients with type 2 diabetes mellitus (T2DM).MethodsWe did a comprehensive search in electronic databases from inception through July 2020 for randomized-controlled trials, using the keywords “sodium-glucose cotransporter-2 inhibitor”, “dapagliflozin”, “heart failure”, “cardiovascular outcomes”, “major adverse cardiovascular events”, “all-cause mortality”, and “cardiovascular death”. Random-effects summary odds ratios (OR) were constructed using M-L heterogeneity model.ResultsFive trials with 5,252 patients were ultimately included. The incidence of hospitalization for heart failure (HHF) (n=4, OR=0.74; 95% CI, 0.61 to 0.88; I2 = 0%) and all-cause mortality (ACM, n=4, OR=0.76; 95% CI, 0.66 to 0.94; I2 = 0%); was reduced by dapagliflozin, respectively, in all heart failure patients, without obvious heterogeneity. The incidence of cardiovascular death in dapagliflozin was lower than that in placebo without statistically significant (CVD, n=5, OR=0.84; 95% CI, 0.69 to 1.03; I2 = 0%). In HFrEF subgroup, dapagliflozin was associated with a reduced incidence of hospitalization for heart failure (n=4, OR=0.74; 95% CI, 0.60 to 0.91; I2 = 0%), cardiovascular death (n=4, OR=0.72; 95% CI, 0.58 to 0.91; I2 = 8%), and all-cause mortality (n=3, OR=0.70; 95% CI, 0.50 to 0.99; I2 = 43%) without significant heterogeneity. In contrast, in the HFpEF subgroup, there was no difference in the incidence of cardiovascular death (n=2, OR=1.45; 95% CI, 0.95 to 2.22; I2 = 0%) and all-cause mortality (n=2, OR=1.04; 95% CI, 0.76 to 1.43; I2 = 0%) between dapagliflozin and placebo.ConclusionIn our study, dapagliflozin performed a statistical reduction in the rate of heart failure hospitalization, cardiovascular death, and all-cause mortality in patients with HFrEF and diabetes. However, in the HFpEF subgroup, dapagliflozin did not show a significant cardiovascular protective effect.

RCVS: Symptoms, Incidence, and Resource Utilization in a Population-Based US Cohort

Objective:To estimate the incidence of hospitalization for reversible cerebral vasoconstriction syndrome (RCVS), we identified RCVS-related hospital admissions across 11 U.S. states in 2016.Methods:We tested the validity of ICD-10 code I67.841 in 79 patients with hospital admissions for RCVS or other cerebrovascular diseases at one academic and one community hospital. After determining that this code had a sensitivity of 100% (95% CI, 82-100%) and a specificity of 90% (95% CI, 79-96%), we applied it to administrative data from the Healthcare Cost and Utilization Project on all ED visits and hospital admissions. Age- and sex-standardized RCVS incidence was calculated using census data. Descriptive statistics were used to analyze associated diagnoses.Results:Across 5,067,250 hospital admissions in our administrative data, we identified 222 patients with a discharge diagnosis of RCVS in 2016. The estimated annual age- and sex-standardized incidence of RCVS hospitalization was 2.7 (95% CI, 2.4-3.1) cases per million adults. Many patients had concomitant neurologic diagnoses, including subarachnoid hemorrhage (37%), ischemic stroke (16%), and intracerebral hemorrhage (10%). In the 90 days before the index admission, 97 patients had an ED visit and 34 patients a hospital admission, most commonly for neurologic, psychiatric, and pregnancy-related diagnoses. Following discharge from the RCVS hospital admission, 58 patients had an ED visit and 31 had a hospital admission, most commonly for neurologic diagnoses.Conclusions:Using population-wide data, we estimated the age- and sex-standardized incidence of hospitalization for RCVS in U.S. adults as approximately 3 per million per year.

Study protocol: The clinical features, epidemiology, and causes of paediatric encephalitis in southern Vietnam

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children’s hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.

Weather temperature and the incidence of hospitalization for cardiovascular diseases in an aging society

Weather temperatures affect the incidence of cardiovascular diseases (CVD), but there is limited information on whether CVD hospitalizations are affected by changes in weather temperatures in a super-aging society. We aimed to examine the association of diurnal weather temperature changes with CVD hospitalizations. We included 1,067,171 consecutive patients who were admitted to acute-care hospitals in Japan between April 1, 2012 and March 31, 2015. The primary outcome was the number of CVD hospitalizations per day. The diurnal weather temperature range (DTR) was defined as the minimum weather temperature subtracted from the maximum weather temperature on the day before hospitalization. Multilevel mixed-effects linear regression models were used to estimate the association of DTR with cardiovascular hospitalizations after adjusting for weather, hospital, and patient demographics. An increased DTR was associated with a higher number of CVD hospitalizations (coefficient, 4.540 [4.310–4.765]/°C change, p < 0.001), with greater effects in those aged 75–89 (p < 0.001) and ≥ 90 years (p = 0.006) than among those aged ≤ 64 years; however, there were no sex-related differences (p = 0.166). Greater intraday weather temperature changes are associated with an increased number of CVD hospitalizations in the super-aging society of Japan, with a greater effect in older individuals.