Diabetic foot disease carries an intrinsic high risk of mortality and other severe outcomes in type 2 diabetes: a propensity score-matched retrospective population-based study.

BACKGROUND: To evaluate the association between diabetic foot disease (DFD) and the incidence of fatal and non-fatal events in individuals with type 2 diabetes (T2DM) from primary-care settings. METHODS: We built a cohort of people with a first DFD episode during 2010-2015, followed up until 2018. These subjects were 1 to 1 propensity score matched to subjects with T2DM without DFD. The incidence of all-cause mortality, the occurrence of new DFD, amputations, cardiovascular diseases, or composite outcome, including all-cause mortality and/or cardiovascular events during the follow-up period, were calculated. A Cox proportional hazard analysis was conducted to evaluate the hazard ratios (HR) for different events. RESULTS: Overall, 11,117 subjects with T2DM with a first episode of DFD were compared with subjects without DFD. We observed higher incidence rates (IRs) for composite outcome (33.9 vs. 14.5 IR per 100 person-years) and a new DFD episode event (22.2 vs. 1.1 IR per 100 person-years) in the DFD group. Compared to those without DFD, those with a first episode of DFD had a higher HR for all events, with excess rates particularly for amputation and new DFD occurrence (HR: 19.4, 95% CI: 16.7-22.6, HR: 15.1, 95% CI: 13.8-16.5, respectively) was found. CONCLUSIONS: Although DFD often coexists with other risk factors, it carries an intrinsic high risk of morbidity and mortality in individuals with T2DM. DFD should be regarded as a severe complication already at its onset, as it carries a poor clinical prognosis.

Risk of severe COVID-19 in unvaccinated patients during the period from wild-type to Omicron variant: real-world evidence from Japan.

BACKGROUND: Many studies have reported that the Omicron variant is less pathogenic than the Delta variant and the wild-type. Epidemiological evidence regarding the risk of severe COVID-19 from the wild-type to the Omicron variant has been lacking. METHODS: Study participants were COVID-19 patients aged 18 and older without previous COVID-19 infection who were notified to the Nara Prefecture Chuwa Public Health Center from January 2020 to March 2023, during the periods from the wild-type to the Omicron variant. The outcome variable was severe COVID-19 (i.e., ICU admission or COVID-19-related death). The explanatory variable was SARS-CoV-2 variant type or the number of COVID-19 vaccinations. Covariates included gender, age, risk factors for aggravation, and the number of general hospital beds per population. The generalized estimating equations of negative binomial regression models were used to estimate the adjusted incidence proportion (AIP) with 95% confidence interval (CI) for severe COVID-19. RESULTS: Among 77,044 patients included in the analysis, 14,556 (18.9%) were unvaccinated and 520 (0.7%) developed severe COVID-19. Among unvaccinated patients, the risk of severe COVID-19 increased in the Alpha/Delta variants and decreased in the Omicron variant compared to the wild-type (AIP [95% CI] was 1.55 [1.06-2.27] in Alpha/Delta and 0.25 [0.15-0.40] in Omicron), but differed by age. Especially in patients aged ≥80, there was no significant difference in the risk of severe COVID-19 between the wild-type and the Omicron variant (AIP [95% CI] = 0.59 [0.27-1.29]). Regarding the preventive effect of vaccines, among all study participants, the number of vaccinations was significantly associated with the prevention of severe COVID-19, regardless of variant type. After stratified analyses by age, patients aged ≥80 remained a significant association for all variant types. On the other hand, the number of vaccinations had no association in Omicron BA.5 of patients aged 18-64. CONCLUSIONS: Patients aged ≥80 had less reduction in risk of severe COVID-19 during the Omicron variant period, and a greater preventive effect of vaccines against severe COVID-19, compared to younger people. Our findings suggest that booster vaccination is effective and necessary for older people, especially aged ≥80.

Protection conferred by COVID-19 vaccination, prior SARS-CoV-2 infection, or hybrid immunity against Omicron-associated severe outcomes among community-dwelling adults.

INTRODUCTION: We assessed protection from COVID-19 vaccines and/or prior SARS-CoV-2 infection against Omicron-associated severe outcomes during successive sublineage-predominant periods. METHODS: We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, PCR-tested adults aged ≥50 years in Ontario, Canada between January 2, 2022 and June 30, 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2-5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection. RESULTS: We included 18,526 cases with Omicron-associated severe outcomes and 90,778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance, but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose, 6-month: 68%, 95%CI 63%-72%; fourth-dose, 6-month: 80%, 95%CI 77%-83%), but was lower and waned quickly during BQ/XBB predominance (third-dose, 6-month: 59%, 95%CI 48%-67%; 12-month: 49%, 95%CI 41%-56%; fourth-dose, 6-month: 62%, 95%CI 56%-68%, 12-months: 51%, 95%CI 41%-56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance, but was reduced during BQ/XBB predominance (third-dose, 6-month: 60%, 95%CI 36%-75%; fourth-dose, 6-month: 63%, 95%CI 42%-76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95%CI 79%-96%). Prior infection alone did not confer lasting protection. CONCLUSION: Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review.

Advanced Age and Increased Risk for Severe Outcomes of Dengue Infection, Taiwan, 2014-2015.

Dengue, a mosquitoborne flavivirus infection, is increasingly a disease of older adults who are more likely to have chronic diseases that confer risk for severe outcomes of dengue infection. In a population-based study in Taiwan, adjusted risks for dengue-related hospitalization, intensive care unit admission, and death increased progressively with age.

Association between vaccination status and severe health consequences among community-dwelling COVID-19 patients during Omicron BA.1/BA.2 and BA.5-predominant periods in Japan.

BACKGROUND: Many previous studies have reported that COVID-19 vaccine effectiveness decreased over time and declined with newly emerging variants. However, there are few such studies in Japan. Using data from a community-based retrospective study, we aimed to assess the association between vaccination status and severe COVID-19 outcomes caused by the Omicron variant, considering the length of time since the last vaccination dose. METHODS: We included all persons aged ≥12 diagnosed with COVID-19 by a doctor and notified to the Chuwa Public Health Center of Nara Prefectural Government during the Omicron BA.1/BA.2 and BA.5-predominant periods in Japan (January 1 to September 25, 2022). The outcome variable was severe health consequences (SHC) (i.e., COVID-19-related hospitalization or death). The explanatory variable was vaccination status of the individuals (i.e., the number of vaccinations and length of time since last dose). Covariates included gender, age, risk factors for aggravation, and the number of hospital beds per population. Using the generalized estimating equations of the multivariable Poisson regression models, we estimated the cumulative incidence ratio (CIR) and 95% confidence interval (CI) for SHC, with stratified analyses by period (BA.1/BA.2 or BA.5) and age (65 and older or 12-64 years). RESULTS: Of the 69,827 participants, 2,224 (3.2%) had SHC, 12,154 (17.4%) were unvaccinated, and 29,032 (41.6%) received ≥3 vaccine doses. Regardless of period or age, there was a significant dose-response relationship in which adjusted CIR for SHC decreased with an increased number of vaccinations and a longer time since the last vaccination. On the one hand, in the BA.5 period, those with ≥175 days after the third dose had no significant difference in people aged 65 and older (CIR 0.77; 95% CI, 0.53-1.12), but significantly lower CIR for SHC in people aged 12-64 (CIR 0.47; 95% CI, 0.26-0.84), compared with those with ≥14 days after the second dose. CONCLUSION: A higher number of vaccinations were associated with lower risk of SHC against both BA.1/BA.2 and BA.5 sublineages. Our findings suggest that increasing the number of doses of COVID-19 vaccine can prevent severe COVID-19 outcomes, and that a biannual vaccination is recommended for older people.

Relative incidence and individual-level severity of seasonal influenza A H3N2 compared with 2009 pandemic H1N1.

BACKGROUND: Two subtypes of influenza A currently circulate in humans: seasonal H3N2 (sH3N2, emerged in 1968) and pandemic H1N1 (pH1N1, emerged in 2009). While the epidemiological characteristics of the initial wave of pH1N1 have been studied in detail, less is known about its infection dynamics during subsequent waves or its severity relative to sH3N2. Even prior to 2009, few data was available to estimate the risk of severe outcomes following infection with one circulating influenza strain relative to another. METHODS: We analyzed antibodies in quadruples of sera from individuals in Hong Kong collected between July 2009 and December 2011, a period that included three distinct influenza virus epidemics. We estimated infection incidence using these assay data and then estimated rates of severe outcomes per infection using population-wide clinical data. RESULTS: Cumulative incidence of infection was high among children in the first epidemic of pH1N1. There was a change towards the older age group in the age distribution of infections for pH1N1 from the first to the second epidemic, with the age distribution of the second epidemic of pH1N1 more similar to that of sH3N2. We found no serological evidence that individuals were infected in both waves of pH1N1. The risks of excess mortality conditional on infection were higher for sH3N2 than for pH1N1, with age-standardized risk ratios of 2.6 [95% CI: 1.8, 3.7] for all causes and 1.5 [95% CI: 1.0, 2.1] for respiratory causes throughout the study period. CONCLUSIONS: Overall increase in clinical incidence of pH1N1 and higher rates of severity in older adults in post pandemic waves were in line with an age-shift in infection towards the older age groups. The absence of repeated infection is good evidence that waning immunity did not cause the second wave. Despite circulating in humans since 1968, sH3N2 is substantially more severe per infection than the pH1N1 strain. Infection-based estimates of individual-level severity have a role in assessing emerging strains; updating seasonal vaccine components; and optimizing of vaccination programs.

TURN Score Predicts 24-Hour Cerebral Edema After IV Thrombolysis.

BACKGROUND AND PURPOSE: Cerebral edema is associated with poor outcome after IV thrombolysis. We recently described the TURN score (Thrombolysis risk Using mRS and NIHSS), a predictor of severe outcome after IV thrombolysis. Our purpose was to evaluate its ability to predict 24-h cerebral edema. METHODS: We retrospectively analyzed data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Measures of brain swelling included edema, mass effect and midline shift assessed at baseline, at 24 h and new onset at 24 h. Outcome was assessed using intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day severe outcome, and 90-day mortality. Statistical associations were assessed by logistic regression reporting odds ratios (OR) and by areas under the receiver operating characteristic curves (AUROC). RESULTS: Baseline brain swelling did not predict poor outcome; however, 24-h brain swelling predicted ICH (OR 5.69, P < 0.001), sICH (OR 9.50, P = 0.01), 90-day severe outcome (OR 7.10, P < 0.001), and 90-day mortality (OR 5.65, P = 0.01). Similar results were seen for new brain swelling at 24 h. TURN predicted 24-hour brain swelling (OR 2.5, P < 0.001; AUROC 0.69, 95 % CI 0.63-0.75) and new brain swelling at 24 h (OR 2.1, P < 0.001; AUROC 0.67, 95 % CI 0.61-0.73). CONCLUSIONS: Cerebral edema at 24 h is associated with poor outcome and 90-day mortality. TURN predicts ischemic stroke patients who will develop 24-h cerebral edema after IV thrombolysis.

COVID-19 outcome trends by vaccination status in Canada, December 2020-January 2022.

Background: The coronavirus disease 2019 (COVID-19) pandemic in Canada has evolved rapidly. Since late 2020, COVID-19 vaccines have been relied on to protect against severe outcomes in the presence of circulating variants of concern (VOC). Objective: This surveillance report provides a retrospective descriptive analysis of national trends in COVID-19 cases and severe outcomes by vaccination status, contextualizing trends against case demographics and circulating VOCs, from December 2020 to January 2022. Methods: Case and vaccination coverage surveillance data were obtained from the National COVID-19 Case Dataset and the Canadian COVID-19 Vaccination Coverage Surveillance System for 12 of 13 provinces and territories. Descriptive analyses were produced to describe trends over time among individuals aged 12 years and older by COVID-19 outcome, vaccination status, and demographics. Age-standardized and age-stratified incidence rates and incidence rate ratios were computed for cases, hospitalizations, and deaths. Results: From mid to late-2021, incidence rates for cases and severe outcomes were consistently lowest among those with a completed primary series and highest among those who were unvaccinated. Unvaccinated individuals were much more likely to be hospitalized or to die compared to those with a completed primary series in all variant periods. Age-specific rates of severe outcomes were consistently highest among those aged 80 years and older across all vaccination statuses. Conclusion: Vaccination remains one of the most important public health interventions, particularly among older adults, to protect against COVID-19 severe outcomes as the pandemic evolves. Routine monitoring of COVID-19 outcomes by vaccination status can identify changes in COVID-19 epidemiology and inform public health action and policy.

Real-world evidence of sotrovimab effectiveness for preventing severe outcomes in patients with COVID-19: A quality improvement propensity-matched retrospective cohort study of a pan-provincial program in Alberta, Canada.

OBJECTIVES: Post-marketing surveillance of sotrovimab's effect during implementation in the Canadian population is limited. METHODS: The study used a propensity score-matched retrospective cohort design. Follow-up began between the periods of December 15, 2021 and April 30 2022. The study assessed any severe outcome defined as all-cause hospital admission or mortality within 30 days of a confirmed COVID-19-positive test. Covariate-adjusted odds ratios between sotrovimab treatment and the severe outcome was conducted using logistic regression. RESULTS: There were 22,289 individuals meeting the treatment criteria for sotrovimab. There were 1603 treated and 6299 untreated individuals included in the analysis. The outcome occurrence in the study was 5.49% (treated) and 4.21% (untreated), with a median time from diagnosis to treatment of 1.00 days (interquartile range 2.00 days). In the propensity-matched cohort, sotrovimab was not associated with lower odds of a severe outcome (odds ratio 1.20, 95% confidence interval 0.91-1.58), adjusting for confounding variables. CONCLUSIONS: After adjusting for confounding variables, sotrovimab treatment was not associated with lower odds of a severe outcome within 30-days of COVID-19-positive date.

The relative effectiveness of three and four doses of COVID-19 vaccine in Victoria, Australia: A data linkage study.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic led to extensive vaccination campaigns worldwide, including in Australia. Immunity waning and the emergence of new viral variants pose challenges to the effectiveness of vaccines. Our study aimed to assess the relative effectiveness (rVE) of 3 and 4 compared with 2 doses of COVID-19 vaccine. The study focuses on the Victorian population, a majority of whom had no prior exposure to the virus before vaccination. METHODS: We used routinely collected data for the state of Victoria, Australia, to assess rVE during an Omicron-dominant period, 1 June 2022 to 1 March 2023. Immunisation, notifications, hospitalisations and mortality data for residents aged 65 years and older were linked for analysis. Cox proportional hazard regression was used to estimate the rVE against COVID-19 hospitalisation or death, accounting for key confounders with vaccination as a time-varying covariate. RESULTS: In 1,070,113 people 65 years or older who had received their second dose, a third and fourth dose of a COVID-19 vaccine significantly reduced the hazard of hospitalisation or death compared to two doses. rVE was highest within two weeks from administration at 40 % (95 % CI: 0 % to 64 %) and 66 % (95 % CI: 60 % to 71 %) for a third and fourth dose, respectively. Additional protection conferred by third and fourth doses waned over time from administration. CONCLUSIONS: Our findings underscore the need for additional vaccine doses and updated vaccine strategies. These findings have implications for public health advice and COVID-19 vaccine strategies. Further research and monitoring of vaccine effectiveness in real-world settings are warranted to inform ongoing pandemic response efforts.

Association between ABO blood type and coronavirus disease 2019 severe outcomes across dominant variant strains.

Objectives: Existing evidence suggests a link between ABO blood type and severe outcomes in coronavirus disease 2019 (COVID-19). We aimed to assess the relationship between blood type and severe outcomes across variant strains throughout the pandemic. Methods: This was a multicenter retrospective observational cohort analysis from a large health system in southeastern Michigan using electronic medical records to evaluate emergency encounters, hospitalization, and severe outcomes in COVID-19 based on ABO blood type. Consecutive adult patients presenting to the emergency department with a primary diagnosis of COVID-19 (U07.1) from March 1, 2020 through December 31, 2022 were assessed. Patients who presented during three distinct time intervals that coincided with Alpha, Delta, and Omicron variant predominance were included in the analysis. Exclusions included no record of ABO blood type, positive PCR COVID-19 test within the preceding 28 days, and if transferred from out of the health system. Severe outcomes were inclusive of intensive care unit admission, mechanical ventilation, or death, which, as a composite, represented our primary outcome. Secondary outcomes were hospital admission and length of stay. A logistic regression model was employed to test the association between ABO blood type and severe outcome, adjusting for age, sex, race, vaccination status, Elixhauser comorbidity indices, and the dominant variant time period in which the encounter occurred. Results: Of the 33,796 COVID-19 encounters, 9416 met inclusion criteria; 4071 (43.2%) were type O, 3417 (36.3%) were type A, 459 (4.9%) were type AB, and 1469 (15.6%) were type B blood. Note that 66.4% of the cohort was female (p = 0.18). The proportion of composite severe disease among the four blood types was similar and ranged between 8.6% and 8.9% (p = 0.98). Note that 53.0% of type A blood patients required hospital admission, compared to 51.9%, 50.4%, and 48.1% of type AB, B, and O blood, respectively (p < 0.001). Compared to patients with O blood type (43.2%), non-O blood type (58.8%; composite of A, AB, and B) exhibited no statistically significant difference in the proportion of composite severe disease (8.8% vs. 8.7%; p = 0.81) Multivariable regression analyses exhibited no significant difference regarding the presence of severe outcomes among the four blood types or O versus non-O blood types during T1, T2, and T3. Conclusions: ABO blood type was not associated with COVID-19 severe outcomes across the Delta, Alpha, and Omicron dominant COVID waves across a large health system in southeastern Michigan. Further research is needed to better understand if ABO blood type is a risk factor for severe disease among evolving COVID-19 variants and other viral upper respiratory infections.

Cold Agglutinin Disease and COVID-19: A Scoping Review of Treatments and Outcomes.

Background: Reports suggest that patients with both acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and cold agglutinin disease (CAD) may experience poorer survival when treated with rituximab. We conducted a scoping review to evaluate severe outcomes, including intensive care unit (ICU) admission and mortality, in coronavirus disease 2019 (COVID-19) patients with CAD on various treatments, including rituximab. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Four literature databases were searched on December 19, 2023, for studies reporting lab-confirmed SARS-CoV-2 and CAD, excluding rheumatological conditions. Results: Of the 741 screened articles, 19 were included. Studies, predominantly case reports (17/19) or case series (2/19), were mainly from the USA (8/19) and India (3/19), with others across Europe and Asia. Among 23 patients (61% female, median age 61 years), 21/23 had a new CAD diagnosis; only two had pre-existing CAD. Overall, 74% recovered, 21% died, and outcomes for one were unreported. Nine (39%) were ICU-admitted. Of rituximab-treated patients (n = 4), 25% were ICU-admitted, none died. Non-rituximab treatments (n = 19) saw 42% ICU admissions and 26% mortality. Conclusions: This review found no increased risk of severe outcomes in CAD and COVID-19 patients treated with rituximab.

The descriptive epidemiology of pre-omicron SARS-CoV-2 breakthrough infections and severe outcomes in Manitoba, Canada.

Introduction: Vaccination plays a key role in curbing severe outcomes resulting from COVID-19 disease. With the Omicron variant and the relaxing of public health protections breakthrough infections are increasingly common, and certain groups remain at higher risk for severe outcomes from breakthrough infections. We analysed population-based public health data from Manitoba, Canada to understand characteristics of those experiencing breakthrough infections and severe outcomes from breakthrough infections. Data from previous pandemic stages can provide valuable information regarding severe outcomes associated with breakthrough infection in the Omicron and future phases. Methods: Positive SARS-CoV-2 PCR tests from Cadham Provincial Laboratory were linked to case information from the population-based Public Health Information Management System. A retrospective design was used with time-to-event analyses to examine severe outcomes among those experiencing breakthrough infection. Results: Breakthrough cases were more likely to have 2 + chronic conditions, compared to age-, sex-, and time-period matched unvaccinated cases (24% vs. 17%), with hypertension (30%), diabetes (17%), and asthma (14%) being the most prevalent chronic conditions amongst breakthrough cases. Severe outcomes resulting from breakthrough infection was associated with age and chronic conditions, with those with 2 + chronic conditions at higher risk of severe outcomes (adjusted hazard ratio: 3.6, 95% confidence intervals: 2.0-6.4). Risk of severe outcomes varied by age group, with those 70 + years at over 13 times the risk of severe outcomes (95% CI: 4.5-39.8), compared to those 18-29 years of age. Discussion: Our results demonstrate the impact of chronic conditions on the likelihood of, and severity of outcomes from breakthrough infections. These findings underscore the importance of vaccination programs prioritizing vulnerable populations.

Risk of Covid-19 Severe Outcomes and Mortality in Migrants and Ethnic Minorities Compared to the General Population in the European WHO Region: a Systematic Review.

The Covid-19 pandemic has had a major impact on migrants and ethnic minorities (MEMs). Socio-economic factors and legal, administrative and language barriers are among the reasons for this increased susceptibility. The aim of the study is to investigate the impact of Covid-19 on MEMs compared to the general population in terms of serious outcomes. We conducted a systematic review collecting studies on the impact of Covid-19 on MEMs compared to the general population in the WHO European Region regarding hospitalisation, intensive care unit (ICU) admission and mortality, published between 01/01/2020 and 19/03/2021. Nine researchers were involved in selection, study quality assessment and data extraction. Of the 82 studies included, 15 of the 16 regarding hospitalisation for Covid-19 reported an increased risk for MEMs compared to the white and/or native population and 22 out of the 28 studies focusing on the ICU admission rates found an increased risk for MEMs. Among the 65 studies on mortality, 43 report a higher risk for MEMs. An increased risk of adverse outcomes was reported for MEMs. Social determinants of health are among the main factors involved in the genesis of health inequalities: a disadvantaged socio-economic status, a framework of structural racism and asymmetric access to healthcare are linked to increased susceptibility to the consequences of Covid-19. These findings underline the need for policymakers to consider the socio-economic barriers when designing prevention plans. Supplementary Information: The online version contains supplementary material available at 10.1007/s12134-023-01007-x.

COVID-19 outbreaks in residential care homes in Hong Kong and effectiveness of vaccine against severe outcomes.

Background: COVID-19 outbreaks in residential care homes for the elderly (RCHEs) and for persons with disability (RCHDs) have caused significant morbidity and mortality during 5th epidemic in Hong Kong. This article reviewed COVID-19 outbreaks situation and estimated the effectiveness of receiving at least two-dose of COVID-19 vaccine in preventing severe outcomes. Methods: To estimate attack rates and vaccination coverage, documentation on COVID-19 infection and their vaccination records of residential care homes (RCH) residents reported between December 31, 2021 and May 31, 2022 were reviewed, and infected cases were follow-up for 4 weeks for severe outcomes or death. Correlation between vaccination coverage against attack rate by types of homes was examined. Infected RCH residents with available information were included in the analysis of vaccine effectiveness against severe outcomes and death. Results: COVID-19 vaccination coverage was low in RCHDs (median 0.46, IQR: 0.24-0.76) and very low in RCHEs (median 0.08, IQR: 0.00-0.19). Higher attack rates were recorded among RCHE residents (median 0.84, IQR: 0.64-0.93) and higher case fatality rate (CFR: 28.1%) than in RCHDs (median 0.58, IQR: 0.31-0.84; CFR: 3.9%). The attack rate decreased when vaccination coverage increased for both RCHEs (ρ = -0.131, p < 0.001) and RCHDs (ρ = -0.333, p < 0.001). Comparing with infected residents who were unvaccinated/vaccinated with one-dose, receiving at least two-dose was estimated to be effective in reducing severe outcomes in 31% and 36% of infected RCHE and RCHD residents respectively; with greater reduction in mortality among RCHD than RCHE residents (54% and 38%, respectively). Vaccine effectiveness of two-dose of BNT162b2 against severe outcomes and death are higher than that of CoronaVac. Conclusions: Increasing COVID-19 vaccination could have significant impact on reducing the risk of COVID-19 outbreaks in RCHs. At least two-dose of COVID-19 vaccine is still effective in reducing severe outcomes and death among infected residents in RCHs during Omicron epidemic.

Development and Validation of Prediction Models for Severe Complications After Acute Ischemic Stroke: A Study Based on the Stroke Registry of Northwestern Germany.

Background The treatment of stroke has been undergoing rapid changes. As treatment options progress, prediction of those under risk for complications becomes more important. Available models have, however, frequently been built based on data no longer representative of today's care, in particular with respect to acute stroke management. Our aim was to build and validate prediction models for 4 clinically important, severe outcomes after stroke. Methods and Results We used German registry data from 152 710 patients with acute ischemic stroke obtained in 2016 (development) and 2017 (validation). We took into account potential predictors that were available at admission and focused on in-hospital mortality, intracranial mass effect, secondary intracerebral hemorrhage, and deep vein thrombosis as outcomes. Validation cohort prediction and calibration performances were assessed using the following 4 statistical approaches: logistic regression with backward selection, l1-regularized logistic regression, k-nearest neighbor, and gradient boosting classifier. In-hospital mortality and intracranial mass effects could be predicted with high accuracy (both areas under the curve, 0.90 [95% CI, 0.90-0.90]), whereas the areas under the curve for intracerebral hemorrhage (0.80 [95% CI, 0.80-0.80]) and deep vein thrombosis (0.73 [95% CI, 0.73-0.73]) were considerably lower. Stroke severity was the overall most important predictor. Models based on gradient boosting achieved better performances than those based on logistic regression for all outcomes. However, area under the curve estimates differed by a maximum of 0.02. Conclusions We validated prediction models for 4 severe outcomes after acute ischemic stroke based on routinely collected, recent clinical data. Model performance was superior to previously proposed approaches. These predictions may help to identify patients at risk early after stroke and thus facilitate an individualized level of care.

Optimising the impact of COVID-19 vaccination on mortality and hospitalisations using an individual additive risk measuring approach based on a risk adjustment scheme.

In this population-based cohort study, billing data from German statutory health insurance (BARMER, 10% of population) are used to develop a prioritisation model for COVID-19 vaccinations based on cumulative underlying conditions. Using a morbidity-based classification system, prevalence and risks for COVID-19-related hospitalisations, ventilations and deaths are estimated. Trisomies, behavioural and developmental disorders (relative risk: 2.09), dementia and organic psychoorganic syndromes (POS) (2.23) and (metastasised) malignant neoplasms (1.99) were identified as the most important conditions for escalations of COVID-19 infection. Moreover, optimal vaccination priority schedules for participants are established on the basis of individual cumulative escalation risk and are compared to the prioritisation scheme chosen by the German Government. We estimate how many people would have already received a vaccination prior to escalation. Vaccination schedules based on individual cumulative risk are shown to be 85% faster than random schedules in preventing deaths, and as much as 57% faster than the German approach, which was based primarily on age and specific diseases. In terms of hospitalisation avoidance, the individual cumulative risk approach was 51% and 28% faster. On this basis, it is concluded that using individual cumulative risk-based vaccination schedules, healthcare systems can be relieved and escalations more optimally avoided.

Cardiovascular comorbidities as predictors for severe COVID-19 infection or death.

AIMS: Pre-existing cardiovascular diseases (CVDs) have been proposed to identify patients at higher risk of adverse coronavirus disease 2019 (COVID-19) outcomes, but existing evidence is conflicting. Thus, it is unclear whether pre-existing CVDs are independently important predictors for severe COVID-19. METHODS AND RESULTS: In a nationwide Danish cohort of hospital-screened COVID-19 patients aged ≥40, we investigated if pre-existing CVDs predict the 30-day risk of (i) composite outcome of severe COVID-19 and (ii) all-cause mortality. We estimated 30-day risks using a Cox regression model including age, sex, each CVD comorbidity, chronic obstructive pulmonary disease-asthma, diabetes, and chronic kidney disease. To illustrate CVD comorbidities' importance, we evaluated the predicted risks of death and severe infection, for each sex, along ages 40-85. In total, 4090 COVID-19 hospital-screened patients were observed as of 26 August 2020; 22.1% had ≥1 CVD, 23.7% had severe infection within 30 days and 12.6% died. Predicted risks of both outcomes at age 75 among men with single CVD comorbidities did not differ in clinically meaningful amounts compared with men with no comorbidities risks for the composite outcome of severe infection; women with heart failure (28.2%; 95% CI 21.1-37.0%) or atrial fibrillation (30.0%; 95% CI: 24.2-36.9%) showed modest increases compared with women with no comorbidities (24.0%; 95% CI: 21.4-26.9%). CONCLUSIONS: The results showing only modest effects of CVDs on increased risks of poor COVID-19 outcomes are important in allowing public health authorities and clinicians to provide more tailored guidance to cardiovascular patients, who have heretofore been grouped together as high risk due to their disease status.

Age-Specific Seasonal Influenza Vaccine Effectiveness against Different Influenza Subtypes in the Hospitalized Population in Lithuania during the 2015-2019 Influenza Seasons.

BACKGROUND: Continuous monitoring of seasonal influenza vaccine effectiveness (SIVE) is needed due to the changing nature of influenza viruses and it supports the decision on the annual update of vaccine composition. Age-specific SIVE was evaluated against different influenza subtypes in the hospitalized population in Lithuania during four influenza seasons. METHODS: A test-negative case-control study design was used. SIVE and its 95% confidence intervals (95% CI) were calculated as (1 - odds ratio (OR)) × 100%. RESULTS: Adjusted SIVE in 18-64-year-old individuals against influenza A, A(H1N1)pdm09 and B/Yamagata were 78.0% (95% CI: 1.7; 95.1%), 88.6% (95% CI: -47.4; 99.1%), and 76.8% (95% CI: -109.9; 97.4%), respectively. Adjusted SIVE in individuals aged 65 years and older against influenza A, influenza B, and B/Yamagata were 22.6% (95% CI: -36.5; 56.1%), 75.3% (95% CI: 12.2; 93.1%) and 73.1% (95% CI: 3.2; 92.5%), respectively. Unadjusted SIVE against influenza A(H3N2) among 18-64-year-old patients was 44.8% (95% CI: -171.0; 88.8%) and among those aged 65 years and older was 5.0% (95% CI: -74.5; 48.3%). CONCLUSIONS: Point estimates suggest high SIVE against influenza A in 18-64-year-old participants, and against influenza B and B/Yamagata in those 65 years old and older.

Epidemiology of severe buprenorphine exposures reported to the U.S. Poison Centers.

OBJECTIVE: This study aims to evaluate the trends and risk factors of severe buprenorphine outcomes (SBO) reported to the U.S. Poison Centers (PCs). METHODS: We queried the National Poison Data System for exposures to buprenorphine from 2011 to 2016. SBO cases were defined as exposures that resulted in either a death or major clinical outcomes. Trends were tested using Poisson regression. Characteristics of the exposures were descriptively assessed. Logistic regression was used to evaluate the risk factors of SBO. RESULTS: SBO cases (967) reported to the PCs increased by 66.6% during this period (114-190, p < 0.001). While adults between 20 and 39 years were more frequent in the SBO group (50.4%) compared to the non-SBO group (38.7%), cases under 6 years (29.6% vs 13.8%) were more common among the non-SBO group. Intentional abuse (20.1% vs 24.9%) and suspected suicides (13.7% vs 37.5%) were significantly higher among the SBO group. Multisubstance exposures were more frequent among the SBO cases (36.4% vs 71.4%). SBO risk increased with age, with cases above 60 years (AOR: 1.66, 95% CI: 1.14-2.42) demonstrating significantly increased odds. Suspected suicide (AOR: 1.87, 95% CI: 1.53-2.28) and abuse (AOR: 1.40, 95% CI: 1.13-1.73) cases were more likely to result in a SBO. Multisubstance exposures significantly increased the risk of a SBO. CONCLUSIONS: This study reflected an increase in the cases of SBO paralleling the rise in the buprenorphine prescriptions. Age, reasons for exposure and multi-substance exposures significantly increased the risk of SBO.