Excess risk for acute myocardial infarction mortality during the COVID-19 pandemic

The COVID-19 pandemic has had a detrimental impact on the healthcare system. Our study armed to assess the extent and the disparity in excess acute myocardial infarction (AMI)-associated mortality during the pandemic, through the recent Omicron outbreak. Using data from the CDC's National Vital Statistics System, we identified 1 522 669 AMI-associated deaths occurring between 4/1/2012 and 3/31/2022. Accounting for seasonality, we compared age-standardized mortality rate (ASMR) for AMI-associated deaths between prepandemic and pandemic periods, including observed versus predicted ASMR, and examined temporal trends by demographic groups and region. Before the pandemic, AMI-associated mortality rates decreased across all subgroups. These trends reversed during the pandemic, with significant rises seen for the youngest-aged females and males even through the most recent period of the Omicron surge (10/2021–3/2022). The SAPC in the youngest and middle-age group in AMI-associated mortality increased by 5.3% (95% confidence interval [CI]: 1.6%–9.1%) and 3.4% (95% CI: 0.1%–6.8%), respectively. The excess death, defined as the difference between the observed and the predicted mortality rates, was most pronounced for the youngest (25–44 years) aged decedents, ranging from 23% to 34% for the youngest compared to 13%–18% for the oldest age groups. The trend of mortality suggests that age and sex disparities have persisted even through the recent Omicron surge, with excess AMI-associated mortality being most pronounced in younger-aged adults.     

COVID-19 mortality rate prediction for India using statistical neural networks and gaussian process regression model

The primary purpose of this research is to identify the best COVID-19 mortality model for India using regression models and is to estimate the future COVID-19 mortality rate for India. Specifically, Statistical Neural Networks (Radial Basis Function Neural Network (RBFNN), Generalized Regression Neural Network (GRNN)), and Gaussian Process Regression (GPR) are applied to develop the COVID-19 Mortality Rate Prediction (MRP) model for India. For that purpose, there are two types of dataset used in this study: One is COVID-19 Death cases, a Time Series Data and the other is COVID-19 Confirmed Case and Death Cases where Death case is dependent variable and the Confirmed case is an independent variable. Hyperparameter optimization or tuning is used in these regression models, which is the process of identifying a set of optimal hyperparameters for any learning process with minimal error. Here, sigma (σ) is a hyperparameter whose value is used to constrain the learning process of the above models with minimum Root Mean Squared Error (RMSE). The performance of the models is evaluated using the RMSE and ''R2 values, which shows that the GRP model performs better than the GRNN and RBFNN.     

Clinical characteristics and risk factors for 28-day mortality in critically ill patients with COVID-19: a retrospective cohort study

BackgroundTo date, the coronavirus disease 2019 (COVID-19) caused more than 2.6 million deaths all around the world. Risk factors for mortality remain unclear. The primary aim was to determine the independent risk factors for 28-day mortality.Materials and MethodsIn this retrospective cohort study, critically ill patients (≥ 18 years) who were admitted to the intensive care unit due to COVID-19 were included. Patient characteristics, laboratory data, radiologic findings, treatments, and complications were analyzed in the study.ResultsA total of 249 patients (median age 71, 69.1% male) were included in the study. 28-day mortality was 67.9% (n = 169). The median age of deceased patients was 75 (66–81). Of them, 68.6% were male. Cerebrovascular disease, dementia, chronic kidney disease, and malignancy were significantly higher in the deceased group. In the multivariate analysis, sepsis/septic shock (OR, 15.16, 95% CI, 3.96–58.11, p < 0.001), acute kidney injury (OR, 4.73, 95% CI, 1.55–14.46,p = 0.006), acute cardiac injury (OR, 9.76, 95% CI, 1.84–51.83, p = 0.007), and chest CT score higher than 15 (OR, 4.49, 95% CI, 1.51-13.38, p = 0.007) were independent risk factors for 28-day mortality.ConclusionEarly detection of the risk factors and the use of chest CT score might improve the outcomes in patients with COVID-19.     

Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis

Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. Information regarding the predictors of mortality in patients with COVID-19 remains scarce. Herein, we performed a systematic review of published articles, from 1 January to 24 April 2020, to evaluate the risk factors associated with mortality in COVID-19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.1; P < .00001), coronary heart disease (OR, 3.8; 95% CI, 2.1-6.9; P < .00001), and diabetes (OR, 2.0; 95% CI, 1.7-2.3; P < .00001) were associated with significantly higher risk of death amongst patients with COVID-19. Those who died, compared with those who survived, differed on multiple biomarkers on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI, 19.0-69.4; P = .0006); C-reactive protein (+66.3 µg/mL, 95% CI, 46.7-85.9; P < .00001); interleukin-6 (+4.6 ng/mL, 95% CI, 3.6-5.6; P < .00001); D-dimer (+4.6 µg/mL, 95% CI, 2.8-6.4; P < .00001); creatinine (+15.3 µmol/L, 95% CI, 6.2-24.3; P = .001); and alanine transaminase (+5.7 U/L, 95% CI, 2.6-8.8; P = .0003); as well as decreased levels of albumin (−3.7 g/L, 95% CI, −5.3 to −2.1; P < .00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end-organ damage are at higher risk of mortality due to COVID-19 infection and should be managed with greater intensity.     

Clinical,radiological, and laboratory characteristics and risk factors for severity and mortality of 289 hospitalized COVID-19 patients

Background

The coronavirus disease 2019 (COVID-19) has become a global pandemic, with 10%-20% of severe cases and over 508 000 deaths worldwide.

Objective

This study aims to address the risk factors associated with the severity of COVID-19 patients and the mortality of severe patients.

Methods

289 hospitalized laboratory-confirmed COVID-19 patients were included in this study. Electronic medical records, including patient demographics, clinical manifestation, comorbidities, laboratory tests results, and radiological materials, were collected and analyzed. According to the severity and outcomes of the patients, they were divided into three groups: nonsurvived (n = 49), survived severe (n = 78), and nonsevere (n = 162) groups. Clinical, laboratory, and radiological data were compared among these groups. Principal component analysis (PCA) was applied to reduce the dimensionality and visualize the patients on a low-dimensional space. Correlations between clinical, radiological, and laboratory parameters were investigated. Univariate and multivariate logistic regression methods were used to determine the risk factors associated with mortality in severe patients. Longitudinal changes of laboratory findings of survived severe cases and nonsurvived cases during hospital stay were also collected.

Results

Of the 289 patients, the median age was 57 years (range, 22-88) and 155 (53.4%) patients were male. As of the final follow-up date of this study, 240 (83.0%) patients were discharged from the hospital and 49 (17.0%) patients died. Elder age, underlying comorbidities, and increased laboratory variables, such as leukocyte count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) on admission, were found in survived severe cases compared to nonsevere cases. According to the multivariate logistic regression analysis, elder age, a higher number of affected lobes, elevated CRP levels on admission, increased prevalence of chest tightness/dyspnea, and smoking history were independent risk factors for death of severe patients. A trajectory in PCA was observed from "nonsevere" toward "nonsurvived" via "severe and survived" patients. Strong correlations between the age of patients, the affected lobe numbers, and laboratory variables were identified. Dynamic changes of laboratory findings of survived severe cases and nonsurvived cases during hospital stay showed that continuing increase of leukocytes and neutrophil count, sustained lymphopenia and eosinopenia, progressing decrease in platelet count, as well as high levels of NLR, CRP, PCT, AST, BUN, and serum creatinine were associated with in-hospital death.

Conclusions

Survived severe and nonsurvived COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principle component analysis. Elder age, increased number of affected lobes, higher levels of serum CRP, chest tightness/dyspnea, and smoking history were risk factors for mortality of severe COVID-19 patients. Longitudinal changes of laboratory findings may be helpful in predicting disease progression and clinical outcome of severe patients.

     

Effects of tocilizumab on mortality in hospitalized patients with COVID-19: a multicentre cohort study

ObjectivesTocilizumab has been proposed as a candidate therapy for patients with severe coronavirus disease 2019 (COVID-19), especially among those with higher systemic inflammation. We investigated the association between receipt of tocilizumab and mortality in a large cohort of hospitalized patients.MethodsIn this cohort study of patients hospitalized with COVID-19 in Spain, the primary outcome was time to death and the secondary outcome time to intensive care unit (ICU) admission or death. We used inverse probability weighting to fit marginal structural models adjusted for time-varying covariates to determine the causal relationship between receipt of tocilizumab and outcome.ResultsData from 1229 patients were analysed, with 261 patients (61 deaths) in the tocilizumab group and 969 patients (120 deaths) in the control group. In the adjusted marginal structural models, a significant interaction between receipt of tocilizumab and high C-reactive protein (CRP) levels was detected. Tocilizumab was associated with decreased risk of death (adjusted hazard ratio 0.34, 95% confidence interval 0.16–0.72, p 0.005) and ICU admission or death (adjusted hazard ratio 0.39, 95% confidence interval 0.19–0.80, p 0.011) among patients with baseline CRP >150 mg/L but not among those with CRP ≤150 mg/L. Exploratory subgroup analyses yielded point estimates that were consistent with these findings.ConclusionsIn this large observational study, tocilizumab was associated with a lower risk of death or ICU admission or death in patients with higher CRP levels. While the results of ongoing clinical trials of tocilizumab in patients with COVID-19 will be important to establish its safety and efficacy, our findings have implications for the design of future clinical trials.     

Risk factors for mortality of critically ill patients with COVID-19 receiving invasive ventilation

Rationale: Early invasive ventilation may improve outcomes for critically ill patients with COVID-19. The objective of this study is to explore risk factors for 28-day mortality of COVID-19 patients receiving invasive ventilation.Methods: 74 consecutive adult invasively ventilated COVID-19 patients were included in this retrospective study. The demographic and clinical data were compared between survivors and non-survivors, and Cox regression analysis was used to explore risk factors for 28-day mortality. The primary outcome was 28-day mortality after initiation of invasive ventilation. Secondary outcome was the time from admission to intubation.Results: Of 74 patients with COVID-19, the median age was 68.0 years, 53 (71.6%) were male, 47 (63.5%) had comorbidities with hypertension, and diabetes commonly presented. The most frequent symptoms were fever and dyspnea. The median time from hospital admission to intubation was similar in survivors and non-survivors (6.5 days vs. 5.0 days). The 28-day mortality was 81.1%. High Sequential Organ Failure Assessment (SOFA) score (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.23-1.92; p < 0.001) and longer time from hospital admission to intubation (HR, 2.41; 95% CI, 1.15-5.07; p = 0.020) were associated with 28-day mortality in invasively ventilated COVID-19 patients.Conclusions: The mortality of invasively ventilated COVID-19 patients was particularly striking. Patients with high SOFA score and receiving delayed invasive ventilation were at high risk of mortality.     

Proton pump inhibitor use and risk for recurrent Clostridioides difficile infection: a systematic review and meta-analysis

ObjectivesProton pump inhibitor (PPI) therapy is a potentially modifiable risk factor for recurrent Clostridioides difficile infection (CDI). Citing an absence of clinical trials, many guidelines do not provide recommendations for addressing PPI management. Our aim was to perform an updated systematic review and meta-analysis evaluating the association between PPI use and recurrent CDI addressing prior methodological limitations.MethodsData sources were MEDLINE and EMBASE. Eligible studies were cohort and case–control studies; there were no restrictions on study setting or duration of follow-up. Participants were adults with prior CDI who did or did not receive PPI therapy and were assessed for recurrent CDI. Summary (unadjusted) odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Prespecified subgroup analyses were performed to explore heterogeneity including study design, study quality, duration of follow-up, adjustment for confounders, and outcome definition.ResultsSixteen studies were included in the meta-analysis, comprising 57 477 patients with CDI, of whom 6870 (12%) received PPIs. The rate of recurrent CDI was 24% in patients treated with PPIs versus 18% in those who were not. A meta-analysis that pooled unadjusted odds ratios demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.69, 95%CI 1.46–1.96) versus those who did not. There was moderate heterogeneity between studies (I² 56%); however, a sensitivity analysis restricted to studies with 56 days of follow-up substantially reduced the heterogeneity (OR 1.59, 95%CI 1.36–1.85; I² 12%). An analysis restricted to multivariate studies that combined adjusted ORs also demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.49, 95%CI 1.12–2.00). No publication bias was identified.ConclusionsWe found significantly higher odds of recurrent CDI among users of PPIs that persisted across multiple sensitivity analyses. These results support stronger recommendations for PPI stewardship at CDI diagnosis.     

Risk factors for disease severity,unimprovement, and mortality in COVID-19 patients in Wuhan,China

ObjectiveIn December 2019, coronavirus disease (COVID-19) emerged in Wuhan. However, the characteristics and risk factors associated with disease severity, unimprovement and mortality are unclear and our objective is to throw some light on these.MethodsAll consecutive patients diagnosed with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 11 to February 6, 2020, were enrolled in this retrospective cohort study.ResultsA total of 663 COVID-19 patients were included in this study. Among these, 247 (37.3%) had at least one kind of chronic disease; 0.5% of the patients (n = 3) were diagnosed with mild COVID-19, while 37.8% (251/663), 47.5% (315/663), and 14.2% (94/663) were in moderate, severe, and critical conditions, respectively. In our hospital, during follow-up 251 of 663 patients (37.9%) improved and 25 patients died, a mortality rate of 3.77%. Older patients (>60 years old) and those with chronic diseases were prone to have a severe to critical COVID-19 condition, to show unimprovement, and to die (p <0.001, <0.001). Multivariate logistic regression analysis identified being male (OR = 0.486, 95%CI 0.311–0.758; p 0.001), having a severe COVID-19 condition (OR = 0.129, 95%CI 0.082–0.201; p <0.001), expectoration (OR = 1.796, 95%CI 1.062–3.036; p 0.029), muscle ache (OR = 0.309, 95%CI 0.153–0.626; p 0.001), and decreased albumin (OR = 1.929, 95%CI 1.199–3.104; p 0.007) as being associated with unimprovement in COVID-19 patients.ConclusionMale sex, a severe COVID-19 condition, expectoration, muscle ache, and decreased albumin were independent risk factors which influence the improvement of COVID-19 patients.     

Rapid review of virus risk communication interventions: Directions for COVID-19

ObjectiveIn response to COVID-19, we conducted a rapid review of risk communication interventions to mitigate risk from viruses to determine if such interventions are efficacious.MethodsWe searched for risk communication interventions in four databases: Medline, PsycInfo, the ProQuest Coronavirus Research Database, and CENTRAL. The search produced 1572 articles. Thirty-one articles were included in the final review.ResultsResults showed risk communication interventions can produce cognitive and behavior changes around viruses. Results were more consistently positive for interventions focused on HIV/AIDS as compared to influenza. There was no consistent best intervention approach when comparing peer health, audio/visual, and intensive multi-media interventions. Tailoring risk communication toward a target population, in comparison to not tailoring, was related to better outcomes.ConclusionThe results suggest that risk communication interventions can be efficacious at reducing risk from viruses. They also highlight the complexity of risk communication interventions. Additional research is needed to understand the mechanisms that lead risk communication to reduce risk from viruses.Practical valueResults support risk communication interventions to reduce risk from viruses.     

Effect of mortality from COVID-19 on inpatient outcomes

When hospitals first encountered coronavirus disease 2019 (COVID-19), there was a dearth of therapeutic options and nearly 1 in 3 patients died from the disease. By the summer of 2020, as deaths from the disease declined nationally, multiple single-center studies began to report declining mortality of patients with COVID-19. To evaluate the effect of COVID-19 on hospital-based mortality, we searched the Vizient Clinical Data Base for outcomes data from approximately 600 participating hospitals, including 130 academic medical centers, from January 2017 through December 2020. More than 32 million hospital admissions were included in the analysis. After an initial spike, mortality from COVID-19 declined in all regions of the country to under 10% by June 2020 and remained constant for the remainder of the year. Despite this, inpatient, all-cause mortality has increased since the beginning of the pandemic, even those without respiratory failure. Inpatient mortality has particularly increased in elderly patients and in those requiring intubation for respiratory failure. Since June 2020, COVID-19 kills one in every 10 patients admitted to the hospital with this diagnosis. The addition of this new disease has raised overall hospital mortality especially those who require intubation for respiratory failure.     

Obesity predisposes to the risk of higher mortality in young COVID-19 patients

Although emerging data demonstrated mortality of young COVID-19 patients, no data have reported the risk factors of mortality for these young patients, and whether obesity is a risk for young COVID-19 patients remains unknown. We conducted a retrospective study including 13 young patients who died of COVID-19 and 40 matched survivors. Logistic regression was employed to characterize the risk factors of mortality in young obese COVID-19 patients. Most of the young deceased COVID-19 patients were mild cases at the time of admission, but the disease progressed rapidly featured by a higher severity of patchy shadows (100.00% vs 48.70%; P = .006), pleural thickening (61.50% vs 12.80%; P = .012), and mild pericardial effusion (76.90% vs 0.00%; P < .001). Most importantly, the deceased patients manifested higher body mass index (odds ratio [OR] = 1.354; 95% confidence interval [CI] = 1.075-1.704; P = .010), inflammation-related index C-reactive protein (OR = 1.014; 95% CI = 1.003-1.025; P = .014), cardiac injury biomarker hs-cTnI (OR = 1.420; 95% CI = 1.112-1.814; P = .005), and increased coagulation activity biomarker D-dimer (OR = 418.7; P = .047), as compared with that of survivors. Our data support that obesity could be a risk factor associated with high mortality in young COVID-19 patients, whereas aggravated inflammatory response, enhanced cardiac injury, and increased coagulation activity are likely to be the mechanisms contributing to the high mortality.     

Do high-dose corticosteroids improve outcomes in hospitalized COVID-19 patients?

Coronavirus disease 2019 (COVID-19) is characterized by dysregulated hyperimmune response and steroids have been shown to decrease mortality. However, whether higher dosing of steroids results in better outcomes has been debated. This was a retrospective observation of COVID-19 admissions between March 1, 2020, and March 10, 2021. Adult patients (≥18 years) who received more than 10 mg daily methylprednisolone equivalent dosing (MED) within the first 14 days were included. We excluded patients who were discharged or died within 7 days of admission. We compared the standard dose of steroids (<40 mg MED) versus the high dose of steroids (>40 mg MED). Inverse probability weighted regression adjustment (IPWRA) was used to examine whether higher dose steroids resulted in improved outcomes. The outcomes studied were in-hospital mortality, rate of acute kidney injury (AKI) requiring hemodialysis, invasive mechanical ventilation (IMV), hospital-associated infections (HAI), and readmissions. Of the 1379 patients meeting study criteria, 506 received less than 40 mg of MED (median dose 30 mg MED) and 873 received more than or equal to 40 mg of MED (median dose 78 mg MED). Unadjusted in-hospital mortality was higher in patients who received high-dose corticosteroids (40.7% vs. 18.6%, p < 0.001). On IPWRA, the use of high-dose corticosteroids was associated with higher odds of death (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.45–3.14, p < 0.001) but not with the development of HAI, readmissions, or requirement of IMV. High-dose corticosteroids were associated with lower rates of AKI requiring hemodialysis (OR 0.33; 95% CI 0.18–0.63). In COVID-19, corticosteroids more than or equal to 40 mg MED were associated with higher in-hospital mortality.     

Clinical characteristics and follow-up analysis of 324 discharged COVID-19 patients in Shenzhen during the recovery period

Objectives: Research on recovering COVID-19 patients could be helpful for containing the pandemic and developing vaccines, but we still do not know much about the clinical features, recovery process, and antibody reactions during the recovery period.Methods: We retrospectively analysed the epidemiological information, discharge summaries, and laboratory results of 324 patients.Results: In all, 15 (8.62%) patients experienced chest distress/breath shortness, where 8 of the 15 were severely ill. This means severely ill patients need an extended amount of time to recover after discharge; next, 20 (11.49%) patients experienced anxiety and 21 (12.07%) had headache/insomnia and a small fraction of them complained of anosmia/ageusia, indicating that these patients need treatment for mental and psychological health issues. Regarding the re-positive patients, their CT and laboratory test results showed no obvious evidence of illness progress or infectivity but a high anti-SARS-CoV-2 antibody expression.Conclusion: Recovered COVID-19 patients need psychological and physiological care and treatment, re-positivity can occur in any person, but juveniles, females, and patients with mild/moderate existing symptoms have higher rates of re-positivity, While there is no evidence that turning re-positive has an impact on their infectivity, but it still alerted us that we need differentiate them in the following managements.     

质子泵抑制剂FR167356对骨质疏松模型兔种植体骨整合的影响

背景：破骨细胞质膜上的空泡型质子泵是骨组织溶解必不可少的关键酶,空泡型质子泵抑制剂对体外培养的破骨细胞有明显的抑制作用。 目的：观察质子泵抑制剂FR167356对骨质疏松家兔种植体周围骨整合的影响。 方法：将24只5月龄雌性家兔随机分成单纯卵巢切除组、质子泵抑制剂组及假手术组,每组8只,前2组家兔切除双侧卵巢,假手术组只切除卵巢周围等量的脂肪组织。卵巢摘除12周后,在所有家兔的双侧胫骨近心端各置入1枚纯钛种植体(长8 mm,直径3.3 mm)。质子泵抑制剂组在种植体周围肌注FR167356,其他2组肌注等量的生理盐水。在种植后4,12周进行X射线片、组织形态学观察及拔出力学实验。 结果与结论：X射线片检查结果显示种植后第4周时,单纯卵巢切除组种植体的高阻射影像、种植体螺纹间隙的低密度影像、骨组织的界限明显比其他2组清楚;12周时,与单纯卵巢切除组相比,假手术组和质子泵抑制剂组种植体螺纹间隙的密度与周围骨组织更接近,种植体与周围骨组织的界限消失的更明显,2组无明显差异。组织学观察结果发现,4周时假手术组和质子泵抑制剂组种植体周围骨质多孔,平行于种植体表面的骨小梁排列紧密,小梁间连接较多,2组无明显差异;12周时假手术组和质子泵抑制剂组种植体周围骨组织量比4周时明显增加,骨小梁增粗且粗细均匀,连接紧密且间隙减小,单纯卵巢切除组没有观察到这种现象。在力学实验中,第4,12周,单纯卵巢切除组的最大拔出力值明显低于其他2组。提示局部应用质子泵抑制剂FR167356对骨质疏松家兔种植体骨整合有显著的促进作用。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：