Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease coronavirus disease 2019 (COVID-19), is a worldwide emergency. Demographic, comorbidity and laboratory ...determinants of death and of ICU admission were explored in all Danish hospitalised patients.
National health registries were used to identify all hospitalized patients with a COVID-19 diagnosis. We obtained demographics, Charlson Comorbidity Index (CCI), and laboratory results on admission and explored prognostic factors for death using multivariate Cox proportional hazard regression and competing risk survival analysis.
Among 2431 hospitalised patients with COVID-19 between February 27 and July 8 (median age 69 years IQR 53-80, 54.1% males), 359 (14.8%) needed admission to an intensive care unit (ICU) and 455 (18.7%) died within 30 days of follow-up. The seven-day cumulative incidence of ICU admission was lower for females (7.9%) than for males (16.7%), (p < 0.001). Age, high CCI, elevated C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), urea, creatinine, lymphopenia, neutrophilia and thrombocytopenia within ±24-h of admission were independently associated with death within the first week in the multivariate analysis. Conditional upon surviving the first week, male sex, age, high CCI, elevated CRP, LDH, creatinine, urea and neutrophil count were independently associated with death within 30 days. Males presented with more pronounced laboratory abnormalities on admission.
Advanced age, male sex, comorbidity, higher levels of systemic inflammation and cell-turnover were independent factors for mortality. Age was the strongest predictor for death, moderate to high level of comorbidity were associated with a nearly two-fold increase in mortality. Mortality was significantly higher in males after surviving the first week.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
There are limited data on outcomes of moderate to severe coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. We ...sought to compare the effectiveness of standard of care (SOC) alone versus SOC plus remdesivir and dexamethasone.
Methods
Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020 were studied. Death within 30 days and need of mechanical ventilation (MV) were compared by inverse probability of treatment weighted (ITPW) logistic regression analysis and shown as odds ratio (OR) with 95% confidence interval (CI).
Results
The 30-days mortality rate of 1694 individuals treated with remdesivir and dexamethasone in addition to SOC was 12.6% compared to 19.7% for 1053 individuals receiving SOC alone. This corresponded to a weighted OR of 30-day mortality of 0.47 (95% CI: .38–.57) for patients treated with remdesivir and dexamethasone compared to patients receiving SOC alone. Similarly, progression to MV was reduced (OR 0.36; 95% CI: .29–.46).
Conclusions
Treatment of moderate to severe COVID-19 during June through December that included remdesivir and dexamethasone was associated with reduced 30-day mortality and need of MV compared to treatment in February through May.
Treatment of moderate to severe coronavirus disease 2019 (COVID-19) with remdesivir and dexamethasone was associated with a lower risk of mechanical ventilation and a significant better overall 30-day survival as compared to standard care alone.
Individuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other ...comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD.
An open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline.
Currently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD.
ClinicalTrials.gov NCT04873856 . Registered on May 3, 2021.
Background
Older adults and immunocompromised individulas are often excluded from vaccine trials.
Aim
We hypothesised that during the coronavirus disease 2019 (COVID-19) pandemic, the proportion of ...trials excluding these patients decreased.
Methods
Using the US Food and Drug Administration and and European Medicines Agency search engines, we identified all vaccines approved against pneumococcal disease, influenza (quadrivalent vaccines), and COVID-19 from 2011 to 2021. Study protocols were screened for direct and indirect age exclusion criteria and exclusion of immunocompromised individuals. In addition, we reviewed the studies with no explicit exclusion criteria and investigated the actual inclusion of those individuals.
Results
We identified 2024 trial records; 1702 were excluded (e.g., use of other vaccine or risk group); and 322 studies were eligible for our review. Among the pneumococcal and influenza vaccine trials (
n
= 193), 81 (42%) had an explicit direct age exclusion, and 150 (78%) had an indirect age-related exclusion. In total, 163 trials (84%) trials were likely to exclude older adults. Among the COVID-19 vaccine trials (
n
= 129), 33 (26%) had direct age exclusion and 82 (64%) had indirect age exclusion; in total, 85 (66%) trials were likely to exclude older adults. Therefore was a 18% decrease in the proportion of trials with age-related exclusion between 2011 and 2021 (only influenza and pneumococcal vaccine trials) and 2020–2021 (only COVID-19 vaccine trials) (
p
= 0.014). In a sub-analysis assessing observational and randomised trials, the decrease was 25% and 9%, respectively. Immunocompromised individuals were included in 87 (45%) of the pneumococcal and influenza vaccine trials compared with 54 (42%) of the COVID-19 vaccine trials (p = 0.058).
Conclusions
During the COVID-19 pandemic, we found a decrease in the exclusion of older adults from vaccine trials but no significant change in the inclusion of immunocompromised individulas.
Mortality due to COVID-19 is higher among elderly patients with comorbidities. Even so, prognostication in COVID-19 remains limited.
We assessed 90-day mortality stratified by comorbidities, routine ...biochemical markers and oxygen need in a consecutive single-centre cohort from 2 March to 2 June 2020.
We included 263 hospitalised patients with laboratory-confirmed COVID-19. On admission, fitness for intensive care was determined in 254 patients including 98 (39%) with a do-not-resuscitate order. Ninety-day overall mortality was 29%, whereas intensive care unit (ICU) mortality was 35% (14/40). Alcohol abuse, liver disease and elevated urea were strongly associated with mortality in univariable analyses. In a mutually adjusted multivariable analysis, we found an independent incremental increase in 90-day mortality with each increasing age by decade (hazard ratio (HR) = 1.5; 95% confidence interval (CI): 1.2-1.9), Charlson Comorbidity Index (CCI) score (HR = 1.2; 95% CI: 1.0-1.4), number of abnormal blood tests (HR = 1.2; 95% CI: 1.1-1.3) and l/min. of supplemental oxygen (HR = 1.1; 95% CI: 1.1-1.2).
The overall mortality was similar to that of other hospitalised patients, whereas the ICU mortality was lower than expected. On admission, each additional age by decade, CCI score, number of abnormal blood tests and magnitude of supplemental oxygen were independently associated with increased mortality.
none.
not relevant.
The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated.
In this nationwide retrospective cohort study, we included 3826 ...patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics.
Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37-0.57) and 0.47 (95% confidence interval, 0.39-0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration.
Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. New, simple, and better-performing diagnostic tools are needed for the diagnosis of tuberculosis (TB). Much effort has been invested in developing an antibody-based test for TB, but to ...date, no such test has performed with sufficient sensitivity and specificity. A key question remaining is the extent to which the disappointing performance of current tests is associated with a high background prevalence of latent TB. Methods. We compared Mycobacterium tuberculosis-specific ESAT-6 and CFP-10 antibody responses in a total of 565 human serum samples from M. tuberculosis-uninfected donors and donors with latent infection, as well as samples from patients with active TB. Our study included samples from 4 countries, representing environments with low, intermediate, and high TB incidences. Results. We demonstrated significant increases in antibody levels in latently infected contacts, compared with M. tuberculosis-uninfected individuals, and in patients with active TB disease, compared with latently infected contacts. Furthermore, we found a striking increase in the magnitude of the antibody responses in samples obtained from infected Ethiopian individuals (with and without disease), compared with Danish and Brazilian infected individuals; this was presumably the result of higher exposure levels. Conclusions. Our study confirms the presence of ESAT-6 and CFP-10 antibodies in patients with TB, and we demonstrate that significant antibody responses are not restricted to active TB disease but can reflect latent infection, particularly in areas with high levels of exposure to M. tuberculosis. This finding is important for the understanding of the poor discriminatory power of current serodiagnostic tests in regions of endemicity, and it may have major implications on the future development of serologic tests.
Vitamin D is essential to immune function, but little is known about the vitamin D status in equatorial populations. A cross-sectional study was conducted among pulmonary tuberculosis (PTB) patients ...in Mwanza, Tanzania to identify the predictors of their vitamin D status. Data on sociodemography, season, and intake of food, alcohol, tobacco, and soil were collected, anthropometric measurements taken, and serum α₁-antichymotrypsin (ACT), ferritin and soluble transferrin receptor (sTfR), and serum 25-hydroxy-(ergocalciferol+cholecalciferol) 25(OH)D determined. Of the 655 patients studied, 79.7% (508/637) were culture-positive (PTB+) and 47.2% HIV infected. Mean serum ACT, an acute phase reactant, was 0.73 ± 0.25 g/L with 69.2% >0.6 g/L. Mean serum 25(OH)D was 86.6 ± 32.9 nmol/L, with 41.2% <75 nmol/L. Serum 25(OH)D was highest during the harvest season, May to July, compared with the remaining year. Single subjects had lower 10.4 (95% CI 4.0; 16.9) nmol/L serum 25(OH)D concentrations than married subjects and PTB+ patients had concentrations lower 8.2 (95% CI 1.5; 14.9) nmol/L than PTB- patients. Serum 25(OH)D increased with consumption of a large freshwater fish but not of small dried fish or other foods. BMI and serum TfR were positive predictors of serum 25(OH)D, whereas neither elevated serum ACT nor HIV were predictors. In conclusion, serum 25(OH)D is a valid measure of vitamin D status during the acute phase response. The lower concentrations in PTB+ patients may reflect lower sun exposure or increased utilization. The health consequences of hypovitaminosis D in low-income equatorial populations, at risk for both infectious and chronic diseases, should be studied.
Mannose-binding lectin (MBL) mediates protection against infections by using the complement system, but certain microorganisms may increase infectivity by exploiting this host defense system. Thus, ...it has been speculated whether genetically determined low MBL levels may confer partial protection against certain intracellular microorganisms, such as Mycobacterium tuberculosis. We investigated MBL alleles in 109 culture-positive human immunodeficiency virus–uninfected patients with tuberculosis living in Denmark and 250 white control subjects. Patients and control subjects were divided into 3 different groups defined by undetectable, low, and high serum MBL concentrations, which correlates to deficient, low, and high expressing MBL genotypes. A significantly decreased frequency of patients with the low-expressing MBL genotype was observed in white patients compared to control subjects. The same tendency also was observed in patients of other ethnic origin. It may be hypothesized that heterozygosity for MBL variant alleles, which encodes low serum MBL levels, is associated with protection against clinical tuberculosis
Genetic susceptibility towards clinical tuberculosis has been proposed in several population studies. We investigated whether polymorphisms in the candidate genes encoding solute carrier 11a1 protein ...(SLC11A1 formerly NRAMP1), mannose-binding lectin (MBL2) and Vitamin D receptor (VDR) were associated with tuberculosis in an East-African setting.
Four hundred and forty-three culture positive pulmonary tuberculosis patients and 426 controls from Mwanza district in the northern part of Tanzania were prospectively included. Polymorphisms in the candidate genes were detected by different PCR-based techniques.
A significant association between pulmonary tuberculosis and a microsatellite marker in the 5′(CA)
n
locus in the
SLC11A1 gene compared with controls (38% versus 30% odds ratio 1.45, 95% CI: 1.06–1.9,
P
=
0.014) was observed. The association was apparent only in HIV negative tuberculosis patients. No association with tuberculosis was seen with 3 other
SLC11A1 loci investigated, which previously have been associated with tuberculosis in other populations or with
MBL2 and
VDR polymorphisms. The tuberculosis associated microsatellite marker was situated on different
SLC11A1 haplotypes.
In this cohort a microsatellite marker in the 5′(CA)
n
locus situated in the
SLC11A1 gene was associated with tuberculosis. The observed association was seen only in HIV negative patients suggesting that this genetic susceptibility for tuberculosis may be surpassed by co-infections.
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