Older adults with cancer use the emergency department (ED) for acute concerns.
Characterize the palliative care needs and clinical outcomes of advanced cancer patients in the ED.
A planned secondary ...data analysis of the Comprehensive Oncologic Emergencies Research Network (CONCERN) data.
Cancer patients who presented to the 18 CONCERN affiliated EDs in the United States.
Survey included demographics, cancer type, functional status, symptom burden, palliative and hospice care enrollment, and advance directive code status.
Of the total (674/1075, 62.3%) patients had advanced cancer and most were White (78.6%) and female (50.3%); median age was 64 (interquartile range 54-71) years. A small proportion of them were receiving palliative (6.5% 95% confidence interval; CI 3.0-7.6;
= 0.005) and hospice (1.3% 95% CI 1.0-3.2;
= 0.52) care and had a higher 30-day mortality rate (8.3%, 95% CI 6.2-10.4).
Patients with advanced cancer continue to present to the ED despite recommendations for early delivery of palliative care.
Purpose
Emergency department (ED) visits by patients with cancer frequently end in hospitalization. As concerns about ED and hospital crowding increase, observation unit care may be an important ...strategy to deliver safe and efficient treatment for eligible patients. In this investigation, we compared the prevalence and clinical characteristics of cancer patients who received observation unit care with those who were admitted to the hospital from the ED.
Methods
We performed a multicenter prospective cohort study of patients with cancer presenting to an ED affiliated with one of 18 hospitals of the Comprehensive Oncologic Emergency Research Network (CONCERN) between March 1, 2016 and January 30, 2017. We compared patient characteristics with the prevalence of observation unit care usage, hospital admission, and length of stay.
Results
Of 1051 enrolled patients, 596 (56.7%) were admitted as inpatients, and 72 (6.9%) were placed in an observation unit. For patients admitted as inpatients, 23.7% had a length of stay ≤2 days. The conversion rate from observation to inpatient was 17.1% (95% CI 14.6–19.4) among those receiving care in an observation unit. The average observation unit length of stay was 14.7 h. Patient factors associated ED disposition to observation unit care were female gender and low Charlson Comorbidity Index.
Conclusion
In this multicenter prospective cohort study, the discrepancy between observation unit care use and short inpatient hospitalization may represent underutilization of this resource and a target for process change.
There are only few data concerning persistence of neutralizing antibodies (NAbs) among SARS-CoV-2-infected healthcare workers (HCW). These individuals are particularly exposed to SARS-CoV-2 infection ...and at potential risk of reinfection. We followed 26 HCW with mild COVID-19 three weeks (D21), two months (M2) and three months (M3) after the onset of symptoms. All the HCW had anti-receptor binding domain (RBD) IgA at D21, decreasing to 38.5% at M3 (p < 0.0001). Concomitantly a significant decrease in NAb titers was observed between D21 and M2 (p = 0.03) and between D21 and M3 (p < 0.0001). Here, we report that SARS-CoV-2 can elicit a NAb response correlated with anti-RBD antibody levels. However, this neutralizing activity declines, and may even be lost, in association with a decrease in systemic IgA antibody levels, from two months after disease onset. This short-lasting humoral protection supports strong recommendations to maintain infection prevention and control measures in HCW, and suggests that periodic boosts of SARS-CoV-2 vaccination may be required.
Resistance to the integrase strand transfer inhibitors raltegravir and elvitegravir is often due to well-identified mutations in the integrase gene. However, the situation is less clear for patients ...who fail dolutegravir treatment. Furthermore, most
experiments to select resistance to dolutegravir have resulted in few mutations of the integrase gene. We performed an
dolutegravir resistance selection experiment by using a breakthrough method. First, MT4 cells were infected with human immunodeficiency virus type 1 (HIV-1) Lai. After integration into the host cell genome, cells were washed to remove unbound virus and 500 nM dolutegravir was added to the cell medium. This high concentration of the drug was maintained throughout selection. At day 80, we detected a virus highly resistant to dolutegravir, raltegravir, and elvitegravir that remained susceptible to zidovudine. Sequencing of the virus showed no mutations in the integrase gene but highlighted the emergence of five mutations, all located in the
region, of which four were clustered in the 3' polypurine tract (PPT). Mutations selected
by dolutegravir, located outside the integrase gene, can confer a high level of resistance to all integrase inhibitors. Thus, HIV-1 can use an alternative mechanism to develop resistance to integrase inhibitors by selecting mutations in the 3' PPT region. Further studies are required to determine to what extent these mutations may explain virological failure during integrase inhibitor therapy.
Integrase strand transfer inhibitors (INSTIs) are increasingly used both as first-line drugs and in rescue therapy because of their low toxicity and high efficacy in both treatment-naive and treatment-experienced patients. Until now, resistance mutations selected by INSTI exposure have either been described in patients or selected
and involve the integrase gene. Most mutations selected by raltegravir, elvitegravir, or dolutegravir exposure are located inside the catalytic site of the integrase gene, but mutations outside the catalytic site of the integrase gene have also been selected with dolutegravir. Following
selection with dolutegravir, we report, for the first time, a virus with selected mutations outside the HIV-1 integrase gene that confer resistance to all integrase inhibitors currently used to treat patients, such as raltegravir, elvitegravir, and dolutegravir. Our observation may explain why some viruses responsible for virological failure in patients treated with dolutegravir did not show mutations in the integrase gene.
Studies are needed to better understand the genomic evolution of the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to describe genomic diversity of ...SARS-CoV-2 by next-generation sequencing (NGS) in a patient with longitudinal follow-up for SARS-CoV-2 infection.
Sequential samples collected between January 29th and February 4th, 2020, from a patient infected by SARS-CoV-2 were used to perform amplification of two genome fragments—including genes encoding spike, envelope, membrane and nucleocapsid proteins—and NGS was carried out with Illumina® technology. Phylogenetic analysis was performed with PhyML and viral variant identification with VarScan.
Majority consensus sequences were identical in most of the samples (5/7) and differed in one synonymous mutation from the Wuhan reference sequence. We identified 233 variants; each sample harboured in median 38 different minority variants, and only four were shared by different samples. The frequency of mutation was similar between genes and correlated with the length of the gene (r = 0.93, p = 0.0002). Most of mutations were substitution variations (n = 217, 93.1%) and about 50% had moderate or high impact on gene expression. Viral variants also differed between lower and upper respiratory tract samples collected on the same day, suggesting independent sites of replication of SARS-CoV-2.
We report for the first time minority viral populations representing up to 1% during the course of SARS-CoV-2 infection. Quasispecies were different from one day to the next, as well as between anatomical sites, suggesting that in vivo this new coronavirus appears as a complex and dynamic distributions of variants.
Background and purpose
An enhanced severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine regimen could improve humoral vaccine response in patients with multiple sclerosis (MS) treated ...by anti‐CD20. The aim was to evaluate the serological response and the neutralizing activity after BNT162b2 primary and booster vaccination in MS patients, including patients on anti‐CD20 receiving a primary vaccine regimen enhanced with three injections.
Methods
In this prospective longitudinal cohort study of 90 patients (47 on anti‐CD20, 10 on fingolimod, 33 on natalizumab, dimethylfumarate or teriflunomide), anti‐SARS‐CoV‐2 receptor binding domain (RBD) immunoglobulin G antibodies were quantified and their neutralization capacity was evaluated by enzyme‐linked immunosorbent assay (GenScript) and a virus neutralization test against B.1 historical strain, Delta and Omicron variants, before and after three to four BNT162b2 injections.
Results
After the primary vaccination scheme, the anti‐RBD positivity rate was strongly decreased in patients on anti‐CD20 (28% 15%; 44% after two shots, 45% 29%; 62% after three shots) and fingolimod (50% 16%; 84%) compared to other treatments (100% 90%; 100%). Neutralization activity was also decreased in patients on anti‐CD20 and fingolimod, and notably low for the Omicron variant in all patients (0%–22%). Delayed booster vaccination was performed in 54 patients, leading to a mild increase of anti‐RBD seropositivity in patients on anti‐CD20 although it was still lower compared to other treatments (65% 43%; 84% vs. 100% 87%; 100% respectively). After a booster, Omicron neutralization activity remained low on anti‐CD20 and fingolimod treated patients but was strongly increased in patients on other treatments (91% 72%; 99%).
Discussion
In MS patients on anti‐CD20, an enhanced primary vaccination scheme moderately increased anti‐RBD seropositivity and anti‐RBD antibody titre, but neutralization activity remained modest even after a fourth booster injection.
Trial registration information
COVIVAC‐ID, NCT04844489, first patient included on 20 April 2021.
PDF
