Identifying asthma patients suitable for biologic therapy includes the assessment of blood biomarkers (IgE and eosinophils (EOS)). How they relate to each other is unclear.
This retrospective, ...database study used routinely collected clinical data to identify and evaluate an asthma cohort (classification code for asthma; ≥ 18 years; ≥1 prescription for asthma; ≥1 estimation of serum IgE, in 2 years prior to index date). Distribution into high and low IgE and EOS groups (IgE cut-point: > or ≤75 kU/L; EOS cut point: >or ≤400 μ/L), and characteristics by group are described.
In patients with severe asthma (British Thoracic Society Step (BTS) ≥4; N = 884), using maximum recorded IgE/EOS, 33% had high IgE/high EOS, 28% low IgE/low EOS and approximately a fifth each had high IgE/low EOS or low IgE/high EOS. Proportions were similar when EOS values measured 2 or 4 weeks before an exacerbation were excluded. Using EOS/IgE ′same day’ measurements (N = 578) only identified half of the high EOS group. Patients in high IgE groups were more likely to be younger males without comorbid COPD; those in high EOS groups were more likely to be on BTS treatment Step 5 vs 4. The low IgE/low EOS group had the lowest incidence of asthma-related hospital attendances, the highest incidence was observed in the high EOS groups.
Maximum available EOS measurement irrespective of exacerbations may be relevant when considering therapy. These data showed low IgE/Low EOS to be more benign and high EOS groups at increased risk of frequent, severe exacerbations.
•The adoption of precision medicine can lead to better patient outcomes.•In the management of severe asthma, IgE and eosinophil (EOS) counts are useful biomarkers.•This study describes the pattern of distribution of these biomarkers in a population.•EOS levels may fluctuate markedly over time.•The low IgE/low EOS endotype appears more benign.
Aims
This study was designed to evaluate whether survival rates in patients with heart failure (HF) are better than those in patients with diagnoses of the four most common cancers in men and women, ...respectively, in a contemporary primary care cohort in the community in Scotland.
Methods and results
Data were obtained from the Primary Care Clinical Informatics Unit from a database of 1.75 million people registered with 393 general practices in Scotland. Sex‐specific survival modelling was undertaken using Cox proportional hazards models, adjusted for potential confounders. A total of 56 658 subjects were eligible for inclusion in the study. These represented a total of 147 938 person‐years of follow‐up (median follow‐up: 2.04 years). In men, HF (reference group; 5‐year survival: 55.8%) had worse mortality outcomes than prostate cancer hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.57–0.65; 5‐year survival: 68.3%, and bladder cancer (HR 0.88, 95% CI 0.81–0.96; 5‐year survival: 57.3%), but better outcomes than lung cancer (HR 3.86, 95% CI 3.65–4.07; 5‐year survival: 8.4%) and colorectal cancer (HR 1.23, 95% CI 1.16–1.31; 5‐year survival: 48.9%). In women, HF (reference group; 5‐year survival: 49.5%) had worse mortality outcomes than breast cancer (HR 0.55, 95% CI 0.51–0.59; 5‐year survival 77.7%), but better outcomes than colorectal cancer (HR 1.21, 95% CI 1.13–1.29; 5‐year survival 51.5%), lung cancer (HR 3.82, 95% CI 3.60–4.05; 5‐year survival 10.4%), and ovarian cancer (HR 1.98, 95% CI 1.80–2.17; 5‐year survival 38.2%).
Conclusions
Despite advances in management, HF remains as ‘malignant’ as some of the common cancers in both men and women.
A randomised controlled trial of substance misuse indicated that many patients who use methadone have respiratory symptoms and/or are prescribed respiratory medications. There is little research in ...this area.
To determine the prevalence of respiratory disease and prescriptions among drug misusers.
This historical cohort study of drug misusers and matched controls analysed routinely collected primary care data. The prevalence of common chronic respiratory diseases, class and number of respiratory medications were examined.
The cohort of 18,570 patients (9,285 per group) was mostly male (64%, n=11,890) and aged 31-59 years (76%, n=14,060). After adjusting for age, gender, deprivation and smoking status, the results showed that more drug misusers than controls had a diagnosis of asthma or chronic obstructive pulmonary disease (17.1% vs. 10.9%; adjusted odds ratio (OR) 1.61, 95% confidence interval (CI) 1.46 to 1.77, and 2.4% vs. 0.8%; OR 1.86, 95% CI 1.42 to 2.44, respectively) and were prescribed more chronic respiratory medications: short-acting β(2)-agonists (16.4% vs. 7.9%; OR 2.00, 95% CI 1.80 to 2.22), long-acting β(2)-agonists (1% vs. 0.4%; OR 1.93, 95% CI 1.29 to 2.89), and inhaled corticosteroids (10.6% vs. 7.6%; OR 1.49, 95% CI 1.33 to 1.67). All differences were statistically significant (p<0.001).
Drug misusers have a significantly higher prevalence of respiratory diseases and respiratory prescriptions than matched controls. Further work is needed to determine the reasons for this.
The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain.
To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19.
In an ...ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021).
Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis.
The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions.
The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 33.6% female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 95% credible interval {CrI}, 0.86-1.23; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 95% CrI, 0.99-1.62; adjusted absolute difference, 5% 95% CrI, -0.2% to 9.5%; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 95% CrI, 1.23-8.28; adjusted absolute risk increase, 0.8% 95% CrI, 0.1%-2.7%; 99.4% probability of harm).
Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days.
ClinicalTrials.gov Identifier: NCT02735707.
The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.
To determine the effect of multiple interventions for critically ill adults with COVID-19 ...on longer-term outcomes.
Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.
Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).
The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.
Among 4869 randomized patients (mean age, 59.3 years; 1537 32.1% women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 95% credible interval {CrI}, 0.61-0.90) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 95% CrI, 0.71-1.03) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 95% CrI, 0.93-1.42), convalescent plasma (99.2%; HR, 0.99 95% CrI, 0.86-1.14), and lopinavir-ritonavir (96.6%; HR, 1.06 95% CrI, 0.82-1.38) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 95% CrI, 0.98-2.29) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 95% CrI, 0.97-2.67) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.
Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
To determine whether angiotensin-converting enzyme (ACE) inhibitor or ...angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 95% bayesian credible interval, 0.58-1.06 for improvement for ACE inhibitor and 0.76 95% credible interval, 0.56-1.05 for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
ClinicalTrials.gov Identifier: NCT02735707.
We describe two methods of breast immobilization using the lateral decubitus position to increase patient comfort and access to the axillary tail for MR-guided biopsy in the postsurgical or ...irradiated breast. The first method uses a compression device with good immobilization but poor patient tolerance. The second approach uses a thermoplastic mesh material to form a rigid exoskeleton around the breast: immobilization is adequate and patient acceptability is good. The latter method is preferred and requires formal evaluation in larger scale trials.
PDF
