Background Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1 -antihistamines ...along with 1 or more add-on therapies. Objectives We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H1 -antihistamines at up to 4 times the approved dose plus H2 -antihistamines, leukotriene receptor antagonists, or both. Methods In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary objective of the study was to evaluate the overall safety of omalizumab compared with placebo. Efficacy (itch severity, hive, and urticaria activity scores) was evaluated at weeks 12 and 24. Results The overall incidence and severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients; the safety profile was consistent with omalizumab in patients with allergic asthma. At week 12, the mean change from baseline in weekly itch severity score was −8.6 (95% CI, −9.3 to −7.8) in the omalizumab group compared with −4.0 (95% CI, −5.3 to −2.7) in the placebo group ( P < .001). Significant improvements were seen for additional efficacy end points at week 12; these benefits were sustained to week 24. Conclusion Omalizumab was well tolerated and reduced the signs and symptoms of CIU/CSU in patients who remained symptomatic despite the use of H1 -antihistamines (up to 4 times the approved dose) plus H2 -antihistamines, leukotriene receptor antagonists, or both.
Conflicting results regarding the impact of repeated vaccination on influenza vaccine effectiveness (VE) may cause confusion regarding the benefits of receiving the current season's vaccine.
We ...systematically searched MEDLINE, Embase, PubMed, and Cumulative Index to Nursing and Allied Health Literature from database inception to August 17, 2016, for observational studies published in English that reported VE against laboratory-confirmed influenza for the following four vaccination groups: current season only, prior season only, both seasons, and neither season. We pooled differences in VE (∆VE) between vaccination groups by influenza season and type/subtype using a random-effects model. The study protocol is registered with PROSPERO (registration number: CRD42016037241).
We identified 3435 unique articles, reviewed the full text of 634, and included 20 for meta-analysis. Compared to prior season vaccination only, vaccination in both seasons was associated with greater protection against influenza H1N1 (∆VE = 25%; 95% CI 14%, 35%) and B (∆VE = 18%; 95% CI 3%, 33%), but not H3N2 (∆VE = 7%; 95% CI - 7%, 21%). Compared to no vaccination for either season, individuals who received the current season's vaccine had greater protection against H1N1 (∆VE = 62%; 95% CI 51%, 70%), H3N2 (∆VE = 45%; 95% CI 35%, 53%), and B (∆VE = 64%; 95% CI 57%, 71%). We observed no differences in VE between vaccination in both seasons and the current season only for H1N1 (∆VE = 3%; 95% CI - 8%, 13%), but less protection against influenza H3N2 (∆VE = - 20%; 95% CI - 36%, - 4%), and B (∆VE = - 11%; 95% CI - 20%, - 2%).
Our results support current season vaccination regardless of prior season vaccination because VE for vaccination in the current season only is higher compared to no vaccination in either season for all types/subtypes, and for H1N1 and influenza B, vaccination in both seasons provides better VE than vaccination in the prior season only. Although VE was lower against H3N2 and B for individuals vaccinated in both seasons compared to those vaccinated in the current season only, it should be noted that past vaccination history cannot be altered and this comparison disregards susceptibility to influenza during the prior season among those vaccinated in the current season only. In addition, our results for H3N2 were particularly influenced by the 2014-2015 influenza season and the impact of repeated vaccination for all types/subtypes may vary from season to season. It is important that future VE studies include vaccination history over multiple seasons to evaluate repeated vaccination in more detail.
Nebulised sargramostim in pulmonary alveolar proteinosis Livingstone, Cameron; Corallo, Carmela; Siemienowicz, Miranda ...
BJCP. British journal of clinical pharmacology/British journal of clinical pharmacology,
July 2022, 2022-Jul, 2022-07-00, 20220701, Volume:
88, Issue:
7
Journal Article
Peer reviewed
Open access
Five patients, comprising nine treatment courses of sargramostim use in pulmonary alveolar proteinosis, are described. The prevailing standard of treatment, whole lung lavage (WLL), is highly ...invasive, resource intensive and carries some procedural risk. Nebulised recombinant human GM‐CSF (sargramostim) offers a pharmacological treatment option, allowing patients to be treated at home, possessing potential advantages in patient experience and wider health resourcing. The majority of reported patients described subjective improvement in symptoms along with radiographical improvement, although this did not translate into significant improvement in pulmonary function testing. Drug scarcity and high drug cost remain potential barriers to accessing this treatment, and so careful patient selection and treatment outcome assessment remain as challenging needs. Incorporating the routine assessment of validated patient symptom scores with objective physiological measures will allow prediction of response to treatment and help guide management. This report describes the largest published experience of sargramostim use in Australia.
The 12-item Short-Form Health Survey version 2 (SF-12v2), a widely used, generic patient-reported measure of health status that provides summary scores of physical and mental health. No study to date ...has examined the measurement properties of the SF-12v2 in patients with lung cancer using Rasch analysis. The aim of this study was to extend the psychometric evaluations of the SF-12 within the lung cancer population to ensure its validity and reliability to assess the health status in this population. A total of 342 participants completed the SF-12v2 three months following their lung cancer diagnosis. The SF-12 Physical Component Score (PCS-12) did not fit the overall Rasch measurement model (chl.sup.2 107.0; p < 0.001). Three items deviated significantly from the Rasch model (item fit residual beyond + or - 2.5) with signs of dependency between item responses and disordered thresholds. Nevertheless, the PCS-12 was uni-dimensional with good internal consistency (person separation index PSI 0.83) and reasonable targeting. In contrast, the SF-12 Mental Component Score (MCS-12) had good overall model fit (chl.sup.2 35.1; p = 0.07), reasonable targeting and good internal consistency (PSI 0.81). Rasch analysis suggests that there is general support for the reliability of the SF-12v2 as a measure of physical and mental health in people with lung cancer. However, the appropriateness of some items (e.g. pain) in the PCS-12 is questionable and further refinement of the scale including changing the response options may be required to improve the ability of the SF-12v2 to more appropriately assess the health status of this population.
Backgrounds
Victoria (Australia) and Denmark have comparable population sizes and high‐quality healthcare systems. Lung cancer surgery, however, is performed in more than 20 Victorian hospitals ...compared to four in Denmark. Such differences in centralization may influence outcomes. We engaged clinical quality registries to enable international benchmarking by exploring patterns of lung cancer surgery including mortality and survival.
Methods
All patients undergoing lung cancer surgery between 2015 and 2018 registered in the Victorian Lung Cancer Registry and the Danish Lung Cancer Registry were included. Analyses on stage concordance, 30 and 90‐day mortality, and overall survival were restricted to a selected subgroup with NSCLC and no neo‐adjuvant therapy or metastatic disease and only one operation.
Results
We included 1554 Victorian and 4319 Danish patients. The resection rate was 26.3% in Victoria and 28% in Denmark, but a higher proportion of Victorian patients underwent wedge resection (19.1% versus 8.8%). Stage concordance was 59.6% and 54.9% in Victoria and Denmark, respectively. The 30‐ and 90‐day mortality was 1.3% and 2.6% in Victoria, compared to 1.4% and 2.8% in Denmark with no difference in overall survival (p = 0.28) or risk‐adjusted survival (HR: 1.10 (95% CI: 0.89–1.37); p = 0.38).
Conclusion
High‐quality surgical lung cancer care was confirmed by similar high resection and low mortality rates including no overall survival difference. The drivers and consequences of stage discordance and differences in patterns of resection deserve further exploration. This study provides a model for international benchmarking using clinical quality registries, although caution remains in the interpretation given disparities in data completeness.
This study provides a model for International benchmarking using clinical quality registries and found similar high resection and low mortality rates including no overall survival difference.
Delays in the assessment, management, and treatment of lung cancer patients may adversely impact prognosis and survival. This study is the first to use machine learning techniques to predict the ...quality and timeliness of care among lung cancer patients, utilising data from the Victorian Lung Cancer Registry (VLCR) between 2011 and 2022, in Victoria, Australia. Predictor variables included demographic, clinical, hospital, and geographical socio-economic indices. Machine learning methods such as random forests, k-nearest neighbour, neural networks, and support vector machines were implemented and evaluated using 20% out-of-sample cross validations via the area under the curve (AUC). Optimal model parameters were selected based on 10-fold cross validation. There were 11,602 patients included in the analysis. Evaluated quality indicators included, primarily, overall proportion achieving “time from referral date to diagnosis date ≤ 28 days” and proportion achieving “time from diagnosis date to first treatment date (any intent) ≤ 14 days”. Results showed that the support vector machine learning methods performed well, followed by nearest neighbour, based on out-of-sample AUCs of 0.89 (in-sample = 0.99) and 0.85 (in-sample = 0.99) for the first indicator, respectively. These models can be implemented in the registry databases to help healthcare workers identify patients who may not meet these indicators prospectively and enable timely interventions.
Patients with predominantly antibody deficiency (PAD) suffer from severe and recurrent infections that require lifelong immunoglobulin replacement and prophylactic antibiotic treatment. Disease ...incidence is estimated to be 1:25,000 worldwide, and up to 68% of patients develop non-infectious complications (NIC) including autoimmunity, which are difficult to treat, causing high morbidity, and early mortality. Currently, the etiology of NIC is unknown, and there are no diagnostic and prognostic markers to identify patients at risk.
To identify immune cell markers that associate with NIC in PAD patients.
We developed a standardized 11-color flow cytometry panel that was utilized for in-depth analysis of B and T cells in 62 adult PAD patients and 59 age-matched controls.
Nine males had mutations in Bruton's tyrosine kinase (BTK) and were defined as having X-linked agammaglobulinemia. The remaining 53 patients were not genetically defined and were clinically diagnosed with agammaglobulinemia (
= 1), common variable immunodeficiency (CVID) (
= 32), hypogammaglobulinemia (
= 13), IgG subclass deficiency (
= 1), and specific polysaccharide antibody deficiency (
= 6). Of the 53, 30 (57%) had one or more NICs, 24 patients had reduced B-cell numbers, and 17 had reduced T-cell numbers. Both PAD-NIC and PAD+NIC groups had significantly reduced Ig class-switched memory B cells and naive CD4 and CD8 T-cell numbers. Naive and IgM memory B cells, Treg, Th17, and Tfh17 cells were specifically reduced in the PAD+NIC group. CD21
B cells and Tfh cells were increased in frequencies, but not in absolute numbers in PAD+NIC.
The previously reported increased frequencies of CD21
B cells and Tfh cells are the indirect result of reduced naive B-cell and T-cell numbers. Hence, correct interpretation of immunophenotyping of immunodeficiencies is critically dependent on absolute cell counts. Finally, the defects in naive B- and T-cell numbers suggest a mild combined immunodeficiency in PAD patients with NIC. Together with the reductions in Th17, Treg, and Tfh17 numbers, these key differences could be utilized as biomarkers to support definitive diagnosis and to predict for disease progression.
Wide variation exists globally in the treatment and outcomes of stage III patients with non-small cell lung cancer (NSCLC). We conducted an up-to-date patterns of care analysis in the state of ...Victoria, Australia, with a particular focus on the proportion of patients receiving treatment with radical intent, treatment trends over time, and survival.
Stage III patients with NSCLC were identified in the Victorian Lung Cancer Registry and categorized by treatment received and treatment intent. Logistic regression was used to explore factors predictive of receipt of radical treatment and the treatment trends over time. Cox regression was used to explore variables associated with overall survival (OS). Covariates evaluated included age, sex, ECOG performance status, smoking status, year of diagnosis, Australian born, Aboriginal or Torres Strait Islander status, socioeconomic status, rurality, public/private status of notifying institution, and multidisciplinary meeting discussion.
A total of 1396 patients were diagnosed between 2012 and 2019 and received treatment with radical intent 67%, palliative intent 23%, unknown intent 5% and no treatment 5%. Radical intent treatment was less likely if patients were >75 years, ECOG ≥1, had T3-4 or N3 disease or resided rurally. Surgery use decreased over time, while concurrent chemoradiotherapy and immunotherapy use increased. Median OS was 38.0, 11.1, and 4.4 months following radical treatment, palliative treatment or no treatment, respectively.
Almost a third of stage III patients with NSCLC still do not receive radical treatment. Strategies to facilitate radical treatment and better support decision making between increasing multimodality options are required.
Exercise training is recommended for non-cystic fibrosis (CF) bronchiectasis, but the long-term effects are unclear. This randomised controlled trial aimed to determine the effects of exercise ...training and review of airway clearance therapy (ACT) on exercise capacity, health related quality of life (HRQOL) and the incidence of acute exacerbations in people with non-CF bronchiectasis.
Participants were randomly allocated to 8 weeks of supervised exercise training and review of ACT, or control. Primary outcomes of exercise capacity and HRQOL (Chronic respiratory disease questionnaire) and secondary outcomes of cough-related QOL (Leicester cough questionnaire) and psychological symptoms (Hospital anxiety and depression scale) were measured at baseline, following completion of the intervention period and at 6 and 12 months follow up. Secondary outcomes of the exacerbation rate and time to first exacerbation were analysed over 12 months.
Eighty-five participants (mean FEV1 74% predicted; median Modified Medical Research Council Dyspnoea grade of 1 (IQR 1-3) were included. Exercise training increased the incremental shuttle walk distance (mean difference to control 62 m, 95% CI 24 to 101 m) and the 6-minute walking distance (mean difference to control 41 m, 95% CI 19 to 63 m), but these improvements were not sustained at 6 or 12 months. Exercise training reduced dyspnoea (p = 0.009) and fatigue (p = 0.01) but did not impact on cough-related QOL or mood. Exercise training reduced the frequency of acute exacerbations (median 1IQR 1-3) compared to the control group (21-3) over 12 months follow up (p = 0.012), with a longer time to first exacerbation with exercise training of 8 months (95% CI 7 to 9 months) compared to the control group (6 months 95% CI 5 to 7 months, p = 0.047).
Exercise training in bronchiectasis is associated with short term improvement in exercise capacity, dyspnoea and fatigue and fewer exacerbations over 12 months.
ClinicalTrials.gov (NCT00885521).
The lung cancer Optimal Care Pathway recommends supportive care and palliative care integration throughout its various steps, with early referral to appropriate services improving the quality of life ...in advanced stage non-small cell lung cancer patients. Using Victorian Lung Cancer Registry data and linked administrative datasets, this retrospective cohort study mapped clinical care pathways of 525 Stage III-IV non-small cell lung cancer patients in Victoria to 11 recommendations in the Optimal Care Pathway, identifying unwarranted variations in clinical care. Supportive care and palliative care delivery were further examined to understand the involvement and timing of specialist care teams. Our findings showed that palliative care utilization is highest at the time of treatment, despite recommendations that it should be provided early after diagnosis to improve patient outcomes and satisfaction. Early supportive care screening was observed in half the cohort and almost three-quarters of the patients had been presented at a multidisciplinary meeting. Multidisciplinary meeting presentations and supportive care provide an opportunity to improve communication about palliative care needs and integration into routine clinical practice, such as at the time of treatment planning.
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