Patient-reported measurement of time to diagnosis in cancer: development of the Cancer Symptom Interval Measure (C-SIM) and randomised controlled trial of method of delivery

Background: The duration between first symptom and a cancer diagnosis is important because, if shortened, may lead to earlier stage diagnosis and improved cancer outcomes. We have previously developed a tool to measure this duration in newly-diagnosed patients. In this two-phase study, we aimed further improve our tool and to conduct a trial comparing levels of anxiety between two modes of delivery: self-completed versus researcher-administered. Methods: In phase 1, ten patients completed the modified tool and participated in cognitive debrief interviews. In phase 2, we undertook a Randomised Controlled Trial (RCT) of the revised tool (Cancer Symptom Interval Measure (C-SIM)) in three hospitals for 11 different cancers. Respondents were invited to provide either exact or estimated dates of first noticing symptoms and presenting them to primary care. The primary outcome was anxiety related to delivery mode, with completeness of recording as a secondary outcome. Dates from a subset of patients were compared with GP records. Results: After analysis of phase 1 interviews, the wording and format were improved. In phase 2, 201 patients were randomised (93 self-complete and 108 researcher-complete). Anxiety scores were significantly lower in the researcher-completed group, with a mean rank of 83.5; compared with the self-completed group, with a mean rank of 104.0 (Mann-Whitney U = 3152, p = 0.007). Completeness of data was significantly better in the researcher-completed group, with no statistically significant difference in time taken to complete the tool between the two groups. When comparing the dates in the patient questionnaires with those in the GP records, there was evidence in the records of a consultation on the same date or within a proscribed time window for 32/37 (86%) consultations; for estimated dates there was evidence for 23/37 consultations (62%). Conclusions: We have developed and tested a tool for collecting patient-reported data relating to appraisal intervals, help-seeking intervals, and diagnostic intervals in the cancer diagnostic pathway for 11 separate cancers, and provided evidence of its acceptability, feasibility and validity. This is a useful tool to use in descriptive and epidemiological studies of cancer diagnostic journeys, and causes less anxiety if administered by a researcher

Health state utilities for metastatic breast cancer

The aim of the study was to obtain United Kingdom-based societal preferences for distinct stages of metastatic breast cancer (MBC) and six common toxicities. Health states were developed based on literature review, iterative cycles of interviews and a focus group with clinical experts. They described the burden of progressive, responding and stable disease on treatment; and also febrile neutropenia, stomatitis; diarrhoea/vomiting; fatigue; hand-foot syndrome (grade 3/4 toxicities) and hair loss. One hundred members of the general public rated them using standard gamble to determine health state utility. Data were analysed with a mixed model analysis. The study sample was a good match to the general public of England and Wales by demographics and current quality of life. Stable disease on treatment had a utility value of 0.72, with a corresponding gain of +0.07 following a treatment response and a decline by 0.27 for disease progression. Toxicities lead to declines in utility between 0.10 (diarrhoea/vomiting) and 0.15 (febrile neutropenia). This study underlines the value that society place on the avoidance of disease progression and severe side effects in MBC. This may be the largest preference study in breast cancer designed to survey a representative general public sample

The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: Results from the Burden of Obstructive Lung Disease (BOLD) study

Background: Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown. Methods: Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN). Results: Almost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease. Conclusion: Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters

Cost-effectiveness analysis of pemetrexed versus docetaxel in the second-line treatment of non-small cell lung cancer in Spain: results for the non-squamous histology population

BackgroundThe objective of this study was to conduct a cost-effectiveness evaluation of pemetrexed compared to docetaxel in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) for patients with predominantly non-squamous histology in the Spanish healthcare setting.MethodsA Markov model was designed consisting of stable, responsive, progressive disease and death states. Patients could also experience adverse events as long as they received chemotherapy. Clinical inputs were based on an analysis of a phase III clinical trial that identified a statistically significant improvement in overall survival for non-squamous patients treated with pemetrexed compared with docetaxel. Costs were collected from the Spanish healthcare perspective.ResultsOutcomes of the model included total costs, total quality-adjusted life years (QALYs), total life years gained (LYG) and total progression-free survival (PFS). Mean survival was 1.03 years for the pemetrexed arm and 0.89 years in the docetaxel arm; QALYs were 0.52 compared to 0.42. Per-patient lifetime costs were € 34677 and € 32343, respectively. Incremental cost-effectiveness ratios were € 23967 per QALY gained and € 17225 per LYG.ConclusionsPemetrexed as a second-line treatment option for patients with a predominantly non-squamous histology in NSCLC is a cost-effective alternative to docetaxel according to the € 30000/QALY threshold commonly accepted in Spain

Association between lung function and dyspnoea and its variation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background: Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. This study aimed to estimate the prevalence of dyspnoea across several world regions and to investigate the association of dyspnoea with lung function. Methods: Dyspnoea was assessed, and lung function was measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis. Results: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC<LLN: OR 2.07, 95 %CI 1.75–2.45) and spirometry airflow obstruction (FEV1/FVC<LLN: OR 3.76, 95 %CI 1.04–4.65). These associations did not significantly differ between sexes, age groups, or smoking history. The association of dyspnoea with airflow obstruction was weaker among obese participants (OR 2.20, 95 %CI 1.61–3.01). Conclusion: The prevalence of dyspnoea varies substantially across the world and is strongly associated with lung function impairment. Using the mMRC scale in epidemiological research should be discussed.info:eu-repo/semantics/publishedVersio

Chronic airflow obstruction and ambient particulate air pollution

Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised

Profiling Trait Anxiety: Transcriptome Analysis Reveals Cathepsin B (Ctsb) as a Novel Candidate Gene for Emotionality in Mice

Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenic trait “anxiety”. We used microarrays to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, and also show signs of comorbid depression-like behavior

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Abstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study

© 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors.info:eu-repo/semantics/publishedVersio