The clinical translation of plastic scintillation dosimetry

Contemporary radiotherapy focuses on achieving the best patient outcomes by delivering highly targeted treatments that often include small fields and high dose gradients. Plastic scintillators outperform traditional dosimeters in these fields as they are close to water-equivalent. However, the translation of scintillation dosimeters into the clinic has been limited by three roadblocks. The generation of Cerenkov radiation in an optic fibre irradiated by megavoltage radiation contaminates the scintillation signal. Two Cerenkov removal methods (spectral discrimination and air core) were found to be accurate in accounting for Cerenkov radiation and their clinical robustness was improved. The light readout system is often the limiting factor for the accuracy of scintillators. PMTs outperform camera-based systems, though their implementation for array dosimetry is complex. A novel system with a multianode PMT was constructed and enabled multiple light signals from an array to be simultaneously measured. Arrays of scintillation dosimeters are difficult to create due to the complex arrangement of detectors and their optical pathways. Two innovative approaches (square waveguides and 3D printing) were used to build prototype scintillation dosimeter arrays. These arrays showed that scintillation dosimeters can measure dose distributions with high spatial and temporal resolution. Addressing these roadblocks has enabled the clinical translation of scintillation dosimeters. In small field dosimetry, an air core dosimeter was used as a reference to calculate and predict correction factors for existing dosimeters. For brachytherapy, an array of scintillators provided real-time dose measurements that improved the safety of the treatment. For rotational treatments, a cylindrical array was used to verify the dose delivered during simulated stereotactic treatments. Traditional dosimeters cannot be used in these applications and this demonstrates the potential of scintillation dosimetry

Somatotypes trajectories during adulthood and their association with COPD phenotypes

Rationale: Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all characterised by airflow limitation. Objectives: We hypothesised that somatotype changes - as a surrogate of adiposity - from early adulthood follow different trajectories to reach distinct phenotypes. Methods: Using the validated Stunkard''s Pictogram, 356 COPD patients chose the somatotype that best reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based trajectory modelling was used to determine somatotype trajectories. We then compared the current COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory. Measurements and main results: At 18 years of age, 88% of the participants described having a lean or medium somatotype (estimated body mass index (BMI) between 19 and 23 kg.m(-2)) while the other 12% a heavier somatotype (estimated BMI between 25 and 27 kg.m(-2)). From age 18 onwards, five distinct trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age 40. Patients with this trajectory were primarily females with low BMI and D-LCO (diffusing capacity of the lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had significantly lower forced expiratory volume in 1 s (FEV1), D-LCO, more emphysema and a worse BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss of tissue (MOLT) phenotype. Conclusions: COPD patients have distinct somatotype trajectories throughout adulthood. Those with the MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in early adulthood deserve particular attention as they seem to develop more severe COPD

Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging: Evidence from the EpiChron Cohort

Background Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD. Methods and findings We included all subjects carrying the diagnosis of COPD (n = 27, 617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727, 241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers'' subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network''s density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking. Conclusion Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Muscle strength and exercise kinetics in COPD patients with a normal fat-free mass index are comparable to control subjects.

Item does not contain fulltextSTUDY OBJECTIVE: This study was designed to investigate the extent of clinical muscle dysfunction in stable patients with COPD who were attending an out-patient pulmonary clinic compared with that of age-matched control subjects without COPD. Design and subjects: Respiratory muscle and hand grip strength, steady-state O(2) kinetics, and body composition were measured in 32 patients with COPD (19 women) [mean (+/- SD) FEV(1), 38 +/- 11% predicted] and 36 age-matched control subjects (13 women). RESULTS: Measurements of handgrip force (mean, 97 +/- 32% vs 106 +/- 26% predicted, respectively), maximal expiratory pressure (mean, 57 +/- 33% vs 61 +/- 22% predicted, respectively), steady-state O(2) kinetics (mean tau, 72 +/- 34 s vs 78 +/- 37 s, respectively) and steady-state CO(2) kinetics (mean tau, 77 +/- 38 s vs 65 +/- 32 s, respectively) at submaximal exercise were similar in patients and control subjects. All the subjects, except for one female COPD patient, had a normal fat-free mass index (FFMI), although on average the FFMI was lower in male patients (19.8 +/- 2.8) than in male control subjects (23.0 +/- 2.8; p < 0.01). CONCLUSIONS: In patients with COPD who were attending a regular outpatient pulmonary clinic, there was no evidence of reduced upper extremity and expiratory muscle strength or prolonged O(2) and CO(2) kinetics during isowork submaximal cardiopulmonary exercise compared to healthy, age-matched control subjects. Also, a normal body composition was found in nearly all COPD patients. This argues against the existence of a clinically significant systemic myopathy in most stable patients with severe COPD and normal FFMI

Comorbidities and mortality risk in adults younger than 50 years of age with chronic obstructive pulmonary disease

Rationale and objective: Patients with chronic obstructive pulmonary disease (COPD), usually diagnosed after the 6th decade, frequently suffer from comorbidities. Whether COPD patients 50 years or younger (Young COPD) have similar comorbidities with the same frequency and mortality impact as aged-matched controls or older COPD patients is unknown. Methods: We compared comorbidity number, prevalence and type in 3 groups of individuals with ≥ 10 pack-years of smoking: A Young (≤ 50 years) COPD group (n = 160), an age-balanced control group without airflow obstruction (n = 125), and Old (> 50 years) COPD group (n = 1860). We also compared survival between the young COPD and control subjects. Using Cox proportional model, we determined the comorbidities associated with mortality risk and generated Comorbidomes for the “Young” and “Old” COPD groups. Results: The severity distribution by GOLD spirometric stages and BODE quartiles were similar between Young and Old COPD groups. After adjusting for age, sex, and pack-years, the prevalence of subjects with at least one comorbidity was 31% for controls, 77% for the Young, and 86% for older COPD patients. Compared to controls, “Young” COPDs’ had a nine-fold increased mortality risk (p < 0.0001). “Comorbidomes” differed between Young and Old COPD groups, with tuberculosis, substance use, and bipolar disorders being distinct comorbidities associated with increased mortality risk in the Young COPD group. Conclusions: Young COPD patients carry a higher comorbidity prevalence and mortality risk compared to non-obstructed control subjects. Young COPD differed from older COPD patients by the behavioral-related comorbidities that increase their risk of premature death. © 2022, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Prognostic value of variables derived from the six-minute walk test in patients with COPD: Results from the ECLIPSE study

In addition to the six-min walk distance (6 MWD), other six-min walk test (6 MWT) derived variables, such as mean walk-speed (6MWSpeed), 6-min walk-work (6 MWW), distance-saturation product (DSP), exercise-induced oxygen desaturation (EID), and unintended stops may be useful for the prediction of mortality and hospitalization in patients with chronic obstructive pulmonary disease (COPD). We studied the association between 6 MWT-derived variables and mortality as well as hospitalization in COPD patients and compared it with the BODE index. A three-year prospective study (ECLIPSE) to evaluate the prognostic value of 6 MWT-derived variables in 2010 COPD patients. Cox&apos;s proportional-hazard regressions were performed to estimate 3-year mortality and hospitalization. During the follow-up, 193 subjects died and 622 were hospitalized. An adjusted Cox&apos;s regression model of hazard ratio [HR] for impaired 6 MWT-derived variables was significant referring to: mortality (6 MWD ≤334 m [2.30], 6MWSpeed ≤0.9 m/sec [2.15], 6 MWW ≤20000 m kg [2.17], DSP ≤290 m% [2.70], EID ≤88% [1.75], unintended stops [1.99]; and hospitalization (6 MWW ≤27000 m kg [1.23], EID ≤88% [1.25], BODE index ≥3 points [1.40]; all p ≤ 0.05). The 6 MWT-derived variables have an additional predictive value of mortality in patients with COPD. The 6 MWW, EID and the BODE index refine the prognosis of hospitalization. © 2015 Elsevier Ltd. All rights reserved

Determinants of exercise-induced oxygen desaturation including pulmonary emphysema in COPD: Results from the ECLIPSE study

Exercise-induced oxygen desaturation (EID) is related to mortality in patients with chronic obstructive pulmonary disease (COPD). We investigated: (1) the prevalence of EID; (2) the relative-weight of several physiological determinants of EID including pulmonary emphysema, and (3) the relationship of EID with certain patients&apos; clinical characteristics. Data from 2050 COPD patients (age: 63.3 ± 7.1years; FEV1: 48.7 ± 15.7%pred.) were analyzed. The occurrence of EID (SpO2post ≤88%) at the six-minute walking test (6MWT) was investigated in association with emphysema quantified by computed-tomography (QCT), and several clinical characteristics. 435 patients (21%) exhibited EID. Subjects with EID had more QCT-emphysema, lower exercise capacity and worse health-status (BODE, ADO indexes) compared to non-EID. Determinant of EID were obesity (BMI≥30 kg/m2), impaired FEV1 (≤44%pred.), moderate or worse emphysema, and low SpO2 at rest (≤93%). Linear regression indicated that each 1-point increase on the ADO-score independently elevates odds ratio (≤1.5fold) for EID. About one in five COPD patients in the ECLIPSE cohort present EID. Advanced emphysema is associated with EID. In addition, obesity, severe airflow limitation, and low resting oxygen saturation increase the risk for EID. Patients with EID in GOLD stage II have higher odds to have moderate or worse emphysema compared those with EID in GOLD stage III-IV. Emphysematous patients with high ADO-score should be monitored for EID. © 2016 Elsevier Lt

The clinical utility of the GOLD classification of COPD disease severity in pulmonary rehabilitation

SummaryThe Global Initiative for Chronic Obstructive Lung Disease (GOLD) has introduced a four-stage classification of chronic obstructive pulmonary disease (COPD) severity. The present study investigated the discriminatory capacity of the GOLD classification for health status outcomes in patients with COPD. An additional analysis was performed to investigate the discriminatory capacity of a multidimensional staging system, i.e. the Body-Mass Index, Degree of Airflow Obstruction and Dyspnea, and Exercise Capacity Index (BODE index) for the outcome of quality of life.Retrospective analysis was performed on 253 COPD patients (30% stage II, 48% stage III, 22% stage IV), referred for outpatient pulmonary rehabilitation. Pulmonary function, exercise capacity, dyspnoea and quality of life were evaluated. Analyses of variance were used to detect differences between GOLD stages and BODE index quartiles, and scatterplots of individual responses were produced as well.The GOLD classification discriminated between stages for pulmonary function (p<0.001), exercise capacity (p<0.001), dyspnoea (p<0.001) and the activities section (p=0.001) of the St. George Respiratory Questionnaire (SGRQ). The BODE index discriminated between quartiles for the activities section (p<0.001), impacts section (p=0.04) and the total score (p=0.01) of the SGRQ. Scatterplots revealed marked inter-individual variation within each GOLD stage or BODE index quartile, and considerable overlap between stages for all health status outcomes.These findings show that the GOLD classification indeed can be used to discern groups of COPD patients, but due to large inter-individual variability it does not seem adequate as a basis for individual management plans in rehabilitation. The BODE index appeared to discriminate slightly better for quality of life, however, it still leaves a significant part of the variance unexplained

A randomised trial of lung sealant versus medical therapy for advanced emphysema

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting. Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis. 57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with &gt;50% of treated patients experiencing clinically important improvements, including some whose lung function improved by &gt;100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events. Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility. Copyright © ERS 2015