Towards high spatial resolution tissue-equivalent dosimetry for microbeam radiation therapy using organic semiconductors.

Spatially fractionated ultra-high-dose-rate beams used during microbeam radiation therapy (MRT) have been shown to increase the differential response between normal and tumour tissue. Quality assurance of MRT requires a dosimeter that possesses tissue equivalence, high radiation tolerance and spatial resolution. This is currently an unsolved challenge. This work explored the use of a 500 nm thick organic semiconductor for MRT dosimetry on the Imaging and Medical Beamline at the Australian Synchrotron. Three beam filters were used to irradiate the device with peak energies of 48, 76 and 88 keV with respective dose rates of 3668, 500 and 209 Gy s-1. The response of the device stabilized to 30% efficiency after an irradiation dose of 30 kGy, with a 0.5% variation at doses of 35 kGy and higher. The calibration factor after pre-irradiation was determined to be 1.02 ±â€…0.005 µGy per count across all three X-ray energy spectra, demonstrating the unique advantage of using tissue-equivalent materials for dosimetry. The percentage depth dose curve was within ±5% of the PTW microDiamond detector. The broad beam was fractionated into 50 microbeams (50 µm FHWM and 400 µm centre-to-centre distance). For each beam filter, the FWHMs of all 50 microbeams were measured to be 51 ±â€…1.4, 53 ±â€…1.4 and 69 ±â€…1.9 µm, for the highest to lowest dose rate, respectively. The variation in response suggested the photodetector possessed dose-rate dependence. However, its ability to reconstruct the microbeam profile was affected by the presence of additional dose peaks adjacent to the one generated by the X-ray microbeam. Geant4 simulations proved that the additional peaks were due to optical photons generated in the barrier film coupled to the sensitive volume. The simulations also confirmed that the amplitude of the additional peak in comparison with the microbeam decreased for spectra with lower peak energies, as observed in the experimental data. The material packaging can be optimized during fabrication by solution processing onto a flexible substrate with a non-fluorescent barrier film. With these improvements, organic photodetectors show promising prospects as a cost-effective high spatial resolution tissue-equivalent flexible dosimeter for synchrotron radiation fields.

Core Decompression and Bone Marrow Aspirate Concentrate in the Treatment of Femoral Head Avascular Necrosis in Pediatric Sickle Cell Disease: Can We Improve Natural History?

INTRODUCTION: Femoral head avascular necrosis (AVN) affects between 10% and 41% of children with sickle cell disease (SCD), resulting in the development of proximal femoral deformity and residual hip pain in the majority of patients without treatment. There have been multiple adult studies published on the outcomes of core decompression with and without the use of bone marrow aspirate concentrate (BMAC) injection both in idiopathic and SCD-related AVN with promising results, however, few studies have reported on outcomes in skeletally immature patients. PURPOSE: This study sought to report on a single surgeon's outcomes for core decompression with BMAC injection in pediatric patients with AVN of the femoral head secondary to underlying SCD. METHODS: A single-center, retrospective review was performed for pediatric patients undergoing core decompression with BMAC injection for femoral head AVN in patients with SCD with a minimum of 12-month follow-up. Demographic, radiographic, and clinical variable were collected. Patients were subdivided based upon presence of open femoral physes at the time of surgery. Successful treatment was defined as the ability to return to activities without limitations. RESULTS: A total of 13 patients (average age 14.1±2.8 y, 84.6% male, 6 skeletally immature and 7 skeletally mature) with 18 affected extremities were identified. Open physes were present in 50% of operative extremities. Skeletally immature patient demonstrated reconstitution of the femoral head in 78% of cases and 89% demonstrated regression of at least 1 Steinberg grade and none had progression. Skeletally immature patients were significantly more likely to return to activities (100% vs. 55.6%, P=0.023) and achieve a final Tonnis grade <2 (89% vs. 44%, P=0.046). CONCLUSION: Core decompression appears to alter the natural history of AVN in skeletally immature patients with SCD. Skeletal immaturity was a positive prognostic factor for the ability to return to activities without pain and achieve a lower Tonnis grade at final follow-up.

Overuse and Misuse of Inhaled Corticosteroids Among Veterans with COPD: a Cross-sectional Study Evaluating Targets for De-implementation.

BACKGROUND: Inhaled corticosteroid (ICS) use among patients with COPD increases the risk of pneumonia and other complications. Current recommendations limit ICS use to patients with frequent or severe COPD exacerbations. However, use of ICS among patients with COPD is common and may be occurring both among those with mild disease (overuse) and those misdiagnosed with COPD (misuse). OBJECTIVE: To identify patients without identifiable indication for ICS and assess patient and provider characteristics associated with potentially inappropriate to targeted in de-implementation efforts DESIGN: We performed a cross-sectional study of patients with COPD in the Veterans Affairs (VA) system with recent spirometry. PARTICIPANTS: After setting an index date, we identified individuals with a clinical diagnosis of COPD who had spirometry completed in the prior 5 years. We excluded individuals with an appropriate indication for ICS based on the 2017 GOLD statement, including asthma and a recent history of frequent or severe exacerbations. MAIN MEASURES: ICS use without identifiable indication KEY RESULTS: We identified 26,536 patients with COPD without an identifiable indication for ICS. Nearly » of patients (n = 6330) filled ≥2 prescriptions for ICS in the year prior to the index date. We found that older age (adjusted prevalence ratio [APR] 1.06 per decade, 95% confidence interval [CI] 1.04-1.08), white race (APR 1.11, 95% CI 1.05-1.19), and more primary care visits (APR 1.05 per visit, 95% CI 1.03-1.07) were associated with increased likelihood of potentially inappropriate use. Primary care clinic complexity and provider training were not associated with ICS use. Among patients misdiagnosed with COPD, we found that 14% used ICS. CONCLUSIONS: Potentially inappropriate ICS use is common among patients with and without airflow obstruction who are diagnosed with COPD. We identified patient comorbidities and patterns of healthcare utilization that increase the likelihood of ICS use that could be targeted for system-level de-implementation interventions.

Manipulating nanoscale structure to control functionality in printed organic photovoltaic, transistor and bioelectronic devices.

Printed electronics is simultaneously one of the most intensely studied emerging research areas in science and technology and one of the fastest growing commercial markets in the world today. For the past decade the potential for organic electronic (OE) materials to revolutionize this printed electronics space has been widely promoted. Such conviction in the potential of these carbon-based semiconducting materials arises from their ability to be dissolved in solution, and thus the exciting possibility of simply printing a range of multifunctional devices onto flexible substrates at high speeds for very low cost using standard roll-to-roll printing techniques. However, the transition from promising laboratory innovations to large scale prototypes requires precise control of nanoscale material and device structure across large areas during printing fabrication. Maintaining this nanoscale material control during printing presents a significant new challenge that demands the coupling of OE materials and devices with clever nanoscience fabrication approaches that are adapted to the limited thermodynamic levers available. In this review we present an update on the strategies and capabilities that are required in order to manipulate the nanoscale structure of large area printed organic photovoltaic (OPV), transistor and bioelectronics devices in order to control their device functionality. This discussion covers a range of efforts to manipulate the electroactive ink materials and their nanostructured assembly into devices, and also device processing strategies to tune the nanoscale material properties and assembly routes through printing fabrication. The review finishes by highlighting progress in printed OE devices that provide a feedback loop between laboratory nanoscience innovations and their feasibility in adapting to large scale printing fabrication. The ability to control material properties on the nanoscale whilst simultaneously printing functional devices on the square metre scale is prompting innovative developments in the targeted nanoscience required for OPV, transistor and biofunctional devices.

Building intermixed donor-acceptor architectures for water-processable organic photovoltaics.

A modified synthesis method for aqueous nanoparticle printing inks, based upon vacuum-assisted solvent removal, is reported. Poly(3-hexylthiophene):phenyl C61 butyric acid methyl ester nanoparticle inks were prepared via this modified miniemulsion method, leading to both an improvement in photoactive layer morphology and a substantial reduction in the ink fabrication time. A combination of UV-visible spectroscopy, photoluminescence spectroscopy and scanning transmission X-ray microscopy measurements revealed a nanoparticle morphology comprising highly intermixed donor-acceptor domains. Consistent with these measurements, dynamic mechanical thermal analysis of the nanoparticles showed a glass transition temperature (Tg) of 104 °C, rather than a pure polymer phase or pure fullerene phase Tg. Together the spectroscopy, microscopy and thermomechanical data indicate that rapid solvent removal generates a more blended nanoparticle morphology. As such, this study highlights a new experimental lever for optimising nanostructure in the photoactive layer of nanoparticulate organic photovoltaic devices by enabling highly intermixed donor-acceptor architectures to be built from customised nanoparticulate inks.

Demographics and Distal Tibial Dimensions of Suitable Distal Tibial Allografts for Glenoid Reconstruction.

PURPOSE: To evaluate whether characteristics such as age, height, weight, sex, or body mass index affected the distal tibial dimensions and radius of curvature (ROC) of a potential donor for anterior glenoid augmentation. METHODS: A retrospective review of magnetic resonance imaging of ankles without bony trauma was performed, and the anteroposterior (AP) and medial-lateral (ML) distances and ROC of the tibial plafond articular surface were measured. Demographic characteristics, including age, sex, height, weight, and body mass index, were recorded. RESULTS: A total of 141 imaging studies were included (73 men and 68 women; average age, 38.2 ± 12.65 years). All potential specimens accommodated harvest of a 10 × 22-mm distal tibial allograft bone block. Men had greater ML (42.74 cm [95% confidence interval (CI), 42.09-43.39 cm] vs 38.01 cm [95% CI, 37.30-38.72 cm]; P < .001) and AP (38.16 cm [95% CI, 37.47-38.85 cm] vs 34.57 cm [95% CI, 33.97-35.17 cm]; P < .001) dimensions. Significant moderately positive correlations were found for AP dimensions with height (r = 0.584, P < .001) and weight (r = 0.383, P < .001) and for ML dimensions with height (r = 0.711, P < .001) and weight (r = 0.467, P < .001). ROC was positively correlated with height (r = 0.509, P < .001) and weight (r = 0.294, P < .001). Patient age was not related to either the AP or ML distal tibial dimensions or ROC. CONCLUSIONS: After magnetic resonance imaging analysis, all potential donors permitted harvest of a standard-sized distal tibial allograft irrespective of sex or common anthropometric measures, and 85.8% showed distal tibial morphology acceptable for glenoid augmentation. AP and ML graft dimensions and ROC correlated significantly with height and weight. LEVEL OF EVIDENCE: Level II, diagnostic study.

Quality of Care Delivered to Veterans with COPD Exacerbation and the Association with 30-Day Readmission and Death.

Quality of chronic obstructive pulmonary disease (COPD) care is thought to be an important intermediate process to improve the well-being of patients admitted to hospital for exacerbation. We sought to examine the quality of inpatient COPD care and the associations with readmission and mortality. We performed a cohort study of 2,364 veterans aged over 40 and hospitalized for COPD between 2005 and 2011 at five Department of Veterans Affairs hospitals. We examined whether patients received six guideline recommended care items including short-acting bronchodilators, corticosteroids, antibiotics, positive-pressure ventilation (in cases of acute hypercarbic respiratory failure), chest imaging, and arterial blood gas measurement. Our primary outcome was all-cause hospital readmission or death within 30 days. Overall quality of care was not significantly associated with readmission or death (acute care aOR 0.98; 95% CI 0.87-1.11; ICU aOR 0.89; 95% CI 0.71-1.13). Delivery of corticosteroids and antibiotics was associated with reduced odds of readmission and death (aOR 0.77; 95% CI 0.61-0.92). Few patients received all of the recommended care items (18% of acute care, 38% of ICU patients). Quality of care did not vary by race or sex but did vary significantly across sites and did not improve over time. Our composite measure of COPD care quality was not associated with readmission or death. Further efforts are needed to improve care delivery to patients hospitalized with COPD.

Systematic review and meta-analysis of pertussis epidemiology in Latin America and the Caribbean: 1980-2015.

OBJECTIVES: In Latin America and the Caribbean (LAC), pertussis disease incidence has reportedly increased since 2000 despite high vaccine coverage. A systematic review of pertussis literature and a meta-analysis was conducted to understand the burden of disease in LAC. METHODS: A systematic literature review was completed, using relevant search terms. Original articles describing pertussis epidemiology and vaccine coverage in LAC published between 1980 and 2015 were identified. Applying a Bayesian meta-analysis random-effects model, we calculated pooled estimates and corresponding 95% credible intervals (95% CrIs) for pertussis incidence, case fatality ratio (CFR), pertussis prevalence among contacts, and coverage with three doses of diphtheria, tetanus, and pertussis (DTP) vaccine (DTP3). RESULTS: A total of 59 studies meeting our selection criteria were identified, representing 15 countries. Of the 59, 15 of them provided incidence data, with 7 of the 15 reporting a pertussis case definition. The pertussis incidence estimate for the 1980-1999 period was 17.8 cases per 100 000 persons (95% CrI: 5.9-29.7); for the 2000-2015 period, it was 2.5 cases per 100 000 persons (95% CrI: 1.8-3.2). For the 1980-2015 period, the CFR, in 19 studies reviewed, was 3.9% (95% CrI: 2.9%-4.9%); for that same period, in 5 studies reviewed, pertussis prevalence among contacts was 24.9% (95% CrI: 13.7%-36.1%). Pooled DTP3 vaccine coverage estimates, in a total of 20 studies reviewed for the following three time periods, were: 1980-1990, 72.4% (95% CrI: 64.6%-80.2%); 1991-2000, 79.0% (95% CrI: 66.1%-91.9%); and 2001-2015, 90.0% (95% CrI: 87.7%-92.3%). CONCLUSION: A decrease in pertussis incidence and an achievement of moderately high DTP3 vaccine coverage since the early 2000s was observed. The review highlights the need for increased publication of pertussis data at the country level and for LAC as a whole in order to better understand the true burden of the disease. Application of a standardized case definition and use of active case finding would aid in obtaining more accurate estimates of the disease burden in LAC.

Fractional Third and Fourth Dose of RTS,S/AS01 Malaria Candidate Vaccine: A Phase 2a Controlled Human Malaria Parasite Infection and Immunogenicity Study.

BACKGROUND: Three full doses of RTS,S/AS01 malaria vaccine provides partial protection against controlled human malaria parasite infection (CHMI) and natural exposure. Immunization regimens, including a delayed fractional third dose, were assessed for potential increased protection against malaria and immunologic responses. METHODS: In a phase 2a, controlled, open-label, study of healthy malaria-naive adults, 16 subjects vaccinated with a 0-, 1-, and 2-month full-dose regimen (012M) and 30 subjects who received a 0-, 1-, and 7-month regimen, including a fractional third dose (Fx017M), underwent CHMI 3 weeks after the last dose. Plasmablast heavy and light chain immunoglobulin messenger RNA sequencing and antibody avidity were evaluated. Protection against repeat CHMI was evaluated after 8 months. RESULTS: A total of 26 of 30 subjects in the Fx017M group (vaccine efficacy [VE], 86.7% [95% confidence interval [CI], 66.8%-94.6%]; P < .0001) and 10 of 16 in the 012M group (VE, 62.5% [95% CI, 29.4%-80.1%]; P = .0009) were protected against infection, and protection differed between schedules (P = .040, by the log rank test). The fractional dose boosting increased antibody somatic hypermutation and avidity and sustained high protection upon rechallenge. DISCUSSIONS: A delayed third fractional vaccine dose improved immunogenicity and protection against infection. Optimization of the RTS,S/AS01 immunization regimen may lead to improved approaches against malaria. CLINICAL TRIALS REGISTRATION: NCT01857869.

The architecture of redox microdomains: Cascading gradients and peroxiredoxins' redox-oligomeric coupling integrate redox signaling and antioxidant protection.

In the cytosol of human cells under low oxidative loads, hydrogen peroxide is confined to microdomains around its supply sites, due to its fast consumption by peroxiredoxins. So are the sulfenic and disulfide forms of the 2-Cys peroxiredoxins, according to a previous theoretical analysis [Travasso et al., Redox Biology 15 (2017) 297]. Here, an extended reaction-diffusion model that for the first time considers the differential properties of human peroxiredoxins 1 and 2 and the thioredoxin redox cycle predicts important new aspects of the dynamics of redox microdomains. The peroxiredoxin 1 sulfenates and disulfides are more localized than the corresponding peroxiredoxin 2 forms, due to the former peroxiredoxin's faster resolution step. The thioredoxin disulfides are also localized. As the H2O2 supply rate (vsup) approaches and then surpasses the maximal rate of the thioredoxin/thioredoxin reductase system (V), these concentration gradients become shallower, and then vanish. At low vsup the peroxiredoxin concentration determines the H2O2 concentrations and gradient length scale, but as vsup approaches V, the thioredoxin reductase activity gains influence. A differential mobility of peroxiredoxin disulfide dimers vs. reduced decamers enhances the redox polarity of the cytosol: as vsup approaches V, reduced decamers are preferentially retained far from H2O2 sources, attenuating the local H2O2 buildup. Substantial total protein concentration gradients of both peroxiredoxins emerge under these conditions, and the concentration of reduced peroxiredoxin 1 far from the H2O2 sources even increases with vsup. Altogether, the properties of 2-Cys peroxiredoxins and thioredoxin are such that localized H2O2 supply induces a redox and functional polarization between source-proximal regions (redox microdomains) that facilitate peroxiredoxin-mediated signaling and distal regions that maximize antioxidant protection.

Historic Use of Race-Based Spirometry Values Lowered Transplant Priority for Black Patients.

BACKGROUND: The lung allocation score (LAS) is a tool used to prioritize patients for lung transplantation. For patients with interstitial lung diseases (ILDs), spirometry data are used for the LAS calculation. Spirometry values such as a FVC are subjected to race-specific equations that determine expected values. The effect of race-specific equations in LAS score remains unknown. RESEARCH QUESTION: Did the use of a race-based spirometry equation lead to longer waitlist times for Black patients? STUDY DESIGN AND METHODS: We performed a retrospective analysis of patients listed for lung transplantation from 2005 through 2020 using publicly available data from the United Network for Organ Sharing. We recalculated LAS scores for Black patients using White-specific equations with the available variables. The primary objective was to evaluate the effect of race-specific equations on LAS scores and time on the transplant waitlist. RESULTS: A total of 33,845 patients listed for lung transplantation were included in the analysis. White patients were listed at lower LAS scores, a higher proportion of White patients underwent transplantation, and White patients died on the waitlist at lower rates. When recalculating LAS scores using White-specific equations, Black patients with ILD had up to a 1.9-point higher score, which resulted in additional waitlist time. INTERPRETATION: Race-specific equations led to longer wait times in Black patients listed for lung transplantation. The use of race-based equations widened already known disparities in pulmonary transplantation.

How do field epidemiologists learn? A protocol for a qualitative inquiry into learning in field epidemiology training programmes.

INTRODUCTION: COVID-19 underscored the importance of field epidemiology training programmes (FETPs) as countries struggled with overwhelming demands. Experts are calling for more field epidemiologists with better training. Since 1951, FETPs have been building public health capacities across the globe, yet explorations of learning in these programmes are lacking. This qualitative study will (1) describe approaches to training field epidemiologists in FETP; (2) describe strategies for learning field epidemiology among FETP trainees and (3) explain the principles and practices aligning training approaches with learning strategies in FETP. METHODS AND ANALYSIS: The research design, implementation and interpretation are collaborative efforts with FETP trainers. Data collection will include interviews with FETP trainers and trainees and participant observations of FETP training and learning events in four FETP in the Western Pacific Region. Data analysis will occur in three phases: (1) we will use the constant comparison method of Charmaz's grounded theory during open coding to identify and prioritise categories and properties in the data; (2) during focused coding, we will use constant comparison and Polkinghorne's analysis of narratives, comparing stories of prioritised categories, to fill out properties of those categories and (3) we will use Polkinghorne's narrative analysis to construct narratives that reflect domains of interest, identifying correspondence among Carr and Kemmis's practices, understandings and situations to explain principles and processes of learning in FETP. ETHICS AND DISSEMINATION: We have obtained the required ethics approvals to conduct this research at The Australian National University (2021/771) and Taiwan's Ministry of Health and Welfare (112206). Data will not be available publicly, but anonymised findings will be shared with FETP for collaborative interpretation. Ultimately, findings and interpretations will appear in peer-reviewed journals and conferences.

Risks of Zolpidem among Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Nonbenzodiazepine benzodiazepine receptor agonists (NBZRA, e.g., zolpidem) are frequently used to treat insomnia among patients with chronic obstructive pulmonary disease (COPD). However, multiple observational studies find that patients with COPD who are prescribed NBZRAs have greater risks for mortality and respiratory complications than patients without such prescriptions. Without an active comparator, these studies are susceptible to confounding by indication. Objectives: Compare the risk of death or inpatient COPD exacerbation among patients receiving zolpidem relative to patients receiving other hypnotics. Methods: Using nationwide Veterans Health Administration (VA) data, we identified patients with clinically diagnosed COPD and new receipt of zolpidem or another hypnotic available on VA formulary without prior authorization (melatonin, trazodone, doxepin). We excluded those receiving traditional benzodiazepines or multiple concurrent hypnotics. We propensity-matched patients receiving zolpidem to other hypnotics on 32 variables, including demographics, comorbidities, and markers of COPD severity. We compared risk of the primary composite outcome of death or inpatient COPD exacerbation over 1 year. In secondary analyses, we propensity-matched patients receiving zolpidem to those without hypnotic receipt. Results: Among 283,740 patients meeting inclusion criteria, 1,126 (0.4%) received zolpidem and 3,057 (1.1%) received other hypnotics. We propensity-matched patients receiving zolpidem 1:1 to peers receiving other hypnotics. We did not find a difference in the primary composite outcome of death or inpatient exacerbation (hazard ratio, 0.97; 95% confidence interval [CI], 0.77-1.23). In secondary analyses comparing patients receiving zolpidem to matched peers without hypnotic receipt, we observed greater risk of death or inpatient exacerbation with zolpidem (hazard ratio, 1.40; 95% CI, 1.09-1.81). Conclusions: Among patients with COPD, we did not observe greater risks after new receipt of zolpidem relative to other hypnotics. However, we did observe greater risks relative to those without hypnotic receipt. This latter finding may reflect: 1) residual, unmeasured confounding related to insomnia; or 2) true adverse effects of hypnotics across classes. Future work is needed to better understand the risks of hypnotics in COPD.

Enhanced Photocatalytic and Photovoltaic Performance Arising from Unconventionally Low Donor-Y6 Ratios.

Development of both organic photovoltaics (OPVs) and organic photocatalysts has focused on utilizing the bulk heterojunction (BHJ). The BHJ promotes charge separation and enhances the carrier lifetime, but may give rise to increased charge traps, hindering performance. Here, high photocatalytic and photovoltaic performance is displayed by electron donor-acceptor (D-A) nanoparticles (NPs) and films, using the nonfullerene acceptor Y6 and polymer donor PIDT-T8BT. In contrast to conventional D-A systems, the charge generation in PIDT-T8BT:Y6 NPs is mainly driven by Y6, allowing a high performance even at a low D:A mass ratio of 1:50. The high performance at the low mass ratio is attributed to the amorphous behavior of PIDT-T8BT. Low ratios are generally thought to yield lower efficiency than the more conventional ≈1:1 ratio. However, the OPVs exhibit peak performance at a D:A ratio of 1:5. Similarly the NPs used for photocatalytic hydrogen evolution show peak performance at the 1:6.7 D:A ratio. Interestingly, for the PIDT-T8BT:Y6 system, as the polymer proportion increases, a reduced photocatalytic and photovoltaic performance is observed. The unconventional D:A ratios provide lower recombination losses and increased charge-carrier lifetime with undisrupted ambipolar charge transport in bulk Y6, enabling better performance than conventional ratios. This work reports novel light-harvesting materials in which performance is reduced due to unfavorable morphology as D:A ratios move toward conventional ratios of 1:1.2-1:1.

Molecular design rule of phthalocyanine dyes for highly efficient near-IR performance in dye-sensitized solar cells.

A series of zinc-phthalocyanine sensitizers (PcS16-18) with different adsorption sites have been designed and synthesized in order to investigate the dependence of adsorption-site structures on the solar-cell performances in zinc-phthalocyanine based dye-sensitized solar cells. The change of adsorption site affected the electron injection efficiency from the photoexcited dye into the nanocrystalline TiO2 semiconductor, as monitored by picosecond time-resolved fluorescence spectroscopy. The zinc-phthalocyanine sensitizer PcS18, possessing one carboxylic acid directly attached to the ZnPc ring and six 2,6-diisopropylphenoxy units, showed a record power conversion efficiency value of 5.9 % when used as a light-harvesting dye on a TiO2 electrode under one simulated solar condition.

Barriers and facilitators to goals of care conversations with Veteran residents of community nursing homes.

BACKGROUND: Despite evidence that structured goals of care conversations (GoCCs) and documentation of life-sustaining treatment (LST) preferences improve the delivery of goal-concordant care for seriously ill patients, rates of completion remain low among nursing home residents. The Preferences Elicited and Respected for Seriously Ill Veterans through Enhanced Decision-Making (PERSIVED) program aims to improve the consistent documentation of LST preferences among Veterans receiving care in veterans affairs (VA)-paid community nursing homes (CNH); however, the barriers and facilitators of completing and documenting GoCCs in this unique context of care have not been described. METHODS: We conducted semi-structured, qualitative interviews with key stakeholders of the VA CNH programs located at six VA Medical Centers between July 2021 and July 2022. With a rapid approach to analysis, interview transcripts were reduced into memo templates using the Tailored Implementation for Chronic Disease Checklist and coded and analyzed using qualitative data analysis software. RESULTS: The 40 participants consisted of nurses (n = 13), social workers (n = 25), and VA physicians (n = 2). Most participants felt confident about conducting GoCC; however, several barriers were identified. At the staff level, our results indicated inconsistent completion of GoCC and documentation due to a lack of training, confusion about roles and responsibilities, and challenging communication within the VA as well as with CNH. At the organizational level, there was a lack of standardization across sites for how LST preferences were documented. At the patient level, we found key barriers related to patient and family readiness and issues finding surrogate decision makers. While COVID-19 brought end-of-life issues to the forefront, lockdowns hindered communication about the goals of care. CONCLUSION: Findings from this pre-implementation evaluation revealed multi-level barriers in conducting and documenting GoCCs with Veterans receiving VA-paid CNH care, as well as several facilitators that can be used to inform strategies for improvement.

Sleep Testing and Mortality in a Propensity-matched Cohort of Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Many advocate the application of propensity-matching methods to real-world data to answer key questions around obstructive sleep apnea (OSA) management. One such question is whether identifying undiagnosed OSA impacts mortality in high-risk populations, such as those with chronic obstructive pulmonary disease (COPD). Objectives: Assess the association of sleep testing with mortality among patients with COPD and a high likelihood of undiagnosed OSA. Methods: We identified patients with COPD and a high likelihood of undiagnosed OSA. We then distinguished those receiving sleep testing within 90 days of index COPD encounters. We calculated propensity scores for testing based on 37 variables and compared long-term mortality in matched groups. In sensitivity analyses, we compared mortality using inverse propensity weighting and instrumental variable methods. We also compared the incidence of nonfatal events including adverse outcomes (hospitalizations and COPD exacerbations) and routine services that are regularly indicated in COPD (influenza vaccination and pulmonary function testing). We compared the incidence of each nonfatal event as a composite outcome with death and separately compared the marginal probability of each nonfatal event independently, with death as a competing risk. Results: Among 135,958 patients, 1,957 (1.4%) received sleep testing. We propensity matched all patients with sleep testing to an equal number without testing, achieving excellent balance on observed confounders, with standardized differences < 0.10. We observed lower mortality risk among patients with sleep testing (incidence rate ratio, 0.88; 95% confidence interval [CI], 0.79-0.99) and similar results using inverse propensity weighting and instrumental variable methods. Contrary to mortality, we found that sleep testing was associated with a similar or greater risk for nonfatal adverse events, including inpatient COPD exacerbations (subhazard ratio, 1.29; 95% CI, 1.02-1.62) and routine services like influenza vaccination (subhazard ratio, 1.26; 95% CI, 1.17-1.36). Conclusions: Our disparate findings can be interpreted in multiple ways. Sleep testing may indeed cause both reduced mortality and greater incidence of nonfatal adverse outcomes and routine services. However, it is also possible that our findings stem from residual confounding by patients' likelihood of accessing care. Given the limitations of propensity-based analyses, we cannot confidently distinguish these two possibilities. This uncertainty highlights the limitations of using propensity-based analyses to guide patient care and policy decisions.

Design and methods of a randomized trial testing "Advancing care for COPD in people living with HIV by implementing evidence-based management through proactive E-consults (ACHIEVE)".

Chronic obstructive pulmonary disease (COPD) is one of the most common comorbid diseases among aging people with HIV (PWH) and is often mismanaged. To address this gap, we are conducting the study, "Advancing care for COPD in people living with HIV by Implementing Evidence-based management through proactive E-consults (ACHIEVE)." This intervention optimizes COPD management by promoting effective, evidence-based care and de-implementing inappropriate therapies for COPD in PWH receiving care at Veteran Affairs (VA) medical centers. Study pulmonologists are proactively supporting ID providers managing a population of PWH who have COPD, offering real-time evidence-based recommendations tailored to each patient. We are leveraging VA clinical and informatics infrastructures to communicate recommendations between the study team and clinical providers through the electronic health record (EHR) as an E-consult. If effective, ACHIEVE could serve as a model of effective, efficient COPD management among PWH receiving care in VA. This paper outlines the rationale and methodology of the ACHIEVE trial, one of a series of studies funded by the National Heart, Lung, and Blood Institute (NHLBI) within the ImPlementation REsearCh to DEvelop Interventions for People Living with HIV (PRECluDE) consortium to study chronic disease comorbidities in HIV populations.