Multisectoral Collaborations to Increase Recruitment and Retention of Diverse Older Adults in Biomedical Research.

BACKGROUND: Older adults, especially minoritized racial-ethnic groups, are historically underrepresented in biomedical research. This study summarizes the development and assesses the impact of a review board involving a multisectoral group of stakeholders with the goal of increasing the diversity of older adults in biomedical research. METHODS: A 25-member board of community members, caregivers, researchers, and clinicians from Upstate New York reviewed 3 projects presented by researchers, clinician-scientists, and a pharmaceutical company between January and December 2022. For each biomedical research project, the reviews provided guidance to increase the recruitment and retention of diverse older adults engaged in the study. Review board members and presenters completed surveys to provide feedback on their experience in this collaboration. RESULTS: There was consistent positive feedback from all members and presenters. From member surveys, feedback trended positive in meetings throughout the year. Community members and caregivers initially indicated discomfort in expressing their views; however, these concerns subsided over time. Presenters had a very positive experience in the review board's impact on their recruitment strategy and study design, and therefore very likely to use this service again. Recommendations were made to adjust membership criteria, presentation format, and funding to sustain this effort. CONCLUSIONS: Lack of diversity for older adults represented in biomedical research contributes to ethical and generalizability ramifications. The positive feedback from all stakeholders in our multisectoral board of community members, caregivers, researchers, and clinicians offers a promising structure for developing similar strategies to increase diversity within and beyond biomedical aging research in other communities.

A retrospective study of crossover ambulatory oxygen walk testing in patients with fibrotic lung disease.

BACKGROUND: Fibrotic interstitial lung disease (ILD) comprises a group of lung conditions that are often progressive, debilitating, and life-shortening. Ambulatory oxygen therapy (AOT) is regularly prescribed to manage symptoms in patients with fibrotic ILD. In our institution, the decision to prescribe portable oxygen is made on the basis of oxygen improving exercise capacity, measured with the single-blinded, crossover ambulatory oxygen walk test (AOWT). This study aimed to investigate the characteristics and survival rates of patients with fibrotic ILD who have either positive or negative results on the AOWT. METHODS: This retrospective cohort study compared the data from 99 patients with fibrotic ILD who underwent the AOWT. These patients were classified into two groups based on whether they showed improvement in the AOWT with supplemental oxygen (positive group) or no improvement (negative group). Patient demographics for both groups were compared to determine any significant differences. A multivariate Cox proportional hazards model was used to analyze the survival rates of the two groups. RESULTS: Out of the 99 patients, 71 were in the positive group. We compared the measured characteristics between the positive and negative groups and found no significant difference, wherein the adjusted hazard ratio was 1.33 (95% confidence interval 0.69-2.60, P = 0.40). CONCLUSIONS: The AOWT can be used to rationalize AOT, but there was no significant difference in baseline characteristics or survival rates between patients whose performance was improved or not in the AOWT.

Longitudinal Evaluation of a Deprescribing Protocol in Skilled Nursing Facilities.

Objective: To determine whether a deprescribing effort reduced several key classes of medications, and the overall number of medication classes per patient, among long-term residents of skilled nursing facilities (SNFs). Design: Retrospective, longitudinal pre/post evaluation. Data from before and during the implementation of the deprescribing effort (2017 through 2019) were compared with data from the post-intervention year (2020). Setting and Patients: Long-term resident data reported through annual comprehensive reviews conducted at two SNFs located in central New York State between 2017 and 2020 (N = 12,144). Interventions: Multifaceted, interdisciplinary deprescribing effort to reduce medications in SNF residence including clinician education, guideline development, and individual chart reviews began in 2019. Results: The mean number of medications prescribed per resident was lower at both facilities after the intervention (mean = 1.74 at both facilities) versus preintervention (1.90 at Facility 1, 1.86 at Facility 2). Significant decreases were observed in the usage rates for diuretics (-4.2%; P = 0.001), opioids (-3.8%; P = 0.001), and antipsychotics (-2.4%; P = 0.010). The raw antidepressant usage rate increased by 1.5% after the intervention but the change was not significant. Effects were robust to covariate adjustment. Conclusion: A combined, comprehensive approach to deprescribing was associated with a reduction in the overall number of medication classes per resident and in several key classes of medications. Additional research with more data and covariate control is in progress for verification of these findings.

Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics.

BACKGROUND: Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate. METHODS: We present the findings of a phase Ib/IIa open label, platform randomised controlled trial of intravenous nafamostat in hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly to standard of care (SoC), nafamostat or an alternative therapy. Nafamostat was administered as an intravenous infusion at a dose of 0.2 mg/kg/h for a maximum of seven days. The analysis population included those who received any dose of the trial drug and all patients randomised to SoC. The primary outcomes of our trial were the safety and tolerability of intravenous nafamostat as an add on therapy for patients hospitalised with COVID-19 pneumonitis. FINDINGS: Data is reported from 42 patients, 21 of which were randomly assigned to receive intravenous nafamostat. 86% of nafamostat-treated patients experienced at least one AE compared to 57% of the SoC group. The nafamostat group were significantly more likely to experience at least one AE (posterior mean odds ratio 5.17, 95% credible interval (CI) 1.10 - 26.05) and developed significantly higher plasma creatinine levels (posterior mean difference 10.57 micromol/L, 95% CI 2.43-18.92). An average longer hospital stay was observed in nafamostat patients, alongside a lower rate of oxygen free days (rate ratio 0.55-95% CI 0.31-0.99, respectively). There were no other statistically significant differences in endpoints between nafamostat and SoC. PK data demonstrated that intravenous nafamostat was rapidly broken down to inactive metabolites. We observed no significant anticoagulant effects in thromboelastometry. INTERPRETATION: In hospitalised patients with COVID-19, we did not observe evidence of anti-inflammatory, anticoagulant or antiviral activity with intravenous nafamostat, and there were additional adverse events. FUNDING: DEFINE was funded by LifeArc (an independent medical research charity) under the STOPCOVID award to the University of Edinburgh. We also thank the Oxford University COVID-19 Research Response Fund (BRD00230).

Temperature but not nutrient addition affects abundance and assemblage structure of colonizing aquatic insects.

Abiotic conditions are important considerations in the species sorting process, which ultimately determines the distribution and abundance of species. Freshwater ecosystems will be impacted by ongoing temperature rise and other anthropogenically induced changes, such as nutrient enrichment and eutrophication. Changing characteristics of freshwater habitats will likely impact organisms in numerous ways, including through effects on colonization dynamics. Species are expected to colonize habitat patches where fitness will be the highest for themselves and their offspring, and how habitat selection interacts with changing environments remains an important question. We conducted a warming experiment to test the habitat selection preferences of aquatic beetles and hemipterans between habitat patches (mesocosms) of varying temperatures (via heaters), nutrient addition, and their interaction. Overall, insect abundance and richness were higher in unheated patches, with taxon-specific variation in response to heating. Although nutrients had limited effects on environmental conditions in mesocosms, their addition had no significant effects on insects. Insect assemblages had unique structures across heating treatments, with lower beta diversity and higher effective numbers of species in the warmest mesocosms. Our data support the importance of spatial variation in abiotic factors during the habitat selection process, and in determining species distributions and abundances as shallow lentic ecosystems are impacted by rising global temperatures.

-------A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS--.

Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation. Results: Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population, it does not impact upon prothrombotic hyperinflammatory neutrophil signatures. Conclusions: Given the crucial role of neutrophils in ARDS and the evidence of a disordered myeloid response observed in COVID-19 patients, this work maps the molecular basis for neutrophil reprogramming in the distinct clinical entities of COVID-19 and non-COVID-19 ARDS.

Practical Implementation of a Single-Night Split-Titration Protocol With BPAP-ST and AVAPS in Patients With Neuromuscular Disease.

STUDY OBJECTIVES: At the sleep laboratory, noninvasive positive pressure ventilation titration protocols in patients with neuromuscular disease (NMD) are based on standard pressure cycle devices in a spontaneous/timed mode (BPAP-ST). Experience integrating protocols on average volume-assured pressure support (AVAPS) mode is limited, prompting us to develop a practical single-night titration protocol that provides information to assist clinicians and patients as they decide between BPAP-ST and AVAPS modes. METHODS: We implemented a sequential titration protocol of BPAP-ST followed by AVAPS during a single-night polysomnography study in patients with NMD and reported polysomnographic and clinical metrics. RESULTS: There were 27 patients who completed the protocol: 14 (52%) were male with median and interquartile range (IQR) 64 (59 to 70) years of age and body mass index of 29.6 (25.6-32) kg/m2. They had median (IQR) maximal percent predicted inspiratory and expiratory pressures, and percent vital capacity of 33 (24 to 54), 34 (22 to 47) and 60 (47 to 74), respectively. At final titration of each device, average tidal volume and nadir non-rapid eye movement sleep oxyhemoglobin saturation (SpO2) were higher and respiratory rate/tidal volume, transcutaneous CO2, and arousal index were lower on AVAPS (P < .05) in comparison with BPAP-ST. Full face mask was used in 23 patients (85%). None of the other ventilatory or sleep parameters differed significantly between BPAP-ST and AVAPS (P > .05) sessions. CONCLUSIONS: A practical single-night split-titration protocol with BPAP-ST and AVAPS can successfully be implemented in patients with NMD, assisting clinicians and patients with the decision on initial treatment modalities and settings.