Examining the utility of near infrared light as pre-exposure therapy to mitigate temporary noise-induced hearing loss in humans.

Introduction: This study sought to determine the effect of Occupational Safety and Health Administration (OSHA) compliant noise on auditory health and assess whether pre-noise near infrared (NIR) light therapy can mitigate the effects of noise exposure. Methods: Over four visits, participants (n = 30, NCT#: 03834714) with normal hearing completed baseline hearing health assessments followed by exposure to open ear, continuous pink noise at 94 dBA for 15 min. Immediately thereafter, post-noise hearing tests at 3000, 4000, and 6000 Hz and distortion product otoacoustic emissions (DPOAEs) were conducted along with the Modified Rhyme Test (MRT), Masking Level Difference Test (MLD), and Fixed Level Frequency Tests (FLFT) [collectively referred to as the Central and Peripheral Auditory Test Battery (CPATB)] to acquire baseline noise sensitivity profiles. Participants were then randomized to either Active or Sham NIR light therapy for 30 min binaurally to conclude Visit 1. Visit 2 (≥24 and ≤ 48 h from Visit 1) began with an additional 30-min session of Active NIR light therapy or Sham followed by repeat CPATB testing and noise exposure. Post-noise testing was again conducted immediately after noise exposure to assess the effect of NIR light therapy. The remaining visits were conducted following ≥2 weeks of noise rest in a cross-over design (i.e., those who had received Active NIR light therapy in Visits 1 and 2 received Sham therapy in Visits 3 and 4). Results: Recovery hearing tests and DPOAEs were completed at the end of each visit. Participants experienced temporary threshold shifts (TTS) immediately following noise exposure, with a mean shift of 6.79 dB HL (±6.25), 10.61 dB HL (±6.89), and 7.30 dB HL (±7.25) at 3000, 4000, and 6000 Hz, respectively, though all thresholds returned to baseline at 3000, 4000, and 6000 Hz within 75 min of noise exposure. Paradoxically, Active NIR light therapy threshold shifts were statistically higher than Sham therapy at 3000 Hz (p = 0.04), but no other differences were observed at the other frequencies tested. An age sub-analysis demonstrated that TTS among younger adults were generally larger in the Sham therapy group versus Active therapy, though this was not statistically different. There were no differences in CPATB test results across Active or Sham groups. Finally, we observed no changes in auditory function or central processing following noise exposure, suggestive of healthy and resilient inner ears. Conclusion: In this study, locally administered NIR prior to noise exposure did not induce a significant protective effect in mitigating noise-induced TTS. Further exploration is needed to implement effective dosage and administration for this promising otoprotective therapy.

Associations of Sarcopenia and Body Composition Measures With Mortality After Transcatheter Aortic Valve Replacement.

BACKGROUND: Frailty associates with worse outcomes after transcatheter aortic valve replacement (TAVR). Sarcopenia underlies frailty, but the association between a comprehensive assessment of sarcopenia-muscle mass, strength, and performance-and outcomes after TAVR has not been examined. METHODS: From a multicenter prospective registry of patients with symptomatic severe aortic stenosis undergoing TAVR, 445 who had a preprocedure computed tomography and clinical assessment of frailty were included. Cross-sectional muscle (psoas and paraspinal) areas were measured on computed tomography and indexed to height. Gait speed and handgrip strength were obtained, and patients were dichotomized into fast versus slow; strong versus weak; and normal versus low muscle mass. As measures of body composition, cross-sectional fat (subcutaneous and visceral) was measured and indexed to height. RESULTS: The frequency of patients who were slow, weak, and had low muscle mass was 56%, 59%, and 42%, respectively. Among the 3 components of sarcopenia, only slower gait speed (muscle performance) was independently associated with increased post-TAVR mortality (adjusted hazard ratio, 1.12 per 0.1 m/s decrease [95% CI, 1.04-1.21]; P=0.004; adjusted hazard ratio, 1.38 per 1 SD decrease [95% CI, 1.11-1.72]; P=0.004). Meeting multiple sarcopenia criteria was not associated with higher mortality risk than fewer. Lower indexed visceral fat area (adjusted hazard ratio, 1.48 per 1 SD decrease [95% CI, 1.15-1.89]; P=0.002) was associated with mortality but indexed subcutaneous fat was not. Death occurred in 169 (38%) patients. CONCLUSIONS: Among patients with symptomatic severe aortic stenosis and comprehensive sarcopenia and body composition phenotyping, gait speed was the only sarcopenia measure associated with post-TAVR mortality. Lower visceral fat was also associated with increased risk pointing to an obesity paradox also observed in other patient populations. These findings reinforce the clinical utility of gait speed as a measure of risk and a potential target for adjunctive interventions alongside TAVR to optimize clinical outcomes.

Airway and Systemic Immune Responses Following the Third COVID-19 Vaccination in COPD Patients.

Introduction: Booster vaccinations are required to maintain protection against COVID-19. COPD patients are at higher risk of developing severe illness following SARS-CoV-2 infection. Previous cross-sectional analysis after the second COVID-19 booster showed similar immune responses in COPD patients and controls, but pre-vaccination samples were not available. This longitudinal study evaluated systemic and airway immune responses in COPD patients using samples obtained pre- and post-third COVID-19 vaccination. Methods: Twelve COPD patients were recruited, with plasma, nasal and sputum (n = 10) samples collected pre-vaccination and 4- and 14-weeks post vaccination. Samples were analyzed for anti-spike IgA and IgG and cellular immunity. The ability of plasma and nasal samples to block ACE2-spike protein interaction was assessed for Wild type, Delta, and Omicron spike variants. Results: Vaccinations increased anti-spike IgG in plasma (p < 0.001), nasal (IgG p < 0.001) and sputum (p = 0.002) samples, IgA in plasma (p < 0.001) and blood cellular immunity (p = 0.001). Plasma and nasal anti-spike IgA levels correlated (rho: 0.6, p = 0.02), with similar results for IgG (rho: 0.79, p = 0.003). Post-vaccination nasal (p = 0.002) and plasma (p < 0.001) samples were less effective at blocking Omicron spike binding to ACE2 compared to the Wild type spike variant. Discussion: Airway and systemic immune responses against SARS-CoV-2 increased in COPD patients following a third COVID-19 vaccination. Nasal and systemic responses in COPD patients were less effective against Omicron variant compared to previous variants.

MicroRNA-375 Is Induced during Astrocyte-to-Neuron Reprogramming and Promotes Survival of Reprogrammed Neurons when Overexpressed.

While astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. To understand the function of miRNAs during the AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on human astrocyte (HA) cultures upon NeuroD1 overexpression. Bioinformatics analyses showed that NeuroD1 not only activated essential neuronal genes to initiate the reprogramming process but also induced miRNA changes in HA. Among the upregulated miRNAs, we identified miR-375 and its targets, neuronal ELAVL genes (nELAVLs), which encode a family of RNA-binding proteins and were also upregulated by NeuroD1. We further showed that manipulating the miR-375 level regulated nELAVLs' expression during NeuroD1-mediated reprogramming. Interestingly, miR-375/nELAVLs were also induced by the reprogramming factors Neurog2 and ASCL1 in HA, suggesting a conserved function to neuronal reprogramming, and by NeuroD1 in the mouse astrocyte culture and spinal cord. Functionally, we showed that miR-375 overexpression improved NeuroD1-mediated reprogramming efficiency by promoting cell survival at early stages in HA and did not appear to compromise the maturation of the reprogrammed neurons. Lastly, overexpression of miR-375-refractory ELAVL4 induced apoptosis and reversed the cell survival-promoting effect of miR-375 during AtN reprogramming. Together, we demonstrated a neuroprotective role of miR-375 during NeuroD1-mediated AtN reprogramming.

MicroRNA-375 is induced during astrocyte-to-neuron reprogramming and promotes survival of reprogrammed neurons when overexpressed.

While astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. MicroRNAs (miRNAs), as post-transcriptional regulators of gene expression, play crucial roles during development and under various pathological conditions. To understand the function of miRNAs during AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on human astrocyte (HA) cultures upon NeuroD1 overexpression. Bioinformatics analyses showed that NeuroD1 not only activates essential neuronal genes to initiate reprogramming process but also induces miRNA changes in HA. Among the upregulated miRNAs, we identified miR-375 and its targets, neuronal ELAVL genes ( nELAVLs ), which encode a family of RNA-binding proteins and are also upregulated by NeuroD1. We further showed that manipulating miR-375 level regulates nELAVLs expression during NeuroD1-mediated reprogramming. Interestingly, miR-375/ nELAVLs are also induced by reprogramming factors Neurog2 and ASCL1 in HA suggesting a conserved function to neuronal reprogramming, and by NeuroD1 in the mouse astrocyte culture and spinal cord. Functionally, we showed that miR-375 overexpression improves NeuroD1-mediated reprogramming efficiency by promoting cell survival at early stages in HA even in cultures treated with the chemotherapy drug Cisplatin. Moreover, miR-375 overexpression doesn't appear to compromise maturation of the reprogrammed neurons in long term HA cultures. Lastly, overexpression of miR-375-refractory ELAVL4 induces apoptosis and reverses the cell survival-promoting effect of miR-375 during AtN reprogramming. Together, we demonstrate a neuro-protective role of miR-375 during NeuroD1-mediated AtN reprogramming and suggest a strategy of combinatory overexpression of NeuroD1 and miR-375 for improving neuronal reprogramming efficiency.

Association of Depression and Cognitive Dysfunction With Patient-Centered Outcomes After Transcatheter Aortic Valve Replacement.

BACKGROUND: Depression and cognitive dysfunction (CD) are not routinely screened for in patients before transcatheter aortic valve replacement (TAVR) and their association with postprocedural outcomes is poorly understood. The objectives of this study are to determine the prevalence of depression and CD in patients with aortic stenosis undergoing TAVR and evaluate their association with mortality and quality of life. METHODS: We analyzed a prospective, multicenter TAVR registry that systematically screened patients for preexisting depression and CD with the Patient Health Questionnaire-2 and Mini-Cog, respectively. The associations with mortality were assessed with Cox proportional hazard models and quality of life (Kansas City Cardiomyopathy Questionnaire and EuroQol visual analogue scale) were evaluated using multivariable ordinal regression models. RESULTS: A total of 884 patients were included; median follow-up was 2.88 years (interquartile range=1.2-3.7). At baseline, depression was observed in 19.6% and CD in 31.8%. In separate models, after adjustment, depression (HR, 1.45 [95% CI, 1.13-1.86]; P<0.01) and CD (HR, 1.27 [95% CI, 1.02-1.59]; P=0.04) were each associated with increased mortality. Combining depression and CD into a single model, mortality was greatest among those with both depression and CD (n=62; HR, 2.06 [CI, 1.44-2.96]; P<0.01). After adjustment, depression was associated with 6.6 (0.3-13.6) points lower on the Kansas City Cardiomyopathy Questionnaire 1-year post-TAVR and 6.7 (0.5-12.7) points lower on the EuroQol visual analogue scale. CD was only associated with lower EuroQol visual analogue scale. CONCLUSIONS: Depression and CD are common in patients that undergo TAVR and are associated with increased mortality and worse quality of life. Depression may be a modifiable therapeutic target to improve outcomes after TAVR.

Metabolic Signatures of Cardiac Dysfunction, Multimorbidity, and Post-Transcatheter Aortic Valve Implantation Death.

Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post-transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25-1.90]; P<0.001), with similar effects in each validation cohort. This metabolite score of diastolic function was simultaneously associated with measures of multimorbidity, suggesting a metabolic link between cardiac and noncardiac state in aortic stenosis. Conclusions Metabolite profiles of cardiac structure identify individuals at high risk for death following transcatheter aortic valve implantation and concurrent multimorbidity. These results call for efforts to address potentially reversible metabolic biology associated with risk to optimize post-transcatheter aortic valve implantation recovery, rehabilitation, and survival.

Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results.

There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50 mg of IT nivolumab. There were no dose-limiting toxicities at any dose level. The recommended IT dose of nivolumab is 50 mg (with IV nivolumab 240 mg) every 2 weeks. Median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. These initial results suggest that concurrent IT and IV nivolumab is safe and feasible with potential efficacy in patients with melanoma LMD, including in patients who had previously received anti-PD1 therapy. Accrual to the study continues, including in patients with lung cancer. ClinicalTrials.gov registration: NCT03025256 .

Dyadic versus individual delivery of a yoga program for family caregivers of glioma patients undergoing radiotherapy: Results of a 3-arm randomized controlled trial.

BACKGROUND: Despite their significant distress, supportive care interventions for caregivers of glioma patients are generally lacking. And, whether caregivers are more likely to benefit from interventions targeting patient-caregiver dyads or caregivers individually is unknown. This pilot randomized controlled trial compared the feasibility and preliminary efficacy of a dyadic yoga (DY) versus an individual caregiver yoga (CY) intervention as a supportive care strategy for family caregivers. METHODS: Patient-caregiver dyads were randomized to a DY, CY or usual care (UC) arm. DY and CY interventions were delivered over 15 sessions. Caregivers completed assessments of their depressive symptoms, quality of life (QOL), and caregiving reactions at baseline, 6 weeks, and 12 weeks, and a subset completed qualitative interviews at 12 weeks. RESULTS: With a consent rate of 63%, 67 dyads were randomized. Attendance in the DY was higher than in the CY group (session means, DY = 12.23, CY = 9.00; p = 0.06). Caregivers (79% female; 78% non-Hispanic White; mean age, 53 years) reported significantly more subjective benefit in the CY arm than in the DY arm (d = 2.1; p < .01), which was consistent with the qualitative assessment. There were medium effect sizes for improved mental QOL (d = 0.46) and financial burden (d = 0.53) in favor of the CY over the UC group. Caregivers in the CY group reported more caregiving esteem (d = 0.56) and less health decline (d = 0.60) than those in the DY group. CONCLUSION: Individual rather than dyadic delivery may be a superior supportive care approach for this vulnerable caregiver population. A larger, adequately powered efficacy trial is warranted.

A Retrospective Analysis of Clinical Utilization Between Patients Who Used Telemedicine and Office Visits in Outpatient Physical Medicine and Rehabilitation Clinics During the COVID-19 Pandemic.

OBJECTIVE: To describe the demographic characteristics of patients who used telemedicine and office visits in physical medicine and rehabilitation during the COVID-19 pandemic and to quantify differences in clinical utilization between groups. Clinical utilization was defined as emergency department, urgent care, and hospital visits. DESIGN: This was a retrospective cohort study of 1096 patients who used telemedicine and 1171 patients who used office visits from April to June 2020 in the outpatient physical medicine and rehabilitation clinics at University of Pittsburgh Medical Center for musculoskeletal-related complaints. RESULTS: The telemedicine groups contained proportionally more people of color and higher comorbidities than the office visit groups. Patients who were seen in the telemedicine groups were more likely to be prescribed opioids than the office visit group. There were no differences in clinical utilizations between the telemedicine and office visit groups. CONCLUSIONS: The higher use of telemedicine in patients of color suggests a need for studying long-term outcomes to evaluate differences in care standards. There is an urgent need to understand how telemedicine affects opioid prescribing practices. Lastly, future studies are needed to understand why there were no differences in clinical utilization between the telemedicine and office visit groups.

Identification of COPD Inflammatory Endotypes Using Repeated Sputum Eosinophil Counts.

Higher blood and sputum eosinophil counts are associated with a greater response to corticosteroids in COPD. Low blood eosinophil counts exhibit greater stability over time whereas higher counts demonstrate more variability. Stability of airway eosinophil levels is less well understood. We have studied the stability of sputum eosinophil counts. Differential cell count data for COPD patients (n = 100) were analysed. Subjects with two sputum eosinophil counts, 6 months apart, were included in the analysis. Patients were stratified based on baseline sputum eosinophil count into 'low', 'intermediate' and 'high' groups: eosinophilLOW (<1%), eosinophilINT (1−3%) and eosinophilHIGH (≥3%). Sputum eosinophil counts showed good stability (rho = 0.61, p < 0.0001, ICC of 0.77), with 67.4% of eosinophilLOW patients remaining in the same category on repeat sampling. Bland−Altman analysis of the whole cohort (median difference between measurements = 0.00%, 90th percentile = −1.4 and 4.7%) showed greater variation at higher counts. This was confirmed by the wider 90th centiles in the eosinophilINT (−1.50 to 5.65) and eosinophilHIGH groups (−5.33 to 9.80) compared to the eosinophilLOW group (−0.40 to 1.40). The repeatability of sputum eosinophil counts was related to the baseline eosinophil count; sputum eosinophilLOW COPD patients were relatively stable over time, while the eosinophilHIGH group showed greater variability. These results can facilitate the identification of COPD endotypes with differential responses to treatment.

Global Longitudinal Strain and Biomarkers of Cardiac Damage and Stress as Predictors of Outcomes After Transcatheter Aortic Valve Implantation.

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction <50% was observed in 19% and impaired GLS (aGLS <15%) in 38%. Elevations in cardiac troponin and NT-proBNP were present in 79% and 89% of those with impaired GLS, respectively, as compared with 63% and 60% of those with normal GLS, respectively (P<0.001 for each). aGLS <15% was associated with increased mortality in univariable analysis (P=0.009), but, in a model with both biomarkers, aGLS, and clinical covariates included, aGLS was not associated with mortality; elevation in each biomarker was associated with an increased hazard of mortality (adjusted hazard ratio, >2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT-proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

Relationships between Airway Remodeling and Clinical Characteristics in COPD Patients.

Background: Airway remodeling is a cardinal feature of chronic obstructive pulmonary disease (COPD) pathology. However, inconsistent findings have been reported regarding the nature of proximal airway remodeling in COPD. This is likely due to the heterogeneity of COPD. This study investigated the histopathological features of airway remodeling in bronchial biopsies of COPD patients compared to smoking controls (S). We tested the hypothesis that histopathological features in bronchial biopsies relate to clinical characteristics in COPD patients, focusing on smoking status, symptom burden, lung function, exacerbation risk and inhaled corticosteroid (ICS) use. Methods: We recruited 24 COPD patients and 10 S. We focused on reticular basement membrane thickness (RBM), surface immunoglobulin A (IgA) expression, goblet cell numbers (periodic acid-Schiff [PAS]+), sub-mucosal remodeling markers including collagen 4, 6 and laminin expression, and inflammatory cell counts (CD45+). Results: RBM thickness was increased in frequent exacerbators, IgA expression was reduced in COPD patients with worse lung function, and goblet cell numbers were increased in COPD patients compared to S but with no difference between the COPD subgroups. Collagen 4 expression was associated with higher symptom burden and worse quality of life. Sub-mucosal inflammatory cell counts were increased in COPD non-inhaled corticosteroid (ICS) users compared to ICS users and S. Conclusion: We observed relationships between the histopathological features of airway remodeling and clinical characteristics in COPD patients. Our data highlight the influence of clinical heterogeneity on diverse patterns of airway remodeling in COPD patients.

Expiratory flow limitation in a cohort of highly symptomatic COPD patients.

The question addressed by the study: Small airway collapse during expiration, known as expiratory flow limitation (EFL), can be detected using oscillometry and is associated with worse clinical outcomes in COPD. This study investigated the prevalence of EFL in a cohort of highly symptomatic patients, evaluated clinical and lung function characteristics of patients with EFL and studied the repeatability of EFL over 6 months. Materials/patients and methods: 70 patients were recruited. Clinical characteristics and lung function metrics were collected at baseline and 6 months. Impulse oscillometry was used to detect the presence of EFL. Patients were defined as EFLHigh (change in reactance measured at 5 Hz (ΔX 5) ≥0.28 kPa·L-1·s-1); EFLIntermediate (ΔX 5 0.1-0.27 kPa·L-1·s-1) and EFLNone (ΔX 5 <0.1 kPa·L-1·s-1). Results: EFLHigh was present in 47.8% of patients at baseline. ΔX 5 showed excellent repeatability over 6 months (ρ=0.78, p<0.0001, intraclass correlation coefficient (ICC) 0.88), with the best repeatability observed in EFLNone and EFLHigh patients (ICC 0.77 and 0.65, respectively). Compared to EFLNone patients, EFLHigh had a higher body mass index, worse health-related quality of life and increased peripheral airway resistance. EFLIntermediate was more variable over time with less severe physiological impairment. Answer to the question: Overall, these data indicate that EFLHigh is a common, and relatively stable, component of disease pathophysiology in highly symptomatic COPD patients. EFLHigh was also associated with worse quality of life and obesity.

Left Ventricular Hypertrophy and Biomarkers of Cardiac Damage and Stress in Aortic Stenosis.

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core-laboratory-measured LV mass index, cTnT, and NT-proBNP. LVH was defined by sex-specific guideline cut-offs and elevated biomarker levels were based on age and sex cut-offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all-cause death out to 5 years. Elevated cTnT and NT-proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P<0.001 for each). After adjustment, compared with no/mild LVH, moderate/severe LVH was associated with an increased hazard of mortality (adjusted hazard ratio [aHR], 1.34; 95% CI 1.01-1.77, P=0.043). cTnT and NT-proBNP each risk stratified patients with moderate/severe LVH (P<0.05). In a model with both biomarkers and LVH included, elevated cTnT (aHR, 2.08; 95% CI 1.45-3.00, P<0.001) and elevated NT-proBNP (aHR, 1.46; 95% CI 1.00-2.11, P=0.049) were each associated with increased mortality risk, whereas moderate/severe LVH was not (P=0.15). Conclusions Elevations in circulating cTnT and NT-proBNP are more common as LVH becomes more pronounced but are also observed in those with no/minimal LVH. As measures of maladaptive remodeling and cardiac injury, cTnT and NT-proBNP predict post-transcatheter aortic valve replacement mortality better than LV mass index. These findings may have important implications for risk stratification and treatment of patients with aortic stenosis.

Face coverings during the pandemic?

The Health Belief Model (HBM), a value-expectancy model, is a leading framework in health behavior and communication research. The model is intended to inform targeted communication strategies that promote positive health behaviors. Individual beliefs associated with health risks such as perceived susceptibility and perceived severity are often incorporated into HBM as predictors of health behavior. However, recent studies point to limitations of the current model. At the same time, researchers have successfully used Cultural Theory (CT) to conceptualize, measure, and predict the cultural influences on health risk management. This study applies OLS regression and graphical analysis to examine the relationship between more intrinsic cultural value-based beliefs and HBM beliefs so as to understand behavioral intentions associated with COVID-19 among the general public in the United States while statistically controlling for the effects of partisanship and demographic factors.

Methacholine challenges: comparison of different tidal breathing challenge methods.

Tidal-breathing methacholine challenges are now recommended by guidelines, to avoid the bronchoprotective effects of deep inhalation. This study compared different tidal breathing methacholine challenge methods; assessed the agreement between tidal dosimetric and continuous output challenges; and assessed challenge repeatability with different methods. 15 asthma patients performed dosimetric challenges and a continuous-output breath-actuated challenge, all ≥3 days apart. All subjects had a pre-bronchodilator forced expiratory volume in 1 s (FEV1) ≥65% predicted, and a cumulative dose causing a 20% reduction in FEV1 (PD20) <1.2 mg. Of the dosimetric challenges, one method increased methacholine concentration (standard dosimetric challenge), and one adjusted nebuliser output time to increase dose (adjusted dosimetric challenge). The adjusted dosimetric and continuous output challenges were performed twice on separate days to assess for repeatability. All challenges were matched for dose at each dose step. The mean PD20 ratio of the standard dosimetric challenge to the adjusted dosimetric challenge was 0.90 (95% CI 0.66-1.23, p=0.49) and intraclass correlation coefficient (ICC) was 0.82. Repeated adjusted dosimetric challenges had an ICC 0.62 for PD20. Repeated continuous output challenges had an ICC 0.74 for PD20. The adjusted dosimetric and continuous output challenges correlated (r=0.69, p=0.0043; ICC 0.65), but PD20 was higher for the adjusted dosimetric challenge (mean PD20 ratio 2.31, 95% CI 1.57-3.40; p=0.0004). Tidal dosimetric methacholine challenge using adjustment of nebuliser output produces results with good repeatability. The results of this adjusted dosimetric method differed from the continuous output method, underscoring that the results of different methacholine challenge methodologies may not be directly comparable.