Low-Dose Aspirin and Progression of Age-Related Hearing Loss: A Secondary Analysis of the ASPREE Randomized Clinical Trial.

Importance: Age-related hearing loss is common in an aging population, affecting communication and contributing to a worsened quality of life. It occurs as a result of cochlear degeneration and may be further exacerbated by inflammation and microvascular changes, as observed in animal models. Objective: To compare the effect of daily low-dose aspirin vs placebo on the progression of age-related hearing loss in healthy older adults. Design, Setting, and Participants: A prespecified secondary analysis was conducted of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial. Participants were 279 healthy community-dwelling individuals living in Australia who were aged 70 years or older and free of overt cardiovascular diseases, dementia, and life-limiting illnesses. Participants were recruited between January 1, 2010, and December 31, 2014, and followed up over 3 years. Statistical analysis was completed from June to December 2023. Intervention: A 100-mg daily dose of enteric-coated aspirin or matching placebo. Main Outcomes and Measures: Hearing measures were air conduction audiometry and binaural speech perception in noise. Assessments were conducted at baseline, 18 months, and 3 years. The change from baseline hearing measures were analyzed using an intention to treat approach. Aspirin and placebo were compared using mixed linear regression models adjusting for age, sex, diabetes, and smoking. Results: Of 279 participants, 154 (55%) were male, and the median age at baseline was 73.1 years (IQR, 71.5-76.2 years). A total of 98 of 138 participants (71%) in the aspirin group and 94 of 141 participants (67%) in the placebo group reported experiencing hearing loss at baseline. Compared with placebo, aspirin did not affect the changes in mean (SD) 4-frequency average hearing threshold from baseline to year 3 (aspirin: baseline, 27.8 [13.3] dB; year 3, 30.7 [13.7] dB; difference, 3.3 [3.9] dB; placebo: baseline, 27.5 [12.6] dB; year 3, 30.9 [13.8] dB; difference, 3.0 [4.8] dB; P = .55) nor any other tested frequencies. An increase in air conduction threshold indicates a deterioration in hearing. Similarly, for the mean (SD) speech reception threshold, there was no significant difference observed between the aspirin and placebo group at the year 3 follow-up assessment (aspirin: baseline, -9.9 [3.8] dB; year 3, -9.1 [3.8] dB; difference, 0.9 [2.9] dB; placebo: baseline, -10.5 [7.1] dB; year 3, -9.6 [4.1] dB; difference, 0.9 [5.9] dB; P = .86). The findings were consistent across sex, age groups, diabetic and smoking status. Conclusions and Relevance: In this secondary analysis of the ASPREE randomized clinical trial, low-dose aspirin did not affect the progression of age-related hearing loss. More investigation is warranted on whether a longer follow-up or the use of a more powerful anti-inflammatory agent might prove beneficial. Trial Registration: anzctr.org.au Identifier: ACTRN12614000496617.

Characteristic Pressure Waveforms Can Distinguish Airway Collapse Patterns in Sleep Apnea Patients: A Pilot Study.

Objective: To use pharyngeal pressure recordings to distinguish different upper airway collapse patterns in obstructive sleep apnea (OSA) patients, and to assess whether these pressure recordings correlate with candidacy assessment for hypoglossal nerve stimulator (HGNS) implantation. Study Design: Prospective case series. Setting: Single tertiary-quaternary care academic center. Methods: Subjects with OSA prospectively underwent simultaneous drug-induced sleep endoscopy (DISE) and transnasal pharyngeal pressure recording with a pressure-transducing catheter. Pressure was recorded in the nasopharynx and oropharynx, and endoscopic collapse patterns were classified based on site, extent, and direction of collapse. Pressure recordings were classified categorically by waveform shape as well as numerically by inspiratory and expiratory amplitudes and slopes. Waveform shape, amplitude, and slope were then compared with the endoscopic findings. Results: Twenty-five subjects with OSA were included. Nasopharyngeal waveform shape was associated with the extent of collapse at the level of the palate (P = .001). Oropharyngeal waveform shape was associated with anatomical site of collapse (P < .001) and direction of collapse (P = .019) below the level of the palate. Pressure amplitudes and slopes were also associated with the extent of collapse at various sites. Waveform shape was also associated with favorable collapse pattern on endoscopy for HGNS implantation (P = .043), as well as surgical candidacy for HGNS (P = .004). Conclusion: Characteristic pharyngeal pressure waveforms are associated with different airway collapse patterns. Pharyngeal pressure is a promising adjunct to DISE in the sleep surgery candidacy evaluation.

Physiologic and anatomic determinants of hyoid motion during drug-induced sleep endoscopy.

PURPOSE: To examine factors accounting for differences in hyoid motion during obstructive breathing events amongst obstructive sleep apnea (OSA) patients. METHODS: This was a prospective cohort study from June 2022 to October 2022. Patients with OSA undergoing evaluation for PAP alternative therapies with drug-induced sleep endoscopy with positive airway pressure titration (DISE-PAP). All patients underwent DISE-PAP and concurrent hyoid-focused ultrasound. DISE-PAP enabled measurement of airway physiology (flow, respiratory effort) and airway collapsibility (pharyngeal opening pressure, PhOP). Hyoid-ultrasound enabled hyoid bone movement during obstructive breathing. Respiratory effort was measured using a retro-epiglottic pressure-sensitive catheter. Hyoid position was measured using a standardized, awake, CT protocol. Regression analyses adjusted for age, race, sex, and BMI were performed to associate indices of respiratory effort and CT data with hyoid motion. RESULTS: On average, the 26 patients in this cohort were older (63.9 ± 10.5 years), male (69%), overweight (29.6 ± 3.99 kg/m2), and with moderate-to-severe OSA (26.8 ± 10.4 events/hour). Greater respiratory effort was associated with increased hyoid motion (ß [95% CI] = 0.034 [0.016,0.052], standardized ß = 0.261,p = 0.0003). Higher hyoid position was associated with greater hyoid displacement (ß [95% CI] = -0.20 [-0.38,-0.01], Standardized ß = -0.57, p = 0.036). CONCLUSION: Our data demonstrate that greater respiratory effort, higher hyoid position, and higher airway collapsibility, but not airflow, are associated with greater hyoid motion during obstructive breathing in DISE. These findings suggest that downward hyoid movement represents a compensatory response to upper airway obstruction. Further studies should investigate the vectors of hyoid motion to better understand its role in sleep-related airway collapse.

Participation in Physical, Cognitive, and Social Activities and the Association with Mobility Disability Transitions in Older Adults.

Development of late-life mobility disability is a dynamic process of transitions between worsening and improving. We tested associations between participation in physical, social, and cognitive activity with mobility disability transitions. Participants (N=2,758, age 78.1 years [SD: 7.7]) from two Rush Alzheimer's Disease Center cohorts completed annual mobility disability questionnaires for 7.6 (SD: 4.4) years. First-order Markov transition models tested associations between baseline self-reported physical, social, and cognitive activity with bidirectional transitions in mobility disability score increases (worsening) and decreases (improving) between consecutive visits. Overall, 75.5% of participants experienced ≥1 transition among 18,318 pairs of consecutive visits-4,174 of which were worsening and 2,606 were improving transitions. Adjusting for covariates, higher participation in each activity type was associated with lower odds of worsening (physical OR=0.71, 95% CI: 0.67-0.75; social OR=0.64, 95% CI: 0.58-0.70; and cognitive OR=0.79, 95% CI: 0.74-0.85), and higher odds of improving (physical OR=1.20, 95% CI: 1.11-1.28; social OR=1.45, 95% CI: 1.30-1.61; and cognitive OR=1.12, 95% CI: 1.03-1.22) in separate models. In combined models, physical and social activity remained associated with worsening and improving; cognitive activity was only associated with worsening. Physical, social, and cognitive activity engagement contributes to lower odds of worsening mobility disability and may promote recovery.

Outcome risk model development for heterogeneity of treatment effect analyses: a comparison of non-parametric machine learning methods and semi-parametric statistical methods.

BACKGROUND: In randomized clinical trials, treatment effects may vary, and this possibility is referred to as heterogeneity of treatment effect (HTE). One way to quantify HTE is to partition participants into subgroups based on individual's risk of experiencing an outcome, then measuring treatment effect by subgroup. Given the limited availability of externally validated outcome risk prediction models, internal models (created using the same dataset in which heterogeneity of treatment analyses also will be performed) are commonly developed for subgroup identification. We aim to compare different methods for generating internally developed outcome risk prediction models for subject partitioning in HTE analysis. METHODS: Three approaches were selected for generating subgroups for the 2,441 participants from the United States enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial. An extant proportional hazards-based outcomes predictive risk model developed on the overall ASPREE cohort of 19,114 participants was identified and was used to partition United States' participants by risk of experiencing a composite outcome of death, dementia, or persistent physical disability. Next, two supervised non-parametric machine learning outcome classifiers, decision trees and random forests, were used to develop multivariable risk prediction models and partition participants into subgroups with varied risks of experiencing the composite outcome. Then, we assessed how the partitioning from the proportional hazard model compared to those generated by the machine learning models in an HTE analysis of the 5-year absolute risk reduction (ARR) and hazard ratio for aspirin vs. placebo in each subgroup. Cochran's Q test was used to detect if ARR varied significantly by subgroup. RESULTS: The proportional hazard model was used to generate 5 subgroups using the quintiles of the estimated risk scores; the decision tree model was used to generate 6 subgroups (6 automatically determined tree leaves); and the random forest model was used to generate 5 subgroups using the quintiles of the prediction probability as risk scores. Using the semi-parametric proportional hazards model, the ARR at 5 years was 15.1% (95% CI 4.0-26.3%) for participants with the highest 20% of predicted risk. Using the random forest model, the ARR at 5 years was 13.7% (95% CI 3.1-24.4%) for participants with the highest 20% of predicted risk. The highest outcome risk group in the decision tree model also exhibited a risk reduction, but the confidence interval was wider (5-year ARR = 17.0%, 95% CI= -5.4-39.4%). Cochran's Q test indicated ARR varied significantly only by subgroups created using the proportional hazards model. The hazard ratio for aspirin vs. placebo therapy did not significantly vary by subgroup in any of the models. The highest risk groups for the proportional hazards model and random forest model contained 230 participants each, while the highest risk group in the decision tree model contained 41 participants. CONCLUSIONS: The choice of technique for internally developed models for outcome risk subgroups influences HTE analyses. The rationale for the use of a particular subgroup determination model in HTE analyses needs to be explicitly defined based on desired levels of explainability (with features importance), uncertainty of prediction, chances of overfitting, and assumptions regarding the underlying data structure. Replication of these analyses using data from other mid-size clinical trials may help to establish guidance for selecting an outcomes risk prediction modelling technique for HTE analyses.

Differences in Positive Airway Pressure Requirements in Obstructive Sleep Apnea Between Black and White Patients.

OBJECTIVE: There are disparities between Black and White patients in the utilization of positive airway pressure (PAP) alternatives for obstructive sleep apnea (OSA). Given low utilization rates among Black patients, there is limited knowledge of PAP alternative outcomes in this group. Therapeutic PAP levels are clinically accessible measures that have been shown to predict PAP alternative outcomes. Herein, we examined differences in PAP requirements between Black and White patients in a large clinical sample. STUDY DESIGN: Cross-sectional. SETTING: Academic sleep center. METHODS: We included OSA patients prescribed autoadjusting PAP between January 2018 and 2020 with baseline apnea-hypopnea index (AHI) ≥ 10. Mean and 90th percentile PAP levels were compared between White and Black patients who used PAP for ≥1 hour daily using linear regression controlling for age, sex, body mass index (BMI), AHI, oxygen saturation nadir, and mask type. RESULTS: There were 157 Black and 234 White patients who were generally obese (BMI, 37.3 ± 8.7) with severe OSA (AHI, 36.9 ± 25.6). Black patients had a 0.68 cm higher (95% confidence interval [CI]: 0.36, 1.35) mean PAP level and 0.85 cm H2O higher (95% CI: 0.36, 1.35) 90th percentile PAP level than white patients. Although statistically significant, differences were small and not clinically meaningful. CONCLUSION: Black and White OSA patients had clinically insignificant differences in PAP requirements, suggesting comparable upper airway collapsibility. Considering the predictive value of therapeutic PAP levels, our findings suggest Black and White patients may have comparable PAP alternative responses from a collapsibility standpoint. Future studies should explore reasons for low utilization of PAP alternatives among Black patients.

Mechanistic insights from sleep endoscopy related to oronasal mask failures: a case report.

A 71-year-old male with severe obstructive sleep apnea (OSA) and nasal septal deviation presented to a positive airway pressure (PAP) alternatives clinic due to persistent obstructive events on both continuous PAP (CPAP) and bilevel PAP (BPAP) therapy delivered via oronasal mask. He underwent drug-induced sleep endoscopy with PAP titration (DISE-PAP) to determine the mechanism of oronasal mask failure. A nasal mask was also applied and titrated for comparison. DISE-PAP showed tongue base collapse which resolved at low pressure using a nasal mask. Application of an oronasal mask increased minimum therapeutic PAP level. Tightening the mask worsened tongue base collapse, which was not resolved by increasing the PAP level. Following nasal surgery, the patient was able to tolerate nasal CPAP at low therapeutic pressure, which resulted in both objective and subjective improvement is his OSA. This case highlights the ability of DISE-PAP to determine the mechanistic cause of oronasal mask failure.

Concordance With Screening and Treatment Guidelines for Chronic Kidney Disease in Type 2 Diabetes.

Importance: Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care. Objective: To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D. Design, Setting, and Participants: This retrospective cohort study was performed at 20 health care systems contributing data to the US National Patient-Centered Clinical Research Network. To evaluate concordance with CKD screening guidelines, adults with an outpatient clinician visit linked to T2D diagnosis between January 1, 2015, and December 31, 2020, and without known CKD were included. A separate analysis reviewed prescription of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with CKD (estimated glomerular filtration rate [eGFR] of 30-90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] of 200-5000 mg/g) and an outpatient clinician visit for T2D between October 1, 2019, and December 31, 2020. Data were analyzed from July 8, 2022, through June 22, 2023. Exposures: Demographics, lifestyle factors, comorbidities, medications, and laboratory results. Main Outcomes and Measures: Screening required measurement of creatinine levels and UACR within 15 months of the index visit. Treatment reflected prescription of ACEIs or ARBs and SGLT2 inhibitors within 12 months before or 6 months following the index visit. Results: Concordance with CKD screening guidelines was assessed in 316 234 adults (median age, 59 [IQR, 50-67] years), of whom 51.5% were women; 21.7%, Black; 10.3%, Hispanic; and 67.6%, White. Only 24.9% received creatinine and UACR screening, 56.5% received 1 screening measurement, and 18.6% received neither. Hispanic ethnicity was associated with lack of screening (relative risk [RR], 1.16 [95% CI, 1.14-1.18]). In contrast, heart failure, peripheral arterial disease, and hypertension were associated with a lower risk of nonconcordance. In 4215 patients with CKD and albuminuria, 3288 (78.0%) received an ACEI or ARB; 194 (4.6%), an SGLT2 inhibitor; and 885 (21.0%), neither therapy. Peripheral arterial disease and lower eGFR were associated with lack of CKD treatment, while diuretic or statin prescription and hypertension were associated with treatment. Conclusions and Relevance: In this cohort study of patients with T2D, fewer than one-quarter received recommended CKD screening. In patients with CKD and albuminuria, 21.0% did not receive an SGLT2 inhibitor or an ACEI or an ARB, despite compelling indications. Patient-level factors may inform implementation strategies to improve CKD screening and treatment in people with T2D.

Gender-specific analysis of social connection patterns and risk of dementia in community-dwelling older people.

INTRODUCTION: Poor social connection is considered a risk factor for dementia. Since socializing behaviors may cluster together or act compensatorily, we aimed to investigate social connection patterns and their association with dementia, for men and women separately. METHODS: A total of 12,896 community-dwelling older adults (mean ± SD age: 75.2 ± 4.3 years, 54% women) without major cognitive impairment were included. Latent class analysis was conducted using 24 baseline social connection indicators. Cox proportional hazards regression was used to estimate the association between latent classes and incident dementia over 12 (median: 8.4) years follow-up. RESULTS: Three distinct classes were identified in both genders: strong social connections with an intermediate friend-relative network (Class 1: men, 43.8%; women, 37.9%), weak social connections (Class 2: men, 29.6%; women, 27.4%), and strong social connections with a larger friend-relative network (Class 3: men, 26.6%; women, 34.7%). Compared to Class 1, men in Class 2 (HR: 1.38, 95% CI: 1.08-1.77) and women in Class 3 (HR: 1.27, 95% CI: 1.01-1.60) had an increased risk of dementia. DISCUSSION: Dementia risk varies with different social connection patterns among older men and women. HIGHLIGHTS: Three distinct social connection patterns were identified based on 24 indicators. These patterns were related to dementia risk differently in men and women. In men, a weak social connection pattern was associated with a higher dementia risk. In women, a strong social connection with a relatively larger friend-relative network was associated with a greater dementia risk.

Correlates of missed or late versus timely diagnosis of dementia in healthcare settings.

INTRODUCTION: There is limited evidence about factors related to the timeliness of dementia diagnosis in healthcare settings. METHODS: In five prospective cohorts at Rush Alzheimer's Disease Center, we identified participants with incident dementia based on annual assessments and examined the timing of healthcare diagnoses in Medicare claims. We assessed sociodemographic, health, and psychosocial correlates of timely diagnosis. RESULTS: Of 710 participants, 385 (or 54%) received a timely claims diagnosis within 3 years prior to or 1 year following dementia onset. In logistic regressions accounting for demographics, we found Black participants (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.21 to 3.82) and those with better cognition at dementia onset (OR = 1.48, 95% CI: 1.10 to 1.98) were at higher odds of experiencing a diagnostic delay, whereas participants with higher income (OR = 0.89, 95% CI: 0.81 to 0.97) and more comorbidities (OR = 0.94, 95% CI: 0.89 to 0.98) had lower odds. DISCUSSION: We identified characteristics of individuals who may miss the optimal window for dementia treatment and support. HIGHLIGHTS: We compared the timing of healthcare diagnosis relative to the timing of incident dementia based on rigorous annual evaluation. Older Black adults with lower income, higher cognitive function, and fewer comorbidities were less likely to be diagnosed in a timely manner by the healthcare system.

The impact of incident stroke on cognitive trajectories in later life.

BACKGROUND: Cognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals. METHODS: 19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke. RESULTS: During a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants. CONCLUSIONS: These findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention.

Association Between Soft Tissue Measures From Computed Tomography and Upper Airway Collapsibility on Drug-Induced Sleep Endoscopy.

OBJECTIVE: Positive airway pressure (PAP) titration during drug-induced sleep endoscopy (DISE) provides objective measures of upper airway collapsibility. While skeletal measurements relate to collapsibility measures on DISE, the influence of soft tissue dimensions on upper airway collapsibility is not known. We analyzed the relationship of measures of upper airway soft tissue volumes, specifically soft palate, pharyngeal lateral walls, and tongue, with metrics of collapsibility. STUDY DESIGN: Cross-sectional analysis from a prospective cohort. SETTING: Academic medical center. METHODS: Patients seeking PAP alternative therapies for obstructive sleep apnea (OSA) underwent standardized supine computed tomography (CT) acquisition and DISE protocols. The CT analysis primarily focused on soft tissue volumes and, secondarily, on airway and skeletal volumetric measures. DISE with PAP administration (DISE-PAP) enabled the determination of the pressure at which inspiratory airflow first commenced (pharyngeal critical pressure, PcritA) and the pressure at which inspiratory flow limitation was abolished (pharyngeal opening pressure, PhOP). Both unadjusted and adjusted correlation analyses were performed to understand the relationship between upper airway anatomy and either PcritA or PhOP. RESULTS: One hundred thirty-nine subjects completed both CT and DISE-PAP. On average, patients were male (70.5%), white (84.2%), middle-aged (56.6 ± 13.5 years), and overweight (29.6 ± 4.7 kg/m2), with moderate-severe apnea-hypopnea index (29.7 ± 21.3 events/h). Adjusted for age, sex, body mass index, and skeletal volumes, soft palate, and lateral pharyngeal wall volumes were not associated with PhOP or PcritA, but a larger tongue was associated with more positive PhOP (⍴ = 0.20, P = .02), and more positive PcritA (⍴ = 0.16, P = .07). Exploratory analyses revealed smaller minimum cross-sectional retropalatal area and intramandibular volume were also associated with increased collapsibility measures. CONCLUSION: After controlling for clinical factors and skeletal volume, greater tongue volume was associated with more severe collapsibility during DISE. These results, in concert with previous work, suggest that greater tongue volume in a smaller skeletal dimensions contribute to the severity of airway collapsibility, a key driver of OSA pathogenesis.

Kidney and Cardiovascular Effectiveness of Empagliflozin Compared With Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes.

Placebo-controlled trials of sodium-glucose co-transporter-2 inhibitors demonstrate kidney and cardiovascular benefits for patients with type 2 diabetes and chronic kidney disease (CKD). We used real-world data to compare the kidney and cardiovascular effectiveness of empagliflozin to dipeptidyl peptidase-4 inhibitors (DPP4is), a commonly prescribed antiglycemic medication, in a diverse population with and without CKD. Using electronic health record data from 20 large US health systems, we leveraged propensity overlap weighting to compare the outcomes for empagliflozin and DPP4i initiators with type 2 diabetes between 2016 and 2020. The primary composite kidney outcome included 40% estimated glomerular filtration rate decrease, incident end-stage kidney disease, or all-cause mortality through 2 years or censoring. We also assessed cardiovascular and safety outcomes. Of 62,197 new users, 20,279 initiated empagliflozin and 41,918 initiated DPP4i. Over a median follow-up of 1.1 years, empagliflozin prescription was associated with a lower risk of the primary outcome (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.65 to 0.87) than DPP4is. The risks for mortality (HR 0.76, 95% CI 0.62 to 0.92) and a cardiovascular composite of stroke, myocardial infarction, or all-cause mortality (HR 0.81, 95% CI 0.70 to 0.95) were also lower for empagliflozin initiators. No difference in heart failure hospitalization risk between groups was observed. Genital mycotic infections were more common in patients prescribed empagliflozin (HR 1.72, 95% CI 1.58 to 1.88). Empagliflozin was associated with a lower risk of the primary outcome in patients with CKD (HR 0.68, 95% CI 0.53 to 0.88) and those without CKD (HR 0.79, 95% CI 0.67 to 0.94). In conclusion, the initiation of empagliflozin was associated with a significantly lower risk of kidney and cardiovascular outcomes than DPP4is over a median of just over 1 year. The association with a lower risk for clinical outcomes was apparent even for patients without known CKD at baseline.

Social Activities and Risk of Dementia in Community-Dwelling Older People: Gender-Specific Findings From a Prospective Cohort Study.

OBJECTIVES: This study examines the gender-specific associations between a wide range of social activities and dementia risk. METHODS: A prospective cohort study was conducted involving community-dwelling older Australians (≥70 years) without significant cognitive impairment at enrolment. During the first year of enrolment, we assessed 25 self-reported social activities covering various aspects, including support from relatives and friends, community participation, social interactions with surroundings, and loneliness. Dementia diagnosis followed DSM-IV criteria, adjudicated by an international expert panel. To estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between social activities and dementia, we performed Cox proportional hazards models, adjusting for age, educational attainment, baseline global cognition, and depressive symptoms. RESULTS: Among 9,936 participants who completed all social activity questionnaires (median [IQR] age: 73.4 [71.6-77.1] years; 47.4% men), dementia was diagnosed in 3.8% of men (n = 181/4,705) and 2.6% of women (n = 138/5,231) over a median 6.4 years (IQR: 5.3-7.6, range: 0.2-10.1) follow-up. Gender-specific relationships emerged: caregiving for a person with illness/disability in women (HR: 0.65, 95% CI: 0.42-0.99), and having ≥9 relatives feeling close to call for help in men (HR: 0.56, 95% CI: 0.33-0.96; reference <9 relatives) were associated with reduced dementia risk. Unexpectedly, in women, having ≥5 friends with whom they felt comfortable discussing private matters were associated with a greater dementia risk (HR: 1.69, 95% CI: 1.10-2.59; reference ≤2 friends). Imputed models further identified that babysitting/childminding was associated with lower dementia risk in men (HR: 0.75, 95% CI: 0.56-0.99). No other social activities showed significant associations with dementia. DISCUSSION: This study provides evidence of social activities influencing dementia risk. Further investigations are required to uncover the mechanisms driving these observed relationships.

Strategies for primary HPV test-based cervical cancer screening programme in resource-limited settings in India: Results from a quasi-experimental pragmatic implementation trial.

BACKGROUND: In order for low and middle income countries (LMIC) to transition to Human Papilloma Virus (HPV) test based cervical cancer screening, a greater understanding of how to implement these evidence based interventions (EBI) among vulnerable populations is needed. This paper documents outcomes of an implementation research on HPV screening among women from tribal, rural, urban slum settings in India. METHODS: A mixed-method, pragmatic, quasi-experimental trial design was used. HPV screening on self-collected cervical samples was offered to women aged 30-60 years. Implementation strategies were 1) Assessment of contextual factors using both qualitative and quantitative methods like key informant interviews (KII), focus group discussions (FGDs), pre-post population sample surveys, capacity assessment of participating departments 2) enhancing provider capacity through training workshops, access to HPV testing facility, colposcopy, thermal ablation/cryotherapy at the primary health care centers 3) community engagement, counselling for self-sampling and triage process by frontline health care workers (HCWs). Outcomes were assessed using the RE-AIM (Reach, Effectiveness, adoption, implementation, maintenance) framework. RESULTS: Screening rate in 8 months' of study was 31.0%, 26.7%, 32.9%, prevalence of oncogenic HPV was 12.1%, 3.1%, 5.5%, compliance to triage was 53.6%, 45.5%, 84.6% in tribal, urban slum, rural sites respectively. Pre-cancer among triage compliant HPV positive women was 13.6% in tribal, 4% in rural and 0% among urban slum women. Unique challenges faced in the tribal setting led to programme adaptations like increasing honoraria of community health workers for late-evening work and recalling HPV positive women for colposcopy by nurses, thermal ablation by gynaecologist at the outreach camp site. CONCLUSIONS: Self-collection of samples combined with HCW led community engagement activities, flexible triage processes and strengthening of health system showed an acceptable screening rate and better compliance to triage, highlighting the importance of identifying the barriers and developing strategies suitable for the setting. TRIAL REGISTRATION: CTRI/2021/09/036130.

The Whimsical Nature of Airway Obstruction during Drug-Induced Sleep Endoscopy.

A 47-year-old male patient diagnosed with severe obstructive sleep apnea (OSA) sought alternatives to positive airway pressure, prompting evaluation with drug-induced sleep endoscopy (DISE). He underwent a specialized DISE with nasal airflow and pharyngeal pressure monitoring. During obstructive apneas, airflow and pressure signals demonstrated dynamic, multilevel upper airway collapse, with shifting sites of airflow obstruction as respiratory effort increased. This case report illustrates how quantitative airflow and pressure measurements can complement the standard DISE exam and aid in surgical decision-making. Laryngoscope, 2024.

State-Dependent Biomechanical Behavior of Oropharyngeal Structures in Apneic and Control Subjects: A Proof-of-Concept Study.

Rationale: Apneic individuals have reduced airway caliber during sleep. The biomechanical changes in upper airway anatomy contributing to this airway narrowing are largely unknown. Objectives: We sought to investigate the state-dependent (wake vs. sleep) biomechanical behavior of the upper airway soft-tissue and craniofacial structures. Methods: Upper airway magnetic resonance imaging was performed in 15 sleep-deprived control subjects (apnea-hypopnea index, <5; 0.3 ± 0.5 events per hour) and 12 sleep-deprived apneic subjects (apnea-hypopnea index, ⩾5; 35.2 ± 18.1 events per hour) during wake and sleep and analyzed for airway measures and soft-tissue/mandibular movement. Results: In the retropalatal region, control subjects showed sleep-dependent reductions (P ⩽ 0.037) in average cross-sectional airway area (CSA), minimum CSA, and anteroposterior and lateral dimensions. Apneic subjects showed sleep-dependent reductions (P ⩽ 0.002) in average CSA, minimum CSA, and anteroposterior and lateral dimensions. In the retroglossal region, control subjects had no sleep-dependent airway reductions. However, apneic subjects had sleep-dependent reductions in minimal CSA (P = 0.001) and lateral dimensions (P = 0.014). Control subjects only showed sleep-dependent posterior movement of the anterior-inferior tongue octant (P = 0.039), whereas apneic subjects showed posterior movement of the soft palate (P = 0.006) and all tongue octants (P ⩽ 0.012). Sleep-dependent medial movement of the lateral walls was seen at the retropalatal minimum level (P = 0.013) in control subjects and at the retropalatal and retroglossal minimum levels (P ⩽ 0.017) in apneic subjects. There was posterior movement of the mandible in apneic subjects (P ⩽ 0.017). Conclusions: During sleep, control and apneic subjects showed reductions in retropalatal airway caliber, but only the apneic subjects showed retroglossal airway narrowing. Reductions in anteroposterior and lateral airway dimensions were primarily due to posterior soft palate, tongue and mandibular movement and to medial lateral wall movement. These data provide important initial insights into obstructive sleep apnea pathogenesis.

The Effect of Surgical Therapy for Obstructive Sleep Apnea on Blood Pressure and Peripheral Arterial Tonometry.

OBJECTIVE: To determine the effect of upper airway surgery on cardiovascular function in patients with obstructive sleep apnea (OSA). STUDY DESIGN: A prospective, self-controlled study from 2018 to 2023. SETTING: Two academic medical centers. METHODS: Seventy-four patients underwent surgery for OSA, including: tonsillectomy, adenoidectomy, epiglottidectomy, modified uvulopalatopharyngoplasty, maxillary expansion, and maxillomandibular advancement. Twenty-four-hour ambulatory blood pressure (BP), peripheral arterial tonometry (PAT)-based home sleep study, and sleep-related patient-reported outcomes (PROs) were captured preoperatively and at 6 months postoperatively. Paired T-tests evaluated changes in outcomes after surgery. RESULTS: Forty-one patients successfully completed preoperative and postoperative assessments. Patients were generally middle-aged (43.8 ± 12.5 years), obese (BMI 33.0 ± 5.8 kg/m2), male (68%), White (71%), and had severe OSA (apnea-hypopnea index [AHI] 33.9 ± 29.5 events/h). The 4% oxygen desaturation index (ODI) decreased from 30.7 ± 27.1 to 12.2 ± 13.6 events/h (P < .01) after surgery. There was no significant difference in 24-h BP following surgery, though clinically meaningful reductions in nocturnal systolic (-1.95 [-5.34, 1.45] mmHg) and nocturnal diastolic (-2.30 [-5.11, 0.52] mmHg) blood pressure were observed. Stratified analysis showed patients undergoing skeletal surgery (n = 17) demonstrated larger average reductions compared to those undergoing soft tissue surgery in nocturnal systolic (-4.12 [-7.72, -0.51] vs -0.10 [-5.78, 5.58] mmHg) and nocturnal diastolic (-3.94 [-7.90, 0.01] vs -0.90 [-5.11, 3.31] mmHg) pressures. No meaningful changes were observed in PAT Autonomic Index (PAI) measurements. CONCLUSION: Surgical therapy for OSA did not demonstrate statistically significant improvements in 24-h BP. However, clinically meaningful reductions in nocturnal BP were observed, particularly in skeletal surgery patients, supporting the need for larger studies of cardiovascular outcomes following OSA surgery.

The Prevalence of Sentinel Central Events (SCent) During Drug-Induced Sleep Endoscopy.

OBJECTIVE: With the recent addition of airflow and respiratory effort channels, our group has observed central and mixed apnea events during drug-induced sleep endoscopy (DISE). We measured the frequency and timing of sentinel central and/or mixed events (SCents), as well as assessed for differences in velum, oropharynx, tongue, and epiglottis (VOTE) classification compared to obstructive events. STUDY DESIGN: Prospective single-cohort study. SETTING: Tertiary Care Academic Medical Center. METHODS: Patients underwent DISE between June 2020 and November 2022. Nasal airflow, thoracoabdominal effort belt signals, and videoendoscopy were simultaneously captured. Demographics, sleep study, and DISE data were compared among patients with and without SCents using Student's T tests or χ2 tests. RESULTS: On average, the cohort (n = 103) was middle-aged (53.5 ± 12.1 years), overweight (body mass index of 29.7 ± 5.3 kg/m2), and had severe obstructive sleep apnea (apnea-hypopnea index of 30.7 ± 18.7 events/h). Forty-seven patients (46%) were found to have at least 1 SCent. Among those with SCent, 45 (95.7%) transitioned to obstructive pathology after an average of 7.91 ± 2.74 minutes, with at least 95% of patients expected to do so within 12.57 minutes. Twenty-nine out of 47 patients (61.2% [95% confidence interval: 46.4.9%, 75.5%]) with SCent had meaningful differences between central/mixed and obstructive VOTE scores. CONCLUSION: Central events were present in almost half of our cohort. At least 95% of patients were expected to transition to obstructive events within 12 to 13 minutes of propofol initiation. In addition, over half of patients demonstrate significantly different VOTE scores between central and obstructive events. These factors should raise awareness of central events and scoring passive apneas during DISE and consider delaying VOTE scoring.