Risk factors of undiagnosed and uncontrolled hypertension in primary care patients with hypertension: a cross-sectional study.

BACKGROUND: Hypertension is a common heart condition in the United States (US) and severely impacts racial and ethnic minority populations. While the understanding of hypertension has grown considerably, there remain gaps in US healthcare research. Specifically, there is a lack of focus on undiagnosed and uncontrolled hypertension in primary care settings. AIM: The present study investigates factors associated with undiagnosed and uncontrolled hypertension in primary care patients with hypertension. The study also examines whether Black/African Americans are at higher odds of undiagnosed and uncontrolled hypertension compared to White patients. METHODS: A cross-sectional study was conducted using electronic health records (EHR) data from the University of Utah primary care health system. The study included for analysis 24,915 patients with hypertension who had a primary care visit from January 2020 to December 2020. Multivariate logistic regression assessed the odds of undiagnosed and uncontrolled hypertension. RESULTS: Among 24,915 patients with hypertension, 28.6% (n = 7,124) were undiagnosed and 37.4% (n = 9,319) were uncontrolled. Factors associated with higher odds of undiagnosed hypertension included age 18-44 (2.05 [1.90-2.21]), Hispanic/Latino ethnicity (1.13 [1.03-1.23]),  Medicaid (1.43 [1.29-1.58]) or self-pay  (1.32 [1.13-1.53]) insurance, CCI 1-2 (1.79 [1.67-1.92]), and LDL-c ≥ 190 mg/dl (3.05 [1.41-6.59]). For uncontrolled hypertension, risk factors included age 65+ (1.11 [1.08-1.34]), male (1.24 [1.17-1.31]), Native-Hawaiian/Pacific Islander (1.32 [1.05-1.62])  or Black/African American race (1.24 [1.11-1.57]) , and self-pay insurance (1.11 [1.03-1.22]). CONCLUSION: The results of this study suggest that undiagnosed and uncontrolled hypertension is prevalent in primary care. Critical risk factors for undiagnosed hypertension include younger age, Hispanic/Latino ethnicity, very high LDL-c, low comorbidity scores, and self-pay or medicaid insurance. For uncontrolled hypertension, geriatric populations, males, Native Hawaiian/Pacific Islanders, and Black/African Americans, continue to experience greater burdens than their counterparts. Substantial efforts are needed to strengthen hypertension diagnosis and to develop tailored hypertension management programs in primary care, focusing on these populations.

Association between a Recalled Positive Airway Pressure (PAP) Device and Incident Cancer: A Population-Based Study.

BACKGROUND: The real-world consequences of a Philips/Respironics recall for positive airway pressure (PAP) devices distributed between 2009 and 2021 are unknown. METHODS: We conducted a retrospective population-based study using health administrative databases (Ontario, Canada) on all new adult PAP users identified through the provincial funding system, free of cancer at baseline, who initiated (claimed) PAP treatment between 2012 and 2018. Everyone was followed from the PAP claim date to the earliest of incident cancer diagnosis, death, or the end of the follow-up (March 2022). We used inverse probability of treatment weighting to balance baseline characteristics between individuals on recalled devices and those on devices from other manufacturers. Weighted hazard ratios of incident cancer were compared between groups. RESULTS: Of 231 692 individuals identified, 58 204 (25.1%) claimed recalled devices, and 173 488 (74.9%) from other manufacturers. A meaningful baseline difference between groups (standardised difference≥0.10) was noted only by location-relevant covariates; other variables were mostly equally distributed (standardised differences≤0.06). Over a median follow-up of 6.3 years (IQR: 4.9-8.0), 11 166 (4.8%) developed cancer: unadjusted rates per 10 000 Person-Year (95 CI%) of 78.8 (76.0-81.7) in the recall group versus74.0 (72.4-75.6) in others (p=0.0034). Propensity score weighting achieved excellent balance in baseline characteristics between groups (standardised differences≤0.07). On a weighted sample, there was no statistical difference in the hazard of incident cancer between groups: cause-specific hazard ratio (recalled versus others) of 0.97, 95% CI: 0.89-1.06. CONCLUSION: In our real-world population study, compared to other manufacturers and adjusting for confounders, recalled devices do not appear to be independently associated with developing cancer.

Development and usability of an EHR-driven hypertension disparities dashboard in primary care: A qualitative study.

Hypertension disparities persist and remain high among racial and ethnic minority populations in the United States (US). Data-driven approaches based on electronic health records (EHRs) in primary care are seen as a strong opportunity to address this situation. This qualitative study evaluated the development, sustainability, and usability of an EHR-integrated hypertension disparities dashboard for health care professionals in primary care. Ten semi-structured interviews, exploring the approach and sustainability, as well as eight usability interviews, using the think aloud protocol were conducted with quality improvement managers, data analysts, program managers, evaluators, and primary care providers. For the results, dashboard development steps include having clear goals, defining a target audience, compiling data, and building multidisciplinary teams. For sustainability, the dashboard can enhance understanding of the social determinants of health or to inform QI projects. In terms of dashboard usability, positive aspects consisted of the inclusion of summary pages, patient's detail pages, and hover-over interface. Important design considerations were refining sorting functions, gender inclusivity, and increasing dashboard visibility. In sum, an EHR-driven dashboard can be a novel tool for addressing hypertension disparities in primary care. It offers a platform where clinicians can identify patients for culturally tailored interventions. Factors such as physician time constraints, data definitions, comprehensive patient demographic information, end-users, and future sustenance, should be considered before implementing a dashboard. Additional research is needed to identify practices for integrating a dashboard into clinical workflow for hypertension.

Long-term outcomes after treatment of delirium during critical illness with antipsychotics (MIND-USA): a randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Delirium is common during critical illness and is associated with long-term cognitive impairment and disability. Antipsychotics are frequently used to treat delirium, but their effects on long-term outcomes are unknown. We aimed to investigate the effects of antipsychotic treatment of delirious, critically ill patients on long-term cognitive, functional, psychological, and quality-of-life outcomes. METHODS: This prespecified, long-term follow-up to the randomised, double-blind, placebo-controlled phase 3 MIND-USA Study was conducted in 16 hospitals throughout the USA. Adults (aged ≥18 years) who had been admitted to an intensive care unit with respiratory failure or septic or cardiogenic shock were eligible for inclusion in the study if they had delirium. Participants were randomly assigned-using a computer-generated, permuted-block randomisation scheme with stratification by trial site and age-in a 1:1:1 ratio to receive intravenous placebo, haloperidol, or ziprasidone for up to 14 days. Investigators and participants were masked to treatment group assignment. 3 months and 12 months after randomisation, we assessed survivors' cognitive, functional, psychological, quality-of-life, and employment outcomes using validated telephone-administered tests and questionnaires. This trial was registered with ClinicalTrials.gov, NCT01211522, and is complete. FINDINGS: Between Dec 7, 2011, and Aug 12, 2017, we screened 20 914 individuals, of whom 566 were eligible and consented or had consent provided to participate. Of these 566 patients, 184 were assigned to the placebo group, 192 to the haloperidol group, and 190 to the ziprasidone group. 1-year survival and follow-up rates were similar between groups. Cognitive impairment was common in all three treatment groups, with a third of survivors impaired at both 3-month and 12-month follow-up in all groups. More than half of the surveyed survivors in each group had cognitive or physical limitations (or both) that precluded employment at both 3-month and 12-month follow-up. At both 3 months and 12 months, neither haloperidol (adjusted odds ratio 1·22 [95% CI 0·73-2.04] at 3 months and 1·12 [0·60-2·11] at 12 months) nor ziprasidone (1·07 [0·59-1·96] at 3 months and 0·94 [0·62-1·44] at 12 months) significantly altered cognitive outcomes, as measured by the Telephone Interview for Cognitive Status T score, compared with placebo. We also found no evidence that functional, psychological, quality-of-life, or employment outcomes improved with haloperidol or ziprasidone compared with placebo. INTERPRETATION: In delirious, critically ill patients, neither haloperidol nor ziprasidone had a significant effect on cognitive, functional, psychological, or quality-of-life outcomes among survivors. Our findings, along with insufficient evidence of short-term benefit and frequent inappropriate continuation of antipsychotics at hospital discharge, indicate that antipsychotics should not be used routinely to treat delirium in critically ill adults. FUNDING: National Institutes of Health and the US Department of Veterans Affairs.

Adjuvant Radiotherapy for Groin Node Metastases Following Surgery for Vulvar Cancer: A Systematic Review.

Background: Lymph node metastasis in vulvar cancer is a critical prognostic factor associated with higher recurrence and decreased survival. A survival benefit is reported with adjuvant radiotherapy but with potential significant morbidity. We aim to clarify whether there is high-quality evidence to support the use of adjuvant radiotherapy in this setting. Objectives: The aim of the study was to assess the effectiveness and safety of adjuvant radiotherapy to locoregional metastatic nodal areas. Search Methods: We conducted a comprehensive and systematic literature search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, ClinicalTrials.gov, and the National Cancer Institute. We considered only randomized controlled trials (RCTs). Main Results: We identified 1,760 records and finally retrieved only one eligible RCT (114 participants with positive inguinofemoral lymph nodes). All women had undergone radical vulvectomy and bilateral inguinal lymphadenectomy and had been randomized to adjuvant radiotherapy or to intraoperative ipsilateral pelvic lymphadenectomy without adjuvant radiotherapy. At 6 years, the overall survival (OS) was 51% versus 41% in favor of radiotherapy (HR 0.61; 95% CI 0.30-1.3) without significance and with very low certainty of evidence. At 6 year, the cumulative incidence of cancer-related deaths was 29% versus 51% in favor of adjuvant radiotherapy (HR 0.49; 95% CI 0.28-0.87). Recurrence-free survival at 6 years was 59% after adjuvant radiotherapy versus 48% after pelvic lymphadenectomy (HR 0.39; 95% CI 0.17-0.88). Three (5.3%) versus 13 (24.1%) groin recurrences were noted, respectively, in the adjuvant radiotherapy and pelvic lymphadenectomy groups. There was no significant difference in acute toxicities for pelvic lymphadenectomy compared to radiotherapy. In women with positive pelvic lymph nodes (20%), the OS at 6 year was 36% compared with 13% in favor of adjuvant radiotherapy. Late cutaneous toxicity rate appeared to be greater after radiotherapy (19% vs. 15%) but with less chronic lymphedema (16% vs. 22%). Conclusion: There is only very low-quality evidence on administering adjuvant radiotherapy for inguinal lymph node metastases. Although the identified study was a multicenter RCT, there was a reasonable imprecision and inconsistency because of small study numbers, wide confidence intervals in the data, and early trial closure, resulting in downgrading of the evidence.

Pathogenesis of sleep disordered breathing in the setting of opioid use: A multiple mediation analysis using physiology.

STUDY OBJECTIVES: Opioid medications are commonly used and are known to impact both breathing and sleep, and are linked with adverse health outcomes including death. Clinical data indicate that chronic opioid use causes central sleep apnea, and might also worsen obstructive sleep apnea. The mechanisms by which opioids influence sleep-disordered breathing pathogenesis are not established. METHODS: Patients who underwent clinically-indicated polysomnography confirming sleep-disordered breathing (SDB) (AHI≥5/hr) were included. Each patient using opioids was matched by sex, age, and BMI to three control individuals not using opioids. Physiology known to influence SDB pathogenesis were determined from validated polysomnography-based signal analysis. PSG and physiology paramters of interest were compared between opioid and control individuals, adjusted for covariates. Mediation analysis was used to evaluate the link between opioids, physiology, and polysomnographic metrics. RESULTS: 178 individuals using opioids were matched to 534 controls (median [IQR] age 59 [50,65] years, BMI 33 [29,41] kg/m2, 57% female, daily morphine equivalent 30 [20,80] mg). Compared with controls, opioids were associated with increased central apneas (2.8 vs 1.7 events/hr; p=0.001) and worsened hypoxemia (5 vs 3% sleep with SpO2<88%; p=0.013), with similar overall AHI. Use of opioids was associated with higher loop gain, a lower respiratory rate and higher respiratory rate variability. Higher loop gain and increased respiratory rate variability mediated the effect of opioids on central apnea, but did not mediate the effect on hypoxemia. CONCLUSIONS: Opioids have multi-level effects impacting SDB. Targeting these factors may help mitigate deleterious respiratory consequences of chronic opioid use.

Effect of obesity on sleep apnea pathogenesis differs in women versus men: multiple mediation analyses in the retrospective SNOOzzzE cohort.

There are multiple mechanisms underlying obstructive sleep apnea (OSA) development. However, how classic OSA risk factors such as body mass index (BMI) and sex portend to OSA development has not been fully described. Thus we sought to evaluate how obesity leads to OSA and assess how these mechanisms differ between men and women. The San Diego Multi-Outcome OSA Endophenotype (SNOOzzzE) cohort includes 3,319 consecutive adults who underwent a clinical in-laboratory polysomnography at the University of California, San Diego, sleep clinic between January 2017 and December 2019. Using routine polysomnography signals, we determined OSA endotypes. We then performed mediation analyses stratified by sex to determine how BMI influenced the apnea-hypopnea index (AHI) using OSA pathophysiological traits as mediators, adjusting for age, race, and ethnicity. We included 2,146 patients of whom 919 (43%) were women and 1,227 (57%) were obese [body mass index (BMI) > 30 kg/m2]. BMI was significantly associated with AHI in both women and men. In men, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (ßstandardized = 0.124), a reduction in circulatory delay (ßstandardized = 0.063), and an increase in arousal threshold (ßstandardized = 0.029; Pboot-strapped,all < 0.05). In women, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (ßstandardized = 0.05) and circulatory delay (ßstandardized = 0.037; Pboot-strapped,all < 0.05). BMI-related OSA pathogenesis differs by sex. An increase in upper airway collapsibility is consistent with prior studies. A reduction in circulatory delay may lead to shorter and thus more events per hour (higher AHI), while the relationship between arousal threshold and OSA is likely complex.NEW & NOTEWORTHY Our data provide important insights into obesity-related obstructive sleep apnea (OSA) pathogenesis, thereby validating, and extending, prior research findings. This is the largest sample size study to examine the relationships between obesity and gender on OSA pathogenesis. The influence of obesity on sleep apnea severity is mediated by different mechanistic traits (endotypes).

Performance of a commercial smart watch compared to polysomnography reference for overnight continuous oximetry measurement and sleep apnea evaluation.

STUDY OBJECTIVES: To evaluate the accuracy and precision of continuous overnight oxygen saturation (SpO2) measurement by a commercial wrist device (WD) incorporating high-grade sensors, and investigate WD estimation of sleep-disordered breathing by quantifying overnight oxygen desaturation index (ODI) compared to polysomnography (PSG) ODI and apnea-hypopnea index (AHI) with and without sleep questionnaire data, to assess WD ability to detect obstructive sleep apnea (OSA) and determine its severity. METHODS: Participants completed sleep questionnaires, had a WD (Samsung Galaxy Watch 4) placed on their wrist, and underwent attending, in-lab overnight PSG (Nihon Kohden) with pulse oximetry probe secured either to a finger or ear lobe. PSG data was scored by a single experienced registered PSG technologist. Statistical analysis included demographic characteristics, continuous SpO2 measurement WD vs PSG root mean square error (RMSE) with Bland Altman plot and linear regression associations. Predictive models for PSG ODI and AHI severity were built using logistic regression with probability cutoffs determined via receiver operating curve (ROC) characteristics. RESULTS: The 51 participants analyzed had median age of 49 (range 22-78) years, 66.7% were male, with median body mass index (BMI) 28.1 (range 20.1, 47.3) kg/m2 with race/ethnicity distribution of 49.0% Caucasian, 25.5% Hispanic, 9.8% African-American, 9.8% Asian, and 5.9% Middle Eastern. WD vs PSG continuous SpO2 measurement in percentage points demonstrated bias of 0.91 (CI95 0.38, 1.45), standard deviation 2.37 (CI95 2.36, 2.38), and RMSE 2.54 (CI95 2.34, 2.73). WD area under the curve (AUC) ROC characteristics for predicting PSG were 0.882 ODI>15/h, 0.894 AHI>30/h, 0.800 AHI>15/h, and 0.803 AHI>5/h. WD plus select sleep questionnaire AUCs for predicting PSG were 0.943 AHI>30/h, 0.868 AHI>15/h, and 0.863 AHI>5/h. CONCLUSIONS: The WD conducted reliable overnight continuous SpO2 monitoring with RMSE <3% vs PSG. Predictive models of PSG AHI based on WD measurements alone, or plus sleep questionnaires, demonstrated excellent to outstanding discrimination for OSA identification and severity. Longitudinal WD use should be evaluated promptly based on WD potential to improve accessibility and accuracy of OSA testing, as well as support treatment follow-up.

Growth of Complex Syntax: Coordinate and Subordinate Clause Use in Elementary School-Aged Children.

PURPOSE: Production of complex syntax is a hallmark of later language development; however, most of the research examining age-related changes has focused on adolescents or analyzed narrative language samples. Research documenting age-related changes in the production of complex syntax in elementary school-aged children in conversational language samples is limited. Therefore, the purpose of this article is to examine age-related changes in the production of coordinate and subordinate clauses in children between 5 and 10 years of age obtained from 50-utterance conversational language samples. METHOD: The analytic sample included 196 children with typical language development, who ranged in age from 5;0 to 10;11 (years;months; girls = 103; boys = 96; three cases were excluded). Fifty-utterance conversational language samples were examined for use of coordinate and subordinate clauses. RESULTS: Results of regression analyses indicated that the production of coordinate and subordinate clauses could be predicted from age. The proportion of utterances that included subordinate clauses increased 0.20% for every month increase in age (p < .001). Coordinate clauses also continued to grow, although at a slower rate (0.10% increase for every month increase in age, p < .001). Finally, the proportion of simple utterances (i.e., utterances without coordinate or subordinate clauses) decreased with age (0.40% decrease for every month increase in age, p < .001). CONCLUSIONS: This study indicated that as children's age increased, they used fewer, simple, one-clause sentences and more utterances that included subordinate clauses, with or without coordinate clauses. These results were obtained from 50-utterance language samples, further supporting use of language sampling to develop intervention goals and monitor progress in therapy. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25262725.

Objectively measured peri-vaccination sleep does not predict COVID-19 breakthrough infection.

Prior studies have shown that sleep duration peri-vaccination influences an individual's antibody response. However, whether peri-vaccination sleep affects real-world vaccine effectiveness is unknown. Here, we tested whether objectively measured sleep around COVID-19 vaccination affected breakthrough infection rates. DETECT is a study of digitally recruited participants who report COVID-19-related information, including vaccination and illness data. Objective sleep data are also recorded through activity trackers. We compared the impact of sleep duration, sleep efficiency, and frequency of awakenings on reported breakthrough infection after the 2nd vaccination and 1st COVID-19 booster. Logistic regression models were created to examine if sleep metrics predicted COVID-19 breakthrough infection independent of age and gender. Self-reported breakthrough COVID-19 infection following 2nd COVID-19 vaccination and 1st booster. 256 out of 5265 individuals reported a breakthrough infection after the 2nd vaccine, and 581 out of 2583 individuals reported a breakthrough after the 1st booster. There was no difference in sleep duration between those with and without breakthrough infection. Increased awakening frequency was associated with breakthrough infection after the 1st booster with 3.01 ± 0.65 awakenings/hour in the breakthrough group compared to 2.82 ± 0.65 awakenings/hour in those without breakthrough (P < 0.001). Cox proportional hazards modeling showed that age < 60 years (hazard ratio 2.15, P < 0.001) and frequency of awakenings (hazard ratio 1.17, P = 0.019) were associated with breakthrough infection after the 1st booster. Sleep duration was not associated with breakthrough infection after COVID vaccination. While increased awakening frequency during sleep was associated with breakthrough infection beyond traditional risk factors, the clinical implications of this finding are unclear.

Temporal Trends in Methamphetamine Use in Patients Admitted to the Hospital: A Retrospective Cohort Study.

OBJECTIVES: Although methamphetamine use is common, the scope of methamphetamine use and outcomes for patients admitted to the hospital is unclear. This study aims to identify the prevalence of methamphetamine use from January 2012 to January 2022, coingestions, hospital course, and readmission rate of admitted patients. METHODS: This was a retrospective cohort study conducted on patients admitted to our center with the following inclusions: age older than 18 years, positive/"pending confirm" value for methamphetamine on urine drug screen, and/or an International Classification of Diseases , Tenth Revision , code related to stimulant use disorder as an active issue. Urine drug screen data are reported as methamphetamine +/- and polysubstance (PS) +/-. Patient demographics, admission diagnosis, and hospital course were extracted. Statistical tests used included t tests and Mann-Whitney U tests. RESULTS: A total of 19,159 encounters were included, representing 12,057 unique patients. The median (interquartile range) age was 43 (33-54) years. Of all encounters, 35.3% were methamphetamine + and PS -, and 46.3% were methamphetamine + and PS +. Hospitalizations increased from 883 in 2012 to 2532 in 2021. The median (IQR) hospital stay was 48 (48-120) hours. Of all encounters, 16.8% included an intensive care unit (ICU) admission, and the median ICU stay was 42 (21-87) hours. A total of 2988 patients (24.7%) were readmitted within the study period, and 4988 (71.5%) returned within 1 year of the previous encounter. In context of all emergency department admissions from 2013 to 2022, 13.1% had a urine drug screen + for methamphetamine. CONCLUSIONS: Hospitalizations with recent methamphetamine use doubled at our institution from 2012 to 2022. In addition, 1 in 4 is readmitted (typically within 1 year), and a minority requires ICU care.

Assessment of Family Medicine Obstetrics Fellowship Websites in the United States: Content and Usability.

INTRODUCTION: The United States is experiencing maternity care shortages. Family physicians can play a role in addressing these shortages. Family medicine obstetrics fellowships train family physicians in obstetrics care. Fellowship websites are important for promoting programs and attracting applicants. However, whether websites provide sufficient program information is unknown. This study aimed to assess completeness and utility of family medicine obstetrics fellowship websites across the United States. METHOD: The study analyzed 46 family medicine obstetrics fellowship websites. The component analysis evaluated the presence of 17 components related to orientation, curriculum, program, personnel, and additional content. The qualitative analysis included ratings for navigation and application, information quality, and esthetics. Analysis included percentages for websites and components and average qualitative ratings. RESULTS: Common components included overviews, training requirements, and contact information. Description of the patient population was the least common component. Usability ratings varied across programs, with higher ratings observed for navigation and application, and information quality. Esthetics and visual appeal received lower ratings. Regional analysis indicated that websites from fellowships in the West and Southwest tended to include more components compared to those in the Southeast. DISCUSSION: Family medicine obstetrics fellowship websites serve as valuable sources of program information for prospective applicants. However, not all websites include essential program details. Some information is rarely provided. Given the shortage of maternity care providers, it is crucial to develop informative and functional websites to attract applicants. Improving website content and design could prove to be a cost-effective strategy to increase the number of applicants.

Impact of a deep learning sepsis prediction model on quality of care and survival.

Sepsis remains a major cause of mortality and morbidity worldwide. Algorithms that assist with the early recognition of sepsis may improve outcomes, but relatively few studies have examined their impact on real-world patient outcomes. Our objective was to assess the impact of a deep-learning model (COMPOSER) for the early prediction of sepsis on patient outcomes. We completed a before-and-after quasi-experimental study at two distinct Emergency Departments (EDs) within the UC San Diego Health System. We included 6217 adult septic patients from 1/1/2021 through 4/30/2023. The exposure tested was a nurse-facing Best Practice Advisory (BPA) triggered by COMPOSER. In-hospital mortality, sepsis bundle compliance, 72-h change in sequential organ failure assessment (SOFA) score following sepsis onset, ICU-free days, and the number of ICU encounters were evaluated in the pre-intervention period (705 days) and the post-intervention period (145 days). The causal impact analysis was performed using a Bayesian structural time-series approach with confounder adjustments to assess the significance of the exposure at the 95% confidence level. The deployment of COMPOSER was significantly associated with a 1.9% absolute reduction (17% relative decrease) in in-hospital sepsis mortality (95% CI, 0.3%-3.5%), a 5.0% absolute increase (10% relative increase) in sepsis bundle compliance (95% CI, 2.4%-8.0%), and a 4% (95% CI, 1.1%-7.1%) reduction in 72-h SOFA change after sepsis onset in causal inference analysis. This study suggests that the deployment of COMPOSER for early prediction of sepsis was associated with a significant reduction in mortality and a significant increase in sepsis bundle compliance.

Loop Gain as a Predictor of Blood Pressure Response in Patients Treated for Obstructive Sleep Apnea: Secondary Analysis of a Clinical Trial.

Rationale: Randomized trials have shown inconsistent cardiovascular benefits from obstructive sleep apnea (OSA) therapy. Intermittent hypoxemia can increase both sympathetic nerve activity and loop gain ("ventilatory instability"), which may thus herald cardiovascular treatment benefit. Objectives: To test the hypothesis that loop gain predicts changes in 24-hour mean blood pressure (MBP) in response to OSA therapy and compare its predictive value against that of other novel biomarkers. Methods: The HeartBEAT (Heart Biomarker Evaluation in Apnea Treatment) trial assessed the effect of 12 weeks of continuous positive airway pressure (CPAP) versus oxygen versus control on 24-hour MBP. We measured loop gain and hypoxic burden from sleep tests and identified subjects with a sleepy phenotype using cluster analysis. Associations between biomarkers and 24-h MBP were assessed in the CPAP/oxygen arms using linear regression models adjusting for various covariates. Secondary outcomes and predictors were analyzed similarly. Results: We included 93 and 94 participants in the CPAP and oxygen arms, respectively. Overall, changes in 24-hour MBP were small, but interindividual variability was substantial (mean [standard deviation], -2 [8] and 1 [8] mm Hg in the CPAP and oxygen arms, respectively). Higher loop gain was significantly associated with greater reductions in 24-hour MBP independent of covariates in the CPAP arm (-1.5 to -1.9 mm Hg per 1-standard-deviation increase in loop gain; P ⩽ 0.03) but not in the oxygen arm. Other biomarkers were not associated with improved cardiovascular outcomes. Conclusions: To our knowledge, this is the first study suggesting that loop gain predicts blood pressure response to CPAP therapy. Eventually, loop gain estimates may facilitate patient selection for research and clinical practice. Clinical trial registered with www.clinicaltrials.gov (NCT01086800).

Upper airway imaging and function in obstructive sleep apnea in people with and without HIV.

Obstructive sleep apnea (OSA) is common in people living with human immunodeficiency virus (HIV) (PLWH), but the underlying mechanisms are unclear. With improved long-term survival among PLWH, aging and obesity are increasingly prevalent in this population. These are also strong risk factors for the development of obstructive sleep apnea. We used magnetic resonance imaging (MRI) to measure upper airway (UA) anatomy and tongue fat content in PLWH with OSA (PLWH + OSA, n = 9) and in age-, sex-, and body mass index (BMI)-matched OSA controls (OSA, n = 11). We also quantified change in UA dimension during tidal breathing (during wakefulness and natural sleep) at four anatomical levels from the hard palate to the epiglottis along with synchronous MRI-compatible electroencephalogram and nasal flow measurements. All participants underwent on a separate night a baseline polysomnogram to assess OSA severity and an additional overnight physiological sleep study to measure OSA traits. We found no difference between the PLWH + OSA and the OSA control group in UA volume [PLWH + OSA: 12.8 mL (10.1-17.0), OSA: 14.0 mL (13.3-17.9), median (IQR)] or tongue volume [PLWH + OSA: 140.2 mL (125.1-156.9), OSA: 132.4 mL (126.8-154.7)] and a smaller tongue fat content in PLWH + OSA [11.2% (10.2-12.4)] than in the OSA controls [14.8% (13.2-15.5), P = 0.046]. There was no difference in the dynamic behavior of the UA between the two groups. When pooled together, both static and dynamic imaging metrics could be correlated with measures of UA mechanical properties. Our data suggest similar underlying UA physiology in OSA in subjects with and without HIV.NEW & NOTEWORTHY Obstructive sleep apnea is common in people living with human immunodeficiency virus (HIV), but the underlying mechanisms are unclear. We did not find differences in upper airway morphology using magnetic resonance imaging (MRI) during wake and natural sleep between people living with HIV (PLWH) with obstructive sleep apnea (OSA) and age, gender, and body mass index (BMI)-matched people with OSA but without HIV. Nor were there differences in tongue volume or changes in airway size during inspiration and expiration. MRI-derived anatomy was correlated with measures of airway collapse.