Publications by authors named "Adam V Benjafield"

21 Publications

  • Page 1 of 1

Positive Airway Pressure Therapy Adherence with Mask Resupply: A Propensity-Matched Analysis.

J Clin Med 2021 Feb 12;10(4). Epub 2021 Feb 12.

Pulmonary, Critical Care and Sleep Medicine, University of California, 9300 Campus Point Drive, La Jolla, San Diego, CA 92037, USA.

There are currently few data on the impact of mask resupply on longer-term adherence to positive airway pressure (PAP) therapy. This retrospective analysis investigated the effects of mask/mask cushion resupply on the adherence to PAP versus no resupply. Deidentified patient billing data for PAP supply items were merged with telemonitoring data from Cloud-connected AirSense 10/AirCurve 10 devices via AirView (ResMed). Eligible patients started PAP between 1 July 2014 and 17 June 2016, had ≥360 days of PAP device data, and achieved initial U.S. Medicare adherence criteria. Patients who received a resupply of mask systems/cushions (resupply group) were propensity-score-matched with those not receiving any mask/cushion resupply (control group). A total of 100,370 patients were included. From days 91 to 360, the mean device usage was 5.6 and 4.5 h/night in the resupply and control groups, respectively ( < 0.0001). The proportion of patients with a mean device usage ≥4 h/night was significantly higher in the resupply group versus the control group (77% vs. 59%; < 0.0001). The therapy termination rate was significantly lower in the resupply group versus the control group (14.7% vs. 31.9%; < 0.0001); there was a trend toward lower therapy termination rates as the number of resupplies increased. The replacement of mask interface components was associated with better longer-term adherence to PAP therapy versus no resupply.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10040720DOI Listing
February 2021

Adherence in children using positive airway pressure therapy: a big-data analysis.

Lancet Digit Health 2020 02 23;2(2):e94-e101. Epub 2019 Dec 23.

Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Background: Positive airway pressure (PAP) has become a prominent treatment for children with sleep-disordered breathing. However, there are no large-scale studies to clarify whether PAP is well tolerated in children, and which factors are associated with better adherence to PAP therapy. In this study, we aimed to clarify adherence patterns of PAP therapy in a large paediatric population.

Methods: We did a cross-sectional big-data analysis in children from Oct 1, 2014, to Aug 1, 2018, using existing data derived from PAP devices uploaded nightly in the AirView cloud database. The AirView database is a usage tracking system available to all patients who are assigned PAP therapy, which requires consent from the patient or parent or guardian. All patients older than 4 years and younger than 18 years who used continuous or automated PAP devices were evaluated. Only patients living in the USA and enrolled with a single insurance company were included. If patients were participating in an engagement programme, programme onset must have been within 7 days of therapy onset. Our primary outcome was the proportion of patients who used PAP continuously over 90 days. The primary outcome was assessed in all patients who met the age inclusion criterion and had reliable age data available. Data on missing PAP use were imputed as zero, but data on other metrics were not imputed and excluded from analysis.

Findings: We used data recorded from Oct 1, 2014, to Aug 1, 2018. Of 40 140 children screened, 36 058 (89·8%) were US residents and 20 553 (90·1%) of them met the eligibility criteria and had accessible data (mean age 13·0 years [SD 3·7]). On the basis of 90 days of monitoring data, 12 699 (61·8%) patients continuously used PAP. Factors significantly associated with adherence included age group, residual apnoea-hypopnoea index, use and onset of patient engagement programmes, PAP pressure, and nightly median PAP mask leak, all over the 90-day study period.

Interpretation: To our knowledge, our study represents the largest analysis of children using PAP therapy to date. The findings suggest that adherence to PAP therapy is lower than in previous reports from adults. However, numerous actionable factors were associated with improvements in adherence and should be used strategically in clinical decision making to improve PAP adherence in children.

Funding: ResMed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2589-7500(19)30214-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847310PMC
February 2020

Adherence with positive airway pressure therapy for obstructive sleep apnea in developing versus developed countries: a big data study.

J Clin Sleep Med 2020 Nov 18. Epub 2020 Nov 18.

ResMed Science Center, Sydney, Australia.

Study Objectives: Minimal focus has been placed on variations in health care delivery for obstructive sleep apnea (OSA). This study compared positive airway pressure (PAP) usage in developing countries (Brazil and Mexico) versus a developed country (United States, US), and investigated the impact of a patient engagement tool (myAir™; ResMed) on adherence.

Methods: De-identified data from the AirView™ database (ResMed) for patients receiving PAP therapy with wirelessly connected Air10 (AirSense and AirCurve) devices in Brazil, Mexico and the US were analyzed. Adherence was defined using US Center for Medicare and Medicaid Services (CMS) criteria (usage ≥4 h/night on ≥70% of nights in the first 90 days).

Results: The analysis included 4,181,490 patients (Brazil: 31,672; Mexico 16,934; US: 4,132,884). 90-day CMS adherence was slightly lower in Latin America versus the US (Brazil: 71.7%; Mexico: 66.4%; US: 74.0%). Significantly fewer patients were using the patient engagement tool in Brazil (8.1%) and Mexico (2.8%) versus the US (26%; both p<0.001). Patients registered to use an engagement tool had a higher rate of CMS adherence and were twice as likely to achieve CMS adherence. Average daily usage and days with usage >4 hours in the first week were the strongest predictors of CMS adherence. Across all countries, >80% of patients meeting CMS criteria at 3 months were still using PAP therapy at 1 year, with 1-year adherences rates of >75%.

Conclusions: Short- and long-term PAP adherence rates in Brazil and Mexico were similar to those achieved in the US. Patients who registered to use an engagement tool consistently had better adherence than those who did not.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5664/jcsm.9008DOI Listing
November 2020

Continuous positive airway pressure versus standard care for the treatment of people with mild obstructive sleep apnoea (MERGE): a multicentre, randomised controlled trial.

Lancet Respir Med 2020 04 2;8(4):349-358. Epub 2019 Dec 2.

National Heart and Lung Institute, Imperial College London, London, UK; Royal Brompton and Harefield NHS Foundation Trust, London, UK.

Background: The evidence base for the treatment of mild obstructive sleep apnoea is limited and definitions of disease severity vary. The MERGE trial investigated the clinical effectiveness of continuous positive airway pressure in patients with mild obstructive sleep apnoea.

Methods: MERGE, a multicentre, parallel, randomised controlled trial enrolled patients (≥18 years to ≤80 years) with mild obstructive sleep apnoea (apnoea-hypopnoea index [AHI] ≥5 to ≤15 events per h using either AASM 2007 or AASM 2012 scoring criteria) from 11 UK sleep centres. Participants were assigned (1:1) to either 3 months of continuous positive airway pressure plus standard care (sleep counselling), or standard care alone, by computer-generated randomisation; neither participants nor researchers were blinded. The primary outcome was a change in the score on the Short Form-36 questionnaire vitality scale in the intention-to-treat population of patients with mild obstructive sleep apnoea diagnosed using the American Academy of Sleep Medicine 2012 scoring criteria. The study is registered with ClinicalTrials.gov, NCT02699463.

Findings: Between Nov 28, 2016 and Feb 12, 2019, 301 patients were recruited and randomised. 233 had mild obstructive sleep apnoea using AASM 2012 criteria and were included in the intention-to-treat analysis: 115 were allocated to receive continuous positive airway pressure and 118 to receive standard care. 209 (90%) of these participants completed the trial. The vitality score significantly increased with a treatment effect of a mean of 10·0 points (95% CI 7·2-12·8; p<0·0001) after 3 months of continuous positive airway pressure, compared with standard care alone (9·2 points [6·8 to 11·6] vs -0·8 points [-3·2 to 1·5]). Using the ANCOVA last-observation-carried-forward analysis, a more conservative estimate, the vitality score also significantly increased with a treatment effect of a mean of 7·5 points (95% CI 5·3 to 9·6; p<0·0001) after 3 months of continuous positive airway pressure, compared with standard care alone (7·5 points [6·0 to 9·0] vs 0·0 points [-1·5 to 1·5]). Three serious adverse events occurred (one allocated to the continuous positive airway pressure group) and all were unrelated to the intervention.

Interpretation: 3 months of treatment with continuous positive airway pressure improved the quality of life in patients with mild obstructive sleep apnoea. These results highlight the need for health-care professionals and providers to consider treatment for patients with mild obstructive sleep apnoea.

Funding: ResMed Ltd.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(19)30402-3DOI Listing
April 2020

Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis.

Lancet Respir Med 2019 08 9;7(8):687-698. Epub 2019 Jul 9.

University of California San Diego, La Jolla, CA, USA. Electronic address:

Background: There is a scarcity of published data on the global prevalence of obstructive sleep apnoea, a disorder associated with major neurocognitive and cardiovascular sequelae. We used publicly available data and contacted key opinion leaders to estimate the global prevalence of obstructive sleep apnoea.

Methods: We searched PubMed and Embase to identify published studies reporting the prevalence of obstructive sleep apnoea based on objective testing methods. A conversion algorithm was created for studies that did not use the American Academy of Sleep Medicine (AASM) 2012 scoring criteria to identify obstructive sleep apnoea, allowing determination of an equivalent apnoea-hypopnoea index (AHI) for publications that used different criteria. The presence of symptoms was not specifically analysed because of scarce information about symptoms in the reference studies and population data. Prevalence estimates for obstructive sleep apnoea across studies using different diagnostic criteria were standardised with a newly developed algorithm. Countries without obstructive sleep apnoea prevalence data were matched to a similar country with available prevalence data; population similarity was based on the population body-mass index, race, and geographical proximity. The primary outcome was prevalence of obstructive sleep apnoea based on AASM 2012 diagnostic criteria in individuals aged 30-69 years (as this age group generally had available data in the published studies and related to information from the UN for all countries).

Findings: Reliable prevalence data for obstructive sleep apnoea were available for 16 countries, from 17 studies. Using AASM 2012 diagnostic criteria and AHI threshold values of five or more events per h and 15 or more events per h, we estimated that 936 million (95% CI 903-970) adults aged 30-69 years (men and women) have mild to severe obstructive sleep apnoea and 425 million (399-450) adults aged 30-69 years have moderate to severe obstructive sleep apnoea globally. The number of affected individuals was highest in China, followed by the USA, Brazil, and India.

Interpretation: To our knowledge, this is the first study to report global prevalence of obstructive sleep apnoea; with almost 1 billion people affected, and with prevalence exceeding 50% in some countries, effective diagnostic and treatment strategies are needed to minimise the negative health impacts and to maximise cost-effectiveness.

Funding: ResMed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(19)30198-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007763PMC
August 2019

Compliance after switching from CPAP to bilevel for patients with non-compliant OSA: big data analysis.

BMJ Open Respir Res 2019 29;6(1):e000380. Epub 2019 Apr 29.

medXcloud Group, San Diego, California, USA.

Introduction: For patients with obstructive sleep apnoea (OSA) who are initially non-compliant with continuous (automatic) positive airway pressure (CPAP/APAP) therapy, a bilevel PAP (Spont/VAuto) therapy transition pathway is available to improve therapy adherence. The aim of this retrospective study was to compare PAP therapy usage data of patients with non-compliant OSA (ncOSA) on CPAP/APAP who were switched to bilevel PAP.

Methods: A PAP telemonitoring database was queried between 1 January 2015 and 31 July 2016 for eligible patients started on CPAP/APAP and non-CMS (United States Center for Medicare and Medicaid Services) compliant and switched to bilevel PAP within 90 days of starting CPAP/APAP therapy. PAP therapy data on all patients were compared before switch (CPAP/APAP) and after switch (VAuto/Spont).

Results: Of the 1496 patients with ncOSA identified, 30.3% used CPAP, 62.3% APAP, and 7.4% both APAP and CPAP before switching to a bilevel mode. 47.8% patients switched to Spont mode and 52.2% to VAuto mode. PAP usage significantly improved by 0.9 h/day (p<0.001) and all other device metrics (residual apnoea-hypopnoea index and unintentional mask leak) also improved after the switch. No patients had achieved US CMS criteria for compliance before the switch, and 56.8% did after.

Conclusion: This shows for the first time that there may be potential benefit from switching from CPAP/APAP to bilevel PAP for patients struggling with PAP adherence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjresp-2018-000380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530496PMC
April 2020

Automatic EPAP intelligent volume-assured pressure support is effective in patients with chronic respiratory failure: A randomized trial.

Respirology 2019 12 22;24(12):1204-1211. Epub 2019 Apr 22.

Department of Medicine and Neurology, Northwestern Medical Hospital, Chicago, IL, USA.

Background And Objective: Patients with chronic respiratory failure are increasingly managed with domiciliary non-invasive ventilation (NIV). There may be limited ability to provide NIV titration for these complex patients, and ventilatory requirements and upper airway support needs may change over time. Therefore, an automatically adjusting expiratory positive airway pressure (AutoEPAP) algorithm may offer advantages over manually adjusted EPAP for treating these patients. This study compared 4% oxygen desaturation index (ODI4%) values during the use of an AutoEPAP algorithm versus manual EPAP titration with the intelligent volume-assured pressure support (iVAPS) algorithm.

Methods: This prospective, single-blind, randomized, crossover study was conducted at six US sites. Patients with chronic respiratory failure (neuromuscular disease, chronic obstructive pulmonary disease, obesity hypoventilation and other aetiologies) and an apnoea-hypopnoea index of >5/h who were already established NIV users underwent a single night of NIV with the iVAPS manual EPAP and iVAPS AutoEPAP in the sleep laboratory in random order.

Results: A total of 38 patients constituted the study population. Mean ODI4% was statistically non-inferior with AutoEPAP versus manual EPAP (P < 0.0001). There was no difference in the effect on ODI4% across respiratory failure subgroups. Ventilation parameters and gas exchange were similar with either NIV mode, indicating equally effective treatment of respiratory failure. Sleep parameters were improved during AutoEPAP versus manual EPAP.

Conclusion: A single night of NIV using the iVAPS with AutoEPAP algorithm was non-inferior to a single night of iVAPS with manual EPAP titration in patients with respiratory failure.

Clinical Trial Registration: NCT02683772 at clinicaltrials.gov.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/resp.13546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007762PMC
December 2019

Adherence to Positive Airway Therapy After Switching From CPAP to ASV: A Big Data Analysis.

J Clin Sleep Med 2018 01 15;14(1):57-63. Epub 2018 Jan 15.

University of California San Diego, La Jolla, California.

Study Objectives: There is a lack of data regarding adherence trajectories when switching from continuous positive airway pressure (CPAP) to adaptive servoventilation (ASV) in the context of persistent or treatment-emergent central sleep apnea (CSA). This study investigated 90-day adherence rates in patients with sleep apnea based on the type of positive airway pressure (PAP) device used and any switching of PAP modality over time.

Methods: Telemonitoring data were obtained from a United States PAP database. Eligible patients were a 30% random sample who started PAP, plus all who started ASV, from January 1, 2015 to October 2, 2015. All received PAP and had at least one session with usage of 1 hour or more. Adherence and device usage were determined in three groups: started on CPAP and stayed on CPAP (CPAP only); started on ASV and stayed on ASV (ASV only); started on CPAP, switched to ASV (Switch). The United States Medicare definition of adherence was used.

Results: The study included 198,890 patients; 189,724 (CPAP only), 8,957 (ASV only) and 209 (Switch). In the Switch group, average apnea-hypopnea index decreased significantly on ASV versus CPAP. At 90 days, adherence rates were 73.8% and 73.2% in the CPAP only and ASV only groups. In the Switch group, CPAP adherence was 62.7%, improving to 76.6% after the switch to ASV. Mean device usage at 90 days was 5.27, 5.31, and 5.73 h/d in the CPAP only, ASV only, and Switch groups, respectively.

Conclusions: Treatment-emergent or persistent CSA during CPAP reduced therapy adherence, but adherence improved early after switching from CPAP to ASV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5664/jcsm.6880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734894PMC
January 2018

Patient Engagement Using New Technology to Improve Adherence to Positive Airway Pressure Therapy: A Retrospective Analysis.

Chest 2018 04 15;153(4):843-850. Epub 2017 Nov 15.

ResMed Science Center, ResMed Corp, San Diego, CA.

Background: Sleep apnea has major neurocognitive and cardiovascular and metabolic risks. Treatment of sleep apnea is suboptimal because of variable adherence to existing therapies.

Methods: This trial compared positive airway pressure adherence among patients who were provided active patient engagement (APE) technology vs those who received usual care monitoring (UCM). The primary outcome was expressed by using the US Medicare definition of adherence. Adherence data from two cloud-based databases (AirView and myAir) were analyzed for patients with sleep apnea. Data were included if a patient's activation date in the APE tool was within 7 days of the therapy start date in the UCM database during a defined time window. Data were propensity matched in a 1:2 ratio (APE:UCM) based on baseline patient characteristics.

Results: A total of 128,037 patients were analyzed. Baseline characteristics were typical of a sleep clinic cohort. APE was associated with more patients achieving adherence criteria (87.3%) compared with UCM patients (70.4%; P < .0001 for the difference). Average therapy usage was 5.9 h per night in the APE group vs 4.9 h per night in the matched UCM patients (P < .0001). Patients with sleep apnea "struggling" with therapy adherence had a 17.6% absolute improvement in adherence using APE compared with UCM.

Conclusions: Robust therapy adherence rates can be achieved by adding modern technology to usual care. Adopting advances in technology in care management may allow clinicians to more effectively and efficiently treat patients who have sleep apnea. Rigorous randomized controlled trials may be required before making strong clinical recommendations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2017.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989636PMC
April 2018

Effect of Telemedicine Education and Telemonitoring on Continuous Positive Airway Pressure Adherence. The Tele-OSA Randomized Trial.

Am J Respir Crit Care Med 2018 01;197(1):117-126

1 Division of Sleep Medicine, Southern California Permanente Medical Group.

Rationale: Automated telemedicine interventions could potentially improve adherence to continuous positive airway pressure (CPAP) therapy.

Objectives: Examining the effects of telemedicine-delivered obstructive sleep apnea (OSA) education and CPAP telemonitoring with automated patient feedback messaging on CPAP adherence.

Methods: This four-arm, randomized, factorial design clinical trial enrolled 1,455 patients (51.0% women; age, 49.1 ± 12.5 yr [mean ± SD]) referred for suspected OSA. Nine hundred and fifty-six underwent home sleep apnea testing, and 556 were prescribed CPAP. Two telemedicine interventions were implemented: 1) web-based OSA education (Tel-Ed) and 2) CPAP telemonitoring with automated patient feedback (Tel-TM). Patients were randomized to 1) usual care, 2) Tel-Ed added, 3) Tel-TM added, or 4) Tel-Ed and Tel-TM added (Tel-both).

Measurements And Main Results: The primary endpoint was 90-day CPAP usage. Secondary endpoints included attendance to OSA evaluation, and change in Epworth Sleepiness Scale score. CPAP average daily use at 90 days was 3.8 ± 2.5, 4.0 ± 2.4, 4.4 ± 2.2, and 4.8 ± 2.3 hours in usual care, Tel-Ed, Tel-TM, and Tel-both groups. Usage was significantly higher in the Tel-TM and Tel-both groups versus usual care (P = 0.0002 for both) but not for Tel-Ed (P = 0.10). Medicare adherence rates were 53.5, 61.0, 65.6, and 73.2% in usual care, Tel-Ed, Tel-TM, and Tel-both groups (Tel-both vs. usual care, P = 0.001; Tel-TM vs. usual care, P = 0.003; Tel-Ed vs. usual care, P = 0.07), respectively. Telemedicine education improved clinic attendance compared with no telemedicine education (show rate, 68.5 vs. 62.7%; P = 0.02).

Conclusions: The use of CPAP telemonitoring with automated feedback messaging improved 90-day adherence in patients with OSA. Telemedicine-based education did not significantly improve CPAP adherence but did increase clinic attendance for OSA evaluation. Clinical trial registered with www.clinicaltrials.gov (NCT02279901).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.201703-0582OCDOI Listing
January 2018

Cardiovascular Outcomes With Minute Ventilation-Targeted Adaptive Servo-Ventilation Therapy in Heart Failure: The CAT-HF Trial.

J Am Coll Cardiol 2017 03;69(12):1577-1587

Herz- und Diabeteszentrum NRW, Ruhr University Bochum, Bad Oeynhausen, Germany.

Background: Sleep apnea is common in hospitalized heart failure (HF) patients and is associated with increased morbidity and mortality.

Objectives: The CAT-HF (Cardiovascular Improvements With MV-ASV Therapy in Heart Failure) trial investigated whether minute ventilation (MV) adaptive servo-ventilation (ASV) improved cardiovascular outcomes in hospitalized HF patients with moderate-to-severe sleep apnea.

Methods: Eligible patients hospitalized with HF and moderate-to-severe sleep apnea were randomized to ASV plus optimized medical therapy (OMT) or OMT alone (control). The primary endpoint was a composite global rank score (hierarchy of death, cardiovascular hospitalizations, and percent changes in 6-min walk distance) at 6 months.

Results: 126 of 215 planned patients were randomized; enrollment was stopped early following release of the SERVE-HF (Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure) trial results. Average device usage was 2.7 h/night. Mean number of events measured by the apnea-hypopnea index decreased from 35.7/h to 2.1/h at 6 months in the ASV group versus 35.1/h to 19.0/h in the control group (p < 0.0001). The primary endpoint did not differ significantly between the ASV and control groups (p = 0.92 Wilcoxon). Changes in composite endpoint components were not significantly different between ASV and control. There was no significant interaction between treatment and ejection fraction (p = 0.10 Cox model); however, pre-specified subgroup analysis suggested a positive effect of ASV in patients with HF with preserved ejection fraction (p = 0.036).

Conclusions: In hospitalized HF patients with moderate-to-severe sleep apnea, adding ASV to OMT did not improve 6-month cardiovascular outcomes. Study power was limited for detection of safety signals and identifying differential effects of ASV in patients with HF with preserved ejection fraction, but additional studies are warranted in this population. (Cardiovascular Improvements With MV ASV Therapy in Heart Failure [CAT-HF]; NCT01953874).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2017.01.041DOI Listing
March 2017

Lessons learned from a clinical trial: Design, rationale, and insights from The Cardiovascular Improvements with Minute Ventilation-targeted Adaptive Sero-Ventilation (ASV) Therapy in Heart Failure (CAT-HF) Study.

Contemp Clin Trials 2016 Mar 19;47:158-64. Epub 2016 Jan 19.

Duke University, Duke Clinical Research Institute, Durham, NC, United States; Inova Heart and Vascular Institute, Falls Church, VA, United States.

Objective: The CAT-HF Study was designed to evaluate the safety and efficacy of minute ventilation-targeted adaptive servo-ventilation (MV-ASV) during sleep in addition to optimized medical therapy (active therapy) versus optimized medical therapy alone (usual care) at 6 months, initiated in patients after hospitalization for acute decompensated heart failure (ADHF). This paper outlines the rationale, design and information learned at the time of study discontinuation.

Background: Sleep disordered breathing (SDB) is common in heart failure patients and is associated with worse outcomes in this patient population. Based on a belief that MV-ASV was safe in stable HF patients, CAT-HF was designed to examine whether MV-ASV improved outcomes in hospitalized HF patients During the course of CAT-HF, new results from SERVE-HF indicated that ASV therapy may be harmful in patients with left ventricular ejection fractions (LVEF)≤45% and central sleep apnea, a subgroup of patients enrolled in CAT-HF.

Methods: CAT-HF was a prospective, randomized, controlled, multicenter clinical trial (NCT: 01953874) in HF patients with either reduced or preserved ejection fraction and an Apnea-Hypopnea Index ≥15 events per hour randomized to usual care or active treatment in a 1:1 ratio. 215 patients were intended to be randomized following a hospitalization for ADHF. At the time of discontinuation, 126 patients were randomized. The primary endpoint is a global rank composite endpoint of death, CV hospitalizations, and Six minute walk distance (6MWD). Secondary endpoints will include changes in functional parameters, biomarkers, quality of life (QOL), sleep, and breathing.

Conclusions: The CAT-HF study was designed to assess the efficacy and safety of MV ASV treatment in patients after hospitalization for ADHF, but was stopped early due to safety concerns in HF patients with (LVEF)≤45% and predominant central sleep apnea.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cct.2016.01.001DOI Listing
March 2016

Assessment of the performance of nasal pillows at high CPAP pressures.

J Clin Sleep Med 2013 Sep;9(9):873-7

ResMed Science Center, ResMed Ltd, Sydney, Australia.

Study Objectives: Compliance with CPAP therapy remains an issue despite its effectiveness. Mask selection is likely to affect a patients experience with CPAP, and multiple mask options are currently available. Nasal pillows have less contact with the face compared to nasal masks and may benefit patients by minimizing side effects; however, they are infrequently used at high CPAP pressures. The aim of this study was to examine the performance of nasal pillows at pressures ≥ 12 cm H2O compared with nasal masks.

Methods: Twenty-one subjects were recruited. Participants were randomized to Swift FX nasal pillows and their current nasal mask for 7 consecutive nights each in a prospective crossover trial. Objective device data and subjective feedback were collected.

Results: There were no differences in objective device data of nasal pillows vs. nasal masks: Daily Usage 7.4 ± 1.4 vs. 7.2 ± 1.4 (h/night); 95(th)%ile Leak 28.6 ± 13.5 vs. 27.9 ± 17.9 (L/min); AHI 1.9 ± 1.3 vs. 1.7 ± 1.1, respectively (all p-values > 0.05). There were no differences between the nasal pillows and nasal masks for subjective ratings of comfort, seal, red marks, side effects such as jetting and dry nose/mouth, and overall performance (all p-values > 0.05). The nasal pillows were rated to be less obtrusive and claustrophobic (both p-values < 0.01), but less stable (p = 0.04). Overall preference was 50% nasal pillows, 45% nasal masks; 5% found no difference.

Conclusion: Nasal pillows are as efficacious as nasal masks at CPAP pressures ≥ 12 cm H2O and are a suitable option for patients requiring high CPAP pressures.

Clinical Trial Registration: NIH Clinical Trials Registry. http://clinicaltrials.gov.

Title: Nasal Pillows at High CPAP Pressure. Identifier: NCT01690923.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5664/jcsm.2984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746714PMC
September 2013

Assessment of the impact on compliance of a new CPAP system in obstructive sleep apnea.

Sleep Breath 2013 Mar;17(1):69-76

ResMed Science Centre, ResMed Ltd,Sydney, Australia.

Background: Despite the efficacy of continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea (OSA), compliance with therapy remains suboptimal.The aim of this study was to determine whether the use of S9TM increased compliance in established CPAP users.

Methods: Subjects with OSA (50) were recruited into the study. When subjects entered the study, 28 days of respective compliance data were downloaded from the patient's usual CPAP device. Subjects trialled the S9 CPAP for 28 days.Subjects then resumed use of their usual CPAP for 28 days.Compliance data from the patient's usual CPAP pre- and post-trialling S9 were compared with data from the S9 CPAP.

Results: Patients were significantly more compliant when using the S9 than their usual CPAP device both pre- and post-S9 based on average daily usage. CPAP pre-S906.58±1.95(mean hours±SD), S907.08±1.18 h and CPAP post-S906.71±1.72 h. The difference between CPAP pre-S9 and S9 was 0.5 h (p00.003). The difference between S9 and CPAP post-S9 was 0.35 h (p00.01). There was no significant difference between CPAP pre-S9 and CPAP post-S9 (p00.34).Patients also completed questionnaires comparing the S9 system to their usual device. Subjective feedback showed a strong preference for the S9.

Conclusions: Participants were significantly more compliant when using the S9 than their usual CPAP device both pre and post-S9 use
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11325-012-0651-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575556PMC
March 2013

No association with hypertension of CLCNKB and TNFRSF1B polymorphisms at a hypertension locus on chromosome 1p36.

J Hypertens 2005 Aug;23(8):1491-6

Basic & Clinical Genomics Laboratory, School of Medical Sciences and Institute for Biomedical Research, The University of Sydney, Australia.

Objective: Chromosome 1p36 has been linked to essential hypertension and systolic blood pressure. This locus contains the chloride channel-Kb gene (CLCNKB) and the tumour necrosis factor receptor 2 gene (TNFRSF1B). Polymorphisms of each of these have shown association with hypertension, and a CLCNKB T481S variant alters receptor function. Here we performed association studies in a well-characterized cohort of hypertensives and normotensives whose blood pressure status matched that of both their parents.

Methods: The study involved 196 essential hypertensives and 321 normotensives. These were genotyped for TNFRSF1B variants T-1710A upstream, A257G in exon 2, a CA-repeat polymorphism in intron 4, E232K and M196R in exon 6, and T1668G and T1690C in the 3'-untranslated region, and the T481S variant of CLCNKB.

Results: The CLCNKB T481S variant showed no association with hypertension. Thermodynamic modelling of the 3'-untranslated region of TNFRSF1B mRNA predicted that the T1668G variant alters the stem-loop structure and thus the mRNA stability and expression. However, neither this nor the other TNFRSF1B polymorphisms, either alone or after haplotype analysis, were associated with hypertension. Moreover, for each gene the blood pressure, body mass index, plasma sodium and plasma lipid concentrations were generally similar across genotypes.

Conclusion: Our data fail to support previous association findings for TNFRSF1B and CLCNKB at the chromosome 1p36 locus implicated in hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.hjh.0000174300.73992.ccDOI Listing
August 2005

Genome-wide scan for hypertension in Sydney Sibships: the GENIHUSS study.

Am J Hypertens 2005 Jun;18(6):828-32

Basic & Clinical Genomics Laboratory, School of Medical Sciences and Institute for Biomedical Research, The University of Sydney, Sydney, Australia.

We report here the results of the GENIHUSS study (GENetic Investigation of Hypertension Undertaken in Sydney Sibships)-a genome-wide scan to identify loci linked to essential hypertension (HT). Subjects were Anglo-Celtic Australian sibpairs resident in or near Sydney, Australia, with onset of HT before age 60 years (mean, 44 +/- 13 SD years). A 10-cM scan involving 400 microsatellite markers and 252 HT sibpairs was followed by fine mapping of the most promising locus using 296 HT sibpairs (481 individuals from 200 families). Multipoint and two-point nonparametric linkage analyses were performed using MAPMAKER/SIBS, GENEHUNTER II, and SPLINK. Suggestive loci were found on chromosomes 1 (4 cM) and 4 (129 cM). The chromosome 4 locus coincided with a QTL for systolic blood pressure (BP) in the Australian Victorian Family Heart Study, and the locus on chromosome 1 contains the chloride channel gene CLCNKB and tumor necrosis factor receptor 2 gene TNFRSF1B, which have each shown association with HT. Our study adds to findings of HT loci emanating from genome scans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjhyper.2004.12.010DOI Listing
June 2005

No association of angiotensin-converting enzyme 2 gene (ACE2) polymorphisms with essential hypertension.

Am J Hypertens 2004 Jul;17(7):624-8

Basic Clinical Genomics Laboratory, School of Medical Sciences and Institute for Biomedical Research, The University of Sydney, Sydney, Australia.

Recent intriguing findings from genetic linkage, knockout, and physiologic studies in mice and rats led us to conduct the first investigation of the novel angiotensin-converting enzyme 2 gene (ACE2) in human hypertension (HT). We genotyped four single nucleotide polymorphisms (SNP) (A-->G at nucleotide 1075 in intron 1, G-->A at nucleotide 8790 in intron 3, C-->G at nucleotide 28330 in intron 11, and G-->C at nucleotide 36787 in intron 16) in HT (n = 152) and normotensive (NT, n = 193) groups having inherently high biological power (>80%) due to our inclusion only of subjects whose parents had the same BP status as themselves. The SNPs were in linkage disequilibrium (D' = 54% to 100%, P =.05 to 0.0001). Because ACE2 is on the X chromosome, data for each sex were analyzed separately. Minor allele frequencies in HT versus NT were as follows: for the intron 1 variant 0.21 versus 0.17 in female subjects (P =.31) and 0.25 versus 0.29 in male subjects (P =.60); intron 3 variant 0.22 versus 0.18 in female subjects (P =.35) and 0.15 versus 0.20 in male subjects (P =.47); intron 11 variant 0.39 versus 0.46 in male subjects (P = 0.17) and 0.31 versus 0.30 in male subjects (P =.96); intron 16 variant 0.20 versus 0.19 in female subjects (P =.72) and 0.17 versus 0.17 in male subjects (P =.95). Haplotype analysis was also negative. These data provide little support for ACE2 in genetic predisposition to HT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjhyper.2004.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110370PMC
July 2004

Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension.

J Hypertens 2004 May;22(5):931-6

Basic & Clinical Genomics Laboratory, School of Medical Sciences and Institute for Biomedical Research, The University of Sydney, Sydney, NSW 2006, Australia.

Objective: To perform association studies of polymorphisms of the potential candidate essential hypertension (HT) genes GRK4, PTP1B and HSD3B1.

Methods: Subjects consisted of 168 unrelated, Caucasian essential hypertensive (HT) patients and 312 normotensive (NT) controls. Biological power was increased by ensuring subjects in each group had parents with the same blood pressure (BP) status as theirs. Three GRK4gamma variants (R65L, A142V and A486V), one HSD3B1 variant (T<---C Leu) and one PTP1B variant (1484insG) were genotyped by polymerase chain reaction and restriction enzyme digestion or by homogenous MassEXTEND Assay.

Results: The V allele of the A486V variant of GRK4gamma, but not the R65L or A142V variants, showed an association with HT (P = 0.02). The V allele was also associated with an elevation in systolic blood pressure (SBP) (P = 0.002). Although the L65 and the V142 alleles tracked with elevation in diastolic (DBP), this was seen only in male HTs (P = 0.009; P = 0.002, respectively). Haplotype frequencies differed between the HT and NT groups, particularly for the R, V, V haplotype combination of R65L, A142V and A486V, respectively. Neither of the HSD3B1 or PTP1B variants were associated with HT.

Conclusion: Genetic variation in GRK4gamma was associated with HT in the subjects studied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00004872-200405000-00014DOI Listing
May 2004

Overweight, but not hypertension, is associated with SAH polymorphisms in Caucasians with essential hypertension.

Hypertens Res 2003 Aug;26(8):591-5

Basic & Clinical Genomics Laboratory, School of Medical Science and Institute for Biomedical Research, The University of Sydney, Sydney, Australia.

The gene SAH (chromosome 16p12.3) is of interest in the etiology of human hypertension. In Caucasians a PstI restriction fragment length polymorphism (RFLP) of SAH has been correlated with body weight in individuals with hypertension. To extend this finding we carried out a case-control study of several recently identified polymorphisms in SAH: 1) an insertion/deletion of TTTAA at nucleotide --1037 in the promoter; 2) an insertion/deletion of two Alu like sequences in intron 1; and 3) an A-G variant in intron 12 located 7 bp upstream from exon 13. Subjects were 121 hypertensives with 2 hypertensive parents and 178 normotensives whose parents were both normotensive. All were Anglo-Celtic Caucasians and 51% of the hypertensives were overweight (body mass index (BMI)>25 kg/m2). The SAH promoter and intron 1 variants, but not the intron 12 or PstI RFLP, were in linkage disequilibrium (LD) (D'=100%, p<0.001). We found no association between any of the polymorphisms and hypertension. However, the frequency of the minor allele of the intron 1 polymorphism (0.20) was higher in overweight than in normal weight hypertensives (0.07) (p=0.013). This association was supported by the weak tracking of plasma lipid variables with this allele (p values=0.01-0.04), although these lost their statistical significance after correction for multiple comparisons. In conclusion, the present data offers support for variation in SAH having a role in predisposition to overweight in hypertensives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1291/hypres.26.591DOI Listing
August 2003

Essential hypertension: genes and dreams.

Clin Chem Lab Med 2003 Jul;41(7):834-44

Basic & Clinical Genomics Laboratory, School of Medical Sciences and Institute for Biomedical Research, The University of Sydney, Sydney, Australia.

Herein we review all of the data from linkage by genome scanning and from association studies in essential hypertension. Genome scans have yielded loci linked to hypertension on almost every chromosome. We tabulate all of these loci to highlight the striking inconsistency. Similarly, association studies have implicated > 66 genes to date, which we also list, but virtually all have failed to show consistent replication in other settings. Nevertheless, we believe that molecular genetics should eventually find all of the major gene variants for essential hypertension. This will be a great scientific achievement and lead to new treatments. The dream, however, of using this information in clinical genetic testing could turn out to be a nightmare. Thus at present the hype surrounding genes for complex polygenic diseases like hypertension far exceeds the reality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/CCLM.2003.127DOI Listing
July 2003

Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension.

J Hypertens 2003 Jul;21(7):1331-7

Department of Physiology, School of Medical Sciences, and Institute for Biomedical Research, The University of Sydney, Sydney, Australia.

Objective: The CYP11B2 locus is an important candidate region in essential hypertension (HT). We therefore investigated CYP11B2 polymorphisms T-344C, T4986C and A6547G for association with essential HT. This included haplotype analysis and measurement of plasma aldosterone levels.

Methods: The three single nucleotide polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis of genomic DNA from 146 HT and 291 normotensive (NT) white subjects of Anglo-Celtic descent, in whom parental blood pressure status was the same as the subjects'. Genotype and allele frequencies in HTs and NTs were compared by chi2 analysis. Linkage disequilibrium and haplotype frequencies were estimated by the program 'snphap'. Phenotype-genotype relationships were tested using one-way analysis of variance.

Results: The T-344C variant was associated with HT (chi2 = 7.4, P = 0.0064). This association was confined to female HTs (P = 0.0061 for genotypes, P = 0.0013 for alleles). A strong association with HT was also seen for the A6547G variant (P = 0.0015), being greatest in females (P < 0.0001). No association was seen for the T4986C variant. Haplotype analysis of the three single nucleotide polymorphisms across eight different haplotype combinations showed a significant association with HT (chi2 = 24, seven degrees of freedom, P < 0.001). No significant tracking of plasma aldosterone with genotype was observed.

Conclusion: The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in females of the Anglo-Celtic population studied. This was reinforced by haplotype analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00004872-200307000-00022DOI Listing
July 2003