Publications by authors named "Lyndia Brumback"

46 Publications

Improving communication about goals of care for hospitalized patients with serious illness: Study protocol for two complementary randomized trials.

Contemp Clin Trials 2022 Aug 10:106879. Epub 2022 Aug 10.

Cambia Palliative Care Center of Excellence at UW Medicine, University of Washington, Seattle, WA, United States of America; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, United States of America.

Background: Although goals-of-care discussions are important for high-quality palliative care, this communication is often lacking for hospitalized older patients with serious illness. Electronic health records (EHR) provide an opportunity to identify patients who might benefit from these discussions and promote their occurrence, yet prior interventions using the EHR for this purpose are limited. We designed two complementary yet independent randomized trials to examine effectiveness of a communication-priming intervention (Jumpstart) for hospitalized older adults with serious illness.

Methods: We report the protocol for these 2 randomized trials. Trial 1 has two arms, usual care and a clinician-facing Jumpstart, and is a pragmatic trial assessing outcomes with the EHR only (n = 2000). Trial 2 has three arms: usual care, clinician-facing Jumpstart, and clinician- and patient-facing (bi-directional) Jumpstart (n = 600). We hypothesize the clinician-facing Jumpstart will improve outcomes over usual care and the bi-directional Jumpstart will improve outcomes over the clinician-facing Jumpstart and usual care. We use a hybrid effectiveness-implementation design to examine implementation barriers and facilitators.

Outcomes: For both trials, the primary outcome is EHR documentation of a goals-of-care discussion within 30 days of randomization; additional outcomes include intensity of end-of-life care. Trial 2 also examines patient- or family-reported outcomes assessed by surveys targeting 3-5 days and 4-8 weeks after randomization including quality of goals-of-care communication, receipt of goal-concordant care, and psychological symptoms.

Conclusions: This novel study incorporates two complementary randomized trials and a hybrid effectiveness-implementation approach to improve the quality and value of care for hospitalized older adults with serious illness.

Clinical Trials Registration: STUDY00007031-A and STUDY00007031-B.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cct.2022.106879DOI Listing
August 2022

Seriously Ill Patients' Prioritized Goals and Their Clinicians' Perceptions of Those Goals.

J Pain Symptom Manage 2022 Jun 11. Epub 2022 Jun 11.

Division of Pulmonary (R.A.E., E.L.N., J.R.C., E.K.K.), Critical Care and Sleep Medicine, University of Washington, Seattle, Washington, USA; Cambia Palliative Care Center of Excellence (R.A.E., E.L.N., L.C.B., J.R.C., E.K.K.), University of Washington, Seattle, Washington, USA.

Context: Seriously ill patients whose prioritized healthcare goals are understood by their clinicians are likely better positioned to receive goal-concordant care.

Objectives: To examine the proportion of seriously ill patients whose prioritized healthcare goal is accurately perceived by their clinician and identify factors associated with accurate perception.

Methods: Secondary analysis of a multicenter cluster-randomized trial of outpatients with serious illness and their clinicians. Approximately two weeks after a clinic visit, patients reported their current prioritized healthcare goal- extending life over relief of pain and discomfort, or relief of pain and discomfort over extending life - and clinicians reported their perception of their patients' current prioritized healthcare goal; matching these items defined accurate perception.

Results: Of 252 patients with a prioritized healthcare goal, 60% had their goal accurately perceived by their clinician, 27% were cared for by clinicians who perceived prioritization of the alternative goal, and 13% had their clinician answer unsure. Patients who were older (OR 1.03 per year; 95%CI 1.01, 1.05), had stable goals (OR 2.52; 95%CI 1.26, 5.05), and had a recent goals-of-care discussion (OR 1.78, 95%CI 1.00, 3.16) were more likely to have their goals accurately perceived.

Conclusion: A majority of seriously ill outpatients are cared for by clinicians who accurately perceive their patients' prioritized healthcare goals. However, a substantial portion are not and may be at higher risk for goal-discordant care. Interventions that facilitate goals-of-care discussions may help align care with goals, as recent discussions were associated with accurate perceptions of patients' prioritized goals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpainsymman.2022.06.004DOI Listing
June 2022

Efficacy of a Communication-Priming Intervention on Documented Goals-of-Care Discussions in Hospitalized Patients With Serious Illness: A Randomized Clinical Trial.

JAMA Netw Open 2022 04 1;5(4):e225088. Epub 2022 Apr 1.

Cambia Palliative Care Center of Excellence at UW Medicine, University of Washington, Seattle.

Importance: High-quality goals-of-care communication is critical to delivering goal-concordant, patient-centered care to hospitalized patients with chronic life-limiting illness. However, implementation and documentation of goals-of-care discussions remain important shortcomings in many health systems.

Objective: To evaluate the efficacy, feasibility, and acceptability of a patient-facing and clinician-facing communication-priming intervention to promote goals-of-care communication for patients hospitalized with serious illness.

Design, Setting, And Participants: This randomized clinical trial enrolled patients from November 6, 2018, to February 18, 2020. The setting was 2 hospitals in an academic health care system in Seattle, Washington. Participants included hospitalized adults with chronic life-limiting illness, aged 65 years or older and with markers of frailty, or aged 80 years or older. Data analysis was performed from August 2020 to August 2021.

Intervention: Patients were randomized to usual care with baseline questionnaires (control) vs the Jumpstart communication-priming intervention. Patients or surrogates in the intervention group and their clinicians received patient-specific Jumpstart Guides populated with data from questionnaires and the electronic health records (EHRs) that were designed to prompt and guide a goals-of-care discussion.

Main Outcomes And Measures: The primary outcome was EHR documentation of a goals-of-care discussion between randomization and hospital discharge. Additional outcomes included patient-reported or surrogate-reported goals-of-care discussions, patient-reported or surrogate-reported quality of communication, and intervention feasibility and acceptability.

Results: Of 428 eligible patients, this study enrolled 150 patients (35% enrollment rate; mean [SD] age, 59.2 [13.6] years; 66 women [44%]; 132 [88%] by patient consent and 18 [12%] by surrogate consent). Seventy-five patients each were randomized to the intervention and control groups. Compared with the control group, the cumulative incidence of EHR-documented goals-of-care discussions between randomization and hospital discharge was higher in the intervention group (16 of 75 patients [21%] vs 6 of 75 patients [8%]; risk difference, 13% [95% CI, 2%-24%]; risk ratio, 2.67 [95% CI, 1.10-6.44]; P = .04). Patient-reported or surrogate-reported goals-of-care discussions did not differ significantly between groups (30 of 66 patients [45%] vs 36 of 66 patients [55%]), although the intrarater consistency of patient and surrogate reports was poor. Patient-rated or surrogate-rated quality of communication did not differ significantly between groups. The intervention was feasible and acceptable to patients, surrogates, and clinicians.

Conclusions And Relevance: In this randomized clinical trial, a patient-facing and clinician-facing communication priming intervention for seriously ill, hospitalized patients promoted EHR-documented goals-of-care discussions before discharge with good feasibility and acceptability. Communication-priming interventions should be reexamined in a larger randomized clinical trial to better understand their effectiveness in the inpatient setting.

Trial Registration: ClinicalTrials.gov Identifier: NCT03746392.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2022.5088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976242PMC
April 2022

Inter-arm systolic blood pressure difference: non-persistence and association with incident cardiovascular disease in the Multi-ethnic Study of Atherosclerosis.

J Hum Hypertens 2022 Mar 16. Epub 2022 Mar 16.

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

We investigated inter-arm systolic blood pressure (sIAD) difference, reproducibility, and incident cardiovascular disease (CVD). We hypothesized that higher sIAD values have low prevalence and nonpersistence over years, but that CVD risk is higher starting from the time of first high absolute sIAD. In Multi-Ethnic Study of Atherosclerosis participants (n = 6725, 53% female, 45-84 years old), Doppler systolic blood pressure (SBP) measurements were made in both arms (10-minute interval) thrice over 9.5 years. Proportional hazards for CVD (coronary heart disease, heart failure, stroke, peripheral arterial disease (PAD)) over 16.4 years were tested according to time-varying absolute inter-arm difference with covariates: (1) age, gender, race, and clinic; (2) model 1 plus height, heart rate, BP, antihypertensives, BMI, smoking status, lipids, lipid lowering medication, and diabetes. High sIAD was not persistent across exams. Maximum absolute sIAD ≥ 15 mmHg was found at least once in 815 persons. Maximum absolute sIAD had a graded relationship with incident stroke or PAD: 6.2% events; model 2 hazard ratio per 10 mmHg 1.34 (95% CI, 1.15-1.56) and this risk was approximately doubled for maximum absolute sIAD ≥ 15 mmHg vs 0-4 mmHg. Total CVD risk (18.4% events) was increased only for maximum absolute sIAD ≥25 mmHg. Associations with incident CVD did not differ for higher SBP in left vs right arm. A higher maximum absolute sIAD at any exam was associated with greater risk for stroke and PAD especially for values ≥ 15 mmHg, and ≥25 mmHg for other CVD. Measuring SBP between arms may help identify individuals at risk for CVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41371-022-00669-xDOI Listing
March 2022

Mixed-methods evaluation of three natural language processing modeling approaches for measuring documented goals-of-care discussions in the electronic health record.

J Pain Symptom Manage 2022 06 16;63(6):e713-e723. Epub 2022 Feb 16.

Department of Medicine (A.M.U., J.R.C., R.A.E., J.T., J.H., S.R.P., E.K.K., R.Y.L.), University of Washington, Seattle, WA; Cambia Palliative Care Center of Excellence at UW Medicine (A.M.U., J.R.C., R.A.E., L.C.B., Y.G., J.S., W.B.L., T.C., J.T., J.H., S.R.P., E.K.K., R.Y.L.), University of Washington, Seattle, WA; Division of Pulmonary, Critical Care, and Sleep Medicine (J.R.C., R.A.E., J.T., J.H., S.R.P., E.K.K., R.Y.L.), Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA.

Context: Documented goals-of-care discussions are an important quality metric for patients with serious illness. Natural language processing (NLP) is a promising approach for identifying goals-of-care discussions in the electronic health record (EHR).

Objectives: To compare three NLP modeling approaches for identifying EHR documentation of goals-of-care discussions and generate hypotheses about differences in performance.

Methods: We conducted a mixed-methods study to evaluate performance and misclassification for three NLP featurization approaches modeled with regularized logistic regression: bag-of-words (BOW), rule-based, and a hybrid approach. From a prospective cohort of 150 patients hospitalized with serious illness over 2018 to 2020, we collected 4391 inpatient EHR notes; 99 (2.3%) contained documented goals-of-care discussions. We used leave-one-out cross-validation to estimate performance by comparing pooled NLP predictions to human abstractors with receiver-operating-characteristic (ROC) and precision-recall (PR) analyses. We qualitatively examined a purposive sample of 70 NLP-misclassified notes using content analysis to identify linguistic features that allowed us to generate hypotheses underpinning misclassification.

Results: All three modeling approaches discriminated between notes with and without goals-of-care discussions (AUC: BOW, 0.907; rule-based, 0.948; hybrid, 0.965). Precision and recall were only moderate (precision at 70% recall: BOW, 16.2%; rule-based, 50.4%; hybrid, 49.3%; AUC: BOW, 0.505; rule-based, 0.579; hybrid, 0.599). Qualitative analysis revealed patterns underlying performance differences between BOW and rule-based approaches.

Conclusion: NLP holds promise for identifying EHR-documented goals-of-care discussions. However, the rarity of goals-of-care content in EHR data limits performance. Our findings highlight opportunities to optimize NLP modeling approaches, and support further exploration of different NLP approaches to identify goals-of-care discussions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpainsymman.2022.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124686PMC
June 2022

Assessment of Discordance Between Physicians and Family Members Regarding Prognosis in Patients With Severe Acute Brain Injury.

JAMA Netw Open 2021 10 1;4(10):e2128991. Epub 2021 Oct 1.

Cambia Palliative Care Center of Excellence, University of Washington, Seattle.

Importance: Shared decision-making requires key stakeholders to align in perceptions of prognosis and likely treatment outcomes.

Objective: For patients with severe acute brain injury, the objective of this study was to better understand prognosis discordance between physicians and families by determining prevalence and associated factors.

Design, Setting, And Participants: This mixed-methods cross-sectional study analyzed a cohort collected from January 4, 2018, to July 22, 2020. This study was conducted in the medical and cardiac intensive care units of a single neuroscience center. Participants included families, physicians, and nurses of patients admitted with severe acute brain injury.

Exposures: Severe acute brain injury was defined as stroke, traumatic brain injury, or hypoxic ischemic encephalopathy with a Glasgow Coma Scale score less than or equal to 12 points after hospital day 2.

Main Outcomes And Measures: Prognosis discordance was defined as a 20% or greater difference between family and physician prognosis predictions; misunderstanding was defined as a 20% or greater difference between physician prediction and the family's estimate of physician prediction; and optimistic belief difference was defined as any difference (>0%) between family prediction and their estimate of physician prediction. Logistic regression was used to identify associations with discordance. Optimistic belief differences were analyzed as a subgroup of prognosis discordance.

Results: Among 222 enrolled patients, prognostic predictions were available for 193 patients (mean [SD] age, 57 [19] years; 106 men [55%]). Prognosis discordance occurred for 118 patients (61%) and was significantly more common among families who identified with minoritized racial groups compared with White families (odds ratio [OR], 3.14; CI, 1.40-7.07, P = .006); among siblings (OR, 4.93; 95% CI, 1.35-17.93, P = .02) and adult children (OR, 2.43; 95% CI, 1.10-5.37; P = .03) compared with spouses; and when nurses perceived family understanding as poor compared with good (OR, 3.73; 95% CI, 1.88-7.40; P < .001). Misunderstanding was present for 80 of 173 patients (46%) evaluated for this type of prognosis discordance, and optimistic belief difference was present for 94 of 173 patients (54%). In qualitative analysis, faith and uncertainty emerged as themes underlying belief differences. Nurse perception of poor family understanding was significantly associated with misunderstanding (OR, 2.06; 95% CI, 1.07-3.94; P = .03), and physician perception with optimistic belief differences (OR, 2.32; 95% CI, 1.10-4.88; P = .03).

Conclusions And Relevance: Results of this cross-sectional study suggest that for patients with severe acute brain injury, prognosis discordance between physicians and families was common. Efforts to improve communication and decision-making should aim to reduce this discordance and find ways to target both misunderstanding and optimistic belief differences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2021.28991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531991PMC
October 2021

Atherothrombotic factors and atherosclerotic cardiovascular events: the multi-ethnic study of atherosclerosis.

Eur Heart J 2022 03;43(10):971-981

Division of Cardiology, Department of Medicine, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.

Aims: Traditional atherosclerotic cardiovascular disease (ASCVD) risk factors fail to address the full spectrum of the complex interplay of atherosclerotic and atherothrombotic factors integral to ASCVD events. This study sought to examine the association between atherothrombotic biomarkers and ASCVD events.

Methods And Results: The association between atherothrombotic biomarkers and 877 ASCVD events with and without adjustment for traditional risk factors was evaluated via Cox proportional hazards models and factor analysis in 5789 Multi-Ethnic Study of Atherosclerosis participants over a median follow-up of 14.7 years. Factor analysis accounted for multidimensional relationship and shared variance among study biomarkers, which identified two new variables: a thrombotic factor (Factor 1), principally defined by shared variance in fibrinogen, plasmin-antiplasmin complex, factor VIII, D-dimer, and lipoprotein(a), and a fibrinolytic factor (Factor 2), principally defined by shared variance of plasminogen and oxidized phospholipids on plasminogen. In a model including both factors, the thrombotic factor was associated with the higher risk of ASCVD events [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.45, 1.70], while the fibrinolytic factor was associated with the lower risk of ASCVD events (HR 0.76, 95% CI 0.70, 0.82), with estimated ASCVD free survival highest for low atherothrombotic Factor 1 and high atherothrombotic Factor 2.

Conclusion: Two atherothrombotic factors, one representative of thrombotic propensity and the other representative of fibrinolytic propensity, were significantly and complementarily associated with incident ASCVD events, remained significantly associated with incident ASCVD after controlling for traditional risk factors, and have promise for identifying patients at high ASCVD event risk specifically due to their atherothrombotic profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899529PMC
March 2022

Advance Care Planning Documentation and Intensity of Care at the End of Life for Adults With Congestive Heart Failure, Chronic Kidney Disease, and Both Illnesses.

J Pain Symptom Manage 2022 02 4;63(2):e168-e175. Epub 2021 Aug 4.

Cambia Palliative Care Center of Excellence, University of Washington (G.M.B., C.L.M., J.R.C.), Seattle, WA; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington (R.A.E., J.R.C.), Seattle, WA.

Context: Heart failure (HF) and chronic kidney disease (CKD) are associated with high morbidity and mortality, especially in combination, yet little is known about the impact of these conditions together on end-of-life care.

Objectives: Compare end-of-life care and advance care planning (ACP) documentation among patients with both HF and CKD to those with either condition.

Methods: We conducted a retrospective analysis of deceased patients (2010-2017) with HF and CKD (n = 1673), HF without CKD (n = 2671), and CKD without HF (n = 1706), excluding patients with cancer or dementia. We compared hospitalizations and intensive care unit (ICU) admissions in the last 30 days of life, hospital deaths, and ACP documentation >30 days before death.

Results: 39% of patients with HF and CKD were hospitalized and 33% were admitted to the ICU in the last 30 days vs. 30% and 28%, respectively, for HF, and 26% and 23% for CKD. Compared to patients with both conditions, those with only 1 were less likely to be admitted to the hospital [HF: adjusted odds ratio (aOR) 0.72, 95%CI 0.63-0.83; CKD: aOR 0.63, 95%CI 0.53-0.75] and ICU (HF: aOR 0.83, 95%CI 0.71-0.94; CKD: aOR 0.68, 95%CI 0.56-0.80) and less likely to have ACP documentation (aOR 0.53, 95%CI 0.47-0.61 and aOR 0.70, 95%CI 0.60-0.81).

Conclusions: Decedents with both HF and CKD had more ACP documentation and received more intensive end-of-life care than those with only 1 condition. These findings suggest that patients with co-existing HF and CKD may benefit from interventions to ensure care received aligns with their goals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpainsymman.2021.07.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814047PMC
February 2022

Facilitating communication for critically ill patients and their family members: Study protocol for two randomized trials implemented in the U.S. and France.

Contemp Clin Trials 2021 08 3;107:106465. Epub 2021 Jun 3.

Cambia Palliative Care Center of Excellence and Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, United States.

Background: Critically-ill patients and their families suffer a high burden of psychological symptoms due, in part, to many transitions among clinicians and settings during and after critical illness, resulting in fragmented care. Communication facilitators may help.

Design And Intervention: We are conducting two cluster-randomized trials, one in the U.S. and one in France, with the goal of evaluating a nurse facilitator trained to support, model, and teach communication strategies enabling patients and families to secure care consistent with patients' goals, beginning in ICU and continuing for 3 months.

Participants: We will randomize 376 critically-ill patients in the US and 400 in France to intervention or usual care. Eligible patients have a risk of hospital mortality of greater than15% or a chronic illness with a median survival of approximately 2 years or less.

Outcomes: We assess effectiveness with patient- and family-centered outcomes, including symptoms of depression, anxiety, and post-traumatic stress, as well as assessments of goal-concordant care, at 1-, 3-, and 6-months post-randomization. The primary outcome is family symptoms of depression over 6 months. We also evaluate whether the intervention improves value by reducing utilization while improving outcomes. Finally, we use mixed methods to explore implementation factors associated with implementation outcomes (acceptability, fidelity, acceptability, penetration) to inform dissemination. Conducting the trial in U.S. and France will provide insights into differences and similarities between countries.

Conclusions: We describe the design of two randomized trials of a communication facilitator for improving outcomes for critically ill patients and their families in two countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cct.2021.106465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429114PMC
August 2021

The association between indices of blood pressure waveforms (PTC1 and PTC2) and incident heart failure.

J Hypertens 2021 04;39(4):661-666

Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.

Objectives: The radial artery pulse waveform is a continuous measure of pressure throughout the cardiac cycle, and thus can provide more information than just systolic and diastolic blood pressures. New indices based on a Windkessel model of the waveform, PTC1 and PTC2, are related to arterial compliance and add information for prediction of incident cardiovascular disease (coronary heart disease, stroke, myocardial infarction) but their association with heart failure is unknown.

Methods: Among 6229 adults (mean age 62 years) from four race/ethnic groups who were initially free of clinical cardiovascular disease and heart failure in 2000-2002, we evaluated the associations of baseline PTC1 and PTC2 with incident heart failure.

Results: Mean ± standard deviation PTC1 and PTC2 were 394 ± 334 and 94 ± 46 ms, respectively. During a median of 15.7 years follow-up, there were 357 heart failure events (148 with reduced, 150 with preserved, and 59 with unknown ejection fraction). After adjustment for traditional risk factors, the hazard ratio for heart failure per 1 standard deviation higher PTC2 was 0.73 (95% confidence interval: 0.63--0.85). Higher PTC2 was also significantly associated with lower risk of heart failure with reduced ejection fraction (hazard ratio = 0.67; 95% confidence interval: 0.56--0.80). There was no evidence of a significant association between PTC2 and heart failure with preserved ejection fraction or between PTC1 and heart failure.

Conclusion: The PTC2 measure of the radial artery pulse waveform may represent a novel phenotype related to heart failure, especially heart failure with reduced ejection fraction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177733PMC
April 2021

Identifying Goals of Care Conversations in the Electronic Health Record Using Natural Language Processing and Machine Learning.

J Pain Symptom Manage 2021 01 25;61(1):136-142.e2. Epub 2020 Aug 25.

Cambia Palliative Care Center of Excellence, University of Washington, Seattle, Washington, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Harborview Medical Center, University of Washington, Seattle, Washington, USA; Department of Biobehavioral Nursing and Health Informatics, University of Washington, Seattle, Washington, USA; Department of Bioethics and Humanities, University of Washington, Seattle, Washington, USA. Electronic address:

Context: Goals-of-care discussions are an important quality metric in palliative care. However, goals-of-care discussions are often documented as free text in diverse locations. It is difficult to identify these discussions in the electronic health record (EHR) efficiently.

Objectives: To develop, train, and test an automated approach to identifying goals-of-care discussions in the EHR, using natural language processing (NLP) and machine learning (ML).

Methods: From the electronic health records of an academic health system, we collected a purposive sample of 3183 EHR notes (1435 inpatient notes and 1748 outpatient notes) from 1426 patients with serious illness over 2008-2016, and manually reviewed each note for documentation of goals-of-care discussions. Separately, we developed a program to identify notes containing documentation of goals-of-care discussions using NLP and supervised ML. We estimated the performance characteristics of the NLP/ML program across 100 pairs of randomly partitioned training and test sets. We repeated these methods for inpatient-only and outpatient-only subsets.

Results: Of 3183 notes, 689 contained documentation of goals-of-care discussions. The mean sensitivity of the NLP/ML program was 82.3% (SD 3.2%), and the mean specificity was 97.4% (SD 0.7%). NLP/ML results had a median positive likelihood ratio of 32.2 (IQR 27.5-39.2) and a median negative likelihood ratio of 0.18 (IQR 0.16-0.20). Performance was better in inpatient-only samples than outpatient-only samples.

Conclusion: Using NLP and ML techniques, we developed a novel approach to identifying goals-of-care discussions in the EHR. NLP and ML represent a potential approach toward measuring goals-of-care discussions as a research outcome and quality metric.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpainsymman.2020.08.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769906PMC
January 2021

Cardiopulmonary Resuscitation Preferences of People Receiving Dialysis.

JAMA Netw Open 2020 08 3;3(8):e2010398. Epub 2020 Aug 3.

Department of Medicine, University of Washington, Seattle.

Importance: Whether the cardiopulmonary resuscitation (CPR) preferences of patients receiving dialysis align with their values and other aspects of end-of-life care is not known.

Objective: To describe the CPR preferences of patients receiving dialysis and how these preferences are associated with their responses to questions about other aspects of end-of-life care.

Design, Setting, And Participants: Cross-sectional survey study of a consecutive sample of patients receiving dialysis at 31 nonprofit dialysis facilities in 2 US metropolitan areas (Seattle, Washington, and Nashville, Tennessee) between April 22, 2015, and October 2, 2018. Analyses for this article were conducted between December 2018 and April 2020.

Exposures: Participants were asked to respond to the question "If you had to decide right now, would you want CPR if your heart were to stop beating?" Those who indicated they would probably or definitely want CPR were categorized as preferring CPR.

Main Outcomes And Measures: This study examined the association between preference for CPR and other treatment preferences, engagement in advance care planning, values, desired place of death, expectations about prognosis, symptoms, and palliative care needs.

Results: Of the 1434 individuals invited to complete the survey, 1009 agreed to participate, and 876 were included in the analytic cohort (61.1%). The final cohort had a mean (SD) age of 62.6 (14.0) years; 492 (56.2%) were men, and 528 (60.3%) were White individuals. Among 738 of 876 participants (84.2%) who indicated that they would definitely or probably want CPR (CPR group), 555 (75.2%) wanted mechanical ventilation vs 13 of 138 (9.4%) of those who did not want CPR (do not resuscitate [DNR] group) (P < .001). A total of 249 of 738 participants (33.7%) in the CPR group vs 84 of 138 (60.9%) in the DNR group had documented treatment preferences (P < .001). In terms of values about future care, 171 participants (23.2%) in the CPR group vs 5 of 138 (3.6%) in the DNR group valued life prolongation (P < .001); 320 in the CPR group (43.4%) vs 109 of 138 in the DNR group (79.0%) valued comfort (P < .001); and 247 participants (33.5%) in the CPR group vs 24 of 138 (17.4%) in the DNR group were unsure about their wishes for future care (P < .001). In the CPR group, 207 (28.0%) had thought about stopping dialysis vs 62 of 138 (44.9%) in the DNR group (P < .001), and 181 (24.5%) vs 58 of 138 (42.0%) had discussed stopping dialysis (P = .001). No statistically significant associations were observed between CPR preference and documentation of a surrogate decision maker, thoughts or discussion of hospice, preferred place of death, expectations about prognosis, reported symptoms, or palliative care needs.

Conclusions And Relevance: The CPR preferences of patients receiving dialysis were associated with some, but not all, other aspects of end-of-life care. How participants responded to questions about these other aspects of end-of-life care were not always aligned with their CPR preference. More work is needed to integrate discussions about code status with bigger picture conversations about patients' values, goals, and preferences for end-of-life care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.10398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445594PMC
August 2020

Association of Physician Orders for Life-Sustaining Treatment With ICU Admission Among Patients Hospitalized Near the End of Life.

JAMA 2020 03;323(10):950-960

Cambia Palliative Care Center of Excellence, University of Washington, Seattle.

Importance: Patients with chronic illness frequently use Physician Orders for Life-Sustaining Treatment (POLST) to document treatment limitations.

Objectives: To evaluate the association between POLST order for medical interventions and intensive care unit (ICU) admission for patients hospitalized near the end of life.

Design, Setting, And Participants: Retrospective cohort study of patients with POLSTs and with chronic illness who died between January 1, 2010, and December 31, 2017, and were hospitalized 6 months or less before death in a 2-hospital academic health care system.

Exposures: POLST order for medical interventions ("comfort measures only" vs "limited additional interventions" vs "full treatment"), age, race/ethnicity, education, days from POLST completion to admission, histories of cancer or dementia, and admission for traumatic injury.

Main Outcomes And Measures: The primary outcome was the association between POLST order and ICU admission during the last hospitalization of life; the secondary outcome was receipt of a composite of 4 life-sustaining treatments: mechanical ventilation, vasopressors, dialysis, and cardiopulmonary resuscitation. For evaluating factors associated with POLST-discordant care, the outcome was ICU admission contrary to POLST order for medical interventions during the last hospitalization of life.

Results: Among 1818 decedents (mean age, 70.8 [SD, 14.7] years; 41% women), 401 (22%) had POLST orders for comfort measures only, 761 (42%) had orders for limited additional interventions, and 656 (36%) had orders for full treatment. ICU admissions occurred in 31% (95% CI, 26%-35%) of patients with comfort-only orders, 46% (95% CI, 42%-49%) with limited-interventions orders, and 62% (95% CI, 58%-66%) with full-treatment orders. One or more life-sustaining treatments were delivered to 14% (95% CI, 11%-17%) of patients with comfort-only orders and to 20% (95% CI, 17%-23%) of patients with limited-interventions orders. Compared with patients with full-treatment POLSTs, those with comfort-only and limited-interventions orders were significantly less likely to receive ICU admission (comfort only: 123/401 [31%] vs 406/656 [62%], aRR, 0.53 [95% CI, 0.45-0.62]; limited interventions: 349/761 [46%] vs 406/656 [62%], aRR, 0.79 [95% CI, 0.71-0.87]). Across patients with comfort-only and limited-interventions POLSTs, 38% (95% CI, 35%-40%) received POLST-discordant care. Patients with cancer were significantly less likely to receive POLST-discordant care than those without cancer (comfort only: 41/181 [23%] vs 80/220 [36%], aRR, 0.60 [95% CI, 0.43-0.85]; limited interventions: 100/321 [31%] vs 215/440 [49%], aRR, 0.63 [95% CI, 0.51-0.78]). Patients with dementia and comfort-only orders were significantly less likely to receive POLST-discordant care than those without dementia (23/111 [21%] vs 98/290 [34%], aRR, 0.44 [95% CI, 0.29-0.67]). Patients admitted for traumatic injury were significantly more likely to receive POLST-discordant care (comfort only: 29/64 [45%] vs 92/337 [27%], aRR, 1.52 [95% CI, 1.08-2.14]; limited interventions: 51/91 [56%] vs 264/670 [39%], aRR, 1.36 [95% CI, 1.09-1.68]). In patients with limited-interventions orders, older age was significantly associated with less POLST-discordant care (aRR, 0.93 per 10 years [95% CI, 0.88-1.00]).

Conclusions And Relevance: Among patients with POLSTs and with chronic life-limiting illness who were hospitalized within 6 months of death, treatment-limiting POLSTs were significantly associated with lower rates of ICU admission compared with full-treatment POLSTs. However, 38% of patients with treatment-limiting POLSTs received intensive care that was potentially discordant with their POLST.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2019.22523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042829PMC
March 2020

PTC1 and PTC2: New Indices of Blood Pressure Waveforms and Cardiovascular Disease.

Am J Epidemiol 2020 07;189(7):726-734

Systolic and diastolic blood pressures provide information about cardiovascular disease (CVD) but are only extremes of the pressure waveform during the cardiac cycle. We developed summaries of the pressure decay, called PTC1 and PTC2, that are related to arterial compliance and to an existing proprietary summary that has been shown to predict CVD. We derived the summaries from a Windkessel model (consisting of a decaying exponential plus a dampened cosine, with an intercept so they are independent of calibration with blood pressure, unlike the proprietary measures), and we estimated them using nonlinear least squares with standard, free software. Among 6,228 adults from the Multi-Ethnic Study of Atherosclerosis, initially free of CVD in 2000-2002, mean PTC2 was 94 (standard deviation, 46) milliseconds. During median 15-year follow-up, there were 911 CVD events (including 609 incidents of coronary heart disease and 270 strokes). One-standard-deviation higher PTC2 was associated with 17% (95% confidence interval: 10, 24) lower CVD risk, after adjustment for traditional risk factors. Results were similar for PTC1. PTC1 and PTC2 are relatively straightforward to compute and add information beyond traditional risk factors for prediction of CVD. Our work enables others to replicate and extend our results with waveforms from any suitable device.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwz280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608079PMC
July 2020

Agreement With Consensus Statements on End-of-Life Care: A Description of Variability at the Level of the Provider, Hospital, and Country.

Crit Care Med 2019 10;47(10):1396-1401

Department of Anesthesiology, Critical Care and Pain Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel.

Objectives: To develop an enhanced understanding of factors that influence providers' views about end-of-life care, we examined the contributions of provider, hospital, and country to variability in agreement with consensus statements about end-of-life care.

Design And Setting: Data were drawn from a survey of providers' views on principles of end-of-life care obtained during the consensus process for the Worldwide End-of-Life Practice for Patients in ICUs study.

Subjects: Participants in Worldwide End-of-Life Practice for Patients in ICUs included physicians, nurses, and other providers. Our sample included 1,068 providers from 178 hospitals and 31 countries.

Interventions: None.

Measurements And Main Results: We examined views on cardiopulmonary resuscitation and withholding/withdrawing life-sustaining treatments, using a three-level linear mixed model of responses from providers within hospitals within countries. Of 1,068 providers from 178 hospitals and 31 countries, 1% strongly disagreed, 7% disagreed, 11% were neutral, 44% agreed, and 36% strongly agreed with declining to offer cardiopulmonary resuscitation when not indicated. Of the total variability in those responses, 98%, 0%, and 2% were explained by differences among providers, hospitals, and countries, respectively. After accounting for provider characteristics and hospital size, the variance partition was similar. Results were similar for withholding/withdrawing life-sustaining treatments.

Conclusions: Variability in agreement with consensus statements about end-of-life care is related primarily to differences among providers. Acknowledging the primary source of variability may facilitate efforts to achieve consensus and improve decision-making for critically ill patients and their family members at the end of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000003922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446953PMC
October 2019

The Influence of Multimorbidity on Health Care Utilization at the End of Life for Patients with Chronic Conditions.

J Palliat Med 2019 10 9;22(10):1260-1265. Epub 2019 Apr 9.

Cambia Palliative Care Center of Excellence, University of Washington, Seattle, Washington.

To evaluate the association between the number of chronic conditions and hospital utilization at the end of life. An understanding of the association of multimorbidity with health care utilization at the end of life may inform interventions to improve quality of care for these patients. A mortality follow-back analysis using Washington State death records and electronic health records. Subject included patients in the UW Medicine system who had at least one chronic condition and died between 2010 and 2015. Utilization was measured by inpatient admissions, emergency department use, and intensive care unit (ICU) admissions in the last 30 days of life. For all utilization types, patients with three or more chronic conditions ( = 5124) had significantly higher utilization ( < 0.001) in the last 30 days of life than those with two ( = 5775) or one condition ( = 11,169). Comparing 3 versus 2 versus 1 conditions, the following percentages of patients had each type of utilization: inpatient admissions (37% vs. 28% vs. 19%), ED admissions (5% vs. 4% vs. 2%), and ICU care (28% vs. 20% vs. 12%). Multimorbidity was associated with greater health care utilization at the end of life among patients representing a range of ages and covered by diverse insurers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jpm.2018.0349DOI Listing
October 2019

"Sleep disordered breathing and ECG R-wave to radial artery pulse delay, The Multi-Ethnic Study of Atherosclerosis".

Sleep Med 2018 08 21;48:172-179. Epub 2018 May 21.

Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.

Background: Electrocardiography R-wave to radial artery pulse delay (RRD) represents pulse transit time inclusive of pre-ejection period (PEP) and arterial pulse propagation time. RRD is proposed to largely reflect arterial stiffness when PEP is accounted for (shorter RRD = higher arterial stiffness). Sleep disordered breathing (SDB) causes intermittent hypoxemia and sympathetic activation, which negatively influences vascular function. We aimed to examine the association of measures of SDB with RRD.

Methods: Our sample consisted of participants in the Multi-Ethnic Study of Atherosclerosis without prevalent cardiovascular disease who underwent a daytime arterial elasticity exam, cardiac magnetic resonance imaging (MRI), and overnight polysomnography. SDB measures of interest included apnea hypopnea index (AHI) and oxygen desaturation index (ODI) (N = 1173). RRD was regressed on each measure of SDB separately, with adjustment for other cardiovascular risk factors as well as for correlates of the PEP, another component of RRD, by including cardiac MRI measures of contractility and preload.

Results: In multivariate analysis, among measures of SDB, ODI, a marker of intermittent hypoxemia, was inversely associated with RRD (β = -60.2 msec per SD [15.5/hr], p = 0.04). No significant association was found with AHI. In gender stratified analyses, ODI and AHI were predictive of RRD in men only (β = -111.3 msec per SD [15.5/hr], p = 0.01 and β = -100.3 msec per SD [16.1/hr], p = 0.02 respectively).

Conclusion: Severity of SDB as measured by ODI was associated with RRD, a marker of arterial stiffness. Thus, association of RRD with measures of SDB appears to be gender-dependent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleep.2018.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051731PMC
August 2018

Evaluating the Economic Impact of Palliative and End-of-Life Care Interventions on Intensive Care Unit Utilization and Costs from the Hospital and Healthcare System Perspective.

J Palliat Med 2017 12 3;20(12):1314-1320. Epub 2017 Oct 3.

6 Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington , Seattle, Washington.

Purpose of report: Understanding the impact of palliative care interventions on intensive care unit (ICU) costs and utilization is critical for demonstrating the value of palliative care. Performing these economic assessments, however, can be challenging. The purpose of this special report is to highlight and discuss important considerations when assessing ICU utilization and costs from the hospital perspective, with the goal of providing recommendations on methods to consider for future analyses.

Findings: ICU length of stay (LOS) and associated costs of care are common and important outcome measures, but must be analyzed properly to yield valid conclusions. There is significant variation in costs by day of stay in the ICU with only modest differences between an ICU day at the end of a stay and the first day on the acute care floor; this variation must be appropriately accounted for analytically. Furthermore, reporting direct variable costs, in addition to total ICU costs, is needed to understand short-term and long-term impact of a reduction in LOS. Importantly, incentives for the hospital to realize savings vary depending on reimbursement policies.

Summary: ICU utilization and costs are common outcomes in studies evaluating palliative care interventions. Accurate estimation and interpretation are key to understanding the economic implications of palliative care interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jpm.2016.0548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706624PMC
December 2017

Comparing Arterial Function Parameters for the Prediction of Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA).

Am J Epidemiol 2016 12 6;184(12):894-901. Epub 2016 Dec 6.

Arterial dysfunction has been linked to decline in cardiac function and increased risk of cardiovascular disease events. We calculated the value of arterial function, measured at baseline (2000-2002), in predicting time to first coronary heart disease (CHD) event (median follow-up, 10.2 years) among participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Measures included the following: C and C, derived from diastolic pulse contour analysis from the radial artery blood pressure waveform obtained by tonometry (n = 6,336); carotid distensibility and Young's elastic modulus at the carotid artery, derived from carotid artery ultrasonography (n = 6,531 and 6,528); and aortic distensibility, measured using cardiac magnetic resonance imaging (n = 3,677). After adjustment, the hazard ratio for a CHD event per standard-deviation increment in arterial function was 0.97 (95% confidence interval (CI): 0.86, 1.10) for C, 0.73 (95% CI: 0.63, 0.86) for C, 0.98 (95% CI: 0.86, 1.11) for carotid distensibility, 0.99 (95% CI: 0.90, 1.09) for Young's modulus, and 0.90 (95% CI: 0.74, 1.10) for aortic distensibility. We examined the area under the receiver operating characteristic curve for the model with full adjustment plus the addition of each measure individually. C provided additional discrimination for the prediction of CHD (area under the curve = 0.736 vs. 0.743; P = 0.04). Lower C was associated with a higher risk of future CHD events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kww113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161085PMC
December 2016

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis.

J Cyst Fibros 2016 05 4;15(3):386-91. Epub 2015 Nov 4.

Division of Pulmonary Medicine, Seattle Children's Hospital and Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.

Background: The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint.

Methods: Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials.

Results: Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0).

Conclusions: iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcf.2015.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854797PMC
May 2016

Late systolic central hypertension as a predictor of incident heart failure: the Multi-ethnic Study of Atherosclerosis.

J Am Heart Assoc 2015 Mar 3;4(3):e001335. Epub 2015 Mar 3.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (D.R.J.) Department of Nutrition, University of Oslo, Norway (D.R.J.).

Background: Experimental studies demonstrate that high aortic pressure in late systole relative to early systole causes greater myocardial remodeling and dysfunction, for any given absolute peak systolic pressure.

Methods And Results: We tested the hypothesis that late systolic hypertension, defined as the ratio of late (last one third of systole) to early (first two thirds of systole) pressure-time integrals (PTI) of the aortic pressure waveform, independently predicts incident heart failure (HF) in the general population. Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 6124 adults. The late/early systolic PTI ratio (L/E(SPTI)) was assessed as a predictor of incident HF during median 8.5 years of follow-up. The L/E(SPTI) was predictive of incident HF (hazard ratio per 1% increase=1.22; 95% CI=1.15 to 1.29; P<0.0001) even after adjustment for established risk factors for HF (HR=1.23; 95% CI=1.14 to 1.32: P<0.0001). In a multivariate model that included brachial systolic and diastolic blood pressure and other standard risk factors of HF, L/E(SPTI) was the modifiable factor associated with the greatest improvements in model performance. A high L/E(SPTI) (>58.38%) was more predictive of HF than the presence of hypertension. After adjustment for each other and various predictors of HF, the HR associated with hypertension was 1.39 (95% CI=0.86 to 2.23; P=0.18), whereas the HR associated with a high L/E was 2.31 (95% CI=1.52 to 3.49; P<0.0001).

Conclusions: Independently of the absolute level of peak pressure, late systolic hypertension is strongly associated with incident HF in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.114.001335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392425PMC
March 2015

Initial evaluation of the Parent Cystic Fibrosis Questionnaire--Revised (CFQ-R) in infants and young children.

J Cyst Fibros 2015 May 28;14(3):403-11. Epub 2014 Nov 28.

University of Miami, Department of Psychology, 5665 Ponce De Leon Blvd., Coral Gables, FL 33146, USA. Electronic address:

Background: There is an urgent need to evaluate treatments for young children with cystic fibrosis (CF); however, efforts have been hampered by a lack of reliable, practical endpoints. To examine whether a patient-reported outcome could be reliable in children 4 to 60 months of age, we assessed the psychometric properties of the modified Parent Cystic Fibrosis Questionnaire--Revised (CFQ-R) using data from the Infant Study of Inhaled Saline (ISIS). We also characterized patterns of symptom presentation and daily functioning in children in this age range to inform future measure development.

Methods: Parents (N=314) completed the CFQ-R and Treatment Adherence Questionnaire (TAQ) at five quarterly visits, as well as a weekly Parent Symptom Diary.

Results: The Parent CFQ-R demonstrated good construct validity and adequate internal consistency (α's .58-.75). Associations with age, TAQ, and Parent Symptom Diary were observed. The Treatment Burden scale demonstrated responsiveness to change.

Conclusions: Parents were reliable observers of young children's symptoms and daily functioning, and PROs show promise for this age group. Research is needed to identify key symptoms in infants and young children with CF, and to develop a parent proxy PRO according to FDA/EMA guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcf.2014.11.002DOI Listing
May 2015

Reflection magnitude as a predictor of mortality: the Multi-Ethnic Study of Atherosclerosis.

Hypertension 2014 Nov 4;64(5):958-64. Epub 2014 Aug 4.

From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).

Arterial wave reflections have been associated with mortality in an ethnically homogenous Asian population. It is unknown whether this association is present in a multiethnic population or whether it is independent of subclinical atherosclerosis. We hypothesized that reflection magnitude (defined as the ratio of the amplitude of the backward wave [Pb] to that of the forward wave [Pf]) is associated with all-cause mortality in a large multiethnic adult community-based sample. We studied 5984 participants enrolled in the Multi-Ethnic Study of Atherosclerosis who had analyzable arterial tonometry waveforms. During 9.8±1.7 years of follow-up, 617 deaths occurred, of which 134 (22%) were adjudicated cardiovascular deaths. In Cox proportional hazards models, each 10% increase in reflection magnitude was associated with a 31% increased risk for all-cause mortality (hazard ratio [HR]=1.31; 95% confidence interval [CI]=1.11-1.55; P=0.001). This relationship persisted after adjustment for various confounders and for markers of subclinical atherosclerosis (HR=1.23; 95% CI=1.01-1.51; P=0.04), including the coronary calcium score, ankle-brachial index, common carotid intima-media thickness, and ascending thoracic aortic Agatston score. Pb was independently associated with all-cause mortality in a similarly adjusted model (HR per 10 mm Hg increase in P(b)=2.18; 95% CI=1.21-3.92; P=0.009). Reflection magnitude (HR=1.71; 95% CI=1.06-2.77; P=0.03) and P(b) (HR=5.02; 95% CI=1.29-19.42; P=0.02) were mainly associated with cardiovascular mortality. In conclusion, reflection magnitude is independently associated with all-cause mortality in a multiethnic population initially free of clinically evident cardiovascular disease. This relationship persists after adjustment for a comprehensive set of markers of subclinical atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192021PMC
November 2014

Pulmonary exacerbations and parent-reported outcomes in children <6 years with cystic fibrosis.

Pediatr Pulmonol 2015 Mar 29;50(3):236-243. Epub 2014 Apr 29.

Seattle Children's Hospital and Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington.

Pulmonary exacerbations (PEs) are used as clinical endpoints in infants and preschool children with cystic fibrosis (CF); however, their characteristics and impact in this age range are poorly understood. We used data from the Infant Study of Inhaled Saline, a multicenter trial of inhaled hypertonic versus isotonic saline, to describe PEs in children with CF <6 years and evaluate associations between PEs and parent-reported outcomes assessed by a weekly parent questionnaire (10 items) and three scales of the Cystic Fibrosis Questionnaire-Revised (CFQ-R), and other participant characteristics. There were 659 PEs among 253 of the 321 ISIS participants (mean age 2.3 years) during 287 participant-years follow-up. Of the 659 PEs, 636 (97%) were treated with oral and 45 (7%) with IV antibiotics (not mutually exclusive). Among 222 participants with PEs who had completed parent questionnaires during a PE and at baseline, 9 of the 10 symptoms were each present in a statistically significantly higher proportion of participants during a PE than at baseline. Lower (worse) baseline Respiratory Symptom and Physical Functioning CFQ-R scores were significantly associated with higher PE rate: rate ratio 1.08 (95%CI: 1.02, 1.14) and 1.21 (1.07, 1.36) per 10 point lower score in respective scale. A higher PE rate was also significantly associated with worse CFQ-R Respiratory Symptom and Physical Functioning scores at the end of the study, adjusted for baseline scores. Though most PEs did not require IV antibiotics, PEs appeared to have a negative impact on parent-reported health outcomes in infants and preschoolers with CF. Pediatr Pulmonol. 2015; 50:236-243. © 2014 Wiley Periodicals, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.23056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213320PMC
March 2015

Left ventricular mass and hypertrophy by echocardiography and cardiac magnetic resonance: the multi-ethnic study of atherosclerosis.

Echocardiography 2014 10;31(1):12-20. Epub 2013 Aug 10.

Division of Cardiology, Johns Hopkins University, Baltimore, Maryland; School of Medicine, University of São Francisco Valley, Petrolina, Pernambuco, Brazil.

Background: Left ventricular mass (LVM) and hypertrophy (LVH) are important parameters, but their use is surrounded by controversies. We compare LVM by echocardiography and cardiac magnetic resonance (CMR), investigating reproducibility aspects and the effect of echocardiography image quality. We also compare indexing methods within and between imaging modalities for classification of LVH and cardiovascular risk.

Methods: Multi-Ethnic Study of Atherosclerosis enrolled 880 participants in Baltimore city, 146 had echocardiograms and CMR on the same day. LVM was then assessed using standard techniques. Echocardiography image quality was rated (good/limited) according to the parasternal view. LVH was defined after indexing LVM to body surface area, height(1.7) , height(2.7) , or by the predicted LVM from a reference group. Participants were classified for cardiovascular risk according to Framingham score. Pearson's correlation, Bland-Altman plots, percent agreement, and kappa coefficient assessed agreement within and between modalities.

Results: Left ventricular mass by echocardiography (140 ± 40 g) and by CMR were correlated (r = 0.8, P < 0.001) regardless of the echocardiography image quality. The reproducibility profile had strong correlations and agreement for both modalities. Image quality groups had similar characteristics; those with good images compared to CMR slightly superiorly. The prevalence of LVH tended to be higher with higher cardiovascular risk. The agreement for LVH between imaging modalities ranged from 77% to 98% and the kappa coefficient from 0.10 to 0.76.

Conclusions: Echocardiography has a reliable performance for LVM assessment and classification of LVH, with limited influence of image quality. Echocardiography and CMR differ in the assessment of LVH, and additional differences rise from the indexing methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/echo.12303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830716PMC
August 2014

Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis. A pilot study using inhaled hypertonic saline.

Am J Respir Crit Care Med 2013 Aug;188(4):456-60

Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, 555 University Avenue, Ontario, Canada.

Rationale: Lung clearance index (LCI), measured by multiple breath washout (MBW), is a noninvasive measure of ventilation inhomogeneity that holds promise as an objective physiologic endpoint for clinical trials in infants and preschool children with cystic fibrosis (CF).

Objectives: To study the feasibility of using LCI to assess treatment effect outcomes in CF trials of infants and preschoolers.

Methods: The Infant Study of Inhaled Saline trial was a multicenter, randomized, controlled trial of hypertonic (7%) versus isotonic (0.9%) saline inhaled twice daily for 48 weeks in children with CF under 6 years of age. LCI measurements were performed in a single-center pilot substudy at baseline and 48 weeks using a respiratory mass spectrometer and sulfur hexafluoride as the tracer gas. LCI measurements were standardized using published normative data (zLCI) to account for height-related changes in LCI during early childhood. A generalized estimating equation model with an interaction between treatment group and test occasion was used to estimate a treatment effect.

Measurements And Main Results: A total of 27 participants were randomized; 25 participants, aged (median [range]) 2.6 (0.34-4.95) years, had acceptable baseline and follow-up LCI measures. On average, LCI decreased in the hypertonic saline group (n = 12) by 1.19 z-scores units (95% confidence interval [CI] = -2.46 to 0.06), and remained stable in the isotonic saline group (n = 13) at 0.81 (95% CI = -0.40 to 2.02). A significant treatment effect was observed for zLCI (2.01; 95% CI = 0.26 to 3.76; P = 0.025).

Conclusions: MBW testing is feasible in an interventional study in infants and preschool children with CF. These pilot findings support the development of MBW and LCI as an objective outcome measure in interventional trials in young children with CF, and provide estimates for sample size calculations for future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.201302-0219OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778738PMC
August 2013

Association of lung function, chest radiographs and clinical features in infants with cystic fibrosis.

Eur Respir J 2013 Dec 30;42(6):1545-52. Epub 2013 May 30.

see the Acknowledgements.

The optimal strategy for monitoring cystic fibrosis lung disease in infancy remains unclear. Our objective was to describe longitudinal associations between infant pulmonary function tests, chest radiograph scores and other characteristics. Cystic fibrosis patients aged ≤24 months were enrolled in a 10-centre study evaluating infant pulmonary function tests four times over a year. Chest radiographs ∼1 year apart were scored using the Wisconsin and Brasfield systems. Associations of infant pulmonary function tests with clinical characteristics were evaluated with mixed effects models. The 100 participants contributed 246 acceptable flow/volume (forced expiratory volume in 0.5 s (FEV0.5) and forced expiratory flow at 75% of the forced vital capacity (FEF75%)), 303 functional residual capacity measurements and 171 chest radiographs. Both Brasfield and Wisconsin chest radiograph scores worsened significantly over the 1-year interval. Worse Wisconsin chest radiograph scores and Staphylococcus aureus were both associated with hyperinflation (significantly increased functional residual capacity), but not with diminished FEV0.5 or FEF75%. Parent-reported cough was associated with significantly diminished forced expiratory flow at 75% but not with hyperinflation. In this infant cohort in whom we previously reported worsening in average lung function, chest radiograph scores also worsened over a year. The significant associations detected between both Wisconsin chest radiograph score and S. aureus and hyperinflation, as well as between cough and diminished flows, reinforce the ability of infant pulmonary function tests and chest radiographs to detect early cystic fibrosis lung disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/09031936.00138412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795977PMC
December 2013

Arterial wave reflections and incident cardiovascular events and heart failure: MESA (Multiethnic Study of Atherosclerosis).

J Am Coll Cardiol 2012 Nov 24;60(21):2170-7. Epub 2012 Oct 24.

Philadelphia VA Medical Center and University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Objectives: This study sought to assess the relationship between central pressure profiles and cardiovascular events (CVEs) in a large community-based sample.

Background: Experimental and physiologic data mechanistically implicate wave reflections in the pathogenesis of left ventricular failure and cardiovascular disease, but their association with these outcomes in the general population is unclear.

Methods: Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 5,960 participants in the Multiethnic Study of Atherosclerosis. The central pressure waveform was separated into forward and reflected waves using a physiologic flow waveform. Reflection magnitude (RM = [Reflected/Forward wave amplitude] × 100), augmentation index ([Second/First systolic peak] × 100) and pulse pressure amplification ([Radial/aortic pulse pressure] × 100) were assessed as predictors of CVEs and congestive heart failure (CHF) during a median follow-up of 7.61 years.

Results: After adjustment for established risk factors, aortic AIx independently predicted hard CVEs (hazard ratio [HR] per 10% increase: 1.08; 95% confidence interval [CI]: 1.01 to 1.14; p = 0.016), whereas PPA independently predicted all CVEs (HR per 10% increase: 0.82; 95% CI: 0.70 to 0.96; p = 0.012). RM was independently predictive of all CVEs (HR per 10% increase: 1.34; 95% CI: 1.08 to 1.67; p = 0.009) and hard CVEs (HR per 10% increase: 1.46; 95% CI: 1.12 to 1.90; p = 0.006) and was strongly predictive of new-onset CHF (HR per 10% increase: 2.69; 95% CI: 1.79 to 4.04; p < 0.0001), comparing favorably to other risk factors for CHF as per various measures of model performance, reclassification, and discrimination. In a fully adjusted model, compared to nonhypertensive subjects with low RM, the HRs (95% CI) for hypertensive subjects with low RM, nonhypertensive subjects with high RM, and hypertensive subjects with high RM were 1.81 (0.85 to 3.86), 2.16 (1.07 to 5.01), and 3.98 (1.96 to 8.05), respectively.

Conclusions: Arterial wave reflections represent a novel strong risk factor for CHF in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2012.07.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065497PMC
November 2012

Lung function from infancy to preschool in a cohort of children with cystic fibrosis.

Eur Respir J 2013 Jan 31;41(1):60-6. Epub 2012 May 31.

Dept of Biostatistics, University of Washington, Children's Hospital Research Institute, Seattle, WA 98195-7232, USA.

This study aimed to describe lung function in a cohort of children with cystic fibrosis (CF) who underwent infant pulmonary function tests (IPFTs) and preschool spirometry. Children performed up to four IPFTs (raised volume rapid thoracic compression technique) over 1 yr and five preschool spirometry tests over up to 2 yrs during participation in prospective, multicentre studies of infant and preschool lung function. All lung function data were reviewed centrally for measurement acceptability. 45 children had 252 acceptable measurements (137 IPFTs and 115 preschool spirometries) at ages 0.3-6.5 yrs. The median number of measurements per participant was 6 (range 3-9). Recent Pseudomonas aeruginosa infection was associated with 5.1% (95% CI 0.01-9.9%) lower forced expiratory volume in 0.5 s (FEV(0.5)) and 16.4% (95% CI 7.0-24.9%) lower forced expiratory flow at 25-25% of forced vital capacity (FEF(25-75%)), after adjustment for length, test type and centre. Recent cough was associated with 5.7% (95% CI 1.1-10.1%) lower FEV(0.5) and 10.1% (95% CI 0.6-18.7%) lower FEF(25-75%). Even after accounting for infection status, cough, sex, length, test type and centre, there was significant inter-individual variability in lung function (p<0.01 for each of FEV(0.5), FEF(25-75%) and forced vital capacity). Recent P. aeruginosa infection and cough are associated with lower lung function in children with CF. Significant inter-individual variability in lung function remains to be explained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/09031936.00021612DOI Listing
January 2013

Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial.

JAMA 2012 Jun;307(21):2269-77

Division of Pulmonary Medicine, Seattle Children's Hospital, Seattle, Washington 98105, USA.

Context: Inhaled hypertonic saline is recommended as therapy for patients 6 years or older with cystic fibrosis (CF), but its efficacy has never been evaluated in patients younger than 6 years with CF.

Objective: To determine if hypertonic saline reduces the rate of protocol-defined pulmonary exacerbations in patients younger than 6 years with CF.

Design, Setting, And Participants: The Infant Study of Inhaled Saline in Cystic Fibrosis (ISIS), a multicenter, randomized, double-blind, placebo-controlled trial conducted from April 2009 to October 2011 at 30 CF care centers in the United States and Canada. Participants were aged 4 to 60 months and had an established diagnosis of CF. A total of 344 patients were assessed for eligibility; 321 participants were randomized; 29 (9%) withdrew prematurely.

Intervention: The active treatment group (n = 158) received 7% hypertonic saline and the control group (n = 163) received 0.9% isotonic saline, nebulized twice daily for 48 weeks. Both groups received albuterol or levalbuterol prior to each study drug dose.

Main Outcome Measures: Rate during the 48-week treatment period of protocol-defined pulmonary exacerbations treated with oral, inhaled, or intravenous antibiotics.

Results: The mean pulmonary exacerbation rate (events per person-year) was 2.3 (95% CI, 2.0-2.5) in the active treatment group and 2.3 (95% CI, 2.1-2.6) in the control group; the adjusted rate ratio was 0.98 (95% CI, 0.84-1.15). Among participants with pulmonary exacerbations, the mean number of total antibiotic treatment days for a pulmonary exacerbation was 60 (95% CI, 49-70) in the active treatment group and 52 (95% CI, 43-61) in the control group. There was no significant difference in secondary end points including height, weight, respiratory rate, oxygen saturation, cough, or respiratory symptom scores. Infant pulmonary function testing performed as an exploratory outcome in a subgroup (n = 73, with acceptable measurements at 2 visits in 45 participants) did not demonstrate significant differences between groups except for the mean change in forced expiratory volume in 0.5 seconds, which was 38 mL (95% CI, 1-76) greater in the active treatment group. Adherence determined by returned study drug ampoules was at least 75% in each group. Adverse event profiles were also similar, with the most common adverse event of moderate or severe severity in each group being cough (39% of active treatment group, 38% of control group).

Conclusion: Among infants and children younger than 6 years with cystic fibrosis, the use of inhaled hypertonic saline compared with isotonic saline did not reduce the rate of pulmonary exacerbations over the course of 48 weeks of treatment.

Trial Registration: clinicaltrials.gov Identifier: NCT00709280.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2012.5214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586815PMC
June 2012
-->