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Purpose of the Review: To highlight recent advances in effective communication among persons with chronic respiratory diseases. The authors focus on communication science related to goals of care (GOC) discussions, medical devices, and life-sustaining invasive treatments. The authors discuss important considerations when working with individuals with low literacy and rurality. Communication handoffs between respiratory clinicians and/or palliative care to hospice clinicians are summarized to ensure effective person-centered and caregiver-centered care., Recent Findings: Studies suggest the following communication approaches: (1) clarify differences between palliative and end of life; (2) conduct conversations early and gradual throughout the illness trajectory; (3) distinguish types of GOC discussions as they relate to treatment preferences; (4) for patients from rural communities, include family members and spiritual leaders; (5) assess literacy and employ supportive strategies; (6) apply time-limited-trial framework for life-sustaining treatment (LST) decisions; and (7) standardize processes for communication handoffs to hospice clinicians to improve communication fidelity., Summary: Effective communication tools for clinicians to engage in GOC discussions for persons with chronic respiratory diseases are grounded in a patient-centered framework. A trained clinician should lead these conversations and include interdisciplinary team members throughout the disease trajectory including at the end of life. These approaches may enable patients to express their values and care preferences as they evolve over time., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lung cancer survivors are at risk of accelerated declines in physical functioning attributed to cancer treatment. However, it is unknown whether patients experience the same rate of functional decline and how symptoms may contribute to different trajectories., Objectives: The aims of this study were to identify interindividual differences in the pattern and rate of change in self-reported functioning in lung cancer survivors and examine whether and how symptoms are related to physical functioning over time., Methods: This was a secondary data analysis in 72 lung cancer survivors. Multilevel modeling was used to estimate trajectories of self-reported physical functioning over 1 year and assess the relation between functioning, fatigue, depressive symptoms, and pain severity across time., Results: Within the sample, average physical functioning did not significantly decrease (coefficient, -0.46; 95% confidence interval [CI] = -2.85 to 0.94) over time. However, among individual lung cancer survivors, baseline physical functioning varied significantly (SD, 20.76; 95% CI, 16.84-25.59) and changed at significantly different rates over 1 year (SD, 3.50; 95% CI, 2.13-5.68). Fatigue, assessed over 1 year, was the only significant symptom predictor of physical functioning changes over time (coefficient = 1.03; 95% CI, 0.79-1.27)., Conclusions: In this sample of lung cancer survivors, not all survivors experienced the same rate of self-reported functional decline and those with lower levels of fatigue reported better physical functioning., Implications for Practice: Nurses should recognize that some lung cancer survivors may have faster rates of functional declines than others, which may be related to fatigue severity. Early identification and management of fatigue could help avoid or delay future disability., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We evaluated the efficacy of a combined short-wavelength-enriched white light and exercise fatigue countermeasure during breaks for flight controllers working overnight shifts., Methods: Twenty NASA flight controllers were studied for two blocks of nightshifts in ISS mission control, randomized to either the control or countermeasure condition. The countermeasure constituted passive exposure to blue-enriched polychromatic lighting for three 20-minute intervals, which included 10 minutes of exercise and occurred before and twice during their shifts. Alertness, performance, and mood were evaluated., Results: Flight controllers reported being significantly more alert (P < 0.0001) and happy (P = 0.003) and had faster reaction times (10% slowest responses; P < 0.05) during the countermeasure condition compared to control., Conclusions: The combined light and exercise countermeasure improved alertness, performance, and mood in shift workers overnight. Further research is necessary to determine their relative contribution., Competing Interests: Barger, Sullivan, Lockley, and Czeisler have no relationships/conditions/circumstances that present potential conflict of interest. Dr Lockley reports commercial interests from the last 3 years (2017–2020) unrelated to the study reported herein but are reported in the interests of full disclosure. SWL has received consulting fees from the BHP Billiton, Delos Living LLC, EyeJust Inc., Noble Insights, Pegasus Captital Advisors, The Rec Room, and Team C Racing; honoraria and/or paid travel from BHP Billiton, DIN, Emory University, IES, Ineos, MIT, Roxbury Latin School, SLTBR, Solemma and Teague; has current consulting contracts with Akili Interactive; Apex 2100 Ltd.; Consumer Sleep Solutions; Headwaters Inc.; Hintsa Performance AG; KBR Wyle Services LLC, Light Cognitive; Lighting Science Group Corporation; Look Optic, Mental Workout; PlanLED; Six Senses; Stantec View Inc.; has received unrestricted equipment gifts from Bionetics Corporation and F. Lux Software LLC; royalties from Oxford University Press; and has served as a paid expert in legal proceedings related to light, sleep and health. He is an unpaid Board Member of the Midwest Lighting Institute (non-profit) and was the Program Leader for “Safety and Productivity Improvements” in the CRC for Alertness, Safety and Productivity from 2015–2019. Dr Lockley's interests were reviewed and managed by Brigham and Women's Hospital and Partners HealthCare in accordance with their conflict of interest policies. Dr Czeisler reports grants to BWH from FAA, NHLBI, NIA, NIOSH, NASA, and DOD; is/was a paid consultant to AARP (2018), American Academy of Dental Sleep Medicine (2017, 2018), Eisenhower Medical Center (2018), Emory University (2019), Ganésco, Inc. (2017), Inselspital Bern (2019), Institute of Digital Media and Child Development (2017, 2018, 2019), Klarman Family Foundation (2017, 2018, 2019), M. Davis and Co (2018), Physician's Seal (2019), Samsung (2016), Sleep Research Society Foundation (2019), State of Washington Board of Pilotage Commissioners (2018), Tencent Holdings Ltd (2019), Teva Pharma Australia (2019, 2020), UC San Diego (2018), University of Michigan (2017), University of Washington (2017, 2018), and Vanda Pharmaceuticals Inc (2017, 2018, 2019, 2020), in which Dr Czeisler also holds an equity interest; received travel support from Annenberg Center for Health Sciences at Eisenhower (2018), Aspen Brain Institute (2018), Bloomage International Investment Group, Inc. (2018, 2019), UK Biotechnology and Biological Sciences Research Council (2019), Bouley Botanical (2017, 2018, 2019), Dr Stanley Ho Medical Development Foundation (2019), European Biological Rhythms Society (2017, 2019), German National Academy of Sciences (Leopoldina) (2019), Illuminating Engineering Society (2018), National Safey Council (2017, 2018, 2019), National Sleep Foundation (2017, 2018, 2019), Society for Research on Biological Rhythms (2018), Sleep Research Society Foundation (2018), Stanford Medical School Alumni Association (2019), Tencent Holdings Ltd (2019), University of Zurich (2018), and Vanda Pharmaceuticals Inc (2017, 2018, 2019), Ludwig-Maximilians-Universität München (2018), National Highway Transportation Safety Administration (2018), Office of Naval Research (2018), Salk Institute for Biological Studies/Fondation Ipsen (2018), The National Academy of Sciences, Engineering, and Medicine (2017), The Wonderful Company (2017), Department of Defense (2017); receives research/education support through BWH from Cephalon, Mary Ann & Stanley Snider via Combined Jewish Philanthropies, Jazz Pharmaceuticals PLC Inc (2017, 2018, 2019, 2020), Philips Respironics Inc (2017, 2018, 2019, 2020), Regeneron Pharmaceuticals (2018, 2019, 2020), Teva Pharmaceuticals Industries Ltd, Sanofi SA, Optum, ResMed, San Francisco Bar Pilots, Sanofi, Schneider, Simmons, Sysco, Philips, Vanda Pharmaceuticals; is/was an expert witness in legal cases, including those involving Advanced Power Technologies, Aegis Chemical Solutions LLC (2019), Amtrak (2019); Casper Sleep Inc (2019), C&J Energy Services (2019), Complete General Construction Co (2017), Dallas Police Association (2019), Enterprise Rent-A-Car (2019), Espinal Trucking/Eagle Transport Group LLC/Steel Warehouse Inc (2017, 2018, 2019), FedEx, Greyhound Lines Inc/Motor Coach Industries/FirstGroup America (2017, 2018, 2019), Pomerado Hospital/Palomar Health District (2017, 2018), PAR Electrical Contractors Inc (2019), Product & Logistics Services LLC/Schlumberger Technology Corp/Gelco Fleet Trust (2019), Puckett Emergency Medical Services LLC (2019), South Carolina Central Railroad Company LLC (2017, 2018), Union Pacific Railroad (2019), United Parcel Service/UPS Ground Freight Inc (2017, 2018), and Vanda Pharmaceuticals (2019, 2020); serves as the incumbent of an endowed professorship provided to Harvard University by Cephalon, Inc.; and receives royalties from McGraw Hill, and Philips Respironics (2017, 2018, 2019) for the Actiwatch-2 and Actiwatch Spectrum devices. Dr Czeisler's interests were reviewed and are managed by the Brigham and Women's Hospital and Mass General Brigham in accordance with their conflict of interest policies., (Copyright © 2020 American College of Occupational and Environmental Medicine.)

Low density lipoprotein (LDL) is the predominant atherogenic lipoprotein particle in the circulation. Conventionally, a fasting lipid profile has been used for atherosclerotic cardiovascular disease (ASCVD) risk assessment. A non-fasting sample is now regarded as a suitable alternative to a fasting sample. In routine clinical practice, the Friedewald equation is used to estimate LDL-cholesterol, but it has limitations. Commercially available direct measures of LDL-cholesterol are not standardised. LDL-cholesterol is a well-established risk factor for ASCVD, being the primary therapeutic target in both primary and secondary prevention. Non-high-density lipoprotein (HDL)-cholesterol is a measure of the cholesterol content in the atherogenic lipoproteins, but it does not reflect the particle number. Non-HDL-cholesterol has the advantage over LDL-cholesterol of including remnant cholesterol and being independent of triglyceride variability, but it is compromised by the non-specificity bias of direct HDL-cholesterol methods used in the calculation. Apolipoprotein (apo) B, the major structural protein in very low-density lipoprotein, intermediate density lipoprotein, LDL and lipoprotein (a), is a measure of the number of atherogenic lipoproteins. ApoB methods are standardised, but the assay comes at an additional, albeit relatively low cost. Non-HDL-cholesterol and apoB are more accurate measures than LDL-cholesterol in hypertriglyceridaemic individuals, non-fasting samples, and in those with very-low LDL-cholesterol concentrations. Accumulating evidence suggests that non-HDL-cholesterol and apoB are superior to LDL-cholesterol in predicting ASCVD risk, and both have been designated as secondary targets in some treatment guidelines. We review the measurement, potential role, utility and current status of non-HDL-cholesterol and apoB when compared with LDL-cholesterol in ASCVD risk assessment., (Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Background: D-dimer, a degradation product of cross-linked fibrin, is a marker for hypercoagulability and thrombotic events. Moderately elevated levels of D-dimer are associated with the risk of venous and arterial events in patients with vascular disease. We assessed the role of D-dimer levels in predicting long-term vascular outcomes, cause-specific mortality, and new cancers in the LIPID trial (Long-Term Intervention with Pravastatin in Ischaemic Disease) in the context of other risk factors., Methods: LIPID randomized patients to placebo or pravastatin 40 mg/d 5 to 38 months after myocardial infarction or unstable angina. D-dimer levels were measured at baseline and at 1 year. Median follow-up was 6.0 years during the trial and 16 years in total., Results: Baseline D-dimer levels for 7863 patients were grouped by quartile (≤112, 112-173, 173-273, >273 ng/mL). Higher levels were associated with older age, female sex, history of hypertension, poor renal function, and elevated levels of B-natriuretic peptide, high-sensitivity C-reactive protein, and sensitive troponin I (each P<0.001). During the first 6 years, after adjustment for up to 30 additional risk factors, higher D-dimer was associated with a significantly increased risk of a major coronary event (quartile 4 versus 1: hazard ratio [HR], 1.45; 95% confidence interval, 1.21-1.74), major cardiovascular disease (CVD) event (HR, 1.45; 95% confidence interval, 1.23-1.71) and venous thromboembolism (HR, 4.03; 95% confidence interval, 2.31-7.03; each P<0.001). During the 16 years overall, higher D-dimer was an independent predictor of all-cause mortality (HR, 1.59), CVD mortality (HR, 1.61), cancer mortality (HR, 1.54), and non-CVD noncancer mortality (HR, 1.57; each P<0.001), remaining significant for deaths resulting from each cause occurring beyond 10 years of follow-up (each P≤0.01). Higher D-dimer also independently predicted an increase in cancer incidence (HR, 1.16; P=0.02).The D-dimer level increased the net reclassification index for all-cause mortality by 4.0 and venous thromboembolism by 13.6., Conclusions: D-dimer levels predict long-term risk of arterial and venous events, CVD mortality, and non-CVD noncancer mortality independent of other risk factors. D-dimer is also a significant predictor of cancer incidence and mortality. These results support an association of D-dimer with fatal events across multiple diseases and demonstrate that this link extends beyond 10 years' follow-up.

Background: Clinical lipid measurements do not show the full complexity of the altered lipid metabolism associated with diabetes mellitus or cardiovascular disease. Lipidomics enables the assessment of hundreds of lipid species as potential markers for disease risk., Methods: Plasma lipid species (310) were measured by a targeted lipidomic analysis with liquid chromatography electrospray ionization-tandem mass spectrometry on a case-cohort (n=3779) subset from the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation). The case-cohort was 61% male with a mean age of 67 years. All participants had type 2 diabetes mellitus with ≥1 additional cardiovascular risk factors, and 35% had a history of macrovascular disease. Weighted Cox regression was used to identify lipid species associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and cardiovascular death during a 5-year follow-up period. Multivariable models combining traditional risk factors with lipid species were optimized with the Akaike information criteria. C statistics and NRIs were calculated within a 5-fold cross-validation framework., Results: Sphingolipids, phospholipids (including lyso- and ether- species), cholesteryl esters, and glycerolipids were associated with future cardiovascular events and cardiovascular death. The addition of 7 lipid species to a base model (14 traditional risk factors and medications) to predict cardiovascular events increased the C statistic from 0.680 (95% confidence interval [CI], 0.678-0.682) to 0.700 (95% CI, 0.698-0.702; P<0.0001) with a corresponding continuous NRI of 0.227 (95% CI, 0.219-0.235). The prediction of cardiovascular death was improved with the incorporation of 4 lipid species into the base model, showing an increase in the C statistic from 0.740 (95% CI, 0.738-0.742) to 0.760 (95% CI, 0.757-0.762; P<0.0001) and a continuous net reclassification index of 0.328 (95% CI, 0.317-0.339). The results were validated in a subcohort with type 2 diabetes mellitus (n=511) from the LIPID trial (Long-Term Intervention With Pravastatin in Ischemic Disease)., Conclusions: The improvement in the prediction of cardiovascular events, above traditional risk factors, demonstrates the potential of plasma lipid species as biomarkers for cardiovascular risk stratification in diabetes mellitus., Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00145925., (© 2016 American Heart Association, Inc.)

Objective: The objective of this study is to compare three methods of administering a sleep health program (SHP) in fire departments., Methods: An SHP, comprising sleep health education and screening for common sleep disorders, was implemented in eight fire departments using three approaches: expert-led, train-the-trainer, and online. Participation rates, knowledge assessments, surveys, and focus group interviews were analyzed to assess the reach and effectiveness of the methodologies., Results: The Expert-led SHP had the highest participation rate, greatest improvement in knowledge scores, and prompted more firefighters to seek clinical sleep disorder evaluations (41%) than the other approaches (20 to 25%). Forty-two percent of focus group participants reported changing their sleep behaviors., Conclusion: All approaches yielded reasonable participation rates, but expert-led programs had the greatest reach and effectiveness in educating and screening firefighters for sleep disorders.

Background: We aimed to assess the long-term effects of treatment with statin therapy on all-cause mortality, cause-specific mortality, and cancer incidence from extended follow-up of the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) trial., Methods and Results: LIPID initially compared pravastatin and placebo over 6 years in 9014 patients with previous coronary heart disease. After the double-blind period, all patients were offered open-label statin therapy. Data were obtained over a further 10 years from 7721 patients, by direct contact for 2 years, by questionnaires thereafter, and from mortality and cancer registries. During extended follow-up, 85% assigned pravastatin and 84% assigned placebo took statin therapy. Patients assigned pravastatin maintained a significantly lower risk of death from coronary heart disease (relative risk [RR] 0.89; 95% confidence interval [CI], 0.81-0.97; P=0.009), from cardiovascular disease (RR, 0.88; 95% CI, 0.81-0.95; P=0.002), and from any cause (RR, 0.91; 95% CI, 0.85-0.97; absolute risk reduction, 2.6%; P=0.003).Cancer incidence was similar by original treatment group during the double-blind period (RR, 0.94; 95% CI, 0.82-1.08; P=0.41), later follow-up (RR, 1.02; 95% CI, 0.91-1.14; P=0.74), and overall (RR, 0.99; 95% CI, 0.91-1.08; P=0.83). There were no significant differences in cancer mortality, or in the incidence of organ-specific cancers. Cancer findings were confirmed in a meta-analysis with other large statin trials with extended follow-up., Conclusions: In LIPID, the absolute survival benefit from 6 years of pravastatin treatment appeared to be maintained for the next 10 years, with a similar risk of death among survivors in both groups after the initial period. Treatment with statins does not influence cancer or death from noncardiovascular causes during long-term follow-up., (© 2016 American Heart Association, Inc.)

Objective: Association between lipoprotein(a) (Lp(a)) level and a first-ever coronary (CHD) event is recognized. Less is evident in patients with overt CHD and stable symptoms in whom we investigated associations between Lp(a) and future events., Approach and Results: Relationships between Lp(a) concentration and CHD and cardiovascular disease outcomes during 6 years' median follow-up were evaluated in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study. Lp(a) concentrations were measured in plasma from 7863 patients who had sustained a previous coronary event and been randomized to pravastatin or placebo. Lp(a) levels were categorized by lowest half, third quartile, 75th to 90th percentile, and highest decile. The prognostic value of Lp(a) on outcomes was assessed by fitting a Cox proportional-hazards model after adjustment for other risk factors and baseline cardiovascular disorders. The prognostic value of a change in Lp(a) at year 1 categorized by quartiles was assessed using Cox regression in a landmark model incorporating the above factors and baseline levels. Baseline Lp(a) concentration was associated with total CHD events (P<0.001), total cardiovascular disease events (P=0.002), and coronary events (P=0.03). Greatest risk occurred at >73 mg/dL, upper decile. For events after year 1, an increase in Lp(a) at 1 year was associated with adverse outcomes for total CHD events and total cardiovascular disease events (P=0.002 each)., Conclusions: In the LIPID study, baseline Lp(a) was associated with future cardiovascular disease and CHD events. Increased Lp(a) concentrations after 1 year were also associated with future events, supporting measurement of Lp(a) for risk assessment of patients with known CHD.

Background: It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk., Methods and Results: We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38,153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels <50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97)., Conclusions: Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.

Objective: The purpose of this study was to determine fenofibrate-induced changes in plasma high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) A-I, and apolipoprotein (apo) A-II and how they relate to changes in plasma homocysteine and creatinine., Methods and Results: FIELD was a double-blind placebo-controlled trial done in Australia, New Zealand, and Finland. All FIELD subjects were included except those who started statin therapy or permanently discontinued fenofibrate. Patients were randomized to receive daily micronized fenofibrate (200 mg) or matching placebo and were followed up for a median of 5 years. Plasma HDL-C, apoA-I, apoA-II, homocysteine, and creatinine were measured. There was an inverse relationship between baseline homocysteine levels and HDL-C in the placebo (P=0.07 for linear trend) and fenofibrate groups (P<0.0001) and apoA-I (P<0.001, both groups). The increases in homocysteine and creatinine in the fenofibrate group correlated positively (P<0.0001). The greater the increase in homocysteine induced by fenofibrate, the smaller the increases in HDL-c and apoA-I (P<0.0001 for linear trends). There was a highly significant and positive relationship between fenofibrate-induced changes in homocysteine and apoA-II levels., Conclusions: PPAR alpha agonists that have a more robust effect on HDL-C and apoA-I would be desirable.

Purpose of Review: A new class of cholesterol-lowering therapy that reduces intestinal sterol absorption has recently been introduced. This increases the number of classes of lipid-lowering agents that directly affect gastrointestinal function and raises questions concerning the overall effect of these agents on absorption and nutritional status., Recent Findings: A recent assessment notes a paucity of information concerning the factors that affect the bioavailability and intestinal absorption of lipophilic nutrients. By contrast, the specificity of the mechanisms of action of new drugs acting on the gastrointestinal tract may circumvent some of the detrimental effects on nutrient and drug bioavailability that have been noted with older forms of treatment., Summary: The clinical imperative for aggressive control of lipid and metabolic risk factors makes widespread use, alone or in combination, of lipid-lowering agents that affect the gastrointestinal tract seem increasingly likely. Whilst the opportunity for therapeutic synergy is attractive, care will be required to avoid interference with intestinal absorptive function.

Our understanding of the pathophysiological role of lipoprotein (a) in cardiovascular disease and its clinical importance has improved, but there are still gaps in our knowledge and analytical performance that hinder the appropriate management of patients. Further information about the physiological functions of lipoprotein (a), if any, and its interactions with other risk factors is required.

We assessed the intralaboratory imprecision and interlaboratory comparability of lipoprotein measurements and related cardiovascular risk functions such as the total to high density lipoprotein cholesterol (TC:HDL) ratio. Analysis of 5 separate plasma pools was carried out in 4 laboratories which regularly perform lipoprotein testing. We also performed a retrospective audit on RCPA-AACB Quality Assurance Programme data from 134 laboratories participating in the Special Lipid Programme in 1991. Intralaboratory imprecision and interlaboratory comparability are reported as coefficient of variation (cv) and its 95% confidence limit. For the national data, we calculated the percentage of laboratories within specified ranges (+/- 3, 5 or 10%) about the national mean (or median) for a given level of each analyte. Intralaboratory imprecision and interlaboratory comparability amongst the 4 laboratories were close to, or within recommended limits for, TC, TG and HDL, but the interlaboratory comparability of LDL and coronary risk functions exceeded these limits. On a national level, interlaboratory comparability of TC:HDL was within +/- 5% for only 43% of laboratories, and even fewer (26%) were within this range at higher values of the ratio. We conclude that it is not possible to recommend the use of coronary risk functions at present because of sub-optimal interlaboratory comparability. Even if measures are introduced to overcome this problem, coronary risk functions may over-simplify coronary vascular disease risk in a variety of clinical situations.