Effectiveness of smoking cessation interventions among persons with cancer: A systematic review.

OBJECTIVES: Continued smoking after cancer diagnosis is associated with worse outcomes, however, many persons diagnosed with cancer who smoke are unable to quit successfully. Effective interventions are needed to promote quitting in this population. The purpose of this systematic review is to understand the most effective interventions for smoking cessation among persons with cancer and to identify gaps in knowledge and methodology to suggest directions for future research. METHODS: Three electronic databases (The Cochrane Central Register of Controlled trials, MEDLINE, and EMBASE) were searched for studies of smoking cessation interventions among persons with cancer, published up to 1 July 2021. Title and abstract screening, full-text review, and data extraction was completed by two independent reviewers, via Covalence software, with any discordance resolved by a third reviewer. A quality assessment was completed using the Cochrane Risk of Bias Tool Version 2. RESULTS: Thirty-six articles were included in the review, including 17 randomized-controlled trials (RCTs) and 19 non-RCT studies. Of the 36 studies, 28 (77.8%) utilized an intervention that included both counseling and medication, with 24 (85.7%) providing medication to participants at no cost. Abstinence rates in the RCT intervention groups (n = 17) ranged from 5.2% to 75%, while the non-RCTs found abstinence rates ranging from 15% to 46%. Overall, studies met a mean of 2.28 out of seven quality items, ranging from 0 to 6. CONCLUSIONS: Our study highlights the importance of utilizing intensive combined behavioral and pharmacological interventions for persons with cancer. While combined therapy interventions seem to be the most effective, more research is needed, as current studies have several quality issues, including the lack of biochemical verification for abstinence.

Endobronchial Ultrasound Image Simulation for Image-Guided Bronchoscopy.

BACKGROUND/OBJECTIVE: Accurate disease diagnosis and staging are essential for patients suspected of having lung cancer. The state-of-the-art minimally invasive tools used by physicians to perform these operations are bronchoscopy, for navigating the lung airways, and endobronchial ultrasound (EBUS), for localizing suspect extraluminal cancer lesions. While new image-guided systems enable accurate bronchoscope navigation close to a lesion, no means exists for guiding the final EBUS localization of an extraluminal lesion. We propose an EBUS simulation method to assist with EBUS localization. METHODS: The method draws on a patient's chest computed-tomography (CT) scan to model the ultrasound signal propagation through the tissue media. The method, which is suitable for simulating EBUS images for both radial-probe and convex-probe EBUS devices, entails three steps: 1) image preprocessing, which generates a 2D CT equivalent of the EBUS scan plane; 2) EBUS scan-line computation, which models ultrasound transmission to map the CT plane into a preliminary simulated EBUS image; and 3) image post-processing, which increases realism by introducing simulated EBUS imaging effects and artifacts. RESULTS: Results show that the method produces simulated EBUS images that strongly resemble images generated live by a real device and compares favorably to an existing ultrasound simulation method. It also produces images at a rate greater than real time (i.e., 53 frames/sec). We also demonstrate a successful integration of the method into an image-guided EBUS bronchoscopy system. CONCLUSION/SIGNIFICANCE: The method is effective and practical for procedure planning/preview and follow-on live guidance of EBUS bronchoscopy.

Prescription Claims for Immunomodulator and Antiinflammatory Drugs Among Persons With Ehlers-Danlos Syndromes.

OBJECTIVE: Joint hypermobility in Ehlers-Danlos Syndromes (EDS) predisposes persons with EDS to frequent subluxations and dislocations, chronic arthralgia, and soft-tissue rheumatism. Epidemiologic trends of rheumatologic conditions among persons with EDS are lacking. Prescription claims databases can reflect underlying disease burdens by using medication claims as disease proxies. We examined the prevalence of prescription claims for commonly prescribed immunomodulator and antiinflammatory (IMD) drugs among persons with EDS compared with their matched control person, and hypothesized peripubertal increases among female persons with EDS. METHODS: We compared the percentages of IMD drug prescription claims among 3,484 persons with EDS (ages 5-62 years) against their age-, sex-, state of residence-, and earliest claim date-matched control persons using 10 years (2005-2014) of private prescription claims data and a minimum 2-year enrollment inclusion criterion. RESULTS: Our cohort comprised 70% adults and 74% female persons. At least 1 IMD medication was prescribed to 65.4% of persons with EDS compared with 47.4% of control persons. We observed 1.3 to 4.2 times higher odds (P < 0.0001) for 5 out of 6 IMD drug classes among persons with EDS compared with matched control persons, except for biologic agents (conditional odds ratio 1.3, 95% confidence interval 0.8-2.0). Peripubertal increases were observed for nonsteroidal antiinflammatory drugs, oral, and injectable steroids. CONCLUSIONS: To our knowledge, our study is the first to examine the full range of IMD drug prescription claim trends among persons with EDS. We believe our research findings can have notable diagnostic and management implications for EDS patients who present with multiple comorbidities and generally require a more granular assessment of their medical conditions.

Heterogeneity of Lung Function Phenotypes in Sarcoidosis: Role of Race and Sex Differences.

Rationale: Historically, sarcoidosis was described as a restrictive lung disease, but several alternative phenotypes of pulmonary function have been observed. Pulmonary function phenotypes in sarcoidosis may represent different clinical and/or molecular phenotypes. Objectives: To characterize the prevalence of different pulmonary function phenotypes in a large and diverse sarcoidosis cohort from a tertiary care referral center. Methods: We identified individuals seen between 2005-2015 with a confirmed diagnosis of sarcoidosis. Data were collected from the first pulmonary function test (PFT) performed at our institution which included spirometry and diffusing capacity of the lung for carbon monoxide (DlCO). Demographics and clinical data were collected. Chi-squared analyses and multiple linear regressions were done to assess statistical differences and associations. Global Lung Function Initiative equations were used to calculate percent predicted measurements for spirometry and DlCO. Results: Of 602 individuals with sarcoidosis, 93% (562) had pulmonary involvement, 64% (385) were female, and 57% (341) were Black. Of those with pulmonary involvement, 56% had abnormal pulmonary function. Lung function impairment phenotypes included: 47% restriction, 22% obstruction, 15% isolated reduction in DlCO, and 16% combined obstructive restrictive phenotype. Restriction was the most common PFT phenotype among Black individuals (41%), while no lung impairment was most common among White individuals (66%) (P < 0.001). Males more frequently had obstruction (19%) compared with females (9%) P = 0.001, and females had more restriction (30%) compared with males (21%) P = 0.031. Conclusions: Among individuals with sarcoidosis and pulmonary function impairment, less than half demonstrated a restrictive phenotype. There were significant differences in pulmonary function phenotypes by race and sex.

Efficient procedure planning for comprehensive lymph node staging bronchoscopy.

Purpose: For a patient at risk of having lung cancer, accurate disease staging is vital as it dictates disease prognosis and treatment. Accurate staging requires a comprehensive sampling of lymph nodes within the chest via bronchoscopy. Unfortunately, physicians are generally unable to plan and perform sufficiently comprehensive procedures to ensure accurate disease staging. We propose a method for planning comprehensive lymph node staging procedures. Approach: Drawing on a patient's chest CT scan, the method derives a multi-destination tour for efficient navigation to a set of lymph nodes. We formulate the planning task as a traveling salesman problem. To solve the problem, we apply the concept of ant colony optimization (ACO) to derive an efficient airway tour connecting the target nodes. The method has three main steps: (1) CT preprocessing, to define important chest anatomy; (2) graph and staging zone construction, to set up the necessary data structures and clinical constraints; and (3) tour computation, to derive the staging plan. The plan conforms to the world standard International Association for the Study of Lung Cancer (IASLC) lymph node map and recommended clinical staging guidelines. Results: Tests with a patient database indicate that the method derives optimal or near-optimal tours in under a few seconds, regardless of the number of target lymph nodes (mean tour length = 1.4% longer than the optimum). A brute force optimal search, on the other hand, generally cannot reach a solution in under 10 min. for patients exhibiting > 16 nodes, and other methods provide poor solutions. We also demonstrate the method's utility in an image-guided bronchoscopy system. Conclusions: The method provides an efficient computational approach for planning a comprehensive lymph node staging bronchoscopy. In addition, the method shows promise for driving an image-guided bronchoscopy system or robotics-assisted bronchoscopy system tailored to lymph node staging.

Multimodal Registration for Image-Guided EBUS Bronchoscopy.

The state-of-the-art procedure for examining the lymph nodes in a lung cancer patient involves using an endobronchial ultrasound (EBUS) bronchoscope. The EBUS bronchoscope integrates two modalities into one device: (1) videobronchoscopy, which gives video images of the airway walls; and (2) convex-probe EBUS, which gives 2D fan-shaped views of extraluminal structures situated outside the airways. During the procedure, the physician first employs videobronchoscopy to navigate the device through the airways. Next, upon reaching a given node's approximate vicinity, the physician probes the airway walls using EBUS to localize the node. Due to the fact that lymph nodes lie beyond the airways, EBUS is essential for confirming a node's location. Unfortunately, it is well-documented that EBUS is difficult to use. In addition, while new image-guided bronchoscopy systems provide effective guidance for videobronchoscopic navigation, they offer no assistance for guiding EBUS localization. We propose a method for registering a patient's chest CT scan to live surgical EBUS views, thereby facilitating accurate image-guided EBUS bronchoscopy. The method entails an optimization process that registers CT-based virtual EBUS views to live EBUS probe views. Results using lung cancer patient data show that the method correctly registered 28/28 (100%) lymph nodes scanned by EBUS, with a mean registration time of 3.4 s. In addition, the mean position and direction errors of registered sites were 2.2 mm and 11.8∘, respectively. In addition, sensitivity studies show the method's robustness to parameter variations. Lastly, we demonstrate the method's use in an image-guided system designed for guiding both phases of EBUS bronchoscopy.

Feasibility of Patient Navigation-Based Smoking Cessation Program in Cancer Patients.

Continued smoking after a cancer diagnosis is causally associated with increased risks of all-cause and cancer-specific mortality, and of smoking-related second primary cancers. Patient navigation provides individualized assistance to address barriers to smoking cessation treatment and represents a promising bridge to smoking cessation in persons with cancer who smoke cigarettes. We conducted a single-arm interventional cohort study of current smokers identified through prospective health record screening and recruited from Penn State Cancer Institute outpatient clinics. Consented participants received two telephone intervention sessions and gain-framed messaging-based smoking cessation educational materials designed for persons with cancer. The primary study outcome was the feasibility of the patient navigation-based intervention; the secondary outcome was the engagement in smoking cessation treatment at the two-month follow-up. Of 1168 unique screened Cancer Institute patients, 134 (11.5%) were identified as current cigarette smokers. Among 67 patients approached at outpatient clinics, 24 (35.8%) were interested in participating, 12 (17.9%) were enrolled, eight (11.9%) completed the intervention sessions and study assessments, and six engaged in smoking cessation treatment. The participants expressed satisfaction with the intervention sessions (median = 8.5, scale 0-10). The low recruitment rates preclude patient navigation as a feasible method for connecting cancer patients to smoking cessation treatment resources.

Longitudinal analysis of symptoms in the Ehlers-Danlos syndromes.

Our study extends a cross-sectional dataset on the Ehlers-Danlos syndromes (EDS) assembled by the National Institute on Aging (NIA), under a protocol entitled Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue. We were successful in contacting 171 of the original 252 participants with EDS. Our study cohort included 91 participants who completed at least one of the following surveys: Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory (MFI-20), and Short Form (SF-36) Health Survey, at both baseline and follow-up. Follow-up surveys occurred a median of 11.6 years after the baseline survey. We used mixed effects linear regression models to examine the change in scores for multiple indices reported by participants. There were small mean changes reflected in our estimates for the EDS population as a whole. There was wide heterogeneity between reported individual experiences, with some participants markedly improved and some dramatically worse. Men had a greater increase in mean pain severity over time than women. This is the first study to report a decade of longitudinal data in EDS.

Respiratory manifestations in the Ehlers-Danlos syndromes.

Persons with the Ehlers-Danlos syndromes (EDS) report a wide range of respiratory symptoms, most commonly shortness of breath, exercise limitation, and cough. Also reported are noisy breathing attributed to asthma, difficulty with deep inhalation, and inspiratory thoracic pain. The literature consists of case reports and small cross-sectional and cohort studies. One case-control study estimated twofold to threefold greater respiratory disease burden among persons with EDS as compared to controls. The differential diagnosis for symptoms is broad. Structural alterations include pectus deformities, scoliosis, recurrent rib subluxations, and tracheobronchomalacia, associated with varying degrees of physiologic impairment. Those with vascular EDS have an increased risk of pneumothorax, intrapulmonary bleeding, cysts, and nonmalignant fibrous nodules. Functional aerodigestive manifestations such as inducible laryngeal obstruction may be misdiagnosed as asthma, with gastro-esophageal dysmotility and reflux as common contributing factors. Inflammatory manifestations include costochondritis, bronchiectasis, and localized respiratory allergic and nonallergic mast cell activation. Cranio-cervical instability can dysregulate respiratory control pathways. There is a need for careful phenotyping using standardized clinical tools and patient-reported outcomes and continuing collaboration with aerodigestive specialists including otolaryngologists and gastroenterologists. Also needed is further evaluation of respiratory symptoms in persons with hypermobility spectrum disorders. Personalized monitoring strategies are invaluable for interpretation and long-term management of respiratory symptoms.

Initial description and evaluation of EDS ECHO: An international effort to improve care for people with the Ehlers-Danlos syndromes and hypermobility spectrum disorders.

The Ehlers-Danlos Society Extension for Community Health Care Outcomes (EDS ECHO) is a portfolio of teleconferencing programs developed around the principles and practices of Project ECHO®, aimed at increasing awareness of Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD) among clinicians, enhancing their confidence in the assessment and management of these complex conditions, and generating networks of clinicians across specialties. We assessed the outcomes of the first EDS ECHO program, launched in April 2019, with two hub locations: Indiana University Health, Indianapolis, Indiana, USA, and The Royal Society of Medicine, London, UK. Clinicians were surveyed before and 6 months after their participation. We describe the initial outcomes of the first four EDS ECHO programs, each comprising nine sessions. Participants reported increased levels of knowledge and confidence in providing care (93% and 95%, respectively) and an increase in referral network participation (65%). Additionally, 80% reported that their interest in EDS and HSD increased; 57% reporting a great increase. Also, 59% reported a decrease in feeling overwhelmed by EDS and HSD, and nearly half reported a decrease in their level of frustration because of participating in EDS ECHO. Clinicians participating in EDS ECHO programs know more, have more confidence in their ability to provide care, and feel energized by their participation.

A case-control study of respiratory medication and co-occurring gastrointestinal prescription burden among persons with Ehlers-Danlos syndromes.

We previously reported increased pain and gastrointestinal (GI) medication prescription claims among persons with Ehlers-Danlos syndromes (EDS) and peripubertal increase in opioid and anti-emetic claims among women with EDS. Herein, we hypothesized a higher proportion of respiratory and co-occurring respiratory and GI medication prescription claims among persons with EDS compared to their matched controls with increases among peripubertal women with EDS. We compared the proportions of respiratory and co-occurring respiratory and GI medication prescription claims among persons with EDS (aged 5-62) against their age-, sex-, state of residence-, and earliest claim date-matched controls using 10 years of private prescription claims data. Prescription claims among persons with EDS versus matched controls were increased for eight medication classes (p < .0001): intranasal/inhaled corticosteroids (ICS) (30.8% vs. 19.0%), oral steroids (30.0% vs. 16.5%), H1-antihistamines (26.2% vs. 12.2%), short-acting beta agonists (22.7% vs. 11.6%), decongestants (21.6% vs. 15.9%), leukotriene modifiers (8.9% vs. 3.6%), ICS/long-acting beta agonists (5.7% vs. 2.9%), muscarinic antagonists (2.5% vs. 0.9%), and co-occurring prescriptions (29% vs. 10%). Our results suggest a critical time window for peripubertal intervention and research and a need to focus on the pathogenesis and clinical evaluation of EDS-specific respiratory and aerodigestive disorders.

The power of patient-led global collaboration.

In late 2017, the global nonprofit, The Ehlers-Danlos Society (TEDS), was awarded a "Pipeline to Proposal" Tier A award from the Patient-Centered Outcomes Research Institute (PCORI). The goal of this application was to form a team of patients, researchers, other community support groups and stakeholders who are focused on establishing the Ehlers-Danlos Comorbidity Coalition to address the common health issues associated with this group of high morbidity, high disease burden conditions. The ongoing Coalition that is now funded by individual donors and expanding in its mission and members, is an example of successful collaboration spanning over borders and priorities.

Image-guided EBUS bronchoscopy system for lung-cancer staging.

The staging of the central-chest lymph nodes is a major step in the management of lung-cancer patients. For this purpose, the physician uses a device that integrates videobronchoscopy and an endobronchial ultrasound (EBUS) probe. To biopsy a lymph node, the physician first uses videobronchoscopy to navigate through the airways and then invokes EBUS to localize and biopsy the node. Unfortunately, this process proves difficult for many physicians, with the choice of biopsy site found by trial and error. We present a complete image-guided EBUS bronchoscopy system tailored to lymph-node staging. The system accepts a patient's 3D chest CT scan, an optional PET scan, and the EBUS bronchoscope's video sources as inputs. System workflow follows two phases: (1) procedure planning and (2) image-guided EBUS bronchoscopy. Procedure planning derives airway guidance routes that facilitate optimal EBUS scanning and nodal biopsy. During the live procedure, the system's graphical display suggests a series of device maneuvers to perform and provides multimodal visual cues for locating suitable biopsy sites. To this end, the system exploits data fusion to drive a multimodal virtual bronchoscope and other visualization tools that lead the physician through the process of device navigation and localization. A retrospective lung-cancer patient study and follow-on prospective patient study, performed within the standard clinical workflow, demonstrate the system's feasibility and functionality. For the prospective study, 60/60 selected lymph nodes (100%) were correctly localized using the system, and 30/33 biopsied nodes (91%) gave adequate tissue samples. Also, the mean procedure time including all user interactions was 6 min 43 s All of these measures improve upon benchmarks reported for other state-of-the-art systems and current practice. Overall, the system enabled safe, efficient EBUS-based localization and biopsy of lymph nodes.

Gastrointestinal medication burden among persons with the Ehlers-Danlos syndromes.

BACKGROUND: The Ehlers-Danlos syndromes (EDSs) are a group of heritable disorders of connective tissue associated with an increased prevalence of both structural and functional GI conditions. METHODS: We used 10 years (2005-2014) of administrative claims data comprised of 4294 people with clinician-diagnosed EDS, aged 5-62 years, and compared their frequency of GI drug prescription claims to their age-, sex-, state of residence-, and earliest claim date-matched controls. We categorized the GI medications into the following groups: acid suppressants, anti-emetics, irritable bowel syndrome drugs, and visceral hypersensitivity (VHS) medications. KEY RESULTS: Compared to controls, a significantly higher proportion of persons with EDS had prescription claims for at least one GI drug group, as well as for drugs in each of the four GI drug groups included in our study. By age-group, 25.7% children and 45.1% adults with EDS had prescription claims for at least one GI drug group compared with only 7.4% and 21.0% of controls, respectively (p < 0.0001). By gender, 44.0% of women and 25.3% of men with EDS had prescription claims for at least one class of GI drugs compared with 19.2% and 9.6% of controls, respectively (p < 0.0001). CONCLUSIONS AND KEY INFERENCES: Predominant medication burden occurs among women with EDS, beginning peri-pubertally for anti-emetics and VHS drugs. High GI medication burden underscores previous evidence that GI dysmotility is common among persons with EDS.

Electronic Health Records and Pulmonary Function Data: Developing an Interoperability Roadmap. An Official American Thoracic Society Workshop Report.

A workshop "Electronic Health Records and Pulmonary Function Data: Developing an Interoperability Roadmap" was held at the American Thoracic Society 2019 International Conference. "Interoperability" is defined as is the ability of different information-technology systems and software applications to directly communicate, exchange data, and use the information that has been exchanged. At present, pulmonary function test (PFT) equipment is not required to be interoperable with other clinical data systems, including electronic health records (EHRs). For this workshop, we assembled a diverse group of experts and stakeholders, including representatives from patient-advocacy groups, adult and pediatric general and pulmonary medicine, informatics, government and healthcare organizations, pulmonary function laboratories, and EHR and PFT equipment and software companies. The participants were tasked with two overarching Aobjectives: 1) identifying the key obstacles to achieving interoperability of PFT systems and the EHR and 2) recommending solutions to the identified obstacles. Successful interoperability of PFT data with the EHR impacts the full scope of individual patient health and clinical care, population health, and research. The existing EHR-PFT device platforms lack sufficient data standardization to promote interoperability. Cost is a major obstacle to PFT-EHR interoperability, and incentives are insufficient to justify the needed investment. The current vendor-EHR system lacks sufficient flexibility, thereby impeding interoperability. To advance the goal of achieving interoperability, next steps include identifying and standardizing priority PFT data elements. To increase the motivation of stakeholders to invest in this effort, it is necessary to demonstrate the benefits of PFT interoperability across patient care and population health.

Switching to Progressively Reduced Nicotine Content Cigarettes in Smokers With Low Socioeconomic Status: A Double-Blind Randomized Clinical Trial.

INTRODUCTION: The Food and Drug Administration issued an advanced notice of proposed rulemaking for setting a product standard for nicotine levels in cigarettes, with an emphasis on minimally or non-addicting very low nicotine content (VLNC). METHODS: A 33 week, two-arm, double-blind randomized trial conducted in Hershey, Pennsylvania, USA and Washington, DC, USA included adult daily cigarette smokers (≥5 cigarettes per day) with less than a college degree, and who had no plans to quit within the next six months. Participants were randomized to either reduced nicotine content (RNC) study cigarettes tapered every three weeks to a final VLNC (0.2 mg/cigarette) for six weeks or to usual nicotine content (UNC) study cigarettes (11.6 mg/cigarette). Outcomes included acceptability of study cigarettes measured by attrition (primary outcome), compliance, reduction in cigarette dependence and tobacco biomarkers, and post-intervention cessation. RESULTS: The RNC (n = 122) versus UNC (n = 123) group had higher attrition (adjusted Hazard Ratio 3.4; 95% confidence interval [CI] 1.99 to 5.81). At the end of the intervention, cotinine levels were 50% lower in the RNC group (mean group difference -137 ng/mL; 95% CI -172, -102). The RNC group smoked fewer CPD (-4.1; 95% CI -6.44, -1.75) and had lower carbon monoxide levels (-4.0 ppm; 95% CI -7.7, -0.4). Forty seven percent (29/62) of the RNC group were biochemically-confirmed compliant with smoking VLNC cigarettes (mean cotinine = 8.9 ng/ml). At three month follow-up, only compliant VLNC smokers quit with an assisted quit attempt (N = 6/22, 27%). CONCLUSIONS: This study supports a VLNC standard in cigarettes. IMPLICATIONS: Differential dropout and noncompliance indicate some smokers had difficulty transitioning to cigarettes with reduced nicotine. These smokers will benefit from supplemental nicotine in medicinal or noncombustible tobacco products if a nicotine reduction standard is established. Other smokers successfully transitioned to very low nicotine content cigarettes exclusively and substantially reduced their exposure to nicotine.

Autofluorescence Bronchoscopy Video Analysis for Lesion Frame Detection.

Because of the significance of bronchial lesions as indicators of early lung cancer and squamous cell carcinoma, a critical need exists for early detection of bronchial lesions. Autofluorescence bronchoscopy (AFB) is a primary modality used for bronchial lesion detection, as it shows high sensitivity to suspicious lesions. The physician, however, must interactively browse a long video stream to locate lesions, making the search exceedingly tedious and error prone. Unfortunately, limited research has explored the use of automated AFB video analysis for efficient lesion detection. We propose a robust automatic AFB analysis approach that distinguishes informative and uninformative AFB video frames in a video. In addition, for the informative frames, we determine the frames containing potential lesions and delineate candidate lesion regions. Our approach draws upon a combination of computer-based image analysis, machine learning, and deep learning. Thus, the analysis of an AFB video stream becomes more tractable. Using patient AFB video, 99.5%/90.2% of test frames were correctly labeled as informative/uninformative by our method versus 99.2%/47.6% by ResNet. In addition, ≥97% of lesion frames were correctly identified, with false positive and false negative rates ≤3%.Clinical relevance-The method makes AFB-based bronchial lesion analysis more efficient, thereby helping to advance the goal of better early lung cancer detection.

Castleman flare or COPD exacerbation- can biomarkers override availability bias?

Effective treatments for human herpes virus 8 (HHV-8) associated multicentric Castleman disease (MCD) have led to prolonged survival for this complex systemic lymphoproliferative inflammatory disease. Nonetheless, significant challenges remain for the recognition of disease exacerbations, particularly when overlapping with common comorbid conditions. We present a case of a 60-year-old man with a 22-year history of MCD, current advanced COPD, and medication-controlled HIV. His recurrent presentations with flares of fatigue, worsening dyspnea, and productive cough were confusing to clinicians who were attempting to distinguish between exacerbations of MCD or COPD. Published biomarkers of MCD flare include HHV-8 and CRP, which were proposed by the patient to his clinicians as useful in guiding treatment. This case illustrates the value of patient insight as an antidote to the problem of availability bias.

Arterial Elasticity in Ehlers-Danlos Syndromes.

Ehlers-Danlos Syndromes (EDS) are a group of heritable disorders of connective tissue (HDCT) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Orthostatic intolerance (OI) is highly prevalent in EDS however mechanisms linking OI to EDS remain poorly understood. We hypothesize that impaired blood pressure (BP) and heart rate control is associated with lower arterial stiffness in people with EDS. Orthostatic vital signs and arterial stiffness were assessed in a cohort of 60 people with EDS (49 female, 36 ± 16 years). Arterial elasticity was assessed by central and peripheral pulse wave velocity (PWV). Central PWV was lower in people with EDS compared to reference values in healthy subjects. In participants with EDS, central PWV was correlated to supine systolic BP (r = 0.387, p = 0.002), supine diastolic BP (r = 0.400, p = 0.002), and seated systolic BP (r = 0.399, p = 0.002). There were no significant correlations between PWV and changes in BP or heart rate with standing (p > 0.05). Between EDS types, there were no differences in supine hemodynamics or PWV measures (p > 0.05). These data demonstrate that increased arterial elasticity is associated with lower BP in people with EDS which may contribute to orthostatic symptoms and potentially provides a quantitative clinical measure for future genotype-phenotype investigations.

Changes in Flavor Preference in a Cohort of Long-Term Electronic Cigarette Users.

Rationale: The use of electronic cigarettes (e-cigarettes) has rapidly increased in the United States, and thousands of e-cigarette flavors are available. However, there remains a dearth of evidence on e-cigarette flavor use patterns among older e-cigarette users.Objectives: This longitudinal study examined changes in flavor use patterns in long-term e-cigarette users, assessed self-reported adverse reactions, and evaluated users' anticipated reactions to possible U.S. Food and Drug Administration e-cigarette flavor regulatory scenarios.Methods: The study population was 383 adult participants who completed two online e-cigarette surveys in 2012-2014 (baseline survey) and in 2017-2019 (follow-up survey). In both surveys, participants were asked, "Thinking about your preferred liquid, what is the name of this liquid flavor?" and to list all flavors used in the past 30 days. Flavor preference was classified using the Penn State Three-Step Flavor Classification method. Participants reported adverse events (open-ended description) with the associated flavor. Regulatory scenarios were presented, and participants selected perceived actions from among a list of 15 options.Results: Participants' age averaged 44 ± 12 years; 86% were exclusive e-cigarette users, and 13% reported "poly-use" (i.e., e-cigarette and other tobacco product use). E-cigarette flavor preference migration occurred in all demographic groups: only 36-44% maintained a preference for their original flavor. Preference for tobacco and menthol or mint decreased over time (40% baseline vs. 22% follow-up); preference for fruit remained stable (23% baseline and follow-up), but chocolate/candy or other sweets preference significantly increased (16% baseline vs. 29% follow-up), and other flavors increased slightly. Migration to sweet flavors was more noticeable in younger adults (18-45 yr); exclusive e-cigarette users preferred sweet flavors more commonly than poly-users did (31% vs. 19%). Flavor-associated adverse reactions, mainly respiratory irritations, were reported by 26 (6.9%) participants. Nearly 50% of the participants reported that they would "find a way" to buy their preferred flavor or add flavoring agents themselves if nontobacco flavors were banned.Conclusions: Flavor migration toward sweet flavors occurred in long-term e-cigarette users, a trend most pronounced in younger and exclusive e-cigarette users. The anticipated maintenance of access to flavors despite regulation suggests an element of e-cigarette-related dependence that requires further evaluation. This information could help clinicians understand the health impacts of e-cigarette flavors, develop appropriate strategies for smoking cessation, and inform the U.S. Food and Drug Administration to plan future regulation of e-cigarette flavors.