Browsing by Subject "Chronic Disease"
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Item Open Access A Systematic Review Investigating Associations Between E-Cigarette Use Among Former Cigarette Smokers and Relapse to Smoking Cigarettes.(Inquiry : a journal of medical care organization, provision and financing, 2023-01) Kim, Mimi M; Kim, Mimi M; Steffensen, Isabella; Miguel, Red Thaddeus D; Babic, Tanja; Carlone, JulienAs e-cigarette use has steadily increased over the recent years, the public health interest in the potential implications of e-cigarette use on cigarette smoking has grown in parallel. With strict adherence to PRISMA guidelines, this systematic review examined the potential associations between e-cigarette use and relapse to cigarette smoking among former cigarette smokers. The protocol was registered on November 06, 2018 (PROSPERO 2018 CRD42018115674). Literature searches were executed from January 01, 2007 to August 20, 2022 and search results were screened according to the PICOS review method. One RCT and 10 adjusted studies examined relapse to cigarette smoking (evidence grade "moderate") among regular e-cigarette users, reporting mixed and inconsistent findings according to varying definitions of e-cigarette use and relapse. Findings were similarly inconsistent among the 8 adjusted studies examining relapse to cigarette smoking among non-regular e-cigarette users. The inconsistency in findings among studies evaluating regular measures of e-cigarette use, combined with the numerous methodological flaws in the overall body of literature, limit the generalizability of results associated with a causal association between e-cigarette use and relapse to cigarette smoking. Based on findings from this review, more robust studies are required to determine whether a causal association exists between e-cigarette use and relapse to cigarette smoking. Future studies should apply consistent measures of regular e-cigarette use to examine causality with future use patterns, and sufficiently account for known or suspected confounding variables to support inform determinations related to e-cigarette use and cigarette smoking behaviors.Item Open Access Amygdala, Hippocampus, and Ventral Medial Prefrontal Cortex Volumes Differ in Maltreated Youth with and without Chronic Posttraumatic Stress Disorder.(Neuropsychopharmacology, 2016-02) Morey, Rajendra A; Haswell, Courtney C; Hooper, Stephen R; De Bellis, Michael DPosttraumatic stress disorder (PTSD) is considered a disorder of recovery where individuals fail to learn and retain extinction of the traumatic fear response. In maltreated youth, PTSD is common, chronic, and associated with comorbidity. Studies of extinction-related structural volumes (amygdala, hippocampus, anterior cingulate cortex (ACC), and ventral medial prefrontal cortex (vmPFC)) and this stress diathesis, in maltreated youth were not previously investigated. In this cross-sectional study, neuroanatomical volumes associated with extinction in maltreated youth with PTSD (N=31), without PTSD (N=32), and in non-maltreated healthy volunteers (n=57) were examined using magnetic resonance imaging. Groups were sociodemographically similar. Participants underwent extensive assessments for strict inclusion/exclusion criteria and DSM-IV disorders. Maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared with both maltreated youth without PTSD and non-maltreated controls. Maltreated youth without PTSD demonstrated larger left amygdala and right hippocampal volumes compared with maltreated youth with PTSD and non-maltreated control youth. PTSD symptoms inversely correlated with right and left hippocampal and left amygdala volumes. Confirmatory masked voxel base morphometry analyses demonstrated greater medial orbitofrontal cortex gray matter intensity in controls than maltreated youth with PTSD. Volumetric results were not influenced by psychopathology or maltreatment variables. We identified volumetric differences in extinction-related structures between maltreated youth with PTSD from those without PTSD. Alterations of the vmPFC may be one mechanism that mediates the pathway from PTSD to comorbidity. Further longitudinal work is needed to determine neurobiological factors related to chronic and persistent PTSD, and to PTSD resilience despite maltreatment.Item Open Access C3a receptor antagonism as a novel therapeutic target for chronic rhinosinusitis.(Mucosal immunology, 2018-09) Mulligan, Jennifer K; Patel, Kunal; Williamson, Tucker; Reaves, Nicholas; Carroll, William; Stephenson, Sarah E; Gao, Peng; Drake, Richard R; Neely, Benjamin A; Tomlinson, Stephen; Schlosser, Rodney J; Atkinson, CarlChronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease with an unknown etiology. Recent studies have implicated the complement system as a potential modulator of disease immunopathology. We performed proteomic pathway enrichment analysis of differentially increased proteins, and found an enrichment of complement cascade pathways in the nasal mucus of individuals with CRSwNP as compared to control subjects. Sinonasal mucus levels of complement 3 (C3) correlated with worse subjective disease severity, whereas no significant difference in systemic C3 levels could be determined in plasma samples. Given that human sinonasal epithelial cells were the predominate sinonasal source of C3 and complement anaphylatoxin 3a (C3a) staining, we focused on their role in in vitro studies. Baseline intracellular C3 levels were higher in CRSwNP cells, and following exposure to Aspergillus fumigatus (Af) extract, they released significantly more C3 and C3a. Inhibition of complement 3a receptor (C3aR) signaling led to a decrease in Af-induced C3 and C3a release, both in vitro and in vivo. Finally, we found in vivo that C3aR deficiency or inhibition significantly reduced inflammation and CRS development in a mouse model of Af-induced CRS. These findings demonstrate that local sinonasal complement activation correlates with subjective disease severity, and that local C3aR antagonism significantly ameliorates Af-induced CRS in a rodent model.Item Open Access Chronic coinfections in patients diagnosed with chronic lyme disease: a systematic review.(Am J Med, 2014-11) Lantos, Paul M; Wormser, Gary PPURPOSE: Often, the controversial diagnosis of chronic Lyme disease is given to patients with prolonged, medically unexplained physical symptoms. Many such patients also are treated for chronic coinfections with Babesia, Anaplasma, or Bartonella in the absence of typical presentations, objective clinical findings, or laboratory confirmation of active infection. We have undertaken a systematic review of the literature to evaluate several aspects of this practice. METHODS: Five systematic literature searches were performed using Boolean operators and the PubMed search engine. RESULTS: The literature searches did not demonstrate convincing evidence of: 1) chronic anaplasmosis infection; 2) treatment-responsive symptomatic chronic babesiosis in immunocompetent persons in the absence of fever, laboratory abnormalities, and detectable parasitemia; 3) either geographically widespread or treatment-responsive symptomatic chronic infection with Babesia duncani in the absence of fever, laboratory abnormalities, and detectable parasitemia; 4) tick-borne transmission of Bartonella species; or 5) simultaneous Lyme disease and Bartonella infection. CONCLUSIONS: The medical literature does not support the diagnosis of chronic, atypical tick-borne coinfections in patients with chronic, nonspecific illnesses.Item Open Access Chronic disease management perspectives of colorectal cancer survivors using the Veterans Affairs healthcare system: a qualitative analysis.(BMC health services research, 2018-03) Zullig, Leah L; Goldstein, Karen M; Bosworth, Hayden B; Andrews, Sara M; Danus, Susanne; Jackson, George L; Provenzale, Dawn; Weinberger, Morris; Kelley, Michael J; Voils, Corrine IBackground
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the US. CRC survivors may have complex healthcare needs requiring care from both specialists and primary care. Our objective was to understand how CRC survivors perceive their survivorship care, especially management of their cardiovascular-related chronic diseases.Methods
We identified patients diagnosed with non-metastatic CRC between 10/1/2007 and 12/31/2015 at Veterans Affairs Medical Centers in North Carolina or Virginia. In 2016, we conducted telephone-based, semi-structured interviews to assess survivors' experiences with cancer survivorship and changes in health priorities. Interviews were conducted until thematic saturation was reached. Interviews were audio-recorded, transcribed, and coded.Results
The 25 participants were, on average, 64 years old and approximately 4 years post-CRC diagnosis at the time of interview; most were white (60%), male (92%), and diagnosed with colon cancer (64%) as opposed to rectal cancer. CRC survivors reported: (1) a shift in focus from surviving cancer to reducing cardiovascular disease risk (e.g., by managing weight); (2) challenges with taking medications for CVD-related conditions; (3) new recognition of the importance of engaging with primary care providers.Conclusions
Experiences with cancer shapes how survivors view their health. Management of cardiovascular-related chronic disease is important to veteran CRC survivors. There is a need to deliver cardiovascular disease risk reduction programs tailored for CRC survivors.Item Open Access Chronic in vivo testing of the Penn State infant ventricular assist device.(ASAIO journal (American Society for Artificial Internal Organs : 1992), 2012-01) Weiss, William J; Carney, Elizabeth L; Clark, J Brian; Peterson, Rebecca; Cooper, Timothy K; Nifong, Thomas P; Siedlecki, Christopher A; Hicks, Dennis; Doxtater, Bradley; Lukic, Branka; Yeager, Eric; Reibson, John; Cysyk, Joshua; Rosenberg, Gerson; Pierce, William SThe Penn State Infant Ventricular Assist Device (VAD) is a 12-14 ml stroke volume pneumatically actuated pump, with custom Björk-Shiley monostrut valves, developed under the National Heart, Lung, and Blood Institute Pediatric Circulatory Support program. In this report, we describe the seven most recent chronic animal studies of the Infant VAD in the juvenile ovine model, with a mean body weight of 23.5 ± 4.1 kg. The goal of 4-6 weeks survival was achieved in five of seven studies, with support duration ranging from 5 to 41 days; mean 26.1 days. Anticoagulation was accomplished using unfractionated heparin, and study animals were divided into two protocol groups: the first based on a target activated partial thromboplastin time of 1.5-2 times normal, and a second group using a target thromboelastography R-time of two times normal. The second group required significantly less heparin, which was verified by barely detectable heparin activity (anti-Xa). In both groups, there was no evidence of thromboembolism except in one animal with a chronic infection and fever. Device thrombi were minimal and were further reduced by introduction of the custom valve. These results are consistent with results of adult VAD testing in animals and are encouraging given the extremely low levels of anticoagulation in the second group.Item Open Access Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity.(Nature communications, 2021-07) Bui, Linh T; Winters, Nichelle I; Chung, Mei-I; Joseph, Chitra; Gutierrez, Austin J; Habermann, Arun C; Adams, Taylor S; Schupp, Jonas C; Poli, Sergio; Peter, Lance M; Taylor, Chase J; Blackburn, Jessica B; Richmond, Bradley W; Nicholson, Andrew G; Rassl, Doris; Wallace, William A; Rosas, Ivan O; Jenkins, R Gisli; Kaminski, Naftali; Kropski, Jonathan A; Banovich, Nicholas E; Human Cell Atlas Lung Biological NetworkPatients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.Item Open Access Chronic Lyme disease.(Infect Dis Clin North Am, 2015-06) Lantos, Paul MChronic Lyme disease is a poorly defined diagnosis that is usually given to patients with prolonged, unexplained symptoms or with alternative medical diagnoses. Data do not support the proposition that chronic, treatment-refractory infection with Borrelia burgdorferi is responsible for the many conditions that get labeled as chronic Lyme disease. Prolonged symptoms after successful treatment of Lyme disease are uncommon, but in rare cases may be severe. Prolonged courses of antibiotics neither prevent nor ameliorate these symptoms and are associated with considerable harm.Item Open Access Chronic Lyme disease: the controversies and the science.(Expert Rev Anti Infect Ther, 2011-07) Lantos, Paul MThe diagnosis of chronic Lyme disease has been embroiled in controversy for many years. This is exacerbated by the lack of a clinical or microbiologic definition, and the commonality of chronic symptoms in the general population. An accumulating body of evidence suggests that Lyme disease is the appropriate diagnosis for only a minority of patients in whom it is suspected. In prospective studies of Lyme disease, very few patients go on to have a chronic syndrome dominated by subjective complaints. There is no systematic evidence that Borrelia burgdorferi, the etiology of Lyme disease, can be identified in patients with chronic symptoms following treated Lyme disease. Multiple prospective trials have revealed that prolonged courses of antibiotics neither prevent nor alleviate such post-Lyme syndromes. Extended courses of intravenous antibiotics have resulted in severe adverse events, which in light of their lack of efficacy, make them contraindicated.Item Open Access Chronic spinal cord electrical stimulation protects against 6-hydroxydopamine lesions.(Scientific reports, 2014-01-23) Yadav, Amol P; Fuentes, Romulo; Zhang, Hao; Vinholo, Thais; Wang, Chi-Han; Freire, Marco Aurelio M; Nicolelis, Miguel ALAlthough L-dopa continues to be the gold standard for treating motor symptoms of Parkinson's disease (PD), it presents long-term complications. Deep brain stimulation is effective, but only a small percentage of idiopathic PD patients are eligible. Based on results in animal models and a handful of patients, dorsal column stimulation (DCS) has been proposed as a potential therapy for PD. To date, the long-term effects of DCS in animal models have not been quantified. Here, we report that DCS applied twice a week in rats treated with bilateral 6-OHDA striatal infusions led to a significant improvement in symptoms. DCS-treated rats exhibited a higher density of dopaminergic innervation in the striatum and higher neuronal cell count in the substantia nigra pars compacta compared to a control group. These results suggest that DCS has a chronic therapeutical and neuroprotective effect, increasing its potential as a new clinical option for treating PD patients.Item Open Access Determining the absolute requirement of G protein-coupled receptor kinase 5 for pathological cardiac hypertrophy: short communication.(Circulation research, 2012-09) Gold, Jessica I; Gao, Erhe; Shang, Xiying; Premont, Richard T; Koch, Walter JRationale
Heart failure (HF) is often the end phase of maladaptive cardiac hypertrophy. A contributing factor is activation of a hypertrophic gene expression program controlled by decreased class II histone deacetylase (HDAC) transcriptional repression via HDAC phosphorylation. Cardiac-specific overexpression of G proteinen-coupled receptor kinase-5 (GRK5) has previously been shown to possess nuclear activity as a HDAC5 kinase, promoting an intolerance to in vivo ventricular pressure overload; however, its endogenous requirement in adaptive and maladaptive hypertrophy remains unknown.Objective
We used mouse models with global or cardiomyocyte-specific GRK5 gene deletion to determine the absolute requirement of endogenous GRK5 for cardiac hypertrophy and HF development after chronic hypertrophic stimuli.Methods and results
Mice with global deletion of GRK5 were subjected to transverse aortic constriction. At 12 weeks, these mice showed attenuated hypertrophy, remodeling, and hypertrophic gene transcription along with preserved cardiac function. Global GRK5 deletion also diminished hypertrophy and related gene expression due to chronic phenylephrine infusion. We then generated mice with conditional, cardiac-specific deletion of GRK5 that also demonstrated similar protection from pathological cardiac hypertrophy and HF after transverse aortic constriction.Conclusions
These results define myocyte GRK5 as a critical regulator of pathological cardiac growth after ventricular pressure overload, supporting its role as an endogenous (patho)-physiological HDAC kinase. Further, these results define GRK5 as a potential therapeutic target to limit HF development after hypertrophic stress.Item Open Access Folic acid supplementation before and during pregnancy in the Newborn Epigenetics STudy (NEST).(BMC public health, 2011-01-21) Hoyo, Cathrine; Murtha, Amy P; Schildkraut, Joellen M; Forman, Michele R; Calingaert, Brian; Demark-Wahnefried, Wendy; Kurtzberg, Joanne; Jirtle, Randy L; Murphy, Susan KBackground
Folic acid (FA) added to foods during fortification is 70-85% bioavailable compared to 50% of folate occurring naturally in foods. Thus, if FA supplements also are taken during pregnancy, both mother and fetus can be exposed to FA exceeding the Institute of Medicine's recommended tolerable upper limit (TUL) of 1,000 micrograms per day (μg/d) for adult pregnant women. The primary objective is to estimate the proportion of women taking folic acid (FA) doses exceeding the TUL before and during pregnancy, and to identify correlates of high FA use.Methods
During 2005-2008, pre-pregnancy and pregnancy-related data on dietary supplementation were obtained by interviewing 539 pregnant women enrolled at two obstetrics-care facilities in Durham County, North Carolina.Results
Before pregnancy, 51% of women reported FA supplementation and 66% reported this supplementation during pregnancy. Before pregnancy, 11.9% (95% CI = 9.2%-14.6%) of women reported supplementation with FA doses above the TUL of 1,000 μg/day, and a similar proportion reported this intake prenatally. Before pregnancy, Caucasian women were more likely to take FA doses above the TUL (OR = 2.99; 95% = 1.28-7.00), compared to African American women, while women with chronic conditions were less likely to take FA doses above the TUL (OR = 0.48; 95%CI = 0.21-0.97). Compared to African American women, Caucasian women were also more likely to report FA intake in doses exceeding the TUL during pregnancy (OR = 5.09; 95%CI = 2.07-12.49).Conclusions
Fifty-one percent of women reported some FA intake before and 66% during pregnancy, respectively, and more than one in ten women took FA supplements in doses that exceeded the TUL. Caucasian women were more likely to report high FA intake. A study is ongoing to identify possible genetic and non-genotoxic effects of these high doses.Item Open Access From Hospital to Home: Impact of Transitional Care on Cost, Hospitalisation and Mortality.(Annals of the Academy of Medicine, Singapore, 2019-10) Ang, Yan Hoon; Ginting, Mimaika Luluina; Wong, Chek Hooi; Tew, Chee Wee; Liu, Chang; Sivapragasam, Nirmali Ruth; Matchar, David BruceItem Open Access Gaps in receipt of regular eye examinations among medicare beneficiaries diagnosed with diabetes or chronic eye diseases.(Ophthalmology, 2014-12) Sloan, Frank A; Yashkin, Arseniy P; Chen, YiqunOBJECTIVE: To examine a wide range of factors associated with regular eye examination receipt among elderly individuals diagnosed with glaucoma, age-related macular degeneration, or diabetes mellitus (DM). DESIGN: Retrospective analysis of Medicare claims linked to survey data from the Health and Retirement Study (HRS). PARTICIPANTS: The sample consisted of 2151 Medicare beneficiaries who responded to the HRS. METHODS: Medicare beneficiaries with ≥ 1 of the 3 study diagnoses were identified by diagnosis codes and merged with survey information. The same individuals were followed for 5 years divided into four 15-month periods. Predictors of the number of periods with an eye examination evaluated were beneficiary demographic characteristics, income, health, cognitive and physical function, health behaviors, subjective beliefs about longevity, the length of the individual's financial planning horizon, supplemental health insurance coverage, eye disease diagnoses, and low vision/blindness at baseline. We performed logit analysis of the number of 15-month periods in which beneficiaries received an eye examination. MAIN OUTCOME MEASURES: The primary outcome measure was the number of 15-month periods with an eye examination. RESULTS: One third of beneficiaries with the study's chronic diseases saw an eye care provider in all 4 follow-up periods despite having Medicare. One quarter only obtained an eye examination at most during 1 of the four 15-month follow-up periods. Among the 3 groups of patients studied, utilization was particularly low for persons with diagnosed DM and no eye complications. Age, marriage, education, and a higher score on the Charlson index were associated with more periods with an eye examination. Male gender, being limited in instrumental activities of daily living at baseline, distance to the nearest ophthalmologist, and low cognitive function were associated with a reduction in frequency of eye examinations. CONCLUSIONS: Rates of eye examinations for elderly persons with DM or frequently occurring eye diseases, especially for DM, remain far below recommended levels in a nationally representative sample of persons with health insurance coverage. Several factors, including limited physical and cognitive function and greater distance to an ophthalmologist, but not health insurance coverage, account for variation in regular use.Item Open Access Global chronic disease research training for fellows: perspectives, challenges, and opportunities.(Circulation, 2010-03-23) Bloomfield, Gerald; Huffman, Mark DItem Open Access Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations.(Hepatology (Baltimore, Md.), 2014-02) Kleiner, David E; Chalasani, Naga P; Lee, William M; Fontana, Robert J; Bonkovsky, Herbert L; Watkins, Paul B; Hayashi, Paul H; Davern, Timothy J; Navarro, Victor; Reddy, Rajender; Talwalkar, Jayant A; Stolz, Andrew; Gu, Jiezhun; Barnhart, Huiman; Hoofnagle, Jay H; Drug-Induced Liver Injury Network (DILIN)Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury.We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome.Item Open Access Hypertension Improvement Project (HIP): study protocol and implementation challenges.(Trials, 2009-02-26) Dolor, Rowena J; Yancy, William S; Owen, William F; Matchar, David B; Samsa, Gregory P; Pollak, Kathryn I; Lin, Pao-Hwa; Ard, Jamy D; Prempeh, Maxwell; McGuire, Heather L; Batch, Bryan C; Fan, William; Svetkey, Laura PBackground
Hypertension affects 29% of the adult U.S. population and is a leading cause of heart disease, stroke, and kidney failure. Despite numerous effective treatments, only 53% of people with hypertension are at goal blood pressure. The chronic care model suggests that blood pressure control can be achieved by improving how patients and physicians address patient self-care.Methods and design
This paper describes the protocol of a nested 2 x 2 randomized controlled trial to test the separate and combined effects on systolic blood pressure of a behavioral intervention for patients and a quality improvement-type intervention for physicians. Primary care practices were randomly assigned to the physician intervention or to the physician control condition. Physician randomization occurred at the clinic level. The physician intervention included training and performance monitoring. The training comprised 2 internet-based modules detailing both the JNC-7 hypertension guidelines and lifestyle modifications for hypertension. Performance data were collected for 18 months, and feedback was provided to physicians every 3 months. Patient participants in both intervention and control clinics were individually randomized to the patient intervention or to usual care. The patient intervention consisted of a 6-month behavioral intervention conducted by trained interventionists in 20 group sessions, followed by 12 monthly phone contacts by community health advisors. Follow-up measurements were performed at 6 and 18 months. The primary outcome was the mean change in systolic blood pressure at 6 months. Secondary outcomes were diastolic blood pressure and the proportion of patients with adequate blood pressure control at 6 and 18 months.Discussion
Overall, 8 practices (4 per treatment group), 32 physicians (4 per practice; 16 per treatment group), and 574 patients (289 control and 285 intervention) were enrolled. Baseline characteristics of patients and providers and the challenges faced during study implementation are presented. The HIP interventions may improve blood pressure control and lower cardiovascular disease risk in a primary care practice setting by addressing key components of the chronic care model. The study design allows an assessment of the effectiveness and cost of physician and patient interventions separately, so that health care organizations can make informed decisions about implementation of 1 or both interventions in the context of local resources.Trial registration
ClinicalTrials.gov identifier NCT00201136.Item Open Access ImPlementation REsearCh to DEvelop Interventions for People Living with HIV (the PRECluDE consortium): Combatting chronic disease comorbidities in HIV populations through implementation research.(Progress in cardiovascular diseases, 2020-03) Gamble-George, Joyonna Carrie; Longenecker, Christopher T; Webel, Allison R; Au, David H; Brown, Arleen F; Bosworth, Hayden; Crothers, Kristina; Cunningham, William E; Fiscella, Kevin A; Hamilton, Alison B; Helfrich, Christian D; Ladapo, Joseph A; Luque, Amneris; Tobin, Jonathan N; Wyatt, Gail E; Implementation Research to Develop Interventions for People Living with HIV (PRECluDE) ConsortiumAntiretroviral therapy (ART) prevented premature mortality and improved the quality of life among people living with the human immunodeficiency virus (PLWH), such that now more than half of PLWH in the United States are 50 years of age and older. Increased longevity among PLWH has resulted in a significant rise in chronic, comorbid diseases. However, the implementation of guideline-based interventions for preventing, treating, and managing such age-related, chronic conditions among the HIV population is lacking. The PRECluDE consortium supported by the Center for Translation Research and Implementation Science at the National Heart, Lung, and Blood Institute catalyzes implementation research on proven-effective interventions for co-occurring heart, lung, blood, and sleep diseases and conditions among PLWH. These collaborative research studies use novel implementation frameworks with HIV, mental health, cardiovascular, and pulmonary care to advance comprehensive HIV and chronic disease healthcare in a variety of settings and among diverse populations.Item Open Access Improving the rates of Aspergillus detection: an update on current diagnostic strategies.(Expert review of anti-infective therapy, 2019-01) Jenks, Jeffrey D; Salzer, Helmut JF; Hoenigl, MartinIntroduction
The spectrum of disease caused by Aspergillus spp. is dependent on the immune system of the host, and ranges from invasive aspergillosis (IA) to chronic pulmonary aspergillosis (CPA). Early and reliable diagnosis of Aspergillus disease is important to decrease associated morbidity and mortality. Areas covered: The following review will give an update on current diagnostic strategies for the diagnosis of IA and CPA. Expert commentary: Several new diagnostics for IA (including point-of-care tests) are now available to complement galactomannan testing. In particular, immunoPET/MRI imaging may be a promising approach for diagnosing IA in the near future. Notably, nearly all new biomarkers and tests for IA have been evaluated in the hematology setting only. Validation of biomarkers and tests is therefore needed for the increasing proportion of patients who develop IA outside the hematology setting. As an important first step, reliable definitions of IA are needed for non-hematology settings as clinical presentation and radiologic findings differ in these settings. CPA diagnosis is based on a combination of radiological findings in chest CT, mycological evidence (e.g. by the Aspergillus-specific IgG assay), exclusion of alternative diagnosis and chronicity. ([18F]FDG) PET/CT and immuno PET/MRI imaging are promising new imaging approaches.Item Open Access Is chronic asthma associated with shorter leukocyte telomere length at midlife?(Am J Respir Crit Care Med, 2014-08-15) Belsky, Daniel W; Shalev, Idan; Sears, Malcolm R; Hancox, Robert J; Lee Harrington, Hona; Houts, Renate; Moffitt, Terrie E; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Caspi, AvshalomRATIONALE: Asthma is prospectively associated with age-related chronic diseases and mortality, suggesting the hypothesis that asthma may relate to a general, multisystem phenotype of accelerated aging. OBJECTIVES: To test whether chronic asthma is associated with a proposed biomarker of accelerated aging, leukocyte telomere length. METHODS: Asthma was ascertained prospectively in the Dunedin Multidisciplinary Health and Development Study cohort (n = 1,037) at nine in-person assessments spanning ages 9-38 years. Leukocyte telomere length was measured at ages 26 and 38 years. Asthma was classified as life-course-persistent, childhood-onset not meeting criteria for persistence, and adolescent/adult-onset. We tested associations between asthma and leukocyte telomere length using regression models. We tested for confounding of asthma-leukocyte telomere length associations using covariate adjustment. We tested serum C-reactive protein and white blood cell counts as potential mediators of asthma-leukocyte telomere length associations. MEASUREMENTS AND MAIN RESULTS: Study members with life-course-persistent asthma had shorter leukocyte telomere length as compared with sex- and age-matched peers with no reported asthma. In contrast, leukocyte telomere length in study members with childhood-onset and adolescent/adult-onset asthma was not different from leukocyte telomere length in peers with no reported asthma. Adjustment for life histories of obesity and smoking did not change results. Study members with life-course-persistent asthma had elevated blood eosinophil counts. Blood eosinophil count mediated 29% of the life-course-persistent asthma-leukocyte telomere length association. CONCLUSIONS: Life-course-persistent asthma is related to a proposed biomarker of accelerated aging, possibly via systemic eosinophilic inflammation. Life histories of asthma can inform studies of aging.