Assessment of Obstructive Sleep Apnea Among Patients With Chronic Obstructive Pulmonary Disease in Primary Care.

Study Objectives: Observational studies link untreated obstructive sleep apnea (OSA) with adverse outcomes in chronic obstructive pulmonary disease (COPD). The first step in addressing OSA is a clinical assessment. However, given competing demands and a lack of high-quality evidence, it is unclear how often such assessments occur. We explored the documentation of OSA assessment among patients with COPD in primary care, and the patient and provider characteristics associated with these assessments. Methods: We conducted a cross-sectional study of patients with clinically diagnosed COPD at 2 primary care practices. We abstracted charts to determine whether providers assessed OSA, defined as documentation of symptoms, treatment, or a referral to sleep medicine. We performed multivariable mixed-effects logistic regression to assess the associations of patient and provider characteristics with OSA assessment. Results: Among 641 patients with clinically diagnosed COPD, 146 (23%) had OSA assessed over a 1-year period. Positive associations with OSA assessment included body mass index ≥ 30 (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-7.0), pulmonary subspecialist visits (OR 3.9, 95%CI 2.4-6.3), and a prior sleep study demonstrating OSA documented within the electronic medical record (OR 18.0, 95%CI 9.0-35.8). Notably, patients identifying as Black were less likely to have OSA assessed than those identifying as White (OR 0.5, 95%CI 0.2-0.9). Conclusions: Providers document an assessment of OSA among a quarter of patients with COPD. Our findings highlight the importance of future work to rigorously test the impact of assessment on important health outcomes. Our findings also reinforce that additional strategies are needed to improve the equitable delivery of care.

Recommendations for Setting a Criterion and Assessing Commutability of Sample Materials Used in External Quality Assessment/Proficiency Testing Schemes.

It is important for external quality assessment materials (EQAMs) to be commutable with clinical samples; i.e., they should behave like clinical samples when measured using end-user clinical laboratory in vitro diagnostic medical devices (IVD-MDs). Using commutable EQAMs makes it possible to evaluate metrological traceability and/or equivalence of results between IVD-MDs. The criterion for assessing commutability of an EQAM between 2 IVD-MDs is that its result should be within the prediction interval limits based on the statistical distribution of the clinical sample results from the 2 IVD-MDs being compared. The width of the prediction interval is, among other things, dependent on the analytical performance characteristics of the IVD-MDs. A presupposition for using this criterion is that the differences in nonselectivity between the 2 IVD-MDs being compared are acceptable. An acceptable difference in nonselectivity should be small relative to the analytical performance specifications used in the external quality assessment scheme. The acceptable difference in nonselectivity is used to modify the prediction interval criterion for commutability assessment. The present report provides recommendations on how to establish a criterion for acceptable commutability for EQAMS, establish the difference in nonselectivity that can be accepted between IVD-MDs, and perform a commutability assessment. The report also contains examples for performing a commutability assessment of EQAMs.

Analytical performance of 17 commercially available point-of-care tests for CRP to support patient management at lower levels of the health system.

Accurate and precise point-of-care (POC) testing for C-reactive protein (CRP) can help support healthcare providers in the clinical management of patients. Here, we compared the analytical performance of 17 commercially available POC CRP tests to enable more decentralized use of the tool. The following CRP tests were evaluated. Eight quantitative tests: QuikRead go (Aidian), INCLIX (Sugentech), Spinit (Biosurfit), LS4000 (Lansionbio), GS 1200 (Gensure Biotech), Standard F200 (SD Biosensor), Epithod 616 (DxGen), IFP-3000 (Xincheng Biological); and nine semi-quantitative tests: Actim CRP (ACTIM), NADAL Dipstick (nal von minden), NADAL cassette (nal von minden), ALLTEST Dipstick (Hangzhou Alltest Biotech), ALLTEST Cassette cut-off 10-40-80 (Hangzhou Alltest Biotech), ALLTEST Cassette cut-off 10-30 (Hangzhou Alltest Biotech), Biotest (Hangzhou Biotest Biotech), BTNX Quad Line (BTNX), BTNX Tri Line (BTNX). Stored samples (n = 660) had previously been tested for CRP using Cobas 8000 Modular analyzer (Roche Diagnostics International AG, Rotkreuz, Switzerland (reference standards). CRP values represented the clinically relevant range (10-100 mg/L) and were grouped into four categories (<10 mg/L, 10-40 mg/L or 10-30 mg/L, 40-80 mg/L or 30-80 mg/L, and > 80mg/L) for majority of the semi-quantitative tests. Among the eight quantitative POC tests evaluated, QuikRead go and Spinit exhibited better agreement with the reference method, showing slopes of 0.963 and 0.921, respectively. Semi-quantitative tests with the four categories showed a poor percentage agreement for the intermediate categories and higher percentage agreement for the lower and upper limit categories. Analytical performance varied considerably for the semi-quantitative tests, especially among the different categories of CRP values. Our findings suggest that quantitative tests might represent the best choice for a variety of use cases, as they can be used across a broad range of CRP categories.

Mentoring and depressive symptoms of youth: Examining prospective and interactive associations with mentoring relationship quality.

A significant body of research has demonstrated that mentoring relationships support positive youth development. The quality of the mentoring relationship has been identified as a predictor of positive youth outcomes. However, limited research has examined how engagement in a mentoring program may be related to youth depressive symptoms specifically. The current study utilized a sample of 2003 youth participating in mentoring programs across the country (Mage = 12.32, SD = 1.42, 55.1% female) from diverse racial and ethnic backgrounds (39.1% Black, 23.6% White, 22.1% Hispanic, 3.3% Native American or Alaskan Native, .4% Asian or Pacific Islander, 1.8% other, and 9.7% Multi-Ethnic) to investigate associations between youth depressive symptoms and mentoring relationship quality. Results revealed that: (1) mean depressive symptoms decreased after participation in a mentoring program; (2) several, but not all, relationship quality indicators predicted change in depressive symptoms; (3) baseline levels of depressive symptoms negatively predicted indicators of relationship quality; and (4) associations between several relationship quality indicators and follow-up depressive symptoms differed by baseline levels of depressive symptoms. These findings highlight the potential benefits of mentoring programs to youth and the need to provide mentors with support around building relationships with youth, especially those experiencing depressive symptoms.

(Not) minding the gap: A qualitative interview study of how social class bias can influence youth mentoring relationships.

This study sought to examine how social class bias may be enacted by mentors and mentoring program staff within community-based youth mentoring relationships and how these biases may influence the mentoring relationship. A narrative thematic analysis was conducted with interviews from mentors, mentees' parents/caregivers, and mentoring program staff representing 36 matches participating in a larger, prospective, mixed-methods study examining factors associated with early match closures. Findings indicate that although some mentors were able to partner with the youth and family to effectively navigate challenges related to the family's economic circumstances, other mentors and some mentoring program staff held deficit views of the youth and their family that appeared to be at least partially rooted in negative social class-based assumptions about attitudes and behaviors. Specifically, we observed tendencies on the part of some mentors and program staff toward (a) deficit-based views of families and youth, (b) individual-level attributions for the family's economic circumstances and blaming of caregivers, and (c) perceiving mentors as being underappreciated by the youth's caregiver. These deficit perspectives contributed to the minimization of parent/caregiver voice in the mentoring process and negative interpretations of parent/caregiver and, in some cases, youth attitudes and behaviors.

Low-Value Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease and the Association with Healthcare Utilization and Costs.

Rationale: Inhaled corticosteroids (ICS) are not first-line therapy for patients with chronic obstructive pulmonary disease (COPD) at low risk of exacerbations, but they are commonly prescribed despite evidence of harm. We consider ICS prescription in this population to be of "low value." The association of low-value ICS with subsequent healthcare utilization and costs is unknown. Understanding this relationship could inform efforts to reduce the delivery of low-value care. Objectives: To determine whether low-value ICS prescribing is associated with higher outpatient healthcare utilization and costs among patients with COPD who are at low risk of exacerbation. Methods: We performed a cohort study between January 1, 2010, and December 31, 2018, identifying a cohort of veterans with COPD who performed pulmonary function tests (PFTs) at 21 Veterans Affairs medical centers nationwide. Patients were defined as having low exacerbation risk if they experienced less than two outpatient exacerbations and no hospital admissions for COPD in the year before PFTs. Our primary exposure was the receipt of an ICS prescription in the 3 months before the date of PFTs. Our primary outcomes were outpatient utilization and outpatient costs in the 1 year after PFTs. For inference, we generated negative binomial models for utilization and generalized linear models for costs, adjusting for confounders. Results: We identified a total of 31,551 patients with COPD who were at low risk of exacerbation. Of these patients, 9,742 were prescribed low-value ICS (mean [standard deviation (SD)] age, 69 [9] yr), and 21,809 were not prescribed low-value ICS (mean [SD] age, 68 [9] yr). Compared with unexposed patients, those exposed to low-value ICS had 0.53 more encounters per patient per year (95% confidence interval CI, 0.23-0.83) and incurred $154.72 higher costs/patient/year (95% CI, $45.58-$263.86). Conclusions: Low-value ICS prescription was associated with higher subsequent outpatient healthcare utilization and costs. Potential mechanisms for the observed association are that 1) low-value ICS may be a marker of poor respiratory symptom control, 2) there is confounding by indication, or 3) low-value ICS results in increased drug costs or utilization. Health systems should identify low-value ICS prescriptions as a target to improve value-based care.

Cortical Cell Diameter Is Key To Energy Costs of Root Growth in Wheat.

Root growth requires substantial amounts of energy and thus carbohydrates. The energy costs of root growth are particularly high in both dry and compacted soil, due to high soil penetration resistance. Consequently, more carbon must be allocated from aboveground plant tissue to roots, which limits crop productivity. In this study, we tested the utility of root cortical cell diameter as a potential selection target to reduce the energy costs of root growth. Isothermal calorimetry was adopted for in situ quantification of the energy costs of root growth of 16 wheat (Triticum aestivum) genotypes under three levels of penetration resistance. We show that cortical cell diameter is a pivotal and heritable trait, which is strongly related to the energy costs of root growth. Genotypic diversity was found for cortical cell diameter and the energy costs of root growth. A large root cortical cell diameter correlated with reduced energy costs of root growth, particularly under high soil penetration resistance. Moreover, significant correlations were found between the ability to radially enlarge cortical cells upon greater penetration resistance (i.e. phenotypic plasticity) and the responsiveness in the energy costs of root growth. A higher degree of phenotypic plasticity in cortical cell diameter was associated with reduced energy costs of root growth as soil penetration resistance increased. We therefore suggest that genotypic diversity and phenotypic plasticity in cortical cell diameter should be harnessed to adapt crops to dry and compacted soils.

BUILD EXITO: a multi-level intervention to support diversity in health-focused research.

BACKGROUND AND PURPOSE: As part of the NIH BUILD initiative to diversify the scientific workforce, the EXITO project is a large multi-institutional effort to provide comprehensive support and training for undergraduates from traditionally underrepresented student populations who aspire to health-related research careers. Portland State University, a major public urban university that prioritizes student access and opportunity, and Oregon Health & Science University, a research-intensive academic health center, lead the EXITO network comprised of eleven 2-year and 4-year institutions of higher education spanning Oregon, Washington, Alaska, Hawaii, Guam, American Samoa, and the Northern Mariana Islands. The EXITO project aims for impact in biomedical research by training diverse scholars from indigenous and underserved communities affected by adverse health disparities. PROJECT APPROACH: Guided by socio-ecological theory, the EXITO project is a multi-level intervention offering a three-year research training pathway for scholars in the biomedical, behavioral, health, and social sciences. Fundamental components of the model include student outreach and engagement, integrated curricular enhancements, intensive research experiences, multi-faceted developmental mentoring, supportive community and services, and rigorous evaluation and quality improvement. EXITO also advances faculty and institutional development in these domains by holding curriculum development conferences, creating research learning communities, awarding pilot project research funding, providing mentor training and ongoing support, collaborating with other research equity programs, and developing campus infrastructure and services to support scholars with diverse backgrounds and needs. HIGHLIGHTS: The large and geographically broad network of EXITO institutions engages a range of diverse students, including indigenous populations and students beginning post-secondary education at community colleges. The EXITO model specifically accommodates many students transferring from 2-year partner institutions and facilitates seamless transfer to the 4-year institution. EXITO features several approaches to research training, including supported summer entry into research placements, the incorporation of responsible conduct of research content into general education curriculum, and the intentional matching of scholars with three types of mentors (e.g., peer, career, research). IMPLICATIONS: EXITO provides an example of a comprehensive research training initiative for traditionally underrepresented students that can be implemented across a diverse range of 2-year and 4-year institutions.

Individual risk assessment of adverse pregnancy outcome by multivariate regression analysis may serve as basis for drug intervention studies: retrospective analysis of 426 high-risk patients including ethical aspects.

OBJECTIVE: To identify patients at very high risk for adverse pregnancy outcome (APO) at the 20- to 23-week scan and to assess the effectiveness of Aspirin (ASS) and low molecular weight heparin (LMWH) starting after this examination. PATIENTS AND METHODS: By applying an algorithm based on multivariate logistic regression analysis using the parameters maternal age, parity, body mass index (BMI), mean pulsatility index of both uterine arteries (meanPI), presence of uni- or bilateral notch, and depth of notch (mean notch index (meanNI), we retrospectively calculated the individual risk for APO of 21,302 singleton pregnancies. We isolated a subgroup of 426 patients with the highest calculated probability for APO (cpAPO > 27.8 %). 147 had been treated with ASS; 73 with LMWH, 15 patients with a combination of ASS and LMWH, and 191 patients had not received anticoagulants. RESULTS: Administration of ASS starting after 20 gestational weeks in comparison to non-treated patients significantly reduced the frequency of intrauterine/neonatal death (IUD/NND), preeclampsia <33 weeks (PE < 33), and preterm delivery <33 weeks (PD < 33), while the frequency of IUGR showed a tendency to be elevated (P = 0.061). The subgroup of high-risk patients treated with LMWH was characterised by a higher a priori risk for APO and showed no significant reduction of any form of APO but an increased frequency of PE. CONCLUSION: Individual assessment of risk for APO by applying a simple algorithm based on biometrical/biographical as well as sonographic parameters may serve as basis for drug intervention studies. The administration of ASS in high-risk patients starting after 20 gestational weeks reduced the frequency of most of the severe forms of adverse pregnancy outcome in high-risk patients. A complication-reducing effect of LMWH starting after 20 weeks of gestation in patients could not be proven. From an ethical point of view, it may not be justified any more to preclude high-risk patients from administration of ASS or to perform studies of ASS against placebo.

Impact of non-profit organizations on drug discovery: opportunities, gaps, solutions.

Non-profit organizations (NPO) play an increasingly important role in drug discovery and development for diseases that are neglected by the pharmaceutical industry because of low or absent commercial incentives. Governments and major private foundations such as the Wellcome Trust and the Bill & Melinda Gates Foundation increasingly step in to provide strategic direction, communication platforms and major resources, motivated by the fact that major healthcare problems remain unsolved. Drug discovery in the field of neglected diseases is fraught with complexities since, in many cases, important tools are lacking including readily available diagnostics, molecular epidemiology, appropriate model systems, representative strain collections, biomarkers, up-to-date trial methodologies and regulatory strategies. On top of this, the high hurdles addressing novel drug targets must be cleared.

Low-cost enumeration of CD4+ T cells using a density-based negative selection method (RosetteSep) for the monitoring of HIV-infected individuals in non-OECD countries.

The CD4 count is the best surrogate marker for monitoring HIV. The reference method for assessing CD4 counts (flow cytometry, FCM), as expensive technique, is not widely used in non-OECD countries. To make HIV-monitoring available to more patients in these countries, we modified a commercially available density-based negative selection assay (RosetteSep) to make it applicable for low-cost cell enumeration. For evaluation (Step 1), blood taken from 25 HIV patients and 29 healthy donors was assayed with the modified negative selection method (MNS) and compared with FCM. For validation (Step 2), this method was performed in blind quintuplicates on 12 HIV+ blood samples according to FDA guidelines. Association of MNS with the FCM is given by regression models for both steps: Step 1: slope = 1.091, intercept = -46.5. Step 2: slope = 1.074, intercept = -38.3 (Step 2). The imprecision of MNS assessed during Step 2 was 21.2% (intraserial) and 18.8% (interserial). The results suggest that MNS is capable of providing an approximate CD4 count. At a cost of 0.30, it is affordable to patients living in resource-restrained areas. The technique has the potential to deliver an accurate, precise, low-cost test to monitor HIV+ patients.

Assessment of the effect of mefloquine on artesunate pharmacokinetics in healthy male volunteers.

The effect of mefloquine on artesunate pharmacokinetics was assessed in 20 volunteers given artesunate for 3 days, followed > or =21 days later by combination therapy for 3 days. The areas under the concentration-time curve from 0 h to infinity for dihydroartemisinin, the active metabolite of artesunate, were similar on day 3 of the two dosing periods (P = 0.12), implying no interaction.

A practical view of 'druggability'.

The introduction of Lipinski's 'Rule of Five' has initiated a profound shift in the thinking paradigm of medicinal chemists. Understanding the difference between biologically active small molecules and drugs became a priority in the drug discovery process, and the importance of addressing pharmacokinetic properties early during lead optimization is a clear result. These concepts of 'drug-likeness' and 'druggability' have been extended to proteins and genes for target identification and selection. How should these concepts be integrated practically into the drug discovery process? This review summarizes the recent advances in the field and examines the usefulness of 'the rules of the game' in practice from a medicinal chemist's standpoint.

MR assessment of fetal lung development using lung volumes and signal intensities.

The purpose of this study was to evaluate the monitoring and diagnostic potential of MRI in fetal lung development and disease using lung volume and signal intensity changes through gestation. Thirty-five healthy fetuses (22-42 weeks) were examined on a 1.5- T MR system using sagittal T2w single-shot fast spin-echo imaging (TR indefinite, TE 90 ms, slice thickness/gap 3-5/0 mm, FOV 26-40 cm, NEX 0.5). Fetal body and lung were segmented manually and volumes calculated. Signal intensities (SI) of fetal lung and three reference values were measured on the section best displaying the lung. Regions of interests were defined by including the maximal organ area possible. The following SI ratios were generated: lung/liver, lung/amniotic fluid, lung/muscle, liver/fluid and liver/muscle. Volumes and ratios were correlated with gestational age. Data from seven fetuses with pulmonary pathology were compared with these normative values. Absolute lung volume varied from 12.3 to 143.5 cm(3) in correlation with gestational age ( P<0.001); lung volume relative to total body volume ranged from 1.6 to 5.0%, decreasing with gestational age ( P=0.001). All SI ratios measured were unrelated to gestational age. Diagnoses in the seven abnormal fetuses were hydrothorax ( n=2), congenital cystic adenomatoid malformation ( n=2), diaphragmatic hernia ( n=2) and pulmonary sequestration ( n=1); their absolute and relative lung volumes were below normal ( P<0.001). The SI ratios did not differ significantly from those in the normal population. Normative MR fetal lung volumes may have important clinical applications in confirming and quantifying intrauterine pulmonary hypoplasia and in complementing ultrasound in the planning of fetal and post-natal surgery. No clinical relevance was found for fetal lung SI values.

Pelvimetry and patient acceptability compared between open 0.5-T and closed 1.5-T MR systems.

Our objective was to compare maternal pelvimetry and patient acceptability between open low-field (0.5-T) and closed 1.5-T MR systems. Thirty women referred for pelvimetry (pregnant: n=15) were scanned twice in the supine position, once in the vertical open system and once in the closed system. Each patient completed a comfort and acceptability questionnaire. Pelvimetric and questionnaire data were compared between systems. Total scan time was double in the open system (7:52+/-1:47 vs 3:12+/-1:20 min). Poor image quality in the open system prevented assessment of interspinous and intertuberous diameters in one woman and all measurements in another, both pregnant, with abdominal circumferences >120 cm. The open system was much more acceptable in terms of claustrophobia and confinement (both p<0.01). Claustrophobia interrupted one closed examination. Thirty-three percent of pregnant women in both systems reported fear of fetal harm. Sixty percent of all women preferred the open system, 7% the closed system, and 33% had no preference. Limits of agreement of 3-5% from the mean for all diameters confirmed good pelvimetric reproducibility. Women's preference for open-system MR pelvimetry is feasible with abdominal circumferences