Basal Gene Expression by Lung CD4+ T Cells in Chronic Obstructive Pulmonary Disease Identifies Independent Molecular Correlates of Airflow Obstruction and Emphysema Extent

Lung CD4+ T cells accumulate as chronic obstructive pulmonary disease (COPD) progresses, but their role in pathogenesis remains controversial. To address this controversy, we studied lung tissue from 53 subjects undergoing clinically-indicated resections, lung volume reduction, or transplant. Viable single-cell suspensions were analyzed by flow cytometry or underwent CD4+ T cell isolation, followed either by stimulation with anti-CD3 and cytokine/chemokine measurement, or by real-time PCR analysis. In lung CD4+ T cells of most COPD subjects, relative to lung CD4+ T cells in smokers with normal spirometry: (a) stimulation induced minimal IFN-γ or other inflammatory mediators, but many subjects produced more CCL2; (b) the T effector memory subset was less uniformly predominant, without correlation with decreased IFN-γ production. Analysis of unstimulated lung CD4+ T cells of all subjects identified a molecular phenotype, mainly in COPD, characterized by markedly reduced mRNA transcripts for the transcription factors controlling TH1, TH2, TH17 and FOXP3+ T regulatory subsets and their signature cytokines. This mRNA-defined CD4+ T cell phenotype did not result from global inability to elaborate mRNA; increased transcripts for inhibitory CD28 family members or markers of anergy; or reduced telomerase length. As a group, these subjects had significantly worse spirometry, but not DLCO, relative to subjects whose lung CD4+ T cells expressed a variety of transcripts. Analysis of mRNA transcripts of unstimulated lung CD4+ T cell among all subjects identified two distinct molecular correlates of classical COPD clinical phenotypes: basal IL-10 transcripts correlated independently and inversely with emphysema extent (but not spirometry); by contrast, unstimulated IFN-γ transcripts correlated independently and inversely with reduced spirometry (but not reduced DLCO or emphysema extent). Aberrant lung CD4+ T cells polarization appears to be common in advanced COPD, but also exists in some smokers with normal spirometry, and may contribute to development and progression of specific COPD phenotypes. Trial Registration ClinicalTrials.gov as NCT0028122

Disparities in preventive procedures: comparisons of self-report and Medicare claims data

BACKGROUND: Racial/ethnic disparities are assessed using either self-report or claims data. We compared these two data sources and examined contributors to discrepancies in estimates of disparities. METHODS: We analyzed self-report and matching claims data from Medicare Beneficiaries 65 and older who participated in the Medicare Current Beneficiary Survey, 1999–2002. Six preventive procedures were included: PSA testing, influenza vaccination, Pap smear testing, cholesterol testing, mammography, and colorectal cancer testing. We examined predictors of self-reports in the absence of claims and claims in the absence of self-reports. RESULTS: With the exception of PSA testing, racial/ethnic disparities in preventive procedures are generally larger when using Medicare claims than when using patients' self-report. Analyses adjusting for age, gender, income, educational level, health status, proxy response and supplemental insurance showed that minorities were more likely to self-report preventive procedures in the absence of claims. Adjusted odds ratios ranged from 1.07 (95% CI: 0.88 – 1.30) for PSA testing to 1.83 (95% CI: 1.46 – 2.30) for Pap smear testing. Rates of claims in the absence of self-report were low. Minorities were more likely to have PSA test claims in the absence of self-reports (1.55 95% CI: 1.17 – 2.06), but were less likely to have influenza vaccination claims in the absence of self-reports (0.69 95% CI: 0.51 – 0.93). CONCLUSION: These findings are consistent with either racial/ethnic reporting biases in receipt of preventive procedures or less efficient Medicare billing among providers with large minority practices

IMPACT-Global Hip Fracture Audit: Nosocomial infection, risk prediction and prognostication, minimum reporting standards and global collaborative audit. Lessons from an international multicentre study of 7,090 patients conducted in 14 nations during the COVID-19 pandemic

AIMS: This international study aimed to assess: 1) the prevalence of preoperative and postoperative COVID-19 among patients with hip fracture, 2) the effect on 30-day mortality, and 3) clinical factors associated with the infection and with mortality in COVID-19-positive patients. METHODS: A multicentre collaboration among 112 centres in 14 countries collected data on all patients presenting with a hip fracture between 1(st) March-31(st) May 2020. Demographics, residence, place of injury, presentation blood tests, Nottingham Hip Fracture Score, time to surgery, management, ASA grade, length of stay, COVID-19 and 30-day mortality status were recorded. RESULTS: A total of 7090 patients were included, with a mean age of 82.2 (range 50-104) years and 4959 (70%) being female. Of 651 (9.2%) patients diagnosed with COVID-19, 225 (34.6%) were positive at presentation and 426 (65.4%) became positive postoperatively. Positive COVID-19 status was independently associated with male sex (odds ratio (OR) 1.38, p=0.001), residential care (OR 2.15, p<0.001), inpatient fall (OR 2.23, p=0.003), cancer (OR 0.63, p=0.009), ASA grade 4-5 (OR 1.59, p=0.008; OR 8.28, p<0.001), and longer admission (OR 1.06 for each increasing day, p<0.001). Patients with COVID-19 at any time had a significantly lower chance of 30-day survival versus those without COVID-19 (72.7% versus 92.6%, p<0.001). COVID-19 was independently associated with an increased 30-day mortality risk (hazard ratio (HR) 2.83, p<0.001). Increasing age (HR 1.03, p=0.028), male sex (HR 2.35, p<0.001), renal disease (HR 1.53, p=0.017), and pulmonary disease (HR 1.45, p=0.039) were independently associated with a higher 30-day mortality risk in patients with COVID-19 when adjusting for confounders. CONCLUSION: The prevalence of COVID-19 in hip fracture patients during the first wave of the pandemic was 9%, and was independently associated with a three-fold increased 30-day mortality risk. Among COVID-19-positive patients, those who were older, male, with renal or pulmonary disease had a significantly higher mortality risk

Disparities in preventive procedures: comparisons of self-report and Medicare claims data.

BackgroundRacial/ethnic disparities are assessed using either self-report or claims data. We compared these two data sources and examined contributors to discrepancies in estimates of disparities.MethodsWe analyzed self-report and matching claims data from Medicare Beneficiaries 65 and older who participated in the Medicare Current Beneficiary Survey, 1999-2002. Six preventive procedures were included: PSA testing, influenza vaccination, Pap smear testing, cholesterol testing, mammography, and colorectal cancer testing. We examined predictors of self-reports in the absence of claims and claims in the absence of self-reports.ResultsWith the exception of PSA testing, racial/ethnic disparities in preventive procedures are generally larger when using Medicare claims than when using patients' self-report. Analyses adjusting for age, gender, income, educational level, health status, proxy response and supplemental insurance showed that minorities were more likely to self-report preventive procedures in the absence of claims. Adjusted odds ratios ranged from 1.07 (95% CI: 0.88 - 1.30) for PSA testing to 1.83 (95% CI: 1.46 - 2.30) for Pap smear testing. Rates of claims in the absence of self-report were low. Minorities were more likely to have PSA test claims in the absence of self-reports (1.55 95% CI: 1.17 - 2.06), but were less likely to have influenza vaccination claims in the absence of self-reports (0.69 95% CI: 0.51 - 0.93).ConclusionThese findings are consistent with either racial/ethnic reporting biases in receipt of preventive procedures or less efficient Medicare billing among providers with large minority practices

Modelling of mechanical properties of randomly oriented strand thermoplastic composites

There is an emerging interest in the aerospace industry to manufacture components with intricate geometries using discontinuous-fibre carbon/polyether-ether-ketone moulding systems (obtained by cutting unidirectional tape into strands). Great formability and high modulus can be achieved with this type of composites, but the high variability of measured properties can have a detrimental effect on the design allowables. When it comes to prediction of mechanical properties, it is important to capture the average strength and modulus as well as their statistical variability. This article proposes a stochastic finite element technique that uses the concept of randomly oriented strands to model variability, and the application of Hashin’s failure criteria and fracture energies to estimate strength. Overall, the model matches the trends observed during experiments and shows that strength of randomly oriented strand composites is significantly lower than that of continuous-fibre laminates due to the ‘weakest-link’ principle. </jats:p