Development of a percutaneous coronary intervention patient level composite measure for a clinical quality registry

© 2020 The Author(s). Background: Composite measures combine data to provide a comprehensive view of patient outcomes. Despite composite measures being a valuable tool to assess post-intervention outcomes, the patient perspective is often missing. The purpose of this study was to develop a composite measure for an established cardiac outcome registry, by combining clinical outcomes following percutaneous coronary interventions (PCI) with a patient-reported outcome measure (PROM) developed specifically for this population (MC-PROM). Methods: Two studies were undertaken. Study 1: Patients who had undergone a PCI at one of the three participating registry hospital sites completed the 5-item MC-PROM. Clinical outcome data for the patients (e.g. death, myocardial infarction, repeat vascularisation, new bleeding event) were collected 30 days post-intervention as part of routine data collection for the cardiac registry. Exploratory factor analysis of clinical outcomes and MC-PROM data was conducted to determine the minimum number of constructs to be included in a composite measure. Study 2: Clinical experts participated in a Delphi technique, consisting of three rounds of online surveys, to determine the clinical outcomes to be included and the weighting of the clinical outcomes and MC-PROM score for the composite measure. Results: Study 1: Routine clinical outcomes and the MC-PROM data were collected from 266 patients 30 days post PCI. The MC-PROM score was not significantly correlated with any clinical outcomes. Study 2: There was a relatively consistent approach to the weighting of the clinical outcomes and MC-PROM items by the expert panel (n = 18) across the three surveys with the exception of the clinical outcome of 'deceased at 30 days'. The final composite measure included five clinical outcomes within 30 days weighted at 90% (new heart failure, new myocardial infarction, new stent thrombosis, major bleeding event, new stroke, unplanned cardiac rehospitalisation) and the MC-PROM score (comprising 10% of the total weighting). Conclusions: A single patient level composite score, which incorporates weighted clinical outcomes and a PROM was developed. This composite score provides a more comprehensive reported measure of individual patient wellbeing at 30 days post their PCI-procedure, and may assist clinicians to further assess and address patient level factors that potentially impact on clinical recovery

Symptoms and feelings valued by patients after a percutaneous coronary intervention: A discrete-choice experiment to inform development of a new patient-reported outcome

Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objective To inform the development of a patient-reported outcome measure, the aim of this study was to identify which symptoms and feelings following percutaneous coronary intervention (PCI) are most important to patients. Design Discrete-choice experiment consisting of two hypothetical scenarios of 10 symptoms and feelings (pain or discomfort; shortness of breath; concern/worry about heart problems; tiredness; confidence to do usual activities; ability to do usual activities; happiness; sleep disturbance; dizziness or light-headedness and bruising) experienced after PCI, described by three levels (never, some of the time, most of the time). Preference weights were estimated using a conditional logit model. Setting Four Australian public hospitals that contribute to the Victorian Cardiac Outcomes Registry (VCOR) and a private insurer's claim database. Participants 138 people aged >18 years who had undergone a PCI in the previous 6 months. Main outcome measures Patient preferences via trade-offs between 10 feelings and symptoms. Results Of the 138 individuals recruited, 129 (93%) completed all 16 choice sets. Conditional logit parameter estimates were mostly monotonic (eg, moving to worse levels for each individual symptom and feeling made the option less attractive). When comparing the magnitude of the coefficients (based on the coefficient of the worst level relative to best level in each item), feeling unhappy was the symptom or feeling that most influenced perception of a least-preferred PCI outcome (OR 0.42, 95% CI 0.34 to 0.51, p<0.0001) and the least influential was bruising (OR 0.81, 95% CI 0.67 to 0.99, p=0.04). Conclusion This study provides new insights into how patients value symptoms and feelings they experience following a PCI

Identification of an α(1→6) mannopyranosyltransferase (MptA), involved in Corynebacterium glutamicum lipomanann biosynthesis, and identification of its orthologue in Mycobacterium tuberculosis

Corynebacterium glutamicum and Mycobacterium tuberculosis share a similar cell wall architecture, and the availability of their genome sequences has enabled the utilization of C. glutamicum as a model for the identification and study of, otherwise essential, mycobacterial genes involved in lipomannan (LM) and lipoarabinomannan (LAM) biosynthesis. We selected the putative glycosyltransferase-Rv2174 from M. tuberculosis and deleted its orthologue NCgl2093 from C. glutamicum. This resulted in the formation of a novel truncated lipomannan (Cg-t-LM) and a complete ablation of LM/LAM biosynthesis. Purification and characterization of Cg-t-LM revealed an overall decrease in molecular mass, a reduction of α(1→6) and α(1→2) glycosidic linkages illustrating a reduced degree of branching compared with wild-type LM. The deletion mutant's biochemical phenotype was fully complemented by either NCgl2093 or Rv2174. Furthermore, the use of a synthetic neoglycolipid acceptor in an in vitro cell-free assay utilizing the sugar donor β-d-mannopyranosyl-1-monophosphoryl-decaprenol together with the neoglycolipid acceptor α-d-Manp-(1→6)-α-d-Manp-O-C8 as a substrate, confirmed NCgl2093 and Rv2174 as an α(1→6) mannopyranosyltransferase (MptA), involved in the latter stages of the biosynthesis of the α(1→6) mannan core of LM. Altogether, these studies have identified a new mannosyltransferase, MptA, and they shed further light on the biosynthesis of LM/LAM in Corynebacterianeae

Structural characterization of a partially arabinosylated lipoarabinomannan variant isolated from a Corynebacterium glutamicum ubiA mutant

Arabinan polysaccharide side-chains are present in both Mycobacterium tuberculosis and Corynebacterium glutamicum in the heteropolysaccharide arabinogalactan (AG), and in M. tuberculosis in the lipoglycan lipoarabinomannan (LAM). This study shows by quantitative sugar and glycosyl linkage analysis that C. glutamicum possesses a much smaller LAM version, Cg-LAM, characterized by single t-Araf residues linked to the α(1→6)-linked mannan backbone. MALDI-TOF MS showed an average molecular mass of 13 800–15 400 Da for Cg-LAM. The biosynthetic origin of Araf residues found in the extracytoplasmic arabinan domain of AG and LAM is well known to be provided by decaprenyl-monophosphoryl-d-arabinose (DPA). However, the characterization of LAM in a C. glutamicum : : ubiA mutant devoid of prenyltransferase activity and devoid of DPA-dependent arabinan deposition into AG revealed partial formation of LAM, albeit with a slightly altered molecular mass. These data suggest that in addition to DPA utilization as an Araf donor, alternative pathways exist in Corynebacterianeae for Araf delivery, possibly via an unknown sugar nucleotide

Quantitative assessment of the conjunctival microcirculation using a smartphone and slit-lamp biomicroscope

Purpose: The conjunctival microcirculation is a readily-accessible vascular bed for quantitative haemodynamic assessment and has been studied previously using a digital charge-coupled device (CCD). Smartphone video imaging of the conjunctiva, and haemodynamic parameter quantification, represents a novel approach. We report the feasibility of smartphone video acquisition and subsequent haemodynamic measure quantification via semi-automated means. Methods: Using an Apple iPhone 6 s and a Topcon SL-D4 slit-lamp biomicroscope, we obtained videos of the conjunctival microcirculation in 4 fields of view per patient, for 17 low cardiovascular risk patients. After image registration and processing, we quantified the diameter, mean axial velocity, mean blood volume flow, and wall shear rate for each vessel studied. Vessels were grouped into quartiles based on their diameter i.e. group 1 (&lt;11 μm), 2 (11–16 μm), 3 (16–22 μm) and 4 (&gt;22 μm). Results: From the 17 healthy controls (mean QRISK3 6.6%), we obtained quantifiable haemodynamics from 626 vessel segments. The mean diameter of microvessels, across all sites, was 21.1μm (range 5.8–58 μm). Mean axial velocity was 0.50mm/s (range 0.11–1mm/s) and there was a modestly positive correlation (r 0.322) seen with increasing diameter, best appreciated when comparing group 4 to the remaining groups (p &lt; .0001). Blood volume flow (mean 145.61pl/s, range 7.05–1178.81pl/s) was strongly correlated with increasing diameter (r 0.943, p &lt; .0001) and wall shear rate (mean 157.31 s − 1, range 37.37–841.66 s − 1) negatively correlated with increasing diameter (r − 0.703, p &lt; .0001). Conclusions: We, for the first time, report the successful assessment and quantification of the conjunctival microcirculatory haemodynamics using a smartphone-based system. </p

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure