Incidence and Predictor Variables of Pressure Injuries in Patients Undergoing Ventricular Assist Device and Total Artificial Heart Surgeries: An Eight-Year Retrospective Review

BACKGROUND Cardiac surgery patients have some of the highest reported incidence and prevalence of pressure injuries (PI). A growing subset of cardiac surgery include patients with end-stage heart failure who undergo ventricular assist device (VAD) or total artificial heart (TAH) surgery. The risk of PI and their natural history of development in this population are unknown and the specific risk factors for PI development remain unexplored. OBJECTIVES To perform a systematic review of the literature to identify the incidence and risk factors of PI development in patients undergoing VAD-TAH surgery and thereby inform study design and variables in an eight-year retrospective study of all patients undergoing VAD-TAH surgery at a large academic university medical center. METHODS The preferred reporting items for systematic reviews and meta-analyses or PRISMA statement guided this systematic review. Quality of evidence was determined using the Johns Hopkins Nursing Evidence-Based Practice Rating Scale. Two reviewers independently appraised manuscripts matching the eligibility criteria for study inclusion. Four databases including PubMed, CINAHL, Web of Science, Google Scholar, and hand searches of journals based on reference lists from included studies were utilized. Initial results of this primary search revealed zero studies that met inclusion and this search methodology was confirmed by medical librarian consultation. Therefore, a follow up retrospective study was necessary to identify incidence of PI in the VAD-TAH population. However, a secondary search, dropping keywords of VAD-TAH and instead focusing on studies of on-pump cardiac surgery and mixed surgical studies where cardiac surgery patients were included, was conducted to establish variables to guide a retrospective study of all VAD-TAH surgeries between 2010-2018. The retrospective study evaluated the incidence of pressure ulcers by case, patient and incidence density for each of the respective 1000 patient days during the study period. Univariate statistics are reported by four different VAD-TAH devices. Variables significant in bivariate analysis were entered in a stepwise logistic regression model. RESULTS In the systematic review, 312 articles were identified from the databases with eight additional articles from hand searches. Following abstract review, 208 were excluded for not meeting inclusion criteria or study quality metrics. 77 articles were read in full, with 61 excluded, leaving 16 articles for inclusion. 31 risk factors were identified for PI development in on-pump cardiac surgery patients with 11 risk factors which were identified as significant in multivariate analysis for inclusion in the retrospective study

Established Risk Factors Account for Most of the Racial Differences in Cardiovascular Disease Mortality

BACKGROUND: Cardiovascular disease (CVD) mortality varies across racial and ethnic groups in the U.S., and the extent that known risk factors can explain the differences has not been extensively explored. METHODS: We examined the risk of dying from acute myocardial infarction (AMI) and other heart disease (OHD) among 139,406 African-American (AA), Native Hawaiian (NH), Japanese-American (JA), Latino and White men and women initially free from cardiovascular disease followed prospectively between 1993–1996 and 2003 in the Multiethnic Cohort Study (MEC). During this period, 946 deaths from AMI and 2,323 deaths from OHD were observed. Relative risks of AMI and OHD mortality were calculated accounting for established CVD risk factors: body mass index (BMI), hypertension, diabetes, smoking, alcohol consumption, amount of vigorous physical activity, educational level, diet and, for women, type and age at menopause and hormone replacement therapy (HRT) use. RESULTS: Established CVD risk factors explained much of the observed racial and ethnic differences in risk of AMI and OHD mortality. After adjustment, NH men and women had greater risks of OHD than Whites (69% excess, P<0.001 and 62% excess, P = 0.003, respectively), and AA women had greater risks of AMI (48% excess, P = 0.01) and OHD (35% excess, P = 0.007). JA men had lower risks of AMI (51% deficit, P<0.001) and OHD (27% deficit, P = 0.001), as did JA women (AMI, 37% deficit, P = 0.03; OHD, 40% deficit, P = 0.001). Latinos had underlying lower risk of AMI death (26% deficit in men and 35% in women, P = 0.03). CONCLUSION: Known risk factors explain the majority of racial and ethnic differences in mortality due to AMI and OHD. The unexplained excess in NH and AA and the deficits in JA suggest the presence of unmeasured determinants for cardiovascular mortality that are distributed unequally across these populations

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Abstracts from the NIHR INVOLVE Conference 2017

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Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research

The association between physical activity and a composite measure of sleep health

PurposePhysical activity has been associated with several individual dimensions of sleep. However, the association between physical activity and sleep health, a construct that emphasizes the multidimensional nature of sleep, has not been explored. This analysis examined the relationship between physical activity and a composite measure of sleep health.MethodsA total of 114 adults (66% female, 60.3 ± 9.2&nbsp;years) were included in the analyses. Participants reported daily light-intensity physical activity (LPA) and moderate- and vigorous-intensity physical activity (MVPA) via diary, while wearing a pedometer (Omron HJ-720ITC) to measure daily steps. Sleep health was measured using the RU_SATED questionnaire, which addresses regularity of sleep patterns, satisfaction with sleep, daytime alertness, and sleep timing, efficiency, and duration. Multiple linear regression, binary logistic regression, and analysis of covariance (ANCOVA) were utilized for analyses.ResultsMean sleep health score was 9.6 ± 2.4 (0 [poor]-12 [good]). Participants reported 62.9 ± 66.0 and 51.2 ± 51.2&nbsp;min/day of LPA and MVPA, respectively, and took 5585.5 ± 2806.7 steps/day. Greater MVPA was associated with better sleep health (β = 0.27, P = 0.005) and sleep health scores differed between those reporting &lt; 30&nbsp;min/day and ≥ 60&nbsp;min/day of MVPA (P = 0.004). Greater MVPA was associated with higher odds of having good sleep satisfaction (OR = 1.58 [1.14-2.20], P &lt; 0.01), timing (OR = 2.07 [1.24-3.46], P &lt; 0.01), and duration (OR = 1.48 [1.02-2.18], P = 0.04). Pedometer-based physical activity and LPA were not related to sleep health or its individual dimensions.ConclusionsIn middle- to older-aged adults, higher-intensity activity, but not lower-intensity or volume of activity, was associated with greater sleep health. These data suggest that physical activity intensity may be important for sleep health

Simultaneous assessment of iodine, iron, vitamin A, malarial antigenemia, and inflammation status biomarkers via a multiplex immunoassay method on a population of pregnant women from Niger

<div><p>Deficiencies of vitamin A, iron, and iodine are major public health concerns in many low- and middle-income countries, but information on their status in populations is often lacking due to high costs and logistical challenges associated with assessing micronutrient status. Accurate, user-friendly, and low-cost analytical tools are needed to allow large-scale population surveys on micronutrient status. We present the expansion of a 7-plex protein microarray tool for the simultaneous measurement of up to seven biomarkers with relevance to the assessment of the key micronutrients iron, iodine, and vitamin A, and inflammation and malaria biomarkers: α-1-acid glycoprotein, C-reactive protein, ferritin, retinol binding protein 4, soluble transferrin receptor, thyroglobulin, and histidine-rich protein II. Assay performance was assessed using international reference standards and then verified by comparing the multiplexed and conventional immunoassay results on a training panel of plasma samples collected from US adults. These data were used to assign nominal concentrations to the calibrators of the assay to further improve performance which was then assessed by interrogating plasma samples from a cohort of pregnant women from Niger. The correlation between assays for each biomarker measured from this cohort was typically good, with the exception of thyroglobulin, and the sensitivity ranged from 74% to 93%, and specificity from 81% to 98%. The 7-Plex micronutrient assay has the potential for use as an affordable tool for population surveillance of vitamin A, iron, and iodine deficiencies as well as falciparum malarial parasitemia infectivity and inflammation. The assay is easy-to-use, requires minimal sample volume, and is scalable, rapid, and accurate—needing only a low-cost reader and basic equipment present in most reference laboratory settings and so may be employed by low and middle income countries for micronutrient surveillance to inform on status in key populations. Micronutrient deficiencies including iron, iodine, and vitamin A affect a significant portion of the world’s population. Efforts to assess the prevalence of these deficiencies in vulnerable populations are challenging, partly due to measurement tools that are inadequate for assessing multiple micronutrients in large-scale population surveys. We have developed a 7-plex immunoassay for the simultaneous measurement of seven biomarkers relevant to assessing iodine, iron, and vitamin A status, inflammation and <i>Plasmodium falciparum</i> parasitemia by measuring levels of thyroglobulin, ferritin, soluble transferrin receptor, retinol binding protein 4, α-1-acid glycoprotein, C-reactive protein, and histidine-rich protein II. This 7-plex immunoassay technique has potential as a rapid and effective tool for use in large-scale surveys and assessments of nutrition intervention programs in low- and middle-income countries.</p></div

Scatter plots of the 7-Plex results versus NiMaNu conventional immunoassay results.

<p>Concentrations of each analyte as measured in the 7-Plex (x-axes) plotted against concentrations measured using conventional assays (y-axes) for the NiMaNu panel. Solid line is linear least squares regression (y = mx+b). For ferritin, 2 outliers were excluded from regression and for Tg, 9 outliers were excluded from regression (the outliers are included in the plots marked as x rather open circles); 3 extremely high NiMaNu Tg values excluded from plot. For HRP2, the plot reflects assay signal intensity rather than concentration as concentration was not available from the NiMaNu dataset. Horizontal dotted line indicates cutoff for positive results based on the conventional immunoassay and vertical line indicates 7-Plex assay results beyond assay saturation. AGP, α-1-acid glycoprotein; CRP, C-reactive protein; HRP2, histidine rich protein II; RBP, retinol binding protein 4; sTfR, soluble transferrin receptor; Tg, thyroglobulin.</p