Modelling care quality for patients after a transient ischaemic attack within the US Veterans Health Administration

Objective Timely preventive care can substantially reduce risk of recurrent vascular events or death after a transient ischaemic attack (TIA). Our objective was to understand patient and facility factors influencing preventive care quality for patients with TIA in the US Veterans Health Administration (VHA). Methods We analysed administrative data from a retrospective cohort of 3052 patients with TIA cared for in the emergency department (ED) or inpatient setting in 110 VHA facilities from October 2010 to September 2011. A composite quality indicator (QI score) pass rate was constructed from four process-related quality measures—carotid imaging, brain imaging, high or moderate potency statin and antithrombotic medication, associated with the ED visit or inpatient admission after the TIA. We tested a multilevel structural equation model where facility and patient characteristics, inpatient admission, and neurological consultation were predictors of the resident’s composite QI score. Results Presenting with a speech deficit and higher Charlson Comorbidity Index (CCI) were positively related to inpatient admission. Being admitted increased the likelihood of neurology consultation, whereas history of dementia, weekend arrival and a higher CCI score made neurological consultation less likely. Speech deficit, higher CCI, inpatient admission and neurological consultation had direct positive effects on the composite quality score. Patients in facilities with fewer full-time equivalent neurology staff were less likely to be admitted or to have a neurology consultation. Facilities having greater organisational complexity and with a VHA stroke centre designation were more likely to provide a neurology consultation. Conclusions Better TIA preventive care could be achieved through increased inpatient admissions, or through enhanced neurology and other care resources in the ED and during follow-up care

Processes of Care Associated With Risk of Mortality and Recurrent Stroke Among Patients With Transient Ischemic Attack and Nonsevere Ischemic Stroke

Importance: Early evaluation and management of patients with transient ischemic attack (TIA) and nonsevere ischemic stroke improves outcomes. Objective: To identify processes of care associated with reduced risk of death or recurrent stroke among patients with TIA or nonsevere ischemic stroke. Design, Setting, and Participants: This cohort study included all patients with TIA or nonsevere ischemic stroke at Department of Veterans Affairs emergency department or inpatient settings from October 2010 to September 2011. Multivariable logistic regression was used to model associations of processes of care and without-fail care, defined as receiving all guideline-concordant processes of care for which patients are eligible, with risk of death and recurrent stroke. Data were analyzed from March 2018 to April 2019. Main Outcomes and Measures: Risk of all-cause mortality and recurrent ischemic stroke at 90 days and 1 year was calculated. Overall, 28 processes of care were examined. Without-fail care was assessed for 6 processes: brain imaging, carotid artery imaging, hypertension medication intensification, high- or moderate-potency statin therapy, antithrombotics, and anticoagulation for atrial fibrillation. Results: Among 8076 patients, the mean (SD) age was 67.8 (11.6) years, 7752 patients (96.0%) were men, 5929 (73.4%) were white, 474 (6.1%) had a recurrent ischemic stroke within 90 days, 793 (10.7%) had a recurrent ischemic stroke within 1 year, 320 (4.0%) died within 90 days, and 814 (10.1%) died within 1 year. Overall, 9 processes were independently associated with lower odds of both 90-day and 1-year mortality after adjustment for multiple comparisons: carotid artery imaging (90-day adjusted odds ratio [aOR], 0.49; 95% CI, 0.38-0.63; 1-year aOR, 0.61; 95% CI, 0.52-0.72), antihypertensive medication class (90-day aOR, 0.58; 95% CI, 0.45-0.74; 1-year aOR, 0.70; 95% CI, 0.60-0.83), lipid measurement (90-day aOR, 0.68; 95% CI, 0.51-0.90; 1-year aOR, 0.64; 95% CI, 0.53-0.78), lipid management (90-day aOR, 0.46; 95% CI, 0.33-0.65; 1-year aOR, 0.67; 95% CI, 0.53-0.85), discharged receiving statin medication (90-day aOR, 0.51; 95% CI, 0.36-0.73; 1-year aOR, 0.70; 95% CI, 0.55-0.88), cholesterol-lowering medication intensification (90-day aOR, 0.47; 95% CI, 0.26-0.83; 1-year aOR, 0.56; 95% CI, 0.41-0.77), antithrombotics by day 2 (90-day aOR, 0.56; 95% CI, 0.40-0.79; 1-year aOR, 0.69; 95% CI, 0.55-0.87) or at discharge (90-day aOR, 0.59; 95% CI, 0.41-0.86; 1-year aOR, 0.69; 95% CI, 0.54-0.88), and neurology consultation (90-day aOR, 0.67; 95% CI, 0.52-0.87; 1-year aOR, 0.74; 95% CI, 0.63-0.87). Anticoagulation for atrial fibrillation was associated with lower odds of 1-year mortality only (aOR, 0.59; 95% CI, 0.40-0.85). No processes were associated with reduced risk of recurrent stroke after adjustment for multiple comparisons. The rate of without-fail care was 15.3%; 1216 patients received all guideline-concordant processes of care for which they were eligible. Without-fail care was associated with a 31.2% lower odds of 1-year mortality (aOR, 0.69; 95% CI, 0.55-0.87) but was not independently associated with stroke risk. Conclusions and Relevance: Patients who received 6 readily available processes of care had lower adjusted mortality 1 year after TIA or nonsevere ischemic stroke. Clinicians caring for patients with TIA and nonsevere ischemic stroke should seek to ensure that patients receive all guideline-concordant processes of care for which they are eligible

Peer-group and price influence students drinking along with planned behaviour

This article is available open access through the publisher’s website at the link below. Copyright @ 2008 The Authors.Aims: To examine the theory of planned behaviour (TPB), as a framework for explaining binge drinking among young adults. Methods: One hundred and seventy-eight students in a cross-sectional design study completed self-report questionnaires examining attitudes to drinking, intention to drink and drinking behaviour in university. Binge drinking was defined for females (and males) as consuming ‘four (males—five) or more pints of beer/glasses of wine/measures of spirits’ in a single session. Results: Drinking alcohol was common; 39.6% of males and 35.9% of females reported binge drinking. The TPB explained 7% of the variance in intention to drink. Overall, 43% of the variance in intention, 83% of the variance in total weekly consumption and 44% of the variance in binge drinking was explained. The frequency of drinking and the drinking behaviour of friends significantly predicted intention to drink and binge drinking, respectively. Binge drinkers were influenced by peers and social-situational factors. Pressure to drink was greater for males; undergraduates were influenced by the size of the drinking group, ‘special offer’ prices, and the availability of alcohol. Conclusions: The TPB appeared to be a weak predictor of student drinking but this may be a result of how constructs were measured. With friends’ drinking behaviour emerging as a significant predictor of alcohol consumption, interventions seeking to reduce excessive drinking should target the role of peers and the university environment in which drinking occurs

The Role of SIRT1 in Skeletal Muscle Function and Repair of Older Mice

Background Sirtuin 1 (SIRT1) is a NAD+ sensitive deacetylase that has been linked to longevity and has been suggested to confer beneficial effects that counter aging-associated deterioration. Muscle repair is dependent upon satellite cell function, which is reported to be reduced with aging; however, it is not known if this is linked to an aging-suppression of SIRT1. This study tested the hypothesis that Sirtuin 1 (SIRT1) overexpression would increase the extent of muscle repair and muscle function in older mice. Methods We examined satellite cell dependent repair in tibialis anterior, gastrocnemius, and soleus muscles of 13 young wild-type mice (20–30 weeks) and 49 older (80+ weeks) mice that were controls (n = 13), overexpressed SIRT1 in skeletal muscle (n = 14), and had a skeletal muscle SIRT1 knockout (n = 12) or a satellite cell SIRT1 knockout (n = 10). Acute muscle injury was induced by injection of cardiotoxin (CTX), and phosphate-buffered saline was used as a vector control. Plantarflexor muscle force and fatigue were evaluated before or 21 days after CTX injection. Satellite cell proliferation and mitochondrial function were also evaluated in undamaged muscles. Results Maximal muscle force was significantly lower in control muscles of older satellite cell knockout SIRT1 mice compared to young adult wild-type (YWT) mice (P \u3c 0.001). Mean contraction force at 40 Hz stimulation was significantly greater after recovery from CTX injury in older mice that overexpressed muscle SIRT1 than age-matched SIRT1 knockout mice (P \u3c 0.05). SIRT1 muscle knockout models (P \u3c 0.05) had greater levels of p53 (P \u3c 0.05 MKO, P \u3c 0.001 OE) in CTX-damaged tissues as compared to YWT CTX mice. SIRT1 overexpression with co-expression of p53 was associated with increased fatigue resistance and increased force potentiation during repeated contractions as compared to wild-type or SIRT1 knockout models (P \u3c 0.001). Muscle structure and mitochondrial function were not different between the groups, but proliferation of satellite cells was significantly greater in older mice with SIRT1 muscle knockout (P \u3c 0.05), but not older SIRT1 satellite cell knockout models, in vitro, although this effect was attenuated in vivo after 21 days of recovery. Conclusions The data suggest skeletal muscle structure, function, and recovery after CTX-induced injury are not significantly influenced by gain or loss of SIRT1 abundance alone in skeletal muscle; however, muscle function is impaired by ablation of SIRT1 in satellite cells. SIRT1 appears to interact with p53 to improve muscle fatigue resistance after repair from muscle injury

Care Trajectories of Veterans in the Twelve Months following Hospitalization for Acute Ischemic Stroke

Background—Recovery after a stroke varies greatly between individuals and is reflected by wide variation in the use of institutional and home care services. This study sought to classify veterans according to their care trajectories in the 12 months after hospitalization for ischemic stroke. Methods and Results—The sample consisted of 3811 veterans hospitalized for ischemic stroke in Veterans Health Administration facilities in 2007. Three outcomes—nursing home care, home care, and mortality—were modeled jointly >12 months using latent class growth analysis. Data on Veterans’ care use and cost came from the Veterans Administration and Medicare. Covariates included stroke severity (National Institutes of Health Stroke Scale), functional status (functional independence measure score), age, marital status, chronic conditions, and prestroke ambulation. Five care trajectories were identified: 49% of Veterans had Rapid Recovery with little or no use of care; 15% had a Steady Recovery with initially high nursing home or home care that tapered off; 9% had Long-Term Home Care; 13% had Long-Term Nursing Home Care; and 14% had an Unstable trajectory with multiple transitions between long-term and acute care settings. Care use was greatest for individuals with more severe strokes, lower functioning at hospital discharge, and older age. Average annual costs were highest for individuals with the Long-Term Nursing Home trajectory ($63 082), closely followed by individuals with the Unstable trajectory ($58 720). Individual with the Rapid Recovery trajectory had the lowest costs ($9271). Conclusions—Care trajectories after stroke were associated with stroke severity and functional dependency and they had a dramatic impact on subsequent costs

Estimating and Reporting on the Quality of Inpatient Stroke Care by Veterans Health Administration Medical Centers

Background—Reporting of quality indicators (QIs) in Veterans Health Administration Medical Centers is complicated by estimation error caused by small numbers of eligible patients per facility. We applied multilevel modeling and empirical Bayes (EB) estimation in addressing this issue in performance reporting of stroke care quality in the Medical Centers. Methods and Results—We studied a retrospective cohort of 3812 veterans admitted to 106 Medical Centers with ischemic stroke during fiscal year 2007. The median number of study patients per facility was 34 (range, 12–105). Inpatient stroke care quality was measured with 13 evidence-based QIs. Eligible patients could either pass or fail each indicator. Multilevel modeling of a patient's pass/fail on individual QIs was used to produce facility-level EB-estimated QI pass rates and confidence intervals. The EB estimation reduced interfacility variation in QI rates. Small facilities and those with exceptionally high or low rates were most affected. We recommended 8 of the 13 QIs for performance reporting: dysphagia screening, National Institutes of Health Stroke Scale documentation, early ambulation, fall risk assessment, pressure ulcer risk assessment, Functional Independence Measure documentation, lipid management, and deep vein thrombosis prophylaxis. These QIs displayed sufficient variation across facilities, had room for improvement, and identified sites with performance that was significantly above or below the population average. The remaining 5 QIs were not recommended because of too few eligible patients or high pass rates with little variation. Conclusions—Considerations of statistical uncertainty should inform the choice of QIs and their application to performance reporting

Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial

IMPORTANCE: Mavacamten, a cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the EXPLORER-HCM study. However, the full extent of mavacamten's effects on exercise performance remains unclear. OBJECTIVE: To investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET). DESIGN, SETTING, AND PARTICIPANTS: Exploratory analyses of the data from the EXPLORER-HCM study, a randomized, double-blind, placebo-controlled, phase 3 trial that was conducted in 68 cardiovascular centers in 13 countries. In total, 251 patients with symptomatic obstructive HCM were enrolled. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to mavacamten or placebo. MAIN OUTCOMES AND MEASURES: The following prespecified exploratory cardiovascular and performance parameters were assessed with a standardized treadmill or bicycle ergometer test protocol at baseline and week 30: carbon dioxide output (VCO2), minute ventilation (VE), peak VE/VCO2 ratio, ventilatory efficiency (VE/VCO2 slope), peak respiratory exchange ratio (RER), peak circulatory power, ventilatory power, ventilatory threshold, peak metabolic equivalents (METs), peak exercise time, partial pressure of end-tidal carbon dioxide (PETCO2), and VO2/workload slope. RESULTS: Two hundred fifty-one patients were enrolled. The mean (SD) age was 58.5 (11.9) years and 59% of patients were male. There were significant improvements with mavacamten vs placebo in the following peak-exercise CPET parameters: peak VE/VCO2 ratio (least squares [LS] mean difference, -2.2; 95% CI, -3.05 to -1.26; P < .001), peak METs (LS mean difference, 0.4; 95% CI, 0.17-0.60; P < .001), peak circulatory power (LS mean difference, 372.9 mL/kg/min × mm Hg; 95% CI, 153.12-592.61; P = .001), and peak PETCO2 (LS mean difference, 2.0 mm Hg; 95% CI, 1.12-2.79; P < .001). Mavacamten also improved peak exercise time compared with placebo (LS mean difference, 0.7 minutes; 95% CI, 0.13-1.24; P = .02). There was a significant improvement in nonpeak-exercise CPET parameters, such as VE/VCO2 slope (LS mean difference, -2.6; 95% CI, -3.58 to -1.52; P < .001) and ventilatory power (LS mean difference, 0.6 mm Hg; 95% CI, 0.29-0.90; P < .001) favoring mavacamten vs placebo. CONCLUSIONS AND RELEVANCE: Mavacamten improved a range of CPET parameters beyond pVO2, indicating consistent and broad benefits on maximal exercise capacity. Although improvements in peak-exercise CPET parameters are clinically meaningful, the favorable effects of mavacamten on submaximal exertional tolerance provide further insights into the beneficial impact of mavacamten in patients with obstructive HCM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03470545

Metallothionein in human oesophagus, Barrett's epithelium and adenocarcinoma

The potential of the metal-binding protein, metallothionein, in assessing the progression of normal oesophagus through Barrett's to adenocarcinoma was investigated. Metallothionein was quantitatively determined in resected tissues from patients undergoing oesophagectomy for high grade dysplasia/adenocarcinoma and in biopsies from patients with Barrett's syndrome. In 10 cancer patients, metallothionein concentrations in adenocarcinoma were not significantly different from normal oesophagus, although six had elevated metallothionein concentrations in the metaplastic tissue bordering the adenocarcinoma. In 17 out of 20 non-cancer patients with Barrett's epithelium, metallothionein was significantly increased by 108% (P<0.004). There was no association between the metallothionein levels in Barrett's epithelium and the presence of inflammatory cells, metaplasia or dysplasia. Metallothionein is a marker of progression from normal to Barrett's epithelium but is not increased in oesophageal adenocarcinoma

Development and Validation of Electronic Quality Measures to Assess Care for Patients With Transient Ischemic Attack and Minor Ischemic Stroke

Background—Despite interest in using electronic health record (EHR) data to assess quality of care, the accuracy of such data is largely unknown. We sought to develop and validate transient ischemic attack and minor ischemic stroke electronic quality measures (eQMs) using EHR data. Methods and Results—A random sample of patients with transient ischemic attack or minor ischemic stroke, cared for in Veterans Health Administration facilities (fiscal year 2011), was identified. We constructed 31 eQMs based on existing quality measures. Chart review was the criterion standard for validating the eQMs. To evaluate eQMs in terms of eligibility, we calculated the proportion of patients who were genuinely not eligible to receive a process (based on chart review) and who were correctly identified as not eligible by the EHR data (specificity). To assess eQMs about classification of whether patients received a process, we calculated the proportion of patients who actually received the process (based on chart review) and who were classified correctly by the EHR data as passing (sensitivity). Seven hundred sixty-three patients were included. About eligibility, specificity varied from 25% (brain imaging; carotid imaging) to 99% (anticoagulation quality). About pass rates, sensitivity varied from 30% (antihypertensive class) to 100% (coronary risk assessment; international normalized ratio measured). The 16 eQMs with ≥70% specificity in eligibility and ≥70% sensitivity in pass rates included coronary risk assessment, international normalized ratio measured, HbA1c measurement, speech language pathology consultation, anticoagulation for atrial fibrillation, discharge on statin, lipid management, neurology consultation, Holter, deep vein thrombosis prophylaxis, oral hypoglycemic intensification, cholesterol medication intensification, antihypertensive intensification, antihypertensive class, carotid stenosis intervention, and substance abuse referral for alcohol. Conclusions—It is feasible to construct valid eQMs for processes of transient ischemic attack and minor ischemic stroke care. Healthcare systems with EHRs should consider using electronic data to evaluate care for their patients with transient ischemic attack and to complement and expand quality measurement programs currently focused on patients with stroke

Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8+ Suppressor T Cells

Human CD8+ regulatory T cells, particularly the CD8+CD28− T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the current study, we develop a novel strategy that combines common gamma chain (γc) cytokines IL-2, IL-7 and IL-15 and donor antigen presenting cells (APCs) to stimulate full HLA-mismatched allogeneic human CD8+ T cells which results in significant expansions of donor-specific CD8+CD28− T suppressor cells in vitro. The expanded CD8+CD28− T cells exhibit increased expressions of CTLA-4, FoxP3, and CD25, while down-regulate expressions of CD56, CD57, CD127, and perforin. Furthermore, these cells suppress proliferation of CD4+ T cells in a contact-dependent and cytokine-independent manner. Interestingly, the specificity of suppression is restricted by the donor HLA class I antigens but promiscuous to HLA class II antigens, providing a potential mechanism for linked suppression. Taken together, our results demonstrate a novel role for common γc cytokines in combination with donor APCs in the expansion of donor-specific CD8+CD28− T suppressor cells, and represent a robust strategy for in vitro generation of such cells for adoptive cellular immunotherapy in transplantation