COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2).

BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

Racial and ethnic disparities in utilization of total knee arthroplasty among older women.

OBJECTIVE: To evaluate racial and ethnic disparities in utilization of total knee arthroplasty (TKA) in relation to demographic, health, and socioeconomic status variables. DESIGN: Prospective study of 102,767 Women's Health Initiative postmenopausal women initially aged 50-79, examining utilization rates of primary TKA between non-Hispanic Black/African American, non-Hispanic White, and Hispanic/Latina women (hereafter referred to as Black, White, and Hispanic). A total of 8,942 Black, 3,405 Hispanic, and 90,420 White women with linked Medicare claims data were followed until time of TKA, death, or transition from fee-for-service coverage. Absolute disparities were determined using utilization rates by racial/ethnic group and relative disparities quantified using multivariable hazards models in adjusting for age, arthritis, joint pain, mobility disability, body mass index, number of comorbidities, income, education, neighborhood socioeconomic status (SES), and geographic region. RESULTS: TKA utilization was higher among White women (10.7/1,000 person-years) compared to Black (8.5/1,000 person-years) and Hispanic women (7.6/1,000 person-years). Among women with health indicators for TKA including diagnosis of arthritis, moderate to severe joint pain, and mobility disability, Black and Hispanic women were significantly less likely to undergo TKA after adjusting for age [Black: HR (95% confidence interval) = 0.70 (0.63-0.79); Hispanic: HR = 0.58 (0.44-0.77)]. Adjustment for SES modestly attenuated the measured disparity, but significant differences remained [Black: HR = 0.75 (0.67-0.89); Hispanic: HR = 0.65 (0.47-0.89)]. CONCLUSIONS: Compared to White women, Black and Hispanic women were significantly less likely to undergo TKA after considering need and appropriateness for TKA and SES. Further investigation into personal-level and provider-level factors that may explain these disparities is warranted.

Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma.

We evaluated whether vitamin D insufficiency (VDI; 25(OH)D <20 ng/ml) was associated with adverse outcomes among follicular lymphoma (FL) patients using an observational prospective cohort study of 642 FL patients enrolled from 2002-2012. The median age at diagnosis was 60 years. At a median follow-up of 59 months, 297 patients (46%) had an event (progression, treatment failure), 78 had died and 42 (6.5%) had a lymphoma-related death. VDI was associated with inferior event-free survival (EFS) at 12 months (EFS12, odds ratio (OR)=2.05; 95% confidence interval (CI) 1.18-3.54), overall survival (OS, hazards ratio (HR)=2.35; 95%CI 1.37-4.02), and lymphoma-specific survival (LSS, HR=2.97; 95% CI 1.52-5.80) for the full cohort. Among patients treated with immunochemotherapy (IC), VDI was associated with inferior EFS12 (OR=3.00; 95% CI 1.26-7.13), OS (HR=2.86; 95% CI 1.39-5.85), and LSS (HR=2.96; 95% CI 1.29-6.79). For observed patients, VDI was associated with inferior OS (HR=2.85; 95% CI 1.20-6.76). For other therapies, VDI was associated with inferior OS (HR=3.06; 95% CI 1.01-9.24). Our work is the first to reveal an association of VDI with early clinical failure, and to demonstrate an association of VDI with adverse outcomes among patients who are observed or treated with therapies other than IC. Our findings suggest a potentially modifiable prognostic factor to address in patients with FL.

Impact of diabetes mellitus on acute outcomes of percutaneous coronary intervention in chronic total occlusions: insights from a US multicentre registry.

AIM: To examine the impact of diabetes mellitus on procedural outcomes of patients who underwent percutaneous coronary intervention for chronic total occlusion. METHODS: We assessed the impact of diabetes mellitus on the outcomes of percutaneous coronary intervention for chronic total occlusion among 1308 people who underwent such procedures at 11 US centres between 2012 and 2015. RESULTS: The participants' mean ± sd age was 66 ± 10 years, 84% of the participants were men and 44.6% had diabetes. As compared with participants without diabetes, participants with diabetes were more likely to have undergone coronary artery bypass graft surgery (38 vs 31%; P = 0.006), and to have had previous heart failure (35 vs 22%; P = 0.0001) and peripheral arterial disease (19 vs 13%; P = 0.002). They also had a higher BMI (31 ± 6 kg/m2 vs 29 ± 6 kg/m2 ; P = 0.001), similar Japanese chronic total occlusion scores (2.6 ± 1.2 vs 2.5 ± 1.2; P = 0.82) and similar final successful crossing technique: antegrade wire escalation (46 vs 47%; P = 0.66), retrograde (30 vs 28%; P = 0.66) and antegrade dissection re-entry (24 vs 25%; P = 0.66). Technical (91 vs 90%; P = 0.80) and procedural (89 vs 89%; P = 0.93) success was similar in the two groups, as was the incidence of major adverse cardiac events (2.2 vs 2.5%; P = 0.61). CONCLUSIONS: In a contemporary cohort of people undergoing percutaneous coronary intervention for chronic total occlusion, nearly one in two (45%) had diabetes mellitus. Procedural success and complication rates were similar in people with and without diabetes.

Telomerase reverse transcriptase expression protects transformed human cells against DNA-damaging agents, and increases tolerance to chromosomal instability.

Reactivation of telomerase reverse transcriptase (TERT) expression is found in more than 85% of human cancers. The remaining cancers rely on the alternative lengthening of telomeres (ALT), a recombination-based mechanism for telomere-length maintenance. Prevalence of TERT reactivation over the ALT mechanism was linked to secondary TERT function unrelated to telomere length maintenance. To characterize this non-canonical function, we created a panel of ALT cells with recombinant expression of TERT and TERT variants: TERT-positive ALT cells showed higher tolerance to genotoxic insults compared with their TERT-negative counterparts. We identified telomere synthesis-defective TERT variants that bestowed similar genotoxic stress tolerance, indicating that telomere synthesis activity is dispensable for this survival phenotype. TERT expression improved the kinetics of double-strand chromosome break repair and reduced DNA damage-related nuclear division abnormalities, a phenotype associated with ALT tumors. Despite this reduction in cytological abnormalities, surviving TERT-positive ALT cells were found to have gross chromosomal instabilities. We sorted TERT-positive cells with cytogenetic changes and followed their growth. We found that the chromosome-number changes persisted, and TERT-positive ALT cells surviving genotoxic events propagated through subsequent generations with new chromosome numbers. Our data confirm that telomerase expression protects against double-strand DNA (dsDNA)-damaging events, and show that this protective function is uncoupled from its role in telomere synthesis. TERT expression promotes oncogene-transformed cell growth by reducing the inhibitory effects of cell-intrinsic (telomere attrition) and cell-extrinsic (chemical- or metabolism-induced genotoxic stress) challenges. These data provide the impetus to develop new therapeutic interventions for telomerase-positive cancers through simultaneous targeting of multiple telomerase activities.

Development and validation of an index to assess hospital quality management systems.

OBJECTIVE: The aim of this study was to develop and validate an index to assess the implementation of quality management systems (QMSs) in European countries. DESIGN: Questionnaire development was facilitated through expert opinion, literature review and earlier empirical research. A cross-sectional online survey utilizing the questionnaire was undertaken between May 2011 and February 2012. We used psychometric methods to explore the factor structure, reliability and validity of the instrument. SETTING AND PARTICIPANTS: As part of the Deepening our Understanding of Quality improvement in Europe (DUQuE) project, we invited a random sample of 188 hospitals in 7 countries. The quality managers of these hospitals were the main respondents. MAIN OUTCOME MEASURE: The extent of implementation of QMSs. RESULTS: Factor analysis yielded nine scales, which were combined to build the Quality Management Systems Index. Cronbach's reliability coefficients were satisfactory (ranging from 0.72 to 0.82) for eight scales and low for one scale (0.48). Corrected item-total correlations provided adequate evidence of factor homogeneity. Inter-scale correlations showed that every factor was related, but also distinct, and added to the index. Construct validity testing showed that the index was related to recent measures of quality. Participating hospitals attained a mean value of 19.7 (standard deviation of 4.7) on the index that theoretically ranged from 0 to 27. CONCLUSION: Assessing QMSs across Europe has the potential to help policy-makers and other stakeholders to compare hospitals and focus on the most important areas for improvement.

The use of on-site visits to assess compliance and implementation of quality management at hospital level.

OBJECTIVE: Stakeholders of hospitals often lack standardized tools to assess compliance with quality management strategies and the implementation of clinical quality activities in hospitals. Such assessment tools, if easy to use, could be helpful to hospitals, health-care purchasers and health-care inspectorates. The aim of our study was to determine the psychometric properties of two newly developed tools for measuring compliance with process-oriented quality management strategies and the extent of implementation of clinical quality strategies at the hospital level. DESIGN: We developed and tested two measurement instruments that could be used during on-site visits by trained external surveyors to calculate a Quality Management Compliance Index (QMCI) and a Clinical Quality Implementation Index (CQII). We used psychometric methods and the cross-sectional data to explore the factor structure, reliability and validity of each of these instruments. SETTING AND PARTICIPANTS: The sample consisted of 74 acute care hospitals selected at random from each of 7 European countries. MAIN OUTCOME MEASURES: The psychometric properties of the two indices (QMCI and CQII). RESULTS: Overall, the indices demonstrated favourable psychometric performance based on factor analysis, item correlations, internal consistency and hypothesis testing. Cronbach's alpha was acceptable for the scales of the QMCI (α: 0.74-0.78) and the CQII (α: 0.82-0.93). Inter-scale correlations revealed that the scales were positively correlated, but distinct. All scales added sufficient new information to each main index to be retained. CONCLUSION: This study has produced two reliable instruments that can be used during on-site visits to assess compliance with quality management strategies and implementation of quality management activities by hospitals in Europe and perhaps other jurisdictions.

Feasibility of using administrative data to compare hospital performance in the EU.

OBJECTIVE: To describe hospitals' organizational arrangements relevant to the abstraction of administrative data, to report on the completeness of administrative data collected and to assess associations between organizational arrangements and completeness of data submission. DESIGN: A cross-sectional STUDY DESIGN: utilizing administrative data. SETTING AND PARTICIPANTS: Randomly selected hospitals from seven European countries (The Czech Republic, France, Germany, Poland, Portugal, Spain, and Turkey). MAIN OUTCOME MEASURES: Completeness of data submission for four quality indicators: mortality after acute myocardial infarction, stroke and hip fractures and complications after normal delivery. RESULTS: In general, hospitals were able to produce data on the four indicators required for this research study. A substantial proportion had missing data on one or more data items. The proportion of hospitals that was able to produce more detailed indicators of relevance for quality monitoring and improvement was low and ranged from 40.1% for thrombolysis performed on patients with acute ischemic stroke to 63.8% for hip-fracture operations performed within 48 h after admission for patients aged 65 or older. National factors were strong predictors of data completeness on the studied indicators. CONCLUSIONS: At present, hospital administrative databases do not seem to be an appropriate source of information for comparison of hospital performance across the countries of the EU. However, given that this is a dynamic field, changes to administrative databases may make this possible in the near future. Such changes could be accelerated by an in-depth comparative analysis of the issues of using administrative data for comparisons of hospital performances in EU countries.

Bowel perforation in intestinal lymphoma: incidence and clinical features.

BACKGROUND: Perforation is a serious life-threatening complication of lymphomas involving the gastrointestinal (GI) tract. Although some perforations occur as the initial presentation of GI lymphoma, others occur after initiation of chemotherapy. To define the location and timing of perforation, a single-center study was carried out of all patients with GI lymphoma. PATIENTS AND METHODS: Between 1975 and 2012, 1062 patients were identified with biopsy-proven GI involvement with lymphoma. A retrospective chart review was undertaken to identify patients with gut perforation and to determine their clinicopathologic features. RESULTS: Nine percent (92 of 1062) of patients developed a perforation, of which 55% (51 of 92) occurred after chemotherapy. The median day of perforation after initiation of chemotherapy was 46 days (mean, 83 days; range, 2-298) and 44% of perforations occurred within the first 4 weeks of treatment. Diffuse large B-cell lymphoma (DLBCL) was the most common lymphoma associated with perforation (59%, 55 of 92). Compared with indolent B-cell lymphomas, the risk of perforation was higher with aggressive B-cell lymphomas (hazard ratio, HR = 6.31, P < 0.0001) or T-cell/other types (HR = 12.40, P < 0.0001). The small intestine was the most common site of perforation (59%). CONCLUSION: Perforation remains a significant complication of GI lymphomas and is more frequently associated with aggressive than indolent lymphomas. Supported in part by University of Iowa/Mayo Clinic SPORE CA97274 and the Predolin Foundation.

Peripheral blood absolute lymphocyte/monocyte ratio recovery during ABVD treatment cycles predicts clinical outcomes in classical Hodgkin lymphoma.

The peripheral blood absolute lymphocyte/monocyte count ratio at diagnosis (ALC/AMC-DX) predicts survival in classical Hodgkin lymphoma (cHL). However, a limitation of the ALC/AMC-DX is the inability to assess sequentially the host/tumor interaction during treatment. Therefore, we retrospectively examined the ALC/AMC ratio, as a surrogate marker of host immunity (ALC) and tumor microenvironment (AMC), at each adriamycin, bleomycin, vinblastine and dacarbazine treatment cycle as a predictor for clinical outcomes. From 1990 until 2008, 190 cHL patients were diagnosed, treated and followed at Mayo Clinic Rochester and qualified for the study. The ALC/AMC ratio at each treatment cycle was a predictor for overall survival (OS) and progression-free survival (PFS). An ALC/AMC ratio 1.1 versus ALC/AMC <1.1 during treatment cycles was an independent predictor for OS (hazard ratio (HR)=0.14; 95% confidence interval (CI): 0.04-0.40; P<0.0002) and for PFS (HR=0.19; 95% CI: 0.05-0.82; P<0.03). The ALC/AMC ratio during treatment cycles is a predictor for survival and provides a platform to develop therapeutic modalities to manipulate the ALC/AMC ratio during chemotherapy to improve clinical outcomes in cHL.

Lymphopenia assessed during routine follow-up after immunochemotherapy (R-CHOP) is a risk factor for predicting relapse in patients with diffuse large B-cell lymphoma.

A specific predictor during routine follow-up to ascertain risk for relapse after standard chemotherapy in non-Hodgkin's lymphoma (NHL) has not been identified. Thus, we studied absolute lymphocyte count (ALC) as a marker of poststandard chemotherapy (rituximab, cyclophosphamide, adriamycin, vincristine and prednisone (R-CHOP)) NHL relapse in patients with diffuse large B-cell lymphoma (DLBCL). ALC was obtained at the time of confirmed relapse and at last follow-up. From 2000 until 2006, 149 consecutive DLBCL patients, originally diagnosed, treated with R-CHOP and followed up at Mayo Clinic, Rochester, were included in this study. Patients at last follow-up without relapse (N=112) had a higher ALC compared with those with relapsed lymphoma ((N=37) median ALC x 10(9)/l of 1.43 (range: 0.33-4.0) versus 0.67 (range: 0.18-1.98), P<0.0001, respectively). ALC at the time of confirmed relapse was a strong predictor for relapse with an area under the curve =0.91 (P<0.0001). An ALC <0.96 x 10(9)/l at the time of confirmed relapse had a positive predictive value of 72% and a positive likelihood ratio of 7.4 to predict relapse after R-CHOP in DLBCL. Patients with an ALC>or=0.96 x 10(9)/l (N=103) had a cumulative incidence of relapse of 6 versus 79% with an ALC <0.96 x 10(9)/l (N=46) (P<0.0001). This study suggests that lymphopenia measured by ALC can be used as a marker to assess risk of DLBCL relapse during routine follow-up after standard chemotherapy.

Surveillance CT scans are a source of anxiety and fear of recurrence in long-term lymphoma survivors.

BACKGROUND: We aimed to assess anxiety and the psychological impact of routine surveillance scans in long-term survivors of adult aggressive lymphoma. PATIENTS AND METHODS: In this cross-sectional observational study of 70 survivors of curable adult aggressive lymphoma, we measured anxiety and the doctor-patient relationship and performed a qualitative interview (n = 30) focused on patient perception of routine follow-up imaging studies. RESULTS: Participants were diagnosed with aggressive lymphoma a median of 4.9 years (2.4-38.0 years) before enrollment. Thirty-seven percent of patients were found to meet criteria for clinically significant anxiety, which was not associated with years since diagnosis. In multivariate analysis, history of relapse and a worse doctor-patient relationship were independently associated with higher anxiety levels. Despite representing a largely cured population, in qualitative interviews patients reported fear of recurrence as a major concern and considerable anxiety around the time of a follow-up imaging scan. CONCLUSIONS: Routine surveillance scans exacerbate underlying anxiety symptoms and fear of recurrence in survivors of aggressive lymphoma. Strategies to minimize follow-up imaging and to improve doctor-patient communication should be prospectively evaluated to address these clinically significant issues.

Reconciling uncertain costs and benefits in Bayes nets for invasive species management.

Bayes nets are used increasingly to characterize environmental systems and formalize probabilistic reasoning to support decision making. These networks treat probabilities as exact quantities. Sensitivity analysis can be used to evaluate the importance of assumptions and parameter estimates. Here, we outline an application of info-gap theory to Bayes nets that evaluates the sensitivity of decisions to possibly large errors in the underlying probability estimates and utilities. We apply it to an example of management and eradication of Red Imported Fire Ants in Southern Queensland, Australia and show how changes in management decisions can be justified when uncertainty is considered.

Lung function and airway cytologic profiles in horses with recurrent airway obstruction maintained in low-dust environments.

BACKGROUND: The effects of long-term environmental management on airway obstruction and inflammation in horses with recurrent airway obstruction (RAO) are unknown. HYPOTHESIS: Horses with RAO maintained in low-dust environments have persistent airway obstruction and neutrophilic inflammation. ANIMALS: Study horses were treated for RAO and then maintained in low-dust environments with no medical management. Horses were classified into 3 groups by years after diagnosis: 1 year (time 1, n = 9), 2-3 years (time 2, n = 7), and 5-6 years (time 3, n = 8). The comparison groups were age-matched healthy horses. METHODS: In this cross-sectional study, a clinical examination was performed, and the clinical score was calculated. Standard lung function, forced expiratory maneuvers, and the cytology of bronchoalveolar lavage fluid (BALF) were evaluated. RESULTS: The clinical scores of the RAO horses were higher than those of the non-RAO horses at time 2 (P = .018). Standard lung function data were not different between the groups at any time point. The forced expiratory flow between 75-95% of exhaled vital capacity was lower in RAO horses than in non-RAO horses at all time points (P < .02), indicating persistent peripheral airway obstruction. Cytologic evaluation of BALF revealed no difference in total nucleated cell numbers or differential cell counts between RAO and non-RAO horses at any time point. CONCLUSIONS AND CLINICAL IMPORTANCE: The peripheral airway obstruction detected in horses with RAO maintained in low-dust environments likely is due to irreversible airway remodeling but is not associated with cytologic evidence of airway inflammation.

Bizarre big belly ball: intraabdominal abscess mimicking stauffer syndrome secondary to uterine leiomyosarcoma.

BACKGROUND: Stauffer syndrome, a very rare paraneoplastic syndrome, refers to reversible intrahepatic cholestasis in the setting of an abdominal malignancy. CASE: A 60-year-old female with a past medical history of uterine leiomyosarcoma status post radical hysterectomy, presented three months later with right upper quadrant abdominal pain. Laboratory evaluation revealed intrabdominal cholestasis and ultrasound of the abdomen showed an echogenic solid mass consistent with a metastatic leiomyosarcoma, and it was felt that her hyperbilirubinemia was due to Stauffer syndrome. However, three days later, blood culture grew gram negative bacilli, and CT scan of the abdomen revealed multiple mesenteric masses with air bubbles consistent with an abdominal abscess. The abscess was drained under CT-scan guidance and her cholestasis gradually came back to nearly normal. CONCLUSION: The case highlights the importance of considering infectious etiologies and Stauffer syndrome in the differential diagnosis of liver dysfunction in patients with intraabdominal malignancies.

Using social judgement theory to model nurses' use of clinical information in critical care education.

Understanding the learning needs of students is a vital step in planning the delivery of effective education. Evaluating the impact of such interventions is not always easy and many methods rely on self-reported behaviour or simple changes in knowledge--whose relationship to action is not always clear. Using conjoint analysis, within the theoretical framework of social judgement theory, this study illustrates a novel means of examining nurses' use of clinical information when diagnosing hypovolemic shock in a series of simulated cases presented via computer. The study examines changes in information usage before and after a traditional lecture. The results show that nurses' information use is not linear and the utility for decision judgement derived from clinical information is not distributed equally. The study also suggests that some clinical information (for example, the Glasgow Coma Score) is not well understood and incorporated into clinical judgement. The study has implications for those designing and evaluating educational interventions and those studying information use, clinical judgement and decision making.