Venous thromboembolism (VTE) in patients with ALK-rearranged non-small cell lung cancer (ALK-LC): A population-based cohort.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6608-6608
Author(s):  
Alona Zer ◽  
Lilach Joseph ◽  
Erez Battat ◽  
Tzippy Shochat ◽  
Avi Leader ◽  
...  

6608 Background: Advanced NSCLC is associated with an increased risk for VTE, with a reported rate of 8-15%. Clinical observations suggest a higher rate of VTE in patients with ALK-rearranged NSCLC. Clalit Health Services (CHS) is both a healthcare payer and provider, covering over 50% of the population in Israel, with individual patient data recorded in a centralized electronic database. We aimed to determine the incidence of VTE in patients with ALK-LC using a population-based cohort. Methods: We identified all patients diagnosed with NSCLC between 01/2012-12/2017 within CHS. Clinical and demographic data (including VTE risk factors, i.e. components of the Khorana score) were extracted from the CHS registry for all patients. Patients with ALK-LC were identified according to crizotinib prescriptions (dispensed after an approved CHS' pre-authorization for an ALK-LC diagnosis). VTE was identified by ICD diagnosis codes 415.xx, 444.xx, 451.xx and 453.xx. VTE risk factors (Khorana score) were also extracted. Association between ALK-LC and VTE were analyzed using logistic regression, estimating univariate and multivariate Odds Ratios (OR). Results: Overall, 4327 patients with a diagnosis of NSCLC were identified. 149 (3%) had at least one prescription for crizotinib for advanced ALK-LC. The rate of VTE in these patients was 25% (38 of 149 patients), while in the non-ALK-LC the rate was 14% (596/4178), OR = 2.05, p = 0.0004. The association was significant also in a multivariate analysis adjusting for, age, smoking status, BMI, platelet count, hemoglobin and Charlson co-morbidity score (OR 1.66, p = 0.018). Conclusions: This pooled analysis of individual patient data confirms prior data from smaller retrospective studies, suggesting ALK-LC is associated with a high risk of VTE. Randomized trials with prophylactic anti-coagulation are unlikely to be performed in this rare subtype, thus increased awareness and consideration of VTE prophylaxis in high risk patients is warranted.

2021 ◽  
Author(s):  
Filip Ottosson ◽  
Einar Smith ◽  
Ulrika Ericson ◽  
Salvatore Di Somma ◽  
Paola Antonini ◽  
...  

Background Obesity is a key risk factor for type 2 diabetes, however, up to 20% of patients are normal weight. Our aim was to identify metabolite patterns reproducibly predictive of BMI, and subsequently to test if lean individuals who carry an obese metabolome are at hidden high risk of obesity related diseases, such as diabetes. Methods We measured 109 metabolites in fasted plasma samples of 7663 individuals from two Swedish and one Italian population-based cohort. Ridge regression models were used to predict BMI using the plasma metabolites. Individuals with a predicted BMI either more than 5 kg/m2 higher (overestimated) or lower (underestimated) than their actual BMI were characterized as outliers and further investigated for obesity related risk factors and future risk of diabetes and mortality. Results The plasma metabolome could predict BMI in all cohorts (r2 = 0.48, 0.26 and 0.19). The overestimated group had a BMI similar to individuals correctly predicted as normal weight, similar waist circumference, were not more likely to change weight over time but had a 2 times higher risk of future diabetes and an 80 % increased risk of all-cause mortality. These associations remained after adjustments for obesity-related risk factors and lifestyle parameters. Conclusions We found that lean individuals with an obese metabolome, have an increased risk for diabetes and all-cause mortality compared to lean individuals with a healthy metabolome. Metabolomics may be used to identify hidden high-risk individuals, in order to initiate lifestyle and pharmacological interventions.


2020 ◽  
pp. 1-9
Author(s):  
Yongqi Zhong ◽  
Steven Pham ◽  
Giovanna Porta ◽  
Antoine Douaihy ◽  
Anna Marsland ◽  
...  

Abstract Background Suicide and cardiovascular disease rank among the leading causes of disability and premature mortality worldwide. Young adult suicide attempters are at increased risk of mortality from cardiovascular disease even compared to those with major depressive disorder suggesting an increased burden of cardiovascular risk factors. We compared the cardiovascular risk burden between youth attempters and other high-risk individuals. Methods Participants were from the Collaborative Psychiatric Epidemiology Surveys (CPES), a U.S. population-based study, aged 18–30 years [suicide attempt (SA): n = 303; suicidal ideation (SI): n = 451; controls: n = 3671]; and psychiatric inpatients admitted for a SA (n = 38) or SI (n = 40) and healthy controls (n = 37) aged 15–30 years. We computed a cardiovascular risk score and high- and low-risk latent classes based on risk factors of high blood pressure, obesity, and smoking. Results Suicide attempters showed an increased cardiovascular risk score (CPES: B = 0.43, 95% confidence interval (CI) 0.31–0.54, p < 0.001; inpatient sample: B = 1.61, 95% CI 0.53–2.68, p = 0.004) compared to controls. They were also more likely to be classified in the high cardiovascular risk group (CPES: odds ratio (OR) 3.36, 95% CI 1.67–6.78, p = 0.001; inpatient sample: OR 9.89, 95% CI 1.38–85.39, p = 0.03) compared to those with SI (CPES: OR 1.15, 95% CI 0.55–2.39, p = 0.71; inpatient sample: OR 1.91, 95% CI 0.25–15.00, p = 0.53). Conclusions Youth attempters show an increased burden for cardiovascular risk compared to other high-risk individuals in inpatient and population-based samples. Clinicians should pay particular attention to cardiovascular risk factors among suicide attempters in order to reduce their risk for cardiovascular events.


Author(s):  
V. J. Apea ◽  
Y. I. Wan ◽  
R. Dhairyawan ◽  
Z. A. Puthucheary ◽  
R. M. Pearse ◽  
...  

AbstractBackgroundPreliminary studies suggest that people from Black, Asian and Minority Ethnic (BAME) backgrounds experience higher mortality from COVID-19 but the underlying reasons remain unclear.MethodsProspective analysis of registry data describing patients admitted to five acute NHS Hospitals in east London, UK for COVID-19. Emergency hospital admissions with confirmed SARS-CoV-2 aged 16 years or over were included. Data, including ethnicity, social deprivation, frailty, patient care and detailed risk factors for mortality, were extracted from hospital electronic records. Multivariable survival analysis was used to assess associations between ethnic group and mortality accounting for the effects of age, sex and various other risk factors. Results are presented as hazard ratios (HR) or odds ratios (OR) with 95% confidence intervals.Findings1996 adult patients were admitted between 1st March and 13th May 2020. After excluding 259 patients with missing ethnicity data, 1737 were included in our analysis of whom 511 had died by day 30 (29%). 538 (31%) were from Asian, 340 (20%) Black and 707 (40%) white backgrounds. Compared to White patients, those from BAME backgrounds were younger, with differing co-morbidity profiles and less frailty. Asian and Black patients were more likely to be admitted to intensive care and to receive invasive ventilation (OR 1·54, [1·06-2·23]; p=0·023 and 1·80 [1·20-2·71]; p=0·005, respectively). After adjustment for age and sex, patients from Asian (HR 1·49 [1·19-1·86]; p<0·001) and Black (HR 1·30 [1·02-1·65]; p=0·036) backgrounds were more likely to die. These findings persisted across a range of risk-factor adjusted analyses.InterpretationPatients from Asian and Black backgrounds are more likely to die from COVID-19 infection despite controlling for all previously identified confounders. Higher rates of invasive ventilation in intensive care indicate greater acute disease severity. Our analyses suggest that patients of Asian and Black backgrounds suffered disproportionate rates of premature death from COVID-19.FundingNoneResearch in contextEvidence before this studyWe searched PubMed, Google Scholar, Medrxiv, Trip Medical Database and internet search engines from inception to May 10th 2020, using the terms “(COVID-19 or 2019-nCoV or SARS-CoV-2) AND (ethnicity)”, with no language restrictions, for research articles, editorials and commentaries. We identified 25 articles. Ten were international opinion pieces, fifteen were research articles reporting analyses of national and cohort datasets, predominantly in the United Kingdom (UK) and United States (US). Each of these studies indicated an increased risk of adverse outcomes in people from BAME backgrounds; either in terms of COVID-19 acquisition, disease severity or mortality. However, the underlying causes were unclear. Aggregated US data determined the relative risk of death for those of Black ethnicity compared to White ethnic groups to be 3.57. Three UK biobank cohort studies, limited by low BAME representation, described ethnicity as an independent risk factor of COVID-19 infection, partially attenuated by socio-economic status (SES). Analysis of a London hospital cohort of 520; experiencing 144 deaths, revealed an age and co-morbidity adjusted mortality odds ratio of 1.72 in Black populations of borderline significance. Age and geographical region-adjusted standardised mortality ratios, derived from UK composite hospital data, emphasised ethnic differences; being 2.41 for Bangladeshis and 3.24 for Black Africans. The impact of gender and deprivation was not explored. Another study of 5683 in-hospital deaths (England alone; 629 (11%) BAME) confirmed increased mortality risks in people from Black and Asian groups only partially attributable to social deprivation and co-morbidity but did not adjust for other vulnerability factors. There remained a need for a more detailed analysis of outcomes across different ethnic groups in a large, high acuity dataset, adjusting for broader clinical and laboratory prognostic factors, alongside SES, smoking status, age, body mass index (BMI) and sex.Added value of this studyWe conducted a large observational cohort study of COVID-19 hospital admissions within an area which experienced the highest rates of COVID-19 infection and mortality in the UK. It offers detailed insight into a majority (60%) ethnically diverse cohort and adds substantial evidence that ethnicity is a predictor of poor outcomes for COVID-19 patients at, and beyond, 30 days. Using robust multivariable survival analyses we have quantified and described the impact on this association of a number of additional prognostic factors such as frailty score and markers of inflammation alongside age, sex, deprivation, co-morbidity, BMI and smoking status. Those of Asian and Black ethnicities were consistently found to have an increased risk of 30 and 90 day mortality and an increased risk of requiring mechanical ventilation as compared to those of White ethnicity. The peak CRP and D-dimer levels in those of Black ethnicity were significantly higher than those of other ethnicities suggesting that these biological differences may accompany greater disease severity and increased risk of adverse outcomes.Implications of all the available evidenceIt is clear that ethnicity is a predictor of a positive SARS-CoV2 result, disease severity and mortality, regardless of age, sex, geographical location, deprivation, smoking status, BMI, co-morbidities and frailty. The association appears to be underpinned by a combination of factors including SES, pre-existing health conditions, biological risk factors such as D-dimers, environmental and structural determinants of health; but their relative contribution is unclear. Understanding these drivers is critical to designing interventions and refining clinical and Public Health policies. The evidence also emphasises the need for robust surveillance of ethnicity in health care research.


2020 ◽  
Author(s):  
Tayler A Buchan ◽  
Behnam Sadeghirad ◽  
Nayeli Schmutz ◽  
Nicolai Goettel ◽  
Farid Foroutan ◽  
...  

Abstract Background: Early identification of patients at risk for postoperative delirium is essential because adequate well-timed interventions could reduce the occurrence of delirium and the related detrimental outcomes.Methods: We will conduct a systematic review and individual patient data (IPD) meta-analysis of prognostic studies evaluating the predictive value of risk factors associated with an increased risk of postoperative delirium in elderly patients undergoing elective surgery. We will identify eligible studies through systematic search of MEDLINE, EMBASE, and CINAHL from their inception to May 2020. Eligible studies will enroll older adults (≥ 50 years) undergoing elective surgery and assess pre-operative prognostic risk factors for delirium and incidence of delirium measured by a trained individual using a validated delirium assessment tool. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible studies. We will contact chief investigators of eligible studies requesting to share the IPD to a secured repository. We will use one-stage approach for IPD meta-analysis and will assess certainty of evidence using the GRADE approach.Discussion: Since we are using existing anonymized data, ethical approval is not required for this study. Our results can be used to guide clinical decisions about the most efficient way to prevent postoperative delirium in elderly patients.


2020 ◽  
Author(s):  
Tayler A Buchan ◽  
Behnam Sadeghirad ◽  
Nayeli Schmutz ◽  
Nicolai Goettel ◽  
Farid Foroutan ◽  
...  

Abstract Background: Early identification of patients at risk for postoperative delirium is essential because adequate well-timed interventions could reduce the occurrence of delirium and the related detrimental outcomes.Methods: We will conduct a systematic review and individual patient data (IPD) meta-analysis of prognostic studies evaluating the predictive value of risk factors associated with an increased risk of postoperative delirium in elderly patients undergoing elective surgery. We will identify eligible studies through systematic search of MEDLINE, EMBASE, and CINAHL from their inception to May 2020. Eligible studies will enroll older adults (³ 50 years) undergoing elective surgery and assess pre-operative prognostic risk factors for delirium and incidence of delirium measured by a trained individual using a validated delirium assessment tool. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible studies. We will contact chief investigators of eligible studies requesting to share the IPD to a secured repository. We will use one-stage approach for IPD meta-analysis and will assess certainty of evidence using the GRADE approach.Discussion: Since we are using existing anonymized data, ethical approval is not required for this study. Our results can be used to guide clinical decisions about the most efficient way to prevent postoperative delirium in elderly patients. Systematic review registration: CRD42020171366


2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Tayler A. Buchan ◽  
Behnam Sadeghirad ◽  
Nayeli Schmutz ◽  
Nicolai Goettel ◽  
Farid Foroutan ◽  
...  

Abstract Background Early identification of patients at risk for postoperative delirium is essential because adequate well-timed interventions could reduce the occurrence of delirium and the related detrimental outcomes. Methods We will conduct a systematic review and individual patient data (IPD) meta-analysis of prognostic studies evaluating the predictive value of risk factors associated with an increased risk of postoperative delirium in elderly patients undergoing elective surgery. We will identify eligible studies through systematic search of MEDLINE, EMBASE, and CINAHL from their inception to May 2020. Eligible studies will enroll older adults (≥ 50 years) undergoing elective surgery and assess pre-operative prognostic risk factors for delirium and incidence of delirium measured by a trained individual using a validated delirium assessment tool. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible studies. We will contact chief investigators of eligible studies requesting to share the IPD to a secured repository. We will use one-stage approach for IPD meta-analysis and will assess certainty of evidence using the GRADE approach. Discussion Since we are using existing anonymized data, ethical approval is not required for this study. Our results can be used to guide clinical decisions about the most efficient way to prevent postoperative delirium in elderly patients. Systematic review registration CRD42020171366.


Author(s):  
Maria Värendh ◽  
Christer Janson ◽  
Caroline Bengtsson ◽  
Johan Hellgren ◽  
Mathias Holm ◽  
...  

Abstract Purpose Humans have a preference for nasal breathing during sleep. This 10-year prospective study aimed to determine if nasal symptoms can predict snoring and also if snoring can predict development of nasal symptoms. The hypothesis proposed is that nasal symptoms affect the risk of snoring 10 years later, whereas snoring does not increase the risk of developing nasal symptoms. Methods In the cohort study, Respiratory Health in Northern Europe (RHINE), a random population from Denmark, Estonia, Iceland, Norway, and Sweden, born between 1945 and 1973, was investigated by postal questionnaires in 1999–2001 (RHINE II, baseline) and in 2010–2012 (RHINE III, follow-up). The study population consisted of the participants who had answered questions on nasal symptoms such as nasal obstruction, discharge, and sneezing, and also snoring both at baseline and at follow-up (n = 10,112). Results Nasal symptoms were frequent, reported by 48% of the entire population at baseline, with snoring reported by 24%. Nasal symptoms at baseline increased the risk of snoring at follow-up (adj. OR 1.38; 95% CI 1.22–1.58) after adjusting for age, sex, BMI change between baseline and follow-up, and smoking status. Snoring at baseline was associated with an increased risk of developing nasal symptoms at follow-up (adj. OR 1.22; 95% CI 1.02–1.47). Conclusion Nasal symptoms are independent risk factors for development of snoring 10 years later, and surprisingly, snoring is a risk factor for the development of nasal symptoms.


2021 ◽  
pp. 239719832110340
Author(s):  
Yasser A Radwan ◽  
Reto D Kurmann ◽  
Avneek S Sandhu ◽  
Edward A El-Am ◽  
Cynthia S Crowson ◽  
...  

Objectives: To study the incidence, risk factors, and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis versus nonsystemic sclerosis comparators. Methods: An incident cohort of patients with systemic sclerosis (1980–2016) from Olmsted County, MN, was compared to age- and sex-matched nonsystemic sclerosis subjects (1:2). Electrocardiograms, Holter electrocardiograms, and a need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: Seventy-eight incident systemic sclerosis cases and 156 comparators were identified (mean age 56 years, 91% female). The prevalence of any conduction disorder before systemic sclerosis diagnosis compared to nonsystemic sclerosis subjects was 15% versus 7% ( p = 0.06), and any rhythm disorder was 18% versus 13% ( p = 0.33). During a median follow-up of 10.5 years in patients with systemic sclerosis and 13.0 years in nonsystemic sclerosis comparators, conduction disorders developed in 25 patients with systemic sclerosis with cumulative incidence of 20.5% (95% confidence interval: 12.4%–34.1%) versus 28 nonsystemic sclerosis patients with cumulative incidence of 10.4% (95% confidence interval: 6.2%–17.4%) (hazard ratio: 2.57; 95% confidence interval: 1.48–4.45), while rhythm disorders developed in 27 patients with systemic sclerosis with cumulative incidence of 27.3% (95% confidence interval: 17.9%–41.6%) versus 43 nonsystemic sclerosis patients with cumulative incidence of 18.0% (95% confidence interval: 12.3%–26.4%) (hazard ratio: 1.62; 95% confidence interval: 1.00–2.64). Age, pulmonary hypertension, and smoking were identified as risk factors. Conclusion: Patients with systemic sclerosis have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to nonsystemic sclerosis patients. These findings warrant increased vigilance and screening for electrocardiogram abnormalities in systemic sclerosis patients with pulmonary hypertension.


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