Association between smoking and recurrence of venous thromboembolism and bleeding in elderly patients with past acute venous thromboembolism.

BACKGROUND: While the association between smoking and arterial cardiovascular events has been well established, the association between smoking and venous thromboembolism (VTE) remains controversial. OBJECTIVES: To assess the association between smoking and the risk of recurrent VTE and bleeding in patients who have experienced acute VTE. PATIENTS/METHODS: This study is part of a prospective Swiss multicenter cohort that included patients aged ≥65years with acute VTE. Three groups were defined according to smoking status: never, former and current smokers. The primary outcome was the time to a first symptomatic, objectively confirmed VTE recurrence. Secondary outcomes were the time to a first major and clinically relevant non-major bleeding. Associations between smoking status and outcomes were analysed using proportional hazard models for the subdistribution of a competing risk of death. RESULTS: Among 988 analysed patients, 509 (52%) had never smoked, 403 (41%) were former smokers, and 76 (8%) current smokers. After a median follow-up of 29.6months, we observed a VTE recurrence rate of 4.9 (95% confidence interval [CI] 3.7-6.4) per 100 patient-years for never smokers, 6.6 (95% CI 5.1-8.6) for former smokers, and 5.2 (95% CI 2.6-10.5) for current smokers. Compared to never smokers, we found no association between current smoking and VTE recurrence (adjusted sub-hazard ratio [SHR] 1.05, 95% CI 0.49-2.28), major bleeding (adjusted SHR 0.59, 95% CI 0.25-1.39), and clinically relevant non-major bleeding (adjusted SHR 1.21, 95% CI 0.73-2.02). CONCLUSIONS: In this multicentre prospective cohort study, we found no association between smoking status and VTE recurrence or bleeding in elderly patients with VTE

How to prevent overdiagnosis

Overdiagnosis is the diagnosis of an abnormality that is not associated with a substantial health hazard and that patients have no benefit to be aware of. It is neither a misdiagnosis (diagnostic error), nor a false positive result (positive test in the absence of a real abnormality). It mainly results from screening, use of increasingly sensitive diagnostic tests, incidental findings on routine examinations, and widening diagnostic criteria to define a condition requiring an intervention. The blurring boundaries between risk and disease, physicians' fear of missing a diagnosis and patients' need for reassurance are further causes of overdiagnosis. Overdiagnosis often implies procedures to confirm or exclude the presence of the condition and is by definition associated with useless treatments and interventions, generating harm and costs without any benefit. Overdiagnosis also diverts healthcare professionals from caring about other health issues. Preventing overdiagnosis requires increasing awareness of healthcare professionals and patients about its occurrence, the avoidance of unnecessary and untargeted diagnostic tests, and the avoidance of screening without demonstrated benefits. Furthermore, accounting systematically for the harms and benefits of screening and diagnostic tests and determining risk factor thresholds based on the expected absolute risk reduction would also help prevent overdiagnosis

Educational Level, Anticoagulation Quality, and Clinical Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Prospective Cohort Study.

Whether the level of education is associated with anticoagulation quality and clinical outcomes in patients with acute venous thromboembolism (VTE) is uncertain. We thus aimed to investigate the association between educational level and anticoagulation quality and clinical outcomes in elderly patients with acute VTE. We studied 817 patients aged ≥65 years with acute VTE from a Swiss prospective multicenter cohort study (09/2009-12/2013). We defined three educational levels: 1) less than high school, 2) high school, and 3) post-secondary degree. The primary outcome was the anticoagulation quality, expressed as the percentage of time spent in the therapeutic INR range (TTR). Secondary outcomes were the time to a first recurrent VTE and major bleeding. We adjusted for potential confounders and periods of anticoagulation. Overall, 56% of patients had less than high school, 25% a high school degree, and 18% a post-secondary degree. The mean percentage of TTR was similar across educational levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P = 0.36). Within three years of follow-up, patients with less than high school, high school, and a post-secondary degree had a cumulative incidence of recurrent VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of 13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was neither associated with anticoagulation quality nor with recurrent VTE or major bleeding. In elderly patients with VTE, we did not find an association between educational level and anticoagulation quality or clinical outcomes

Use of biomarkers or echocardiography in pulmonary embolism: the Swiss Venous Thromboembolism Registry

Background: Cardiac biomarkers and echocardiography for assessing right ventricular function are recommended to risk stratify patients with acute non-massive pulmonary embolism (PE), but it remains unclear if these tests are performed systematically in daily practice. Design and methods: Overall, 587 patients with acute non-massive PE from 18 hospitals were enrolled in the Swiss Venous Thromboembolism Registry (SWIVTER): 178 (30%) neither had a biomarker test nor an echocardiographic evaluation, 196 (34%) had a biomarker test only, 47 (8%) had an echocardiogram only and 166 (28%) had both tests. Results: Among the 409 (70%) patients with biomarkers or echocardiography, 210 (51%) had at least one positive test and 67 (16%) had positive biomarkers and right ventricular dysfunction. The ICU admission rates were 5.1% without vs. 5.6% with testing (P = 0.78), and thrombolysis or embolectomy were performed in 2.8% vs. 4.9%, respectively (P = 0.25). In multivariate analysis, syncope [odds ratio (OR): 3.49, 95% confidence interval (CI): 1.20-10.15; P = 0.022], tachycardia (OR: 2.31, 95% CI: 1.37-3.91; P = 0.002) and increasing age (OR: 1.02; 95% CI: 1.01-1.04; P < 0.001) were associated with testing of cardiac risk; outpatient status at the time of PE diagnosis (OR: 2.24, 95% CI: 1.49-3.36; P < 0.001), cancer (OR: 1.81, 95% CI: 1.17-2.79; P = 0.008) and provoked PE (OR: 1.58, 95% CI: 1.05-2.40; P = 0.029) were associated with its absence. Conclusions: Although elderly patients and those with clinically severe PE were more likely to receive a biomarker test or an echocardiogram, these tools were used in only two-thirds of the patients with acute non-massive PE and rarely in combinatio

Polypharmacy and specific comorbidities in university primary care settings.

Polypharmacy is associated with adverse events and multimorbidity, but data are limited on its association with specific comorbidities in primary care settings. We measured the prevalence of polypharmacy and inappropriate prescribing, and assessed the association of polypharmacy with specific comorbidities. We did a cross-sectional analysis of 1002 patients aged 50-80years followed in Swiss university primary care settings. We defined polypharmacy as ≥5 long-term prescribed drugs and multimorbidity as ≥2 comorbidities. We used logistic mixed-effects regression to assess the association of polypharmacy with the number of comorbidities, multimorbidity, specific sets of comorbidities, potentially inappropriate prescribing (PIP) and potential prescribing omission (PPO). We used multilevel mixed-effects Poisson regression to assess the association of the number of drugs with the same parameters. Patients (mean age 63.5years, 67.5% ≥2 comorbidities, 37.0% ≥5 drugs) had a mean of 3.9 (range 0-17) drugs. Age, BMI, multimorbidity, hypertension, diabetes mellitus, chronic kidney disease, and cardiovascular diseases were independently associated with polypharmacy. The association was particularly strong for hypertension (OR 8.49, 95%CI 5.25-13.73), multimorbidity (OR 6.14, 95%CI 4.16-9.08), and oldest age (75-80years: OR 4.73, 95%CI 2.46-9.10 vs.50-54years). The prevalence of PPO was 32.2% and PIP was more frequent among participants with polypharmacy (9.3% vs. 3.2%, p&lt;0.006). Polypharmacy is common in university primary care settings, is strongly associated with hypertension, diabetes mellitus, chronic kidney disease and cardiovascular diseases, and increases potentially inappropriate prescribing. Multimorbid patients should be included in further trials for developing adapted guidelines and avoiding inappropriate prescribing

Association between computed tomography obstruction index and mortality in elderly patients with acute pulmonary embolism: A prospective validation study.

Computed tomography pulmonary angiography (CTPA) has not only become the method of choice for diagnosing acute pulmonary embolism (PE), it also allows for risk stratification of patients with PE. To date, no study has specifically examined the predictive value of CTPA findings to assess short-term prognosis in elderly patients with acute PE who are particularly vulnerable to adverse outcomes. We studied 291 patients aged ≥65 years with acute symptomatic PE in a prospective multicenter cohort. Outcomes were 90-day overall and PE-related mortality, recurrent venous thromboembolism (VTE), and length of hospital stay (LOS). We examined associations of the computed tomography obstruction index (CTOI) and the right ventricular (RV) to left ventricular (LV) diameter ratio with mortality and VTE recurrence using survival analysis, adjusting for provoked VTE, Pulmonary Embolism Severity Index (PESI), and anticoagulation as a time-varying covariate. Overall, 15 patients died within 90 days. There was no association between the CTOI and 90-day overall mortality (adjusted hazard ratio per 10% CTOI increase 0.92; 95% confidence interval [CI] 0.70-1.21; P = 0.54), but between the CTOI and PE-related 90-day mortality (adjusted sub-hazard ratio per 10% CTOI increase 1.36; 95% CI 1.03-1.81; P = 0.03). The RV/LV diameter ratio was neither associated with overall nor PE-related 90-day mortality. The CTOI and the RV/LV diameter ratio were significantly associated with VTE recurrence and LOS. In elderly patients with acute PE, the CTOI was associated with PE-related 90-day mortality but not with overall 90-day mortality. The RV/LV diameter ratio did not predict mortality. Both measures predicted VTE recurrence and LOS. The evaluated CTPA findings do not appear to offer any advantage over the PESI in terms of mortality prediction

Reasons Why Emergency Department Providers Do Not Rely on the Pneumonia Severity Index to Determine the Initial Site of Treatment for Patients with Pneumonia

Background. Many emergency department (ED) providers do not follow guideline recommendations for the use of the pneumonia severity index (PSI) to determine the initial site of treatment for patients with community-acquired pneumonia (CAP). We identified the reasons why ED providers hospitalize low-risk patients or manage higher-risk patients as outpatients. Methods. As a part of a trial to implement a PSI-based guideline for the initial site of treatment of patients with CAP, we analyzed data for patients managed at 12 EDs allocated to a high-intensity guideline implementation strategy study arm. The guideline recommended outpatient care for low-risk patients (nonhypoxemic patients with a PSI risk classification of I, II, or III) and hospitalization for higher-risk patients (hypoxemic patients or patients with a PSI risk classification of IV or V). We asked providers who made guideline-discordant decisions on site of treatment to detail the reasons for nonadherence to guideline recommendations. Results. There were 1,306 patients with CAP (689 low-risk patients and 617 higher-risk patients). Among these patients, physicians admitted 258 (37.4%) of 689 low-risk patients and treated 20 (3.2%) of 617 higher-risk patients as outpatients. The most commonly reported reasons for admitting low-risk patients were the presence of a comorbid illness (178 [71.5%] of 249 patients); a laboratory value, vital sign, or symptom that precluded ED discharge (73 patients [29.3%]); or a recommendation from a primary care or a consulting physician (48 patients [19.3%]). Higher-risk patients were most often treated as outpatients because of a recommendation by a primary care or consulting physician (6 [40.0%] of 15 patients). Conclusion. ED providers hospitalize many low-risk patients with CAP, most frequently for a comorbid illness. Although higher-risk patients are infrequently treated as outpatients, this decision is often based on the request of an involved physicia

Comparison of Cardiac and Non-Cardiac Biomarkers for Risk Stratification in Elderly Patients with Non-Massive Pulmonary Embolism.

Biomarkers unrelated to myocardial necrosis, such as cystatin C, copeptin, and mid-regional pro-adrenomedullin (MR-proADM), showed promise for cardiovascular risk prediction. Knowing whether they are comparable to cardiac biomarkers such as high-sensitive cardiac-troponin T (hs-cTnT) or N-terminal pro-Brain natriuretic peptide (NT-proBNP) in elderly patients with acute non-massive pulmonary embolism (NMPE) remains elusive. This study aims at comparing the prognostic accuracy of cardiac and non-cardiac biomarkers in patients with NMPE aged ≥65 years over time. In the context of the SWITCO65+ cohort, we evaluated 227 elderly patients with an available blood sample taken within one day from diagnosis. The primary study endpoint was defined as PE-related mortality and the secondary endpoint as PE-related complications. The biomarkers' predictive ability at 1, 3, 12 and 24 months was determined using C-statistics and Cox regression. For both study endpoints, C-statistics (95% confidence interval) were stable over time for all biomarkers, with the highest value for hs-cTnT, ranging between 0.84 (0.68-1.00) and 0.80 (0.70-0.90) for the primary endpoint, and between 0.74 (0.63-0.86) and 0.65 (0.57-0.73) for the secondary endpoint. For both study endpoints, cardiac biomarkers were found to be independently associated with risk, NT-proBNP displaying a negative predictive value of 100%. Among non-cardiac biomarkers, only copeptin and MR-proADM were independent predictors of PE-related mortality but they were not independent predictors of PE-related complications, and displayed lower negative predictive values. In elderly NMPE patients, cardiac biomarkers appear to be valuable prognostic to identify very low-risk individuals. ClinicalTrials.gov NCT00973596

Thyroid dysfunction and anaemia in a large population-based study.

OBJECTIVE AND BACKGROUND: Anaemia and thyroid dysfunction are common and often co-occur. Current guidelines recommend the assessment of thyroid function in the work-up of anaemia, although evidence on this association is scarce. PATIENTS AND METHODS: In the 'European Prospective Investigation of Cancer' (EPIC)-Norfolk population-based cohort, we aimed to examine the prevalence and type of anaemia (defined as haemoglobin &lt;13 g/dl for men and &lt;12 g/dl for women) according to different thyroid function groups. RESULTS: The mean age of the 8791 participants was 59·4 (SD 9·1) years and 55·2% were women. Thyroid dysfunction was present in 437 (5·0%) and anaemia in 517 (5·9%) participants. After excluding 121 participants with three most common causes of anaemia (chronic kidney disease, inflammation, iron deficiency), anaemia was found in 4·7% of euthyroid participants. Compared with the euthyroid group, the prevalence of anaemia was significantly higher in overt hyperthyroidism (14·6%, P &lt; 0·01), higher with borderline significance in overt hypothyroidism (7·7%, P = 0·05) and not increased in subclinical thyroid dysfunction (5·0% in subclinical hypothyroidism, 3·3% in subclinical hyperthyroidism). Anaemia associated with thyroid dysfunction was mainly normocytic (94·0%), and rarely macrocytic (6·0%). CONCLUSION: The prevalence of anaemia was higher in overt hyperthyroidism, but not increased in subclinical thyroid dysfunction. Systematic measurement of thyroid-stimulating hormone in anaemic patients is likely to be useful only after excluding common causes of anaemia

Pathways for outpatient management of venous thromboembolism in a UK centre.

It has become widely recognised that outpatient treatment may be suitable for many patients with venous thromboembolism. In addition, non-vitamin K antagonist oral anticoagulants that have been approved over the last few years have the potential to be an integral component of the outpatient care pathway, owing to their oral route of administration, lack of requirement for routine anticoagulation monitoring and simple dosing regimens. A robust pathway for outpatient care is also vital; one such pathway has been developed at Sheffield Teaching Hospitals in the UK. This paper describes the pathway and the arguments in its favour as an example of best practice and value offered to patients with venous thromboembolism. The pathway has two branches (one for deep vein thrombosis and one for pulmonary embolism), each with the same five-step process for outpatient treatment. Both begin from the point that the patient presents (in the Emergency Department, Thrombosis Clinic or general practitioner's office), followed by diagnosis, risk stratification, treatment choice and, finally, follow-up. The advantages of these pathways are that they offer clear, evidence-based guidance for the identification, diagnosis and treatment of patients who can safely be treated in the outpatient setting, and provide a detailed, stepwise process that can be easily adapted to suit the needs of other institutions. The approach is likely to result in both healthcare and economic benefits, including increased patient satisfaction and shorter hospital stays