Long-term performance of risk scores for venous thromboembolism in ambulatory cancer patients.

The long-term performance of prediction scores for venous thromboembolism (VTE) in cancer patients has been poorly investigated. We evaluated the discriminatory performance of the Khorana, PROTECHT, CONKO, and ONKOTEV scores for the first 3-6 months and for 12 months, and re-assessed scores after 3-6 months to determine the influence of variations in patients' risk classification on performance. Retrospective cohort of ambulatory patients with active cancer who were scheduled to receive first or new line of chemotherapy. The primary outcome was symptomatic or incidental VTE. A total of 776 patients were included of whom 540 (70%) had distant metastases. The time-dependent c-statistics of Khorana, PROTECHT, CONKO, and ONKOTEV scores at 6 months were 0.61 (95% CI 0.56 to 0.66), 0.61 (95% CI 0.55 to 0.66), 0.60 (95% CI 0.54 to 0.66), and 0.59 (0.52 to 0.66), respectively, with a tendency to decrease during follow-up. None of the scores discriminated between high and low risk patients at the conventional 3-point positivity threshold. The use of a 2-point positivity threshold improved performance of all scores and captured a higher proportion of VTE. The accuracy of risk scores re-assessed at 3-6 months was modest. The Khorana, PROTECHT, CONKO, and ONKOTEV scores are not sufficiently accurate when used at a conventional threshold of 3 points. Performance improves at positivity threshold of 2 points, as evaluated in recent randomized studies on VTE prophylaxis. Score accuracy tends to decrease over time suggesting the need of periodic re-evaluation to estimate possible variation of risk.

The performance of non-invasive tests to rule-in and rule-out significant coronary artery stenosis in patients with stable angina: a meta-analysis focused on post-test disease probability.

Aims: To determine the ranges of pre-test probability (PTP) of coronary artery disease (CAD) in which stress electrocardiogram (ECG), stress echocardiography, coronary computed tomography angiography (CCTA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance (CMR) can reclassify patients into a post-test probability that defines (>85%) or excludes (<15%) anatomically (defined by visual evaluation of invasive coronary angiography [ICA]) and functionally (defined by a fractional flow reserve [FFR] ≤0.8) significant CAD. Methods and results: A broad search in electronic databases until August 2017 was performed. Studies on the aforementioned techniques in >100 patients with stable CAD that utilized either ICA or ICA with FFR measurement as reference, were included. Study-level data was pooled using a hierarchical bivariate random-effects model and likelihood ratios were obtained for each technique. The PTP ranges for each technique to rule-in or rule-out significant CAD were defined. A total of 28 664 patients from 132 studies that used ICA as reference and 4131 from 23 studies using FFR, were analysed. Stress ECG can rule-in and rule-out anatomically significant CAD only when PTP is ≥80% (76-83) and ≤19% (15-25), respectively. Coronary computed tomography angiography is able to rule-in anatomic CAD at a PTP ≥58% (45-70) and rule-out at a PTP ≤80% (65-94). The corresponding PTP values for functionally significant CAD were ≥75% (67-83) and ≤57% (40-72) for CCTA, and ≥71% (59-81) and ≤27 (24-31) for ICA, demonstrating poorer performance of anatomic imaging against FFR. In contrast, functional imaging techniques (PET, stress CMR, and SPECT) are able to rule-in functionally significant CAD when PTP is ≥46-59% and rule-out when PTP is ≤34-57%. Conclusion: The various diagnostic modalities have different optimal performance ranges for the detection of anatomically and functionally significant CAD. Stress ECG appears to have very limited diagnostic power. The selection of a diagnostic technique for any given patient to rule-in or rule-out CAD should be based on the optimal PTP range for each test and on the assumed reference standard.

Bleeding and venous thromboembolic events in patients with active cancer hospitalized for an acute medical illness.

BACKGROUND: Cancer patients hospitalized for an acute medical illness are considered to be at high risk of venous thromboembolism (VTE). Information on bleeding and symptomatic VTE in these patients remains scant. The objectives of this study were to evaluate the incidence of bleeding and VTE during hospitalization and after discharge in a prospective cohort of hospitalized medically-ill cancer patients. METHODS: Consecutive patients with active cancer admitted for an acute medical illness. The primary outcome was the incidence of clinically relevant bleeding. Secondary outcomes included symptomatic and incidentally detected VTE. Outcomes were recorded during hospitalization up to three months after discharge. RESULTS: The study population consisted of 330 patients with a mean age of 73.2 (±12.1) years. During a median hospitalization of eight days, six patients (1.8%) developed a clinically relevant bleeding. Pharmacological thromboprophylaxis was administered to four of these six patients (66.6%), and 108 of 324 (33.3%) patients without bleeding. Twelve (3.6%) were diagnosed with VTE, of whom two had received thromboprophylaxis. In ten patients, VTE was detected incidentally. After discharge, 11 patients experienced major bleeding and two developed symptomatic VTE during a median follow-up of 92 days (range 19-110). Two thirds of all major bleeding events were gastrointestinal, and 87% occurred in patients with gastrointestinal or genitourinary cancer. CONCLUSIONS: In patients with active cancer admitted for an acute medical illness, the risk of bleeding and symptomatic VTE appeared to be low during hospitalization. After discharge, the risk of bleeding was higher and significantly outweighed that of VTE.

Effects of multiple inherited and acquired thrombophilia on outcomes of in-vitro fertilization.

INTRODUCTION: The effects of multiple inherited and acquired thrombophilic defects on the outcome of in-vitro fertilization (IVF) remain unexplored. The aim of this study was to evaluate the association between multiple thrombophilia and clinical outcomes in a large prospective cohort of women undergoing IVF. MATERIALS AND METHODS: Consecutive women scheduled for IVF were eligible. The primary study outcome was live birth. Secondary outcomes included spontaneous abortion, clinical pregnancy, and symptomatic venous thromboembolism. RESULTS: 687 women with a mean age of 34.6 (±3.2) years were included. Overall, 22 women (3.2%) had two or more thrombophilic defects. The probability of live birth was not statistically significantly different between women with ≥2 thrombophilia (odds ratio [OR] 0.62; 95% confidence interval [CI], 0.18 to 2.11) or ≥1 thrombophilia (OR 0.67;95% CI, 0.41 to 1.09) and women without any thrombophilia. None of the individual inherited thrombophilia nor positivity to antiphospholipid antibodies or lupus anticoagulant were associated with live birth. Single positivity for lupus anticoagulant carried a more than threefold higher risk of abortion (OR 3.74; 95% CI, 1.30 to 10.75). There were no statistically significant associations between individual or multiple thrombophilic defects and clinical pregnancy or pregnancy test results. No woman had a history of venous thromboembolism and none developed a thrombotic event during the study. CONCLUSIONS: In women undergoing IVF, the presence of two or more thrombophilic defects was rare and showed no statistically significant associations with IVF outcomes.

Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis.

OBJECTIVE: To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease. DESIGN: Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease. DATA SOURCES: Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation. MAIN OUTCOME MEASURE: All cause mortality. RESULTS: 100 trials in 93,553 patients with 262,090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably reduced by coronary artery bypass grafting (0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus (Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29, 0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59 to 0.81) compared with medical treatment. CONCLUSION: Among patients with stable coronary artery disease, coronary artery bypass grafting reduces the risk of death, myocardial infarction, and subsequent revascularisation compared with medical treatment. All stent based coronary revascularisation technologies reduce the need for revascularisation to a variable degree. Our results provide evidence for improved survival with new generation drug eluting stents but no other percutaneous revascularisation technology compared with medical treatment.

Can falls risk prediction tools correctly identify fall-prone elderly rehabilitation inpatients? A systematic review and meta-analysis.

BACKGROUND: Falls of elderly people may cause permanent disability or death. Particularly susceptible are elderly patients in rehabilitation hospitals. We systematically reviewed the literature to identify falls prediction tools available for assessing elderly inpatients in rehabilitation hospitals. METHODS AND FINDINGS: We searched six electronic databases using comprehensive search strategies developed for each database. Estimates of sensitivity and specificity were plotted in ROC space graphs and pooled across studies. Our search identified three studies which assessed the prediction properties of falls prediction tools in a total of 754 elderly inpatients in rehabilitation hospitals. Only the STRATIFY tool was assessed in all three studies; the other identified tools (PJC-FRAT and DOWNTON) were assessed by a single study. For a STRATIFY cut-score of two, pooled sensitivity was 73% (95%CI 63 to 81%) and pooled specificity was 42% (95%CI 34 to 51%). An indirect comparison of the tools across studies indicated that the DOWNTON tool has the highest sensitivity (92%), while the PJC-FRAT offers the best balance between sensitivity and specificity (73% and 75%, respectively). All studies presented major methodological limitations. CONCLUSIONS: We did not identify any tool which had an optimal balance between sensitivity and specificity, or which were clearly better than a simple clinical judgment of risk of falling. The limited number of identified studies with major methodological limitations impairs sound conclusions on the usefulness of falls risk prediction tools in geriatric rehabilitation hospitals.

Meta-analysis of selective serotonin reuptake inhibitors in patients with depression and coronary heart disease.

The occurrence of depression in patients with coronary heart disease (CHD) substantially increases the likelihood of a poorer cardiovascular prognosis. Although antidepressants are generally effective in decreasing depression, their use in patients with CHD is controversial. We carried out a meta-analysis to evaluate the health effects of selective serotonin reuptake inhibitors (SSRIs) versus placebo or no antidepressants in patients with CHD and depression. Observational studies and randomized controlled trials (RCTs) were searched in MEDLINE, EMBASE, PsycINFO, Cochrane Controlled Clinical Trial Register and other trial registries, and references of relevant articles. Primary outcomes were readmission for CHD (including myocardial infarction, unstable angina, and stroke) and all-cause mortality; the secondary outcome was severity of depression symptoms. Seven articles on 6 RCTs involving 2,461 participants were included. One study incorrectly randomized participants, and another was a reanalysis of RCT data. These were considered observational and analyzed separately. When only properly randomized trials were considered (n = 734 patients), patients on SSRIs showed no significant differences in mortality (risk ratio 0.39, 95% confidence interval 0.08 to 2.01) or CHD readmission rates (0.74, 0.44 to 1.23) compared to controls. Conversely, when all studies were included, SSRI use was associated with a significant decrease in CHD readmission (0.63, 0.46 to 0.86) and mortality rates (0.56, 0.35 to 0.88). A significantly greater improvement in depression symptoms was always apparent in patients on SSRIs with all selected indicators. In conclusion, in patients with CHD and depression, SSRI medication decreases depression symptoms and may improve CHD prognosis.