Reticulated Platelets as Predictor of Myocardial Injury and 30 Day Mortality After Non-cardiac Surgery

Objective: A pre-operative marker for identification of patients at risk of peri-operative adverse events and 30 day mortality might be the percentage of young, reticulated platelets (pRP). This study aimed to determine the predictive value of pre-operative pRP on post-operative myocardial injury (PMI) and 30 day mortality, in patients aged ≥ 60 years undergoing moderate to high risk non-cardiac surgery. Methods: The incidence of PMI (troponin I > 0.06 μg/L) and 30 day mortality was compared for patients with normal and high pRP (≥2.82%) obtained from The Utrecht Patient Orientated Database. The predictive pRP value was assessed using logistic regression. A prediction model for PMI or 30 day mortality with known risk factors was compared with a model including increased pRP using the area under the receiving operator characteristics curve (AUROC). Results: In total, 26.5% (607/2289) patients showed pre-operative increased pRP. Increased pRP was associated with more PMI and 30 day mortality compared with normal pRP (36.1% vs. 28.3%, p < .001 and 8.6% vs. 3.6%, p < .001). The median pRP was higher in patients suffering PMI and 30 day mortality compared with not (2.21 [IQR: 1.57–3.11] vs. 2.07 [IQR: 1.52–1.78], p = .002, and 2.63 [IQR: 1.76–4.15] vs. 2.09 [IQR: 1.52–3.98], p < .001). pRP was independently related to PMI (OR: 1.28 [95% CI: 1.04–1.59], p = .02) and 30 day mortality (OR: 2.35 [95% CI: 1.56–3.55], p < .001). Adding increased pRP to the predictive model of PMI or 30 day mortality did not increase the AUROC 0.71 vs. 0.72, and 0.80 vs. 0.81. Conclusion: In patients undergoing major non-cardiac surgery, increased pre-operative pRP is related to 30 day mortality and PMI

Accuracy of physicians' intuitive risk estimation in the diagnostic management of pulmonary embolism: An Individual Patient Data Meta-Analysis

BACKGROUND: In patients clinically suspected of having pulmonary embolism (PE), physicians often rely on intuitive estimation ("gestalt") of PE presence. Although shown to be predictive, gestalt is criticized for its assumed variation across physicians and lack of standardization. OBJECTIVES: To assess the diagnostic accuracy of gestalt in the diagnosis of PE and gain insight into its possible variation. METHODS: We performed an individual patient data meta-analysis including patients suspected of having PE. The primary outcome was diagnostic accuracy of gestalt for the diagnosis of PE, quantified as risk ratio (RR) between gestalt and PE based on 2-stage random-effect log-binomial meta-analysis regression as well as gestalts' sensitivity and specificity. The variability of these measures was explored across different health care settings, publication period, PE prevalence, patient subgroups (sex, heart failure, chronic lung disease, and items of the Wells score other than gestalt), and age. RESULTS: We analyzed 20 770 patients suspected of having PE from 16 original studies. The prevalence of PE in patients with and without a positive gestalt was 28.8% vs 9.1%, respectively. The overall RR was 3.02 (95% CI, 2.35-3.87), and the overall sensitivity and specificity were 74% (95% CI, 68%-79%) and 61% (95% CI, 53%-68%), respectively. Although variation was observed across individual studies (I 2, 90.63%), the diagnostic accuracy was consistent across all subgroups and health care settings. CONCLUSION: A positive gestalt was associated with a 3-fold increased risk of PE in suspected patients. Although variation was observed across studies, the RR of gestalt was similar across prespecified subgroups and health care settings, exemplifying its diagnostic value for all patients suspected of having PE

Evolution of Sociology Freshmen into a Friendship Network

In this paper we both describe and analyze the meeting process and the evolution of a friendship network among sociology freshmen in the Netherlands. We develop a theory that explains how changes in the network structure depend on one or more of four main effects: proximity, visible similarity, invisible similarity, and network opportunity. We formulate expectations with regard to what factors are important at what stages of the friendship development, making a distinction between ‘meeting’ and ‘mating.’ To some extent, the results confirm our expectations. The proximity and visible similarity variables determine change in network structure in the early stages, whereas network opportunity is important during all stages. Unfortunately, no significant effects of invisible similarity are found.

Validation and impact of a simplified clinical decision rule for diagnosing pulmonary embolism in primary care : design of the PECAN prospective diagnostic cohort management study

Introduction Combined with patient history and physical examination, a negative D-dimer can safely rule-out pulmonary embolism (PE). However, the D-dimer test is frequently false positive, leading to many (with hindsight) 'unneeded' referrals to secondary care. Recently, the novel YEARS algorithm, incorporating flexible D-dimer thresholds depending on pretest risk, was developed and validated, showing its ability to safely exclude PE in the hospital environment. Importantly, this was accompanied with 14% fewer computed tomographic pulmonary angiography than the standard, fixed D-dimer threshold. Although promising, in primary care this algorithm has not been validated yet. Methods and analysis The PECAN (Diagnosing Pulmonary Embolism in the context of Common Alternative diagNoses in primary care) study is a prospective diagnostic study performed in Dutch primary care. Included patients with suspected acute PE will be managed by their general practitioner according to the YEARS diagnostic algorithm and followed up in primary care for 3 months to establish the final diagnosis. To study the impact of the use of the YEARS algorithm, the primary endpoints are the safety and efficiency of the YEARS algorithm in primary care. Safety is defined as the proportion of false-negative test results in those not referred. Efficiency denotes the proportion of patients classified in this non-referred category. Additionally, we quantify whether C reactive protein measurement has added diagnostic value to the YEARS algorithm, using multivariable logistic and polytomous regression modelling. Furthermore, we will investigate which factors contribute to the subjective YEARS item 'PE most likely diagnosis'. Ethics and dissemination The study protocol was approved by the Medical Ethical Committee Utrecht, the Netherlands. Patients eligible for inclusion will be asked for their consent. Results will be disseminated by publication in peer-reviewed journals and presented at (inter)national meetings and congresses

Safety of switching from vitamin K antagonist to non-vitamin K antagonist oral anticoagulant in frail elderly with atrial fibrillation : rationale and design of the FRAIL-AF randomised controlled trial

INTRODUCTION: Clinical guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) for stroke prevention in most patients with atrial fibrillation (AF). Frail elderly were under-represented in the landmark NOAC-trials, leaving a knowledge gap on the optimal anticoagulant management (VKA or NOAC) in this increasing population. The aim of the Frail-AF (FRAIL-AF) study is to assess whether switching from international normalised ratio (INR)-guided VKA-management to a NOAC-based treatment strategy compared with continuing VKA-management is safe in frail elderly patients with AF. METHODS AND ANALYSIS: The FRAIL-AF study is a pragmatic, multicentre, open-label, randomised controlled clinical trial. Frail elderly (age ≥75 years plus a Groningen Frailty Indicator score ≥3) who receive VKA-treatment for AF in the absence of a mechanical heart valve or severe mitral valve stenosis will be randomised to switch to a NOAC-based treatment strategy or to continue INR-guided VKA-management. Patients with severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m2) will be excluded from randomisation. Based on existing trial evidence in non-frail patients, we will aim to explore whether NOAC-treatment is superior to VKA-therapy in reducing major or clinically relevant non-major bleeding events. Secondary outcomes include minor bleeding, the composite of ischaemic and haemorrhagic stroke, health-related quality of life and cost-effectiveness. The follow-up period for all subjects is 12 months. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Research Ethics Committee of the University Medical Center Utrecht, the Netherlands and by the Central Committee on Research Involving Human Subjects, the Netherlands. All patients are asked written informed consent. Results are expected in 2022 and will be disseminated through peer-reviewed journals as well as presentations at national and international conferences. TRIAL REGISTRATION NUMBER: EudraCT: 2017-000393-11; The Netherlands Trial Registry: 6721 (FRAIL-AF study)

Transfusion burden in early childhood plays an important role in iron overload in Diamond-Blackfan anaemia

In Diamond-Blackfan anaemia (DBA), iron overload (IO) is common in transfusion-dependent patients, yet has also been reported in non-transfusion-dependent patients. We explored the incidence of IO in transfusion-dependent and non-transfusion-dependent DBA patients. We observed hepatic IO in 65% of patients analysed with MRI, including three patients that were only treated with transfusions in the past. Whereas overall ferritin levels and liver iron content correlated, ferritin levels did not reflect total body iron adequately. Our data suggest that transfusion burden in the past plays an important role in IO in DBA, and should be taken into account during follow up