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Background: Few studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women., Objectives: The aim of this study was to establish the safety and efficiency of the Wells rule with fixed and adapted D-dimer threshold, and the YEARS algorithm, combined with compression ultrasonography (CUS), in pregnant women with suspected PE in an individual patient data meta-analysis., Methods: We performed a systematic review to identify prospective diagnostic management studies in pregnant women with suspected PE. Primary outcomes were safety, defined as the failure rate, ie, the 3-month venous thromboembolism (VTE) incidence after excluding PE without chest imaging, and efficiency, defined as the proportion of patients in whom chest imaging could be avoided., Results: We identified 2 relevant studies, of which individual patient-level data were analyzed in a fixed-effect meta-analysis, totaling 893 pregnant women. The Wells rule with fixed and adapted D-dimer threshold as well as the YEARS algorithm could safely rule out acute PE (failure rate, 0·37%-1·4%), but efficiency improved considerably when applying pretest probability-adapted D-dimer thresholds. The efficiency of bilateral CUS was limited (2·3% overall; number needed to test 43), especially in patients without symptoms of deep-vein thrombosis (efficiency 0·79%; number needed to test 127)., Conclusion: This study supports the latest guideline recommendations (European Society of Cardiology 2019) to apply pretest probability assessment and D-dimer tests to rule out PE in pregnant women. From an efficiency perspective, the use of a strategy with pretest probability-adapted D-dimer threshold is preferred. The yield of CUS was very limited in patients without concomitant symptoms of deep-vein thrombosis., (Copyright © 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Objectives: There is controversy whether non-specific symptoms can be related to previous Lyme borreliosis (LB). Positive serology can be considered a proxy for previous or persistent LB. We assessed non-specific symptoms and serology in patients suspected of LB referred to a Lyme centre., Methods: Included were adult patients who visited a Lyme centre between 2008 and 2014. Before medical consultation, serum samples were taken and questionnaires on non-specific symptoms completed. The prevalence of non-specific symptoms was calculated for patients with positive and negative IgG serology. Logistic regression was used to obtain odds ratios (ORs) with 95% confidence interval (CI) for an association between positive serology and non-specific symptoms., Results: Of 1439 included patients, 31.6% (455/1439) had positive serology. The most common non-specific symptoms were severe fatigue (61.4%, 883/1439), sleep disturbances (54.8%, 789/1439) and stiffness of neck/back (52.6%, 757/1439). The prevalence of severe fatigue was 53.0% (241/455) in patients with positive serology vs. 65.2% (642/984) in patients with negative serology (OR = 0.74; 95% CI, 0.58-0.94). The prevalence of sleep disturbances was respectively 46.2% (210/455) vs. 58.8% (579/984) (OR = 0.73; 95% CI, 0.58-0.93). The prevalence of stiffness of neck/back was respectively 47.7% (217/455) vs. 54.9% (540/984) (OR = 0.85; 95% CI, 0.67-1.06)., Conclusions: In patients referred to a Lyme centre, non-specific symptoms did not occur more frequently in patients with positive serology compared to patients with negative serology. Hence, a questionnaire on non-specific symptoms cannot be used for identifying patients with possible post-LB symptoms in clinical practice., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A two-step testing strategy is recommended in serological testing for Lyme borreliosis; positive and indeterminate enzyme-linked immunosorbent assay (ELISA) results are confirmed with immunoblots. Several ELISAs quantify the concentration of antibodies tested, however, no recommendation exists for an upper cut-off value at which an IgG ELISA is sufficient and the immunoblot can be omitted. The study objective was to determine at which IgG antibody level an immunoblot does not have any additional predictive value compared to ELISA results. Data of adult patients who visited a tertiary Lyme centre between 2008 and 2014 were analysed. Both an ELISA (Enzygnost Lyme link VlsE IgG) and immunoblot (recomLine blot Borrelia) were performed. Clinical data were extracted from the patient's digital medical record. Positive predictive values (PPVs) for either previous or active infection with Borrelia burgdorferi s.l. were calculated for different cut-off ELISA IgG antibody levels where the immunoblot was regarded as reference test. In total, 1454 patients were included. According to the two-step test strategy, 486 (33%), 69 (5%) and 899 (62%) patients had positive, indeterminate and negative Borrelia IgG serology, respectively. At IgG levels of 500 IU/ml and higher, all immunoblots were positive, resulting in a 100% PPV (95% CI: 97.0-100). At IgG levels of 200 IU/ml and higher, the PPV was 99.3% (95% CI: 97.4-99.8). In conclusion, at IgG levels of 200 IU/ml and higher, an ELISA was sufficient to detect antibodies to Borrelia burgdorferi s.l. At those IgG levels, a confirmatory immunoblot may be omitted in patients referred to a tertiary Lyme centre. Before these results can be implemented in routine diagnosis of Lyme borreliosis, confirmation of the results is necessary in other patient populations and using other quantitative ELISAs and immunoblots., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Background: Validated diagnostic algorithms in patients with suspected pulmonary embolism are often not used correctly or only benefit subgroups of patients, leading to overuse of computed tomography pulmonary angiography (CTPA). The YEARS clinical decision rule that incorporates differential D-dimer cutoff values at presentation, has been developed to be fast, to be compatible with clinical practice, and to reduce the number of CTPA investigations in all age groups. We aimed to prospectively evaluate this novel and simplified diagnostic algorithm for suspected acute pulmonary embolism., Methods: We did a prospective, multicentre, cohort study in 12 hospitals in the Netherlands, including consecutive patients with suspected pulmonary embolism between Oct 5, 2013, to July 9, 2015. Patients were managed by simultaneous assessment of the YEARS clinical decision rule, consisting of three items (clinical signs of deep vein thrombosis, haemoptysis, and whether pulmonary embolism is the most likely diagnosis), and D-dimer concentrations. In patients without YEARS items and D-dimer less than 1000 ng/mL, or in patients with one or more YEARS items and D-dimer less than 500 ng/mL, pulmonary embolism was considered excluded. All other patients had CTPA. The primary outcome was the number of independently adjudicated events of venous thromboembolism during 3 months of follow-up after pulmonary embolism was excluded, and the secondary outcome was the number of required CTPA compared with the Wells' diagnostic algorithm. For the primary outcome regarding the safety of the diagnostic strategy, we used a per-protocol approach. For the secondary outcome regarding the efficiency of the diagnostic strategy, we used an intention-to-diagnose approach. This trial is registered with the Netherlands Trial Registry, number NTR4193., Findings: 3616 consecutive patients with clinically suspected pulmonary embolism were screened, of whom 151 (4%) were excluded. The remaining 3465 patients were assessed of whom 456 (13%) were diagnosed with pulmonary embolism at baseline. Of the 2946 patients (85%) in whom pulmonary embolism was ruled out at baseline and remained untreated, 18 patients were diagnosed with symptomatic venous thromboembolism during 3-month follow-up (0·61%, 95% CI 0·36-0·96) of whom six had fatal pulmonary embolism (0·20%, 0·07-0·44). CTPA was not indicated in 1651 (48%) patients with the YEARS algorithm compared with 1174 (34%) patients, if Wells' rule and fixed D-dimer threshold of less than 500 ng/mL would have been applied, a difference of 14% (95% CI 12-16)., Interpretation: In our study pulmonary embolism was safely excluded by the YEARS diagnostic algorithm in patients with suspected pulmonary embolism. The main advantage of the YEARS algorithm in our patients is the absolute 14% decrease of CTPA examinations in all ages and across several relevant subgroups., Funding: This study was supported by unrestricted grants from the participating hospitals., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: To investigate markers of autonomic tone on a standard electrocardiogram in relation to mortality in old age., Methods: A total of 599 inhabitants of Leiden, the Netherlands, were enrolled in a population-based follow-up study at their 85th birthday. Electrocardiograms (ECGs) were taken on entry and annually thereafter. ECGs were analysed automatically to determine four markers of autonomic tone, i.e. heart rate, the occurrence of ventricular extrasystoles and two time domain measures of heart rate variability. All participants were followed up for mortality., Results: Participants with a heart rate in the highest quartile had a 1.8-fold increased total mortality risk (95% confidence interval (CI) 1.0-3.4), but not an increased cardiovascular mortality risk. The occurrence of at least one ventricular extrasystole was related with a 2.3-fold increased total mortality risk (95% CI 1.3-3.9) and a 3.6-fold increased cardiovascular mortality (95% CI 1.6-8.2). In stratified analyses, the prognostic effect was confined to males. Both measures of heart rate variability were not related to mortality., Conclusion: High heart rate and the occurrence of a ventricular extrasystole, both markers of sympathetic dominance, were predictive of mortality in old age. Two short-term measures of heart rate variability as measured on a standard 10-s ECG were not related to mortality, and hence may not reflect autonomic tone in old age.

Objective: The objective of this study was to explore the relationship between home hazards and the incidence of falls in the oldest old population., Study Design and Setting: The Leiden 85-plus Study is a population-based study of all 85-year-old inhabitants of Leiden in the birth-cohort 1912-1914. Participants and general practitioners were interviewed at baseline and annually there after. We analyzed the incidence of falling in the first year dependent on the presence of home hazards at baseline. There were no exclusion criteria other than the inability to walk alone., Results: During the 1-year follow-up, 44% of the participants experienced one or more falls. Participants without preceding falls (n=246) had a 4-fold risk for falls in the presence of six or seven home hazards (relative risk 3.58, 95% confidence interval 1.75-5.05) compared with those without home hazards. Participants with preceding falls (n=234) had no increased risk of falls with increasing numbers of home hazards, although they had a higher risk to fall. The data confirmed the known increased risk for falls in participants with physical impairments., Conclusion: We conclude that participants without a history of preceding falls have an increased risk of falling due to the presence of home hazards.