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Background: Since data on the safety and effectiveness of home telemonitoring and oxygen therapy started directly after Emergency Department (ED) assessment in COVID-19 patients are sparse but could have many advantages, we evaluated these parameters in this study. Methods: All COVID-19 patients ≥18 years eligible for receiving home telemonitoring (November 2020-February 2022, Albert Schweitzer hospital, the Netherlands) were included: patients started directly after ED assessment (ED group) or after hospital admission (admission group). Safety (number of ED reassessments and hospital readmissions) and effectiveness (number of phone calls, duration of oxygen usage and home telemonitoring) were described in both groups. Results: 278 patients were included (n = 65 ED group, n = 213 admission group). ED group: 23.8% (n = 15) was reassessed, 15.9% (n = 10) was admitted and 7.7% (n = 5) ICU admitted. Admission group: 15.8% (n = 37) was reassessed, 6.5% (n = 14) was readmitted and 2.4% (n = 5) ICU (re)admitted. Ten patients died, of whom 7 due to COVID-19 (1 in ED group; 6 in the admission group). ED group: median duration of oxygen therapy was 9 (IQR 7–13) days; the total duration of home telemonitoring was 14 (IQR 9–18) days. Admission group: duration of oxygen therapy was 10 (IQR 6–16) days; total duration of home telemonitoring was 14 (IQR 10–20) days. Conclusion: it appears to be safe to start home telemonitoring and oxygen therapy directly after ED assessment.

Aims D-dimer is a product of fibrinolysis. In clinical practice, D-dimer levels are commonly used to rule out venous thromboembolism. Antiplatelet drugs may influence D-dimer levels, potentially affecting the accuracy of this diagnostic tool. To evaluate the effect of antiplatelet drugs on D-dimer levels, we performed a systematic review and meta-analysis of all published articles on this topic (PROSPERO registration number CRD42017058932). Methods and results We electronically searched EMBASE, MEDLINE Epub, Cochrane, Web of Science, and Google Scholar (100 top relevance) (last search on October 5, 2017). We included randomized controlled trials, cohort studies, and cross-sectional studies conducted in humans, with a drug exposure time of at least 7 days. Two reviewers independently selected eligible articles and extracted the data. Five controlled trials, 7 cohort studies, and 5 cross-sectional studies were finally included. Meta-analysis involving all 1117 participants showed no change in dimer levels (standardized mean difference: -0.015, 95% confidence interval, 0.182-0.151, P = 0.855). Conclusions In conclusion, antiplatelet drugs do not seem to influence D-dimer levels.

We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non-rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8 center dot 75 min (95% CI -13 center dot 8 to -3 center dot 72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (-0 center dot 05 U/ml; 95% CI -0 center dot 07 to -0 center dot 02 and -4 center dot 77%; 95% CI -6 center dot 81 to -2 center dot 73, respectively). PAI-1 levels did not change and fibrinogen levels were 0 center dot 17 g/l (95% CI 0 center dot 04-0 center dot 29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non-statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE.

Background Acute pulmonary embolism may be ruled out by combining nonhigh clinical probability and a normal D‐dimer level. Both antiplatelet drugs and HMG‐CoA reductase inhibitors (statins) have been associated with effects on thrombus formation, potentially influencing D‐dimer levels in this setting, leading to a higher rate of false‐negative tests. Therefore, we determined whether D‐dimer levels in patients with suspected pulmonary embolism are affected by concomitant use of antiplatelet drugs and/or statins and evaluated whether the effect of antiplatelet drugs or statins might affect diagnostic accuracy. Materials and methods We performed a posthoc analysis in the YEARS diagnostic study, comparing age‐ and sex‐adjusted D‐dimer levels among users of antiplatelet drugs, statins and nonusers. We then reclassified patients within the YEARS algorithm by developing a model in which we adjusted D‐dimer cut‐offs for statin use and evaluated diagnostic accuracy. Results We included 156 statins users, 147 antiplatelet drugs users and 726 nonusers of either drugs, all with suspected pulmonary embolism. Use of antiplatelet drugs did not have a significant effect, whereas statin use was associated with 15% decrease in D‐dimer levels (95% CI, −28% to −0.6%). An algorithm with lower D‐dimer thresholds in statin users yielded lower specificity (0.42 compared to 0.33) with no difference in false‐negative tests. Conclusions We conclude that use of statins but not of antiplatelet agents is associated with a modest decrease in D‐dimer levels. Adjusting D‐dimer cut‐offs for statin use did, however, not result in a safer diagnostic strategy in our cohort.

Statins are generally believed to have cardiovascular protective effects independent of low-density lipoprotein-cholesterol (LDL-C) lowering, such as antithrombotic effects characterized by a decrease in D-dimer levels. For the recently introduced Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors antithrombotic effects are yet unknown. We determined the effect of starting PCSK9 inhibitors on D-dimer and fibrinogen levels as most robust markers for thrombogenicity in statin-intolerant patients with familial hypercholesterolemia. We determined D-dimer and fibrinogen levels before and after start of evolocumab (n = 19) or alirocumab (n = 11). Baseline median D-dimer levels were 0.34 mg/L (IQR 0.24–0.59 mg/L) and baseline median fibrinogen levels 3.2 g/L (IQR 2.88–3.63 g/L). At follow-up D-dimer levels (median 0.31 mg/L (IQR 0.25-0.59 mg/L); p = 0.37), and fibrinogen levels (median 3.4 g/L (IQR 2.98–3.62 g/L); p = 0.38) did not change significantly. We therefore conclude PCSK9 inhibitors do not seem to have a profound antithrombotic effect, although a more subtle effect can not been excluded.

Summary 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.

A 47-year-old woman with a history of ulcerative colitis and rheumatoid arthritis presented with a large ulcer with an erythematous halo of the right lower leg. The clinical course and the histopathological results were indicative of pyoderma gangrenosum.

BACKGROUND: Asymptomatic cerebral lesions on MRI such as white matter lesions (WML), lacunes and microbleeds are commonly seen in older people. We examined the role of a series of candidate genes involved in blood pressure regulation and amyloid metabolism.MATERIALS AND METHODS: The study was embedded in a family-based cohort sampled from a Dutch genetically isolated population. We selected individuals between 55 and 75 years of age with hypertension (N=129). Volumes of WML and presence of lacunes and microbleeds were assessed with MRI. We studied three genes involved in blood pressure regulation (angiotensin, angiotensin II type 1 receptor, α-adducin) and two genes involved in the amyloid pathway (apolipoprotein E (APOE) and sortilin-related receptor gene (SORL1)).RESULTS: All participants had WML (median volume, 3.1 ml; interquartile range, 1.5-6.5 ml); lacunar infarcts were present in 15.5% and microbleeds in 23.3%. Homozygosity for the APOE ε4 allele was associated with lacunes (OR, 4.8; 95% CI, 1.2 to 19.3). Individuals carrying two copies of the variant allele of four single nucleotide polymorphism (SNPs) located at the 3'-end of SORL1 (rs1699102, rs3824968, rs2282649, rs1010159) had significantly more often microbleeds (highest OR, 6.87; 95% CI, 1.78 to 26.44).CONCLUSION: The association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.

Background Depression has a strong genetic component but candidate gene studies conducted to date have not shown consistent associations. Methods We conducted a genome-wide parametric and nonparametric linkage analysis in a large-scale family-based study including 115 individuals with depression who were identified based on the Hospital Anxiety Depression Scale, Center for Epidemiologic Studies Depression Rating Scale, or use of antidepressive medication. Further, we investigated the most promising chromosomal regions found in the genome-wide linkage analysis with an association analysis in 734 individuals in the family-based study and 2373 individuals in the population-based study. Results Our study demonstrated evidence for significant linkage of depression to chromosome 2p16.1-15 (logarithm of odds [LOD] = 5.13; parametric analysis) and suggestive evidence for linkage in nonparametric analysis to chromosome 5p15.33 (LOD = 2.14), 11q25 (LOD = 2.27), and 19p13.3 (LOD = 2.66). The subsequent association analysis in the family-based study showed region-wide significant association in intron 1 of the OPCML gene on chromosome 11q25 (empirical p value=.04). The association analysis in the population-based study did not show any region-wide significant association, yet showed suggestive association in intron 1 of the APLP2 gene on chromosome 11q25. Conclusions Our linkage and association studies suggest a locus for depression on chromosomes 2p16.1-15 and 11q25. The linkage to chromosome 11q25 may be, in part, explained by the OPCML or the APLP2 gene. Further, there is evidence for a role of the GNG7 gene (chromosome 19p13.3).