Essentials
Direct oral anticoagulants (DOACs) do not require laboratory monitoring currently.
DOAC specific measurements were performed at trough in patients with atrial fibrillation.
Patients who ...developed thromboembolic events showed lower DOAC plasma levels.
This study supports the concept of measuring DOAC levels at steady state.
Summary
Background
Direct oral anticoagulants (DOACs) are administered at fixed doses without the need for dose adjustment according to laboratory testing. High interindividual variability in drug blood levels has been shown with all DOACs. To evaluate a possible relationship between DOAC C‐trough anticoagulant levels and thromboembolic events, 565 consecutive naive patients with atrial fibrillation (AF) were enrolled in this study performed within the START Laboratory Registry.
Methods
DOAC‐specific measurements (diluted thrombin time or anti‐activated factor II calibrated for dabigatran; anti‐activated FX calibrated for rivaroxaban or apixaban) at C‐trough were performed locally at steady state within 15–25 days after the start of treatment. For each DOAC, the interval of C‐trough levels, from the limit of quantification to the highest value, was subdivided into four equal classes, and results were attributed to these classes; the median values of results were also calculated. Thromboembolic complications occurring during 1 year of follow‐up were recorded.
Results
Thromboembolic events (1.8%) occurred in 10 patients who had baseline C‐trough levels in the lowest class of drug levels. The incidence of thromboembolic events among patients with DOAC C‐trough levels in the lowest level class was 2.4%, and that in the remaining groups was 0%. The patients with thrombotic complications also had a higher mean CHA2DS2‐VASc score than that of the total patient population: 5.3 (95% confidence interval CI 4.3–6.3 versus 3.0 (95% CI 2.9–3.1).
Conclusion
In this study cohort, thrombotic complications occurred only in DOAC‐treated AF patients who had very low C‐trough levels, with a relatively high CHA2DS2‐VASc score. Larger studies are warranted to confirm these preliminary observations.
Background Some patients with bipolar disorder (BD) demonstrate neuropsychological deficits even when stable. However, it remains unclear whether these differ qualitatively from those seen in ...schizophrenia (SZ). Methods We compared the nature and severity of cognitive deficits shown by 106 patients with SZ and 66 patients with BD to 316 healthy adults (NC). All participants completed a cognitive battery with 19 individual measures. After adjusting their test performance for age, sex, race, education, and estimated premorbid IQ, we derived regression-based T-scores for each measure and the six cognitive domains. Results Both patient groups performed significantly worse than NCs on most (BD) or all (SZ) cognitive tests and domains. The resulting effect sizes ranged from .37 to 1.32 (mean = .97) across tests for SZ patients and from .23 to .87 (mean = .59) for BD patients. The Pearson correlation of these effect sizes was .71 ( p < .001). Conclusions Patients with bipolar disorder suffer from cognitive deficits that are milder but qualitatively similar to those of patients with schizophrenia. These findings support the notion that schizophrenia and bipolar disorder show greater phenotypic similarity in terms of the nature than severity of their neuropsychological deficits.
Introduction
Treatment Resistant Depression (TRD) is a complex, heterogeneous and multifactorial clinical condition that affects patients’ quality of life, their psychosocial functioning as well as ...suicidal risk. Intranasal esketamine is a new add-on treatment specifically approved for TRD.
Objectives
The aim of the study was to evaluate the efficacy and safety of intranasal esketamine treatment combined with intensive Cognitive Behavioral psychotherapy (CBT), together with treatment satisfaction, in two complex clinical cases of TRD with high suicidal risk in a 12 months follow-up.
Methods
Two male patients, 67 and 63 years old, with TRD, defined by at least two therapeutic failures with SSRI/SNRI and positive screening for high suicidal risk at the Columbia Suicide Severity Rating Scale, were selected for treatment with intranasal esketamine + CBT as an add-on to SSRI/SNRI antidepressant therapy. Psychopathological assessment were made by means of Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Columbia Suicide Severity Rating Scale (C-SSRS), Clinical Global Impression (CGI), Short Form Health Questionnaire (SF-36 items) at T0, every 7 days for the first 3 months, then every month. Treatment satisfaction was evaluated by means of the Client Satisfaction Questionnaire (CSQ-8), administered by trained nursing staff at 1, 3, 6 and 12 months. CBT specifically focused on depression was administered by a certified psychotherapist, weekly for the first 4 months, fortnightly for the next 3 months, monthly for the remaining 3 months.
Results
After 2 administrations of esketamine the total HAM-D score was reduced by an average of 10 units and the suicidal risk was progressively reduced to zero according to C-SSRS. After 12 months one of the two patients reached and actually maintains clinical remission; the other one maintains a condition of mild depression; both without suicidal ideation and with a significant increase in perceived quality of life. Treatment was well tolerated, with mild and temporary adverse effects, self-limited to the administration sessions. CBT has contributed to increasing insight, cognitive resources, social interaction and self-esteem, and has made it possible to structure and carry on new life projects. The variation of the mean scores for CSQ-8 shows that esketamine + CBT treatment was considered as very satisfactory throughout the observation period.
Conclusions
Intranasal esketamine associated with intensive CBT sessions showed to be effective, safe and satisfactory in the real world clinical management of two complex cases of TRD with high suicidal risk, improving quality of life, social functioning and eliminating suicidal ideation within 12 months follow-up. Satisfaction with the treatment contributed to strengthening adherence and improving the operator-patient therapeutic relationship.
Disclosure of Interest
None Declared
Essentials
Tests for direct oral anticoagulants (DOACs) are not widely applied.
These tests are perceived to be difficult to run and subjected to large between‐lab variation.
We carried out ...proficiency testing surveys for DOAC testing in Italy.
Interlab variability was small and similar to that of the international normalised ratio.
Summary
Background
Tests for direct oral anticoagulants (DOACs) are not widely available. The perception that they are difficult to perform and are subject to large between‐laboratory variation makes their implementation difficult.
Aims
We carried out proficiency‐testing surveys for DOACs within the activity of the external quality‐assessment scheme of the Italian Federation of Thrombosis Centers.
Design
Participants were provided with coded freeze‐dried plasmas without or with graded concentrations of the three main DOACs, and asked to measure prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time and DOAC concentrations with dedicated tests. The results were centralized for statistical analysis.
Results and conclusions
All participants (n = 235) reported results for PT and APTT, and approximately one‐third reported results for DOAC concentration. PT and APTT showed variable responsiveness to DOACs: PT was more responsive to rivaroxaban than to dabigatran or apixaban. APTT was more responsive to dabigatran than to rivaroxaban or apixaban. The thrombin time ratio (test/normal) was close to unity for plasmas without dabigatran, and was high (i.e. 7.6‐fold or 15.4‐fold longer than the plasma free from the drug) for plasmas containing dabigatran at low (i.e. 42 ng mL−1) or high (i.e. 182 ng mL−1) concentration. Dedicated tests were responsive to the respective drugs, and their interlaboratory variability was relatively small (overall coefficients of variation of 8.7%, 8.4% or 10.3% for dabigatran, rivaroxaban and apixaban, respectively) and was comparable to that observed within the same survey for the International Normalized Ratio (i.e. 11.4%). In conclusion, tests for DOAC measurement performed reasonably well in a national quality‐control scheme. Regulatory authorities should urgently issue recommendations on their use, and clinical laboratories should make them available.
Summary
The Personality Assessment Inventory (PAI) is a widely used self‐report questionnaire designed to detect and quantify dimensions of adult psychopathology. Previous studies that examined the ...ability of the PAI to differentiate between patients with psychogenic nonepileptic seizures (PNES) and those with epilepsy (EPIL) have yielded inconsistent results. We compared the full PAI profiles of 62 patients with PNES, 55 with EPIL, and 45 normal control (NC) participants to determine the diagnostic accuracy of the PAI. We also sought to highlight psychopathologic symptoms that may inform psychological treatment of patients with PNES or epilepsy. PNES and EPIL patients reported more somatic concerns and symptoms of anxiety and depression than did NC persons. PNES patients reported more unusual somatic symptoms, as well as greater physical symptoms of anxiety and depression than did patients with EPIL. Classification accuracy of the “NES Indicator” was not much better than chance, whereas the Conversion subscale alone had reasonable sensitivity (74%) and specificity (67%). Overall, the PAI demonstrated only moderate classification accuracy in an epilepsy monitoring unit sample. However, the inventory appears to identify specific psychopathological symptoms that may be targets of psychological/psychiatric intervention.
See also Galli M. The antiphospholipid triangle. This issue, pp 234–6.
Summary. Background: The characteristics and the clinical course of antiphospholipid syndrome (APS) in high‐risk patients that ...are positive for all three recommended tests that detect the presence of antiphospholipid (aPL) antibodies have not been described. Methods: This retrospective analysis of prospectively collected data examined patients referred to Italian Thrombosis Centers that were diagnosed with definite APS and tested positive for aPL lupus anticoagulant (LA), anti‐cardiolipin (aCL), and anti‐β2‐glycoprotein I (β2GPI) antibodies. Laboratory data were confirmed in a central reference laboratory. Results: One hundred and sixty patients were enrolled in this cohort study. The qualifying events at diagnosis were venous thromboembolism (76 cases; 47.5%), arterial thromboembolism (69 cases; 43.1%) and pregnancy morbidity (11 cases; 9.7%). The remaining four patients (2.5%) suffered from catastrophic APS. The cumulative incidence of thromboembolic events in the follow‐up period was 12.2% (95%CI, 9.6–14.8) after 1 year, 26.1% (95%CI, 22.3–29.9) after 5 years and 44.2% (95%CI, 38.6–49.8) after 10 years. This was significantly higher in those patients not taking oral anticoagulants as compared with those on treatment (HR=2.4 95%CI 1.3–4.1; P < 0.003). Major bleeding associated with oral anticoagulant therapy was low (0.8% patient/years). Ten patients died (seven were cardiovascular deaths). Conclusions: Patients with APS and triple positivity for aPL are at high risk of developing future thromboembolic events. Recurrence remains frequent despite the use of oral anticoagulants, which significantly reduces the risk of thromboembolism.
The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is a consensus neuropsychological battery with established reliability and validity. One of the difficulties in ...implementing the MACFIMS in clinical settings is the reliance on manualized norms from disparate sources. In this study, we derived regression-based norms for the MACFIMS, using a unique data set to control for standard demographic variables (i.e., age, age2, sex, education). Multiple sclerosis (MS) patients (n = 395) and healthy volunteers (n = 100) did not differ in age, level of education, sex, or race. Multiple regression analyses were conducted on the performance of the healthy adults, and the resulting models were used to predict MS performance on the MACFIMS battery. This regression-based approach identified higher rates of impairment than manualized norms for many of the MACFIMS measures. These findings suggest that there are advantages to developing new norms from a single sample using the regression-based approach. We conclude that the regression-based norms presented here provide a valid alternative to identifying cognitive impairment as measured by the MACFIMS.
Background
A novel flash glucose monitoring system (FGMS) (FreeStyle Libre, Abbott, UK) was recently developed for humans. It continuously measures the interstitial glucose (IG) concentrations for 14 ...days.
Objectives
To assess the clinical and analytical accuracy of the FGMS in diabetic dogs.
Animals
Ten client‐owned diabetic dogs on insulin treatment.
Methods
Prospective and observational study. The FGMS was placed on the neck for up to 14 days. During the 1st–2nd, 6–7th, and 13–14th days from application, the IG measurements were compared with the plasma (EDTA) glucose (PG) concentrations analyzed by a reference hexokinase based method.
Results
The application and the use of the FGMS were apparently painless, easy, and well tolerated by all dogs. Mild erythema at the site of the application was found in 5/10 dogs at the end of the wearing period. A good correlation between IG and PG concentrations (rho = 0.94; P < .001) was found. The FGMS was 93, 99, and 99% accurate at low, normal, and high blood glucose concentrations. Mean ± standard deviation difference from the reference method was 2.3 ± 46.8 mg/dL.
Conclusion and clinical importance
The FGMS is easy to use and is accurate for IG glucose measurement in diabetic dogs.
Coronavirus disease 2019 (COVID-19) is associated with extreme inflammatory response, disordered hemostasis and high thrombotic risk. A high incidence of thromboembolic events has been reported ...despite thromboprophylaxis, raising the question of a more effective anticoagulation. First-line hemostasis tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and D-dimers are proposed for assessing thrombotic risk and monitoring hemostasis, but are vulnerable to many drawbacks affecting their reliability and clinical relevance. Specialized hemostasis-related tests (soluble fibrin complexes, tests assessing fibrinolytic capacity, viscoelastic tests, thrombin generation) may have an interest to assess the thrombotic risk associated with COVID-19. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment, especially unfractionated heparin in the setting of an extreme inflammatory response. This review aimed at evaluating the role of hemostasis tests in the management of COVID-19 and discussing their main limitations.
Summary
Introduction
D‐dimer assay, generally evaluated according to cutoff points calibrated for VTE exclusion, is used to estimate the individual risk of recurrence after a first idiopathic event ...of venous thromboembolism (VTE).
Methods
Commercial D‐dimer assays, evaluated according to predetermined cutoff levels for each assay, specific for age (lower in subjects <70 years) and gender (lower in males), were used in the recent DULCIS study. The present analysis compared the results obtained in the DULCIS with those that might have been had using the following different cutoff criteria: traditional cutoff for VTE exclusion, higher levels in subjects aged ≥60 years, or age multiplied by 10.
Results
In young subjects, the DULCIS low cutoff levels resulted in half the recurrent events that would have occurred using the other criteria. In elderly patients, the DULCIS results were similar to those calculated for the two age‐adjusted criteria. The adoption of traditional VTE exclusion criteria would have led to positive results in the large majority of elderly subjects, without a significant reduction in the rate of recurrent event.
Conclusion
The results confirm the usefulness of the cutoff levels used in DULCIS.
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