Pulmonary embolism (PE)‐related death is often a component of the primary outcome in venous thromboembolism (VTE) clinical studies. Definitions for PE‐related death vary widely, which may lead to ...biased risk estimates of clinical outcomes, thereby affecting both internal and external validity of study results. We here provide a standardized definition of PE‐related death and propose guidance for classification and reporting of the cause of death for clinical studies in VTE. The proposal was developed in a four‐step process, including a systematic review of definitions used for PE‐related death in previous studies, two subsequent surveys with VTE experts, and meetings held within the Scientific and Standardization Committee (SSC) working group until consensus on the proposal was reached. The proposed classification comprises three categories: Category A: PE‐related death, category B: undetermined cause of death, and category C: cause of death other than PE. Category A includes A1: autopsy‐confirmed PE in the absence of another more likely cause of death; A2: objectively confirmed PE before death in the absence of another more likely cause of death; and A3: PE is not objectively confirmed, but is most likely the main cause of death. Category B includes B1: cause of death is undetermined, despite available information; and B2: insufficient clinical information available to determine the cause of death. The use of the proposed definition will hopefully improve the accuracy of study outcomes, between‐study comparisons, meta‐analyses, and validity of future clinical VTE studies.
Abstract
Objectives
To evaluate the dolutegravir+lamivudine combination in virologically suppressed patients living with HIV.
Methods
The ANRS 167 LAMIDOL trial was an open-label, single arm, ...multicentre trial assessing once-daily dolutegravir (50 mg)+lamivudine (300 mg) in virologically suppressed HIV-1 patients on first-line triple-drug regimens. The main criteria for inclusion in the trial were plasma viral load (pVL) ≤50 copies/mL for ≥2 years, CD4 nadir >200 cells/mm3 and WT HIV prior to treatment initiation. From week −8 (W−8) to day 0 (D0) (Phase 1), the current third agent was switched to dolutegravir. From D0 to W48 (Phase 2), patients received once-daily dolutegravir+lamivudine, except if intolerant or if pVL >50 copies/mL during Phase 1. Virological failure was defined as pVL >50 copies/mL in two consecutive samples. The study was designed to show that the strategy had an efficacy of ≥80%, assuming a 90% success rate with a type I error of 5% and a power of 90%.
Results
In total, 104 of 110 patients enrolled in Phase 1 were included in Phase 2. These 104 patients were 86% male, 72% MSM and 87% CDC stage A. Their characteristics were (median): age 45 years, CD4 nadir 339 cells/mm3, baseline CD4 743 cells/mm3 and duration of viral suppression 4.5 years. The overall success rate at W48 was 97% (95% CI: 94%–100%), meeting the design expectation/assumption. Three therapeutic failures occurred: one virological failure at W4, one lost to follow-up at W32 and one interruption of therapeutic strategy at W40 after a blip (pVL 59 copies/mL but control pVL <50 copies/mL). Three viral blips occurred in two additional patients. Neither M184V nor integrase resistance mutations were detected after failure or blips.
Conclusions
Dolutegravir+lamivudine is a promising maintenance therapy in HIV-1-infected patients with controlled virological suppression.
This article focuses on the coordination of long-term social-ecological monitoring programmes between different organisations. Effective long-term social-ecological monitoring (LTSEM) is considered ...to be of crucial importance to inform conservation policies in an era of accelerating global changes. However, many LTSEM programmes are led by individual organisations with a narrow thematic and spatial focus, and fail to provide an integrated understanding of the trajectories of social-ecological systems. Inter-organisational coordination is increasingly presented as a promising way to overcome this limitation of LTSEM programmes, but in practice it remains limited. Our article contributes to understanding this situation by empirically documenting how inter-organisational coordination of LTSEM programmes is organised and enacted in practice. It proposes a working heuristic framework to characterise patterns of inter-organisational coordination based on two criteria: the degree of monitoring centrality and the degree of verticality of inter-organisational coordination. This framework can be used to compare patterns of inter-organisational coordination both across cases and over time. The article also proposes recommendations for the coordination of LTSEM programmes led by different organisations, especially in the early stages of the coordination process.
•Long-term social-ecological monitoring (LTSEM) supports conservation policies.•Inter-organisational coordination is crucial for effective LTSEM.•There are several patterns of inter-organisational coordination.•Verticality of relationships and centrality of monitoring characterise these patterns.•Inter-organisational heterogeneity in status and power is important to consider.
HIV testing is an important step towards diminishing incident infections. Rapid self-tests whose use is becoming more common in France could help increase access to testing, yet could fail to ...diagnose HIV during acute HIV infection (AHI). The aim of the present study was to evaluate HIV-detection sensitivity of a commonly used rapid self-test (STAT-VIEW HIV1/2), compared with another point-of-care rapid test (INSTI), among patients presenting with AHI.
Individuals tested at Saint-Antoine Hospital (Paris, France) with negative or indeterminate western blot (WB) results and detectable HIV-RNA were included. Rapid tests were performed retrospectively on stored serum. Patients with and without reactive rapid tests were compared, while probability of having a reactive test was modelled across infection duration using logistic regression.
Of the 40 patients with AHI, 23 (57.5%) had a reactive STAT-VIEW rapid test. Patients with non-reactive versus reactive tests had a significantly shorter median time since infection (p=0.01), time since onset of symptoms (p=0.009), higher proportion with Fiebig stage III versus IV (p=0.003), negative WB results (p=0.007), higher HIV-RNA levels (p=0.001) and lower CD4+ and CD8+ cell count (p=0.03, p<0.001, respectively). When examining sensitivity over the course of AHI duration, the probability of HIV detection was 75.5% at 5 weeks from HIV transmission. The INSTI provided similar results with respect to proportion of reactive tests (62.5%), determinants for non-reactive test and probability of HIV detection at 5 weeks of infection (85.0%).
Over half of AHI patients had reactive serology using the STAT-VIEW rapid self-test when performed on serum samples. Considering that detection sensitivity increased substantially over infection time, individuals should not rely on a negative result to accurately exclude HIV infection within at least 5 weeks of potential HIV exposure. Notwithstanding strong recommendations against rapid test use during AHI, some utility in detecting HIV is observed 5-12 weeks after transmission.
Background
The International Society on Thrombosis and Haemostasis (ISTH)’s Scientific and Standardization Committee (SSC) recently proposed a definition of pulmonary embolism (PE)‐related death.
...Objectives
To evaluate the accuracy and interrater reliability of the ISTH definition of PE‐related death in an autopsy cohort.
Methods
We reviewed reports of 1064 consecutive adult autopsies that were performed at the NewYork‐Presbyterian Hospital from January 2010 until July 2019. We included all patients with autopsy‐confirmed PE‐related death (cases) during that time frame, combined with patients who died in 2018 from a cause other than PE (controls). Based on clinical summaries, two adjudicators independently adjudicated the cause of death in each patient using the ISTH classification for the cause of death, blinded to the case/control status and ratio. The primary outcome was autopsy‐confirmed PE‐related death. We determined the sensitivity and specificity of the ISTH definition to identify autopsy‐confirmed PE‐related death, and its interrater reliability using the percentage agreement and Cohen's kappa.
Results
A total of 126 patients who underwent autopsy were included in the analysis (median age, 68 years range, 21–94, 60 48% women), of which 29 (23%) had died from PE as confirmed by autopsy. The ISTH definition's sensitivity and specificity for autopsy‐confirmed PE‐related death were 45% (95% CI, 26–64) and 99% (95% CI, 94–100), respectively. Interrater reliability for PE‐related death was substantial (percentage agreement, 94% 95% CI, 89–97; kappa, 0.73 95% CI, 0.55–0.97).
Conclusion
Adjudication of the cause of death using the ISTH definition resulted in very high specificity, moderate sensitivity, and good interrater reliability for PE‐related death.
We previously determined good agreement and high specificity of the International Society on Thrombosis and Haemostasis (ISTH) definition of pulmonary embolism (PE)-related death among an expert ...central adjudication committee (CAC). CACs are often composed of experts in the corresponding research field. Involving physician trainees in CACs would allow investigators to divide the workload and foster trainees’ research experience.
To evaluate the accuracy of the ISTH definition of PE-related death for PE- versus non–PE-related deaths as confirmed by autopsy and its interrater agreement among physician trainees.
This retrospective autopsy cohort included all patients with PE-related deaths between January 2010 and July 2019 as well as patients who died in 2018 from a cause other than PE at the New York-Presbyterian Hospital. Based on premortem clinical summaries, two physician trainees independently determined the cause of death using the ISTH definition of PE-related death. We calculated the sensitivity and specificity of the ISTH definition to identify autopsy-confirmed PE-related death and its interrater agreement.
Overall, 126 death events were adjudicated (median age, 68 years; 60 48% women), of which 29 (23%) were due to PE, as confirmed by autopsy. Sensitivity and specificity of the ISTH definition for autopsy-confirmed PE-related death was 48% (95% CI, 29-67) and 100% (95% CI, 96-100), respectively. Interrater reliability for PE-related death was good (percentage agreement, 93%; 95% CI, 87-96, Cohen’s Kappa, 0.67; 95% CI, 44-85).
Our findings are consistent with our previous validation study. They further support the use of the ISTH definition of PE-related death and revealed high agreement between adjudicators with varied experience.
•We evaluated the accuracy of the International Society on Thrombosis and Haemostasis definition of pulmonary embolism-related death in an autopsy cohort.•Physician trainees determined the cause of death in 126 patients based on clinical summaries.•The definition had a high specificity and moderate sensitivity for pulmonary embolism-related death upon autopsy.•Our results support the use of the International Society on Thrombosis and Haemostasis definition by adjudicators with diverse experience.
Introduction
Pulmonary embolism (PE)‐related death is often part of the primary outcome in venous thromboembolism (VTE) studies. The Scientific and Standardization Committee (SSC) of the ...International Society on Thrombosis and Haemostasis developed a definition for PE‐related death and classification of the cause of death. The present survey evaluated a preliminary version of this definition and classification.
Methods
Sixty‐nine VTE experts from nine countries were invited for a cross‐sectional online survey on January 15, 2019, including multiple‐choice and open‐ended questions on a seven‐subcategory classification of the cause of death. Descriptive statistics were used to describe the results; qualitative comments were summarized.
Results
Forty of 69 (58%) invitees completed the survey. All respondents agreed that guidance on classification of the cause of death in VTE studies is required. There was high agreement on the proposal (median overall score, 6; interquartile range, 6‐7; scale from 1 poor to 7 excellent). All respondents approved the wording and content of the seven subcategories, except for one disagreeing vote for two subcategories (A3: “PE is not objectively confirmed, but is most likely the main cause of death” and C1: “Another cause of death is more likely than PE but has not been objectively confirmed”). Suggestions for improvement mainly concerned the extensiveness of the criteria and clinical situations described to define the cause of death.
Conclusion
Acceptance of the proposal was excellent. Suggestions for improvement were incorporated in the SSC communication on the definition of PE‐related death and classification of the cause of death in VTE studies.
Intermittent treatment could improve the convenience, tolerability and cost of ART, as well as patients' quality of life. We conducted a 48 week multicentre study of a 4-days-a-week antiretroviral ...regimen in adults with controlled HIV-1-RNA plasma viral load (VL).
Eligible patients were adults with VL < 50 copies/mL for at least 1 year on triple therapy with a ritonavir-boosted PI (PI/r) or an NNRTI. The study protocol consisted of the same regimen taken on four consecutive days per week followed by a 3 day drug interruption. The primary outcome was the proportion of participants remaining in the strategy with VL < 50 copies/mL up to week 48. The study was designed to show an observed success rate of > 90%, with a power of 87% and a 5% type 1 error. The study was registered with ClinicalTrials.gov (NCT02157311) and EudraCT (2014-000146-29).
One hundred patients (82 men), median age 47 years (IQR 40-53), were included. They had been receiving ART for a median of 5.1 (IQR 2.9-9.3) years and had a median CD4 cell count of 665 (IQR 543-829) cells/mm3. The ongoing regimen included PI/r in 29 cases and NNRTI in 71 cases. At 48 weeks, 96% of participants (95% CI 90%-98%) had no failure while remaining on the 4-days-a-week regimen. Virological failure occurred in three participants, who all resumed daily treatment and became resuppressed. One participant stopped the strategy. No severe treatment-related events occurred.
Antiretroviral maintenance therapy 4 days a week was effective for 48 weeks in 96% of patients, leading to potential reduction of long-term toxicities, high adherence to the antiretroviral regimen and drug cost saving.
The aim of this study was to characterise the mechanical behaviour of Cooper’s ligaments. Such ligaments are collagenous breast tissue that create a three-dimensional structure over the entire breast ...volume. Ten ligaments were extracted from a human cadaver, from which 28 samples were cut and used to perform uniaxial tensile tests. Histological analysis showed that the main direction of the fibres visible to the naked eye corresponds to the orientation of the fibres on a microscopic scale. The specimens were cut according to this orientation, which allowed the sample to be stretched in the main fibre direction. From these experimental stretch/stress curves, an original anisotropic hyperelastic constitutive law is proposed to model the behaviour of Cooper’s ligaments and the material parameter validity is discussed.
PDF
