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1.
Chest ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38458430

RESUMO

The CHEST Antithrombotic Therapy for Venous Thromboembolism Disease evidence-based guidelines are now updated in a more frequent, focused manner. Guidance statements from the most recent full guidelines and two subsequent updates have not been gathered into a single source. An international panel of experts with experience in prior antithrombotic therapy guideline development reviewed the 2012 CHEST antithrombotic therapy guidelines and its two subsequent updates. All guideline statements and their associated patient, intervention, comparator, and outcome questions were assembled. A modified Delphi process was used to select statements considered relevant to current clinical care. The panel further endorsed minor phrasing changes to match the standard language for guidance statements using the modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) format endorsed by the CHEST Guidelines Oversight Committee. The panel appended comments after statements deemed as relevant, including suggesting that statements be updated in future guidelines because of interval evidence. We include 58 guidance statements from prior versions of the antithrombotic therapy guidelines, with updated phrasing as needed to adhere to contemporary nomenclature. Statements were classified as strong or weak recommendations based on high-certainty, moderate-certainty, and low-certainty evidence using GRADE methodology. The panel suggested that five statements are no longer relevant to current practice. As CHEST continues to update guidance statements relevant to antithrombotic therapy for VTE disease, this article serves as a unified collection of currently relevant statements from the preceding three guidelines. Suggestions have been made to update specific statements in future publications.

2.
Ann Intern Med ; 176(12): JC143, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38048580

RESUMO

SOURCE CITATION: Meaidi A, Mascolo A, Sessa M, et al. Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study. BMJ. 2023;382:e074450. 37673431.


Assuntos
Trombose , Tromboembolia Venosa , Feminino , Humanos , Tromboembolia Venosa/induzido quimicamente , Estudos de Coortes , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Fatores de Risco
3.
Res Pract Thromb Haemost ; 7(7): 102202, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37840688

RESUMO

Background: Deep vein thrombosis (DVT) is common in pregnancy, yet data are limited on the best diagnostic strategies in pregnant patients suspected of DVT. Objectives: We conducted a prospective cohort study to evaluate the rate of symptomatic DVT in the 90 days after a negative whole-leg compression ultrasound (CUS) in pregnant women presenting with DVT symptoms. Methods: In this prospective cohort study, we enrolled pregnant patients suspected of DVT between 2011 and 2019 who were referred to the vascular imaging laboratory at a tertiary care center and had anticoagulation held after a negative whole-leg CUS. Primary outcome was objectively confirmed DVT or pulmonary embolism or death due to venous thromboembolism (VTE). Results: Whole-leg CUS yielded normal results in 186 patients (97.9%) and identified DVT in 4 (2.1%). The mean age was 30 and 164 were White. Among the 186 patients with a negative, initial whole-leg CUS who did not receive anticoagulation, there were 2 DVT events identified over the 90-day follow-up period, for an overall rate of 1.1% (95% CI: 0.2-3.4%). The study was terminated before full planned accrual for administrative reasons. Conclusion: The rate of symptomatic DVT is low in pregnant patients who have a single, negative whole-leg CUS and did not receive anticoagulation. Adequately powered studies should prospectively assess whole-leg CUS in a larger population alone and in combination with pre-test probability scores and/or D-dimer to determine its role in the evaluation of suspected DVT in pregnancy.

4.
Ann Intern Med ; 176(10): JC118, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37782927

RESUMO

SOURCE CITATION: Planer D, Yanko S, Matok I, et al. Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis. CMAJ. 2023;195:E833-E843. 37336568.


Assuntos
Fibrinolíticos , Embolia Pulmonar , Humanos , Anticoagulantes/uso terapêutico , Catéteres , Fibrinolíticos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica , Resultado do Tratamento
5.
J Thromb Haemost ; 21(12): 3581-3588, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37739038

RESUMO

BACKGROUND: In patients with acute deep vein thrombosis (DVT) treated with catheter-based thrombolysis and venous stenting, poststenting anticoagulant management is uncertain. OBJECTIVES: To determine the type and duration of antithrombotic therapy used in patients who have received venous stents for treatment of acute lower extremity DVT. METHODS: We created an international registry of patients with leg DVT from 2005 to 2019 who received venous stents as part of their acute management. We collected data on baseline clinical characteristics and pre-venous and post-venous stent antithrombotic therapy. RESULTS: We studied 173 patients with venous stents: 101 (58%) were aged ≤50 years, 105 (61%) were female, and 128 (74%) had risk factors for thrombotic disease. DVT was iliofemoral in 150 (87%) patients, and catheter-based treatment was given within 7 days of diagnosis in 92 (53%) patients. After venous stenting, 109 (63%) patients received anticoagulant-only therapy with a direct oral anticoagulant (29%), warfarin (22%), or low-molecular-weight heparin (10%), and 59 (34%) received anticoagulant-antiplatelet therapy. In patients taking anticoagulant-only therapy, 29% received indefinite treatment; in patients on anticoagulant-antiplatelet therapy, 19% received indefinite treatment. Factors associated with combined anticoagulant-antiplatelet therapy vs anticoagulant-only therapy were use of thrombolytic, thrombectomy, and aspiration interventions (odds ratio [OR], 5.11; 95% CI, 1.45-18.05); use of balloon angioplasty (OR, 2.62; 95% CI, 1.20-5.76); and immediate stent restenosis (OR, 7.2; 95% CI, 1.45-5.89). CONCLUSION: Anticoagulant therapy without concomitant antiplatelet therapy appears to be the most common antithrombotic strategy in patients with DVT and venous stenting. More research is needed to determine outcomes of venous stenting in relation to antithrombotic therapy.


Assuntos
Fibrinolíticos , Trombose Venosa , Humanos , Feminino , Masculino , Fibrinolíticos/efeitos adversos , Terapia Trombolítica/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Resultado do Tratamento , Veia Femoral , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Anticoagulantes/efeitos adversos , Stents , Estudos Retrospectivos
6.
Thromb Res ; 227: 45-50, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37235947

RESUMO

BACKGROUND: Post-hospitalization thromboprophylaxis can reduce venous thromboembolism (VTE) risk for non-surgical patients but may carry bleeding risks. We aimed to externally validate the Intermountain Risk Scores for hospital-associated venous thromboembolism (HA-VTE IMRS) and major bleeding (HA-MB IMRS) for VTE and bleeding outcomes. METHODS: Retrospective cohort study of adult patients discharged alive from medical services between 2015 and 2019. HA-VTE IMRS and HA-MB IMRS were calculated at the time of hospital discharge and dichotomized as high- or low-risk as described in the derivation manuscript. 90-day post-discharge VTE outcomes were assessed from diagnostic radiology reports, and bleeding outcomes were assessed using ICD-10 codes and blood bank transfusion records. RESULTS: Among 113,578 patients in the study, 66,340 patients (58.4 %) had a low-risk HA-VTE IMRS <7, versus 47,238 (41.6 %) high-risk ≥7. For bleed prediction, 71,576 patients (63 %) had a low-risk HA-MB IMRS <8, versus 42,002 (37 %) high-risk ≥8. VTE incidence was 1.1 % and 0.6 % while major bleeding incidence was 1.3 % and 0.1 % in high-risk versus low-risk cohorts, respectively. AUCs for VTE and bleed outcome discrimination were 0.59 and 0.78, respectively. Patients with a combined high-risk VTE score and low-risk bleeding score comprised 14.5 % of the population. CONCLUSION: In this external validation study, the HA-VTE IMRS had poor discrimination for VTE but the HA-MB IMRS had good discriminatory ability for major bleeding events. A sizable minority of patients were categorized as high VTE risk with low bleed risk, a population which may have an optimal risk-benefit profile for post-hospital thromboprophylaxis.


Assuntos
Tromboembolia Venosa , Humanos , Tromboembolia Venosa/tratamento farmacológico , Alta do Paciente , Anticoagulantes/uso terapêutico , Estudos Retrospectivos , Assistência ao Convalescente , Fatores de Risco , Hemorragia/induzido quimicamente , Biomarcadores
7.
Transplant Direct ; 9(3): e1453, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36875941

RESUMO

Venous thromboembolism (VTE) occurs in 0.4% to 15.5% and bleeding occurs in 20% to 35% of patients after liver transplantation (LT). Balancing the risk of bleeding from therapeutic anticoagulation and risk of thrombosis in the postoperative period is challenging. Little evidence exists regarding the best treatment strategy for these patients. We hypothesized that a subset of LT patients who develop postoperative deep vein thromboses (DVTs) could be managed without therapeutic anticoagulation. We implemented a quality improvement (QI) initiative using a standardized Doppler ultrasound-based VTE risk stratification algorithm to guide parsimonious implementation of therapeutic anticoagulation with heparin drip. Methods: In a prospective management QI initiative for DVT management, we compared 87 LT historical patients (control group; January 2016-December 2017) to 182 LT patients (study group; January 2018-March 2021). We analyzed the rates of immediate therapeutic anticoagulation after DVT diagnosis within 14 d of LT, clinically significant bleeding, return to the operating room, readmission, pulmonary embolism, and death within 30 d of LT before and after the QI initiative. Results: Ten patients (11.5%) in the control group and 23 patients (12.6%; P = 0.9) in the study group developed DVTs after LT. Immediate therapeutic anticoagulation was used in 7 of 10 and 5 of 23 patients in the control and study groups, respectively (P = 0.024). The study group had lower odds of receiving immediate therapeutic anticoagulation after VTE (21.7% versus 70%; odds ratio = 0.12; 95% confidence interval, 0.019-0.587; P = 0.013) and a lower rate of postoperative bleeding (8.7% versus 40%; odds ratio = 0.14, 95% confidence interval, 0.02-0.91; P = 0.048). All other outcomes were similar. Conclusions: Implementing a risk-stratified VTE treatment algorithm for immediate post-LT patients appears to be safe and feasible. We observed a decrease in the use of therapeutic anticoagulation and a lower rate of postoperative bleeding without adverse impacts on early outcomes.

8.
J Arrhythm ; 38(6): 997-1008, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36524040

RESUMO

Background: Atrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Anticoagulation use and efficacy impact long-term risk of dementia in AF patients in observational trials. Methods: The cognitive decline and dementia in patients with non-valvular atrial fibrillation (CAF) Trial was a randomized, prospective, open-label vanguard clinical study with blinded endpoint assessment involving patients with moderate- to high-risk (CHADS2 or CHA2DS2-Vasc scores of ≥2) non-valvular AF assigned to dabigatran etexilate or warfarin. The primary endpoint was incident dementia or moderate cognitive decline at 24 months. Results: A total of 101 patients were enrolled [mean age:73.7 ± 6.0 years, male: 54(53.5%)]. Prior stroke and stroke risk factors were similar between groups. Average INR over the study was 2.41 ± 0.68 in the warfarin group. No patient experienced a stroke or developed dementia. Mini-Mental Status Evaluation, Hachinski Ischemic scale, cognitive subscale of the Alzheimer's Disease Assessment Scale, Disability Assessment for Dementia, Quality of Life Improvement as assessed by Minnesota Living with Heart Failure Scale and the Anti-Clot Treatment Scale Quality of Life Survey scores did not vary at baseline or change over 2 years. Biomarker analysis indicated a similar efficacy of anticoagulation strategies. Conclusion: Use of dabigatran and well-managed warfarin therapy were associated with similar risks of stroke, cognitive decline, and dementia at 2 years, suggestive that either strategy is acceptable. The results of this Vanguard study did not support the pursuit of a larger formally powered study.

9.
J Am Coll Emerg Physicians Open ; 3(5): e12801, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36226236

RESUMO

Background: Structured reporting is an efficient and replicable method of presenting diagnostic results that eliminates variability inherent in narrative descriptive reporting and may improve clinical decisions. Synoptic element reporting can generate discrete coded data that then may inform clinical decision support and trigger downstream actions in computerized electronic health records. Objective: Limited evidence exists for use of synoptic reporting for computed tomography pulmonary arteriography (CTPA) among patients suspected of pulmonary embolism. We reported the accuracy of synoptic reporting for the outcome of pulmonary embolism among patients who presented to an integrated health care system with CTPA performed for suspected pulmonary embolism. Methods: Structured radiology reports with embedded synoptic elements were implemented for all CTPA examinations on March 1, 2018. Four hundred CTPA reports between January 4, 2019 and July 30, 2020 (200 reports each for which synoptic reporting recorded the presence or absence of pulmonary embolism [PE]) were selected at random. One non-diagnostic study was excluded from analysis. We then assessed the accuracy of synoptic reporting compared with the gold standard of manual chart review. Results: Synoptic reporting and manual review agreed in 99.2% of patients undergoing CTPA for suspected PE, agreed on the presence of PE in 196 of 199 (98.5%) cases, the absence of PE in 200 of 200 (100%) cases with a sensitivity of 87.6% (76.1-96.1) a specificity of 99.9% (99.7%-100%), a positive predictive value of 99.5% (98.1-100), and a negative predictive value of 98% (95.7%-99.5%). Conclusion: The overall rate of agreement was 99.2%, but we observed an unacceptable false-negative rate for clinical reliance on synoptic element reporting in isolation from dictated reports.

10.
Cardiol Res Pract ; 2022: 8244047, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275928

RESUMO

Background: Elderly patients undergoing hip or knee arthroplasty are at a risk for myocardial injury after noncardiac surgery (MINS). We evaluated the ability of five common cardiac risk scores, alone or combined with baseline high-sensitivity cardiac troponin I (hs-cTnI), in predicting MINS and postoperative day 2 (POD2) hs-cTnI levels in patients undergoing elective total hip or knee arthroplasty. Methods: This study is ancillary to the Genetics-InFormatics Trial (GIFT) of Warfarin Therapy to Prevent Deep Venous Thrombosis, which enrolled patients 65 years and older undergoing elective total hip or knee arthroplasty. The five cardiac risk scores evaluated were the atherosclerotic cardiovascular disease calculator (ASCVD), the Framingham risk score (FRS), the American College of Surgeon's National Surgical Quality Improvement Program (ACS-NSQIP) calculator, the revised cardiac risk index (RCRI), and the reconstructed RCRI (R-RCRI). Results: None of the scores predicted MINS in women. Among men, the ASCVD (C-statistic of 0.66; p=0.04), ACS-NSQIP (C-statistic of 0.69; p=0.01), and RCRI (C-statistic of 0.64; p=0.04) predicted MINS. Among all patients, spearman correlations (r s) of the risk scores with the POD2 hs-cTnI levels were 0.24, 0.20, 0.11, 0.11, and 0.08 for the ASCVD, Framingham, ACS-NSQIP, RCRI, and R-RCRI scores, respectively, with p values of <0.001, <0.001, <0.001, 0.006, and 0.025. Baseline hs-cTnI predicted MINS (C-statistics: 0.63 in women and 0.72 in men) and postoperative hs-cTnI (r s = 0.51, p=0.001). Conclusion: In elderly patients undergoing elective hip or knee arthroplasty, several of the scores modestly predicted MINS in men and correlated with POD2 hs-cTnI.

11.
Res Pract Thromb Haemost ; 6(5): e12765, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35873221

RESUMO

Background: Venous thromboembolism (VTE) risk is increased in patients with COVID-19 infection. Understanding which patients are likely to develop VTE may inform pharmacologic VTE prophylaxis decision making. The hospital-associated venous thromboembolism-Intermountain Risk Score (HA-VTE IMRS) and the hospital-associated major bleeding-Intermountain Risk Score (HA-MB IMRS) are risk scores predictive of VTE and bleeding that were derived from only patient age and data found in the complete blood count (CBC) and basic metabolic panel (BMP). Objectives: We assessed the HA-VTE IMRS and HA-MB IMRS for predictiveness of 90-day VTE and major bleeding, respectively, among patients diagnosed with COVID-19, and further investigated if adding D-dimer improved these predictions. We also reported 30-day outcomes. Patients/Methods: We identified 5047 sequential patients with a laboratory confirmed diagnosis of COVID-19 and a CBC and BMP between 2 days before and 7 days following the diagnosis of COVID-19 from March 12, 2020, to February 28, 2021. We calculated the HA-VTE IMRS and the HA-MB IMRS for all patients. We assessed the added predictiveness of D-dimer obtained within 48 hours of the COVID test. Results: The HA-VTE IMRS yielded a c-statistic of 0.70 for predicting 90-day VTE and adding D-dimer improved the c-statistic to 0.764 with the corollary sensitivity/specificity/positive/negative predictive values of 49.4%/75.7%/6.7%/97.7% and 58.8%/76.2%/10.9%/97.4%, respectively. Among hospitalized and ambulatory patients separately, the HA-VTE IMRS performed similarly. The HA-MB IMRS predictiveness for 90-day major bleeding yielded a c-statistic of 0.64. Conclusion: The HA-VTE IMRS and HA-MB IMRS predict 90- and 30-day VTE and major bleeding among COVID-19 patients. Adding D-dimer improved the predictiveness of the HA-VTE IMRS for VTE.

12.
J Osteopath Med ; 122(10): 521-529, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35802066

RESUMO

CONTEXT: The United States has witnessed a disproportionate rise in substance use disorders (SUD) and co-occurring mental health disorders, paired with housing instability, especially among racially minoritized communities. Traditional in-patient residential treatment programs for SUD have proven inconsistent in their effectiveness in preventing relapse and maintaining attrition among these patient populations. There is evidence showing that peer recovery programs led by individuals who have lived experience with SUD can increase social support and foster intrinsic motivation within participants to bolster their recovery. These peer recovery programs, when coupled with a standardized training program for peer recovery coaches, may be very efficacious at improving patient health outcomes, boosting performance on Substance Abuse and Mental Health Services Administration (SAMHSA) national outcome measures (NOMs), and helping participants build an overall better quality of life. OBJECTIVES: The goal of this study is to highlight the efficacy of a peer recovery program, the Minority Aids Initiative, in improving health outcomes and associated NOMs in men with SUD and/or co-occurring mental health disorder. METHODS: Participants received six months of peer recovery coaching from trained staff. Sessions were guided by the Manual for Recovery Coaching and focused on 10 different domains of recovery. Participants and coaches set long-term goals and created weekly action plans to work toward them. Standardized assessments (SAMHSA's Government Performance and Results Act [GPRA] tool, Addiction Severity Index [ASI]) were administered by recovery coaches at intake and at the 6-month time point to evaluate participant progress. Analyses of participant recovery were carried out according to SAMHSA's six NOMs and assessed the outcomes of the intervention and their significance. RESULTS: A total of 115 participants enrolled in the program over a 2-year period. Among them, 53 were eligible for 6-month follow-up interviews. In total, 321 sessions were held, with an average of three sessions per participant. Participants showed marked improvement across five of the six NOMs at the end of the 6-month course and across all ASI outcomes, with the exception of three in which participants reported an absence or few symptoms at intake. CONCLUSIONS: Our study shows that participants receive benefits across nearly all NOM categories when paired with recovery coaches who are well trained in medication-assisted treatment (MAT) and medications for opioid use disorder (MOUD) over a 6-month period. We see the following: a higher rate of abstinence; increased housing stability; lower health, behavioral, and social consequences; lower depression and anxiety; longer participant-recovery coach exposure time; and higher follow-up rates. We hope that our results can contribute to advancements and greater acceptance in the implementation of peer recovery coaching as well as an improvement in the lives of the communities affected by substance use.


Assuntos
Tutoria , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Qualidade de Vida , Tratamento Domiciliar , Transtornos Relacionados ao Uso de Substâncias/terapia , Resultado do Tratamento , Estados Unidos
14.
Int J Biometeorol ; 66(8): 1665-1681, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35759147

RESUMO

Recent studies have characterized individually experienced temperatures or individually experienced heat indices, including new exposure metrics that capture dimensions of exposure intensity, frequency, and duration. Yet, few studies have examined the personal thermal exposure in underrepresented groups, like outdoor workers, and even fewer have assessed corresponding changes in physiologic heat strain. The objective of this paper is to examine a cohort of occupationally exposed grounds and public safety workers (n = 25) to characterize their heat exposure and resulting heat strain. In addition, a secondary aim of this work is to compare individually heat index exposure (IHIE) across exposure metrics, fixed-site in situ weather stations, and raster-derived urban heat island (UHI) measurements in Charleston, SC, a humid coastal climate in the Southeastern USA. A Bland-Altman (BA) analysis was used to assess the level of agreement between the personal IHIE measurements and weather-station heat index (HI) and Urban Heat Island (UHI) measurements. Linear mixed-effect models were used to determine the association between individual risk factors and in situ weather station measurements significantly associated with IHIE measurements. Multivariable stepwise Cox proportional hazard modeling was used to identify the individual and workplace factors associated with time to heat strain in workers. We also examined the non-linear association between heat strain and exposure metrics using generalized additive models. We found significant heterogeneity in IHIE measurements across participants. We observed that time to heat strain was positively associated with a higher IHIE, older age, being male, and among Caucasian workers. Important nonlinear associations between heat strain occurrence and the intensity, frequency, and duration of personal heat metrics were observed. Lastly, our analysis found that IHIE measures were significantly similar for weather station HI, although differences were more pronounced for temperature and relative humidity measurements. Conversely, our IHIE findings were much lower than raster-derived UHI measurements. Real-time monitoring can offer important insights about unfolding temperature-health trends and emerging behaviors during thermal extreme events, which have significant potential to provide situational awareness.


Assuntos
Temperatura Alta , Tempo (Meteorologia) , Cidades , Clima , Feminino , Humanos , Masculino , Temperatura
15.
Blood Adv ; 6(6): 1661-1670, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-34662890

RESUMO

Thrombotic antiphospholipid syndrome (TAPS) is characterized by venous, arterial, or microvascular thrombosis. Patients with TAPS merit indefinite anticoagulation, and warfarin has historically been the standard treatment. Apixaban is an oral factor Xa inhibitor anticoagulant that requires no dose adjustment or monitoring. The efficacy and safety of apixaban compared with warfarin for TAPS patients remain unknown. This multicenter prospective randomized open-label blinded endpoint study assigned anticoagulated TAPS patients to apixaban or warfarin (target international normalized ratio 2-3) for 12 months. The primary efficacy outcome was clinically overt thrombosis and vascular death. Apixaban was first given at 2.5 mg twice daily. Two protocol changes were instituted based on recommendations from the data safety monitoring board. After the twenty-fifth patient was randomized, the apixaban dose was increased to 5 mg twice daily, and after the thirtieth patient was randomized, subjects with prior arterial thrombosis were excluded. Primary outcomes were adjudicated by independent experts blinded to treatment allocation. Patients randomized between 23 February 2015 and 7 March 2019 to apixaban (n = 23) or warfarin (n = 25) were similar. Among the components of the primary efficacy outcome, only stroke occurred in 6 of 23 patients randomized to apixaban compared with 0 of 25 patients randomized to warfarin. The study ended prematurely after the forty-eighth patient was enrolled. Conclusions from our study are limited due to protocol modifications and low patient accrual. Despite these limitations, our results suggest that apixaban may not be routinely substituted for warfarin to prevent recurrent thrombosis (especially strokes) among patients with TAPS. This trial was registered at www.clinicaltrials.gov as #NCT02295475.


Assuntos
Síndrome Antifosfolipídica , Acidente Vascular Cerebral , Trombose , Anticoagulantes/efeitos adversos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Humanos , Estudos Prospectivos , Pirazóis , Piridonas , Trombose/tratamento farmacológico , Trombose/etiologia , Trombose/prevenção & controle , Varfarina/efeitos adversos
16.
Pharmaceutics ; 13(11)2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34834231

RESUMO

Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. Here, we present the progress in the development of targeted liposomal nanocarriers designed for preferential collagen IV binding under simulated static vascular flow conditions. PEGylated liposomes (PLPs), previously established as effective delivery systems in vascular cells types, served as non-targeting controls. Collagen-targeting liposomes (CT-PLPs) were formed by conjugating established collagen-binding peptides to modified lipid heads via click chemistry (CTL), and inserting them at varying mol% either at the time of PLP assembly or via micellar transfer. All groups included fluorescently labeled lipid species for imaging and quantification. Liposomes were exposed to collagen IV matrices statically or via hemodynamic flow, and binding was measured via fluorometric analyses. CT-PLPs formed with 5 mol% CTL at the time of assembly demonstrated the highest binding affinity to collagen IV under static conditions, while maintaining a nanoparticle characterization profile of ~50 nm size and a homogeneity polydispersity index (PDI) of ~0.2 favorable for clinical translation. When liposomes were exposed to collagen matrices within a pressurized flow system, empirically defined CT-PLPs demonstrated significant binding at shear stresses mimetic of physiological through pathological conditions in both the venous and arterial architectures. Furthermore, when human saphenous vein explants were perfused with liposomes within a closed bioreactor system, CT-PLPs demonstrated significant ex vivo binding to diseased vascular tissue. Ongoing studies aim to further develop CT-PLPs for controlled targeting in a rodent model of vascular injury. The CT-PLP nanocarriers established here show promise as the framework for a spatially controlled delivery platform for future application in targeted vascular therapeutics.

17.
Chest ; (21)20210908.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1292258

RESUMO

This is the second update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Patients, Interventions, Comparators, Outcomes) questions, four of which have not been addressed previously. We generate strong and weak recommendations based on high, moderate, and low-certainty evidence, using GRADE methodology. The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of venous thromboembolism from initial management through secondary prevention and risk reduction of post-thrombotic syndrome. Four new guidance statements are added that did not appear in the 9th edition (2012) or first update (2016). Eight statements have been substantially modified from the first update. New evidence has emerged since 2016 which further informs the standard of care for patients with venous thromboembolism. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.


Assuntos
Humanos , Tromboembolia Venosa/tratamento farmacológico , Síndrome Pós-Trombótica/prevenção & controle , Antibacterianos/uso terapêutico
18.
Chest ; (21)20210908.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1292431

RESUMO

This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously. We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update. New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.


Assuntos
Humanos , Trombose Venosa/tratamento farmacológico , Síndrome Pós-Trombótica/prevenção & controle , Fibrinolíticos/uso terapêutico , Embolia Pulmonar/prevenção & controle
19.
Chest ; 160(6): e545-e608, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34352278

RESUMO

BACKGROUND: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously. METHODS: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. RESULTS: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update. CONCLUSION: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.


Assuntos
Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Anticoagulantes/administração & dosagem , Síndrome Antifosfolipídica/complicações , Quimioterapia Combinada , Medicina Baseada em Evidências , Fibrinolíticos/administração & dosagem , Humanos , Hipotensão/complicações , Neoplasias/complicações , Embolia Pulmonar/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagem
20.
Chest ; 160(6): 2247-2259, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34352279

RESUMO

BACKGROUND: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously. METHODS: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. RESULTS: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update. CONCLUSION: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.


Assuntos
Fibrinolíticos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica/métodos , Trombose Venosa/tratamento farmacológico , Quimioterapia Combinada , Medicina Baseada em Evidências , Fondaparinux/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Coeficiente Internacional Normatizado , Medição de Risco , Vitamina K/antagonistas & inibidores
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