The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with ...apixaban would be safe and more effective than short-term prophylaxis with enoxaparin.
In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated.
A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome--2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval CI, 0.62 to 1.23; P=0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P=0.04).
In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparin. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00457002.).
Venous thromboembolism (VTE) is responsible for the hospitalization of >250 000 Americans annually and represents a significant risk for morbidity and mortality. Despite the publication of ...evidence-based clinical practice guidelines to aid in the management of VTE in its acute and chronic forms, the clinician is frequently confronted with manifestations of VTE for which data are sparse and optimal management is unclear. In particular, the optimal use of advanced therapies for acute VTE, including thrombolysis and catheter-based therapies, remains uncertain. This report addresses the management of massive and submassive pulmonary embolism (PE), iliofemoral deep vein thrombosis (IFDVT),and chronic thromboembolic pulmonary hypertension (CTEPH). The goal is to provide practical advice to enable the busy clinician to optimize the management of patients with these severe manifestations of VTE. Although this document makes recommendations for management, optimal medical decisions must incorporate other factors, including patient wishes, quality of life, and life expectancy based on age and comorbidities. The appropriateness of these recommendations for a specific patient may vary depending on these factors and will be best judged by the bedside clinician.
The efficacy and safety of thrombolysis in patients with cancer with pulmonary embolism is uncertain. Therefore we studied the effects of thrombolysis in 57 patients with cancer and 254 patients ...without cancer who were treated in five clinical trials with tissue plasminogen activator or urokinase for pulmonary embolism. Immediately after thrombolysis, the proportion of patients with and without cancer who improved on follow-up angiography (77% vs 73%;
p = 0.65) was similar. The angiographic reduction in clot burden (1.83 ± 0.27 vs 1.38 ± 0.13;
p = 0.13) was somewhat greater in patients with cancer than in patients without cancer. Twenty-four hours after initiation of thrombolytic therapy, the proportion of patients who improved on follow-up perfusion scan continued to be similar (72% vs 78%;
p = 0.40). However, the extent of reperfusion at 24 hours was less in patients with cancer than in patients without cancer (6% vs 13% reperfusion of lung tissue;
p = 0.007). These data suggest that patients with cancer should receive effective anticoagulation in the upper portion of the therapeutic range immediately after thrombolysis. It is possible that such a strategy might preserve initial improvement from thrombolysis and prevent attenuation of benefit during the ensuing 24 hours. (Am Heart J 1997;134:603-7.)
Background Atrial fibrillation (AF) is associated with high rates of morbidity and mortality. Patients with AF carry a fivefold increased risk of stroke and the risk of death from AF-related stroke ...is doubled. Current management is often inadequate, leaving patients at risk for a potentially fatal or disabling event. The purpose of the GARFIELD registry is to evaluate the management and outcomes of patients with newly diagnosed non-valvular AF at risk for stroke. Design The GARFIELD registry is an observational, multicenter, prospective study of patients with newly diagnosed AF and one or more additional risk factors for stroke. The aim is to enroll 55,000 patients at >1,000 centers in 50 countries. Enrollment will take place in five independent, sequential, prospective cohorts. An additional retrospective validation cohort of 5,000 patients with established AF and at least one additional risk factor for stroke will be conducted in parallel with cohort one. The study started in December 2009, with a planned recruitment period of 4 years and a minimum of 2-year follow-up for each patient. Summary The GARFIELD registry will provide valuable insights into the clinical management and related outcomes of AF patients throughout many regions of the world and across the spectrum of healthcare systems. By capturing data from unselected patients treated in everyday practice, the registry has the potential to identify best practices as well as deficiencies in available treatment options for specific patient populations and to describe how therapeutic strategies, patient care, and outcomes will evolve over time.
This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic ...Endovascular System (EKOS, Bothell, Washington).
Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%.
Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation.
Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage.
Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) SEATTLE II; NCT01513759).
The Surgeon Generals Call to Action to Prevent Deep Vein Thrombosis and Pubnonamy Embolism estimates that more than 100000 deaths occur annually from pulmonary embolism in the US alone. Many of these ...deaths are preventable by prescribing proved prophylactic measures during hospitalization. In addition, venous thromboembolism and its complications place a substantial burden on the US health care system. The sequelae of deep vein thrombosis and pulmonary embolism--post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension--respectively, are sources of morbidity, diminished quality of life, and loss in functional status. Patient safety has taken center stage in the discussion of one's nation's health care system. Medicare's most recent strategy to reduce medical errors is to withhold payment to hospitals for treatment of serious preventable illnesses or complications termed "never events." The President's Fiscal Year 2009 Budget outlined this approach. This legislation prohibits hospitals from billing for these events. The legislation also requires that hospitals report occurrence of these "never events." Here, Goldhaber and Piazza explore the merits and implications of classifying venous thromboembolism after total knee of hip replacement as "never event."
Tuberculosis can be treated, prevented, and cured. Rapid, sustained declines in tuberculosis deaths in many countries during the past 50 years provide compelling evidence that ending the pandemic is ...feasible. Yet this disease—which has plagued humanity since before recorded history and has killed hundreds of millions of people over the past two centuries—remains a relentless scourge. In 2017, 1·6 million people died from tuberculosis, including 300 000 people with HIV, representing more deaths than any other infectious disease. Moreover, in many parts of the world, drugresistant forms of tuberculosis threaten struggling control efforts. The world can no longer ignore the enormous pall cast by the tuberculosis epidemic. Going forward, the global tuberculosis response must be an inclusive, comprehensive response within the broader sustainable development agenda. No one-size-fits-all approach can succeed.
Opioid use disorder (OUD) is a significant cause of morbidity and mortality in the US, yet many individuals with OUD do not receive treatment.
To assess the cost-effectiveness of OUD treatments and ...association of these treatments with outcomes in the US.
This model-based cost-effectiveness analysis included a US population with OUD.
Medication-assisted treatment (MAT) with buprenorphine, methadone, or injectable extended-release naltrexone; psychotherapy (beyond standard counseling); overdose education and naloxone distribution (OEND); and contingency management (CM).
Fatal and nonfatal overdoses and deaths throughout 5 years, discounted lifetime quality-adjusted life-years (QALYs), and costs.
In the base case, in the absence of treatment, 42 717 overdoses (4132 fatal, 38 585 nonfatal) and 12 660 deaths were estimated to occur in a cohort of 100 000 patients over 5 years, and 11.58 discounted lifetime QALYs were estimated to be experienced per person. An estimated reduction in overdoses was associated with MAT with methadone (10.7%), MAT with buprenorphine or naltrexone (22.0%), and when combined with CM and psychotherapy (range, 21.0%-31.4%). Estimated deceased deaths were associated with MAT with methadone (6%), MAT with buprenorphine or naltrexone (13.9%), and when combined with CM, OEND, and psychotherapy (16.9%). MAT yielded discounted gains of 1.02 to 1.07 QALYs per person. Including only health care sector costs, methadone cost $16 000/QALY gained compared with no treatment, followed by methadone with OEND ($22 000/QALY gained), then by buprenorphine with OEND and CM ($42 000/QALY gained), and then by buprenorphine with OEND, CM, and psychotherapy ($250 000/QALY gained). MAT with naltrexone was dominated by other treatment alternatives. When criminal justice costs were included, all forms of MAT (with buprenorphine, methadone, and naltrexone) were associated with cost savings compared with no treatment, yielding savings of $25 000 to $105 000 in lifetime costs per person. The largest cost savings were associated with methadone plus CM. Results were qualitatively unchanged over a wide range of sensitivity analyses. An analysis using demographic and cost data for Veterans Health Administration patients yielded similar findings.
In this cost-effectiveness analysis, expanded access to MAT, combined with OEND and CM, was associated with cost-saving reductions in morbidity and mortality from OUD. Lack of widespread MAT availability limits access to a cost-saving medical intervention that reduces morbidity and mortality from OUD. Opioid overdoses in the US likely reached a record high in 2020 because of COVID-19 increasing substance use, exacerbating stress and social isolation, and interfering with opioid treatment. It is essential to understand the cost-effectiveness of alternative forms of MAT to treat OUD.
Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy (DMD), affecting the heart as well as skeletal muscle. Here, we report that clinical-stage ...cardiac progenitor cells, known as cardiosphere-derived cells (CDCs), improve cardiac and skeletal myopathy in the mdx mouse model of DMD. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity, and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs in mdx mice and in human induced pluripotent stem cell-derived Duchenne cardiomyocytes. Surprisingly, CDCs and their exosomes also transiently restored partial expression of full-length dystrophin in mdx mice. The findings further motivate the testing of CDCs in Duchenne patients, while identifying exosomes as next-generation therapeutic candidates.
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•CDCs improve cardiac and skeletal myopathy in the mdx mouse model of DMD•CDC exosomes reproduce the benefits of CDCs•CDCs and their exosomes transiently restored partial expression of dystrophin
In this article, Marbán and colleagues show that exosomes mediate benefits of cell therapy in mouse and human models of Duchenne muscular dystrophy.
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