Background
The CAVA (Ultrasound‐Accelerated Catheter‐Directed Thrombolysis Versus Anticoagulation for the Prevention of Post‐Thrombotic Syndrome) trial did not show a reduction of post‐thrombotic ...syndrome (PTS) after additional ultrasound‐accelerated catheter‐directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1‐year follow‐up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long‐term follow‐up.
Methods and Results
Patients aged 18 to 85 years with a first‐time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound‐accelerated catheter‐directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow‐up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow‐up of 39.0 months (interquartile range, 23.3–63.8), 120 patients (79.8%) participated in the final follow‐up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio OR, 0.54; 95% CI, 0.26 to 1.15
P
=0.11), with an absolute difference between groups of −14.2% (95% CI, −32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 46.8% versus 40 69.0%) (OR, 0.40; 95% CI, 0.19–0.84
P
=0.01) with an absolute difference between groups of −22.2% (95% CI, −39.8% to −2.8%). No new major bleedings occurred following the 12‐month follow‐up.
Conclusions
The impact of additional ultrasound‐accelerated catheter‐directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life.
Registration
URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00970619.
Early thrombus removal might prevent post-thrombotic syndrome by preserving venous function and restoring flow. Previous trials comparing additional catheter-directed thrombolysis to standard ...treatment showed conflicting outcomes. We aimed to assess the benefit of additional ultrasound-accelerated catheter-directed thrombolysis for the prevention of post-thrombotic syndrome compared with standard therapy in patients with iliofemoral deep-vein thrombosis.
We did a multicentre, randomised, single-blind, allocation-concealed, parallel group, superiority trial in 15 hospitals in the Netherlands. Patients aged 18-85 years with a first-time acute iliofemoral deep-vein thrombosis and symptoms for no more than 14 days were randomly assigned (1:1) to either standard treatment with additional ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. Randomisation was done with a web-based automatic programme and a random varying block size (2-12), stratified by age and centre. Standard treatment included anticoagulant therapy, compression therapy (knee-high elastic compression stockings; 30-40 mmHg), and early ambulation. Additional ultrasound-accelerated catheter-directed thrombolysis was done with urokinase with a starting bolus of 250 000 international units (IU) in 10 mL NaCl followed by a continuous dose of 100 000 IU/h for a maximum of 96 h through the Ekos Endowave-system. Adjunctive percutaneous transluminal angioplasty, thrombosuction, or stenting was performed at the discretion of the physician who performed the intervention. The primary outcome was the proportion of patients with post-thrombotic syndrome at 12 months diagnosed according to the original Villalta criteria-a Villalta-score of at least 5 on two consecutive occasions at least 3 months apart or the occurrence of venous ulceration-and was assessed in a modified intention-to-treat population of all randomly assigned patients who passed screening and started treatment. The safety analysis was assessed in the same modified intention-to-treat population. This study is complete and is registered at ClinicalTrials.gov, NCT00970619.
Between May 28, 2010, and Sept 18, 2017, 184 patients were randomly assigned to either additional ultrasound-accelerated catheter-directed thrombolysis (n=91) or standard treatment alone (n=93). Exclusion because of screening failure or early withdrawal of informed consent resulted in 77 patients in the intervention group and 75 in the standard treatment group starting allocated treatment. Median follow-up was 12·0 months (IQR 6·0-12·0). 12-month post-thrombotic syndrome occurred in 22 (29%) patients allocated to additional treatment versus 26 (35%) patients receiving standard treatment alone (odds ratio 0·75 95% CI 0·38 to 1·50; p=0·42). Major bleeding occurred in four (5%) patients in the intervention group, with associated neuropraxia or the peroneal nerve in one patient, and no events in the standard treatment group. No serious adverse events occurred. None of the four deaths (one 1% in the intervention group vs three 4% in the standard treatment group) were treatment related.
This study showed that additional ultrasound-accelerated catheter-directed thrombolysis does not change the risk of post-thrombotic syndrome 1 year after acute iliofemoral deep-vein thrombosis compared with standard therapy alone. Although this trial is inconclusive, the outcome suggests the possibility of a moderate beneficial effect with additional ultrasound-accelerated catheter-directed thrombolysis. Further research is therefore warranted to better understand this outcome in the context of previous trials, preferably by combining the available evidence in an individual patient data meta-analysis.
The Netherlands Organisation for Health Research and Development (ZonMw), Maastricht University Medical Centre, BTG-Interventional Medicine.
Background
Carotid intima-media thickness (CIMT) is increasingly used as a prognostic indicator for early atherosclerosis and the development of cardiovascular disease. The objective of this study is ...to assess the exact effects of bariatric surgery on CIMT reduction in different age groups.
Methods
CIMT was measured just proximal to the bifurcation of the carotid artery in 166 patients with mean body mass index of 43.4 kg/m
2
before and at 6 and 12 months after bariatric surgery. Preoperative CIMT and Framingham Risk Score (FRS) were compared to measurements at 6 and 12 months, postoperatively. Impact of age on CIMT change and cardiovascular risk reduction was analyzed.
Results
Median follow-up was 12 months; 12% were lost to follow-up. Mean CIMT values at 12 months after bariatric surgery were significantly lower compared to baseline (0.619 vs. 0.587 mm,
p
= 0.005 in women and 0.675 vs. 0.622 mm,
p
= 0.037 in men, respectively), and these effects were statistically significant in all age groups. The mean reduction of CIMT for patients < 50 years at 12 months was 0.043 mm (− 7.0%), while CIMT was reduced with 0.013 mm for patients ≥ 50 years (− 1.9%,
p
= 0.022). At 12 months after bariatric surgery, FRS had decreased with 52% in patients < 50 years as compared with 35% in patients ≥ 50 years (
p
= 0.025).
Conclusions
Bariatric surgery resulted in a significant CIMT decrease in patients with morbid obesity in all evaluated age categories. These beneficial effects of bariatric surgery were more pronounced in younger patients, while cardiovascular risk reduction by bariatric surgery appeared inferior in patients of 50 years and older.
Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function.
To ...evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI).
Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013.
Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months.
The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure.
At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range IQR, 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L IQR, 70-87 µmol/L vs 79 µmol/L IQR, 72-89 µmol/L, P = .61) and glycated hemoglobin (5.9% IQR, 5.6%-6.1% vs 5.9% IQR, 5.7%-6.1%, P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed.
Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting.
clinicaltrials.gov Identifier: NCT01217307.
To assess anterolateral complex (ALC) injuries in patients with acute anterior cruciate ligament (ACL) rupture on magnetic resonance imaging (MRI).
Patients with acute ACL rupture who underwent ACL ...surgery between 2015 and 2017 and underwent MRI within 6 weeks of the initial trauma were included. Two radiologists assessed magnetic resonance images retrospectively for the status of the ALC, including the iliotibial band (ITB), Kaplan fibers, and anterolateral ligament (ALL), as follows: grade 0, normal; grade 1, periligamentous edema; grade 2, partial tear; and grade 3, complete tear. The findings were analyzed using the Friedman test and weighted κ values.
Sixty-nine MRI scans were reviewed. Of the 69 patients, 51% had associated injuries to the ITB (grade 1, n = 31; grade 2, n = 4), 33% had associated injuries to the Kaplan fibers (grade 1, n = 21; grade 2, n = 2), and 57% had associated injuries to the ALL (grade 1, n = 12; grade 2, n = 22; grade 3, n = 5). We found a significant difference in the frequency and grading between ITB, Kaplan fiber, and ALL injuries (P ≤ .032). Inter-reader agreement for assessing the ALC on MRI was almost perfect (κ ≥ 0.922).
On the basis of MRI analysis, ALL injuries were found with varying degrees of severity and intensity with noted injuries to associated surrounding fibers in patients with acute ACL rupture.
Level IV, case series.
Purpose:
Lifelong follow-up after endovascular abdominal aortic aneurysm repair (EVAR) is recommended due to a continued risk of complications, especially if the first postoperative imaging shows ...abnormal findings. We studied the long-term outcomes in patients with abnormalities on the first postoperative computed tomography angiography (CTA) following EVAR.
Materials and Methods:
This is a retrospective study of all consecutive patients who underwent elective EVAR for nonruptured abdominal aortic aneurysm (AAA) between January 2007 and January 2012 in 16 Dutch hospitals with follow-up until December 2018. Patients were included if the first postoperative CTA showed one of the following abnormal findings: endoleak type I–IV, endograft kinking, infection, or limb occlusion. AAA diameter, complications, and secondary interventions during follow-up were registered. Primary endpoint was overall survival, and other endpoints were secondary interventions and intervention-free survival. Kaplan-Meier analyses were used to estimate overall and intervention-free survival. Cox regression analyses were used to identify the association of independent determinants with survival and secondary interventions.
Results:
A total of 502 patients had abnormal findings on the first postoperative CTA after EVAR and had a median follow-up (interquartile range IQR) of 83.0 months (59.0). The estimated overall survival rate at 1, 5, and 10 years was 84.7%, 51.0%, and 30.8%, respectively. Age hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.05 to 1.10 and American Society of Anesthesiologists (ASA) classification (ASA IV HR 3.20, 95% CI 1.99 to 5.15) were significantly associated with all-cause mortality. Overall, 167 of the 502 patients (33.3%) underwent 238 secondary interventions in total. Fifty-eight patients (12%) underwent an intervention based on a finding on the first postoperative CTA. Overall survival was 38.4% for patients with secondary interventions and 44.5% for patients without (log rank; p=0.166). The intervention-free survival rate at 1, 5, and 10 years was 82.9%, 61.3%, and 45.6%, respectively.
Conclusions:
Patients with abnormalities on the first postoperative CTA after elective EVAR for infrarenal AAA cannot be discharged from regular imaging follow-up due to a high risk of secondary interventions. Patients who had a secondary intervention had similar overall survival as those without secondary interventions.
•Impact of morbidity on quality of life (QOL) of cancer survivors depends on severity and persistence.•Prospective data from EMBRACE-I allowed to assess the association for cervical cancer ...survivors.•All persistent symptoms were significantly associated with QOL aspects, but with different magnitude.•Role functioning and global health/general QOL were the most impaired aspects reported by patients.•Persistent pain and fatigue were more detrimental compared to other organ-related symptoms.
To quantify the association of persistent morbidity with different aspects of quality of life (QOL) in locally advanced cervical cancer (LACC) survivors.
Longitudinal outcome from the EMBRACE-I study was evaluated. Patient-reported symptoms and QOL were prospectively scored (EORTC-C30/CX24) at baseline and regular follow-ups. Physician-assessed symptoms were also reported (CTCAEv.3). Persistent symptoms were defined if present in at least half of the follow-ups. QOL items were linearly transformed into a continuous scale. Linear mixed-effects models (LMM) were applied to evaluate and quantify the association of persistent symptoms with QOL. Overall QOL deterioration was evaluated by calculating the integral difference in QOL over time obtained with LMM for patients without and with persistent symptoms.
Out of 1416 patients enrolled, 741 with baseline and ≥ 3 late follow-ups were analyzed (median 59 months). Proportions of persistent EORTC symptoms ranged from 21.8 % to 64.9 % (bowel control and tiredness). For CTCAE the range was 11.3–28.6 % (limb edema and fatigue). Presence of any persistent symptom was associated with QOL, although with varying magnitude. Role functioning and Global health/QOL were the most impaired aspects. Fatigue and pain showed large differences, with reductions of around 20 % for most of the QOL aspects. Among organ-related symptoms, abdominal cramps showed the largest effect.
Persistent symptoms are associated with QOL reductions in LACC survivors. Organ-related symptoms showed smaller differences than general symptoms such as fatigue and pain. In addition to optimizing treatment to minimize organ-related morbidity, effort should be directed towards a more comprehensive and targeted morbidity management.
Purpose What is the level of knowledge of pharmacists concerning pain management and the use of opioids at the end of life, and how do they cooperate with physicians? Methods A written questionnaire ...was sent to a sample of community and hospital pharmacists in the Netherlands. The questionnaire was completed by 182 pharmacists (response rate 45%). Results Pharmacists were aware of the most basic knowledge about opioids. Among the respondents, 29% erroneously thought that life-threatening respiratory depression was a danger with pain control, and 38% erroneously believed that opioids were the preferred drug for palliative sedation. One in three responding pharmacists did not think his/her theoretical knowledge was sufficient to provide advice on pain control. Most pharmacists had working agreements with physicians on euthanasia (81%), but fewer had working agreements on palliative sedation (46%) or opioid therapy (25%). Based on the experience of most of responding pharmacists (93%), physicians were open to unsolicited advice on opioid prescriptions. The majority of community pharmacists (94%) checked opioid prescriptions most often only after dispensing, while it was not a common practice among the majority of hospital pharmacists (68%) to check prescriptions at all. Conclusions Although the basic knowledge of most pharmacists was adequate, based on the responses to the questionnaire, there seems to be a lack of knowledge in several areas, which may hamper pharmacists in improving the quality of care when giving advice to physicians and preventing or correcting mistakes if necessary. If education is improved, a more active role of the pharmacist may improve the quality of end-of-life pharmacotherapy.
Primary repair of the anterior cruciate ligament (ACL) is being performed increasingly in the treatment of acute proximal ACL ruptures. Advantages of ACL repair over surgical reconstruction with a ...tendon graft include preservation of the anatomy and proprioceptive function of the native ACL, and therefore, faster rehabilitation. The addition of an internal brace protects the repair during ACL healing and can increase the success rate of the procedure. Given this evolution of ACL surgical treatment, radiologists should be familiar with the new repair techniques and their appearances on postoperative imaging. In this article, we describe two different surgical techniques for primary ACL repair, dynamic intraligamentary stabilisation and internal brace ligament augmentation, and provide an overview of the normal and abnormal appearances after this type of repair at magnetic resonance imaging (MRI) follow-up.
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