Effectiveness of placebo interventions for patients with nonspecific low back pain: a systematic review and meta-analysis.

ABSTRACT: Little is known about the effectiveness of placebo interventions in patients with nonspecific low back pain (LBP). This systematic review assessed the magnitude of the effects of placebo interventions as compared to no intervention in randomized controlled trials (RCTs) including patients with LBP. Embase, MEDLINE (Ovid), and Cochrane CENTRAL databases were searched from inception to December 5, 2019. Randomized controlled trials comparing placebo intervention vs no intervention in adult patients with nonspecific LBP were included. Pain intensity, physical functioning, and health-related quality of life measured at short-term, medium-term, and long-term follow-up were the outcomes of this review. Twenty-one randomized controlled trials were included; one concerning acute LBP and one subacute LBP, whereas 19 studies reported on chronic LBP. In chronic LBP, placebo interventions were more effective than no intervention at short-term follow-up for pain intensity (standardized mean difference = -0.37, 95% confidence interval [CI] = -0.55 to -0.18, moderate-quality evidence), physical functioning (standardized mean difference -0.19, 95% CI = -0.39-0.01, moderate-quality evidence), and physical quality of life (mean difference = -2.71, 95% CI = -4.71-0.71, high-quality evidence), respectively. These effects were not significant at medium-term follow-up, and no data were available at long-term follow-up. These results show placebo interventions are more effective than no intervention at short-term follow-up in patients with chronic LBP. However, the magnitude of the effects is probably not clinically relevant (approximately 8 points on a 0-100 pain scale). Future research should identify effect modifiers and causal mechanisms explaining the short-term effects of placebo interventions in patients with chronic LBP.

Prevalence of venous obstructions in (recurrent) venous thromboembolism: a case-control study.

BACKGROUND: The role of venous obstructions as a risk factor for recurrent venous thromboembolism has never been evaluated. This study aimed to determine whether there is a difference in prevalence of venous obstructions between patients with and without recurrent venous thromboembolism. Furthermore, its influence on the development of post-thrombotic syndrome and patient-reported quality of life was assessed. METHODS: This matched nested case-control study included 32 patients with recurrent venous thromboembolism (26 recurrent deep-vein thrombosis and 6 pulmonary embolism) from an existing prospective cohort of deep-vein thrombosis patients and compared them to 24 age and sex matched deep-vein thrombosis patients without recurrent venous thromboembolism. All participants received standard post-thrombotic management and underwent an additional extensive duplex ultrasonography. Post-thrombotic syndrome was assessed by the Villalta-scale and quality of life was measured using the SF36v2 and VEINES-QOL/Sym-questionnaires. RESULTS: Venous obstruction was found in 6 patients (18.8%) with recurrent venous thromboembolism compared to 5 patients (20.8%) without recurrent venous thromboembolism (Odds ratio 0.88, 95%CI 0.23-3.30, p = 1.000). After a median follow-up of 60.0 months (IQR 41.3-103.5) the mean Villalta-score was 5.55 ± 3.02 versus 5.26 ± 2.63 (p = 0.909) and post-thrombotic syndrome developed in 20 (62.5%) versus 14 (58.3%) patients, respectively (Odds ratio 1.19, 95%CI 0.40-3.51, p = 0.752). If venous obstruction was present, it was mainly located in the common iliac vein (n = 7, 63.6%). In patients with an objectified venous obstruction the mean Villalta-score was 5.11 ± 2.80 versus 5.49 ± 2.87 in patients without venous obstruction (p = 0.639). Post-thrombotic syndrome developed in 6 (54.5%) versus 28 (62.2%) patients, respectively (Odds ratio 1.37, 95%CI 0.36-5.20, p = 0.736). No significant differences were seen regarding patient-reported quality of life between either groups. CONCLUSIONS: In this exploratory case-control study patients with recurrent venous thromboembolism did not have a higher prevalence of venous obstruction compared to patients without recurrent venous thromboembolism. The presence of recurrent venous thromboembolism or venous obstruction had no impact on the development of post-thrombotic syndrome or the patient-reported quality of life.

Ultrasound-accelerated catheter-directed thrombolysis versus anticoagulation for the prevention of post-thrombotic syndrome (CAVA): a single-blind, multicentre, randomised trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: The Netherlands Organisation for Health Research and Development (ZonMw), Maastricht University Medical Centre, BTG-Interventional Medicine.

The value of hemodynamic measurements by air plethysmography in diagnosing venous obstruction of the lower limb.

OBJECTIVE: Air plethysmography (APG) is a functional, noninvasive test that can assess volumetric changes in the lower limb and might therefore be used as a diagnostic tool in chronic deep venous disease. However, use of APG in chronic deep venous obstructive disease remains debatable. This study assessed the clinical value of APG in identifying chronic deep venous obstruction. METHODS: All patients referred to our tertiary, outpatient clinic between January 2011 and August 2013 with chronic venous complaints and suspected outflow obstruction underwent an outflow fraction (OF), ejection fraction (EF), and residual volume fraction (RVF) test using APG. Duplex ultrasound and magnetic resonance venography were used to establish whether and where obstruction was present. Diagnostic values of these tests were assessed for obstructions at different levels of the deep venous system. RESULTS: A total of 312 limbs in 248 patients were tested. Mean age was 45.5 ± 14.0 years, and 62.5% were female. In post-thrombotic disease, specificity and positive predictive value for OF were as high as 98.4% and 95.0%, respectively; however, sensitivity was 34.8% and negative predictive value was 29.6%, with no clinically relevant positive or negative likelihood ratios. No clinically relevant differences were observed in stratifying for level of obstruction. EF and RVF were as inconclusive. Neither could these parameters be used in diagnosing nonthrombotic iliac vein compression. CONCLUSIONS: We found a poor correlation between OF, EF, or RVF, determined by APG, and the presence of chronic deep venous obstruction. Therefore, use of its relative parameters is unwarranted in daily clinical practice.

Ultrasound-accelerated catheter-directed thrombolysis in acute iliofemoral deep venous thrombosis.

BACKGROUND: Iliofemoral deep venous thrombosis (DVT) is associated with a high incidence of the post-thrombotic syndrome. The current CHEST guidelines suggest that catheter-directed thrombolysis can be used for patients with acute iliofemoral DVT and severe leg complaints. Current literature shows that catheter-directed thrombolysis increases patency of the affected tract and may reduce post-thrombotic complications, but treatment time and bleeding complications are high. Ultrasound-accelerated catheter-directed thrombolysis (UACDT) uses ultrasound waves to enhance clot lysis, which should lower treatment time and bleeding complications with the same or higher patency rates. We report our clinical experience with UACDT on patency and complications in patients with acute iliofemoral DVT. METHODS: Patients treated with UACDT for acute iliofemoral DVT were included in our analyses. Diagnosis of iliofemoral DVT was confirmed using duplex sonography and magnetic resonance venography. In addition to thrombolysis, stents were placed or an arteriovenous fistula was created to ensure patency of the treated vein, if indicated. The main outcome is patency after 1 year. Secondary outcome measures are treatment time, bleeding complications, and pulmonary embolism. Patency was assessed using duplex sonography. RESULTS: In total, 37 patients (average age at intervention, 42 years; range, 5-76 years) were included. The DVT location was unilateral in 33 patients (20 left side, 13 right side), and four were bilateral. The average treatment time was 43 ±17 hours. The success rate of thrombolysis was 95% (n = 35); re-thrombosis occurred in 11 (30%) patients. Major bleeding occurred in one patient (3%), and three minor bleedings occurred at the insertion side of the catheter (8%). One pulmonary embolism was encountered (3%). One patient had fever with positive blood cultures for Staphylococcus aureus. Additional procedures were required in 54% (n = 20) of patients. Primary patency was 70% at 1 year; secondary patency was 87% after 1-year follow up. CONCLUSIONS: UACDT of acute iliofemoral DVT is feasible and safe. Supplementary percutaneous transluminal angioplasty and stenting play an important role in preventing re-thrombosis.

[Catheter-directed thrombolysis in iliofemoral deep-vein thrombosis]. / Kathetergeleide trombolyse bij iliofemorale diepveneuze trombose.

Despite optimal treatment of acute deep-vein thrombosis (DVT) there is a great chance of recurrent DVT and development of post-thrombotic syndrome (PTS) in the long term. The degree of spontaneous recanalization differs per patient and per thrombus location. 90% of all femoropopliteal occlusions will fully recanalize within 1 year; however, in the case of an iliofemoral thrombosis, recanalization occurs only in a minority of cases. Post-thrombotic complications occur more often following iliofemoral thrombosis, and the chance of recurrent thrombosis is greater than following thrombosis in a more distal location. An anatomical variation or abnormality also more often underlies an iliofemoral thrombosis. It is important to identify patients with a greater chance of developing PTS promptly and to treat them in order to prevent post-thrombotic damage. There are still insufficient trial data available to implement catheter-directed thrombolysis as standard therapy for iliofemoral thrombosis