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Study Design: Randomized controlled trial.Objective: To evaluate the efficacy of adjunctive topical tranexamic acid (tTXA) in reducing postoperative blood loss and packed red cell (PRC) transfusion in patients who underwent palliative decompressive spinal metastasis surgery for malignant epidural spinal cord compression.Summary Of Background Data: Palliative decompressive spinal metastasis surgery is associated with massive postoperative blood loss and increased transfusion rate. tTXA reduces blood loss in traumatic or degenerative spinal surgery; however, the role of topical TXA in decompressive spinal metastasis surgery remains controversial.Method: A total of 65 patients who underwent palliative decompressive thoracolumbar spinal metastasis surgery were included in this study. In 33 patients, 1 g of tTXA (20 mL) was soaked in an absorbable gelatin sponge and placed lateral to the decompressive site. The remaining 32 patients in the control group received the same procedures with normal saline at the same volume, instead of TXA. All of the patients received standard 1 g intravenous TXA, just before initiating the operation. The primary outcome was postoperative blood loss, and the secondary outcomes were postoperative PRC transfusion and complications.Results: No differences were found in postoperative blood loss between tTXA and placebo group (P50 778 mL [IQR 347, 1,122 mL] versus P50 490 mL [IQR 295, 920 mL]; P = 0.238). The number of patients requiring postoperative PRC transfusion were quite similar in tTXA and placebo groups (PRC transfusion in 15 patients [45.45%] versus 16 patients [50%]; P = 0.585). No complications related to TXA and absorbable gelatin sponge were observed.Conclusion: We do not recommend tTXA as an adjunctive treatment for patients undergoing decompressive spinal metastasis surgery since it does not provide additional benefit to prophylactic intravenous TXA in postoperative blood loss and transfusion rate.Level of Evidence: 2. [ABSTRACT FROM AUTHOR]

Abstract: Chronic low back pain can be caused by impaired control and degeneration of the multifidus muscles and consequent functional instability of the lumbar spine. Available treatment options have limited effectiveness and prognosis is unfavorable. We conducted an international randomized, double-blind, sham-controlled trial at 26 multidisciplinary centers to determine safety and efficacy of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms (clinicaltrials.gov identifier: NCT02577354). Two hundred four eligible participants with refractory mechanical (musculoskeletal) chronic LBP and a positive prone instability test indicating impaired multifidus control were implanted and randomized to therapeutic (N = 102) or low-level sham (N = 102) stimulation of the medial branch of the dorsal ramus nerve (multifidus nerve supply) for 30 minutes twice daily. The primary endpoint was the comparison of responder proportions (≥30% relief on the LBP visual analogue scale without analgesics increase) at 120 days. After the primary endpoint assessment, participants in the sham-control group switched to therapeutic stimulation and the combined cohort was assessed through 1 year for long-term outcomes and adverse events. The primary endpoint was inconclusive in terms of treatment superiority (57.1% vs 46.6%; difference: 10.4%; 95% confidence interval, -3.3% to 24.1%, P = 0.138). Prespecified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related adverse events (3.9%) compared favorably with other neuromodulation therapies for chronic pain. [ABSTRACT FROM AUTHOR]

Background: Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody-coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population.Methods: The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021.Results: A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; P (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26-2.41]; P=0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37-3.61]; P=0.0012).Conclusions: The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03216733. [ABSTRACT FROM AUTHOR]

Background: Regulators are evaluating the use of noninterventional real-world evidence (RWE) studies to assess the effectiveness of medical products. The RCT DUPLICATE initiative (Randomized, Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology) uses a structured process to design RWE studies emulating randomized, controlled trials (RCTs) and compare results. We report findings of the first 10 trial emulations, evaluating cardiovascular outcomes of antidiabetic or antiplatelet medications.Methods: We selected 3 active-controlled and 7 placebo-controlled RCTs for replication. Using patient-level claims data from US commercial and Medicare payers, we implemented inclusion and exclusion criteria, selected primary end points, and comparator populations to emulate those of each corresponding RCT. Within the trial-mimicking populations, we conducted propensity score matching to control for >120 preexposure confounders. All study measures were prospectively defined and protocols registered before hazard ratios and 95% CIs were computed. Success criteria for the primary analysis were prespecified for each replication.Results: Despite attempts to emulate RCT design as closely as possible, differences between the RCT and corresponding RWE study populations remained. The regulatory conclusions were equivalent in 6 of 10. The RWE emulations achieved a hazard ratio estimate that was within the 95% CI from the corresponding RCT in 8 of 10 studies. In 9 of 10, either the regulatory or estimate agreement success criteria were fulfilled. The largest differences in effect estimates were found for RCTs where second-generation sulfonylureas were used as a proxy for placebo regarding cardiovascular effects. Nine of 10 replications had a standardized difference between effect estimates of <2, which suggests differences within expected random variation.Conclusions: Agreement between RCT and RWE findings varies depending on which agreement metric is used. Interim findings indicate that selection of active comparator therapies with similar indications and use patterns enhances the validity of RWE. Even in the context of active comparators, concordance between RCT and RWE findings is not guaranteed, partially because trials are not emulated exactly. More trial emulations are needed to understand how often and in what contexts RWE findings match RCTs. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03936049, NCT04215523, NCT04215536, NCT03936010, NCT03936036, NCT03936062, NCT03936023, NCT03648424, NCT04237935, NCT04237922. [ABSTRACT FROM AUTHOR]

Objectives: There is little evidence to guide fluid administration to patients admitted to the ICU following cardiac surgery. This study aimed to determine if a protocolized strategy known to reduce fluid administration when compared with usual care reduced ICU length of stay following cardiac surgery.Design: Prospective, multicenter, parallel-group, randomized clinical trial.Setting: Five cardiac surgical centers in New Zealand conducted from November 2016 to December 2018 with final follow-up completed in July 2019.Patients: Seven-hundred fifteen patients undergoing cardiac surgery; 358 intervention and 357 usual care.Interventions: Randomization to protocol-guided strategy utilizing stroke volume variation to guide administration of bolus fluid or usual care fluid administration until desedation or up to 24 hours. Primary outcome was length of stay in ICU. Organ dysfunction, mortality, process of care measures, patient-reported quality of life, and disability-free survival were collected up to day 180.Measurements and Main Results: Overall 666 of 715 (93.1%) received at least one fluid bolus. Patients in the intervention group received less bolus fluid (median [interquartile range], 1,000 mL [250-2,000 mL] vs 1,500 mL [500-2,500 mL]; p < 0.0001) and had a lower overall fluid balance (median [interquartile range], 319 mL [-284 to 1,274 mL] vs 673 mL [38-1,641 mL]; p < 0.0001) in the intervention period. There was no difference in ICU length of stay between the two groups (27.9 hr [21.8-53.5 hr] vs 25.6 hr [21.9-64.6 hr]; p = 0.95). There were no differences seen in development of organ dysfunction, quality of life, or disability-free survival at any time points. Hospital mortality was higher in the intervention group (4% vs 1.4%; p = 0.04).Conclusions: A protocol-guided strategy utilizing stroke volume variation to guide administration of bolus fluid when compared with usual care until desedation or up to 24 hours reduced the amount of fluid administered but did not reduce the length of stay in ICU. [ABSTRACT FROM AUTHOR]

Background: Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP)-lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules, in patients with masked hypertension.Methods: Patients with an office BP of <140/90 mm Hg and daytime ambulatory BP of 135 to 150 mm Hg systolic or 85 to 95 mm Hg diastolic were randomly assigned 1:1 to the treatment of gastrodia-uncaria granules or placebo 5 to 10 g twice daily for 4 weeks. The primary efficacy variable was the change in daytime ambulatory BP.Results: At baseline, office and daytime BP of the 251 participants (mean age, 50.4 years; 53.4% men; mean body mass index 24.5 kg/m2; and 2.8%, 1.6%, and 30.7% with cardiovascular disease, diabetes, and smoking, respectively) averaged 129/82 and 135/89 mm Hg, respectively. In the intention-to-treat analysis, daytime systolic/diastolic BP was reduced by 5.44/3.39 and 2.91/1.60 mm Hg in the gastrodia-uncaria granules and placebo groups, respectively. The between-group difference in BP reductions was significant for the daytime (2.52/1.79 mm Hg; P≤0.025) and 24-hour BP (2.33/1.49 mm Hg; P≤0.012), but not for the clinic and nighttime BPs (P≥0.162). The per-protocol analysis in 229 patients produced similar results. Only 1 adverse event (sleepiness during the day) was reported, and no serious adverse event occurred.Conclusions: BP-lowering treatment with Chinese traditional medicine gastrodia-uncaria granules is efficacious for patients with masked hypertension. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02156024. [ABSTRACT FROM AUTHOR]

Background: Equipoise exists between the use of leaflet resection and preservation for surgical repair of mitral regurgitation caused by prolapse. We therefore performed a randomized, controlled trial comparing these 2 techniques, particularly in regard to functional mitral stenosis.Methods: One hundred four patients with degenerative mitral regurgitation surgically amenable to either leaflet resection or preservation were randomized at 7 specialized cardiac surgical centers. Exclusion criteria included anterior leaflet or commissural prolapse, as well as a mixed cause for mitral valve disease. Using previous data, we determined that a sample size of 88 subjects would provide 90% power to detect a 5-mm Hg difference in mean mitral valve gradient at peak exercise, assuming an SD of 6.7 mm with a 2-sided test with α=5% and 10% patient attrition. The primary end point was the mean mitral gradient at peak exercise 12 months after repair.Results: Patient age, proportion who were female, and Society of Thoracic Surgeons risk score were 63.9±10.4 years, 19%, and 1.4±2.8% for those who were assigned to leaflet resection (n=54), and 66.3±10.8 years, 16%, and 1.9±2.6% for those who underwent leaflet preservation (n=50). There were no perioperative deaths or conversions to replacement. At 12 months, moderate mitral regurgitation was observed in 3 subjects in the leaflet resection group and 2 in the leaflet preservation group. The mean transmitral gradient at 12 months during peak exercise was 9.1±5.2 mm Hg after leaflet resection and 8.3±3.3 mm Hg after leaflet preservation (P=0.43). The participants had similar resting peak (8.3±4.4 mm Hg versus 8.4±2.6 mm Hg; P=0.96) and mean resting (3.2±1.9 mm Hg versus 3.1±1.1 mm Hg; P=0.67) mitral gradients after leaflet resection and leaflet preservation, respectively. The 6-minute walking distance was 451±147 m for those in the leaflet resection versus 481±95 m for the leaflet preservation group (P=0.27).Conclusions: In this adequately powered randomized trial, repair of mitral prolapse with either leaflet resection or leaflet preservation was associated with similar transmitral gradients at peak exercise at 12 months postoperatively. These data do not support the hypothesis that a strategy of leaflet resection (versus preservation) is associated with a risk of functional mitral stenosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier NCT02552771. [ABSTRACT FROM AUTHOR]

Chronic pain is a significant health problem worldwide with limited pharmacological treatment options. This study evaluated the relative efficacy of 4 treatment sessions each of 4 nonpharmacological treatments: (1) hypnotic cognitive therapy (using hypnosis to alter the meaning of pain); (2) standard cognitive therapy; (3) hypnosis focused on pain reduction, and (4) pain education. One hundred seventy-three individuals with chronic pain were randomly assigned to receive 4 sessions of 1 of the 4 treatments. Primary (pain intensity) and secondary outcome measures were administered by assessors unaware of treatment allocation at pretreatment, posttreatment, and 3-, 6-, and 12-month follow-up. Treatment effects were evaluated using analysis of variance, a generalized estimating equation approach, or a Fisher exact test, depending on the outcome domain examined. All 4 treatments were associated with medium to large effect size improvements in pain intensity that maintained up to 12 months posttreatment. Pretreatment to posttreatment improvements were observed across the 4 treatment conditions on the secondary outcomes of pain interference and depressive symptoms, with some return towards pretreatment levels at 12-month follow-up. No significant between-group differences emerged in omnibus analyses, and few statistically significant between-group differences emerged in the planned pairwise analyses, although the 2 significant effects that did emerge favored hypnotic cognitive therapy. Future research is needed to determine whether the significant differences that emerged are reliable. [ABSTRACT FROM AUTHOR]

Study Design: Randomized controlled trial.Objective: The aim of this study was to determine whether postoperative blood salvage and autotransfusion versus traditional closed suction drainage reduces the rate of homologous blood transfusions in patients undergoing surgery for adult spinal deformity.Summary Of Background Data: The use of intraoperative blood salvage has become commonplace in spine surgery; however, the collection and reinfusion of blood drained from the wound postoperatively have not been employed routinely because of increased cost and questionable benefit.Methods: Adult patients undergoing long posterior fusions were randomized to either a blood salvage and reinfusion system (OrthoPat - Group 1) or a standard subfascial closed suction drain (Group 2). Blood collected in Group 1 was reinfused according to the manufacturer's protocol. Reinfusion drains were converted to standard closed suction drains when output was <50 mL during 4 hours, and drains were removed when output was minimal. Patients received autologous or homologous blood transfusions when hemoglobin (Hg) <8 g/dL or they had symptomatic anemia.Results: Thirty-four patients were randomized into Group 1 and 36 patients into Group 2. There were no differences in preoperative or intraoperative parameters. Patients in Group 1 had higher hemoglobin levels on postoperative day (POD) 2 and POD 3 compared to those in Group 2. However, there was no significant difference in the percentage of patients requiring homologous blood transfusion between the two groups (41% Group 1 vs. 60% Group 2, P = 0.17). Similarly a subgroup analysis in patients with estimated blood loss >2000 mL also showed no difference in homologous blood transfusion rates (67% Group 1 vs. 76% Group 2, P = 0.58). There were no differences in the rate or type of postoperative complications.Conclusion: Postoperative blood salvage and reinfusion result in a higher hemoglobin level in the early postoperative period, but does not significantly reduce the need for homologous blood transfusion.Level Of Evidence: 1. [ABSTRACT FROM AUTHOR]

This clinical trial evaluated the independent and combined effects of a tricyclic antidepressant (desipramine) and cognitive behavioral therapy (CBT) for chronic back pain relative to an active placebo treatment. Participants (n = 142) were patients experiencing daily chronic back pain at an intensity of ≥4/10 who were randomized to a single-center, double-blind, 12-week, 4-arm, parallel groups controlled clinical trial of (1) low concentration desipramine titrated to reach a serum concentration level of 15 to 65 ng/mL; (2) CBT and active placebo medication (benztropine mesylate, 0.125 mg); (3) low concentration desipramine and CBT; and (4) active benztropine placebo medication. Participants completed the Differential Description Scale and Roland Morris Disability Questionnaires before and after treatment as validated measures of outcomes in back pain intensity and disability, respectively. Participants within each condition showed significant reductions from pre-treatment to post-treatment in pain intensity (mean changes ranged from = -2.58 to 3.87, Cohen's d's = 0.46-0.84) and improvements in pain disability (mean changes = -3.04 to 4.29, Cohen's d's = 0.54-0.88). However, intent-to-treat analyses at post-treatment showed no significant differences between any condition, with small effect sizes ranging from 0.06 to 0.27. The results from this clinical trial did not support the hypothesis that desipramine, CBT, or their combination would be statistically superior to an active medicine placebo for reducing chronic back pain intensity or disability. Key limitations included recruiting 71% of the planned sample size and use of multiple inclusion/exclusion criteria that may limit generalizability to broader populations of patients with chronic back pain. [ABSTRACT FROM AUTHOR]

Study Design: A prospective randomized controlled study.Objective: To clarify whether percutaneous transforaminal endoscopic discectomy (PTED) has better clinical outcomes and less surgical trauma compared with microendoscopic discectomy (MED).Summary Of Background Data: Two kinds of minimally invasive spine surgeries, PTED and MED, are now widely used for the treatment of lumbar disc herniation (LDH). It is still a controversial issue to choose the proper surgical approach.Methods: In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed LDH, and were randomly allocated to PTED or MED group. The primary outcome was the score of Oswestry Disability Index (ODI) and the secondary outcomes included the score of Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain and physical function scales, European Quality of Life-5 Dimensions, and Visual Analogue Scales for back pain and leg pain.Results: A total of 250 participants were randomly assigned to two treatment groups, 241 of that received the specific surgical procedure. Two hundred twenty-two patients (92.1%) have completed the 2-year follow-up. Both the primary and secondary outcomes did not differ significantly between the two treatment groups at each prespecified follow-up time (P > 0.05). For PTED, the postoperative improvement of ODI score in the median herniation subgroup was less compared with paramedian subgroup. For MED, less improvement of ODI score was found in far-lateral herniation subgroup compared with paramedian subgroup. Total complication rate over the course of 2 year was 13.44% in PTED group and 15.57% in MED group (P = 0.639). Ten cases (8.40%) in PTED group and five cases (4.10%) in MED group suffered from residue/recurrence of herniation, for which reoperation was required.Conclusion: Over the 2-year follow-up period, PTED did not show superior clinical outcomes and did not appear to be safer procedure for patients with LDH compared with MED. PTED had inferior results for median disc herniation, whereas MED did not appear to be the best option for far-lateral disc herniation.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Objectives: Trauma resuscitations are complex critical care events that present patient safety-related risk. Simulation-based leadership training is thought to improve trauma care; however, there is no robust evidence supporting the impact of leadership training on clinical performance. The objective of this study was to assess the clinical impact of simulation-based leadership training on team leadership and patient care during actual trauma resuscitations.Design: Randomized controlled trial.Setting: Harborview Medical Center (level 1 trauma center).Subjects: Seventy-nine second- and third-year residents were randomized and 360 resuscitations were analyzed.Interventions: Subjects were randomized to a 4-hour simulation-based leadership training (intervention) or standard orientation (control) condition.Measurements and Main Results: Participant-led actual trauma resuscitations were video recorded and coded for leadership behaviors and patient care. We used random coefficient modeling to account for the nesting effect of multiple observations within residents and to test for post-training group differences in leadership behaviors while controlling for pre-training behaviors, Injury Severity Score, postgraduate training year, and days since training occurred. Sixty participants completed the study. There was a significant difference in post-training leadership behaviors between the intervention and control conditions (b1 = 4.06, t (55) = 6.11, p < 0.001; intervention M = 11.29, SE = 0.66, 95% CI, 9.99-12.59 vs control M = 7.23, SE = 0.46, 95% CI, 6.33-8.13, d = 0.92). Although patient care was similar between conditions (b = 2.00, t (55) = 0.99, p = 0.325; predicted means intervention M = 62.38, SE = 2.01, 95% CI, 58.43-66.33 vs control M = 60.38, SE = 1.37, 95% CI, 57.69-63.07, d = 0.15), a test of the mediation effect between training and patient care suggests leadership behaviors mediate an effect of training on patient care with a significant indirect effect (b = 3.44, 95% CI, 1.43-5.80). Across all trauma resuscitations leadership was significantly related to patient care (b1 = 0.61, SE = 0.15, t (273) = 3.64, p < 0.001).Conclusions: Leadership training resulted in the transfer of complex skills to the clinical environment and may have an indirect effect on patient care through better team leadership. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia.Design: Prospective, randomized, controlled study.Setting: Thirty-three hospitals in China.Patients: A total of 710 adults 18-75 years old with severe community-acquired pneumonia.Interventions: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo.Measurements and Main Results: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9-21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4-15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively (p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients (p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [p = 0.235]).Conclusions: In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay. [ABSTRACT FROM AUTHOR]

Study Design: A multicenter, randomized, intrapatient controlled trial.Objective: This study investigated whether lumbar fusion patients blinded to the harvest site (A) can identify the iliac crest used for bone harvesting and (B) whether this iliac crest is more painful than the contralateral side.Summary Of Background Data: Spinal fusion with iliac crest autograft is a frequently performed surgical procedure. A widely reported disadvantage of the harvesting procedure is potential donor site morbidity. This has driven the development of many bone graft substitutes. However, more recently the incidence and severity of donor site pain is debated, especially in lumbar fusion surgery.Methods: Ninety-two nontraumatic adult patients underwent a posterolateral (thoraco)lumbar fusion. Iliac crest bone graft was harvested unilaterally through the primary midline incision. At 6 weeks, 3 months, 6 months, and 1 year follow-up, patients were asked to identify the donor site and to rate pain in their back, left iliac crest and right iliac crest on a Visual Analogue Scale (VAS).Results: Ninety patients, 44 males and 46 females with a mean age of 54 years, were analyzed. The left/right distribution of the iliac crest donor site was 50/50 and 89% of the patients underwent a lumbar fusion below L3. Only 24% patients identified the harvest site correctly. Moreover, the VAS pain scores for the donor site and contralateral iliac crest did not differ and were at each timepoint lower than the scores for back pain.Conclusion: This study showed that, during the first year after lumbar fusion surgery via a single midline incision approach, patients could not reliably identify the iliac crest used for bone graft harvesting and this iliac crest was not more painful than the untouched contralateral iliac crest. Therefore, donor site pain should not be the main reason to use bone graft alternatives for lumbar spinal fusion.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow-derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy.Methods: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications.Results: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, -0.3 to 0.8; P=0.330). There were no significant differences between the groups on any of the secondary efficacy measures.Conclusions: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337. [ABSTRACT FROM AUTHOR]

Objectives: Occurrence of delirium in the ICU is associated with a longer stay in the ICU. To examine whether the use of ramelteon, a melatonin agonist, can prevent delirium and shorten the duration of ICU stay of critically ill patients.Design: A single-center, triple-blinded, randomized placebo-controlled trial.Setting: ICU of an academic hospital.Patients: Eligible patients were ICU patients who could take medicines orally or through a nasogastric tube during the first 48 hours of admission.Interventions: The intervention group received ramelteon (8 mg/d), and the control group received placebo (1 g/d of lactose powder) at 20:00 hours every day until discharge from the ICU.Measurements and Main Results: A total of 88 subjects were randomized to the ramelteon group (45 subjects) or the placebo group (43 subjects). As the primary endpoint, there was a trend toward decrease in the duration of ICU stay (4.56 d) in the ramelteon group compared with the placebo group (5.86 d) (p = 0.082 and p = 0.028 before and after adjustments). As the secondary endpoints, statistically significant decreases in the occurrence rate (24.4% vs 46.5%; p = 0.044) and duration (0.78 vs 1.40 d; p = 0.048) of delirium were observed in the ramelteon group. The nonintubated patients of the ramelteon group showed statistically significantly fewer awakenings per night and a higher proportion of nights without awakenings.Conclusions: Ramelteon tended to decrease the duration of ICU stay as well as decreased the occurrence rate and duration of delirium statistically significantly. [ABSTRACT FROM AUTHOR]

Attention bias for pain-related information is theorised to maintain chronic pain, indicating that changing this bias could improve pain-related outcomes. Modifying attention biases in adolescents, when chronic pain often first emerges, may be particularly beneficial. We report here a randomized, placebo-controlled, parallel-group trial of attention bias modification (ABM) training in adolescents with chronic noncancer pain. Adolescent patients (N = 66) were randomly assigned to complete multiple sessions of dot-probe ABM training (N = 23), placebo training (N = 22), or no training (waitlist; N = 21) across a period of 4 weeks. Patients completed all assessments at a hospital-based pediatric pain clinic and completed all training at home. We examined the relative effects of ABM on attention bias and attention control, as well as pain symptomatology (primary outcome), pain catastrophizing, anxiety and depression symptoms, and functional disability (secondary outcomes) immediately after training and 3 months later. We found no evidence that ABM changed attention bias or attention control in comparison with placebo training or no training. We also found that pain and pain-related outcomes were no different for those undergoing ABM compared with placebo training or no training when tested immediately after training or 3 months later. Overall, we found no evidence to support the efficacy of dot-probe ABM for improving pain-related outcomes in adolescents with chronic pain. This study was registered on the NIHR Clinical Research Network Portfolio in August 2014 (UK Clinical Trials Gateway: CPMS 17251) and funded by a Research Training Fellowship awarded to Lauren Heathcote by Action Medical Research for Children. [ABSTRACT FROM AUTHOR]

Background: In nonrandomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), fewer symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and midrange or preserved ejection fraction (EF ≥40%). We conducted the first randomized sham-controlled trial to evaluate the IASD in HF with EF ≥40%.Methods: REDUCE LAP-HF I (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association class III or ambulatory class IV HF, EF ≥40%, exercise PCWP ≥25 mm Hg, and PCWP-right atrial pressure gradient ≥5 mm Hg. Participants were randomized (1:1) to the IASD versus a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness end point was exercise PCWP at 1 month. The primary safety end point was major adverse cardiac, cerebrovascular, and renal events at 1 month. PCWP during exercise was compared between treatment groups using a mixed-effects repeated measures model analysis of covariance that included data from all available stages of exercise.Results: A total of 94 patients were enrolled, of whom 44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years, and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared with sham control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mm Hg in the treatment group versus 0.5±5.0 mm Hg in the control group (P=0.14). There were no peri-procedural or 1-month major adverse cardiac, cerebrovascular, and renal events in the IASD group and 1 event (worsening renal function) in the control group (P=1.0).Conclusions: In patients with HF and EF ≥40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation.Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02600234. [ABSTRACT FROM AUTHOR]

Chronic low back pain (LBP) is a common condition, usually with the involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first phase II, randomized, double-blind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate-to-severe chronic LBP with and without neuropathic pain component. Patients were treated for 14 weeks with cebranopadol 200, 400, or 600 μg once daily, tapentadol 200 mg twice daily, or placebo. The primary efficacy endpoints were the change from baseline pain to the weekly average 24-hour pain during the entire 12 weeks and during week 12 of the maintenance phase. Cebranopadol demonstrated analgesic efficacy, with statistically significant and clinically relevant improvements over placebo for all doses as did tapentadol. The responder analysis (≥30% or ≥50% pain reduction) confirmed these results. Cebranopadol and tapentadol displayed beneficial effects on sleep and functionality. Cebranopadol treatment was safe, with higher doses leading to higher treatment discontinuations because of treatment-emergent adverse events occurring mostly during titration. Those patients reaching the target doses had an acceptable tolerability profile. The incidence rate of most frequently reported treatment-emergent adverse events during maintenance phase was ≤10%. Although further optimizing the titration scheme to the optimal dose for individual patients is essential, cebranopadol is a new drug candidate with a novel mechanistic approach for potential chronic LBP treatment. [ABSTRACT FROM AUTHOR]

Background: Exposure to ambient particulate matter (PM) is associated with a number of adverse health outcomes, but potential mechanisms are largely unknown. Metabolomics represents a powerful approach to study global metabolic changes in response to environmental exposures. We therefore conducted this study to investigate changes in serum metabolites in response to the reduction of PM exposure among healthy college students.Methods: We conducted a randomized, double-blind crossover trial in 55 healthy college students in Shanghai, China. Real and sham air purifiers were placed in participants' dormitories in random order for 9 days with a 12-day washout period. Serum metabolites were quantified by using gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-mass spectrometry. Between-treatment differences in metabolites were examined using orthogonal partial least square-discriminant analysis and mixed-effect models. Secondary outcomes include blood pressure, corticotropin-releasing hormone, adrenocorticotropic hormone, insulin resistance, and biomarkers of oxidative stress and inflammation.Results: The average personal exposure to PMs with aerodynamic diameters ≤2.5 μm was 24.3 μg/m3 during the real purification and 53.1 μg/m3 during the sham purification. Metabolomics analysis showed that higher exposure to PMs with aerodynamic diameters ≤2.5 μm led to significant increases in cortisol, cortisone, epinephrine, and norepinephrine. Between-treatment differences were also observed for glucose, amino acids, fatty acids, and lipids. We found significantly higher blood pressure, hormones, insulin resistance, and biomarkers of oxidative stress and inflammation among individuals exposed to higher PMs with aerodynamic diameters ≤2.5 μm.Conclusions: This study suggests that higher PM may induce metabolic alterations that are consistent with activations of the hypothalamus-pituitary-adrenal and sympathetic-adrenal-medullary axes, adding potential mechanistic insights into the adverse health outcomes associated with PM. Furthermore, our study demonstrated short-term reductions in stress hormone following indoor air purification.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02712333. [ABSTRACT FROM AUTHOR]

Study Design: Meta-analysis of randomized controlled trials (RCTs).Objective: The aim of this study was to evaluate the effectiveness of intrathecal morphine (ITM) in reducing postoperative pain and opioid analgesic consumption following spine surgery.Summary Of Background Data: The use of ITM following adult spine surgery is of particular interest because of the ease of access to the thecal sac and the potential to provide adequate analgesia at low doses. However, previous studies of ITM have been limited by small sample sizes and conflicting results.Methods: A comprehensive search of PubMed, Web of Science, Clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials for prospective RCTs was performed by two independent reviewers. Postoperative opioid consumption, pain scores, and complications were documented from the identified studies. Standard mean differences (SMDs) were applied to continuous outcomes and odds ratios were determined for dichotomous outcomes.Results: Eight RCTs involving 393 subjects met inclusion criteria and were included in this meta-analysis. Patients receiving ITM (ITM group) as an adjunct to postoperative opioid analgesic were compared to patients receiving postoperative opioids only (control group). Postoperative morphine equivalent consumption was significantly lower during the first 24 hours postoperative in the ITM group (P < 0.001). Pain scores were similarly lower in the first 24 hours following spine surgery in those who received ITM (P < 0.001). In patients administered ITM, a greater percentage experienced pruritus (P < 0.001). Respiratory depression was solely encountered in the ITM group (P = 0.25). There were no significant differences between the ITM and control groups in terms of sedation (P = 0.18), nausea (P = 0.67), vomiting (P = 0.62), or length of stay (P = 0.13).Conclusion: In patients undergoing spine surgery, use of ITM significantly reduced opioid analgesic consumption and Visual Analogue Schores pain scores compared to controls within the first 24 hours postoperatively. High-quality, follow-up RCTs with large sample sizes are recommended to determine the potential of supplementary ITM in spine surgery and complete the side effects profile.Level Of Evidence: 1. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have reported favorable outcomes using drug-coated balloons (DCBs) for treatment of symptomatic peripheral artery disease of the superficial femoral and popliteal arteries. However, the treatment effect compared with an uncoated balloon has differed greatly among the randomized trials, with better outcomes observed with higher-dose DCBs. This European trial was designed to assess the safety and effectiveness of a next-generation low-dose (2-µg/mm2 surface dose of paclitaxel) DCB.Methods: This was a prospective, randomized, multicenter, single-blinded trial. Patients were randomized (3:1) to treatment with a low-dose DCB or an uncoated percutaneous transluminal angioplasty (PTA) balloon. The primary safety end point was a composite of freedom from device- and procedure-related death through 30 days after the procedure and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months after the procedure. The primary effectiveness end point was primary patency at 12 months.Results: Patients were randomized to treatment with a DCB (222 patients, 254 lesions) or uncoated PTA balloon (72 patients, 79 lesions) after successful predilatation. Mean lesion length was 7.2 and 7.1 cm, and 19.2% and 19.0% of lesions represented total occlusions, respectively. The primary safety end point was met, and superiority was demonstrated; freedom from a primary safety event was 94.1% (193 of 205) with DCB and 83.3% (50 of 60) with PTA, for a difference of 10.8% (95% confidence interval, 0.9%-23.0%). The primary effectiveness end point was met, and superiority of DCB over PTA was achieved (83.9% [188 of 224] versus 60.6% [40 of 66]; P<0.001). Outcomes with DCB were also superior to PTA per the Kaplan-Meier estimate for primary patency (89.0% versus 65.0% at 365 days; log-rank P<0.001) and for rates of clinically driven target lesion revascularization (5.9% versus 16.7%; P=0.014).Conclusions: Superiority with a low-dose DCB for femoropopliteal interventions was demonstrated over PTA for both the safety and effectiveness end points.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01858363. [ABSTRACT FROM AUTHOR]

For patients with chronic pain conditions such as rheumatoid arthritis (RA), who experience elevated levels of distress, tailored-guided internet-based cognitive-behavioral treatment may be effective in improving psychological and physical functioning, and reducing the impact of RA on daily life. A multicenter, randomized controlled trial was conducted for RA patients with elevated levels of distress as assessed by a disease-specific measure. The control group (n = 71) received standard care and the intervention group (n = 62) additionally received an internet-based tailored cognitive-behavioral intervention. Main analyses were performed using a linear mixed model estimating differences between the intervention and control groups in scores of psychological functioning, physical functioning, and impact of RA on daily life at preassesment and postassessment, and at 3, 6, 9, and 12 months. Patients who received the internet-based intervention reported a larger improvement in psychological functioning compared with the control group, indicating less depressed mood (P < 0.001, d = 0.54), negative mood (P = 0.01, d = 0.38), and anxiety (P < 0.001, d = 0.48) during the course of the 1-year follow-up period. Regarding physical functioning, a trend was found for the intervention group reporting less fatigue than the control group (P = 0.06, d = 0.24), whereas no effect was found on pain. No effects were found for the impact of RA on daily life, except for the intervention group experiencing fewer role limitations due to emotional problems (P < 0.001, d = 0.53). Offering guided internet-based cognitive-behavioral therapy is a promising development to aid patients with psychological distress particularly in improving psychological functioning. Further research on adherence and specific intervention ingredients is warranted. [ABSTRACT FROM AUTHOR]

Objectives: Hypothermia reduces intracranial hypertension in patients with traumatic brain injury but was associated with harm in the Eurotherm3235Trial. We stratified trial patients by International Mission for Prognosis and Analysis of Clinical Trials in [Traumatic Brain Injury] (IMPACT) extended model sum scores to determine where the balance of risks lay with the intervention.Design: The Eurotherm3235Trial was a randomized controlled trial, with standardized and blinded outcome assessment. Patients in the trial were split into risk tertiles by IMPACT extended model sum scores. A proportional hazard analysis for death between randomization and 6 months was performed by intervention and IMPACT extended model sum scores tertiles in both the intention-to-treat and the per-protocol populations of the Eurotherm3235Trial.Setting: Forty-seven neurologic critical care units in 18 countries.Patients: Adult traumatic brain injury patients admitted to intensive care who had suffered a primary, closed traumatic brain injury; increased intracranial pressure; an initial head injury less than 10 days earlier; a core temperature at least 36°C; and an abnormal brain CT.Intervention: Titrated Hypothermia in the range 32-35°C as the primary intervention to reduce raised intracranial pressure.Measurements and Main Results: Three hundred eighty-six patients were available for analysis in the intention-to-treat and 257 in the per-protocol population. The proportional hazard analysis (intention-to-treat and per-protocol populations) showed that the treatment effect behaves similarly across all risk stratums. However, there is a trend that indicates that patients in the low-risk group could be at greater risk of suffering harm due to hypothermia.Conclusions: Hypothermia as a first line measure to reduce intracranial pressure to less than 20 mm Hg is harmful in patients with a lower severity of injury and no clear benefit exists in patients with more severe injuries. [ABSTRACT FROM AUTHOR]

Objective: To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock.Design: Single center, randomized, double-blind controlled trial.Setting: Teaching hospital.Patients: Adult cancer patients with septic shock in the first 6 hours of ICU admission.Interventions: Patients were randomized to the liberal (hemoglobin threshold, < 9 g/dL) or to the restrictive strategy (hemoglobin threshold, < 7 g/dL) of RBC transfusion during ICU stay.Measurements and Main Results: Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0-3] vs 0 [0-2] unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53-1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53-0.97; p = 0.03).Conclusions: We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed. [ABSTRACT FROM AUTHOR]

Study Design: A monocentric open-label randomized controlled trial (MRCT).Objective: Comparison of clinical and radiological outcomes between isolated instrumented posterior fusion (PLF) and associated instrumented posterior fusion and interbody fusion by transforaminal approach (PLF + TLIF) for patients suffering from one-level lumbar degenerative spondylolisthesis (DS) undergoing surgery.Summary Of Background Data: DS is a common cause of symptomatic lumbar stenosis. PLF has shown better clinical outcome than decompression with noninstrumented posterolateral fusion. TLIF with interbody cage showed better fusion rate than PLF. There is a need for randomized controlled trials to compare PLF with and without TLIF as to clinical and radiological outcomes.Methods: This is a MRCT comparing PLF and TLIF techniques in surgical treatment of DS. Sixty patients were included in a secured database from 2009 to 2011 and randomized into two groups: 30 PLF with posterior pedicle screws and intertransverse autologuous graft, and 30 TLIF in which an interbody fusion by transforaminal approach was added. Data included clinical (pain and disability), surgical (blood loss and operating time), and radiological (alignment and fusion) parameters at baseline and 2-year follow-up. Comparison was made by Student t test and Chi-square test.Results: There was a significant improvement in each group for pain and disability but no difference between the groups. Radiographic assessment showed better posterolateral fusion rate for TLIF without superiority in segmental lordosis improvement. A case of deformity cascade with spino-pelvic mismatch at baseline was noted in PLF.Conclusion: Posterior decompression and instrumented fusion is an efficient technique that proved its significant clinical benefit in the surgical treatment of DS. TLIF did not show its superiority neither in clinical nor alignment parameters despite a better fusion rate. These results suggest that TLIF is not mandatory in this specific indication. Sagittal alignment analysis by standing full-body images should be considered in DS care.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Background: The biological functions of high-density lipoproteins (HDLs) contribute to explaining the cardioprotective role of the lipoprotein beyond quantitative HDL cholesterol levels. A few small-scale interventions with a single antioxidant have improved some HDL functions. However, to date, no long-term, large-scale, randomized controlled trial has been conducted to assess the effects of an antioxidant-rich dietary pattern (such as a traditional Mediterranean diet [TMD]) on HDL function in humans.Methods: This study was performed in a random subsample of volunteers from the PREDIMED Study (Prevención con Dieta Mediterránea; n=296) after a 1-year intervention. We compared the effects of 2 TMDs, one enriched with virgin olive oil (TMD-VOO; n=100) and the other enriched with nuts (TMD-Nuts; n=100), with respect to a low-fat control diet (n=96). We assessed the effects of both TMDs on the role of HDL particles on reverse cholesterol transport (cholesterol efflux capacity, HDL ability to esterify cholesterol, and cholesteryl ester transfer protein activity), HDL antioxidant properties (paraoxonase-1 arylesterase activity and total HDL antioxidant capacity on low-density lipoproteins), and HDL vasodilatory capacity (HDL ability to induce the release of nitric oxide in endothelial cells). We also studied the effects of a TMD on several HDL quality-related characteristics (HDL particle oxidation, resistance against oxidative modification, main lipid and protein composition, and size distribution).Results: Both TMDs increased cholesterol efflux capacity relative to baseline (P=0.018 and P=0.013 for TMD-VOO and TMD-Nuts, respectively). The TMD-VOO intervention decreased cholesteryl ester transfer protein activity (relative to baseline, P=0.028) and increased HDL ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity (relative to control, P=0.039, P=0.012, and P=0.026, respectively). Adherence to a TMD induced these beneficial changes by improving HDL oxidative status and composition. The 3 diets increased the percentage of large HDL particles (relative to baseline, P<0.001).Conclusions: The TMD, especially when enriched with virgin olive oil, improved HDL atheroprotective functions in humans.Clinical Trial Registration: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639. [ABSTRACT FROM AUTHOR]

Study Design: A randomized, controlled, single-center pilot study.Objective: The aim of this study was to investigate the feasibility of running a trial to explore if early intervention in individuals with chronic low back pain (CLBP) would lead to an early return to work (RTW) and reduce sick leave during 12 months of follow-up compared with patients on a 3-month waiting list.Summary Of Background Data: Back pain is the reason for numerous absent days from work. In Norway, the government initiated a priority program, Earlier Return to Work (ERTW), to reduce work absences through early intervention. However, no proper evaluation has been performed on populations with CLBP. There is no consensus on how RTW should be measured. Only a few studies have examined how waiting time affects RTW.Methods: Fifty-eight patients were included in the study. The group with early intervention was examined within 2 weeks, and the group on the waiting list was examined after 12 weeks. The intervention was identical in both groups and consisted of an outpatient, intensive back school. The data were obtained by questionnaire after 3, 6, and 12 months. The primary outcome was absence from work.Results: The sample size in a full-scale study must comprise at least 382 patients on the basis of the assumptions in the pilot. In the pilot study, early intervention directly compared with an ordinary waiting list did not significantly affect the number of sick leave days after 12 months of follow-up.Conclusion: A prerequisite for launching a full-scale clinical trial is a redesign of the intervention, an improvement of procedures concerning inclusion and randomization, and finally a more precise definition of RTW.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

This randomized pilot study aimed to determine whether a single session of psychoeducation improved mental health outcomes, attitudes toward treatment, and service engagement among urban, impoverished, culturally diverse, trauma-exposed adults. Sixty-seven individuals were randomly assigned to a single-session psychoeducation treatment or a delayed treatment comparison control group. The control group was found to be superior to the treatment group at posttest with respect to symptoms of posttraumatic stress disorder, anxiety, and occupational and family disability. At follow-up, all participants had completed the psychoeducation treatment, and a mixed-effects model indicated significant improvements over time in symptoms of posttraumatic stress disorder, anxiety, depression, somatization, and attitudes toward treatment. Ninety-eight percent of the participants reported the psychoeducation was helpful at follow-up. Participants also reported a 19.1% increase in mental health service utilization at follow-up compared with baseline. Implications for treatment and future research are discussed. [ABSTRACT FROM AUTHOR]

Purpose: Fatigue is a common problem among colon cancer patients and typically increases during chemotherapy. Exercise during chemotherapy might have beneficial effects on fatigue. To investigate the short- and long-term effects of an exercise program in colon cancer patients during adjuvant treatment, the Physical Activity During Cancer Treatment study was conducted. Methods: In this multicenter randomized controlled trial, 33 colon cancer patients under-going chemotherapy (21 men and 12 women) were randomly assigned to either a group receiving an 18-wk supervised exercise program (n = 17) or to usual care (n = 16). The primary outcome was fatigue as measured by the Multidimensional Fatigue Inventory and the Fatigue Quality List. Secondary outcomes were quality of life, physical fitness, anxiety, depression, body weight, and chemotherapy completion rate. Outcome assessment took place at baseline, postintervention (18 wk) and at 36 wk. Results: Intention-to-treat mixed linear model analyses showed that patients in the intervention group experienced significantly less physical fatigue at 18 wk and general fatigue at 36 wk (mean between group differences, -3.2; 95% confidence interval [CI], -6.2 to -0.2; effect size [ES], -0.9 and -2.7; 95% CI, -5.2 to -0.1; ES, -0.8, respectively), and reported higher physical functioning (12.3; 95% CI, 3.3-21.4; ES, 1.0) compared with patients in the usual care group. Conclusion: The Physical Activity During Cancer Treatment trial shows that an 18-wk supervised exercise program in colon cancer patients during chemotherapy is safe and feasible. The intervention significantly reduced physical fatigue at 18 wk and general fatigue at 36 wk. Considering the number of patients included in the present study, replication in a larger study population is required. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium (Intensive Care Delirium Screening Checklist ≥ 4) administered to critically ill adults with subsyndromal delirium (Intensive Care Delirium Screening Checklist = 1-3).Design: Randomized, double-blind, placebo-controlled trial.Setting: Three 10-bed ICUs (two medical and one surgical) at an academic medical center in the United States.Patients: Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery, or requiring deep sedation.Interventions: Patients were randomly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred (Intensive Care Delirium Screening Checklist ≥ 4 with psychiatric confirmation), 10 days of therapy had elapsed, or ICU discharge.Measurements and Main Results: Baseline characteristics were similar between the haloperidol (n = 34) and placebo (n = 34) groups. A similar number of patients given haloperidol (12/34 [35%]) and placebo (8/34 [23%]) developed delirium (p = 0.29). Haloperidol use reduced the hours per study day spent agitated (Sedation Agitation Scale ≥ 5) (p = 0.008), but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma (Sedation Agitation Scale ≤ 2) or delirium (p = 0.36), the time to first delirium occurrence (p = 0.22), nor delirium duration (p = 0.26). Days of mechanical ventilation (p = 0.80), ICU mortality (p = 0.55), and ICU patient disposition (p = 0.22) were similar in the two groups. The proportion of patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.31), excessive sedation (p = 0.31), or new-onset hypotension (p = 1.0) that resulted in study drug discontinuation was comparable between the two groups.Conclusions: Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium. [ABSTRACT FROM AUTHOR]

Background: We assessed the effect of automated treatment adherence support delivered via mobile phone short message system (SMS) text messages on blood pressure.Methods and Results: In this pragmatic, single-blind, 3-arm, randomized trial (SMS-Text Adherence Support [StAR]) undertaken in South Africa, patients treated for high blood pressure were randomly allocated in a 1:1:1 ratio to information only, interactive SMS text messaging, or usual care. The primary outcome was change in systolic blood pressure at 12 months from baseline measured with a validated oscillometric device. All trial staff were masked to treatment allocation. Analyses were intention to treat. Between June 26, 2012, and November 23, 2012, 1372 participants were randomized to receive information-only SMS text messages (n=457), interactive SMS text messages (n=458), or usual care (n=457). Primary outcome data were available for 1256 participants (92%). At 12 months, the mean adjusted change in systolic blood pressure compared with usual care was -2.2 mm Hg (95% confidence interval, -4.4 to -0.04) with information-only SMS and -1.6 mm Hg (95% confidence interval, -3.7 to 0.6) with interactive SMS. Odds ratios for the proportion of participants with a blood pressure <140/90 mm Hg were 1.42 (95% confidence interval, 1.03-1.95) for information-only messaging and 1.41 (95% confidence interval, 1.02-1.95) for interactive messaging compared with usual care.Conclusions: In this randomized trial of an automated adherence support program delivered by SMS text message in a general outpatient population of adults with high blood pressure, we found a small reduction in systolic blood pressure control compared with usual care at 12 months. There was no evidence that an interactive intervention increased this effect.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02019823. South African National Clinical Trials Register, number SANCTR DOH-27-1212-386; Pan Africa Trial Register, number PACTR201411000724141. [ABSTRACT FROM AUTHOR]

Internet-delivered interventions are emerging as a strategy to address barriers to care for individuals with chronic pain. This is the first large multicenter randomized controlled trial of Internet-delivered cognitive-behavioral therapy (CBT) for pediatric chronic pain. Participants included were 273 adolescents (205 females and 68 males), aged 11 to 17 years with mixed chronic pain conditions and their parents, who were randomly assigned in a parallel-group design to Internet-delivered CBT (n = 138) or Internet-delivered Education (n = 135). Assessments were completed before treatment, immediately after treatment, and at 6-month follow-up. All data collection and procedures took place online. The primary analysis used linear growth models. Results demonstrated significantly greater reduction on the primary outcome of activity limitations from baseline to 6-month follow-up for Internet CBT compared with Internet education (b = -1.13, P = 0.03). On secondary outcomes, significant beneficial effects of Internet CBT were found on sleep quality (b = 0.14, P = 0.04), on reducing parent miscarried helping (b = -2.66, P = 0.007) and protective behaviors (b = -0.19, P = 0.001), and on treatment satisfaction (P values < 0.05). On exploratory outcomes, benefits of Internet CBT were found for parent-perceived impact (ie, reductions in depression, anxiety, self-blame about their adolescent's pain, and improvement in parent behavioral responses to pain). In conclusion, our Internet-delivered CBT intervention produced a number of beneficial effects on adolescent and parent outcomes, and could ultimately lead to wide dissemination of evidence-based psychological pain treatment for youth and their families. [ABSTRACT FROM AUTHOR]

Study Design: A prospective, multicenter, randomized, controlled, investigational device exemption (IDE) noninferiority trial.Objective: The aim of this study was to evaluate the comparative safety and effectiveness of lumbar total disc replacement (TDR) in the treatment of patients with symptomatic degenerative disc disease (DDD) who are unresponsive to nonsurgical therapy.Summary Of Background Data: Lumbar TDR has been used to alleviate discogenic pain and dysfunction while preserving segmental range of motion and restoring stability. There is a paucity of data available regarding the comparative performance of lumbar TDR.Methods: Patients presenting with symptomatic single-level lumbar DDD who failed at least 6 months of nonsurgical management were randomly allocated (2:1) to treatment with an investigational TDR device (activL, n = 218) or FDA-approved control TDR devices (ProDisc-L or Charité, n = 106). The hypothesis of this study was that a composite effectiveness outcome at 2 years in patients treated with activL would be noninferior (15% delta) to that in controls.Results: The primary composite endpoint of this study was met, which demonstrated that the activL TDR was noninferior to control TDR (P < 0.001). A protocol-defined analysis of the primary composite endpoint also confirmed that activL was superior to controls (P = 0.02). Radiographic success was higher with activL versus controls (59% vs. 43%; P < 0.01). Mean back pain severity improved by 74% with activL and 68% with controls. Oswestry Disability Index scores decreased by 67% and 61% with activL and controls, respectively. Patient satisfaction with treatment was over 90% in both groups at 2 years. Return to work was approximately 1 month shorter (P = 0.08) with activL versus controls. The rate of device-related serious adverse events was lower in patients treated with activL versus controls (12% vs. 19%; P = 0.13). Surgical reintervention rates at the index level were comparable (activL 2.3%, control 1.9%).Conclusion: The single-level activL TDR is safe and effective for the treatment of symptomatic lumbar DDD through 2 years.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Background: Drug-coated balloon angioplasty (DCBA) was shown to be superior to standard balloon angioplasty (POBA) in terms of restenosis prevention for de novo superficial femoral artery disease. For in-stent restenosis, the benefit of DCBA over POBA remains uncertain.Methods and Results: One hundred nineteen patients with superficial femoral artery in-stent restenosis and chronic limb ischemia were recruited over 34 months at 5 German clinical sites and prospectively randomized to either DCBA (n=62) or POBA (n=57). Mean lesion length was 82.2±68.4 mm. Thirty-four (28.6%) lesions were totally occluded; 30 (25.2%) were moderately or heavily calcified. Clinical and duplex ultrasound follow-up was conducted at 6 and 12 months. The primary end point of recurrent in-stent restenosis assessed by ultrasound at 6 months was 15.4% (8 of 52) in the DCBA and 44.7% (21 of 47) in the POBA group (P=0.002). Freedom from target lesion revascularization was 96.4% versus 81.0% (P=0.0117) at 6 months and 90.8% versus 52.6% (P<0.0001) at 12 months, respectively. At 12 months, clinical improvement by ≥1 Rutherford category without the need for target lesion revascularization was observed in 35 of 45 DCBA patients (77.8%) and 23 of 44 POBA patients (52.3%; P=0.015). No major amputation was needed. Two patients in the DCBA and 3 patients in the POBA group died. No death was procedure related.Conclusions: DCBA for superficial femoral artery in-stent restenosis is associated with less recurrent restenosis and a better clinical outcome than POBA without an apparent difference in safety.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01305070. [ABSTRACT FROM AUTHOR]

Opioid analgesics are commonly used for the treatment of chronic low back pain (CLBP); however, abuse potential is a major concern. This study used a randomized, double-blind, placebo-controlled, enriched-enrollment randomized-withdrawal study design to evaluate the safety, tolerability, and analgesic efficacy of an abuse-deterrent formulation of extended-release oxycodone, Xtampza ER, in opioid-naive and opioid-experienced adults with moderate-to-severe CLBP. Patients entered an open-label titration phase (N = 740); those who were successfully titrated on Xtampza ER (≥40 to ≤160 mg oxycodone hydrochloride equivalent per day) were randomized to active drug (N = 193) or placebo (N = 196) for 12 weeks. Primary efficacy results showed a statistically significant difference in average pain intensity from randomization baseline to treatment week 12 between the Xtampza ER and placebo groups (mean [±SE], -1.56 [0.267]; P < 0.0001). All sensitivity analyses results supported the primary result of the study. Secondary efficacy outcomes indicated that Xtampza ER vs placebo had more patients with improvement in patient global impression of change (26.4% vs 14.3%; P < 0.0001), longer time-to-exit from the study (58 vs 35 days; P = 0.0102), and a greater proportion of patients with ≥30% (49.2% vs 33.2%; P = 0.0013) and ≥50% (38.3% vs 24.5%; P = 0.0032) improvement in pain intensity. There was less rescue medication (acetaminophen) use in the Xtampza ER treatment group than in the placebo group. Xtampza ER had an adverse event profile consistent with other opioids and was well tolerated; no new safety concerns were identified. In conclusion, Xtampza ER resulted in clinically and statistically significant efficacy in patients with CLBP. [ABSTRACT FROM AUTHOR]

Background: Patients with a first episode of unprovoked venous thromboembolism have a high risk of recurrence after discontinuation of anticoagulant therapy. Extending anticoagulation reduces the risk of recurrence but is associated with increased bleeding. Sulodexide, a glycosaminoglycan, exerts antithrombotic and profibrinolytic actions with a low bleeding risk when administered orally, but its benefit for preventing recurrent venous thromboembolism is not well known.Methods and Results: In this multicenter, double-blind study, 615 patients with first-ever unprovoked venous thromboembolism who had completed 3 to 12 months of oral anticoagulant treatment were randomly assigned to sulodexide 500 lipasemic units twice daily or placebo for 2 years, in addition to elastic stockings. The primary efficacy outcome was recurrence of venous thromboembolism. Major or clinically relevant bleeding was the primary safety outcome. Venous thromboembolism recurred in 15 of the 307 patients who received sulodexide and in 30 of the 308 patients who received placebo (hazard ratio, 0.49; 95% confidence interval [CI], 0.27-0.92; P=0.02). The analysis in which lost to follow-up was assigned to failure yielded a risk ratio among treated versus control subjects of 0.54 (95% confidence interval, 0.35-0.85; P=0.009). No major bleeding episodes occurred; 2 patients in each treatment group had a clinically relevant bleeding episode. Adverse events were similar in the 2 groups.Conclusion: Sulodexide given after discontinuation of anticoagulant treatment reduced the risk of recurrence in patients with unprovoked venous thromboembolism, with no apparent increase of bleeding risk.Clinical Trial Registration: URL: https://www.clinicaltrialsregister.eu/. Identifier: EudraCT number 2009-016923-77. [ABSTRACT FROM AUTHOR]

Health communication campaigns often seek to diminish stigma and promote care seeking, with public service announcements (PSAs) frequently prominent in these campaigns. One example is the Australian-based beyondblue campaign. As an alternative approach, campaigns may seek to reduce stigma by promoting stories of recovery. Participants completed measures of stigmatizing and empowering attitudes at pre-, post-, and 72-hour follow-up after being randomized to a PSA recovery-oriented video, treatable disease-oriented video (beyondblue), or control. When exposed to the recovery-oriented PSA, participants showed significant reduction in stigmatizing attitudes from pre- to posttest than beyondblue or the control group with the emergence of nonsignificant trends identified at follow-up. Findings suggest a recovery-oriented video leads to better change on measures of stigma and affirming attitudes than beyondblue. Despite the aforementioned findings, results failed to show either the recovery or beyondblue videos had a significant impact on intent to seek treatment. [ABSTRACT FROM AUTHOR]