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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: Cardiac arrest is a major public health concern worldwide. The extent and types of randomized controlled trials (RCT)-our most reliable source of clinical evidence-conducted in these high-risk patients over recent years are largely unknown.Methods and Results: We performed a systematic review, identifying all RCTs published in PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library from 1995 to 2014 that focused on the acute treatment of nontraumatic cardiac arrest in adults. We then extracted data on the setting of study populations, types and timing of interventions studied, risk of bias, outcomes reported, and how these factors have changed over time. Over this 20-year period, 92 RCTs were published containing 64 309 patients (median, 225.5 per trial). Of these, 81 RCTs (88.0%) involved out-of-hospital cardiac arrest, whereas 4 (4.3%) involved in-hospital cardiac arrest and 7 (7.6%) included both. Eighteen RCTs (19.6%) were performed in the United States, 68 (73.9%) were performed outside the United States, and 6 (6.5%) were performed in both settings. Thirty-eight RCTs (41.3%) evaluated drug therapy, 39 (42.4%) evaluated device therapy, and 15 (16.3%) evaluated protocol improvements. Seventy-four RCTs (80.4%) examined interventions during the cardiac arrest, 15 (16.3%) examined post cardiac arrest treatment, and 3 (3.3%) studied both. Overall, reporting of the risk of bias was limited. The most common outcome reported was return of spontaneous circulation: 86 (93.5%) with only 22 (23.9%) reporting survival beyond 6 months. Fifty-three RCTs (57.6%) reported global ordinal outcomes, whereas 15 (16.3%) reported quality-of-life. RCTs in the past 5 years were more likely to be focused on protocol improvements and postcardiac arrest care.Conclusions: Important gaps in RCTs of cardiac arrest treatments exist, especially those examining in-hospital cardiac arrest, protocol improvement, postcardiac arrest care, and long-term or quality-of-life outcomes. [ABSTRACT FROM AUTHOR]

The article focuses on cardiovascular disease (CVD) treatment by repurposing metformin, which is considered the cornerstone of diabetic drug management in patients with type 2 diabetes mellitus. Critical topics being discussed include treating patients who have (CVD) with diabetes comorbidity as well as metformin’s cellular mechanism.

The article focuses on pediatric cardiac arrest (CA) with return of circulation (ROC) from in-hospital (IH) and out-of-hospital (OH) setting. The study aims to determine the difference in IH and OH pediatric cardiac arrest that is significant for the clinical trial of therapeutic hypothermia (TH). The study found out that mortality is greater in the OH event due to neurologic indications. It is suggested that future researchers for the efficacy of TH should consider independent clinical trials.

The article reports on the review of clinical trial design issues related to control groups. The patients included in the studies have lethal conditions. The majority of intensive care patients suffer from syndromes which cannot be precisely assessed. the treatment consists of interacting therapies.

The article reports that the highest level of evidence on the usefulness of therapy is obtained from double-blind clinical trials. Traditional statistics have been used predominantly but a Bayesian approach offer more flexibility by leveraging more information from clinical trials. Innovative designs can limit the number of patients included in a trial and decrease the chance of maintaining a patient on an unfavorable treatment.

Abstract: Since pain-related fear may contribute to the development and maintenance of chronic low back pain (CLBP), an exposure in vivo treatment (EXP) was developed for CLBP patients. We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant graded activity (GA) directly and 6 months post-treatment in a multi-centre randomized controlled trial. In total, 85 patients suffering from disabling non-specific CLBP reporting at least moderate pain-related fear were randomly allocated to EXP or GA. It was demonstrated that EXP, despite excelling in diminishing pain catastrophizing and perceived harmfulness of activities, was equally effective as GA in improving functional disability and main complaints, although the group difference almost reached statistical significance favouring EXP. Both treatment conditions did not differ in pain intensity and daily activity levels either. Nor was EXP superior to GA in the subgroup of highly fearful patients. Irrespective of treatment, approximately half the patients reported clinically relevant improvements in main complaints and functional disability, although for the latter outcome the group difference was almost significant favouring EXP. Furthermore, the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities. In sum, this study demonstrates that up to 6 months after treatment EXP is an effective treatment, but not more effective than GA, in moderately to highly fearful CLBP patients, although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established. Possible explanations for these findings are discussed. [Copyright &y& Elsevier]

The article presents a clinical trial on the effect of enhanced services on virologic outcomes in a directly administered antiretroviral therapy trial for HIV-infected drug users. Even though directly administered antiretroviral therapy (DAART) is helpful in HIV treatment, there are still unknown elements in the DAART program. The results showed that on-site medical and case management services should be integrated into DAART interventions.

Abstract: The aim of this study was to compare the effect of a physical therapy regimen including active exercises with the current standard treatment on reduction of pain 6 weeks and 6 months after whiplash injury caused by motor vehicle collision. Two hundred patients were enrolled in a prospective randomized controlled trial. In the standard group, treatment consisted of immobilization with a soft collar over 7 days. In the physical therapy group, patients were scheduled for 10 physical therapy appointments including active exercises within 14 days after enrollment. Pain intensity was rated by all patients daily during the first week, the sixth week, and 6 months after recruitment, using a numeric rating scale (0–10). Data analyses were performed by comparing the mean (over 1 week) pain scores between the two different treatment groups. Ninety-seven patients were randomly assigned to the standard treatment group and 103 to the physical therapy group. During the first week, there was no significant difference in mean pain intensity between the standard treatment group (4.76±2.15) and the physical therapy group (4.36±2.14). However, after 6 weeks, mean pain intensity was significantly (p =0.002) lower in the physical therapy group (1.49±2.26 versus 2.7±2.78). Similarly, after 6 months, significantly (p <0.001) less pain was reported in the physical therapy group (1.17±2.13) than the standard treatment group (2.33±2.56). We conclude that a physical therapy regimen which includes active exercises is superior in reducing pain 6 weeks and 6 months after whiplash injury compared to the current standard treatment with a soft collar. [Copyright &y& Elsevier]

Patient, provider, and clinical investigator expectations concerning treatments are believed to play important roles in patient response. This study examined the association of patient and research nurse/physician pretreatment expectations of pain relief with actual pain relief, the accuracy of patient and research nurse guesses about patient medication assignment, and changes in research nurse and patient pain relief expectations over the course of a randomized double-blind trial of amitriptyline versus an active placebo for patients with chronic pain and spinal cord injuries (SCI). Patient expectations of pain relief with amitriptyline were associated significantly with actual pain decrease for patients in the amitriptyline, but not placebo, condition. Research nurse/physician expectations did not predict patient pain relief. Both patients and the research nurse were able to guess patient medication assignment at a rate significantly greater than chance. The research nurse''s, but not the patients’, expectations of pain relief with amitriptyline decreased significantly over the course of the study. These findings have implications for future randomized controlled trials. Fully double-blind conditions are very difficult to achieve, and it is informative to assess patient and research clinician expectations and guesses regarding medication assignment. [Copyright &y& Elsevier]