Pain Trials Research Articles

Multimodal Sensory Stimulation of the Masseter Muscle Reduced Precision but Not Accuracy of Jaw-Opening Movements.

A functional integration between the trigeminal and craniocervical sensorimotor systems has been demonstrated, with simultaneous jaw and head–neck movements during jaw opening–closing. We previously showed that pain induction in the masseter muscle increased the relative contribution of the neck component of integrated jaw–neck movements. Induced pain or manipulation of proprioception by vibration did not affect accuracy during a jaw-opening task in men. It is not known how multimodal sensory stimulation, with a combination of pain induction and vibration, affects jaw-opening accuracy and precision. The aim was to investigate how jaw–neck movements, and specifically accuracy and precision of jaw-opening, are affected during concomitant nociceptive and proprioceptive stimulation of the masseter muscle. Twenty-one healthy men performed jaw-opening to a target position, defined as 75% of individual maximum jaw opening, during control (Ctr), vibration of masseter muscles (Vib), pain induction in the masseter (Pain), and concomitant vibration and pain induction in the masseter muscle (VibPain). Simultaneous jaw and head movements were recorded with an optoelectronic system and amplitudes calculated for each jaw opening–closing cycle. Accuracy of jaw movements was defined as the achievement of the target position. Precision of jaw movements was defined as the cycle-to-cycle variability from the mean of cycles 2–10 (coefficient of variation, CV). Differences between the trials were analyzed with Friedman’s test, Dunn’s test, and Benjamini–Hochberg correction. There were no significant differences between the trials for jaw movement amplitudes. For head movements, amplitudes for cycles 2–10 were larger during Pain compared to Ctr and Vib (both p = 0.034), and larger during VibPain compared to Ctr (p = 0.034) and Vib (p = 0.035). There were no differences in accuracy of jaw movements between the trials. For precision of jaw movements, the cycle-to-cycle variability was larger during VibPain compared to Ctr (p = 0.027) and Vib (p = 0.018). For integrated jaw–neck motor strategy, there was a difference between pain and non-pain trials, but no differences between unimodal and multimodal stimulation trials. For achievement of jaw-opening to a target position, the results show no effect on accuracy, but a reduced precision of jaw movements during combined proprioceptive and nociceptive multimodal stimulation.

P1735Two-hour algorithm for early diagnosis of acute myocardial infarction using a novel high-sensitivity cardiac troponin I assay

Abstract Background We aimed to derive and externally validate a 0/2h-algorithm using the novel high-sensitivity cardiac troponin I (hs-cTnI-Access) assay. Methods We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI) in two prospective chest pain trials. Two independent cardiologists adjudicated the final diagnosis including all available medical information including cardiac imaging. Hs-cTnI concentrations were measured at presentation and after 2h. Primary diagnostic endpoint was the derivation and validation of an hs-cTnI-Access specific 0/2h-algorithm. Primary prognostic endpoint was overall survival of patients after 30- and 720-days of follow-up. Results AMI was the adjudicated final diagnosis in 164/1131 (14.5%) patients in the derivation and in 88/1280 (6.9%) patients in the validation cohort. Median hs-cTnI Access concentrations at presentation were significantly higher in patients with AMI as compared to patients with non-AMI in both cohorts (104 ng/L versus 3.4 ng/L and 29 ng/L vs. 2.3 ng/L, p-value both <0.001) Applying the derived hs-cTnI-Access 0/2h-algorithm (Figure 1A) to the validation cohort (Figure 1B), 77.9% of patients were ruled-out (sensitivity 97.7% [95% CI, 92–99.7], negative predictive value [NPV] 99.8% [95% CI, 99.3–100]), and 5.8% of patients were ruled-in (specificity 98.6% [95% CI, 97.7–99.2], positive predictive value [PPV] 77% [95% CI, 65.8–86]). Among 1617 patients ruled-out for AMI in both cohorts together, 3 (0.2%) patients with AMI have been missed, of whom 2 patients had type 2 myocardial infarction (both with tachyarrhythmia). Patients ruled-out by the 0/2h-algorithm had a survival rate of 98.4% and 99.9% after two years or one year of follow up in both cohorts, respectively. Figure 1 Conclusions Diagnostic performance of the hs-cTnI Access 0/2h-algorithm for triage of AMI is excellent with high safety for rule-out and high accuracy for rule-in. Acknowledgement/Funding European Union, Swiss National Foundation, University Hospital Basel, University Basel

Interobserver agreement of an electronic von Frey device for measuring mechanical sensory thresholds in normal dogs

Electronic von Frey Aesthesiometry (VFA) has been previously reported as a useful method of mechanical quantitative sensory testing (QST) for evaluating neuropathic pain in dogs. Intraobserver agreement has been shown to be good to excellent; however, interobserver agreement has not been evaluated and is vital to the use of this technique in multicenter veterinary clinical trials in neuropathic pain. The goal of this study was to evaluate the interobserver agreement of sensory thresholds obtained using electronic VFA in a group of normal small breed dogs. Twenty healthy dogs (<20 kg) were recruited from the general practice population at the Ohio State University Veterinary Medical Center. Three clinically experienced yet QST novice evaluators used an electronic von Frey device to measure mechanical sensory threshold (ST) after a standardised training session conducted by an expert evaluator. Each dog was assessed by all three evaluators on the same day with both evaluator and limb test order randomised and testing sessions separated by 5 min. Mean ST values were averaged for all four limbs to produce a single value per dog for comparison between evaluators. Agreement between evaluators was determined using the intra-class correlation coefficient (ICC; two-way model for consistency, single measures).ICC across all three evaluators was 0.48, indicating moderate agreement. Moderate interobserver agreement is not sufficient to support the use of this technique in multi-center clinical trials, and our results underscore the importance of using a single evaluator for this QST technique until better agreement can be demonstrated.

Rescue and concomitant analgesics in placebo-controlled trials of pharmacotherapy for neuropathic pain and low back pain.

Rescue medication is commonly offered to participants in placebo-controlled trials of analgesic drugs. The use of pain medication in addition to the placebo or experimental drug may complicate the interpretation of effects and tolerability, but this issue has received little methodological attention. This study examined the handling and reporting of rescue and concomitant analgesic use in trials of pharmacotherapy for neuropathic pain and low back pain. We based our review on 265 trials included in 2 recent systematic reviews: 83 trials of low back pain and 182 of neuropathic pain. In total, 117 (44%) trials permitted rescue medication and 126 (48%) allowed participants to continue all or some of their usual analgesics. The utilization of rescue medication increased over time, occurring in 18% of trials before 2000 compared with 55% after 2000. Forty-one trials (16%) permitted both rescue analgesics and continued use of prestudy analgesics. More than one-third of the trials permitting rescue medication did not report the actual rescue drug consumption, and over half of the trials allowing concomitant analgesics did not report whether intake changed during the trial. Only 22 (19%) of the trials permitting rescue medication included complete information about whether rescue medication was used as an outcome, specified the drugs used, specified how consumption was assessed and measured, and reported and analyzed the use of rescue medication in each trial arm. Our findings suggest that poorly described procedures and incomplete reporting are likely to hinder the interpretation, critical appraisal, and replication of trial results.

Paracetamol is ineffective for acute low back pain even for patients who comply with treatment: complier average causal effect analysis of a randomized controlled trial

In 2014, the Paracetamol for Acute Low Back Pain (PACE) trial demonstrated that paracetamol had no effect compared with placebo in acute low back pain (LBP). However, noncompliance was a potential limitation of this trial. The aim of this study was to investigate the efficacy of paracetamol in acute LBP among compliers. Using individual participant data from the PACE trial (ACTN12609000966291), complier average causal effect (CACE), intention-to-treat, and per protocol estimates were calculated for pain intensity (primary), disability, global rating of symptom change, and function (all secondary) after 2 weeks of follow-up. Compliance was defined as intake of an average of at least 4 of the prescribed 6 tablets of regular paracetamol per day (2660 mg in total) during the first 2 weeks after enrolment. Exploratory analyses using alternative time points and definitions of compliance were conducted. Mean between-group differences in pain intensity on a 0 to 10 scale using the primary time point and definition of compliance were not clinically relevant (propensity-weighted CACE 0.07 [-0.37 to 0.50] P = 0.76; joint modelling CACE 0.23 [-0.16 to 0.62] P = 0.24; intention-to-treat 0.11 [-0.20 to 0.42] P = 0.49; per protocol 0.29 [-0.07 to 0.65] P = 0.12); results for secondary outcomes and for exploratory analyses were similar. Paracetamol is ineffective for acute LBP even for patients who comply with treatment. This reinforces the notion that management of acute LBP should focus on providing patients advice and reassurance without the addition of paracetamol.

Rehabilitation interventions in randomized controlled trials for low back pain: proof of statistical significance often is not relevant

BackgroundAn observed statistically significant difference between two interventions does not necessarily imply that this difference is clinically important for patients and clinicians. We aimed to assess if treatment effects of randomized controlled trials (RCTs) for low back pain (LBP) are statistically significant and clinically relevant, and if RCTs were powered to achieve clinically relevant differences on continuous outcomes.MethodsWe searched for all RCTs included in Cochrane Systematic Reviews focusing on the efficacy of rehabilitation interventions for LBP and published until April 2017. RCTs having sample size calculation and a planned minimal important difference were considered. In the primary analysis, we calculated the proportion of RCTs classified as “statistically significant and clinically relevant”, “statistically significant but not clinically relevant”, “not statistically significant but clinically relevant”, and “not statistically significant and not clinically relevant”. Then, we investigated how many times the mismatch between statistical significance and clinical relevance was due to inadequate power.ResultsFrom 20 eligible SRs including 101 RCTs, we identified 42 RCTs encompassing 81 intervention comparisons. Overall, 60% (25 RCTs) were statistically significant while only 36% (15 RCTs) were both statistically and clinically significant. Most trials (38%) did not discuss the clinical relevance of treatment effects when results did not reached statistical significance. Among trials with non-statistically significant findings, 60% did not reach the planned sample size, therefore being at risk to not detect an effect that is actually there (type II error).ConclusionOnly a minority of positive RCT findings was both statistically significant and clinically relevant. Scarce diligence or frank omissions of important tactic elements of RCTs, such as clinical relevance, and power, decrease the reliability of study findings to current practice.

Electronic Versus Traditional Data Collection: A Multicenter Randomized Controlled Perioperative Pain Trial

ABSTRACTBackground: Electronic data collection is increasingly available as a means to collect pain-related clinical trial data; however, effectiveness and costs relative to traditional data collection are uncertain.Aims: The aim of this study was to evaluate data quality, protocol adherence, satisfaction, and resource requirements of electronic data collection (i.e., Internet-based electronic submission) compared to traditional data collection methods (i.e., paper-based diaries and telephone interviews) in a perioperative factorial randomized controlled trial.Methods: This study was an open-label two-arm parallel randomized controlled trial. Women (18–75 years) undergoing breast cancer surgery were allocated to either electronic or traditional data collection and completed pain-related questionnaires at baseline, postoperative period, and 3-month follow-up (NCT02240199).Results: We acquired outcome data at all time points from 78 randomized patients, 38 in the electronic group and 40 in the traditional group. The number of data queries (e.g., erroneously entered data) per patient was higher in the electronic data group (4.92 [SD = 4.67] vs. 1.88 [SD = 1.51]; P < 0.001). No between-group differences were observed for compliance with medications, data completeness, loss to follow-up, or patient or research assistant satisfaction. More research assistant time per patient was spent collecting data in the traditional group (42.6 min [SD = 12.8] vs. 9.92 min [SD = 7.6]; P < 0.001); however, costs per patient were higher in the electronic group ($176.85 [SD = 2.90] vs. $16.33 [SD = 4.90]; P < 0.001).Conclusion: Electronic data collection is feasible for perioperative pain clinical trials. Additional trials, including different surgical populations, are needed to confirm our findings and optimize use of electronic data capture methods.

Assessing depression improvement with the remission evaluation and mood inventory tool (REMIT)

ObjectiveThe Remission Evaluation and Mood Inventory Tool (REMIT) was developed as a brief complementary measure to provide a more robust assessment of depression improvement than tracking DSM-V symptom improvement alone. This study provides further validation of the REMIT tool and examines its utility in predicting depression improvement. MethodsThe sample comprised 294 primary care patients enrolled in a telecare trial of pain plus depression and/or anxiety. Assessments collected included: REMIT, PHQ-9 and measures assessing anxiety, pain, sleep, fatigue, somatization, health-related quality of life and disability. Data was analyzed to assess the REMIT's validity, its minimally important difference (MID), and its utility in predicting 6-month depression improvement. ResultsConvergent and construct validity of REMIT was supported by moderate correlations with mental health measures and weaker correlation with physical health measures. MID of approximately 2 points for REMIT was estimated by two metrics: 0.5 standard deviation and 1 standard error of measurement. Both baseline and 3-month change in REMIT scores predicted depression improvement at 6 months. Indeed, REMIT was as good or better predictor than the PHQ-9. ConclusionThe REMIT measure is a brief 5-item tool that augments core DSM-V symptom-oriented metrics in assessing and predicting recovery from major depression.

Development and implementation of the physiotherapy-led exercise interventions for the treatment of rotator cuff disorders for the ‘Getting it Right: Addressing Shoulder Pain’ (GRASP) trial

ObjectivesThe Getting it Right: Addressing Shoulder Pain (GRASP) trial is a large-scale, multicentre, 2×2 factorial randomised controlled trial investigating clinical and cost-effectiveness of a progressive exercise programme versus best-practice advice, with or without corticosteroid injection, for treating people with rotator cuff disorders. Here we describe the development, implementation and details of the physiotherapy-led interventions. MethodsMedical Research Council guidance for developing complex interventions were used, taking into account clinical guidelines, expert and patient opinion, research evidence, current practice variation, and deliverability. A stakeholder meeting of 26 experts, clinicians, researchers, and patient representatives was used to design key components of the interventions. Stakeholders prioritised strengthening posterior rotator cuff muscles and using practical, easy-to-do exercises. The interventions were designed to be deliverable across the UK National Health Service. ResultsProgressive exercise consists of up to six sessions with a physiotherapist over 16 weeks. The best-practice advice consists of one face-to-face session with a physiotherapist with substantially greater reliance on self-management. Both interventions include self-management advice, home-exercise instruction, and behaviour-change strategies to target exercise adherence. All participants receive a Participant Information Booklet. The best-practice advice intervention is a self-guided system of progressively challenging exercises, with demonstration videos and written materials. The progressive exercise intervention has a wider range of exercise options, and greater flexibility for tailoring, progression, supervised practice and feedback. ConclusionGRASP has recruited 708 participants and will provide high quality evidence to inform management of people with shoulder pain due to a rotator cuff disorder. Results are anticipated in 2020. Trial registration numberISRCTN16539266; EudraCT number:2016-002991-28.

Improper Communication Makes for Squat: A Qualitative Study of the Health-Care Processes Experienced By Older Adults in a Clinical Trial for Back Pain.

Background:The study focused on perceptions of older adults toward the healthcare processes they experienced during a clinical trial for back pain that involved family medicine residents and licensed chiropractors.Methods:Individual semi-structured interviews were conducted with 115 older adults after a 12-week, 3-arm, randomized controlled trial. Two researchers conducted thematic analysis with inductive coding using qualitative software to identify participants’ salient experiences of the doctor–patient relationship, healthcare process, and collaboration between study providers. Investigators categorized thematic codes within an existing framework of clinical excellence in primary care.Results:Participants emphasized provider communication and interpersonal relationships, professionalism and passion for patient care, clinical and diagnostic acumen, and skillful negotiation of the health-care system. Older adults also described the importance of interdisciplinary collaboration and their preferences for receiving hands-on treatments for musculoskeletal conditions.Conclusion:These older adults valued doctors who communicated clearly and spent time listening to their concerns. Many participants appreciated clinicians who supported an active role for patients in their health-care and who provided touch-based care for musculoskeletal conditions.

Commentary on "Cognitive Functional Therapy in Patients with Non-Specific Chronic Low Back Pain".

In this issue, you will find a paper by Vibe Fersum et al., entitled “Cognitive Functional Therapy in Patients with Non Specific Chronic Low Back Pain: A Randomized Controlled Trial 3-year Follow Up” (Vibe Fersum et al., 2019). This interesting and well done paper reports on 3 year outcomes from a previously reported randomized trial. The primary findings are lower self-reported disability for those randomized to receive cognitive functional therapy instead of manual therapy and exercise. This is a strong contribution to the literature as there is growing interest in psychologically informed approaches to managing musculoskeletal pain. In particular, the authors are to be commended for reporting 3-year data, as follow up beyond 12 or 24 months is rare in conservative treatment trials for low back pain. This commentary will introduce some issues for readers to consider when interpreting the results of this study. The primary issue when reading this paper is to consider the potential impact that loss to follow up has on the long-term effects of cognitive functional therapy. This issue is mentioned by the authors as a primary limitation in the paper, and I will expand on it briefly. Only 52% (63/121) of those from the original trial provided follow up data at 3 years. The authors have taken appropriate care statistically in accounting for this loss to follow up via sensitivity analyses using mixed models and multiple imputation. However, the fact remains that this was a relatively small trial to begin with and the 3-year attrition rate has substantially eroded the original sample size. The absolute number of subjects providing follow up data is small enough (n< 50 per treatment group) that the precision of reported treatment effects is limited. Further drawing attention to this issue is the evidence of differential loss to follow up that suggests those providing 3-year data had lower psychosocial distress. This is a clinical relevant baseline difference because psychological distress is often an important mediator of treatment outcome. The authors do account for this by adjusting analyses for baseline scores. While that is an acceptable statistical solution, it doesn’t entirely account for the impact selective follow-up could have on the 3-year results. Another issue to consider when reading this paper is the timing of the treatment effects. At 3-years group differences still exist for disability and most of this gain appears to have much earlier (i.e. at 3 month follow up). This is evidence supporting that after an initial period of receiving a treatment a favourable trajectory is established. Statistically the treatment effect was sustained at 3 years but the size of the effect is cut in half from when the benefit was largest (i.e. 3 month follow up). Even with a smaller absolute effect at 3 years, the effect sizes reported remain large when compared to others in this field. This deserves mention both in the “good news” category (i.e. even at 3 years these effect sizes are larger than what you see in the typical trial) but also in the “need more studies” category (i.e. can these effect sizes be replicated when the treatment is delivered by others in different settings). Several of the next steps one could take from this clinical trial are well aligned with recent research priorities identified for psychological informed practice. For example, cognitive functional therapy was associated with improved self-reported disability but identifying specific factors involved in the process of achieving better outcomes were not part of these analyses. Future studies could consider measures of pain intensity, self-efficacy, fear of pain and catastrophizing and identify which are key mediators of favourable outcomes when receiving cognitive functional therapy. Another seemingly informative study would be to investigate the impact of “booster sessions” for cognitive functional therapy that could be delivered as part of group sessions or tele-health. Use of such post-treatment booster sessions could help determine if the size of treatment effects initially obtained able to be maintained at later follow up times. I appreciate the chance to provide additional insight into this article. The authors are to be congratulated for presenting work that provides valuable information on longer term effects of cognitive functional therapy and also helps to plan future clinical research. None declared.

Subliminal emotional pictures are capable of modulating early cerebral responses to pain in fibromyalgia.

Pain experience involves a complex relationship between sensory and both emotional and cognitive factors, which appear to be mediated by different neural pathways. Previous evidence has shown that whereas conscious processing of unpleasant stimuli enhances pain perception, the influence of emotions on pain under unaware conditions is much less known. The need to better characterise the relationship between pain processing and emotional factors is crucial for dealing with chronic pain conditions. Therefore, the present study aimed to explore the neural correlates relating to the influence of visual masking emotional stimulation on the processing of painful stimuli in chronic pain patients suffering from fibromyalgia (FM). Twenty FM and 22 healthy control (HC) women participated in the study. The experimental masking paradigm consisted of a rapid succession of two types of stimuli, where a masked picture (neutral, negative or pain-related) was followed by a laser stimulus (painful or not painful). LEP activity was recorded at sixty scalp electrodes. An LEP-amplitude approach was used to quantify the main cerebral waves linked to pain response. ANOVAs indicated that the posterior regions of the P1 component were sensitive to experimental manipulation (p<0.05). Specifically, FM patients showed higher amplitudes to painful stimuli preceded by pain-related pictures compared with painful trials preceded by other emotional pictures. The FM group also showed greater amplitudes than those in the HC group in P2a and P2b waves. In addition to the scalp data, at the neural level the posterior cingulate cortex, lingual gyrus and insular cortex showed higher activation in the FM group than in the HC group. Our findings show an early cerebral modulation of pain (as reflected by the P1) in FM patients, suggesting that only pain-related information, even when it is unconsciously perceived, is capable to enhance exogenous (automatic) attention, increasing the neural activity involved in processing painful stimulation. Further research is needed to fully understand unconscious emotional influences on pain in fibromyalgia.

Can Training Increase Reporting Accuracy and Study Power in Human Pain Trials

Can Training Increase Reporting Accuracy and Study Power in Human Pain Trials

Checklist for the preparation and review of pain clinical trial publications: a pain-specific supplement to CONSORT.

Randomized clinical trials (RCTs) are considered the gold standard when assessing the efficacy of interventions because randomization of treatment assignment minimizes bias in treatment effect estimates. However, if RCTs are not performed with methodological rigor, many opportunities for bias in treatment effect estimates remain. Clear and transparent reporting of RCTs is essential to allow the reader to consider the opportunities for bias when critically evaluating the results. To promote such transparent reporting, the Consolidated Standards of Reporting Trials (CONSORT) group has published a series of recommendations starting in 1996. However, a decade after the publication of the first CONSORT guidelines, systematic reviews of clinical trials in the pain field identified a number of common deficiencies in reporting (e.g., failure to identify primary outcome measures and analyses, indicate clearly the numbers of participants who completed the trial and were included in the analyses, or report harms adequately). Qualitative review of a diverse set of published recommendations and systematic reviews that addressed the reporting of clinical trials, including those related to all therapeutic indications (e.g., CONSORT) and those specific to pain clinical trials. A checklist designed to supplement the content covered in the CONSORT checklist with added details relating to challenges specific to pain trials or found to be poorly reported in recent pain trials was developed. Authors and reviewers of analgesic RCTs should consult the CONSORT guidelines and this checklist to ensure that the issues most pertinent to pain RCTs are reported with transparency.

Ethical considerations in the design, execution, and analysis of clinical trials of chronic pain treatments.

Introduction:In the field of pain research, clinical trials may randomize over 500 subjects and include more than 150 sites spanning over a dozen countries.Methods:This review examines the ethical considerations affecting clinical trial design, execution, and analysis of trials for chronic pain. The Belmont Report has been the touchstone for human studies protection efforts since 1979. Commissioned by the U.S. government in response to ethical failures in medical research, such as the Tuskegee Syphilis Study, the report emphasizes 3 basic principles: respect for persons, beneficence, and justice. Trial design and sample size have important ethical implications.Conclusions:Measures to enhance trial transparency and combat publication and many other types of bias should be implemented.

The ACTTION Guide to Clinical Trials of Pain Treatments: standing on the shoulders of giants.

The ACTTION Guide to Clinical Trials of Pain Treatments: standing on the shoulders of giants.

Designing and conducting proof-of-concept chronic pain analgesic clinical trials.

Introduction:The evolution of pain treatment is dependent on successful development and testing of interventions. Proof-of-concept (POC) studies bridge the gap between identification of a novel target and evaluation of the candidate intervention's efficacy within a pain model or the intended clinical pain population.Methods:This narrative review describes and evaluates clinical trial phases, specific POC pain trials, and approaches to patient profiling.Results:We describe common POC trial designs and their value and challenges, a mechanism-based approach, and statistical issues for consideration.Conclusion:Proof-of-concept trials provide initial evidence for target use in a specific population, the most appropriate dosing strategy, and duration of treatment. A significant goal in designing an informative and efficient POC study is to ensure that the study is safe and sufficiently sensitive to detect a preliminary efficacy signal (ie, a potentially valuable therapy). Proof-of-concept studies help avoid resources wasted on targets/molecules that are not likely to succeed. As such, the design of a successful POC trial requires careful consideration of the research objective, patient population, the particular intervention, and outcome(s) of interest. These trials provide the basis for future, larger-scale studies confirming efficacy, tolerability, side effects, and other associated risks.

Current methods and challenges for acute pain clinical trials.

The clinical setting of acute pain has provided some of the first approaches for the development of analgesic clinical trial methods. This article reviews current methods and challenges and provides recommendations for future design and conduct of clinical trials of interventions to treat acute pain. Growing knowledge about important diverse patient factors as well as varying pain responses to different acute pain conditions and surgical procedures has highlighted several emerging needs for acute pain trials. These include development of early-phase trial designs that minimize variability and thereby enhance assay sensitivity, minimization of bias through blinding and randomization to treatment allocation, and measurement of clinically relevant outcomes such as movement-evoked pain. However, further improvements are needed, in particular for the development of trial methods that focus on treating complex patients at high risk of severe acute pain.

Patients’ experiences and perceptions of chronic intractable pain: a qualitative study nested within a neuropathic pain trial

Intensification of aquaculture production systems requires more nutritionally complete diets to maximize productive performance, metabolic processes and overall fish health. In previous studies, dietary supplementation with choline (both choline chloride and phosphatidylcholine) improved productive performance of tilapia cultivated in clear water. Nevertheless, choline has not been tested in a biofloc technology system (BFT), a culture system inhabited by diverse microorganisms that serve as food sources for fish. The objective of this study was to determine whether supplementation with phosphatidylcholine, also known as vegetable choline (0, 400, 800 and 1200 mg/kg of feed), in diets of Nile tilapia (Oreochromis niloticus) in a biofloc system would stimulate energy metabolism and the serum antioxidant system, with consequent improvements in productive performance. Juvenile Nile tilapia (≅ 8 g) were tested over 40 days. During this period, zootechnical performance was evaluated. Blood, gills and liver were collected at the end of the experiment for biochemical and energetic analyses. There were no significant differences between the treatments with respect to parameters of zootechnical performance (body weight, biomass gain, feed conversion, specific growth rate and hepatosomatic index) (P > 0.05). Alanine aminotransferase levels were significantly lower in fish fed 800 mg/kg of phosphatidylcholine than in control; total protein levels increased as a result of increased globulin levels. Activities of creatine kinase enzyme (800 and 1200 mg choline/kg treatments) and pyruvate kinase (1200 mg choline/kg) were significantly higher in choline-treated fish than in controls. Supplementation with the three doses of choline reduced hepatic lipid peroxidation and stimulated glutathione S-transferase activity. By contrast, the activities of other antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase) were altered in the livers of fish that consumed the highest doses of phosphatidylcholine. We conclude that, in a biofloc system, supplementation with phosphatidylcholine had no effect on the zootechnical performance of tilapia; however, it stimulated energy metabolism and contributed to activation of hepatic GST and lower levels of lipid peroxidation.

Telehealth Therapy Effects of Nurses and Mental Health Professionals From 2 Randomized Controlled Trials for Chronic Back Pain.

To compare the efficacy of mental health professional versus primary care nurse-delivered telehealth cognitive-behavioral therapy (CBT) and supportive care (SC) treatments for chronic low back pain, using data from 2 separate randomized controlled trials. Both trials were completed in the same hospital and used the same study design, research team, and outcome measures. Participants from Study 1 (Mental Health Professional Study) (N=66; 2007 to 2011) and Study 2 (Nursing Study) (N=61; 2012 to 2016) were patients with chronic low back pain (≥4/10 intensity) randomized to either an 8-week CBT or an SC telehealth condition matched for contact frequency, format, and time. Participants completed validated measures of improvement in back pain disability (Roland Morris Disability Questionnaire [RMDQ]), pain intensity (Numeric Rating Scale [NRS]), depressive symptoms (Beck Depression Inventory 2 [BDI-2]), pain catastrophizing (Pain Catastrophizing Scale [PCS]), and overall improvement (Global Clinical Impressions [GCI]). Intent-to-treat analyses at posttreatment showed that scores on the RMDQ (Cohen d=0.33 to 0.55), NRS (d=0.45 to 0.90), PCS (d=0.21 to 0.41), and GCI (18.5% to 39.1%) improved significantly in both studies and in both treatments from pretreatment to posttreatment. Changes in BDI scores were inconsistent (d=-0.06 to 0.51). The analyses revealed no significant differences in treatment efficacy between the trained nurse versus the mental health professionals on the RMDQ, NRS, PCS, or GCI measures (P>0.20). Results from these clinical trials suggest that the benefits of home-based, telehealth-delivered CBT and SC treatments for chronic back pain were comparable when delivered by a primary care nurse or mental health professional.