A Systematic Review of the Reporting Quality of Observational Studies That Use Mediation Analyses

Mediation analysis is a common statistical method used to investigate mechanisms of health exposure and interventions. The reporting quality of mediation studies used in randomised controlled trials has been considered heterogeneous and incomplete. The reporting quality of mediation analysis in observational studies is unknown. We conducted a systematic review to describe the reporting standards of recently published observational studies that used mediation analysis to understand the mechanism of health exposures. We searched for studies published between June 2017 and June 2019 indexed in EMBASE, MEDLINE and PsycINFO. Two reviewers screened articles and selected a random sample of 50 eligible studies for inclusion. We included studies across 13 healthcare fields and ten different health conditions. Most studies (74%) collected data on healthy individuals to assess their risk of developing a health disorder. Psychosocial and behavioural factors (self-control, self-esteem, alcohol consumption, pain) were the most prevalent exposures (n = 30, 60%), outcomes (n = 23, 46%) and mediators (n = 29, 58%). Most studies used a cross-sectional design (64%, n = 32), and a few studies reported sample size calculations (4%, n = 8). In 20% (n = 10) of the studies, adjustment for confounders was reported. Only 10% (n = 5) of studies reported the assumptions underlying the mediation analysis, and 14% (n = 7) of studies conducted some sensitivity analysis to assess the degree which unmeasured confounders would affect the estimate of the mediation effect. Mediation analysis is a common method used to investigate mechanisms in prevention research. The reporting of mediation analysis in observational studies is incomplete and may impact reproducibility, evidence synthesis and implementation

Depressive symptoms moderate functional connectivity within the emotional brain in chronic pain

Background Depressive symptoms are often comorbid with chronic pain. These conditions share aberrant emotion processing and regulation, as well as having common brain networks. However, the relationship between depressive symptoms and chronic pain and the effects on emotional brain function are unclear. Aims The present study aimed to disentangle the effects of chronic pain and depressive symptoms on functional connectivity between regions implicated in both these conditions. Method Twenty-six individuals with chronic pain (referred to as the pain group) and 32 healthy controls underwent resting-state functional magnetic resonance imaging and completed the Beck Depression Inventory. Main effects of group, depressive symptoms (total severity score) and their interaction on the functional connectivity of three seed regions (the left and right amygdalae and the medial prefrontal cortex; mPFC) with the rest of the brain were evaluated. In cases of significant interaction, moderation analyses were conducted. Results The group × depressive symptoms interaction was significantly associated with changes in connectivity between the right amygdala and the mPFC (family-wise error-corrected P-threshold (pFWEc = 0.008). In the moderation analysis, the pain group showed weaker connectivity between these regions at lower levels of depressive symptoms (P = 0.020), and stronger connectivity at higher levels of depressive symptoms (P = 0.003), compared with the healthy controls. In addition, the strength of connectivity decreased in the healthy controls (P = 0.005) and increased in the pain group (P = 0.014) as the severity of depressive symptoms increased. Conclusions Depressive symptoms moderate the impact of chronic pain on emotional brain function, with potential implications for the choice of treatment for chronic pain

Corrigendum: Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain(Front. Neurol., (2019), 10, (1110), 10.3389/fneur.2019.01110)

In the original article, there was an error in the Author Contributions. It has been updated to align with the guidelines of the International Committee of Medical Journal Editors. A correction has been made to the Author Contributions

Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain

© Copyright © 2019 Naylor, Hesam-Shariati, McAuley, Boag, Newton-John, Rae and Gustin. A decrease in glutamate in the medial prefrontal cortex (mPFC) has been extensively found in animal models of chronic pain. Given that the mPFC is implicated in emotional appraisal, cognition and extinction of fear, could a potential decrease in glutamate be associated with increased pessimistic thinking, fear and worry symptoms commonly found in people with chronic pain? To clarify this question, 19 chronic pain subjects and 19 age- and gender-matched control subjects without pain underwent magnetic resonance spectroscopy. Both groups also completed the Temperament and Character, the Beck Depression and the State Anxiety Inventories to measure levels of harm avoidance, depression, and anxiety, respectively. People with chronic pain had significantly higher scores in harm avoidance, depression and anxiety compared to control subjects without pain. High levels of harm avoidance are characterized by excessive worry, pessimism, fear, doubt and fatigue. Individuals with chronic pain showed a significant decrease in mPFC glutamate levels compared to control subjects without pain. In people with chronic pain mPFC glutamate levels were significantly negatively correlated with harm avoidance scores. This means that the lower the concentration of glutamate in the mPFC, the greater the total scores of harm avoidance. High scores are associated with fearfulness, pessimism, and fatigue-proneness. We suggest that chronic pain, particularly the stress-induced release of glucocorticoids, induces changes in glutamate transmission in the mPFC, thereby influencing cognitive, and emotional processing. Thus, in people with chronic pain, regulation of fear, worry, negative thinking and fatigue is impaired

Corrigendum: Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain.

[This corrects the article DOI: 10.3389/fneur.2019.01110.]

Efficacy, acceptability, and safety of muscle relaxants for adults with non-specific low back pain: Systematic review and meta-analysis

AbstractObjective To investigate the efficacy, acceptability, and safety of muscle relaxants for low back pain. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and WHO ICTRP from inception to 23 February 2021. Eligibility criteria for study selection Randomised controlled trials of muscle relaxants compared with placebo, usual care, waiting list, or no treatment in adults (≥18 years) reporting non-specific low back pain. Data extraction and synthesis Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty of the evidence using the Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development and Evaluations, respectively. Random effects meta-analytical models through restricted maximum likelihood estimation were used to estimate pooled effects and corresponding 95% confidence intervals. Outcomes included pain intensity (measured on a 0-100 point scale), disability (0-100 point scale), acceptability (discontinuation of the drug for any reason during treatment), and safety (adverse events, serious adverse events, and number of participants who withdrew from the trial because of an adverse event). Results 49 trials were included in the review, of which 31, sampling 6505 participants, were quantitatively analysed. For acute low back pain, very low certainty evidence showed that at two weeks or less non-benzodiazepine antispasmodics were associated with a reduction in pain intensity compared with control (mean difference -7.7, 95% confidence interval-12.1 to-3.3) but not a reduction in disability (-3.3, -7.3 to 0.7). Low and very low certainty evidence showed that non-benzodiazepine antispasmodics might increase the risk of an adverse event (relative risk 1.6, 1.2 to 2.0) and might have little to no effect on acceptability (0.8, 0.6 to 1.1) compared with control for acute low back pain, respectively. The number of trials investigating other muscle relaxants and different durations of low back pain were small and the certainty of evidence was reduced because most trials were at high risk of bias. Conclusions Considerable uncertainty exists about the clinical efficacy and safety of muscle relaxants. Very low and low certainty evidence shows that non-benzodiazepine antispasmodics might provide small but not clinically important reductions in pain intensity at or before two weeks and might increase the risk of an adverse event in acute low back pain, respectively. Large, high quality, placebo controlled trials are urgently needed to resolve uncertainty. Systematic review registration PROSPERO CRD42019126820 and Open Science Framework https://osf.io/mu2f5/

The relationship between neurocognitive performance and HRV parameters in nurses and non-healthcare participants.

Nurses represent the largest sector of the healthcare workforce, and it is established that they are faced with ongoing physical and mental demands that leave many continuously stressed. In turn, this chronic stress may affect cardiac autonomic activity, which can be non-invasively evaluated using heart rate variability (HRV). The association between neurocognitive parameters during acute stress situations and HRV has not been previously explored in nurses compared to non-nurses and such, our study aimed to assess these differences. Neurocognitive data were obtained using the Mini-Mental State Examination and Cognistat psychometric questionnaires. ECG-derived HRV parameters were acquired during the Trier Social Stress Test. Between-group differences were found in domain-specific cognitive performance for the similarities (p = .03), and judgment (p = .002) domains and in the following HRV parameters: SDNNbaseline, (p = .004), LFpreparation (p = .002), SDNNpreparation (p = .002), HFpreparation (p = .02), and TPpreparation (p = .003). Negative correlations were found between HF power and domain-specific cognitive performance in nurses. In contrast, both negative and positive correlations were found between HRV and domain-specific cognitive performance in the non-nurse group. The current findings highlight the prospective use of autonomic HRV markers in relation to cognitive performance while building a relationship between autonomic dysfunction and cognition

Efficacy and safety of medicines targeting neurotrophic factors in the management of low back pain: Protocol for a systematic review and meta-analysis

Background: Low back pain (LBP) is the leading cause of years lived with disability worldwide. Most people with LBP receive the diagnosis of nonspecific LBP or sciatica. Medications are commonly prescribed but have limited analgesic effects and are associated with adverse events. A novel treatment approach is to target neurotrophins such as nerve growth factor (NGF) to reduce pain intensity. NGF inhibitors have been tested in some randomized controlled trials (RCTs) in recent years, showing promise for the treatment of chronic LBP; however, their efficacy and safety need to be evaluated to guide regulatory actions. Objective: The aim of this study is to evaluate the efficacy and safety of medicines targeting neurotrophins in patients with LBP and sciatica. Methods: In this systematic review, we will include published and unpublished records of parallel RCTs and the first phase of crossover RCTs that compare the effects of medicines targeting neurotrophins with any control group. We will search the CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, EU Clinical Trials Register, and WHO International Clinical Registry Platform databases from inception. Pairs of authors will independently screen the records for eligibility, and we will independently extract data in duplicate. We will conduct a quantitative synthesis (meta-analysis) with the studies that report sufficient data and compare the medicines of interest versus placebo. We will use random-effects models and calculate estimates of effects and heterogeneity for each outcome. We will assess the risk of bias for each study using the Cochrane Collaboration tool, and form judgments of confidence in the evidence according to GRADE recommendations. We will use the PRISMA statement to report the findings. We plan to conduct subgroup analyses by condition, type of medication, and time point. We will also assess the impact of a potential new trial on an existing meta-analysis. Data from studies that meet inclusion criteria but cannot be included in the meta-analysis will be reported narratively. Results: The protocol was registered on the Open Science Framework on May 19, 2020. As of December 2020, we have identified 1932 records. Conclusions: This systematic review and meta-analysis will assess the evidence for the efficacy and safety of NGF inhibitors for pain in patients with nonspecific LBP and sciatica. The inclusion of new studies and unpublished data may improve the precision of the effect estimates and guide regulatory actions of the medications for LBP and sciatica

Internet-Delivered Dialectical Behavioral Therapy Skills Training for Chronic Pain: Protocol for a Randomized Controlled Trial

Background: Emotion dysregulation is key to the development and maintenance of chronic pain, feeding into a cycle of worsening pain and disability. Dialectical behavioral therapy (DBT), an evidence-based treatment for complex transdiagnostic conditions presenting with high emotion dysregulation, may be beneficial to manage and mitigate the emotional and sensory aspects of chronic pain. Increasingly, DBT skills training as a key component of standard DBT is being delivered as a stand-alone intervention without concurrent therapy to help develop skills for effective emotion regulation. A previous repeated-measure single-case trial investigating a novel technologically driven DBT skills training, internet-delivered DBT skills training for chronic pain (iDBT-Pain), revealed promising findings to improve both emotion dysregulation and pain intensity. Objective: This randomized controlled trial aims to examine the efficacy of iDBT-Pain in comparison with treatment as usual to reduce emotion dysregulation (primary outcome) for individuals with chronic pain after 9 weeks and at the 21-week follow-up. The secondary outcomes include pain intensity, pain interference, anxiety symptoms, depressive symptoms, perceived stress, posttraumatic stress, harm avoidance, social cognition, sleep quality, life satisfaction, and well-being. The trial also examines the acceptability of the iDBT-Pain intervention for future development and testing. Methods: A total of 48 people with chronic pain will be randomly assigned to 1 of 2 conditions: treatment and treatment as usual. Participants in the treatment condition will receive iDBT-Pain, consisting of 6 live web-based group sessions led by a DBT skills trainer and supervised by a registered psychologist and the iDBT-Pain app. Participants in the treatment-as-usual condition will not receive iDBT-Pain but will still access their usual medication and health interventions. We predict that iDBT-Pain will improve the primary outcome of emotion dysregulation and the secondary outcomes of pain intensity, pain interference, anxiety symptoms, depressive symptoms, perceived stress, harm avoidance, social cognition, sleep quality, life satisfaction, and well-being. A linear mixed model with random effects of individuals will be conducted to investigate the differences between the baseline, 9-week (primary end point), and 21-week (follow-up) assessments as a function of experimental condition. Results: Recruitment started in February 2023, and the clinical trial started in March 2023. Data collection for the final assessment is planned to be completed by July 2024. Conclusions: If our hypothesis is confirmed, our findings will contribute to the evidence for the efficacy and acceptability of a viable intervention that may be used by health care professionals for people with chronic pain. The results will add to the chronic pain literature to inform about the potential benefits of DBT skills training for chronic pain and will contribute evidence about technologically driven interventions

Emotion regulation skills-focused interventions for chronic pain: A systematic review and meta-analysis

Objectives: To investigate the effect of emotion regulation skills-focused (ERSF) interventions to reduce pain intensity and improve psychological outcomes for people with chronic pain and to narratively report on safety and intervention compliance. Methods: Six databases and four registries were searched for randomized controlled trials (RCTs) up to 29 April 2022. Risk of bias was evaluated using the Cochrane RoB 2.0 tool, and certainty of evidence was assessed according to the Grading, Assessment, Development and Evaluation (GRADE). Meta-analyses for eight studies (902 participants) assessed pain intensity (primary outcome), emotion regulation, affect, symptoms of depression and anxiety, and pain interference (secondary outcomes), at two time points when available, post-intervention (closest to intervention end) and follow-up (the first measurement after the post-intervention assessment). Results: Compared to TAU, pain intensity improved post-intervention (weighted mean difference [WMD] = −10.86; 95% confidence interval [CI] [−17.55, −2.56]) and at follow-up (WMD = −11.38; 95% CI [−13.55, −9.21]). Emotion regulation improved post-intervention (standard mean difference [SMD] = 0.57; 95% CI [0.14, 1.01]), and depressive symptoms improved at follow-up (SMD = −0.45; 95% CI [−0.66, −0.24]). Compared to active comparators, anxiety symptoms improved favouring the comparator post-intervention (SMD = 0.10; 95% CI [0.03, 0.18]), and compared to CBT, pain interference improved post-intervention (SMD = −0.37; 95% CI [−0.69, −0.04]). Certainty of evidence ranged from very low to moderate. Significance: The findings provide evidence that ERSF interventions reduce pain intensity for people with chronic pain compared to usual treatment. These interventions are at least as beneficial to reduce pain intensity as the current gold standard psychological intervention, CBT. However, the limited number of studies and certainty of evidence mean further high-quality RCTs are warranted. Additionally, further research is needed to identify whether ERSF interventions may be more beneficial for specific chronic pain conditions