Flawed, futile, and fabricated-features that limit confidence in clinical research in pain and anaesthesia: a narrative review.

The randomised controlled trial is the foundation of clinical research; yet there is concern that many trials have flaws in design, conduct, and reporting that undermine trustworthiness. Common flaws in trials include high risk of bias, small size, outcomes irrelevant to clinical care and patient's experience, and inability to detect efficacy even if present. These flaws carry forward into systematic reviews, which can confer the label of 'high-quality evidence' on inadequate data. Trials can be futile because their flaws mean that they cannot deliver any meaningful result in that different results in a small number of patients would be sufficient to change conclusions. Some trials have been discovered to be fabricated, the number of which is growing. The fields of anaesthesia and pain have more fabricated trials than other clinical fields, possibly because of increased vigilance. This narrative review examines these themes in depth whilst acknowledging an inescapable conclusion: that much of our clinical evidence is in trouble, and special measures are needed to bolster quality and confidence.

Psychological therapies delivered remotely for the management of chronic pain (excluding headache) in adults.

BACKGROUND: Chronic pain (pain lasting three months or more) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Common types (excluding headache) include back pain, fibromyalgia, and neuropathic pain. Access to traditional face-to-face therapies can be restricted by healthcare resources, geography, and cost. Remote technology-based delivery of psychological therapies has the potential to overcome treatment barriers. However, their therapeutic effectiveness compared to traditional delivery methods requires further investigation. OBJECTIVES: To determine the benefits and harms of remotely-delivered psychological therapies compared to active control, waiting list, or treatment as usual for the management of chronic pain in adults. SEARCH METHODS: We searched for randomised controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and PsycINFO to 29 June 2022. We also searched clinical trials registers and reference lists. We conducted a citation search of included trials to identify any further eligible trials. SELECTION CRITERIA: We included RCTs in adults (≥ 18 years old) with chronic pain. Interventions included psychological therapies with recognisable psychotherapeutic content or based on psychological theory. Trials had to have delivered therapy remote from the therapist (e.g. Internet, smartphone application) and involve no more than 30% contact time with a clinician. Comparators included treatment as usual (including waiting-list controls) and active controls (e.g. education). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: We included 32 trials (4924 participants) in the analyses. Twenty-five studies delivered cognitive behavioural therapy (CBT) to participants, and seven delivered acceptance and commitment therapy (ACT). Participants had back pain, musculoskeletal pain, opioid-treated chronic pain, mixed chronic pain, hip or knee osteoarthritis, spinal cord injury, fibromyalgia, provoked vestibulodynia, or rheumatoid arthritis. We assessed 25 studies as having an unclear or high risk of bias for selective reporting. However, across studies overall, risk of bias was generally low. We downgraded evidence certainty for primary outcomes for inconsistency, imprecision, and study limitations. Certainty of evidence ranged from moderate to very low. Adverse events were inadequately reported or recorded across studies. We report results only for studies in CBT here. Cognitive behavioural therapy (CBT) versus treatment as usual (TAU) Pain intensity Immediately after treatment, CBT likely demonstrates a small beneficial effect compared to TAU (standardised mean difference (SMD) -0.28, 95% confidence interval (CI) -0.39 to -0.16; 20 studies, 3206 participants; moderate-certainty evidence). Participants receiving CBT are probably more likely to achieve a 30% improvement in pain intensity compared to TAU (23% versus 11%; risk ratio (RR) 2.15, 95% CI 1.62 to 2.85; 5 studies, 1347 participants; moderate-certainty evidence). They may also be more likely to achieve a 50% improvement in pain intensity (6% versus 2%; RR 2.31, 95% CI 1.14 to 4.66; 4 studies, 1229 participants), but the evidence is of low certainty. At follow-up, there is likely little to no difference in pain intensity between CBT and TAU (SMD -0.04, 95% CI -0.17 to 0.09; 8 studies, 959 participants; moderate-certainty evidence). The evidence comparing CBT to TAU on achieving a 30% improvement in pain is very uncertain (40% versus 24%; RR 1.70, 95% CI 0.82 to 3.53; 1 study, 69 participants). No evidence was available regarding a 50% improvement in pain. Functional disability Immediately after treatment, CBT may demonstrate a small beneficial improvement compared to TAU (SMD -0.38, 95% CI -0.53 to -0.22; 14 studies, 2672 participants; low-certainty evidence). At follow-up, there is likely little to no difference between treatments (SMD -0.05, 95% CI -0.23 to 0.14; 3 studies, 461 participants; moderate-certainty evidence). Quality of life Immediately after treatment, CBT may not have resulted in a beneficial effect on quality of life compared to TAU, but the evidence is very uncertain (SMD -0.16, 95% CI -0.43 to 0.11; 7 studies, 1423 participants). There is likely little to no difference between CBT and TAU on quality of life at follow-up (SMD -0.16, 95% CI -0.37 to 0.05; 3 studies, 352 participants; moderate-certainty evidence). Adverse events Immediately after treatment, evidence about the number of people experiencing adverse events is very uncertain (34% in TAU versus 6% in CBT; RR 6.00, 95% CI 2.2 to 16.40; 1 study, 140 participants). No evidence was available at follow-up. Cognitive behavioural therapy (CBT) versus active control Pain intensity Immediately after treatment, CBT likely demonstrates a small beneficial effect compared to active control (SMD -0.28, 95% CI -0.52 to -0.04; 3 studies, 261 participants; moderate-certainty evidence). The evidence at follow-up is very uncertain (mean difference (MD) 0.50, 95% CI -0.30 to 1.30; 1 study, 127 participants). No evidence was available for a 30% or 50% pain intensity improvement. Functional disability Immediately after treatment, there may be little to no difference between CBT and active control on functional disability (SMD -0.26, 95% CI -0.55 to 0.02; 2 studies, 189 participants; low-certainty evidence). The evidence at follow-up is very uncertain (MD 3.40, 95% CI -1.15 to 7.95; 1 study, 127 participants). Quality of life Immediately after treatment, there is likely little to no difference in CBT and active control (SMD -0.22, 95% CI -1.11 to 0.66; 3 studies, 261 participants; moderate-certainty evidence). The evidence at follow-up is very uncertain (MD 0.00, 95% CI -0.06 to 0.06; 1 study, 127 participants). Adverse events Immediately after treatment, the evidence comparing CBT to active control is very uncertain (2% versus 0%; RR 3.23, 95% CI 0.13 to 77.84; 1 study, 135 participants). No evidence was available at follow-up. AUTHORS' CONCLUSIONS: Currently, evidence about remotely-delivered psychological therapies is largely limited to Internet-based delivery of CBT. We found evidence that remotely-delivered CBT has small benefits for pain intensity (moderate certainty) and functional disability (moderate to low certainty) in adults experiencing chronic pain. Benefits were not maintained at follow-up. Our appraisal of quality of life and adverse events outcomes post-treatment were limited by study numbers, evidence certainty, or both. We found limited research (mostly low to very low certainty) exploring other psychological therapies (i.e. ACT). More high-quality studies are needed to assess the broad translatability of psychological therapies to remote delivery, the different delivery technologies, treatment longevity, comparison with active control, and adverse events.

Antidepressants for pain management in adults with chronic pain: a network meta-analysis.

BACKGROUND: Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions. OBJECTIVES: To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022. SELECTION CRITERIA: We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm.  DATA COLLECTION AND ANALYSIS: Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal. MAIN RESULTS: This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain.  Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes. AUTHORS' CONCLUSIONS: Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.

The STAR care pathway for patients with chronic pain after total knee replacement: four-year follow-up of a randomised controlled trial.

BACKGROUND: The Support and Treatment After Replacement (STAR) care pathway is a clinically important and cost-effective intervention found to improve pain outcomes over one year for people with chronic pain three months after total knee replacement (TKR). We followed up STAR trial participants to evaluate the longer-term clinical- and cost-effectiveness of this care pathway. METHODS: Participants who remained enrolled on the trial at one year were contacted by post at a median of four years after randomisation and invited to complete a questionnaire comprising the same outcomes collected during the trial. We captured pain (co-primary outcome using the Brief Pain Inventory (BPI) pain severity and interference scales; scored 0-10, best to worst), function, neuropathic characteristics, emotional aspects of pain, health-related quality of life, and satisfaction. Electronic hospital informatics data on hospital resource use for the period of one to four years post-randomisation were collected from participating hospital sites. The economic evaluation took an National Health Service (NHS) secondary care perspective, with a four-year time horizon. RESULTS: Overall, 226/337 (67%) of participants returned completed follow-up questionnaires, yielding adjusted between-group differences in BPI means of -0.42 (95% confidence interval, CI (-1.07, 0.23); p = 0.20) for pain severity and - 0.64 (95% CI -1.41, 0.12); p = 0.10) for pain interference. Analysis using a multiple imputed data set (n = 337) showed an incremental net monetary benefit in favour of the STAR care pathway of £3,525 (95% CI -£990 to £8,039) at a £20,000/QALY willingness-to-pay threshold, leading to a probability that the intervention was cost-effective of 0.94. CONCLUSIONS: The magnitude of the longer-term benefits of the STAR care pathway are uncertain due to attrition of trial participants; however, there is a suggestion of some degree of sustained clinical benefit at four years. The care pathway remained cost-effective at four years. TRIAL REGISTRATION: ISRCTN: 92,545,361.

[Psychological aspects of pain prevention : German version]. / Psychologische Aspekte der Schmerzprävention : Deutsche Fassung.

How to prevent the onset, maintenance, or exacerbation of pain is a major focus of clinical pain science. Pain prevention can be distinctly organised into primary, secondary, and tertiary prevention. Primary prevention describes avoiding hurt or pain, secondary prevention describes reducing pain when pain is unavoidable, and tertiary prevention describes preventing or reducing ongoing negative consequences such as high functional disability or distress due to chronic pain. Each poses separate challenges where unique psychological factors will play a role. In this short review article, we highlight psychological factors important to primary, secondary, and tertiary prevention and provide direction for the field. We present 2 case studies on secondary prevention in children and adolescents and tertiary prevention in adults with chronic pain. Finally, we provide research directions for progression in this field, highlighting the importance of clear theoretical direction, the identification of risk factors for those most likely to develop pain, and the importance of treatment.

System-level policies on appropriate opioid use, a multi-stakeholder consensus.

BACKGROUND: This consensus statement was developed because there are concerns about the appropriate use of opioids for acute pain management, with opposing views in the literature. Consensus statement on policies for system-level interventions may help inform organisations such as management structures, government agencies and funding bodies. METHODS: We conducted a multi-stakeholder survey using a modified Delphi methodology focusing on policies, at the system level, rather than at the prescriber or patient level. We aimed to provide consensus statements for current developments and priorities for future developments. RESULTS: Twenty-five experts from a variety of fields with experience in acute pain management were invited to join a review panel, of whom 23 completed a modified Delphi survey of policies designed to improve the safety and quality of opioids prescribing for acute pain in the secondary care setting. Strong agreement, defined as consistent among> 75% of panellists, was observed for ten statements. CONCLUSIONS: Using a modified Delphi study, we found agreement among a multidisciplinary panel, including patient representation, on prioritisation of policies for system-level interventions, to improve governance, pain management, patient/consumers care, safety and engagement.

Experiences of recovery and a new care pathway for people with pain after total knee replacement: qualitative research embedded in the STAR trial.

BACKGROUND: Approximately 20% of people experience chronic postsurgical pain after total knee replacement. The STAR randomised controlled trial (ISCRTN92545361) evaluated the clinical- and cost-effectiveness of a new multifaceted and personalised care pathway, compared with usual care, for people with pain at three months after total knee replacement. We report trial participants' experiences of postoperative pain and the acceptability of the STAR care pathway, which consisted of an assessment clinic at three months, and up to six follow-up telephone calls over 12 months. METHODS: Semi-structured interviews were conducted with 27 people (10 men, 17 women) between February 2018 and January 2020. Participants were sampled purposively from the care pathway intervention group and interviewed after completion of the final postoperative trial questionnaire at approximately 15 months after knee replacement. Interviews were audio-recorded, transcribed, anonymised and analysed using inductive thematic analysis. FINDINGS: Many participants were unprepared for the severity and impact of postoperative pain, which they described as extreme and constant and that tested their physical and mental endurance. Participants identified 'low points' during their recovery, triggered by stiffening, pain or swelling that caused feelings of anxiety, depression, and pain catastrophising. Participants described the STAR assessment clinic as something that seemed "perfectly normal" suggesting it was seamlessly integrated into NHS care. Even in the context of some ongoing pain, the STAR care pathway had provided a source of support and an opportunity to discuss concerns about their ongoing recovery. CONCLUSIONS: People who have knee replacement may be unprepared for the severity and impact of postoperative pain, and the hard work of recovery afterwards. This highlights the challenges of preparing patients for total knee replacement and suggests that clinical attention is needed if exercise and mobilising is painful beyond the three month postoperative period. The STAR care pathway is acceptable to people with pain after total knee replacement.

Sociodevelopmental Challenges Faced by Young People with Chronic Pain: A Scoping Review.

OBJECTIVE: Map the current literature investigating autonomy development, identity development, and peer relationships in young people aged 10-24 years with chronic pain. METHODS: A scoping review method was used to systematically search four databases (APA PsycNET, PubMed, Web of Science, and Cinahl) for peer-reviewed articles. Search results were screened against inclusion and exclusion criteria to ensure they met the objective. Eligible papers were assessed for quality, their data relating to the objective were extracted, and results are synthesized. RESULTS: Searches returned 3,815 papers after the removal of duplicates, with 42 papers included in the full review. The majority of papers investigated peer relationships (86%). Fewer papers investigated autonomy (43%) and identity (21%) development. Included papers were mostly quantitative (64%), with fewer qualitative (34%) and mixed-methods papers (2%). Overall, we found bidirectional relationships between chronic pain in young people, their social development, and a range of functional outcomes. However, the mechanisms underlying these relationships remain relatively unexplored. CONCLUSIONS: Review results are mapped onto the model proposed by Palermo et al. (2014). Guided by this model, clinical treatment for young people with chronic pain should consider social development. The model also sets out a future research agenda focused on exploring: (a) identity development, (b) the mechanisms underlying the relationships between social-developmental domains, pain, and outcomes, (c) a variety of participants and populations, and (d) a variety of methods, including longitudinal study designs.

Implanted spinal neuromodulation interventions for chronic pain in adults.

BACKGROUND: Implanted spinal neuromodulation (SNMD) techniques are used in the treatment of refractory chronic pain. They involve the implantation of electrodes around the spinal cord (spinal cord stimulation (SCS)) or dorsal root ganglion (dorsal root ganglion stimulation (DRGS)), and a pulse generator unit under the skin. Electrical stimulation is then used with the aim of reducing pain intensity. OBJECTIVES: To evaluate the efficacy, effectiveness, adverse events, and cost-effectiveness of implanted spinal neuromodulation interventions for people with chronic pain. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, Web of Science (ISI), Health Technology Assessments, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry from inception to September 2021 without language restrictions, searched the reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing SNMD interventions with placebo (sham) stimulation, no treatment or usual care; or comparing SNMD interventions + another treatment versus that treatment alone. We included participants ≥ 18 years old with non-cancer and non-ischaemic pain of longer than three months duration. Primary outcomes were pain intensity and adverse events. Secondary outcomes were disability, analgesic medication use, health-related quality of life (HRQoL) and health economic outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened database searches to determine inclusion, extracted data and evaluated risk of bias for prespecified results using the Risk of Bias 2.0 tool. Outcomes were evaluated at short- (≤ one month), medium- four to eight months) and long-term (≥12 months). Where possible we conducted meta-analyses. We used the GRADE system to assess the certainty of evidence. MAIN RESULTS: We included 15 unique published studies that randomised 908 participants, and 20 unique ongoing studies. All studies evaluated SCS. We found no eligible published studies of DRGS and no studies comparing SCS with no treatment or usual care. We rated all results evaluated as being at high risk of bias overall. For all comparisons and outcomes where we found evidence, we graded the certainty of the evidence as low or very low, downgraded due to limitations of studies, imprecision and in some cases, inconsistency. Active stimulation versus placebo SCS versus placebo (sham) Results were only available at short-term follow-up for this comparison. Pain intensity Six studies (N = 164) demonstrated a small effect in favour of SCS at short-term follow-up (0 to 100 scale, higher scores = worse pain, mean difference (MD) -8.73, 95% confidence interval (CI) -15.67 to -1.78, very low certainty). The point estimate falls below our predetermined threshold for a clinically important effect (≥10 points). No studies reported the proportion of participants experiencing 30% or 50% pain relief for this comparison. Adverse events (AEs) The quality and inconsistency of adverse event reporting in these studies precluded formal analysis. Active stimulation + other intervention versus other intervention alone SCS + other intervention versus other intervention alone (open-label studies) Pain intensity Mean difference Three studies (N = 303) demonstrated a potentially clinically important mean difference in favour of SCS of -37.41 at short term (95% CI -46.39 to -28.42, very low certainty), and medium-term follow-up (5 studies, 635 participants, MD -31.22 95% CI -47.34 to -15.10 low-certainty), and no clear evidence for an effect of SCS at long-term follow-up (1 study, 44 participants, MD -7 (95% CI -24.76 to 10.76, very low-certainty). Proportion of participants reporting ≥50% pain relief We found an effect in favour of SCS at short-term (2 studies, N = 249, RR 15.90, 95% CI 6.70 to 37.74, I2 0% ; risk difference (RD) 0.65 (95% CI 0.57 to 0.74, very low certainty), medium term (5 studies, N = 597, RR 7.08, 95 %CI 3.40 to 14.71, I2 = 43%; RD 0.43, 95% CI 0.14 to 0.73, low-certainty evidence), and long term (1 study, N = 87, RR 15.15, 95% CI 2.11 to 108.91 ; RD 0.35, 95% CI 0.2 to 0.49, very low certainty) follow-up. Adverse events (AEs) Device related No studies specifically reported  device-related adverse events at short-term follow-up. At medium-term follow-up, the incidence of lead failure/displacement (3 studies N = 330) ranged from 0.9 to 14% (RD 0.04, 95% CI -0.04 to 0.11, I2 64%, very low certainty). The incidence of infection (4 studies, N = 548) ranged from 3 to 7% (RD 0.04, 95%CI 0.01, 0.07, I2 0%, very low certainty). The incidence of reoperation/reimplantation (4 studies, N =5 48) ranged from 2% to 31% (RD 0.11, 95% CI 0.02 to 0.21, I2 86%, very low certainty). One study (N = 44) reported a 55% incidence of lead failure/displacement (RD 0.55, 95% CI 0.35, 0 to 75, very low certainty), and a 94% incidence of reoperation/reimplantation (RD 0.94, 95% CI 0.80 to 1.07, very low certainty) at five-year follow-up. No studies provided data on infection rates at long-term follow-up. We found reports of some serious adverse events as a result of the intervention. These included autonomic neuropathy, prolonged hospitalisation, prolonged monoparesis, pulmonary oedema, wound infection, device extrusion and one death resulting from subdural haematoma. Other No studies reported the incidence of other adverse events at short-term follow-up. We found no clear evidence of a difference in otherAEs at medium-term (2 studies, N = 278, RD -0.05, 95% CI -0.16 to 0.06, I2 0%) or long term (1 study, N = 100, RD -0.17, 95% CI -0.37 to 0.02) follow-up. Very limited evidence suggested that SCS increases healthcare costs. It was not clear whether SCS was cost-effective. AUTHORS' CONCLUSIONS: We found very low-certainty evidence that SCS may not provide clinically important benefits on pain intensity compared to placebo stimulation. We found low- to very low-certainty evidence that SNMD interventions may provide clinically important benefits for pain intensity when added to conventional medical management or physical therapy. SCS is associated with complications including infection, electrode lead failure/migration and a need for reoperation/re-implantation. The level of certainty regarding the size of those risks is very low. SNMD may lead to serious adverse events, including death. We found no evidence to support or refute the use of DRGS for chronic pain.

Psychological therapies for the management of chronic pain (excluding headache) in adults.

BACKGROUND: Chronic non-cancer pain, a disabling and distressing condition, is common in adults. It is a global public health problem and economic burden on health and social care systems and on people with chronic pain. Psychological treatments aim to reduce pain, disability and distress. This review updates and extends its previous version, published in 2012. OBJECTIVES: To determine the clinical efficacy and safety of psychological interventions for chronic pain in adults (age > 18 years) compared with active controls, or waiting list/treatment as usual (TAU). SEARCH METHODS: We identified randomised controlled trials (RCTs) of psychological therapies by searching CENTRAL, MEDLINE, Embase and PsycINFO to 16 April 2020. We also examined reference lists and trial registries, and searched for studies citing retrieved trials. SELECTION CRITERIA: RCTs of psychological treatments compared with active control or TAU of face-to-face therapies for adults with chronic pain. We excluded studies of headache or malignant disease, and those with fewer than 20 participants in any arm at treatment end. DATA COLLECTION AND ANALYSIS: Two or more authors rated risk of bias, extracted data, and judged quality of evidence (GRADE). We compared cognitive behavioural therapy (CBT), behavioural therapy (BT), and acceptance and commitment therapy (ACT) with active control or TAU at treatment end, and at six month to 12 month follow-up. We did not analyse the few trials of other psychological treatments. We assessed treatment effectiveness for pain intensity, disability, and distress. We extracted data on adverse events (AEs) associated with treatment. MAIN RESULTS: We added 41 studies (6255 participants) to 34 of the previous review's 42 studies, and now have 75 studies in total (9401 participants at treatment end). Most participants had fibromyalgia, chronic low back pain, rheumatoid arthritis, or mixed chronic pain. Most risk of bias domains were at high or unclear risk of bias, with selective reporting and treatment expectations mostly at unclear risk of bias. AEs were inadequately recorded and/or reported across studies. CBT The largest evidence base was for CBT (59 studies). CBT versus active control showed very small benefit at treatment end for pain (standardised mean difference (SMD) -0.09, 95% confidence interval (CI) -0.17 to -0.01; 3235 participants; 23 studies; moderate-quality evidence), disability (SMD -0.12, 95% CI -0.20 to -0.04; 2543 participants; 19 studies; moderate-quality evidence), and distress (SMD -0.09, 95% CI -0.18 to -0.00; 3297 participants; 24 studies; moderate-quality evidence). We found small benefits for CBT over TAU at treatment end for pain (SMD -0.22, 95% CI -0.33 to -0.10; 2572 participants; 29 studies; moderate-quality evidence), disability (SMD -0.32, 95% CI -0.45 to -0.19; 2524 participants; 28 studies; low-quality evidence), and distress (SMD -0.34, 95% CI -0.44 to -0.24; 2559 participants; 27 studies; moderate-quality evidence). Effects were largely maintained at follow-up for CBT versus TAU, but not for CBT versus active control. Evidence quality for CBT outcomes ranged from moderate to low. We rated evidence for AEs as very low quality for both comparisons. BT We analysed eight studies (647 participants). We found no evidence of difference between BT and active control at treatment end (pain SMD -0.67, 95% CI -2.54 to 1.20, very low-quality evidence; disability SMD -0.65, 95% CI -1.85 to 0.54, very low-quality evidence; or distress SMD -0.73, 95% CI -1.47 to 0.01, very low-quality evidence). At follow-up, effects were similar. We found no evidence of difference between BT and TAU (pain SMD -0.08, 95% CI -0.33 to 0.17, low-quality evidence; disability SMD -0.02, 95% CI -0.24 to 0.19, moderate-quality evidence; distress SMD 0.22, 95% CI -0.10 to 0.54, low-quality evidence) at treatment end. At follow-up, we found one to three studies with no evidence of difference between BT and TAU. We rated evidence for all BT versus active control outcomes as very low quality; for BT versus TAU. Evidence quality ranged from moderate to very low. We rated evidence for AEs as very low quality for BT versus active control. No studies of BT versus TAU reported AEs. ACT We analysed five studies (443 participants). There was no evidence of difference between ACT and active control for pain (SMD -0.54, 95% CI -1.20 to 0.11, very low-quality evidence), disability (SMD -1.51, 95% CI -3.05 to 0.03, very low-quality evidence) or distress (SMD -0.61, 95% CI -1.30 to 0.07, very low-quality evidence) at treatment end. At follow-up, there was no evidence of effect for pain or distress (both very low-quality evidence), but two studies showed a large benefit for reducing disability (SMD -2.56, 95% CI -4.22 to -0.89, very low-quality evidence). Two studies compared ACT to TAU at treatment end. Results should be interpreted with caution. We found large benefits of ACT for pain (SMD -0.83, 95% CI -1.57 to -0.09, very low-quality evidence), but none for disability (SMD -1.39, 95% CI -3.20 to 0.41, very low-quality evidence), or distress (SMD -1.16, 95% CI -2.51 to 0.20, very low-quality evidence). Lack of data precluded analysis at follow-up. We rated evidence quality for AEs to be very low. We encourage caution when interpreting very low-quality evidence because the estimates are uncertain and could be easily overturned. AUTHORS' CONCLUSIONS: We found sufficient evidence across a large evidence base (59 studies, over 5000 participants) that CBT has small or very small beneficial effects for reducing pain, disability, and distress in chronic pain, but we found insufficient evidence to assess AEs. Quality of evidence for CBT was mostly moderate, except for disability, which we rated as low quality. Further trials may provide more precise estimates of treatment effects, but to inform improvements, research should explore sources of variation in treatment effects. Evidence from trials of BT and ACT was of moderate to very low quality, so we are very uncertain about benefits or lack of benefits of these treatments for adults with chronic pain; other treatments were not analysed. These conclusions are similar to our 2012 review, apart from the separate analysis of ACT.

Psychological interventions for parents of children and adolescents with chronic illness.

BACKGROUND: Psychological therapies for parents of children and adolescents with chronic illness aim to improve parenting behavior and mental health, child functioning (behavior/disability, mental health, and medical symptoms), and family functioning.This is an updated version of the original Cochrane Review (2012) which was first updated in 2015. OBJECTIVES: To evaluate the efficacy and adverse events of psychological therapies for parents of children and adolescents with a chronic illness. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, and trials registries for studies published up to July 2018. SELECTION CRITERIA: Included studies were randomized controlled trials (RCTs) of psychological interventions for parents of children and adolescents with a chronic illness. In this update we included studies with more than 20 participants per arm. In this update, we included interventions that combined psychological and pharmacological treatments. We included comparison groups that received either non-psychological treatment (e.g. psychoeducation), treatment as usual (e.g. standard medical care without added psychological therapy), or wait-list. DATA COLLECTION AND ANALYSIS: We extracted study characteristics and outcomes post-treatment and at first available follow-up. Primary outcomes were parenting behavior and parent mental health. Secondary outcomes were child behavior/disability, child mental health, child medical symptoms, and family functioning. We pooled data using the standardized mean difference (SMD) and a random-effects model, and evaluated outcomes by medical condition and by therapy type. We assessed risk of bias per Cochrane guidance and quality of evidence using GRADE. MAIN RESULTS: We added 21 new studies. We removed 23 studies from the previous update that no longer met our inclusion criteria. There are now 44 RCTs, including 4697 participants post-treatment. Studies included children with asthma (4), cancer (7), chronic pain (13), diabetes (15), inflammatory bowel disease (2), skin diseases (1), and traumatic brain injury (3). Therapy types included cognitive-behavioural therapy (CBT; 21), family therapy (4), motivational interviewing (3), multisystemic therapy (4), and problem-solving therapy (PST; 12). We rated risk of bias as low or unclear for most domains, except selective reporting bias, which we rated high for 19 studies due to incomplete outcome reporting. Evidence quality ranged from very low to moderate. We downgraded evidence due to high heterogeneity, imprecision, and publication bias.Evaluation of parent outcomes by medical conditionPsychological therapies may improve parenting behavior (e.g. maladaptive or solicitous behaviors; lower scores are better) in children with cancer post-treatment and follow-up (SMD -0.28, 95% confidence interval (CI) -0.43 to -0.13; participants = 664; studies = 3; SMD -0.21, 95% CI -0.37 to -0.05; participants = 625; studies = 3; I2 = 0%, respectively, low-quality evidence), chronic pain post-treatment and follow-up (SMD -0.29, 95% CI -0.47 to -0.10; participants = 755; studies = 6; SMD -0.35, 95% CI -0.50 to -0.20; participants = 678; studies = 5, respectively, moderate-quality evidence), diabetes post-treatment (SMD -1.39, 95% CI -2.41 to -0.38; participants = 338; studies = 5, very low-quality evidence), and traumatic brain injury post-treatment (SMD -0.74, 95% CI -1.25 to -0.22; participants = 254; studies = 3, very low-quality evidence). For the remaining analyses data were insufficient to evaluate the effect of treatment.Psychological therapies may improve parent mental health (e.g. depression, anxiety, lower scores are better) in children with cancer post-treatment and follow-up (SMD -0.21, 95% CI -0.35 to -0.08; participants = 836, studies = 6, high-quality evidence; SMD -0.23, 95% CI -0.39 to -0.08; participants = 667; studies = 4, moderate-quality evidence, respectively), and chronic pain post-treatment and follow-up (SMD -0.24, 95% CI -0.42 to -0.06; participants = 490; studies = 3; SMD -0.20, 95% CI -0.38 to -0.02; participants = 482; studies = 3, respectively, low-quality evidence). Parent mental health did not improve in studies of children with diabetes post-treatment (SMD -0.24, 95% CI -0.90 to 0.42; participants = 211; studies = 3, very low-quality evidence). For the remaining analyses, data were insufficient to evaluate the effect of treatment on parent mental health.Evaluation of parent outcomes by psychological therapy typeCBT may improve parenting behavior post-treatment (SMD -0.45, 95% CI -0.68 to -0.21; participants = 1040; studies = 9, low-quality evidence), and follow-up (SMD -0.26, 95% CI -0.42 to -0.11; participants = 743; studies = 6, moderate-quality evidence). We did not find evidence for a beneficial effect for CBT on parent mental health at post-treatment or follow-up (SMD -0.19, 95% CI -0.41 to 0.03; participants = 811; studies = 8; SMD -0.07, 95% CI -0.34 to 0.20; participants = 592; studies = 5; respectively, very low-quality evidence). PST may improve parenting behavior post-treatment and follow-up (SMD -0.39, 95% CI -0.64 to -0.13; participants = 947; studies = 7, low-quality evidence; SMD -0.54, 95% CI -0.94 to -0.14; participants = 852; studies = 6, very low-quality evidence, respectively), and parent mental health post-treatment and follow-up (SMD -0.30, 95% CI -0.45 to -0.15; participants = 891; studies = 6; SMD -0.21, 95% CI -0.35 to -0.07; participants = 800; studies = 5, respectively, moderate-quality evidence). For the remaining analyses, data were insufficient to evaluate the effect of treatment on parent outcomes.Adverse eventsWe could not evaluate treatment safety because most studies (32) did not report on whether adverse events occurred during the study period. In six studies, the authors reported that no adverse events occurred. The remaining six studies reported adverse events and none were attributed to psychological therapy. We rated the quality of evidence for adverse events as moderate. AUTHORS' CONCLUSIONS: Psychological therapy may improve parenting behavior among parents of children with cancer, chronic pain, diabetes, and traumatic brain injury. We also found beneficial effects of psychological therapy may also improve parent mental health among parents of children with cancer and chronic pain. CBT and PST may improve parenting behavior. PST may also improve parent mental health. However, the quality of evidence is generally low and there are insufficient data to evaluate most outcomes. Our findings could change as new studies are conducted.

Psychological therapies (remotely delivered) for the management of chronic and recurrent pain in children and adolescents.

BACKGROUND: This is the first update of a review published in 2015, Issue 1. Chronic pain is common during childhood and adolescence and is associated with negative outcomes, such as increased severity of pain, reduced function, and low mood. Psychological therapies, traditionally delivered face-to-face with a therapist, are efficacious at reducing pain intensity and disability. To address barriers to treatment access, such as distance and cost of treatment, technology is being used to deliver these psychological therapies remotely. Therapies delivered remotely, such as via the Internet, computer-based programmes, and smartphone applications, can be used to deliver treatment to children and adolescents with chronic pain. OBJECTIVES: To determine the efficacy of psychological therapies delivered remotely compared to waiting list, treatment as usual, or active control treatments, for the management of chronic pain in children and adolescents. SEARCH METHODS: We searched four databases (CENTRAL, MEDLINE, Embase, and PsycINFO) from inception to May 2018 for randomised controlled trials (RCTs) of remotely-delivered psychological interventions for children and adolescents with chronic pain. We searched for chronic pain conditions including, but not exclusive to, headache, recurrent abdominal pain, musculoskeletal pain, and neuropathic pain. We also searched online trial registries, reference sections, and citations of included studies for potential trials. SELECTION CRITERIA: We included RCTs that investigated the efficacy of a psychological therapy delivered remotely via technology in comparison to an active, treatment as usual, or waiting-list control. We considered blended treatments, which used a combination of technology and up to 30% face-to-face interaction. Interventions had to be delivered primarily via technology to be included, and we excluded interventions delivered via telephone. We included studies that delivered interventions to children and adolescents (up to 18 years of age) with a chronic pain condition or where chronic pain was a primary symptom of their condition (e.g. juvenile arthritis). We included studies that reported 10 or more participants in each comparator arm, at each extraction point. DATA COLLECTION AND ANALYSIS: We combined all psychological therapies in the analyses. We split pain conditions into headache and mixed (non-headache) pain and analysed them separately. We extracted pain severity/intensity, disability, depression, anxiety, and adverse events as primary outcomes, and satisfaction with treatment as a secondary outcome. We considered outcomes at two time points: first immediately following the end of treatment (known as 'post-treatment'), and second, any follow-up time point post-treatment between three and 12 months (known as 'follow-up'). We assessed risk of bias and all outcomes for quality using the GRADE assessment. MAIN RESULTS: We found 10 studies with 697 participants (an additional 4 studies with 326 participants since the previous review) that delivered treatment remotely; four studies investigated children with headache conditions, one study was with children with juvenile idiopathic arthritis, one included children with sickle cell disease, one included children with irritable bowel syndrome, and three studies included children with different chronic pain conditions (i.e. headache, recurrent abdominal pain, musculoskeletal pain). The average age of children receiving treatment was 13.17 years.We judged selection, detection, and reporting biases to be mostly low risk. However, we judged performance and attrition biases to be mostly unclear. Out of the 16 planned analyses, we were able to conduct 13 meta-analyses. We downgraded outcomes for imprecision, indirectness of evidence, inconsistency of results, or because the analysis only included one study.Headache conditionsFor headache pain conditions, we found headache severity was reduced post-treatment (risk ratio (RR) 2.02, 95% confidence interval (CI) 1.35 to 3.01); P < 0.001, number needed to treat to benefit (NNTB) = 5.36, 7 studies, 379 participants; very low-quality evidence). No effect was found at follow-up (very low-quality evidence). There were no effects of psychological therapies delivered remotely for disability post-treatment (standardised mean difference (SMD) -0.16, 95% CI -0.46 to 0.13; P = 0.28, 5 studies, 440 participants) or follow-up (both very low-quality evidence). Similarly, no effect was found for the outcomes of depression (SMD -0.04, 95% CI -0.15 to 0.23, P = 0.69, 4 studies, 422 participants) or anxiety (SMD -0.08, 95% CI -0.28 to 0.12; P = 0.45, 3 studies, 380 participants) at post-treatment, or follow-up (both very low-quality evidence).Mixed chronic pain conditionsWe did not find any beneficial effects of psychological therapies for reducing pain intensity post-treatment for mixed chronic pain conditions (SMD -0.90, 95% CI -1.95 to 0.16; P = 0.10, 5 studies, 501 participants) or at follow-up. There were no beneficial effects of psychological therapies delivered remotely for disability post-treatment (SMD -0.28, 95% CI -0.74 to 0.18; P = 0.24, 3 studies, 363 participants) and a lack of data at follow-up meant no analysis could be run. We found no beneficial effects for the outcomes of depression (SMD 0.04, 95% CI -0.18 to 0.26; P = 0.73, 2 studies, 317 participants) and anxiety (SMD 0.53, 95% CI -0.63 to 1.68; P = 0.37, 2 studies, 370 participants) post-treatment, however, we are cautious of our findings as we could only include two studies in the analyses. We could not conduct analyses at follow-up. We judged the evidence for all outcomes to be very low quality.All conditionsAcross all chronic pain conditions, six studies reported minor adverse events which were not attributed to the psychological therapies. Satisfaction with treatment is described qualitatively and was overall positive. However, we judged both these outcomes as very low quality. AUTHORS' CONCLUSIONS: There are currently a small number of trials investigating psychological therapies delivered remotely, primarily via the Internet. We are cautious in our interpretations of analyses. We found one beneficial effect of therapies to reduce headache severity post-treatment. For the remaining outcomes there was either no beneficial effect at post-treatment or follow-up, or lack of evidence to determine an effect. Overall, participant satisfaction with treatment was positive. We judged the quality of the evidence to be very low, meaning we are very uncertain about the estimate. Further studies are needed to increase our confidence in this potentially promising field.

Advancing shared decision making for symptom monitoring in people living beyond cancer.

Wellbeing after successful cancer treatment depends on more than merely reducing the risk of disease recurrence. Cancer survival can be characterised by uncertainty, fear, and the interpretation of bodily sensations as potentially symptomatic of cancer recurrence. This fear can lead to over-vigilance about bodily sensations and precautionary visits to the doctor, both of which can increase the chance of early detection but can also increase anxiety and decrease quality of life. In this Personal View, we consider the medical, psychological, and ethical issues related to the practice of self-directed symptom monitoring after completion of cancer treatment, focusing on the role of doctor-patient communication. We ask how clinicians can account for the plurality of values that patients might have when it comes to deciding on how to manage and respond to experiences of post-cancer symptoms. We advocate a shared decision-making approach that incorporates the assessment of an individual's cancer recurrence risks as well as psychosocial considerations regarding fear of cancer recurrence and mental health. We aim to raise awareness of the potential quality-of-life implications of symptom-monitoring practices, emphasising the need for a balance between physical and psychological health in people living beyond cancer.

Assessment of Pain Anxiety, Pain Catastrophizing, and Fear of Pain in Children and Adolescents With Chronic Pain: A Systematic Review and Meta-Analysis.

Objective: To conduct a systematic review of pain anxiety, pain catastrophizing, and fear of pain measures psychometrically established in youth with chronic pain. The review addresses three specific aims: (1) to identify measures used in youth with chronic pain, summarizing their content, psychometric properties, and use; (2) to use evidence-based assessment criteria to rate each measure according to the Society of Pediatric Psychology (SPP) guidelines; (3) to pool data across studies for meta-analysis of shared variance in psychometric performance in relation to the primary outcomes of pain intensity, disability, generalized anxiety, and depression. Methods: We searched Medline, Embase, PsycINFO, and relevant literature for possible studies to include. We identified measures studied in youth with chronic pain that assessed pain anxiety, pain catastrophizing, or fear of pain and extracted the item-level content. Study and participant characteristics, and correlation data were extracted for summary and meta-analysis, and measures were rated using the SPP evidence-based assessment criteria. Results: Fifty-four studies (84 papers) met the inclusion criteria, including seven relevant measures: one assessed pain anxiety, three pain catastrophizing, and three fear of pain. Overall, five measures were rated as "well established." We conducted meta-analyses on four measures with available data. We found significant positive correlations with the variables pain intensity, disability, generalized anxiety, and depression. Conclusion: Seven measures are available to assess pain anxiety, pain catastrophizing, and fear of pain in young people with chronic pain, and most are well established. We present implications for practice and directions for future research.

Psychological therapies for the management of chronic and recurrent pain in children and adolescents.

BACKGROUND: This is an update of the original Cochrane review first published in Issue 1, 2003, and previously updated in 2009, 2012 and 2014. Chronic pain, defined as pain that recurs or persists for more than three months, is common in childhood. Chronic pain can affect nearly every aspect of daily life and is associated with disability, anxiety, and depressive symptoms. OBJECTIVES: The aim of this review was to update the published evidence on the efficacy of psychological treatments for chronic and recurrent pain in children and adolescents.The primary objective of this updated review was to determine any effect of psychological therapy on the clinical outcomes of pain intensity and disability for chronic and recurrent pain in children and adolescents compared with active treatment, waiting-list, or treatment-as-usual care.The secondary objective was to examine the impact of psychological therapies on children's depressive symptoms and anxiety symptoms, and determine adverse events. SEARCH METHODS: Searches were undertaken of CENTRAL, MEDLINE, MEDLINE in Process, Embase, and PsycINFO databases. We searched for further RCTs in the references of all identified studies, meta-analyses, and reviews, and trial registry databases. The most recent search was conducted in May 2018. SELECTION CRITERIA: RCTs with at least 10 participants in each arm post-treatment comparing psychological therapies with active treatment, treatment-as-usual, or waiting-list control for children or adolescents with recurrent or chronic pain were eligible for inclusion. We excluded trials conducted remotely via the Internet. DATA COLLECTION AND ANALYSIS: We analysed included studies and we assessed quality of outcomes. We combined all treatments into one class named 'psychological treatments'. We separated the trials by the number of participants that were included in each arm; trials with > 20 participants per arm versus trials with < 20 participants per arm. We split pain conditions into headache and mixed chronic pain conditions. We assessed the impact of both conditions on four outcomes: pain, disability, depression, and anxiety. We extracted data at two time points; post-treatment (immediately or the earliest data available following end of treatment) and at follow-up (between three and 12 months post-treatment). MAIN RESULTS: We identified 10 new studies (an additional 869 participants) in the updated search. The review thus included a total of 47 studies, with 2884 children and adolescents completing treatment (mean age 12.65 years, SD 2.21 years). Twenty-three studies addressed treatments for headache (including migraine); 10 for abdominal pain; two studies treated participants with either a primary diagnosis of abdominal pain or irritable bowel syndrome, two studies treated adolescents with fibromyalgia, two studies included adolescents with temporomandibular disorders, three were for the treatment of pain associated with sickle cell disease, and two studies treated adolescents with inflammatory bowel disease. Finally, three studies included adolescents with mixed pain conditions. Overall, we judged the included studies to be at unclear or high risk of bias.Children with headache painWe found that psychological therapies reduced pain frequency post-treatment for children and adolescents with headaches (risk ratio (RR) 2.35, 95% confidence interval (CI) 1.67 to 3.30, P < 0.01, number needed to treat for an additional beneficial outcome (NNTB) = 2.86), but these effects were not maintained at follow-up. We did not find a beneficial effect of psychological therapies on reducing disability in young people post-treatment (SMD -0.26, 95% CI -0.56 to 0.03), but we did find a beneficial effect in a small number of studies at follow-up (SMD -0.34, 95% CI -0.54 to -0.15). We found no beneficial effect of psychological interventions on depression or anxiety symptoms.Children with mixed pain conditionsWe found that psychological therapies reduced pain intensity post-treatment for children and adolescents with mixed pain conditions (SMD -0.43, 95% CI -0.67 to -0.19, P < 0.01), but these effects were not maintained at follow-up. We did find beneficial effects of psychological therapies on reducing disability for young people with mixed pain conditions post-treatment (SMD -0.34, 95% CI -0.54 to -0.15) and at follow-up (SMD -0.27, 95% CI -0.49 to -0.06). We found no beneficial effect of psychological interventions on depression symptoms. In contrast, we found a beneficial effect on anxiety at post-treatment in children with mixed pain conditions (SMD -0.16, 95% CI -0.29 to -0.03), but this was not maintained at follow-up.Across all pain conditions, we found that adverse events were reported in seven trials, of which two studies reported adverse events that were study-related.Quality of evidenceWe found the quality of evidence for all outcomes to be low or very low, mostly downgraded for unexplained heterogeneity, limitations in study design, imprecise and sparse data, or suspicion of publication bias. This means our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect, or we have very little confidence in the effect estimate; or the true effect is likely to be substantially different from the estimate of effect. AUTHORS' CONCLUSIONS: Psychological treatments delivered predominantly face-to-face might be effective for reducing pain outcomes for children and adolescents with headache or other chronic pain conditions post-treatment. However, there were no effects at follow-up. Psychological therapies were also beneficial for reducing disability in children with mixed chronic pain conditions at post-treatment and follow-up, and for children with headache at follow-up. We found no beneficial effect of therapies for improving depression or anxiety. The conclusions of this update replicate and add to those of a previous version of the review which found that psychological therapies were effective in reducing pain frequency/intensity for children with headache and mixed chronic pain conditions post-treatment.

The tripartite structure of pain-related affect: a confirmatory factor analysis.

Numerous emotion-based constructs seem related to pain and pain-related disability. These include general affect constructs such as anxiety and depression, as well as specific anxiety-related constructs such as anxiety sensitivity and fear of pain. Few studies examine the relationships between these constructs. Those that have suggest they can be reduced to three or four underlying components. We used a confirmatory approach to test the models of pain-related anxiety found in previous exploratory studies. Adult participants (N = 294) completed commonly used measures of affect-related constructs relevant to pain. Confirmatory Factor Analyses tested three models to determine the best fit. The tripartite model, with small modifications, was found to provide the best fit. The model consisted of: 1) General distress, 2) Fear of pain from injury/insult, and 3) Cognitive intrusion of pain.

Ketamine as an adjuvant to opioids for cancer pain.

BACKGROUND: This is an update of a review first published in 2003 and updated in 2012.Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of refractory cancer pain, when opioids alone or in combination with appropriate adjuvant analgesics prove to be ineffective. Ketamine is known to have psychomimetic (including hallucinogenic), urological, and hepatic adverse effects. OBJECTIVES: To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids for refractory cancer pain in adults. SEARCH METHODS: For this update, we searched MEDLINE (OVID) to December 2016. We searched CENTRAL (CRSO), Embase (OVID) and two clinical trial registries to January 2017. SELECTION CRITERIA: The intervention considered by this review was the addition of ketamine, given by any route of administration, in any dose, to pre-existing opioid treatment given by any route and in any dose, compared with placebo or active control. We included studies with a group size of at least 10 participants who completed the trial. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results and performed 'Risk of bias' assessments. We aimed to extract data on patient-reported pain intensity, total opioid consumption over the study period; use of rescue medication; adverse events; measures of patient satisfaction/preference; function; and distress. We also assessed participant withdrawal (dropout) from trial. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: One new study (185 participants) was identified by the updated search and included in the review. We included a total of three studies in this update.Two small studies, both with cross-over design, with 20 and 10 participants respectively, were eligible for inclusion in the original review. One study with 20 participants examined the addition of intrathecal ketamine to intrathecal morphine, compared with intrathecal morphine alone. The second study with 10 participants examined the addition of intravenous ketamine bolus in two different doses to ongoing morphine therapy, compared with placebo. Both of these studies reported reduction in pain intensity and reduction in morphine requirements when ketamine was added to opioid for refractory cancer pain. The new study identified by the updated search had a parallel group design and 185 participants. This placebo-controlled study examined rapid titration of subcutaneous ketamine to high dose (500 mg) in participants who were using different opioids. There were no differences between groups for patient-reported pain intensity.Pooling of the data from the three included trials was not appropriate because of clinical heterogeneity.The study examining intrathecal drug administration reported no adverse events related to ketamine. In the study using intravenous bolus administration, ketamine caused hallucinations in four of 10 participants. In the rapid dose escalation/high-dose subcutaneous ketamine study, there was almost twice the incidence of adverse events in the ketamine group, compared to the placebo group, with the most common adverse events being needle site irritation and cognitive disturbance. Two serious adverse events (bradyarrhythmia and cardiac arrest) thought to be related to ketamine were also reported in this trial.For all three studies there was an unclear risk of bias overall. Using GRADE, we judged the quality of the evidence to be very low due to study limitations and imprecision due to the small number of participants in all comparisons. AUTHORS' CONCLUSIONS: Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of refractory cancer pain. The evidence was of very low quality, meaning that it does not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different is high. Rapid dose escalation of ketamine to high dose (500 mg) does not appear to have clinical benefit and may be associated with serious adverse events. More randomised controlled trials (RCTs) examining specific low-dose ketamine clinical regimens in current use are needed.

Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents.

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammation properties. They are commonly used within paediatric pain management. Non-steroidal anti-inflammatory drugs are currently licensed for use in Western countries, however they are not approved for infants under three months old. The main adverse effects include renal impairment and gastrointestinal issues. Common side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain. OBJECTIVES: To assess the analgesic efficacy and adverse events of NSAIDs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, as well as online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing any NSAID with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed GRADE and created three 'Summary of findings' tables. MAIN RESULTS: We included seven studies with a total of 1074 participants (aged 2 to 18 years) with chronic juvenile polyarthritis or chronic juvenile rheumatoid arthritis. All seven studies compared an NSAID with an active comparator. None of the studies were placebo controlled. No two studies investigated the same type of NSAID compared with another. We were unable to perform a meta-analysis.Risk of bias varied. For randomisation and allocation concealment, one study was low risk and six studies were unclear risk. For blinding of participants and personnel, three studies were low risk and four studies were unclear to high risk. For blinding of outcome assessors, all studies were unclear risk. For attrition, four studies were low risk and three studies were unclear risk. For selective reporting, four studies were low risk, two studies were unclear risk, and one study was high risk. For size, three studies were unclear risk and four studies were high risk. For other potential sources of bias, seven studies were low risk. Primary outcomesThree studies reported participant-reported pain relief of 30% or greater, showing no statistically significant difference in pain scores between meloxicam and naproxen, celecoxib and naproxen, or rofecoxib and naproxen (P > 0.05) (low-quality evidence).One study reported participant-reported pain relief of 50% or greater, showing no statistically significant difference in pain scores between low-dose meloxicam (0.125 mg/kg) and high-dose meloxicam (0.25 mg/kg) when compared to naproxen 10 mg/kg (P > 0.05) (low-quality evidence).One study reported Patient Global Impression of Change, showing 'very much improved' in 85% of ibuprofen and 90% of aspirin participants (low-quality evidence). Secondary outcomesAll seven studies reported adverse events. Participants reporting an adverse event (one or more per person) by drug were: aspirin 85/202; fenoprofen 28/49; ibuprofen 40/45; indomethacin 9/30; ketoprofen 9/30; meloxicam 18/47; naproxen 44/202; and rofecoxib 47/209 (very low-quality evidence).All seven studies reported withdrawals due to adverse events. Participants withdrawn due to an adverse event by drug were: aspirin 16/120; celecoxib 10/159; fenoprofen 0/49; ibuprofen 0/45; indomethacin 0/30; ketoprofen 0/30; meloxicam 10/147; naproxen 17/285; and rofecoxib 3/209 (very low-quality evidence).All seven studies reported serious adverse events. Participants experiencing a serious adverse event by drug were: aspirin 13/120; celecoxib 5/159; fenoprofen 0/79; ketoprofen 0/30; ibuprofen 4/45; indomethacin 0/30; meloxicam 11/147; naproxen 10/285; and rofecoxib 0/209 (very low-quality evidence).There were few or no data for our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning as defined by validated scales; and quality of life as defined by validated scales (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) for our primary and secondary outcomes as very low because there were limited data from studies and no opportunity for a meta-analysis. AUTHORS' CONCLUSIONS: We identified only a small number of studies, with insufficient data for analysis.As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of NSAIDs to treat chronic non-cancer pain in children and adolescents. Similarly, we cannot comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.We know from adult randomised controlled trials that some NSAIDs, such as ibuprofen, naproxen, and aspirin, can be effective in certain chronic pain conditions.

Paracetamol (acetaminophen) for chronic non-cancer pain in children and adolescents.

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in children and adolescents in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications: nociceptive, neuropathic, idiopathic, visceral, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and other unknown reasons.Paracetamol (acetaminophen) is one of the most widely used analgesics in both adults and children. The recommended dosage in the UK, Europe, Australia, and the USA for children and adolescents is generally 10 to 15 mg/kg every four to six hours, with specific age ranges from 60 mg (6 to 12 months old) up to 500 to 1000 mg (over 12 years old). Paracetamol is the only recommended analgesic for children under 3 months of age. Paracetamol has been proven to be safe in appropriate and controlled dosages, however potential adverse effects of paracetamol if overdosed or overused in children include liver and kidney failure. OBJECTIVES: To assess the analgesic efficacy and adverse events of paracetamol (acetaminophen) used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing paracetamol with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and numbers needed to treat, using standard methods where data were available. We assessed GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a 'Summary of findings' table. MAIN RESULTS: No studies were eligible for inclusion in this review. We rated the quality of the evidence as very low. We downgraded the quality of evidence by three levels due to the lack of data reported for any outcome. AUTHORS' CONCLUSIONS: There was no evidence from randomised controlled trials to support or refute the use of paracetamol (acetaminophen) to treat chronic non-cancer pain in children and adolescents. We are unable to comment about efficacy or harm from the use of paracetamol to treat chronic non-cancer pain in children and adolescents.We know from adult randomised controlled trials that paracetamol, can be effective, in certain doses, and in certain pain conditions (not always chronic).This means that no conclusions could be made about efficacy or harm in the use of paracetamol (acetaminophen) to treat chronic non-cancer pain in children and adolescents.