What is the association between childhood adversity and subsequent chronic pain in adulthood? A systematic review.

Background: Adverse childhood experiences and chronic pain are complex problems affecting millions of people worldwide, and result in significant healthcare utilisation. Our review aimed to determine known associations between adversity in childhood and chronic pain in adulthood. Methods: We performed a prospectively registered systematic review (PROSPERO ID: 135625). Six electronic databases (Pubmed, Medline, Cochrane, Scopus, APA PsycNet, Web of Science) were searched from January 1, 2009 until May 30, 2022. Titles and abstracts were screened, and all original research studies examining associations between adverse childhood experiences and chronic pain in adulthood were considered for inclusion. Full texts were reviewed, and a narrative synthesis was used to identify themes from extracted data. Ten percent of studies were dual reviewed to assess inter-rater reliability. Quality assessment of study methodology was undertaken using recognised tools. Results: Sixty-eight eligible studies describing 196 130 participants were included. Studies covered 15 different types of childhood adversity and 10 different chronic pain diagnoses. Dual reviewed papers had a Cohen's kappa reliability rating of 0.71. Most studies were of retrospective nature and of good quality. There were consistent associations between adverse childhood experiences and chronic pain in adulthood, with a 'dose'-dependent relationship. Poor mental health was found to mediate the detrimental connection between adverse childhood experiences and chronic pain. Conclusion: A strong association was found between adverse childhood experiences and chronic pain in adulthood. Adverse childhood experiences should be considered in patient assessment, and early intervention to prevent adverse childhood experiences may help reduce the genesis of chronic pain. Further research into assessment and interventions to address adverse childhood experiences is needed.

Advances and challenges in neuropathic pain: a narrative review and future directions.

Over the past few decades, substantial advances have been made in neuropathic pain clinical research. An updated definition and classification have been agreed. Validated questionnaires have improved the detection and assessment of acute and chronic neuropathic pain; and newer neuropathic pain syndromes associated with COVID-19 have been described. The management of neuropathic pain has moved from empirical to evidence-based medicine. However, appropriately targeting current medications and the successful clinical development of drugs acting on new targets remain challenging. Innovative approaches to improving therapeutic strategies are required. These mainly encompass rational combination therapy, drug repurposing, non-pharmacological approaches (such as neurostimulation techniques), and personalised therapeutic management. This narrative review reports historical and current perspectives regarding the definitions, classification, assessment, and management of neuropathic pain and explores potential avenues for future research.

The effect of adverse childhood experiences on chronic pain and major depression in adulthood: a systematic review and meta-analysis.

BACKGROUND: Adverse childhood experiences have been linked to increased multimorbidity, with physical and mental health consequences throughout life. Chronic pain is often associated with mood disorders, such as major depressive disorder (MDD); both have been linked to adverse childhood experiences. It is unclear how the effect of adverse childhood experiences on neural processing impacts on vulnerability to chronic pain, MDD, or both, and whether there are shared mechanisms. We aimed to assess evidence for central neural changes associated with adverse childhood experiences in subjects with chronic pain, MDD, or both using systematic review and meta-analysis. METHODS: Electronic databases were systematically searched for neuroimaging studies of adverse childhood experiences, with chronic pain, MDD, or both. Two independent reviewers screened title, abstracts, and full text, and assessed quality. After extraction of neuroimaging data, activation likelihood estimate meta-analysis was performed to identify significant brain regions associated with these comorbidities. RESULTS: Forty-nine of 2414 studies were eligible, of which 43 investigated adverse childhood experiences and MDD and six investigated adverse childhood experiences and chronic pain. None investigated adverse childhood experiences, chronic pain, and MDD together. Functional and structural brain abnormalities were identified in the superior frontal, lingual gyrus, hippocampus, insula, putamen, superior temporal, inferior temporal gyrus, and anterior cerebellum in patients with MDD exposed to adverse childhood experiences. In addition, brain function abnormalities were identified for patients with MDD or chronic pain and exposure to adverse childhood experiences in the cingulate gyrus, inferior parietal lobule, and precuneus in task-based functional MRI studies. CONCLUSIONS: We found that adverse childhood experiences exposure can result in different functional and structural brain alterations in adults with MDD or chronic pain compared with those without adverse childhood experiences. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021233989.

A Meta-Analysis of the Genome-Wide Association Studies on Two Genetically Correlated Phenotypes Suggests Four New Risk Loci for Headaches.

Headache is one of the commonest complaints that doctors need to address in clinical settings. The genetic mechanisms of different types of headache are not well understood while it has been suggested that self-reported headache and self-reported migraine were genetically correlated. In this study, we performed a meta-analysis of genome-wide association studies (GWAS) on the self-reported headache phenotype from the UK Biobank and the self-reported migraine phenotype from the 23andMe using the Unified Score-based Association Test (metaUSAT) software for genetically correlated phenotypes (N = 397,385). We identified 38 loci for headaches, of which 34 loci have been reported before and four loci were newly suggested. The LDL receptor related protein 1 (LRP1)-Signal Transducer and Activator of Transcription 6 (STAT6)-S hort chain D ehydrogenase/R eductase family 9C member 7 (SDR9C7) region in chromosome 12 was the most significantly associated locus with a leading p value of 1.24 × 10-62 of rs11172113. The One Cut homeobox 2 (ONECUT2) gene locus in chromosome 18 was the strongest signal among the four new loci with a p value of 1.29 × 10-9 of rs673939. Our study demonstrated that the genetically correlated phenotypes of self-reported headache and self-reported migraine can be meta-analysed together in theory and in practice to boost study power to identify more variants for headaches. This study has paved way for a large GWAS meta-analysis involving cohorts of different while genetically correlated headache phenotypes. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00078-7.

Effect of a continuous perineural levobupivacaine infusion on pain after major lower limb amputation: a randomised double-blind placebo-controlled trial.

OBJECTIVES: Randomised controlled trial of the effect of a perineural infusion of levobupivacaine on moderate/severe phantom limb pain 6 months after major lower limb amputation. SETTING: Single-centre, UK university hospital. PARTICIPANTS: Ninety patients undergoing above-knee and below-knee amputation for chronic limb threatening ischaemia under general anaesthesia. Exclusion criteria were patients having surgery under neuraxial anaesthesia; inability to operate a patient-controlled analgesia device or complete a Visual Analogue Scale; amputation for trauma or malignancy; or contraindication to levobupivacaine. INTERVENTIONS: Either levobupivacaine 0.125% or saline 0.9% (10 mL bolus, infusion of 8 mL/hour for 96 hours) via a sciatic or posterior tibial nerve sheath catheter placed under direct vision during surgery. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the presence of phantom limb pain, residual limb pain and phantom limb sensations up to 6 months after amputation. Secondary outcome measures included early postoperative pain and morphine requirements after surgery. RESULTS: Data from 81 participants were analysed; 6-month follow-up data were available for 62 patients. Pain and morphine requirements varied widely before and after amputation in both groups. The incidences of moderate/severe phantom limb pain, residual limb pain and phantom limb sensations were low from 6 weeks with no significant differences between groups in phantom limb pain at rest (OR 0.56, 95% CI 0.14 to 2.14, p=0.394) or movement (OR 0.58, 95% CI 0.15 to 2.21, p=0.425) at 6 months. Early postoperative pain scores were low in both groups with no between-group differences in residual limb pain or phantom limb sensations (rest or movement) at any time point. High postoperative morphine consumption was associated with worsening phantom limb pain both at rest (-17.51, 95% CI -24.29 to -10.74; p<0.001) and on movement (-18.54, 95% CI -25.58 to -11.49; p<0.001). The incidence of adverse effects related to the study was low in both groups: postoperative nausea, vomiting and sedation scores were similar, and there were no features of local anaesthetic toxicity. CONCLUSIONS: Long-term phantom limb pain, residual limb pain and phantom limb sensations were not reduced significantly by perineural infusion of levobupivacaine, although the study was underpowered to show significant differences in the primary outcome. The incidence of phantom limb pain was lower than previously reported, possibly attributable to frequent assessment and early intervention to identify and treat postoperative pain when it occurred. There were large variations in postoperative pain scores, high requirements for analgesics before and after surgery and some problems maintaining recruitment and long -term follow-up. Knowledge of these potential problems should inform future research in this group of patients. Further work should investigate the association between perioperative morphine requirements and late phantom limb pain. TRIAL REGISTRATION NUMBERS: EudraCT 2007-000619-27; ISRCTN68691928.

Cross-sectional study examining the epidemiology of chronic pain in Nepal.

Introduction: The World Health Organization recognizes chronic pain as a global public health concern; however, there is a bias towards research conducted in relatively affluent nations. There is a dearth of large-scale epidemiological studies in Nepal using rigorously validated, cross-culturally adapted instruments. Objectives: The aim of this study was to examine the prevalence of both chronic pain and chronic pain of predominantly neuropathic origin and their associations with a range of sociodemographic and psychosocial characteristics. Methods: We conducted a cross-sectional study of adults (≥18 years) in all households in Ranipani, Baluwa Village Development Committee, Nepal. All adults (n = 887) were approached, and those consenting, who met the inclusion criteria (n = 520, 58.6%), participated. Questionnaires validated in Nepali were used to examine several constructs: demographics; chronic pain; neuropathic pain; pain catastrophizing; resilience, pain intensity; pain interference; sleep disturbance; and depression. Results: The point prevalence of chronic pain was 53.3% (n = 277). The point prevalence of chronic pain of predominantly neuropathic origin was 12.7% (n = 66). Chronic pain was associated with female gender, older age, and manual labour occupations. Using standardized scoring techniques, compared with available population estimates from other countries, those with chronic pain were associated with lower pain intensity and resilience scores and higher pain catastrophizing, pain interference, and depression scores. Conclusion: These findings are broadly comparable to epidemiological studies from other countries, and these indicate areas for targeting interventions (eg, occupational and mental health). For comparison, more data are needed, from larger population samples in this region.

Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition impacting 30% of cancer survivors. This study is the first to explore whether a brain-based vulnerability to chronic sensory CIPN exists. METHODS: This prospective, multicentre cohort study recruited from three sites across Scotland. Brain functional MRI (fMRI) scans (3 Tesla) were carried out on chemotherapy naïve patients at a single fMRI centre in Edinburgh, Scotland. Nociceptive stimuli (with a 256 mN monofilament) were administered during the fMRI. Development of chronic sensory/painful CIPN (CIPN+) was determined based upon European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 changes conducted 9 months after chemotherapy, and imaging data analysed using standard software. RESULTS: Of 30 patients recruited (two lung, nine gynaecological, and 19 colorectal malignancies), data from 20 patients at 9 months after chemotherapy was available for analysis. Twelve were classified as CIPN+ (mean age, 63.2[9.6] yr, 9.6; six female), eight as CIPN- (mean age 62.9 [SD 5.5] yr, four female). In response to punctate stimulation, group contrast analysis showed that CIPN+ compared with CIPN- had robust activity in sensory, motor, attentional, and affective brain regions. An a priori chosen region-of-interest analysis focusing on the periaqueductal grey, an area hypothesised as relevant for developing CIPN+, showed significantly increased responses in CIPN- compared with CIPN+ patients. No difference in subcortical volumes between CIPN+ and CIPN- patients was detected. CONCLUSIONS: Before administration of any chemotherapy or appearance of CIPN symptoms, we observed altered patterns of brain activity in response to nociceptive stimulation in patients who later developed chronic sensory CIPN. This suggests the possibility of a pre-existing vulnerability to developing CIPN centred on brainstem regions of the descending pain modulatory system.

Development and external validation of multivariable risk models to predict incident and resolved neuropathic pain: a DOLORisk Dundee study.

Neuropathic pain is difficult to treat, and an understanding of the risk factors for its onset and resolution is warranted. This study aimed to develop and externally validate two clinical risk models to predict onset and resolution of chronic neuropathic pain. Participants of Generation Scotland: Scottish Family Health Study (GS; general Scottish population; n = 20,221) and Genetic of Diabetes Audit and Research in Tayside Scotland (GoDARTS; n = 5236) were sent a questionnaire on neuropathic pain and followed- -up 18 months later. Chronic neuropathic pain was defined using DN4 scores (≥ 3/7) and pain for 3 months or more. The models were developed in GS using logistic regression with backward elimination based on the Akaike information criterion. External validation was conducted in GoDARTS and assessed model discrimination (ROC and Precision-Recall curves), calibration and clinical utility (decision curve analysis [DCA]). Analysis revealed incidences of neuropathic pain onset (6.0% in GS [236/3903] and 10.7% in GoDARTS [61/571]) and resolution (42.6% in GS [230/540] and 23.7% in GoDARTS [56/236]). Psychosocial and lifestyle factors were included in both onset and resolved prediction models. In GoDARTS, these models showed adequate discrimination (ROC = 0.636 and 0.699), but there was evidence of miscalibration (Intercept = - 0.511 and - 0.424; slope = 0.623 and 0.999). The DCA indicated that the models would provide clinical benefit over a range of possible risk thresholds. To our knowledge, these are the first externally validated risk models for neuropathic pain. The findings are of interest to patients and clinicians in the community, who may take preventative or remedial measures.

The core minimum dataset for measuring pain outcomes in pain services across Scotland. Developing and testing a brief multi-dimensional questionnaire.

Background: There is currently no agreed minimum dataset to inform specialist chronic pain service provision. We aimed to develop a Core Minimum Dataset (CMD) for pain services in Scotland and perform preliminary analysis to evaluate its psychometric properties in adults with chronic pain. Methods: The questionnaire was developed following a review of existing relevant data collection instruments and national consultation. The CMD questionnaire was completed alongside a routine pre-clinic questionnaire by patients attending two pain services over 3 months. Concurrent validity was tested by comparing scores between the CMD and pre-existing questionnaires. Reliability was assessed by test-retest and discriminative validity via receiver operating characteristic (ROC) curves. Results: The final CMD questionnaire consisted of five questions on four domains: pain severity (Chronic Pain Grade [CPG] Q1); pain interference (CPG Q5); emotional impact (Patient Health Questionnaire-2 [PHQ-2], two questions); and quality of life (Short Form Health Survey-36 [SF-36] Q1). 530 patients completed the questionnaire. Strong correlation was found with the Hospital Anxiety and Depression Scale (rs = 0.753, p < 0.001). Moderate correlations were found with the Brief Pain Inventory for pain interference (rs = 0.585, p < 0.001) and pain severity (rs = 0.644, p < 0.001). Moderate to good reliability was demonstrated (Intra-class Correlation Coefficient = 0.572-0.845). All items indicated good discrimination for relevant health states. Conclusions: The findings represent initial steps towards developing an accurate questionnaire that is feasible for assessing chronic pain in adults attending specialist pain clinics and measuring service improvements in Scotland. Further validation testing, in clinical settings, is now required.

Assessing the impact of a national clinical guideline for the management of chronic pain on opioid prescribing rates: a controlled interrupted time series analysis.

BACKGROUND: Opioids can be effective analgesics, but long-term use may be associated with harms. In 2013, the first national, comprehensive, evidence-based pain management guideline was published, from the Scottish Intercollegiate Guideline Network (SIGN 136: Management of Chronic Pain) with key recommendations on analgesic prescribing. This study aimed to examine the potential impact on national opioid prescribing rates in Scotland. METHODS: Trends in national and regional community opioid prescribing data for Scotland were analysed from quarter one (Q1) 2005 to Q2 2020. Interrupted time series regression examined the association of SIGN 136 publication with prescribing rates for opioid-containing drugs. Gabapentinoid prescribing was used as a comparison drug. RESULTS: After a positive prescribing trend pre-publication, the timing of SIGN 136 publication was associated with a negative change in the trend of opioid prescribing rates (-2.82 items per 1000 population per quarter [PTPPQ]; P < 0.01). By Q2 2020, the relative reduction in the opioid prescribing rate was -20.67% (95% CI: -23.61, -17.76). This persisted after correcting for gabapentinoid prescribing and was mainly driven by the reduction in weak opioids, whereas strong opioid prescribing rates continued to rise. Gabapentinoid prescribing showed a significant rise in level (8.00 items per 1000 population; P = 0.01) and trend (0.27 items PTPPQ; P = 0.01) following SIGN 136 publication. CONCLUSIONS: The publication of SIGN 136 was associated with a reduction in opioid prescribing rates. This suggests that changes in clinical policy through evidence-based national clinical guidelines may affect community opioid prescribing, though this may be partially replaced by gabapentinoids, and other factors may also contribute.

Characteristics of non-fatal overdoses and associated risk factors in patients attending a specialist community-based substance misuse service.

Introduction: There are concerns about rising drug-related deaths and the potential contribution of prescription analgesics. There is limited understanding regarding the role of prescription analgesics in non-fatal overdoses (NFODs), nor is there a good understanding of what factors are associated with more severe overdose. Objectives: To explore risk factors and characteristics of NFODs among people attending a specialist community-based substance misuse service. Methods: After Caldicott approval, data on NFODs, in people attending the Tayside Substance Misuse Service (TSMS), were extracted from the Scottish Ambulance Service database, along with opioid replacement therapy (ORT) prescribing data. Statistical analysis was performed using R studio and Microsoft Excel. Results: 557 people (78% [434/556] male, mean age ± standard deviation 38.4 ± 7.95) had an NFOD. Repeat NFODs were more likely in males compared to females (p < .0065). Males were more likely to be administered naloxone (OR = 1.94, 95% CI = 1.10-3.40, p < .02). NFODs at home were more likely to be moderate to severe (categorized by Glasgow Comma Scale [p < .02, OR = 4.95, 95% CI = 1.24-24.38]). Methadone (321/557, 57.63%), benzodiazepines (281/557, 50.45%) and heroin (244/557, 43.81%) were the commonest substances: prescribed methadone overdose was more likely than buprenorphine (p < .00001). Opioids and benzodiazepines were often taken together (275/557, 49.40%), with almost all gabapentinoid NFODs also involving opioids (60/61, 98.40%). Conclusions: Polysubstance use with opioids prescribed for ORT, such as methadone, is highly likely to be implicated in NFOD, with males being at the highest risk of severe and repeat NFOD. Future work should focus on strategies to further reduce NFODs.

Coupling cognitive and brainstem dysfunction in multiple sclerosis-related chronic neuropathic limb pain.

Chronic pain in multiple sclerosis is common and difficult to treat. Its mechanisms remain incompletely understood. Dysfunction of the descending pain modulatory system is known to contribute to human chronic pain conditions. However, it is not clear how alterations in executive function influence this network, despite healthy volunteer studies linking function of the descending pain modulatory system, to cognition. In adults with multiple sclerosis-associated chronic neuropathic limb pain, compared to those without pain, we hypothesized altered functional connectivity of the descending pain modulatory system, coupled to executive dysfunction. Specifically we hypothesized reduced mental flexibility, because of potential importance in stimulus reappraisal. To investigate these hypotheses, we conducted a case-control cross-sectional study of 47 adults with relapsing remitting multiple sclerosis (31 with chronic neuropathic limb pain, 16 without pain), employing clinical, neuropsychological, structural, and functional MRI measures. We measured brain lesions and atrophy affecting descending pain modulatory system structures. Both cognitive and affective dysfunctions were confirmed in the chronic neuropathic limb pain group, including reduced mental flexibility (Delis Kaplan Executive Function System card sorting tests P < 0.001). Functional connectivity of rostral anterior cingulate and ventrolateral periaqueductal gray, key structures of the descending pain modulatory system, was significantly lower in the group experiencing chronic neuropathic pain. There was no significant between-group difference in whole-brain grey matter or lesion volumes, nor lesion volume affecting white matter tracts between rostral anterior cingulate and periaqueductal gray. Brainstem-specific lesion volume was higher in the chronic neuropathic limb pain group (P = 0.0017). Differential functional connectivity remained after correction for brainstem-specific lesion volume. Gabapentinoid medications were more frequently used in the chronic pain group. We describe executive dysfunction in people with multiple sclerosis affected by chronic neuropathic pain, along with functional and structural MRI evidence compatible with dysfunction of the descending pain modulatory system. These findings extend understanding of close inter-relationships between cognition, function of the descending pain modulatory system, and chronic pain, both in multiple sclerosis and more generally in human chronic pain conditions. These findings could support application of pharmacological and cognitive interventions in chronic neuropathic pain associated with multiple sclerosis.

The Value of In Vivo Reflectance Confocal Microscopy as an Assessment Tool in Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study.

BACKGROUND: There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN. PATIENTS AND METHODS: Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 × 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical detection thresholds), Grooved pegboard test, and patient-reported outcomes measures (PROMS) were conducted for comparison. RESULTS: In controls (25 females, 20 males; 24-81 years), females exhibited greater mean MC density compared with males (49.9 ± 7.1 vs 30.9 ± 4.2 MC/3 × 3 mm; P = .03). Differences existed across age by decade (P < .0001). Meissner's corpuscle density was correlated with mechanical detection (ρ = -0.51), warm detection (ρ = -0.47), cold pain (ρ = 0.49) thresholds (P < .01); and completion time on the Grooved pegboard test in both hands (P ≤ .02). At baseline, patients had reduced MC density vs age and gender-matched controls (P = .03). Longitudinal assessment of MC density revealed significant relationships with QST and PROMS. Inter-rater reliability of MC count showed an intraclass correlation of 0.96 (P < .0001). CONCLUSIONS: The findings support the clinical utility of RCM in CIPN as it provides meaningful markers of sensory nerve dysfunction. Novel, prospective assessment demonstrated the ability to detect subclinical deficits in patients at risk of CIPN and potential to monitor neuropathy progression.

Bayesian methods in palliative care research: cancer-induced bone pain.

OBJECTIVE: To show how a simple Bayesian analysis method can be used to improve the evidence base in patient populations where recruitment and retention are challenging. METHODS: A Bayesian conjugate analysis method was applied to binary data from the Thermal testing in Bone Pain (TiBoP) study: a prospective diagnostic accuracy/predictive study in patients with cancer-induced bone pain (CIBP). This study aimed to evaluate the clinical utility of a simple bedside tool to identify who was most likely to benefit from palliative radiotherapy (XRT) for CIBP. RESULTS: Recruitment and retention of patients were challenging due to the frail population, with only 27 patients available for the primary analysis. The Bayesian method allowed us to make use of prior work done in this area and combine it with the TiBoP data to maximise the informativeness of the results. Positive and negative predictive values were estimated with greater precision, and interpretation of results was facilitated by use of direct probability statements. In particular, there was only 7% probability that the true positive predictive value was above 80%. CONCLUSIONS: Several advantages of using Bayesian analysis are illustrated in this article. The Bayesian method allowed us to gain greater confidence in our interpretation of the results despite the small sample size by allowing us to incorporate data from a previous similar study. We suggest that this method is likely to be useful for the analysis of small diagnostic or predictive studies when prior information is available.

Analgesic use and associated adverse events in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Treating pain in the context of chronic kidney disease (CKD) is challenging because of altered pharmacokinetics and pharmacodynamics, with an increased risk of toxicity and drug adverse events in this population. The aims of this systematic review and meta-analysis were to assess the prevalence of analgesic use and establish the risk of analgesics-related adverse events, in patients with CKD. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Medline, Embase, CINAHL, and CENTRAL were searched until January 2021. Random-effects meta-analyses and meta-regression were conducted to pool and summarise prevalence data and measures of association between analgesic use and adverse events. RESULTS: Sixty-two studies relevant to the prevalence of analgesic use and 33 to analgesic-related adverse events were included, combining data on 2.3 and 3 million individuals, respectively. Pooled analyses found that 41% (95% confidence interval [CI], 35-48) of the CKD population regularly use analgesia. The annual period prevalence was estimated at 50% for opioids and 21% for nonsteroidal anti-inflammatory drugs (NSAID). Overall, 20% and 7% of patients with CKD are on chronic opioid or NSAID therapy, respectively. Opioid use was associated with an increased risk of death (1.61; 95% CI, 1.12-2.31; n= 7, I2= 91%), hospitalisation (1.38; 95% CI, 1.32-1.45; n=2, I2=0%), and fractures (1.51; 95% CI, 1.16-1.96; n=3, I2=54%). CONCLUSION: High levels of analgesic consumption and related serious adverse outcomes were found in patients with CKD. Consideration needs to be given to how these patients are assessed and managed in order to minimise harms and improve outcomes. CLINICAL TRIAL REGISTRATION: CRD42019156491 (PROSPERO).

Validation of the Nepali Version of the Self-reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) in Adults With Chronic Pain and Predominantly Low-literacy Levels.

Neuropathic pain research and clinical care is limited in low- and middle-income countries with high prevalence of chronic pain such as Nepal. We translated and cross-culturally adapted the Self-report version of the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS)-a commonly used, reliable and valid instrument to screen for pain of predominantly neuropathic origin (POPNO)-into Nepali (S-LANSS-NP) and validated it using recommended guidelines. We recruited 30 patients with chronic pain in an outpatient setting for cognitive debriefing and recruited 287 individuals with chronic pain via door-to-door interviews for validation. For known-group validity, we hypothesized that the POPNO group would report significantly more pain intensity and pain interference than the chronic pain group without POPNO using a cut-off score of ≥10/24. The S-LANSS-NP was comprehensible based on the ease of understanding the questionnaire and lack of missing responses. The validation sample consisted of predominantly low-levels of literacy (81% had 5 years or less education); 23% were classified as having POPNO. Internal consistency was good (alpha = .80). Known-group validity was supported (chronic pain with POPNO reported significantly greater pain intensity than those without). The S-LANSS-NP is a comprehensible, unidimensional, internally consistent, and valid instrument to screen POPNO in individuals with chronic pain with predominantly low-levels of literacy for clinical and research use. PERSPECTIVE: This paper shows that the Nepali version of the S-LANSS is comprehensible, reliable and valid in adults with chronic pain and predominantly low-levels of literacy in rural Nepal. The study could potentially develop research and clinical care of neuropathic pain in this resource-limited setting where chronic pain is a significant problem.

The prevalence of pain among patients with chronic kidney disease using systematic review and meta-analysis.

Pain is a common but often undertreated symptom in patients with chronic kidney disease (CKD) with a much higher prevalence than in the general population. The aim of this systematic review was to synthesize all available quantitative evidence, in order to gain a better understanding of pain prevalence and pain types in patients with CKD. Four databases and the grey literature were searched until 15th January 2021. Random-effect meta-analyses were conducted with multiple subgroup analyses and meta-regressions to further explore the between-study heterogeneity. The quality of studies included was assessed using the Newcastle-Ottawa scale and the level of evidence was determined using the GRADE approach. One hundred sixteen studies reported data on 40,678 individuals. Results from meta-analyses yielded an overall prevalence of 60% (95% confidence interval 56-64) for pain, 48% (42-55) for chronic pain and 10% (6-15) for neuropathic pain. The prevalence of pain was lower among kidney transplant recipients 46% (37-56) compared with patients undergoing dialysis 63% (57-68) and those with non-dialysis CKD 63% (55-70). Musculoskeletal pain appeared to be the most common pain symptom among patients with CKD managed conservatively 42% (28-56) or receiving dialysis 45% (36-55) whilst abdominal pain was most prevalent in kidney transplant recipients 41% (7-86). Thus, all subgroups of patients with CKD suffer from a high burden of pain. Hence, greater awareness and recognition of this issue is vital to inform policy and service provision in this area.

Examination of the clinical factors associated with attendance at emergency departments for chronic pain management and the cost of treatment relative to that of other significant medical conditions.

ABSTRACT: Little is known about risk factors for emergency department (ED) attendance for chronic pain (CP) management and the relative service burden. We examined ED utilisation in patients with CP, identified risk factors associated with attendance for chronic musculoskeletal pain (CMP), and estimated the comparative cost of treatment. The study cohort comprised a random sample of 3700 adults from the general population in Tayside, Scotland. Linked regional extracts, spanning a 12-month period, were obtained from national registers, providing information on ED attendances, community-dispensed prescribing, and outpatient clinic attendances. The National Health Service Scotland Cost Book was used to ascertain the current average cost of an ED attendance (£130; ∼$167). All-cause ED attendance was higher in those with CP (68.5%; n = 252) than without (29.3%; n = 967). In the entire cohort, more patients attended the ED for the treatment of CMP than for any other medical condition (n = 119; 32.3% of those with CP). Risk factors for ED attendance for CMP were: recent analgesic dose decreases (OR = 4.55); and transitioning from opioid to nonopioid analgesics (OR = 5.08). Characteristics protective of ED attendance for CMP were: being in receipt of strong opioids (OR = 0.21); transitioning from nonopioid to opioid analgesics (OR = 0.25); recent analgesic dose increases (OR = 0.24); and being prescribed tricyclic antidepressants (OR = 0.10), benzodiazepines (OR = 0.46), or hypnotics (OR = 0.45). Chronic musculoskeletal pain was one of the most expensive conditions to treat (£17,680 [∼$22,668] per annum), conferring a substantial burden on ED services. Improved understanding of the risk/protective factors could inform healthcare redesign to reduce avoidable ED attendances for CMP management.

Perioperative management of patients with suspected or confirmed COVID-19: review and recommendations for perioperative management from a retrospective cohort study.

BACKGROUND: Current guidelines for perioperative management of coronavirus disease 19 (COVID-19) are mainly based on extrapolated evidence or expert opinion. We aimed to systematically investigate how COVID-19 affects perioperative management and clinical outcomes, to develop evidence-based guidelines. METHODS: First, we conducted a rapid literature review in EMBASE, MEDLINE, PubMed, Scopus, and Web of Science (January 1 to July 1, 2020), using a predefined protocol. Second, we performed a retrospective cohort analysis of 166 women undergoing Caesarean section at Tongji Hospital, Wuhan during the COVID-19 pandemic. Demographic, imaging, laboratory, and clinical data were obtained from electronic medical records. RESULTS: The review identified 26 studies, mainly case reports/series. One large cohort reported greater mortality in elective surgery patients diagnosed after, rather than before surgery. Higher 30 day mortality was associated with emergency surgery, major surgery, poorer preoperative condition and surgery for malignancy. Regional anaesthesia was favoured in most studies and personal protective equipment (PPE) was generally used by healthcare workers (HCWs), but its use was poorly described for patients. In the retrospective cohort study, duration of surgery, oxygen therapy and hospital stay were longer in suspected or confirmed patients than negative patients, but there were no differences in neonatal outcomes. None of the 262 participating HCWs was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when using level 3 PPE perioperatively. CONCLUSIONS: When COVID-19 is suspected, testing should be considered before non-urgent surgery. Until further evidence is available, HCWs should use level 3 PPE perioperatively for suspected or confirmed patients, but research is needed on its timing and specifications. Further research must examine longer-term outcomes. CLINICAL TRIAL REGISTRATION: CRD42020182891 (PROSPERO).