The association of sensory phenotype and concomitant mood, sleep and functional impairment with the outcome of carpal tunnel surgery

Background Up to 25% of people who have had carpal tunnel release surgery (CTR) fail to report improvement; however, evidence for prognostic indicators in this surgical cohort is limited. To identify candidate prognostic factors, this study investigated the association of quantitative sensory testing (QST) derived sensory phenotype and attendant impairment with patient-reported surgical outcome. Methods With ethical approval and informed consent, this prospective observational longitudinal study recruited patients from two London hospitals. Multimodal phenotyping measures including quantitative sensory testing (QST), pain parameters, insomnia, pain-related worry, mood and function, were evaluated prior to; and at 3- and 6-months post-surgery. Pain in median nerve distribution with electrophysiologically confirmed conduction delay and DN4 score ≥ 4 was defined as neuropathic. Primary outcome was patient-rated change at 6 months, dichotomised as poor outcome; “worse” or “no change” and good outcome; “slightly better”, “much better” or “completely cured”. Results Seventy-six patients participated. Prior to surgery, substantial heterogeneity in established categories of somatosensory function was observed with 21% of participants categorised as having a healthy sensory phenotype; 29% with thermal hyperalgesia; 32% mechanical hyperalgesia and 18% sensory loss. Seventy six percent of participants were classified as having neuropathic pain, 33% with high levels of pain related worry and 64% with clinical insomnia. Observed differences in pain, sleep impairment, psychological factors and function, between sensory phenotypic groups, was not significant. At 3- and 6-months post-surgery there was significant improvement in all phenotyping measures with a moderate to large effect size. Thermal and mechanical measures of somatosensation improved (p < 0.001), as did functional ability (p < 0.001). Symptom severity diminished (p < 0.001), as did pain-related worry (p < 0.001), anxiety (p = 0.02) and insomnia (p < 0.001). Patient-rated surgical outcome was good in 92% of the cohort, poor in 8%. Baseline sensory phenotype category was not associated with surgical outcome however pain-related worry, anxiety and functional interference were significantly associated with outcome (p ≤ 0.05). Conclusion In patients undergoing carpal tunnel surgery, pain-related worry, anxiety and pain functional interference are candidate prognostic outcome factors and require further elucidation.

Pain in Hemodialysis Patients: Prevalence, Intensity, Location, and Functional Interference in Daily Activities

Although pain is a frequent complaint of patients with chronic kidney disease who undergo hemodialysis, few studies have assessed the functional interference of pain in activities of daily living (ADLs). Hence, the aim of this study was to evaluate the prevalence, location, intensity, and functional interference of pain in ADLs of chronic kidney disease patients undergoing hemodialysis and to estimate the association of specific pain sites with severe functional interference by pain in ADLs. This cross-sectional study included patients with chronic kidney disease undergoing hemodialysis. The prevalence, intensity, and functional interference of pain in ADLs were assessed using the brief pain inventory. Poisson regression was used to calculate the prevalence ratio. A total of 65 patients participated in the study. The overall prevalence of pain was 89.23%; the prevalence of headache was 18.46% and that of pain in the trunk was 55.38%, upper limbs was 35.38%, and lower limbs was 60.00%. The prevalence of moderate and severe pain at the time of hemodialysis was 13.85% and 21.54%, respectively. A high prevalence of severe functional interference of pain in general activity (61.54%), mobility (56.92%), and disposition (55.38%) was observed. Pain is a frequent complaint in patients undergoing hemodialysis, mainly musculoskeletal and intradialytic, and it interferes with ADLs and incapacitates the patient. Pain was highly prevalent in the upper and lower limbs and the trunk. Furthermore, a higher prevalence of severe pain at the time of hemodialysis and functional interference of pain, mainly in general activity, mobility, and disposition, were observed.

Pain Related Functional Limitations of Persons Injured in Car Accidents

Background: In medical psychology, the Brief Pain Inventory (BPI) allows for a separate assessment of pain intensity (scales of worst, least, and average pain) and of daily functional limitations due to pain (impairments of mood, ability to walk, work, interpersonal relations, sleep, and enjoyment of life). The present study evaluates the convergent validity of BPI’s measure of such functional limitations by calculating its correlations to other relevant clinical measures of psychological impairments caused by motor vehicle accidents (MVAs). Method: De-identified archival data were available on 50 persons injured in MVAs (age 20 to 86 years, mean=42.1 years, SD=16.4; 23 males, 27 females). Their MVA occurred 11 to 280 weeks prior to psychological testing with the BPI (average time lapse 73.3 weeks, SD=53.8). All patients were still experiencing active post-MVA symptoms requiring medical attention and therapy. With respect to convergent validity, we examined Pearson correlations of the BPI to the Insomnia Severity Index (ISI), Rivermead Post-Concussion Symptoms Scale, Subjective Neuropsychological Symptoms Scale (SNPSS), and to measures of depression, anger, and anxiety (Items 10 to 12 of the Whiplash Disability Questionnaire). Results: Functional interference of pain with daily activities (sum of BPI Items 9B to 9G) correlated significantly at p<0.05, 2-tailed with Rivermead post-concussion scores (r=0.39), post-MVA subjective neuropsychological symptoms (r=0.45), insomnia scores (r=0.41), and ratings of depression (r=0.52), anger (r=0.46), and anxiety (r=0.44). When the sum of BPI ratings of worst, least, and average pain was added to the functional interference/limitations score, then this sum of 9 BPI items correlated significantly at p<0.05, 2-tailed with Rivermead post-concussion scores (r=0.36), post-MVA subjective neuropsychological symptoms (r=0.46), insomnia scores (r=0.37), and ratings of depression (r=0.53), anger (r=0.50), and anxiety (r=0.40). Discussion and Conclusion: The results lend support to convergent validity of the BPI when applied to persons injured in vehicular accidents.

The effect of depressive symptoms on pain in a substance-using population with persistent pain: a cross-sectional cohort study

Background In light of the ongoing opioid overdose crisis, there is an urgent need for research on the impacts of mental health among people presenting with concurrent pain and substance use. This study examined the effect of depressive symptoms on pain severity and functional interference among people who use drugs (PWUD) during a community-wide overdose crisis. Methods From December 1st 2016 to December 31st 2018, 288 participants in two cohort studies of PWUD in Vancouver, Canada completed interviewer-administered questionnaires that included the Brief Pain Inventory and PROMIS Emotional Distress–Depression instruments. Generalized linear regression modelling (GLM) was used to examine the cross-sectional effect of depressive symptoms and other confounding factors on pain severity and interference. Results Moderate to severe depressive symptoms were significantly associated with greater pain-related functional interference (adjusted β = 1.24, 95% confidence interval [CI] = 0.33–2.15), but not significantly associated with greater average pain severity (adjusted β = 0.22, 95% CI = − 0.3 – 0.82), when controlling for confounding variables. Reported daily heroin use (adjusted β = 1.26, 95% CI = 0.47–2.05) and non-fatal overdose (adjusted β = 1.02, 95% CI = 0.08–1.96) were also significantly associated with greater pain-related functional interference. Conclusions In a substance-using population, greater pain-related functional interference was positively associated with depressive symptoms as well as overdose and daily heroin use. These findings emphasize the need to address the functional impact of pain, mental health comorbidity, and high-risk substance use that may contribute to overdose and other harms.

Ctnna3 Deficiency Promotes Heart Regeneration by Enhancing Cardiomyocyte Proliferation in Neonatal Mice

Heart regeneration requires renewal of lost cardiomyocytes. However, the mammalian heart loses its proliferative capacity soon after birth, and the molecular signaling underlying the loss of cardiac proliferation postnatally is not fully understood. Here we report that ablation of Ctnna3, coding for an αT-catenin protein and highly expressed in hearts, accelerated heart regeneration following heart apex resection in neonatal mice. Our results show that Ctnna3 deficiency enhances cardiomyocyte proliferation in hearts from P7 mice by upregulating Yap expression. Our study demonstrates that Ctnna3 deficiency is sufficient to promote heart regeneration and cardiomyocyte proliferation in neonatal mice and indicates that functional interference of α-catenins might help to stimulate myocardial regeneration after injury.

More than hurt feelings: The wear and tear of day-to-day discrimination in adults with chronic pain

Objective To examine the extent to which self-reported experiences of discrimination are associated with pain interference among men and women with chronic non-cancer pain. Methods Data are from the Study of Midlife in the United States (MIDUS) Refresher Cohort. The analytic sample consisted of 207 adults with chronic pain (54.2 ± 12.8 years; 53.6% female) who completed the Major Experiences of Discrimination and Everyday Discrimination scales. Regression analyses examined cross-sectional relations between discrimination and pain interference. Results On average, the level of pain interference was moderate in the sample (M = 3.46, SD = 2.66; observed range 0 - 10). Approximately a third of respondents reported at least one major discriminatory event in their lifetime, while 22% reported 3 or more discriminatory lifetime events. Everyday discrimination scores averaged 14.19 ± 5.46 (observed range 0 - 33). Adjusting for sociodemographics, physical health, cognitive and psychological factors, social isolation, and loneliness, everyday discrimination was associated with increased pain interference (B = .099; 95% confidence interval [CI], .02 to .17). Conclusion These findings add weight to the importance of day-to-day experiences of interpersonal discrimination by documenting independent associations with functional interference in adults with chronic pain.

Transporter tandems: precise tools for normalizing active transporter in the plasma membrane

The transport efficiency (TE) describes the performance of a transport protein for a specific substrate. To compare the TE of different transporters, the number of active transporters in the plasma membrane must be monitored, as it may vary for each transporter and experiment. Available methods, like LC–MS quantification of tryptic peptides, fail to discriminate inactive intracellular transporters or, like cell-surface biotinylation followed by affinity chromatography and Western blotting, are imprecise and very laborious. We wanted to normalize active transporters by the activity of a second transporter. A transporter tandem, generated by joining two transporter cDNAs into a single open reading frame, should guarantee a 1 : 1 stoichiometry. Here we created a series of tandems with different linkers between the human ergothioneine (ET) transporter ETT (gene symbol SLC22A4) and organic cation transporter OCT2 (SLC22A2). The linker sequence strongly affected the expression strength. The stoichiometry was validated by absolute peptide quantification and untargeted peptide analysis. Compared with wild-type ETT, the normalized ET clearance of the natural variant L503F was higher (f = 1.34); G462E was completely inactive. The general usefulness of the tandem strategy was demonstrated by linking several transporters with ETT; every construct was active in both parts. Transporter tandems can be used - without membrane isolation or protein quantification — as precise tools for transporter number normalization, to identify, for example, relevant transporters for a drug. It is necessary, however, to find suitable linkers, to check the order of transporters, and to verify the absence of functional interference by saturation kinetics.

Expanding the reach of research: Using remote research technologies to engage people who hear voices (Preprint)

BACKGROUND Similar to other populations with highly stigmatized medical or psychiatric conditions, people who hear voices (i.e., experience auditory verbal hallucinations or AVH) are often hard to identify and reach for research. Technology-assisted remote research strategies reduce barriers to research recruitment; however, few studies have reported on the efficiency and effectiveness of these approaches. OBJECTIVE The present study introduces and evaluates the efficacy of technology-assisted remote research designed for people who experience AVH. METHODS Our group developed an integrated, automated/human complementary online recruitment and enrollment apparatus which incorporated Google Ads, online screening, identification verification, and hybrid automation and interaction with live staff. We examined the efficacy of that apparatus by examining (1) the number of online ad impressions (i.e. number of times the online ad was viewed), (2) clicks on that ad, (3) engagement with online research materials, as well as the extent to which it succeeded at representing a broad sample of individuals with AVH, assessed through the self-reported AVH symptom severity and demographic representativeness (relative to the U.S. population) of the sample recruited. RESULTS Over an 18-month period, our Google Ads were viewed 872,496 times and was clicked on 11,183 times. A total amount of $4,429.25 was spent on Google Ads, resulting in 772 individuals who experience AVH providing consent to participate in an entirely remote research study ($0.40 per click on the ad, and $5.73 per consented participant) after verifying their phone number, passing a competency screening questionnaire, and providing consent. These participants reported high levels of AVH frequency (88.1% daily or more), distress (91.3%) and functional interference (92.4%). They also represented a broad sample of diversity that mirrored U.S. population demographics. Approximately a third (34.9%) of participants had never received treatment for their AVH and, therefore, were unlikely to be identified via traditional clinic-based research recruitment strategies. CONCLUSIONS Online procedures allow for time-saving, cost-efficient, and representative recruitment of individuals with AVH, and can serve as a model for future studies focusing on hard-to-reach populations. CLINICALTRIAL N/A

Effects of electroacupuncture and auricular acupuncture for chronic pain in cancer survivors: The PEACE randomized controlled trial.

12004 Background: The national opioid crisis has created new challenges in oncology pain management and highlighted an urgent need for non-pharmacological treatments. We evaluated the comparative effectiveness of electro-acupuncture (EA) and auricular acupuncture (AA) versus usual care (UC) for chronic musculoskeletal pain in cancer survivors. Methods: We conducted a randomized controlled trial of cancer survivors experiencing moderate-severe musculoskeletal pain for at least 3 months. EA used a semi-individualized protocol involving electrical stimulation of needles placed in the body. AA used the standardized Battlefield Acupuncture protocol involving up to 10 needles placed in the ears. EA and AA groups received 10 weekly treatments, whereas participants in the UC group received standard care prescribed by their providers. The primary endpoint was average pain severity change measured by the Brief Pain Inventory at week 12 compared to baseline. Functional interference and quality of life were secondary outcomes. We analyzed longitudinal mixed-effects models based on intent-to-treat principles. Results: Among 360 participants, mean age (SD) was 62.1 (12.7) years, 251 (69.7%) were women, and 88 (24.4%) were non-white. Compared from baseline to week 12, EA significantly reduced pain severity by 1.9 points (95% Confidence Interval 1.5-2.3, p < 0.001), and AA significantly reduced pain severity by 1.6 points (1.1-2.0, p < 0.001). AA was non-inferior to EA at reducing pain severity (p = 0.04). Both EA and AA also significantly improved functional interference (both p < 0.001), physical health (both p < 0.001), and mental health (p = 0.003, p < 0.001) compared to UC. Adverse events (AEs) were mild in both groups; however, 16 (11.2%) in AA stopped treatment due to AEs (mostly ear discomfort) as compared to 1 in EA (0.7%), p = 0.001. Conclusions: Among cancer survivors with chronic musculoskeletal pain, both EA and AA effectively reduced pain and improved quality of life. AA was non-inferior to EA at reducing pain but associated with higher discontinuation rates. These results will guide implementation of acupuncture in oncology care to address the unmet pain management needs of cancer survivors in the era of the opioid epidemic. Clinical trial information: NCT02979574 .