Trajectories of opioid consumption as predictors of patient-reported outcomes among individuals attending multidisciplinary pain treatment clinics.

PURPOSE: This study aimed to identify opioid consumption trajectories among persons living with chronic pain (CP) and put them in relation to patient-reported outcomes 6 months after initiating multidisciplinary pain treatment. METHODS: This study used data from the Quebec Pain Registry (2008-2014) linked to longitudinal Quebec health insurance databases. We included adults diagnosed with CP and covered by the Quebec public prescription drug insurance plan. The daily cumulative opioid doses in the first 6 months after initiating multidisciplinary pain treatment were transformed into morphine milligram equivalents. An individual-centered approach involving principal factor and cluster analyses applied to longitudinal statistical indicators of opioid use was conducted to classify trajectories. Multivariate regression models were applied to evaluate the associations between trajectory group membership and outcomes at 6-month follow-up (pain intensity, pain interference, depression, and physical and mental health-related quality of life). RESULTS: We identified three trajectories of opioid consumption: "no or very low and stable" opioid consumption (n = 2067, 96.3%), "increasing" opioid consumption (n = 40, 1.9%), and "decreasing" opioid consumption (n = 39, 1.8%). Patients in the "no or very low and stable" trajectory were less likely to be current smokers, experience polypharmacy, use opioids or benzodiazepine preceding their first visit, or experience pain interference at treatment initiation. Patients in the "increasing" opioid consumption group had significantly greater depression scores at 6-month compared to patients in the "no or very low and stable" trajectory group. CONCLUSION: Opioid consumption trajectories do not seem to be important determinants of most PROs 6 months after initiating multidisciplinary pain treatment.

Virtual group psychotherapy for chronic pain: exploring the impact of the virtual medium on participants' experiences.

BACKGROUND: Virtual psychotherapy for chronic pain (CP) has been shown to be feasible, efficacious, and acceptable; however, little is known about how virtual delivery of group psychotherapy affects participants' experiences. This study aimed to explore the impact of a virtual medium during the coronavirus disease 2019 (COVID-19) pandemic on social interactions and therapeutic processes in the context of group psychotherapy for CP management. METHODS: This qualitative, interview-based study collected data on 18 individuals who participated in virtual group psychotherapy in a tertiary care pain management unit. RESULTS: Results of the thematic analysis showed 4 themes. First, the ability to participate and connect was modified by not meeting in person. Connections also occurred differently as the usual patterns of interactions changed. Participants described important shifts in how emotions are communicated and subsequent experience of empathy. Finally, the commonality of chronic pain experience was identified as a central driver of connection between participants. CONCLUSIONS: Mixed impacts of the virtual medium on group psychotherapy dynamics and processes were found. Future research could explore ways to mitigate the negative impacts.

A Prospective Cohort Study of Acute Pain and In-Hospital Opioid Consumption After Cardiac Surgery: Associations With Psychological and Medical Factors and Chronic Postsurgical Pain.

BACKGROUND: Understanding the association of acute pain intensity and opioid consumption after cardiac surgery with chronic postsurgical pain (CPSP) can facilitate implementation of personalized prevention measures to improve outcomes. The objectives were to (1) examine acute pain intensity and daily mg morphine equivalent dose (MME/day) trajectories after cardiac surgery, (2) identify factors associated with pain intensity and opioid consumption trajectories, and (3) assess whether pain intensity and opioid consumption trajectories are risk factors for CPSP. METHODS: Prospective observational cohort study design conducted between August 2012 and June 2020 with 1-year follow-up. A total of 1115 adults undergoing cardiac surgery were recruited from the preoperative clinic. Of the 959 participants included in the analyses, 573 completed the 1-year follow-up. Main outcomes were pain intensity scores and MME/day consumption over the first 6 postoperative days (PODs) analyzed using latent growth mixture modeling (GMM). Secondary outcome was 12-month CPSP status. RESULTS: Participants were mostly male (76%), with a mean age of 61 ± 13 years. Three distinct linear acute postoperative pain intensity trajectories were identified: "initially moderate pain intensity remaining moderate" (n = 62), "initially mild pain intensity remaining mild" (n = 221), and "initially moderate pain intensity decreasing to mild" (n = 251). Age, sex, emotional distress in response to bodily sensations, and sensitivity to pain traumatization were significantly associated with pain intensity trajectories. Three distinct opioid consumption trajectories were identified on the log MME/day: "initially high level of MME/day gradually decreasing" (n = 89), "initially low level of MME/day remaining low" (n = 108), and "initially moderate level of MME/day decreasing to low" (n = 329). Age and emotional distress in response to bodily sensations were associated with trajectory membership. Individuals in the "initially mild pain intensity remaining mild" trajectory were less likely than those in the "initially moderate pain intensity remaining moderate" trajectory to report CPSP (odds ratio [95% confidence interval, CI], 0.23 [0.06-0.88]). No significant associations were observed between opioid consumption trajectory membership and CPSP status (odds ratio [95% CI], 0.84 [0.28-2.54] and 0.95 [0.22-4.13]). CONCLUSIONS: Those with moderate pain intensity right after surgery are more likely to develop CPSP suggesting that those patients should be flagged early on in their postoperative recovery to attempt to alter their trajectory and prevent CPSP. Emotional distress in response to bodily sensations is the only consistent modifiable factor associated with both pain and opioid trajectories.

Association between weight gain and knee osteoarthritis: a systematic review.

OBJECTIVE: Although weight loss is recommended to manage knee osteoarthritis (KOA), adults tend to gain weight with age which may affect KOA symptoms and progression. We conducted a systematic review and data synthesis to investigate the association between weight gain and KOA, defined by clinical features, structural progression, and total knee replacement (TKR). DESIGN: MEDLINE and EMBASE were systematically searched for controlled trials and cohort studies of participants with (or at risk of) KOA examining the relationship between weight gain and KOA clinical features (pain, function, quality of life), structural progression, and TKR. Risk of bias was assessed using the ROBINS-I tool. Results were organised by outcome, with meta-analyses performed where appropriate. RESULTS: Twenty-three studies were included. Results showed significant detrimental effects of weight gain on pain (4 of 7 studies), stiffness (2 of 2 studies), function (5 of 6 studies), and the single studies examining quality of life, and clinical and radiographic KOA. Weight gain adversely affected cartilage (6 of 9 studies), bone marrow lesions (1 of 4 studies), meniscal damage (1 of 3 studies) and effusion/synovitis (1 of 1 study). Weight gain significantly increased TKR (3 of 6 studies): meta-analysis of 2 with available data demonstrated significant increases in TKR/5 kg weight gain in women, HR 1.34 (95% CI 1.18-1.51), and in men, HR 1.25 (95% CI 1.16-1.34). CONCLUSIONS: Weight gain in adults is associated with increased clinical and structural KOA and TKR. Prevention of weight gain should be considered to improve outcomes in KOA.

Sickle cell bone disease and response to intravenous bisphosphonates in children.

Children with sickle cell disease (SCD) have the potential for extensive and early-onset bone morbidity. This study reports on the diversity of bone morbidity seen in children with SCD followed at three tertiary centers. IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications. INTRODUCTION: To evaluate bone morbidity and the response to intravenous (IV) bisphosphonate therapy in children with SCD. METHODS: We conducted a retrospective review of patient records from 2003 to 2019 at three Canadian pediatric tertiary care centers. Radiographs, magnetic resonance images, and computed tomography scans were reviewed for the presence of avascular necrosis (AVN), bone infarcts, and myositis. IV bisphosphonates were offered for bone pain management. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA). RESULTS: Forty-six children (20 girls, 43%) had bone morbidity at a mean age of 11.8 years (SD 3.9) including AVN of the femoral (17/46, 37%) and humeral (8/46, 17%) heads, H-shaped vertebral body deformities due to endplate infarcts (35/46, 76%), and non-vertebral body skeletal infarcts (15/46, 32%). Five children (5/26, 19%) had myositis overlying areas of AVN or bone infarcts visualized on magnetic resonance imaging. Twenty-three children (8/23 girls) received IV bisphosphonate therapy. They all reported significant or complete resolution of bone pain. There were no reports of sickle cell hemolytic crises, pain crises, or stroke attributed to IV bisphosphonate therapy. CONCLUSION: Children with SCD have the potential for extensive and early-onset bone morbidity. In this series, IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications.

Bimekizumab for the treatment of moderate-to-severe plaque psoriasis: efficacy, safety, pharmacokinetics, pharmacodynamics and transcriptomics from a phase IIa, randomized, double-blind multicentre study.

BACKGROUND: Bimekizumab is a monoclonal antibody that selectively inhibits both interleukin (IL)-17A and IL-17F, which is currently under investigation for treatment of moderate-to-severe plaque psoriasis. Maintenance dosing every 4 weeks is well established with IL-17 inhibitors for psoriasis. OBJECTIVES: To investigate the possible dosing interval during bimekizumab maintenance therapy to maintain clear skin, to inform phase III studies. METHODS: Forty-nine patients with moderate-to-severe plaque psoriasis received bimekizumab 320 mg at weeks 0/4, followed at week 16 by bimekizumab 320 mg (n = 17) or placebo (n = 32). Efficacy, safety, pharmacokinetics, immunogenicity and biopsy transcriptomic analyses were assessed to week 28. RESULTS: At week 8, 47% of patients achieved a 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100), increasing to 57% at week 12 (8 weeks after the second dose) before decreasing. In those who received bimekizumab at week 16, PASI 100 rate increased to comparable peak levels at week 20, but reduced by week 28 to 41% (12 weeks after the third dose). The week 8 transcriptional signature observed in lesional psoriatic skin rapidly normalized to levels consistent with nonlesional skin, resulting in molecular remission. Keratinocyte-related gene products such as CXCL1 (C-X-C motif chemokine ligand 1), IL-8 (encoded by the CXCL8 gene), CCL20 (C-C motif chemokine 20), IL-36γ and IL-17C were profoundly normalized to levels associated with nonlesional skin. CONCLUSIONS: Here, inhibition of IL-17F in addition to IL-17A resulted in rapid, deep clinical responses. Additionally, profound normalization of keratinocyte biology and the psoriatic transcriptome was observed, including normalization of both IL17 and IL23 gene expression by week 8. These data provide evidence to support evaluation of bimekizumab maintenance dosing both every 8 and every 4 weeks in phase III clinical trials.

French-Canadian Translation and Cultural Adaptation of the Clinical Opiate Withdrawal Scale: The COWS-FC.

OBJECTIVE: The main objective of the present study was to develop a French-Canadian translation and adaptation of the COWS (i.e., the COWS-FC) for the assessment of opioid withdrawal symptoms in clinical and research settings. METHODS: The French-Canadian translation and cultural adaptation of the COWS was performed following guidelines for the translation and cross-cultural adaptation of self-report measures. The steps consisted of (1) initial translation from English to French, (2) synthesis of the translation, (3) back-translation from French to English, (4) expert committee meeting, (5) test of the prefinal version among healthcare professionals and (6) review of final version by the expert committee. The expert committee considered four major areas where the French-Canadian version should achieve equivalence with the original English-version of the COWS. These areas were (1) semantic equivalence; (2) idiomatic equivalence; (3) experiential equivalence and (4) conceptual equivalence. RESULTS: Rigorous steps based on the guidelines for the translation and cultural adaptation of assessment tools were followed, which led to a semantically equivalent version of the COWS. After a pretest among healthcare professionals, members from the expert committee agreed upon slight modifications to the French-Canadian version of the COWS to yield a final COWS-FC version. CONCLUSIONS: A French-Canadian translation and adaptation of the COWS (i.e., the COWS-FC) was developed. The COWS-FC could be used for the assessment of opioid withdrawal symptoms in clinical and research settings.

Generation and Reactions of ε-Carbonyl Cations via Group 13 Catalysis.

The generation of ε-carbonyl cations and their reactions with nucleophiles is accomplished readily without transition metal cation stabilization, using the ε-bromide dienoate or dienone starting materials and GaCl3 or InCl3 catalysis. Arene nucleophiles are somewhat more straightforward than allyltrimethylsilane, but allyltrimethylsilane and propiophenone trimethysilyl enol ether each react successfully with InCl3 catalysis. The viability of these cations is supported by DFT calculations.

Chronic pain experience and health inequities during the COVID-19 pandemic in Canada: qualitative findings from the chronic pain & COVID-19 pan-Canadian study.

BACKGROUND: Chronic pain affects about 20 % of the Canadian population and can lead to physical, psychological and social vulnerabilities. However, this condition remains poorly recognized and undertreated. During 2020, as the COVID-19 pandemic disrupted daily living and health care systems, the situation of people with chronic pain has drawn little public attention. METHODS: This qualitative study was part of a pan-Canadian mixed-methods project and aimed to understand the experiences and challenges of people living with chronic pain during the COVID-19 pandemic in Canada. Between May and August 2020, we conducted in-depth semi-structured interviews with 22 individuals living with chronic pain across the country. We used reflexive thematic analysis to interpret data. RESULTS: Our findings underscored four dimensions of the chronic pain experience during the pandemic: (1) Reinforced vulnerability due to uncertainties regarding pain and its management; (2) Social network as a determinant of pain and psychological condition; (3) Increasing systemic inequities intermingling with the chronic pain experience; (4) More viable living conditions due to confinement measures. Though several participants reported improvements in their quality of life and reduced social pressure in the context of stay-at-home orders, participants from socio-economically deprived groups and minorities reported more challenges in accessing pain relief, health care services, and psychosocial support. CONCLUSIONS: The COVID-19 pandemic has revealed and intensified pre-existing disparities and challenges among people living with chronic pain in terms of material resources, psychosocial condition, social support, and access to care. In post-pandemic times, it will be essential to address flaws in health and welfare policies to foster equity and social inclusiveness of people with chronic pain.

Chronic pain patients' willingness to share personal identifiers on the web for the linkage of medico-administrative claims and patient-reported data: The chronic pain treatment cohort.

PURPOSE: The linkage between patient-reported data and medico-administrative claims is of great interest for epidemiologic research. The goal of this study was to assess the willingness of people living with chronic pain to share personal identifiers on the web for the linkage of medico-administrative and patient-reported data. METHODS: This methodological investigation was achieved in the context of the implementation of the chronic pain treatment (COPE) cohort. A web-based recruitment initiative targeting adults living with chronic pain was conducted in the province of Quebec (Canada). RESULTS: A total of 1935 participants completed the questionnaire (mean age: 49.86 ± 13.27; females: 83.69%), 921 (47.60%) of which agreed to data linkage and shared their personal identifiers (name, date of birth, health insurance number online). The most common reasons for refusal were: (1) concerns regarding data security/privacy (25.71%) and (2) the belief that the requested data were too personal/intrusive (13.52%). Some participants did not understand the relevance of data linkage (11.81%). Participants from the COPE cohort and those from the subsample who agreed to data linkage were comparable to other random samples of chronic pain individuals in terms of age and pain characteristics. CONCLUSIONS: Although approximately half of the participants refused data linkage, our approach allowed for the implementation of a data platform that contains a diverse and substantial sample. This investigation has also led to the formulation of recommendations for web-based data linkage, including placing items designed to assess willingness to share personal identifiers at the end of the questionnaire, adding explanatory videos, and using a mixed-mode questionnaire.

The Stressful Characteristics of Pain That Drive You NUTS: A Qualitative Exploration of a Stress Model to Understand the Chronic Pain Experience.

OBJECTIVE: Despite decades of research on the identification of specific characteristics of situations that trigger a physiological stress response (novelty, unpredictability, threat to the ego, and sense of low control [NUTS]), no integrative research has examined the validity of this framework applied to pain experiences. This study aimed to 1) explore the stressful characteristics of pain among individuals living with chronic pain and 2) examine whether the NUTS framework comprehensively captures the stressful nature of pain. SUBJECTS: Participants were 41 adult participants living with chronic pain. METHODS: Interviews in six focus groups were conducted in French using a semistructured interview guide. Participants first discussed how pain is stressful. Then, they were introduced to the NUTS framework and commented on the extent to which it captured their experience. The verbatim transcriptions of interviews were reviewed using reflexive thematic analysis. Analyses were conducted in French; quotes and themes were translated into English by a professional translator. RESULTS: The pain-NUTS framework adequately captured participants' experiences. Multiple aspects of pain (pain intensity fluctuations, pain flare-up duration, pain quality and location, functional limitations, diagnosis and treatment) were associated with one or more stress-inducing characteristics. In addition, a second layer of meaning emerged in the context of chronic pain that provided contextual information regarding when, how, and why pain became more or less stressful. CONCLUSIONS: The NUTS characteristics seem to offer a comprehensive framework to understand how pain and its context of chronicity can be a source of stress. This study provides preliminary support for the pain-NUTS framework to allow the formal integration of pain and stress research.

Patient-reported outcomes in those consuming medical cannabis: a prospective longitudinal observational study in chronic pain patients.

PURPOSE: We investigated patients with chronic pain seeking medical cannabis. We assessed their demographics, patterns of cannabis use, and the long-term effectiveness of cannabis on their pain and functional domains. METHODS: This observational study enrolled patients between 8 September 2015 and 31 July 2018 from community-based cannabis clinics in Ontario, Canada. In addition to collecting demographic information, the primary outcomes studied were pain intensity and pain-related interference scores assessed at baseline, three, six, and 12 months. Using validated questionnaires, we also assessed anxiety, depression, quality of life (QoL), general health symptoms, neuropathic pain, self-reported opioid consumption, and adverse events. RESULTS: Of the 1,000 patients consented, 757 (76%) participated at one or more of the study time points. At six and 12 months, 230 (30.4%) and 104 (13.7%) of participants were followed up, respectively. Most participants were female (62%), Caucasian (91%), and sought cannabis for pain relief (88%). Time was a significant factor associated with improvement in pain intensity (P < 0.001), pain-related interference scores (P < 0.001), QoL (P < 0.001), and general health symptoms (P < 0.001). Female sex was significantly associated with worse outcomes than male sex including pain intensity (P < 0.001) and pain-related interference (P < 0.001). The proportion of individuals who reported using opioids decreased by half, from 40.8% at baseline to 23.9% at 12 months. CONCLUSION: Despite significant challenges to collecting long-term observational data on patients who attempted a trial of cannabis products, approximately one-third of patients in the cohort remained on medical cannabis for six months. In this cohort, pain intensity and pain-related interference scores were reduced and QoL and general health symptoms scores were improved compared with baseline.

RéSUMé: OBJECTIF: Nous avons étudié des patients souffrant de douleur chronique et cherchant à obtenir du cannabis médical. Nous avons évalué leurs données démographiques, leurs habitudes de consommation de cannabis et l'efficacité à long terme du cannabis sur leur douleur et leurs domaines fonctionnels. MéTHODE: Cette étude observationnelle a recruté des patients entre le 8 septembre 2015 et le 31 juillet 2018 dans des cliniques communautaires de cannabis en Ontario, au Canada. En plus de recueillir des renseignements démographiques, les critères d'évaluation principaux étudiés étaient l'intensité de la douleur et les scores d'interférence liés à la douleur évalués au début de l'étude et à trois, six et 12 mois. À l'aide de questionnaires validés, nous avons également évalué l'anxiété, la dépression, la qualité de vie (QdV), les symptômes généraux de santé, la douleur neuropathique, la consommation d'opioïdes rapportée et les effets indésirables. RéSULTATS: Sur les 1000 patients consentants, 757 (76 %) ont participé à un ou plusieurs des points d'analyse de l'étude. À six et douze mois, 230 (30,4 %) et 104 (13,7 %) patients ont participé, respectivement. La plupart des participants étaient des femmes (62 %) d'origine caucasienne (91 %) et cherchaient à soulager leur douleur avec du cannabis (88 %). Le temps était un facteur important associé à l'amélioration de l'intensité de la douleur (P < 0,001), aux scores d'interférence liés à la douleur (P < 0,001), à la QdV (P < 0,001), et aux symptômes de santé généraux (P < 0,001). Le sexe féminin a été significativement associé à des pronostics moins bons que le sexe masculin, y compris en matière d'intensité de la douleur (P < 0,001) et d'interférences liées à la douleur (P < 0,001). La proportion de personnes qui ont déclaré utiliser des opioïdes a diminué de moitié, passant de 40,8 % au début de l'étude à 23,9 % à 12 mois. CONCLUSION: Malgré des défis importants dans la collecte de données observationnelles à long terme concernant les patients qui participent à une étude sur les produits du cannabis, environ un tiers des patients de la cohorte ont continué à prendre du cannabis médical pendant six mois. Dans cette cohorte, l'intensité de la douleur et les scores d'interférence liés à la douleur ont été réduits, et les scores de QdV et de symptômes généraux de santé se sont améliorés par rapport au début de la période à l'étude.

The Experiences of People Living With Chronic Pain During a Pandemic: "Crumbling Dreams With Uncertain Futures".

People living with chronic pain experience multiple challenges in their daily activities. Chronic pain is complex and often provokes life circumstances that create increased social isolation. Living with chronic pain during the pandemic may add additional layers of complexity to their daily lives. The researchers endeavored to explore the experiences of people living with chronic pain during the COVID-19 pandemic. Researchers conducted semi-structured, open-ended interviews about how the pandemic influenced participants' lives. The interviews were recorded and analyzed using an applied philosophical hermeneutics approach. The findings were feeling socially isolated, losing their sense of livinghood, and experiencing augmented stress levels which, in most cases, aggravated their chronic pain. In addition to gaining an in-depth understanding of the needs of people living with chronic pain, these findings may guide policy decisions with the intention of improving health care access and the overall experiences of people living with chronic conditions during a pandemic.

Conversations About Opioids: Impact of the Opioid Overdose Epidemic on Social Interactions for People Who Live With Chronic Pain.

The objective of this study was to understand the impact of the opioid overdose epidemic on the social lives of people suffering from chronic pain, focusing on interactions within their personal and professional circles. The study was based on 22 in-depth interviews with people living with chronic pain in Canada. Using thematic analysis, we documented three main impacts of the opioid overdose epidemic: (a) increased worries of people in pain and their families regarding the dangers of opioids; (b) prejudices, stigma, and discrimination faced during conversations about opioids; and (c) stigma management attempts, which include self-advocacy and concealment of opioid use. This study represents important knowledge advancement on how people manage stigma and communicate about chronic disease during everyday life interactions. By showing negative effects of the epidemic's media coverage on the social experiences of people with chronic pain, we underscore needs for destigmatizing approaches in public communication regarding opioids.

Predictors of one year chronic post-surgical pain trajectories following thoracic surgery.

PURPOSE: Chronic post-surgical pain (CPSP) is a highly prevalent complication following thoracic surgery. This is a prospective cohort study that aims to describe the pain trajectories of patients undergoing thoracic surgery beginning preoperatively and up to 1 year after surgery METHODS: Two hundred and seventy nine patients undergoing elective thoracic surgery were enrolled. Participants filled out a preoperative questionnaire containing questions about their sociodemographic information, comorbidities as well as several psychological and pain-related statuses. They were then followed-up during their immediate postoperative period and at the three, six and 12 month time-points to track their postoperative pain, complications and pain-related outcomes. Growth mixture modeling was used to construct pain trajectories. RESULTS: The first trajectory is characterized by 185 patients (78.1%) with mild pain intensity across the 12 month period. The second is characterized by 32 patients (7.5%) with moderate pain intensity immediately after surgery which decreases markedly by 3 months and remains low at the 12 month follow-up. The final trajectory is characterized by 20 patients (8.4%) with moderate pain intensity immediately after surgery which persists at 12 months. Patients with moderate to severe postoperative pain intensity were much more likely to develop CPSP compared to patients with mild pain intensity. Initial pain intensity levels immediately following surgery as well as levels of pain catastrophizing at baseline were predicting pain trajectory membership. None of the surgical or anesthetic-related variables were significantly associated with pain trajectory membership. CONCLUSION: Patients who undergo thoracic surgery can have postoperative pain that follows one of the three different types of trajectories. Higher levels of immediate postoperative pain and preoperative pain catastrophizing were associated with moderately severe CPSP.

Interest of registries in neuropathic pain research.

Neuropathic pain is frequent in the general population, with 7 to 10% of adults presenting with chronic neuropathic pain. To date, the gold standard to evaluate treatments is based on randomized controlled trials. Nonetheless, such design is run on a limited sample and for a limited period. Moreover, many treatments will never be compared directly in sufficiently large and representative populations. A way to overcome several of these limitations is to use real-world data. Indeed, the International Association for the Study of Pain (IASP) includes a special interest group focusing on pain registries and promoting the use of such approaches. In this short narrative review, several of the main chronic pain registries are presented. The strengths and weaknesses of this approach are presented. Indication bias is frequent in observational studies because the choice of treatment is generally influenced by the patients' characteristics. However, a propensity score can be computed to adjust for these differences. The use of propensity score is briefly explained. Some data specific to neuropathic pain are discussed.

What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review.

BACKGROUND: Epidemiological studies indicate that gene-environment interactions play a role in atopic dermatitis (AD). OBJECTIVES: To review the evidence for gene-environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations. METHODS: A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis. RESULTS: Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG-environment interactions in six of the studies (P-value for interaction ≤ 0·05), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions. CONCLUSIONS: Evidence on FLG-environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411.

A lever action hypothesis for pendulous hummingbird flowers: experimental evidence from a columbine.

BACKGROUND AND AIMS: Pendulous flowers (due to a flexible pedicel) are a common, convergent trait of hummingbird-pollinated flowers. However, the role of flexible pedicels remains uncertain despite several functional hypotheses. Here we present and test the 'lever action hypothesis': flexible pedicels allow pendulous flowers to move upwards from all sides, pushing the stigma and anthers against the underside of the feeding hummingbird regardless of which nectary is being visited. METHODS: To test whether this lever action increased pollination success, we wired emasculated flowers of serpentine columbine, Aquilegia eximia, to prevent levering and compared pollination success of immobilized flowers with emasculated unwired and wire controls. KEY RESULTS: Seed set was significantly lower in wire-immobilized flowers than unwired control and wire control flowers. Video analysis of visits to wire-immobilized and unwired flowers demonstrated that birds contacted the stigmas and anthers of immobilized flowers less often than those of flowers with flexible pedicels. CONCLUSIONS: We conclude that flexible pedicels permit the levering of reproductive structures onto a hovering bird. Hummingbirds, as uniquely large, hovering pollinators, differ from flies or bees which are too small to cause levering of flowers while hovering. Thus, flexible pedicels may be an adaptation to hummingbird pollination, in particular due to hummingbird size. We further speculate that this mechanism is effective only in radially symmetric flowers; in contrast, zygomorphic hummingbird-pollinated flowers are usually more or less horizontally oriented rather than having pendulous flowers and flexible pedicels.

Prevalence, Characteristics, and Management of Chronic Noncancer Pain Among People Who Use Drugs: A Cross-Sectional Study.

INTRODUCTION: Most studies on chronic noncancer pain (CNCP) in people who use drugs (PWUD) are restricted to people attending substance use disorder treatment programs. This study assessed the prevalence of CNCP in a community-based sample of PWUD, identified factors associated with pain, and documented strategies used for pain relief. METHODS: This was a cross-sectional study nested in an ongoing cohort of PWUD in Montreal, Canada. Questionnaires were administered to PWUD seen between February 2017 and January 2018. CNCP was defined as pain lasting three or more months and not associated with cancer. RESULTS: A total of 417 PWUD were included (mean age = 44.6 ± 10.6 years, 84% men). The prevalence of CNCP was 44.8%, and the median pain duration (interquartile range) was 12 (5-18) years. The presence of CNCP was associated with older age (>45 years old; odds ratio [OR] = 1.8, 95% CI = 1.2-2.7), male sex (OR = 2.3, 95% CI = 1.2-4.2), poor health condition (OR = 1.9, 95% CI = 1.3-3.0), moderate to severe psychological distress (OR = 2.9, 95% CI = 1.8-4.7), and less frequent cocaine use (OR = 0.5, 95% CI = 0.3-0.9). Among CNCP participants, 20.3% used pain medication from other people, whereas 22.5% used alcohol, cannabis, or illicit drugs to relieve pain. Among those who asked for pain medication (N = 24), 29.2% faced a refusal from the doctor. CONCLUSIONS: CNCP was common among PWUD, and a good proportion of them used substances other than prescribed pain medication to relieve pain. Close collaboration of pain and addiction specialists as well as better pain assessment and access to nonpharmacological treatments could improve pain management in PWUD.

Predictors of Long-Term Opioid Effectiveness in Patients With Chronic Non-Cancer Pain Attending Multidisciplinary Pain Treatment Clinics: A Quebec Pain Registry Study.

OBJECTIVE: This study aimed to identify characteristics of individuals who are most likely to benefit from long-term opioid therapy in terms of reduction in pain severity and improved mental health-related quality of life (mQoL) without considering potential risks. METHODS: This was a retrospective cohort study of 116 patients (age = 51.3 ± 12.5 years, male = 42.2%) enrolled in the Quebec Pain Registry between 2008 and 2011 and who initiated opioid therapy after their first appointment in a multidisciplinary pain clinic and persisted with this treatment for at least 12 months. Clinically significant improvement was defined as a 2-point decrease on the PEG (pain, enjoyment of life, and general activity) Scale of pain severity (scored from 0 to 10) at 12-month follow-up and a 10-point increase on the Short-Form-12 Health Survey version 2 (SF12-v2) Mental Health-Related Quality of Life Summary Scale, which corresponds to 1 standard deviation (SD) of the mean in the general population (mean = 50, SD = 10). RESULTS: Clinically significant reduction in pain severity was observed in 26.7% of patients, while improvement in mQoL was reported by 20.2% of patients on long-term opioid therapy. Older age (odds ratio [OR] = 1.04; 95% confidence interval [CI]: 1.0 to 1.08; P = 0.032) and alcohol or drug problems (OR = 0.26; 95% CI: 0.07 to 0.96; P = 0.044) were weakly associated with pain severity at 12-month follow-up. Baseline higher pain severity (OR = 0.62; 95% CI: 0.43 to 0.91; P = 0.014) and baseline higher mQoL (OR = 0.89; 95% CI: 0.83 to 0.95; P = 0.001) were associated with non-improvement in mQoL. CONCLUSION: The analysis failed to identify clinically meaningful predictors of opioid therapy effectiveness, making it difficult to inform clinicians about which patients with chronic non-cancer pain are most likely to benefit from long-term opioid therapy.