Broad evidence of xylazine in the UK illicit drug market beyond heroin supplies: Triangulating from toxicology, drug-testing and law enforcement.

BACKGROUND AND AIMS: Xylazine is a non-opioid sedative which has spread rapidly throughout the US illicit drug supply. This study aimed to describe the spread of xylazine throughout the UK illicit drug supply. METHODS: Xylazine detections in human biological samples were collated from toxicology laboratories operating in the United Kingdom with the date, location, case type, xylazine concentration and co-detected drugs (with quantifications where performed) detailed, where permitted, by the corresponding coroner. Drug-testing cases positive for xylazine were collated from the Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) drug-testing postal service with the date, location, purchase intent and co-detected drugs detailed. Drug seizures made by UK law enforcement were communicated by the Office for Health Improvement and Disparities with the date and location detailed. RESULTS: By the end of August 2023, xylazine was detected in 35 cases from throughout toxicology, drug-testing and drug seizure sources covering England, Scotland and Wales. There were no cases reported from Northern Ireland. Xylazine was detected in biological samples from 16 people. In most cases where full toxicology results were provided, xylazine was detected with heroin and/or a strong opioid (n = nine of 11), but this polydrug use pattern was not evident in all cases (n = two of 11), suggesting a wider circulation of xylazine in the UK illicit drug market beyond heroin supplies. Evidence from WEDINOS supports this claim, as all 14 drug samples (100%) submitted from across the UK contained xylazine; however, in none of these cases was heroin the purchase intent but rather counterfeit prescription medication tablets (n = 11 of 14), tetrahydrocannabinol (THC) vapes (n = two of 14) or white powder (n = one of 14). Additional evidence for the spread of illicit xylazine comes from five drug seizures made by law enforcement. CONCLUSIONS: Xylazine has penetrated the UK illicit drug market and is not limited to heroin supplies.

'Are dynamic procedures superior to static in treating the paralytic eyelid in facial paralysis?'

BACKGROUND: Facial nerve weakness can cause deficient eye closure with reduced corneal protection. Surgical remedies can be static to oppose the levator muscle (lid loading) or dynamic procedures, which act to increase the strength of closure. This retrospective cohort study compares these groups. The hypothesis is that dynamic reconstruction has advantages over static techniques in terms of eye closure, symptomatic improvement, blink restoration, and complication rate. METHODS: Two cohorts were compared: those treated with a gold weight insertion into the upper eyelid and those who had received dynamic reconstruction. These included temporalis transfer; cross face nerve grafting alone (CFNG) and CFNG followed by free tissue transfer. Assessments included standard photography and video; measurement of eyelid excursion including residual gap and if full eye closure was possible. The presence of the blink reflex and symptoms of dry eye was assessed. RESULTS: Overall improvement in eye closure was similar with the gold weight compared to dynamic procedures (5.1 mm vs 5.3 mm). Dynamic procedures however gave improved results in terms of symptom relief and restoration of blink. They also had fewer complications and revision rates overall. CONCLUSION: The study confirms the hypothesis that dynamic reconstructions of the paralysed eyelid confer advantages compared to simple lid loading techniques. Improvements in lid excursion are similar, but symptom improvement and blink restoration are significantly better. A decision regarding eyelid reanimation should be made early in the patient's journey of facial reanimation to allow for accurate planning and placement of nerve grafts at an early stage.

Fat Grafting in Facial Palsy: A Secondary Revision Technique to Improve the Facial Aesthetics.

We report our experience of using autologous fat grafting (AFG) as an adjunct to dynamic and static facial reanimation surgical techniques in patients with facial palsy. A consecutive series of patients with facial palsy (congenital or acquired) treated by AFG between September 2007 and October 2017 were reviewed. Multiple strategies for initial dynamic facial reanimation have been utilized. Indications for AFG included asymmetry, volume deficiency, and visible muscle tethering. Standard AFG technique was used with fat harvested from the lower abdomen or thigh and injected into multiple affected areas. Fat grafting was repeated as necessary. Two-dimensional analysis was performed using standardized pre- and postoperative photographs to assess facial symmetry. Patient, surgeon, and independent evaluator satisfaction was recorded using a five-point Likert scale (0-4). Thirty-two patients with a mean age of 43 ± 15.5 years were treated with AFG following facial reanimation. A mean of 1.7 ± 1.4 secondary procedures were performed following initial dynamic reanimation before fat grafting. The average number of AFG episodes was 2.2 ± 1.4 with a mean volume of 12.9 ± 6.0 ml. Minimal complications were seen in either the donor or the recipient sites. There was significant improvement (P ≤ 0.001) of postoperative quantitative facial symmetry following fat grafting. At one-year follow-up, surgeon, patient, and independent evaluator were mostly satisfied (3.06 ± 0.62, 3.31 ± 0.59, and 3.16 ± 0.57, respectively). We report a positive experience of correction of facial asymmetry, contour abnormality and visible muscle pull with fat transplantation following dynamic facial reanimation. The procedure has been shown to be quick and simple, with few complications.

Can cannabis kill? Characteristics of deaths following cannabis use in England (1998-2020).

BACKGROUND: Cannabis is the most widely used illegal drug but is rarely considered a causal factor in death. AIMS: This study aimed to understand trends in deaths in England where cannabinoids were detected at post-mortem, and to evaluate the clinical utility of post-mortem cannabinoid concentrations in coronial investigations. METHODS: Deaths with cannabinoid detections reported to the National Programme on Substance Abuse Deaths (NPSAD) were extracted and analysed. RESULTS: From 1998 to 2011, on average 7% of all cases reported to NPSAD had a cannabinoid detected (n = 110 deaths per year), rising to 18% in 2020 (n = 350). Death following cannabis use alone was rare (4% of cases, n = 136/3455). Traumatic injury was the prevalent underlying cause in these cases (62%, n = 84/136), with cannabis toxicity cited in a single case. Polydrug use was evident in most cases (96%, n = 3319/3455), with acute drug toxicity the prevalent underlying cause (74%, n = 2458/3319). Cardiac complications were the most cited physiological underlying cause of death (4%, n = 144/3455). The median average Δ9-tetrahydrocannabinol post-mortem blood concentrations were several magnitudes lower than previously reported median blood concentrations in living users (cannabis alone: 4.3 µg/L; cannabis in combination with other drugs: 3.5 µg/L). CONCLUSIONS: Risk of death due to cannabis toxicity is negligible. However, cannabis can prove fatal in circumstances with risk of traumatic physical injury, or in individuals with cardiac pathophysiologies. These indirect harms need careful consideration and further study to better elucidate the role cannabis plays in drug-related mortality. Furthermore, the relevance of cannabinoid quantifications in determining cause of death in coronial investigations is limited.

Quantitation of Synthetic Cannabinoid Receptor Agonists in Postmortem Blood Using a Single Point Calibration.

Synthetic cannabinoid receptor agonists (SCRA) share minimal structural similarities to tetrahydrocannabinol or themselves. Due to their heterogeneous structures and the rapid appearance and disappearance of new SCRA on the drug scene, the quantitation of SCRA has not been attempted extensively. We present a wide series of SCRA concentrations based on a single-point calibration using peak height ratios for the extracted ion chromatogram of the protonated precursor ion against that of the internal standard. These concentrations are viewed as indicative only given the use of a single concentration "calibrator" based on the response of a deuterated analogue of a structurally related compound. What is of note, is that, despite the potential differences in potency the majority of SCRA seem to have relatively similar concentrations in postmortem cases.

Quantification of Flualprazolam in Blood by LC-MS-MS: A Case Series of Nine Deaths.

The emergence of novel designer benzodiazepines continues to be a public health concern. Flualprazolam is one of these drugs. It was initially identified in 2017. User forums suggest it is slightly more potent than alprazolam and has longer-lasting central nervous system depressant effects. Here we report a simple, sensitive liquid chromatography-tandem mass spectrometry method for flualprazolam and report a series of nine cases in which flualprazolam was quantified. As is typical of forensic toxicology in the twenty-first century, all the cases had more than one drug present. None of the deaths could be directly attributed to flualprazolam alone, but all were likely due to a combination of sedative drugs. However, this paper still adds to the data available to allow interpretation of postmortem flualprazolam concentrations.

The First Reported Case of a Synthetic Cannabinoid Ethyl Ester Detected in a Postmortem Blood Toxicological Analysis.

Metabolites of synthetic cannabinoids (SCs) are widely used as markers for identifying SCs' intake. Polydrug use involving SCs and ethanol may generate new metabolites, namely SC ethyl esters, hereby shown for the first time as new blood markers of SC-alcohol concomitant abuse. We report a case involving both the presence of 5F-PB22 and ethanol and the detection of their transesterifcation product, namely 5F-PB22 ethyl ester, in a postmortem blood sample. This marker was found retrospectively in a preserved femoral blood analyzed via liquid chromatography-high-resolution mass spectrometry. A single-point calibration was used to estimate the concentration of 5F-PB22-Et in the sample, which found to be 0.4 µg/L. Retention time and fragment ions (within ±1 mmu extraction window) of 5F-PB22-Et in the sample gave a remarkable match with a synthetic reference material. To the best of our knowledge, this is the first case report of an SC ethyl ester in a biological sample to indicate SCs and ethanol co-consumption.

Femoral blood concentrations of the designer benzodiazepine etizolam in post-mortem cases.

Etizolam is a thienodiazepine that although licensed for clinical usage in Japan, India and South Korea is commonly abused and detected in post-mortem cases around the world. To date, there are limited data in the literature to allow for the interpretation of blood concentrations of etizolam in post-mortem cases. A liquid chromatography with tandem mass spectrometry method was used to quantitate etizolam concentrations in 28 post-mortem cases where etizolam was detected. The median concentration of etizolam in femoral blood was 8.5 ng/mL (range 1.0-172.0 ng/mL; n = 24); in antemortem plasma, the etizolam concentration range was 4-44 ng/mL (n = 4). The mean age of the individuals abusing etizolam was 38.5 ± 8.4 years (median 39 years), with the majority being male (86%). In all of the cases, multiple drugs were detected, with the most common being pregabalin (61%) followed by morphine/heroin (54%), diazepam (54%) and benzoylecgonine (21%), illustrating the increasing problem of poly-substance use in drug abusers. The cause of death in the cases in which etizolam was detected was multi-drug toxicity in 87.5% of the cases, with 12.5% unrelated to drug use (hangings and blunt-force trauma). These data will further help forensic practitioners with the interpretation of post-mortem etizolam concentrations.

Combining an end to side nerve to masseter transfer with cross face nerve graft for functional upgrade in partial facial paralysis-an observational cohort study.

BACKGROUND: Results of a single stage technique combining cross facial nerve graft(s) (CFNG) with an ipsilateral end to side nerve to masseter transfer (NTM) in incomplete facial paralysis are assessed in a retrospective cohort study. The hypothesis is that the technique can safely improve the quality of smile in these patients. End to side coaptations for the recipient facial nerve minimise the risk of iatrogenic function loss, contrasting with the end to end neurorrhaphies used in conventional babysitting procedures. METHODS: A series of 27 patients was studied through case note review and standardised assessments. Surgical technique involves extensive exposure of the facial nerve and the NTM on the affected side and access is by bilateral preauricular incisions. End to end coaptations are made to the facial nerve on the donor side and on the recipient a standard CFNG is combined with an end to side NTM coaptation. Follow up was a minimum of 9 months from surgery. RESULTS: Overall improvement in the Sunnybrook scale averaged 33, from a pre-operative score of 40 (p < 0.05). Average upgrade of 4.7 mm of increased movement at the modiolus was achieved (p < 0.05), 43% improvement compared to the normal side. An improved resting symmetry of 3.8 mm was achieved in relevant cases. Where eye closure was strengthened the average improvement was 5 mm of increased lid closure. The smile achieved was spontaneous in 22 of 27 cases. CONCLUSION: The study confirms the hypothesis that CFNG with NTM transfer offers a physiological upgrade of facial movement in partial facial paralysis, applicable in both early and longstanding cases.

Flubromazolam: Detection in five post-mortem cases.

Flubromazolam is a potent triazole benzodiazepine with moderately long-lasting central nervous system-depressant effects relative to other benzodiazepines such as commonly prescribed diazepam. Flubromazolam has been studied in the living. However, there are no published reports including measured drug concentrations in post-mortem cases. We report five cases in which flubromazolam was detected in a systematic screen using high-resolution mass spectrometry and then quantified in femoral blood. In none of the five cases was the cause of death directly attributed to flubromazolam toxicity, as there was a variety of both sedative and stimulant drugs also present. However, it is important that the drug concentrations that were measured are made available for future post-mortem forensic interpretation.

Post-mortem diagnosis of kidney impairment: An experimental study.

The determination of the role that drugs may have played in a death is an important part of the investigation into unexplained deaths. Renal impairment may lead to a reduction in drug excretion rate and therefore an accumulation of drugs or metabolites, leading to possible toxic or lethal effects. Creatinine levels are known to be stable in the post mortem period and in life can give an indication of kidney function. There are however widely reported limitations when using creatinine in isolation and so we investigated the usefulness of using estimated glomerular filtration rate (eGFR) for scoring an individual as having renal impairment using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. We analysed unpreserved vitreous for creatinine in 812 individuals using an isotope dilution mass spectrometry (ID-MS) traceable enzymatic. We found that the biochemical analysis of post mortem vitreous creatinine and subsequent calculation of eGFR is a useful adjunct to the standard testing that takes place during a post-mortem examination and can assist in death investigation. Using an eGFR of <60 mL/min/1.73 m2 gave a sensitivity of 94.3% and specificity of 97.3% when scoring an individual as having renal impairment. We therefore recommend the calculation of eGFR for the determination of possible renal impairment in post mortem investigations. It is, of course, always pertinent to interpret any results using a wealth of case information. Extreme caution should be exercised in cases where insufficient clinical information/history is available, particularly in cases in which there is suspected diabetic ketoacidosis, dehydration or hospitalisation prior to death.

The relationship between antemortem and postmortem morphine concentrations.

Context of the Article: An important forensic problem is whether the presence of a drug such as morphine caused or contributed to a death or was merely incidental. The reliance that can be based on postmortem drug concentrations remains controversial. To investigate this further we obtained antemortem and postmortem samples of individuals admitted to hospital who were receiving morphine and who died in hospital.Methods: Eleven subjects were recruited. Samples were sent for analysis for free and total morphine concentrations.Results: The median difference (postmortem - antemortem) free morphine concentration was 25.5 (range 0 to +126) µg/L, p < .01; the mean difference between postmortem and antemortem total morphine concentration was 34.5 (range -225 to 342) µg/L (not significant).Discussion: Our study supports previous investigators who note that there is an inconstant and sometimes tenuous relationship between ante- and postmortem morphine concentrations.

Meta-analysis of the psychometric properties of the Pain Catastrophizing Scale and associations with participant characteristics.

The aims of this study were to review the psychometric properties of the widely used Pain Catastrophizing Scale (PCS) using meta-analytic methods and to investigate the relationship between PCS scores and participant characteristics. A systematic search from 1995 found 229 experimental, quasi-experimental, and correlational studies that report PCS scores. Multivariate regression explored variables related to pain catastrophizing and participant demographics. Across studies, good internal reliability (α = 0.92, 95% confidence interval 0.91-0.93) and test-retest reliability scores (Spearman ρ = 0.88, 95% confidence interval 0.83-0.93) were found for PCS total scores but not for subscales. Pain Catastrophizing Scale scores were unrelated to age or sex, but strongly related to participants' pain type, highest in those with generalized pain. Language of the PCS also affected PCS scores, with further research necessary to determine linguistic, cultural, or methodological (eg, sampling strategy) influences. Study type influenced PCS scores with nonrandomized controlled trials reporting higher PCS scores than other study types, but results were confounded with pain diagnosis, as controlled trials were more likely than quasi-experimental studies to recruit clinical samples. The meta-analytic results provide insights into demographic influences on pain catastrophizing scores and highlight areas for further research. The advantages of systematic review and meta-analytic methods to achieve greater understanding and precision of psychometric properties-in this case, of the PCS-are applicable to other widely used outcome tools.

Pilomatrixoma: A Comprehensive Review of the Literature.

INTRODUCTION: Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a superficial benign skin tumor that arises from hair follicle matrix cells. Although pilomatrixomas are well-recognized lesions, clinically they are frequently misdiagnosed as other skin conditions. By reviewing all the literature over the past 10 years, the aims of this article are to analyze the cause, clinical presentation, management, and outcome of pilomatrixoma among children and adults to gain a more complete understanding of this lesion in today's clinical context. METHODS: A MEDLINE and EMBASE search was conducted from January 2005 to February 2015 using a combination of the terms: "child," "childhood," "adult," and keywords: "pilomatrixoma," "pilomatricoma," and "calcifying epithelioma of Malherbe." A total of 150 articles were reviewed. RESULTS: The lesions occurred most commonly in the first and second decades (mean age 16 years and 7 months). The commonest presentation was of an asymptomatic, firm, slowly growing, mobile nodule. Only 16% were accurately diagnosed on clinical examination. Imaging in the form of ultrasound, computed tomography, and magnetic resonance imaging has been reported. Pathological diagnosis was achieved through incision, punch, and shave biopsies. Pathological findings are discussed and summarized in this review. CONCLUSION: Pilomatrixomas are thought to arise from mutation in the Wnt pathway and has been linked to several genetic conditions. It is commonly misdiagnosed preoperatively; however, with better awareness of the lesion, it can be appropriately treated while avoiding unnecessary diagnostic tests. Complete surgical excision with clear margins is almost always curative.

Multiple fatalities in the North of England associated with synthetic fentanyl analogue exposure: Detection and quantitation a case series from early 2017.

BACKGROUND: Synthetic fentanyl analogues are highly potent opioid drugs which have no pharmaceutical use in humans. We detected the synthetic fentanyl analogues; carfentanil, butyryl fentanyl, fluorobutyrylfentanyl, furanylfentanyl, and alfentanil as well as fentanyl itself in 25 cases in early 2017. There have been no previous reports of synthetic fentanyl deaths in the United Kingdom (UK). METHODS: Cases in which the history clearly stated drug use but where a post mortem blood morphine concentration was lower than would be expected to explain the sudden death, were referred for further analysis by high resolution accurate mass (HRAM) mass spectrometry. RESULTS: 25 post mortem cases in which synthetic fentanyl analogues were implicated in the cause of death were reported from January to May 2017. No cases were seen in June 2017. The age range was 21-54 years and 22 were male. There was a history of heroin use, or markers of heroin use on toxicology screening in 21/25 cases. Carfentanil and fentanyl were detected in 7 cases. Multiple synthetic fentanyl analogues were present in 13 cases, with the remaining 5 cases having only carfentanil present. Synthetic fentanyl analogues were detected in combination with other drugs in all cases. Significant concentrations of ethanol were detected in only 2 cases. The concentration range of carfentanil in blood was 90-4004pg/mL. Of note, the 3 cases in which ante mortem carfentanil was quantified ranged from 21 to 98pg/mL. In all cases, death was attributed to combined central nervous system depression. CONCLUSIONS: This paper highlights a new and rapid emergence of these drugs into the UK illicit drug arena. Synthetic fentanyl analogues represent a significant challenge both analytically and clinically within the groups who misuse drugs. It is worthwhile considering the possibility of the presence of these drugs in cases in which a toxicological cause of death is not apparent analytically but there is a history of drug use and circumstantial evidence exists to support a drug-related death as the most likely cause. It may be that synthetic fentanyl analogues should be screened for routinely to avoid reporting any false negative results, but the cost implications and viability of this have not been fully evaluated.

Self-management toolkit and delivery strategy for end-of-life pain: the mixed-methods feasibility study.

BACKGROUND: Pain affects most people approaching the end of life and can be severe for some. Opioid analgesia is effective, but evidence is needed about how best to support patients in managing these medicines. OBJECTIVES: To develop a self-management support toolkit (SMST) and delivery strategy and to test the feasibility of evaluating this intervention in a future definitive trial. DESIGN: Phase I - evidence synthesis and qualitative interviews with patients and carers. Phase II - qualitative semistructured focus groups and interviews with patients, carers and specialist palliative care health professionals. Phase III - multicentre mixed-methods single-arm pre-post observational feasibility study. PARTICIPANTS: Phase I - six patients and carers. Phase II - 15 patients, four carers and 19 professionals. Phase III - 19 patients recruited to intervention that experienced pain, living at home and were treated with strong opioid analgesia. Process evaluation interviews with 13 patients, seven carers and 11 study nurses. INTERVENTION: Self-Management of Analgesia and Related Treatments at the end of life (SMART) intervention comprising a SMST and a four-step educational delivery approach by clinical nurse specialists in palliative care over 6 weeks. MAIN OUTCOME MEASURES: Recruitment rate, treatment fidelity, treatment acceptability, patient-reported outcomes (such as scores on the Brief Pain Inventory, Self-Efficacy for Managing Chronic Disease Scale, Edmonton Symptom Assessment Scale, EuroQol-5 Dimensions, Satisfaction with Information about Medicines Scale, and feasibility of collecting data on health-care resource use for economic evaluation). RESULTS: Phase I - key themes on supported self-management were identified from evidence synthesis and qualitative interviews. Phase II - the SMST was developed and refined. The delivery approach was nested within a nurse-patient consultation. Phase III - intervention was delivered to 17 (89%) patients, follow-up data at 6 weeks were available on 15 patients. Overall, the intervention was viewed as acceptable and valued. Descriptive analysis of patient-reported outcomes suggested that interference from pain and self-efficacy were likely to be candidates for primary outcomes in a future trial. No adverse events related to the intervention were reported. The health economic analysis suggested that SMART could be cost-effective. We identified key limitations and considerations for a future trial: improve recruitment through widening eligibility criteria, refine the SMST resources content, enhance fidelity of intervention delivery, secure research nurse support at recruiting sites, refine trial procedures (including withdrawal process and data collection frequency), and consider a cluster randomised design with nurse as cluster unit. LIMITATIONS: (1) The recruitment rate was lower than anticipated. (2) The content of the intervention was focused on strong opioids only. (3) The fidelity of intervention delivery was limited by the need for ongoing training and support. (4) Recruitment sites where clinical research nurse support was not secured had lower recruitment rates. (5) The process for recording withdrawal was not sufficiently detailed. (6) The number of follow-up visits was considered burdensome for some participants. (7) The feasibility trial did not have a control arm or assess randomisation processes. CONCLUSIONS: A future randomised controlled trial is feasible and acceptable. STUDY AND TRIAL REGISTRATION: This study is registered as PROSPERO CRD42014013572; Current Controlled Trials ISRCTN35327119; and National Institute for Health Research (NIHR) Portfolio registration 162114. FUNDING: The NIHR Health Technology Assessment programme.

Death from Ingestion of E-Liquid.

BACKGROUND: The use of e-liquids is becoming more prevalent. There is a risk that such liquids may be ingested by mouth rather than being vaped/ inhaled. Due to the high concentration of drugs such as nicotine in these liquids, there may be toxic, and possibly fatal consequences. CASE REPORT: We report the death of a 32-year-old male who ingested nicotine-containing e-liquid while under the influence of alcohol. A serum sample taken 24 h after collapse contained nicotine at a concentration of 1600 ng/mL of nicotine. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Death secondary to e-liquid ingestion is still very rare, but has the potential for causing deaths due to the easy access of such liquids to the general public. Such toxicity should be considered in individuals who present in the early phases with symptoms of stimulant toxicity, but also in the latter phase where there may be autonomic depressive effects.

The experimental analysis of the interruptive, interfering, and identity-distorting effects of chronic pain.

Pain is an unpleasant sensory and emotional experience urging the individual to take action to restore the integrity of the body. The transition from a common episode of acute pain to a state of intermittent or chronic pain has been a constant preoccupation of researchers and clinicians alike. In this review, we approach chronic pain from a modern learning perspective that incorporates cognitive, affective, behavioral and motivational aspects. We view pain as a biologically hard-wired signal of bodily harm that competes with other demands in the person's environment. The basic tenet is that pain urges people to interrupt ongoing activity, elicits protective responses that paradoxically increase interference with daily activities, and compromises the sense of self. Here we briefly summarize existing evidence showing how pain captures attention, and how attention for pain can be controlled. We also consider pain as a strong motivator for learning, and review the recent evidence on the acquisition and generalization of pain-related fear and avoidance behavior, which are likely to interfere with daily life activities. We highlight the paradoxical effects of pain avoidance behavior, and review treatment effects of exposure in vivo. A generally neglected area of research is the detrimental consequences of repeated interference by pain with daily activities on one's sense of "self". We end this review with a plea for the implementation of single-case experimental designs as a means to help customize and develop novel cognitive-behavioral treatments for individuals for chronic pain aimed at reducing the suffering of this large group of individuals.