Alkyl Cyclopropyl Ketones in Catalytic Formal [3 + 2] Cycloadditions: The Role of SmI2 Catalyst Stabilization.

Alkyl cyclopropyl ketones are introduced as versatile substrates for catalytic formal [3 + 2] cycloadditions with alkenes and alkynes and previously unexplored enyne partners, efficiently delivering complex, sp3-rich products. The key to effectively engaging this relatively unreactive new substrate class is the use of SmI2 as a catalyst in combination with substoichiometric amounts of Sm0; the latter likely acting to prevent catalyst deactivation by returning SmIII to the catalytic cycle. In the absence of Sm0, background degradation of the SmI2 catalyst can outrun product formation. For the most recalcitrant alkyl cyclopropyl ketones, catalysis is "switched-on" using these new robust conditions, and otherwise unattainable products are delivered. Combined experimental and computational studies have been used to identify and probe reactivity trends among alkyl cyclopropyl ketones, including more complex bicyclic alkyl cyclopropyl ketones, which react quickly with various partners to give complex products. In addition to establishing alkyl cyclopropyl ketones as a new substrate class in a burgeoning field of catalysis, our study provides vital mechanistic insight and robust, practical approaches for the nascent field of catalysis with SmI2.

Variability in the prevalence of depression among adults with chronic pain: UK Biobank analysis through clinical prediction models.

BACKGROUND: The prevalence of depression among people with chronic pain remains unclear due to the heterogeneity of study samples and definitions of depression. We aimed to identify sources of variation in the prevalence of depression among people with chronic pain and generate clinical prediction models to estimate the probability of depression among individuals with chronic pain. METHODS: Participants were from the UK Biobank. The primary outcome was a "lifetime" history of depression. The model's performance was evaluated using discrimination (optimism-corrected C statistic) and calibration (calibration plot). RESULTS: Analyses included 24,405 patients with chronic pain (mean age 64.1 years). Among participants with chronic widespread pain, the prevalence of having a "lifetime" history of depression was 45.7% and varied (25.0-66.7%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.66; good calibration on the calibration plot) included age, BMI, smoking status, physical activity, socioeconomic status, gender, history of asthma, history of heart failure, and history of peripheral artery disease. Among participants with chronic regional pain, the prevalence of having a "lifetime" history of depression was 30.2% and varied (21.4-70.6%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.65; good calibration on the calibration plot) included age, gender, nature of pain, smoking status, regular opioid use, history of asthma, pain location that bothers you most, and BMI. CONCLUSIONS: There was substantial variability in the prevalence of depression among patients with chronic pain. Clinically relevant factors were selected to develop prediction models. Clinicians can use these models to assess patients' treatment needs. These predictors are convenient to collect during daily practice, making it easy for busy clinicians to use them.

Alcohol-alcohol cross-coupling enabled by SH2 radical sorting.

Alcohols represent a functional group class with unparalleled abundance and structural diversity. In an era of chemical synthesis that prioritizes reducing time to target and maximizing exploration of chemical space, harnessing these building blocks for carbon-carbon bond-forming reactions is a key goal in organic chemistry. In particular, leveraging a single activation mode to form a new C(sp3)-C(sp3) bond from two alcohol subunits would enable access to an extraordinary level of structural diversity. In this work, we report a nickel radical sorting-mediated cross-alcohol coupling wherein two alcohol fragments are deoxygenated and coupled in one reaction vessel, open to air.

Development of a General Organophosphorus Radical Trap: Deoxyphosphonylation of Alcohols.

Here we report the design of a general, redox-switchable organophosphorus alkyl radical trap that enables the synthesis of a broad range of C(sp3)-P(V) modalities. This "plug-and-play" approach relies upon in situ activation of alcohols and O═P(R2)H motifs, two broadly available and inexpensive sources of molecular complexity. The mild, photocatalytic deoxygenative strategy described herein allows for the direct conversion of sugars, nucleosides, and complex pharmaceutical architectures to their organophosphorus analogs. This includes the facile incorporation of medicinally relevant phosphonate ester prodrugs.

A digital health intervention to support patients with chronic pain during prescription opioid tapering: a pilot randomised controlled trial.

Introduction: Recent changes in opioid prescribing guidelines have led to an increasing number of patients with chronic pain being recommended to taper. However, opioid tapering can be challenging, and many patients require support. Objectives: We evaluated the feasibility, acceptability, and potential efficacy of a codesigned digital health intervention to support patients with chronic pain during voluntary prescription opioid tapering. Methods: In a pilot randomised controlled trial, participants received a psychoeducational video and 28 days of text messages (2 SMS/day) in addition to their usual care (intervention) or usual care alone (control). The feasibility, acceptability, and potential efficacy of the intervention were evaluated. The primary outcome was opioid tapering self-efficacy. Secondary outcomes were pain intensity and interference, anxiety and depression symptom severity, pain catastrophising, and pain self-efficacy. Results: Of 28 randomised participants, 26 completed the study (13 per group). Text message delivery was high (99.2%), but fidelity of video delivery was low (57.1%). Most participants rated the messages as useful, supportive, encouraging, and engaging; 78.5% would recommend the intervention to others; and 64.2% desired a longer intervention period. Tapering self-efficacy (Cohen d = 0.74) and pain self-efficacy (d = 0.41) were higher, and pain intensity (d = 0.65) and affective interference (d = 0.45) were lower in the intervention group at week 4. Conclusion: First evidence supports the feasibility, acceptability, and potentially efficacy of a psychoeducational video and SMS text messaging intervention to support patients with chronic pain during voluntary prescription opioid tapering. Definitive trials with longer intervention duration are warranted.

Flavin-Mediated Photocatalysis Provides a General Platform for Sulfide C-H Functionalization.

Functionalized sulfides are important in many areas of science, ranging from chemical biology through drug discovery to organic materials chemistry. Sulfides bearing pendant reactive groups in the α-position are particularly useful; however, methods for the selective valorization of simple sulfides or the late-stage functionalization of complex sulfides by the convenient addition of valuable functionality are underexplored. Here we exemplify a general reaction platform for sulfide functionalization by showcasing three modes of α-sulfur C-H functionalization; cyanation, alkenylation, and alkynylation. Using inexpensive and commercially available riboflavin tetraacetate and visible light, decoration of both feedstock and complex sulfides proceeds in a good yield and with high selectivity. Methionine-containing peptides can also be selectively functionalized and a tolerance screen using amino-acid dopants suggests that the platform is compatible with most amino-acid side chains and thus is a potential tool for bioconjugation.

Sustained Increase in Pediatric Inflammatory Bowel Disease Incidence Across the South West United Kingdom Over the Last 10 Years.

BACKGROUND: Pediatric inflammatory bowel disease (pIBD) incidence has increased over the last 25 years. We aim to report contemporaneous trends across the South West United Kingdom. METHODS: Data were provided from centers covering the South West United Kingdom (Bristol, Oxford, Cardiff, Exeter, and Southampton), with a total area at-risk population (<18 years of age) of 2 947 534. Cases were retrieved from 2013 to 2022. Incident rates were reported per 100 000 at-risk population, with temporal trends analyzed through correlation. Subgroup analysis was undertaken for age groups (0-6, 6-11, and 12-17 years of age), sex, and disease subtype. Choropleth maps were created for local districts. RESULTS: In total, 2497 pIBD cases were diagnosed between 2013 and 2022, with a mean age of 12.6 years (38.7% female). Diagnosis numbers increased from 187 to 376, with corresponding incidence rates of 6.0 per 100 000 population per year (2013) to 12.4 per 100 000 population per year (2022) (b = 0.918, P < .01). Female rates increased from 5.1 per 100 000 population per year in 2013 to 11.0 per 100 000 population per year in 2022 (b = 0.865, P = .01). Male rates increased from 5.7 per 100 000 population per year to 14.4 per 100 000 population per year (b = 0.832, P = .03). Crohn's disease incidence increased from 3.1 per 100 000 population per year to 6.3 per 100 000 population per year (b = 0.897, P < .01). Ulcerative colitis increased from 2.3 per 100 000 population per year to 4.3 per 100 000 population per year (b = 0.813, P = .04). Inflammatory bowel disease unclassified also increased, from 0.6 per 100 000 population per year to 1.8 per 100 000 population per year (b = 0.851, P = .02). Statistically significant increases were seen in those ≥12 to 17 years of age, from 11.2 per 100 000 population per year to 24.6 per 100 000 population per year (b = 0.912, P < .01), and the 7- to 11-year-old age group, with incidence rising from 4.4 per 100 000 population per year to 7.6 per 100 000 population per year (b = 0.878, P = .01). There was no statistically significant increase in very early onset inflammatory bowel disease (≤6 years of age) (b = 0.417, P = .231). CONCLUSIONS: We demonstrate significant increases in pIBD incidence across a large geographical area including multiple referral centers. Increasing incidence has implications for service provision for services managing pIBD.

Incidence of inflammatory bowel disease continues to increase in childhood, particularly in older children. This is demonstrated in a contemporary dataset collected over a 10-year period, and covering an at-risk population of nearly 3 000 000. These data have significant implications for service provision.

A gene pathogenicity tool "GenePy" identifies missed biallelic diagnoses in the 100,000 Genomes Project.

PURPOSE: The 100,000 Genomes Project diagnosed a quarter of affected participants, but 26% of diagnoses were not on the applied gene panel(s); with many being de novo variants. Assessing biallelic variants without a gene panel is more challenging. METHODS: We sought to identify missed biallelic diagnoses using GenePy, which incorporates allele frequency, zygosity, and a user-defined deleterious metric, generating an aggregate GenePy score per gene, per participant. We calculated GenePy scores for 2862 recessive disease genes in 78,216 100,000 Genomes Project participants. For each gene, we ranked participant GenePy scores and scrutinized affected participants without a diagnosis, whose scores ranked among the top 5 for each gene. In cases which participant phenotypes overlapped with the disease gene of interest, we extracted rare variants and applied phase, ClinVar, and ACMG classification. RESULTS: 3184 affected individuals without a molecular diagnosis had a top-5-ranked GenePy score and 682 of 3184 (21%) had phenotypes overlapping with a top-ranking gene. In 122 of 669 (18%) phenotype-matched cases (excluding 13 withdrawn participants), we identified a putative missed diagnosis (2.2% of all undiagnosed participants). A further 334 of 669 (50%) cases have a possible missed diagnosis but require functional validation. CONCLUSION: Applying GenePy at scale has identified 456 potential diagnoses, demonstrating the value of novel diagnostic strategies.

Inflammatory bowel disease: recent developments.

Paediatric-onset inflammatory bowel disease (IBD) is a complex and heterogenous condition. Incidence of disease in those aged <18 years has doubled over the last 25 years, with concurrent increased prevalence and no decrease in disease severity. The tools available at diagnosis for investigation have developed over the last 10 years, including better utilisation of faecal calprotectin, improved small bowel imaging and video capsule endoscopy. Alongside this, management options have increased and include biological and small molecule therapies targeting alternative pathways (such as interleukin 12/23, integrins and Janus kinase/signal transducers and activators of transcription, JAK-STAT pathways) and better understanding of therapeutic drug monitoring for more established agents, such as infliximab. Dietary manipulation remains an interesting but contentious topic.This review summarises some of the recent developments in the diagnosis, investigation and management of IBD in children and young people. IBD is increasingly recognised as a continuum of disease, with a proportion of patients presenting with classical Crohn's disease or ulcerative colitis phenotypes. Future implementation of personalisation and stratification strategies, including clinical and molecular biomarkers, implementation of predictors of response and outcome and use of additional therapies, will continue to require working within clinical networks and multiprofessional teams.

NIMBUS study protocol: a single-centre feasibility study of non-invasive monitoring with bowel ultrasound in paediatric inflammatory bowel disease.

INTRODUCTION: Incidence of inflammatory bowel disease (IBD) is increasing in childhood and treatment increasingly targets mucosal healing. Monitoring bowel inflammation requires endoscopy or MRI enterography which are invasive, expensive and have long waiting lists.We aim to examine the feasibility of a non-invasive monitoring tool-bowel ultrasound (BUS)-in children with IBD and explore correlations with inflammatory markers and disease activity measures. Some BUS criteria have been found to correlate with these markers; however, this has not been validated in children.We aim to examine the feasibility of BUS for monitoring inflammation in this population; highlighting useful parameters for this purpose. We aim to inform a larger scale randomised controlled trial using BUS. METHODS AND ANALYSIS: This prospective observational feasibility study will be carried out over 24 months at the Noah's Ark Children's Hospital for Wales, Cardiff; with the endpoint recruitment of 50 participants. Children aged 2-18 years with a modified Porto criteria diagnosis of IBD will be included.Patients without IBD or who have previously undergone IBD-related surgery will be excluded; as will families unable to give informed consent.Ultrasound scan images and reports will be collected, as well as laboratory results and clinical outcomes.The primary aim will assess the feasibility of targeted BUS for disease monitoring; including recruitment statistics. The secondary aims will involve data collection and correlation analysis for targeted ultrasound parameters, biomarkers, disease activity scores and prediction of changes in treatment. The statistical methods will include: feasibility metrics, descriptive statistics, cross-tabulation and χ2 analysis, correlation analysis, regression analysis. ETHICS AND DISSEMINATION: Ethical approval is granted by NHS Research Ethics Committee. The sponsor is Cardiff and Vale University Health Board. We will publish the results in a peer-reviewed medical journal. TRIAL REGISTRATION NUMBER: NCT05673278.

Optimal cut-offs of depression screening tools during the COVID-19 pandemic: a systematic review.

BACKGROUND: Studies have reported an increase in the prevalence of depression during the COVID-19 pandemic. The accuracy of screening tools may change with the prevalence and distribution of a disease in a population or sample: the "Spectrum Effect". METHODS: First, we selected commonly used screening tools and developed search strategies for the inclusion of original studies during the pandemic. Second, we searched PsycINFO, EMBASE, and MEDLINE from March 2020 to September 2022 to obtain original studies that investigated the accuracy of depression screening tools during the pandemic. We then searched these databases to identify meta-analyses summarizing the accuracy of these tools conducted before the pandemic and compared the optimal cut-offs for depression screening tools during the pandemic with those before. RESULT: Four original studies evaluating the optimal cut-offs for four screening tools (Beck Depression Inventory [BDI-II], Hospital Anxiety and Depression Scale-Depression [HADS-D], Patient Health Questionnaire-9 [PHQ-9], and Geriatric Depression Scale-4 [GDS-4]) were published during the pandemic. Four meta-analyses summarizing these tools before the pandemic. We found that the optimal cut-off of BDI-II was 14 during the pandemic (23.8% depression prevalence, screening patients with Type 2 diabetes) and 14.5 before the pandemic (17.6% depression prevalence, screening psychiatric, primary care, and healthy populations); HADS-D was 10 during the pandemic (23.8% depression prevalence, screening patients with type 2 diabetes) and 7 before the pandemic (15.0% depression prevalence, screening medically ill patients); PHQ-9 was 11 during the pandemic (14.5% depression prevalence, screening university students) and 8 before the pandemic (10.9% depression prevalence, screening the unrestricted population), and GDS-4 was 1.8 during the pandemic (29.0% depression prevalence, screening adults seen in a memory clinic setting) and 3 before the pandemic (18.5% depression prevalence, screening older adults). CONCLUSION: The optimal cut-off for different screening tools may be sensitive to changes in study populations and reference standards. And potential spectrum effects that should be considered in post-COVID time which aiming to improve diagnostic accuracy.

Recent developments in the assessment and management of inflammatory bowel disease in childhood: a narrative review.

Background and Objective: The landscape of paediatric inflammatory bowel disease (pIBD) continues to evolve in an era of increasing incidence. There have been rapid developments in understanding, as we begin to perceive IBD as a spectrum of conditions, alongside advancements in monitoring and treatment. The objective of this article was to provide an overview of recent advances and challenges in the management of pIBD, with a focus on sustainable healthcare, personalised therapy, genomics, new drugs and avenues for future optimisation. Methods: We present a narrative review that synthesises and summarises recent research (2017-2022) related to pIBD. We undertook a structured search of the literature (PubMed and Medline) and additional articles were identified through manual searches of reference lists. Evidence tables were compiled for disease outcomes. Key Content and Findings: In this review we outline current practice, integrating clinical guidelines and contemporary research. We discuss initial investigations (including suggested threshold for paediatric faecal calprotectin), specialist investigations for disease monitoring [with reference to video capsule endoscopy (VCE) and therapeutic drug levels] and outline new and established treatment options. Biomarkers and genomic testing are examined as important tools for individualising care and identifying potential therapeutic targets, including for top-down therapy. Despite these advances, significant challenges remain, including the need for further research to understand the mechanisms of disease and the translation of these advances into real-world improvements in practice. Conclusions: Recent advances in understanding of the pathogenesis of pIBD, alongside genomic and pharmacological developments have added more tools to the armamentarium for the treatment of these conditions and highlighted ongoing areas of research need.

Improved clinical outcomes with early anti-tumour necrosis factor alpha therapy in children with newly diagnosed Crohn's disease: real world data from the international prospective PIBD-SETQuality inception cohort study.

BACKGROUND & AIMS: Treatment guidelines for paediatric Crohn's disease (CD) suggest early use of anti-tumour necrosis factor alpha (anti-TNF) in high-risk individuals. The aim is to evaluate the effect of early anti-TNF in a real-world cohort. METHODS: Children with newly-diagnosed CD were prospectively recruited at 28 participating sites of the international observational PIBD-SETQuality study. Outcomes were compared at 3 months, 1 and 2 years between patients receiving early anti-TNF (<90 days after diagnosis) and those not receiving early anti-TNF. Outcomes included sustained steroid-free remission (SSFR) without treatment intensification (specified as SSFR*) and sustained steroid-free mild/inactive disease without treatment intensification (specified as SSFMI*). Penalised logistic regression model-based standardisation was applied to estimate the relative risks (RR) of early therapy on outcomes. RRs were estimated for high-risk and low-risk patients based on presence of predictors of poor outcome (POPOs) and disease activity at diagnosis. RESULTS: In total, 331 children (median age 13.9 years [IQR 12.2 - 15.3]) were enrolled, with 135 (41%) receiving early anti-TNF. At 1 year, patients on early anti-TNF had higher rates of SSFR* (30% vs. 14%, p<0.001) and SSFMI* (69% vs. 33%, p<0.001), with RRs of 2.95 (95%CI 1.63-5.36) and 4.67 (95%CI 2.46-8.87) respectively. At 1 year, the RRs for SSFMI* were higher, and statistically significant in high-risk patients, i.e. those with moderate/severe disease compared to mild/inactive disease at diagnosis (5.50 [95%CI 2.51-12.05]) vs. 2.91 [95%CI 0.92-9.11]), and those with any POPO compared to no POPO (5.05 [95%CI 2.45-10.43] vs. 3.41 [95%CI 0.54-21.7]). CONCLUSION: In this cohort of children with newly-diagnosed CD, early anti-TNF demonstrated superior effectiveness in high-risk patients.

Text messaging intervention to support patients with chronic pain during prescription opioid tapering: protocol for a double-blind randomised controlled trial.

INTRODUCTION: Increases in pain and interference with quality of life is a common concern among people with chronic non-cancer pain (CNCP) who are tapering opioid medications. Research indicates that access to social and psychological support for pain self-management may help people to reduce their opioid dose without increasing pain and interference. This study evaluates the efficacy of a text messaging intervention designed to provide people with CNCP with social and psychological support for pain self-management while tapering long-term opioid therapy (LTOT) under the guidance of their prescriber. METHODS AND ANALYSIS: A double-blind randomised controlled trial will be conducted. Patients with CNCP (n=74) who are tapering LTOT will be enrolled from across Australia. Participants will continue with their usual care while tapering LTOT under the supervision of their prescribing physician. They will randomly receive either a psychoeducational video and supportive text messaging (two Short Message Service (SMS) per day) for 12 weeks or the video only. The primary outcome is the pain intensity and interference assessed by the Pain, Enjoyment of Life and General Activity scale. Secondary outcomes include mood, self-efficacy, pain cognitions, opioid dose reduction, withdrawal symptoms, and acceptability, feasibility, and safety of the intervention. Participants will complete questionnaires at baseline and then every 4 weeks for 12 weeks and will be interviewed at week 12. This trial will provide evidence for the efficacy of a text messaging intervention to support patients with CNCP who are tapering LTOT. If proven to be efficacious and safe, this low-cost intervention can be implemented at scale. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the Northern Sydney Local Health District (Australia). Study results will be published in peer-reviewed journals and presented at scientific and professional meetings. TRIAL REGISTRATION NUMBER: ACTRN12622001423707.

Experiences of misuse and symptoms of dependence among people who use gabapentinoids: a qualitative systematic review protocol.

INTRODUCTION: Gabapentinoids are among the most widely prescribed pain medications. However, there is growing evidence to suggest that gabapentinoids may be associated with dependence and misuse. The aim of this systematic review is to synthesise the qualitative literature on gabapentinoid misuse and symptoms of dependence. The findings of this study will inform efforts to mitigate emerging harms. METHODS AND ANALYSIS: A systematic review of qualitative research will explore lived experiences of misuse and symptoms of dependence among people who use gabapentinoids. Six databases (MEDLINE, Scopus, Web of Science, CINAHL, EMBASE and PsycINFO) and grey literature sources will be searched from inception to May 2023. Qualitative studies that include people with lived experiences of gabapentinoid misuse and symptoms of gabapentinoid dependence will be included. Reference lists of included studies will also be screened for additional studies. The methodological quality of included studies will be appraised using the Critical Appraisal Skills Programme qualitative checklist, and higher quality studies will be prioritised in the thematic synthesis. The GRADE-CERQual approach will be used to assess confidence in the overall findings of the review. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review. The findings of this review will be disseminated in peer-reviewed journals, at conferences and on social media. PROSPERO REGISTRATION NUMBER: CRD42023401832.

Variation in access and prescription of vedolizumab and ustekinumab in paediatric patients with inflammatory bowel disease: a UK-wide study.

BACKGROUND: Therapeutic options for paediatric inflammatory bowel disease (IBD) are limited, especially for younger children. Unlike in adults, vedolizumab and ustekinumab are not licensed for paediatric use in the UK. We aimed to understand the real-world access to, and use of, these therapies in the paediatric population. METHODS: We surveyed UK IBD centres to assess the incident use of vedolizumab and ustekinumab from 1 January 2021 to 31 December 2021. We collected information on funding, dose escalations and therapeutic drug monitoring. RESULTS: 18 of 21 centres responded, covering an estimated 5260 patients. One hundred and thirteen were started on vedolizumab, prescription incidence 2.2%, median prescriptions per centre was 4 (range 1-20). Considering ustekinumab, 73 patients were commenced, prescription incidence 1.4%. Median prescription per centre was 3.5 (range 1-13). Prescription rates at each centre were not predicted by patient number cared for at that centre (p=0.2). Dose escalation was common in vedolizumab (66.7% centres) and ustekinumab (55.5%).Funding strategies varied substantially, and multiple funding sources were used; 12 of 18 centres (66.7%) reported funding through routine National Health Service (NHS) England/Scottish arrangements. There was local NHS trust funding in 8 of 18 centres (44.4%). Individual funding requests (IFRs) were used in 5 of 18 (27.8%), although IFRs are reserved for patients with unique additional characteristics. Four centres were unable to achieve funding in pre-pubescent children. CONCLUSIONS: There is widespread use of vedolizumab and ustekinumab across the UK, although practice is highly variable. Access to therapy appeared to differ substantially. There is a growing disparity between international guidelines and real-world practice. Establishing early and effective therapy in all patients remains a priority.

"We were all looking for the magic pill": A qualitative study of patient experiences using gabapentinoids for chronic pain.

BACKGROUND: Gabapentinoid medications are increasingly being used in chronic pain management, yet very little is known about the experiences of those using them. The aim of this study was to address this gap in the literature by qualitatively exploring the lived experiences of patients using gabapentinoids for chronic pain. METHODS: Semi-structured interviews were conducted with 12 adults prescribed a gabapentinoid medication - either pregabalin or gabapentin - for chronic pain in Australia. Interviews were conducted in May 2022 via telephone or online video chat. Audio recordings of the interviews were transcribed verbatim, and data were analysed using reflexive thematic analysis. The Medication Adherence Model was used as a framework for synthesising the data and organising themes. RESULTS: For participants in this study, the initial decision to use gabapentinoids for chronic pain was driven by a level of desperation for pain relief, a perceived lack of pain management alternatives, and a belief that the medication was safer and easier to access than opioids. However, once using gabapentinoids, experiences varied considerably with some viewing the medication as effective and safe, and others viewing it as useless or harmful. Some participants expressed concern that they were not adequately informed by their prescribers about the risks of gabapentinoid use. CONCLUSION: These findings emphasise the importance of patient-provider communication and taking a patient-centred approach to gabapentinoid prescribing and de-prescribing. Future qualitative research in this area should involve primary care providers to gain a better understanding of factors driving increased gabapentinoid prescribing in chronic pain management as well as barriers to patient education.

Supervised Machine Learning Classifies Inflammatory Bowel Disease Patients by Subtype Using Whole Exome Sequencing Data.

BACKGROUND: Inflammatory bowel disease [IBD] is a chronic inflammatory disorder with two main subtypes: Crohn's disease [CD] and ulcerative colitis [UC]. Prompt subtype diagnosis enables the correct treatment to be administered. Using genomic data, we aimed to assess machine learning [ML] to classify patients according to IBD subtype. METHODS: Whole exome sequencing [WES] from paediatric/adult IBD patients was processed using an in-house bioinformatics pipeline. These data were condensed into the per-gene, per-individual genomic burden score, GenePy. Data were split into training and testing datasets [80/20]. Feature selection with a linear support vector classifier, and hyperparameter tuning with Bayesian Optimisation, were performed [training data]. The supervised ML method random forest was utilised to classify patients as CD or UC, using three panels: 1] all available genes; 2] autoimmune genes; 3] 'IBD' genes. ML results were assessed using area under the receiver operating characteristics curve [AUROC], sensitivity, and specificity on the testing dataset. RESULTS: A total of 906 patients were included in analysis [600 CD, 306 UC]. Training data included 488 patients, balanced according to the minority class of UC. The autoimmune gene panel generated the best performing ML model [AUROC = 0.68], outperforming an IBD gene panel [AUROC = 0.61]. NOD2 was the top gene for discriminating CD and UC, regardless of the gene panel used. Lack of variation in genes with high GenePy scores in CD patients was the best classifier of a diagnosis of UC. DISCUSSION: We demonstrate promising classification of patients by subtype using random forest and WES data. Focusing on specific subgroups of patients, with larger datasets, may result in better classification.

A digital health intervention to support patients with chronic pain during prescription opioid tapering: a pilot randomised controlled trial.

Introduction: Recent changes in opioid prescribing guidelines have led to an increasing number of patients with chronic pain being recommended to taper. However, opioid tapering can be challenging, and many patients require support. Objectives: We evaluated the feasibility, acceptability, and potential efficacy of a co-designed psycho-educational video and SMS text messaging intervention to support patients with chronic pain during prescription opioid tapering. Methods: A pilot randomised controlled trial was conducted. In addition to their usual care, participants in the intervention group received a psycho-educational video and 28 days of text messages (two SMS/day). The control group received usual care. The feasibility, acceptability, and potential efficacy of the intervention were evaluated. The primary outcome was opioid tapering self-efficacy. Secondary outcomes were pain intensity and interference, anxiety and depression symptom severity, pain catastrophising, and pain self-efficacy. Results: Of 28 randomised participants, 26 completed the study (13 in each group). Text message delivery was 99.2% successful. Most participants rated the messages as useful, supportive, encouraging, and engaging, 78.5% would recommend the intervention to others, and 64% desired a longer intervention period. Tapering self-efficacy (Cohen's d = 0.74) and pain self-efficacy (d = 0.41) were higher and pain intensity (d = 0.65) and affective interference (d = 0.45) lower in the intervention group at week 4. Conclusions: It is feasible, acceptable, and potentially efficacious to support patients with chronic pain during prescription opioid tapering with a psycho-educational video and SMS text messaging intervention. A definitive trial has been initiated to test a 12-week intervention.