EUS-directed transgastric ERCP with EUS-guided rendezvous for difficult biliary cannulation in a patient with Roux-en-Y gastric bypass.

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Duodenal quantitative mucosal morphometry in children with environmental enteric dysfunction: a cross-sectional multi-country analysis.

BACKGROUND: Environmental enteric dysfunction (EED), a chronic inflammatory condition of the small intestine, is an important driver of childhood malnutrition globally. Quantifying intestinal morphology in EED allows for exploration of its association with functional and disease outcomes. OBJECTIVE: We sought to define morphometric characteristics of childhood EED and determine whether morphology features were associated with disease pathophysiology. METHODS: Morphometric measurements and histology were assessed on duodenal biopsy slides for this cross-sectional study from children with EED in Bangladesh, Pakistan, and Zambia (n=69), and those with no pathologic abnormality (NPA; n=8) or celiac disease (n=18) in North America. Immunohistochemistry was also conducted on 46, 8, and 18 biopsy slides, respectively. Linear mixed-effects regression models were used to reveal morphometric differences between EED compared to NPA or celiac disease, and identify associations between morphometry and histology or immunohistochemistry amongst children with EED. RESULTS: In duodenal biopsies, median EED villus height (248 µm), crypt depth (299 µm), and villus:crypt (V:C) ratio (0.9) values ranged between those of NPA (396 µm villus height; 246 µm crypt depth; 1.6 V:C ratio) and celiac disease (208 µm villus height; 365 µm crypt depth; 0.5 V:C ratio). Among EED biopsy slides, morphometric assessments were not associated with histologic parameters or immunohistochemical markers, other than pathologist determined subjective semi-quantitative villus architecture. CONCLUSIONS: Morphometric analysis of duodenal biopsy slides across geographies identified morphologic features of EED, specifically short villi, elongated crypts, and a smaller V:C ratio relative to NPA slides; although not as severe as in celiac slides. Morphometry did not explain other EED features, suggesting that EED histopathologic processes may be operating independently of morphology. While acknowledging the challenges with obtaining relevant tissue, these data form the basis for further assessments of the role of morphometry in EED.

Cognitive Functional Therapy compared with usual physiotherapy care in people with persistent low back pain: a mixed methods feasibility randomised controlled trial in the United Kingdom National Health Service.

OBJECTIVES: To determine the feasibility of completing a definitive randomised controlled trial (RCT), evaluating the clinical and cost-effectiveness of Cognitive Functional Therapy (CFT) in comparison to usual physiotherapy care (UPC), for people with persistent low back pain (LBP). DESIGN AND SETTING: A two-arm parallel feasibility RCT completed in a United Kingdom (UK) Secondary Care National Health Service (NHS) physiotherapy service. PARTICIPANTS: Sixty adult participants who reported LBP lasting for more than three months, that was not attributable to a serious (e.g. cancer) or specific (e.g. radiculopathy) underlying cause, were invited to participate. Participants were allocated at random to receive CFT or UPC. INTERVENTIONS: Cognitive Functional Therapy and Usual Physiotherapy Care for persistent LBP. MAIN OUTCOME MEASURES: The primary outcome was the feasibility of completing a definitive RCT, defined by recruitment of at least 5 participants per month, delivery of CFT per protocol and securing relevant and acceptable outcome measures. Data concerning study processes, resources, management and participant reported outcome measures were collected at baseline, 3, 6 and 12-month follow-up. RESULTS: Sixty participants (n = 30 CFT and n = 30 UPC) were recruited with 80% (n = 48), 72% (n = 43) and 53% (n = 32) retained at 3, 6 and 12-month follow-up respectively. NHS physiotherapists were trained to competence and delivered CFT with fidelity. CFT was tolerated by participants with no adverse events. Relevant and clinically important outcome data were collected at all time points (0.4%, 3%, 1% and 0.8% of data was missing from the returned outcome measure booklets at baseline and 3, 6 and 12-month follow-up respectively). The Roland-Morris disability questionnaire was considered the most suitable primary outcome measure with a proposed sample size of 540 participants for a definitive cluster RCT. CONCLUSION: It is feasible to conduct a randomised study of CFT in comparison to UPC for NHS patients. A future study should incorporate an internal pilot to address aspects of feasibility further, including participant retention strategies. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN12965286 CONTRIBUTION OF THE PAPER.

Australian physiotherapists attitudes, perceptions, and behaviours towards psychosocial screening tools: a qualitative interpretive description study.

PURPOSE: Psychosocial factors are a barrier to recovery for people with musculoskeletal pain and psychosocial screening tools are consistently recommended by best practice guidelines to assist in identification. However, many physiotherapists do not use these tools. Presently, the perspectives on psychosocial screening tools of Australian physiotherapists are unknown. Exploration of these factors may create targets for increased uptake. The purpose of this paper is to qualitatively explore Australian physiotherapists' attitudes, perceptions, and behaviours towards psychosocial screening tools for musculoskeletal pain conditions. MATERIALS AND METHODS: An Interpretive description qualitative study design was employed. Seventeen Australian physiotherapists were interviewed about their attitudes, perceptions, and behaviours towards psychosocial screening tools. Interviews were transcribed verbatim and analysed according to interpretive description. RESULTS: Analysis highlighted three major themes: (1) understanding the patient through psychosocial screening, (2) confidence and competence with psychosocial factors, and (3) factors outside of my control influence screening. CONCLUSIONS: This study presents a deeper understanding of Australian physiotherapists' diverse attitudes and practices regarding psychosocial screening tools. The research highlights not only the variability in perspectives towards the relevance of psychosocial factors in patient assessments, but also the influence of external elements such as patient demographics and clinic culture on the utilization of these screening methods.

Australian physiotherapists' varying attitudes and limited understanding of the impact of psychosocial factors may hinder the use of recommended psychosocial screening.Concerns about scope of practice, tool appropriateness for different patients, and clinic culture further challenge the integration of psychosocial assessments.The findings from this study indicate the need to provide more education to Australian physiotherapists on the importance and use of psychosocial risk factor screening, as part of clinical care standards and best practice guidelines in the management of patients, with musculoskeletal pain conditions.The findings from this study can support the creation of targeted training/innovations to improve the uptake of screening tools in Australian musculoskeletal clinical practice, to improve the care of patients with musculoskeletal pain conditions.

Illness perceptions in people with chronic and disabling non-specific neck pain seeking primary healthcare: a qualitative study.

BACKGROUND: Illness perceptions can affect the way people with musculoskeletal pain emotionally and behaviorally cope with their health condition. Understanding patients illness perceptions may help facilitate patient-centered care. The purpose of this study was to explore illness perceptions and the origin of those perceptions in people with chronic disabling non-specific neck pain seeking primary care. METHODS: A qualitative study using a deductive and inductive analytical approach was conducted in 20 people with persistent (> 3 months) and disabling (i.e., Neck Disability Index ≥ 15) neck pain. Using a semi-structured format, participants were interviewed about their illness perceptions according to Leventhal's Common Sense Model. Purposive sampling and member checking were used to secure validity of study results. RESULTS: Participants reported multiple symptoms, thoughts and emotions related to their neck pain, which continuously required attention and action. They felt trapped within a complex multifactorial problem. Although some participants had a broader biopsychosocial perspective to understand their symptoms, a biomedical perspective was dominant in the labelling of their condition and their way of coping (e.g., limiting load, building strength and resilience, regaining mobility, keep moving and being meaningful). Their perceptions were strongly influenced by information from clinicians. Several participants indicated that they felt uncertain, because the information they received was contradictory or did not match their own experiences. CONCLUSION: Most participants reported that understanding their pain was important to them and influenced how they coped with pain. Addressing this 'sense making process' is a prerequisite for providing patient-centered care.

How Movement Is Assessed Matters. Changes in Forward Bending During Cognitive Functional Therapy Treatment for People With Chronic Low Back Pain.

OBJECTIVE: To investigate forward bending range of motion (ROM) and velocity in patients with low back pain who were receiving Cognitive Functional Therapy and determine (1) the amount and timing of change occurring at the trunk and pelvis (global angles), and lumbar spine (intersensor angle), and (2a) differences in changes between participants with and without sensor biofeedback, and (2b) participants with and without baseline movement limitation. DESIGN: Observational study. METHODS: Two hundred sixty-one participants attended Cognitive Functional Therapy treatment and wore sensors at the T12 and S2 spine levels while performing forward bending. Measures included ROM and velocity from both sensors, and the intersensor angle. Regression models estimated changes over time. Time-group interactions tested participants who were subgrouped by treatment and baseline movement. RESULTS: During the 90-day evaluation period, most change occurred in the first 21 days. Changes in ROM observed at T12 (3.3°, 95% CI: 1.0°, 5.5°; P = .001) and S2 (3.3°, 95% CI: 1.2°, 5.4°; P = .002) were similar. Intersensor angle remained similar (0.2°, 95% CI: -2.0°, -1.6°; P = .81). Velocity measured at T12 and S2, and the intersensor angle increased 8.5°/s (95% CI: 6.7°/s, 10.3°/s; P<.0001), 5.3°/s (95% CI: 4.0°/s, 6.5°/s; P<.0001), and 3.4°/s (95% CI: 2.4°/s, 4.5°/s; P<.0001), respectively, for 0 to 21 days. There were minimal differences in participants who received biofeedback. Larger increases occurred in participants with restricted ROM and slower velocity at baseline. CONCLUSION: During 0 to 21 days, we observed changes at the trunk and pelvis (especially in people with reduced ROM), and velocity changes across all measures (especially in people with baseline movement limitations). Biofeedback did not augment the changes. When targeting forward bending in people with low back pain, clinicians should monitor changes in velocity and global ROM. J Orthop Sports Phys Ther 2024;54(3):1-13. Epub 19 December 2023. doi:10.2519/jospt.2023.12023.

Preclinical development of a chimeric antigen receptor T cell therapy targeting FGFR4 in rhabdomyosarcoma.

Pediatric patients with relapsed or refractory rhabdomyosarcoma (RMS) have dismal cure rates, and effective therapy is urgently needed. The oncogenic receptor tyrosine kinase fibroblast growth factor receptor 4 (FGFR4) is highly expressed in RMS and lowly expressed in healthy tissues. Here, we describe a second-generation FGFR4-targeting chimeric antigen receptor (CAR), based on an anti-human FGFR4-specific murine monoclonal antibody 3A11, as an adoptive T cell treatment for RMS. The 3A11 CAR T cells induced robust cytokine production and cytotoxicity against RMS cell lines in vitro. In contrast, a panel of healthy human primary cells failed to activate 3A11 CAR T cells, confirming the selectivity of 3A11 CAR T cells against tumors with high FGFR4 expression. Finally, we demonstrate that 3A11 CAR T cells are persistent in vivo and can effectively eliminate RMS tumors in two metastatic and two orthotopic models. Therefore, our study credentials CAR T cell therapy targeting FGFR4 to treat patients with RMS.

Open-Label Trial of Amikacin Liposome Inhalation Suspension in Mycobacterium abscessus Lung Disease.

BACKGROUND: Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance. RESEARCH QUESTION: Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease? STUDY DESIGN AND METHODS: In an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance. RESULTS: Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%). INTERPRETATION: In a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03038178; URL: www. CLINICALTRIALS: gov.

Process of change for people with knee osteoarthritis undergoing cognitive functional therapy: a replicated single-case experimental design study.

PURPOSE: To examine the applicability and process of change of Cognitive Functional Therapy (CFT) in the management of pain and disability in people with knee osteoarthritis who were offered knee replacement surgery and had risk factors for poor response to surgery. METHODS: Single-case experimental design with a mixed-methods, repeated measures approach was used to investigate the process of change through CFT in four participants. Qualitative interviews investigated beliefs, behaviours and coping responses, and self-reported measures assessed pain, disability, psychological factors, and function at 25 timepoints. Study registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12619001491156). RESULTS: Qualitative data indicate that CFT promoted helpful changes in all participants, with two responses observed. One reflected a clear shift to a biopsychosocial conceptualisation of osteoarthritis, behavioural re-engagement and the view that a knee replacement was no longer necessary. The other response reflected a mixed conceptualisation with dissonant beliefs about osteoarthritis and its management. Psychological and social factors were identified as potential treatment barriers. Overall, quantitative measures supported the qualitative findings. CONCLUSION: The process of change varies between and within individuals over time. Psychological and social barriers to treatment have implications for future intervention studies for the management of knee osteoarthritis.IMPLICATIONS FOR REHABILITATIONCognitive Functional Therapy is applicable in the management of knee osteoarthritis.Reconceptualisation of osteoarthritis reflected a helpful change.Psychological and social factors emerged as barriers to recovery.

Physiotherapists' perceptions on using a multidimensional clinical reasoning form during psychologically informed training for low back pain.

PURPOSE: Building clinical reasoning skills is important to effectively implement psychologically informed practice. We developed a multidimensional clinical reasoning form (CRF) to be used by physiotherapists in a psychologically informed practice training programme for low back pain. In this paper we describe the development of the CRF, how the CRF was used in the training, and present an evaluation of physiotherapists' perceptions of the CRF. METHODS: Qualitative semi-structured interviews were conducted with ten physiotherapists purposively sampled in primary care. Data were gathered through pre, and post training focus group interviews and a secondary analysis of individual physiotherapist interviews conducted after the training. Thematic analysis was used to analyse the data and capture the emergent themes. RESULTS: Two main themes emerged before the training: (1) the CRF 'needs formal training' and (2) 'lacked instruction'. Three main themes emerged after the training (1) it provided 'a helpful framework for multidimensional clinical reasoning' (2) the CRF, and accompanying operational definitions, helped physiotherapists 'elicit information, with 'question prompts' helpful in facilitating patient disclosure (3) 'Utility' - although the CRF was not formally used by the physiotherapists it provided a conceptual reasoning framework to work from with more challenging patients. CONCLUSION: The CRF was not designed to be used in isolation by clinicians without training. However, when used as a training adjunct it appears to be valued by physiotherapists to help develop their critical thinking and better characterise patients' presentations in order to personalise care from a bio-psychosocial perspective.

Cognitive functional therapy with or without movement sensor biofeedback versus usual care for chronic, disabling low back pain (RESTORE): a randomised, controlled, three-arm, parallel group, phase 3, clinical trial.

BACKGROUND: Low back pain is the leading cause of years lived with disability globally, but most interventions have only short-lasting, small to moderate effects. Cognitive functional therapy (CFT) is an individualised approach that targets unhelpful pain-related cognitions, emotions, and behaviours that contribute to pain and disability. Movement sensor biofeedback might enhance treatment effects. We aimed to compare the effectiveness and economic efficiency of CFT, delivered with or without movement sensor biofeedback, with usual care for patients with chronic, disabling low back pain. METHODS: RESTORE was a randomised, controlled, three-arm, parallel group, phase 3 trial, done in 20 primary care physiotherapy clinics in Australia. We recruited adults (aged ≥18 years) with low back pain lasting more than 3 months with at least moderate pain-related physical activity limitation. Exclusion criteria were serious spinal pathology (eg, fracture, infection, or cancer), any medical condition that prevented being physically active, being pregnant or having given birth within the previous 3 months, inadequate English literacy for the study's questionnaires and instructions, a skin allergy to hypoallergenic tape adhesives, surgery scheduled within 3 months, or an unwillingness to travel to trial sites. Participants were randomly assigned (1:1:1) via a centralised adaptive schedule to usual care, CFT only, or CFT plus biofeedback. The primary clinical outcome was activity limitation at 13 weeks, self-reported by participants using the 24-point Roland Morris Disability Questionnaire. The primary economic outcome was quality-adjusted life-years (QALYs). Participants in both interventions received up to seven treatment sessions over 12 weeks plus a booster session at 26 weeks. Physiotherapists and patients were not masked. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12618001396213. FINDINGS: Between Oct 23, 2018 and Aug 3, 2020, we assessed 1011 patients for eligibility. After excluding 519 (51·3%) ineligible patients, we randomly assigned 492 (48·7%) participants; 164 (33%) to CFT only, 163 (33%) to CFT plus biofeedback, and 165 (34%) to usual care. Both interventions were more effective than usual care (CFT only mean difference -4·6 [95% CI -5·9 to -3·4] and CFT plus biofeedback mean difference -4·6 [-5·8 to -3·3]) for activity limitation at 13 weeks (primary endpoint). Effect sizes were similar at 52 weeks. Both interventions were also more effective than usual care for QALYs, and much less costly in terms of societal costs (direct and indirect costs and productivity losses; -AU$5276 [-10 529 to -24) and -8211 (-12 923 to -3500). INTERPRETATION: CFT can produce large and sustained improvements for people with chronic disabling low back pain at considerably lower societal cost than that of usual care. FUNDING: Australian National Health and Medical Research Council and Curtin University.

An Exploration of the Influence of Non-Biomechanical Factors on Lifting-Related LBP.

Objective: The primary objective was to compare non-biomechanical factors between manual workers with and without a history of LBP related to lifting. A secondary objective was to investigate associations between the change in pain intensity during repeated lifting (termed pain ramp) and non-biomechanical factors tested in the LBP group. Methods: Manual workers currently in lifting occupations with and without a history of lifting-related LBP were recruited (21 LBP and 20 noLBP) and took part in a repeated (100) lift task. A series of non-biomechanical factors, including psychological, work-related, lifestyle, whole health and psychophysical factors, were collected. Psychophysical factors (pressure pain thresholds (PPTs) and fatigue) were also measured at different time points. Associations between pain ramp during lifting and non-biomechanical factors were investigated with linear regression. Results: The LBP group reported worse perceived sleep quality, more musculoskeletal pain sites other than LBP and greater symptoms related to gastrointestinal complaints and pseudo-neurology compared to the group with no history of LBP. The group with LBP were also slightly more worried about the lifting task and felt more fatigued at the end of the lifting task. The feeling of fatigue during lifting was positively associated with pain ramp in the LBP group. Anxiety and gastrointestinal complaints were weakly negatively associated with pain ramp during lifting. Conclusions: The group differences of poorer perceived sleep, greater non-specific health complaints, slightly more worry about the lifting task and more perceived fatigue in the LBP group highlight the complex and multi-factorial nature of LBP related to lifting. The feeling of fatigue was positively associated with pain ramp in the LBP group, suggesting a close relationship with pain and fatigue during lifting that requires further exploration.