Transition-Metal-Free Continuous-Flow Synthesis of 2,5-Diaryl Furans: Access to Medicinal Building Blocks and Optoelectronic Materials.

The direct transformation of 1,3-dienes into valuable 2,5-diarylfurans using transition-metal-free conditions is presented. By employing a simple oxidation─dehydration sequence on readily accessible 1,3-dienes, important 2,5-diarylfuran building blocks frequently used in medicinal and material chemistry are prepared. The oxidation step is realized using singlet oxygen, and the intermediate endoperoxide is dehydrated under metal-free conditions and at ambient temperature using the Appel reagent. Notably, this sequence can be streamlined into continuous flow, thereby eliminating the isolation of the intermediate, often unstable endoperoxide. This leads to a significant improvement in isolated yields (ca. 27% average increase) of the 2,5-diarylfurans while also increasing safety and reducing waste. Our transition-metal-free synthetic approach to 2,5-diarylfurans delivers several important furan building blocks used commonly in medicinal chemistry and as optoelectronic materials, including short-chain linearly conjugated furan oligomers. Consequently, we also complete a short study of the optical and electrochemical properties of a selection of these novel materials.

Clinical indicators to identify neuropathic pain in low back related leg pain: a modified Delphi study.

BACKGROUND: Neuropathic pain (NP) is common in patients presenting with low back related leg pain. Accurate diagnosis of NP is fundamental to ensure appropriate intervention. In the absence of a clear gold standard, expert opinion provides a useful methodology to progress research and clinical practice. The aim of this study was to achieve expert consensus on a list of clinical indicators to identify NP in low back related leg pain. METHODS: A modified Delphi method consisting of three rounds was designed in accordance with the Conducting and Reporting Delphi Studies recommendations. Recruitment involved contacting experts directly and through expressions of interest on social media. Experts were identified using pre-defined eligibility criteria. Priori consensus criteria were defined for each round through descriptive statistics. Following completion of round 3 a list of clinical indicators that achieved consensus were generated. RESULTS: Thirty-eight participants were recruited across 11 countries. Thirty-five participants completed round 1 (92.1%), 32 (84.2%) round 2 and 30 (78.9%) round 3. Round 1 identified consensus (Kendall's W coefficient of concordance 0.456; p < 0.001) for 10 clinical indicators out of the original 14, and 9 additional indicators were added to round 2 following content analysis of qualitative data. Round 2 identified consensus (Kendall's W coefficient of concordance 0.749; p < 0.001) for 10 clinical indicators out of 19, and 1 additional indicator was added to round 3. Round 3 identified consensus for 8 indicators (Kendall's W coefficient of concordance 0.648; p < 0.001). Following completion of the third round, an expert derived consensus list of 8 items was generated. Two indicators; pain variously described a burning, electric shock like and/or shooting into leg and pain in association with other neurological symptoms (e.g. pins and needles, numbness, weakness), were found to have complete agreement amongst expert participants. CONCLUSIONS: Good agreement was found for the consensus derived list of 8 clinical indicators to identify NP in low back related leg pain. This list of indicators provide some indication of the criteria upon which clinicians can identify a NP component to low back related leg pain; further research is needed for stronger recommendations to be made.

Diagnostic utility of patient history, clinical examination and screening tool data to identify neuropathic pain in low back related leg pain: a systematic review and narrative synthesis.

BACKGROUND: Low back-related leg pain (LBLP) is a challenge for healthcare providers to manage. Neuropathic pain (NP) is highly prevalent in presentations of LBLP and an accurate diagnosis of NP in LBLP is essential to ensure appropriate intervention. In the absence of a gold standard, the objective of this systematic review was to evaluate the diagnostic utility of patient history, clinical examination and screening tool data for identifying NP in LBLP. METHODS: This systematic review is reported in line with PRISMA and followed a pre-defined and published protocol. CINAHL, EMBASE, MEDLINE, Web of Science, Cochrane Library, AMED, Pedro and PubMed databases, key journals and the grey literature were searched from inception to 31 July 2019. Eligible studies included any study design reporting primary diagnostic data on the diagnostic utility of patient history, clinical examination or screening tool data to identify NP in LBLP, in an adult population. Two independent reviewers searched information sources, assessed risk of bias (QUADAS-2) and used GRADE to assess overall quality of evidence. RESULTS: From 762 studies, 11 studies were included. Nine studies out of the 11 were at risk of bias. Moderate level evidence supports a cluster of eight signs (age, duration of disease, paroxysmal pain, pain worse in leg than back, typical dermatomal distribution, worse on coughing/sneezing/straining, finger to floor distance and paresis) for diagnosing lumbosacral nerve root compression, demonstrating moderate/high sensitivity (72%) and specificity (80%) values. Moderate level evidence supports the use of the StEP tool for diagnosing lumbar radicular pain, demonstrating high sensitivity (92%) and specificity (97%) values. CONCLUSIONS: Overall low-moderate level evidence supports the diagnostic utility of patient history, clinical examination and screening tool data to identify NP in LBLP. The weak evidence base is largely due to methodological flaws and indirectness regarding applicability of the included studies. The most promising diagnostic tools include a cluster of 8 patient history/clinical examination signs and the StEP tool. Low risk of bias and high level of evidence diagnostic utility studies are needed, in order for stronger recommendations to be made.

The biopsychosocial factors associated with development of chronic musculoskeletal pain. An umbrella review and meta-analysis of observational systematic reviews.

AIM: The aim of this umbrella review was to establish which biopsychosocial factors are associated with development of chronic musculoskeletal pain. METHODS: Ovid Medline, Embase, Web of Science Core Collection, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, PsycINFO, CINAHL, PEDro, PROSPERO, Google Scholar and grey literature were searched from database inception to 4th April 2023. Systematic reviews of observational prospective longitudinal studies, including populations with <3 months (not chronic) musculoskeletal pain, investigating biopsychosocial factors that contribute to development of chronic (>3 months) musculoskeletal pain. Two reviewers searched the literature, assessed risk of bias (Assessing the Methodological Quality of Systematic Reviews-2), and evaluated quality (Grading of Recommendations, Assessment, Development and Evaluation) to provide an overall statement on the certainty of evidence for each biopsychosocial factor. Data analysis was performed through random effects meta-analysis (including meta-analysis of meta-analyses where possible) and descriptive synthesis. RESULTS: 13 systematic reviews were included comprising 185 original research studies (n = 489,644 participants). Thirty-four biopsychosocial factors are associated with development of chronic musculoskeletal pain. Meta-analyses of odds and/or likelihood ratios were possible for 25 biopsychosocial factors. There is moderate certainty evidence that smoking (OR 1.24 [95%CI, 1.14-1.34), fear avoidance (LR+ 2.11 [95%CI, 1.59-2.8]; LR- 0.5 [95%CI, 0.35-0.71]) poorer support networks (OR 1.21 [95%CI, 1.14-1.29]), lower socioeconomic status (OR 2.0 [95%CI, 1.64-2.42]), and high levels of pain (OR 5.61 [95%CI, 3.74-8.43]) are associated with development of chronic musculoskeletal pain (all P<0.001). Remaining factors are of low or very low certainty evidence. CONCLUSIONS AND RELEVANCE: There is moderate certainty evidence that smoking, fear avoidance, poorer support networks, lower socioeconomic status, and high levels of pain are associated with development of chronic musculoskeletal pain. High risk of bias was evident in most included reviews; this highlights the need for higher quality systematic reviews.

Diagnostic utility of diagnostic investigations to identify neuropathic pain in low back-related leg pain: protocol for a systematic review.

INTRODUCTION: Neuropathic pain in low back-related leg pain has gained increasing interest in contemporary research. Identification of neuropathic pain in low back-related leg pain is essential to inform precision management. Diagnostic investigations are commonly used to identify neuropathic pain in low back-related leg pain; yet the diagnostic utility of these investigations is unknown. This systematic review aims to investigate the diagnostic utility of diagnostic investigations to identify neuropathic pain in low back-related leg pain. METHODS AND ANALYSIS: This protocol has been designed and reported in accordance with the Cochrane Handbook for Diagnostic Test Accuracy studies, Centre for Reviews and Dissemination and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols checklist, respectively. The search strategy will involve two independent reviewers searching electronic databases (CINAHL, EMBASE, MEDLINE, Web of Science, Cochrane Library, AMED, Pedro), key journals (Spine, The Clinical Journal of Pain, PAIN, European Journal of Pain, The Journal of Pain, Musculoskeletal Science and Practice) and grey literature (British National Bibliography for report literature, OpenGrey, EThOS) from inception to 31 July 2023 to identify studies. Studies evaluating the diagnostic accuracy of diagnostic investigation to identify neuropathic pain in patients with low back-related leg pain will be eligible, studies not written in English will be excluded. The reviewers will extract the data from included studies, assess risk of bias (Quality Assessment of Diagnostic Accuracy Studies 2) and determine confidence in findings (Grading of Recommendations, Assessment, Development and Evaluation guidelines). Methodological heterogeneity will be assessed to determine if a meta-analysis is possible. If pooling of data is not possible then a narrative synthesis will be done. ETHICS AND DISSEMINATION: Ethical approval is not required. Findings will be published in a peer-reviewed journal, presented at relevant conferences and shared with the Patient Partner Advisor Group at Western University, Canada. PROSPERO REGISTRATION NUMBER: CRD42023438222.

Patient satisfaction with advanced physiotherapy practice internationally: Protocol for a systematic mixed studies review.

RATIONALE: Patient satisfaction is a complex construct consisting of human and system attributes. Patient satisfaction can afford insight into patient experience, itself a key component of evaluating healthcare quality. Internationally, advanced physiotherapy practice (APP) extends across clinical fields and is characterised as a higher level of practice with a high degree of autonomy and complex decision making. Patient satisfaction with APP appears positive. While evidence synthesis of patient satisfaction with APP exists, no systematic review has synthesised evidence across clinical fields. Therefore, the objectives of this systematic review are 1) to evaluate patient satisfaction with APP internationally, and 2) to evaluate human and system attributes of patient satisfaction with APP. MATERIALS AND METHODS: A systematic mixed studies review using a parallel-results convergent synthesis design will be conducted. Searches of Medline, Embase, Web of Science, CINAHL, Cochrane, PEDro and grey literature databases will be conducted from inception to 18/7/2023. Studies of APP (World Physiotherapy definition) whereby practitioners a) have advanced clinical and analytical skills that influence service improvement and provide clinical leadership, b) have post-registration masters level specialisation (or equivalence), c) deliver safe, competent care to patients with complex needs and d) may use particular occupational titles; that measure patient satisfaction across all clinical fields and countries will be included. Two reviewers will screen studies, extract data, assess methodological quality of included studies (mixed methods appraisal tool), and contribute to data synthesis. Quantitative data will undergo narrative synthesis (textual descriptions) and qualitative data thematic synthesis (analytical themes). Integration of data syntheses will inform discussion. IMPLICATIONS: This systematic review will provide insight into patient satisfaction with APP internationally, exploring attributes that influence satisfaction. This will aid design, implementation, or improvement of APP and facilitate the delivery of patient-centred, high-quality healthcare. Lastly, this review will inform future methodologically robust research investigating APP patient satisfaction and experience.

Physical functioning outcome measures in the lumbar spinal surgery population and measurement properties of the physical outcome measures: protocol for a systematic review.

INTRODUCTION: Low back pain can lead to substantial decline in physical functioning. For disabling pain not responsive to conservative management, surgical intervention can enhance physical functioning. Measurements of physical functioning include patient-reported outcome measures and physical outcome measures using evaluations of impairments, performance on a standardised task or activity in a natural environment. Selecting outcome measures with adequate measurement properties is fundamental to evaluating effectiveness of interventions. The purpose of this systematic review is to identify outcome measures (patient reported and physical) used to evaluate physical functioning (stage 1) and assess the measurement properties of physical outcome measures of physical functioning (stage 2) in the lumbar spinal surgery population. METHODS AND ANALYSIS: This protocol aligns with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Using a two-staged approach, searches will be performed in MEDLINE, EMBASE, Health and Psychosocial Instruments, CINAHL, Web of Science, Scopus, PEDro and the grey literature from inception until 15 December 2021. Stage 1 will identify studies evaluating physical functioning with patient-reported or physical outcome measures in the lumbar spinal surgery population. Stage 2 will search for studies evaluating measurement properties (validity, reliability, responsiveness) of the physical outcome measures identified in stage 1 in the lumbar spinal surgery population. Two independent reviewers will evaluate studies for inclusion, extract data, assess risk of bias (COSMIN risk of bias tool and checklist) and quality of evidence (modified Grading of Recommendations Assessment, Development and Evaluation approach). Results for each measurement property per physical outcome measure will be quantitatively pooled if there is adequate clinical and methodological homogeneity or qualitatively synthesised if there is high heterogeneity in studies. ETHICS AND DISSEMINATION: Ethics approval is not required. Results will be disseminated through peer-reviewed journal publication and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42021293880.

Classification criteria for cervical radiculopathy: An international e-Delphi study.

BACKGROUND: Establishing a set of uniform classification criteria (CC) for cervical radiculopathy (CR) is required to aid future recruitment of homogenous populations to clinical trials. OBJECTIVES: To establish expert informed consensus on CC for CR. DESIGN: A pre-defined four round e-Delphi study in accordance with the guidance on Conducting and Reporting Delphi Studies. METHODS: Individuals with a background in physiotherapy who had authored two or more peer-reviewed publications on CR were invited to participate. The initial round asked opinions on CC for CR. Content analysis was performed on round one output and a list of discrete items were generated forming the round two survey. In rounds two to four, participants were asked to rate the level of importance of each item on a six-point Likert scale. Data were analysed descriptively using median, interquartile range and percentage agreement. Items reaching pre-defined consensus criteria were carried forward to the next round. Items remaining after the fourth round constituted expert consensus on CC for CR. RESULTS: Twelve participants participated with one drop out. The final round identified one inclusion CC and 12 exclusion CC. The inclusion CC that remained achieved 82% agreement and was a cluster criterion consisting of radicular pain with arm pain worse than neck pain; paraesthesia or numbness and/or weakness and/or altered reflex; MRI confirmed nerve root compression compatible with clinical findings. CONCLUSIONS: The CC identified can be used to inform eligibility criteria for future CR trials although caution should be practiced as consensus on measurement tools requires further investigation.

Which biopsychosocial factors are associated with the development of chronic musculoskeletal pain? Protocol for an umbrella review of systematic reviews.

INTRODUCTION: Recent systematic reviews have identified many biopsychosocial factors associated with the development of chronic musculoskeletal pain (CMP). Despite often being specific to a particular musculoskeletal condition, findings are similar across systematic reviews. Research is needed to aggregate these findings to identify consistent factors across musculoskeletal disorders that are associated with the development of CMP. The objective of this study is to provide a meta-level synthesis of all biopsychosocial factors associated with the development of CMP. METHODS AND ANALYSIS: An umbrella review and meta-level narrative synthesis±meta-analysis has been designed informed by Joanna Briggs Institute and Cochrane guidance. This protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-P. Sources will include Ovid Medline, Embase, Web of Science Core Collection, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, PsycINFO, CINAHL, PEDro, PROSPERO, Google Scholar and grey literature. INCLUSION CRITERIA: any systematic review which investigates biopsychosocial factors which may be associated with the development of CMP through prospective longitudinal methods. The outcome is musculoskeletal pain lasting beyond 3 months. Two independent reviewers will be involved in all stages; screening, selection, data extraction and risk of bias evaluation using the Assessing the Methodological Quality of Systematic Reviews-2 guidelines. A meta-level narrative synthesis will be conducted based on (a) factors associated with development of CMP, (b) the range of musculoskeletal disorders for which the same/similar findings have been established and (c) the quality of studies informing these findings. Where possible, meta-analysis will be performed. The Grading of Recommendations, Assessment, Development and Evaluation guidelines will be followed to determine the level of evidence for each biopsychosocial factor. ETHICS AND DISSEMINATION: This umbrella review does not require ethical approval. Findings will be presented at conferences and published in a peer reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020193081.

Clinical indicators to identify neuropathic pain in low back-related leg pain: protocol for a modified Delphi study.

INTRODUCTION: Neuropathic low back-related leg pain (LBLP) can be a challenge to healthcare providers to diagnose and treat. Accurate diagnosis of neuropathic pain is fundamental to ensure appropriate intervention is given. However, to date there is no gold standard to diagnose neuropathic LBLP. A Delphi study will therefore be conducted to obtain an expert-derived consensus list of clinical indicators to identify a neuropathic component to LBLP. METHODS/ANALYSIS: Included participants will be considered experts within the field as measured against a predefined eligibility criterion. Through an iterative multistage process, participants will rate their agreement with a list of clinical indicators and suggest any missing clinical indicators during each round. Agreement will be measured using a 5-point Likert scale. Descriptive statistics will be used to measure agreement; median, IQR and percentage of agreement. A priori consensus criteria will be defined for each round. Data analysis at the end of round three will enable a list of clinical indicators to be derived. ETHICS AND DISSEMINATION: Ethical approval was gained from the University of Birmingham (ERN_19-1142). On completion of the study, findings will be disseminated in a peer-reviewed journal and presented at relevant conferences.

Diagnostic utility of patient history, clinical examination and screening tool data to identify neuropathic pain in low back-related leg pain: protocol for a systematic review.

INTRODUCTION: Neuropathic low back-related leg pain (LBLP) can be a challenge to healthcare providers to diagnose and treat. Accurate diagnosis of neuropathic pain is fundamental to ensure appropriate intervention is given. However, to date there is no gold standard to diagnose neuropathic LBLP. Patient examination guidelines and screening tools have been developed and validated for the purpose of diagnosing neuropathic pain in LBLP; however, there has been no systematic review conducted to compare the diagnostic validity of these methods. Therefore, this systematic review will investigate the diagnostic utility of patient history, clinical examination and screening tool data to identify neuropathic pain in LBLP. METHODS AND ANALYSIS: This protocol is informed and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Protocols. CINAHL, EMBASE, MEDLINE, Web of Science, Cochrane Library, AMED, Pedro, PubMed, key journals and grey literature will be searched rigorously to find diagnostic accuracy studies investigating patient examination data to identify neuropathic pain in LBLP patients. Two independent reviewers will conduct the search, extract the data and assess risk of bias for included studies using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. The overall quality of included studies will be evaluated using Grading of Recommendations, Assessment, Development and Evaluation guidelines. A meta-analysis will be conducted if deemed appropriate. Otherwise, a narrative synthesis will be conducted. ETHICS AND DISSEMINATION: No research ethics is required for this systematic review since patient data will not be collected. This review will help to inform healthcare professionals and researchers on the most effective means in which to diagnose neuropathic pain in LBLP. Results of this review will be submitted for publication in a peer-review journal and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42019140861.