The smallest worthwhile effect on pain intensity of exercise therapy for people with chronic low back pain: a discrete choice experiment study.

OBJECTIVE: To identify the smallest worthwhile effect (SWE) of exercise therapy for people with non-specific chronic low back pain (CLBP). DESIGN: Discrete choice experiment. METHODS: The SWE was estimated as the lowest reduction in pain that participants would consider exercising worthwhile, compared to not exercising i.e., effects due to natural history and other components (e.g., regression to the mean). We recruited English-speaking adults in Australia with non-specific CLBP to our online survey via email obtained from a registry of previous participants and advertisements on social media. We used discrete choice experiment to estimate the SWE of exercise compared to no exercise for pain intensity. We analysed the discrete choice experiment using a mixed logit model, and mitigated hypothetical bias through certainty calibration, with sensitivity analyses performed with different certainty calibration thresholds. RESULTS: Two-hundred and thirteen participants completed the survey. The mean age (±SD) was 50.7±16.5, median (IQR) pain duration 10 years (5-20), and mean pain intensity (±SD) was 5.8±2.3 on a 0-10 numerical rating scale. For people with CLBP the SWE of exercise was a between-group reduction in pain of 20%, compared to no exercise. In the sensitivity analyses, the SWE varied with different levels of certainty calibration; from 0% without certainty calibration to 60% with more extreme certainty calibration. CONCLUSION: This patient-informed threshold of clinical importance could guide the interpretation of findings from randomised trials and meta-analyses of exercise therapy compared to no exercise.

Barriers and enablers to exercise adherence in people with nonspecific chronic low back pain: a systematic review of qualitative evidence.

ABSTRACT: Exercise is a first-line treatment for chronic low back pain (CLBP), reducing pain and disability in the short term. However, exercise benefits decrease over time, with a lack of long-term exercise adherence a potential reason for this. This study aimed to synthesize the perceptions and beliefs of individuals with CLBP and identify their barriers and enablers to exercise adherence. We searched CENTRAL, Embase, CINAHL, SPORTDiscus, PubMed, PsycINFO, and Scopus databases from inception to February 28, 2023, for qualitative studies that explored the factors influencing exercise adherence for people with CLBP. A hybrid approach combining thematic synthesis with the Theoretical Domains Framework was used to analyze data. We assessed methodological quality using the Critical Appraisal Skills Programme checklist and the level of confidence of the themes generated using the Confidence in the Evidence from Reviews of Qualitative Studies. Twenty-three papers (n = 21 studies) were included (n = 677 participants). Four main themes affected exercise adherence: (1) exercise, pain, and the body, (2) psychological factors, (3) social factors, and (4) external factors. These themes contained 16 subthemes that were predominantly both barriers and enablers to exercise adherence. The individual's experiences of barriers and enablers were most appropriately represented across a spectrum, where influencing factors could be a barrier or enabler to exercise adherence, and these could be specific to pre-exercise, during-exercise, and post-exercise situations. These findings may be used to improve exercise adherence and ultimately treatment outcomes in people with CLBP.

Dermal absorption of high molecular weight parent and alkylated polycyclic aromatic hydrocarbons from manufactured gas plant soils using in vitro assessment.

An enhanced in vitro human dermal bioavailability method was developed to measure the release of twenty parent and seven alkylated high molecular weight (HMW) polycyclic aromatic hydrocarbons (PAHs) from contaminated soils collected from five former manufactured Gas Plants (MGP) in England. GC-MS/MS was used to quantify HMW PAHs in soil, Strat-M artificial membrane representing skin, and synthetic receptor solution (RS) representing systemic circulation at 1-h, 10-h, and 24-h timesteps. Fluoranthene and pyrene exhibited the highest fluxes from soils to membrane (ranging from 9.5 - 281 ng/cm2/h) and soil to RS (

Exploring the Role of Guidelines in Contributing to Medication Errors: A Descriptive Analysis of National Patient Safety Incident Data.

INTRODUCTION: Clinical guidelines can contribute to medication errors but there is no overall understanding of how and where these occur. OBJECTIVES: We aimed to identify guideline-related medication errors reported via a national incident reporting system, and describe types of error, stages of medication use, guidelines, drugs, specialties and clinical locations most commonly associated with such errors. METHODS: Retrospective analysis of reports to the National Reporting and Learning System for England and Wales. A hierarchical task analysis (HTA) was developed, describing expected practice when using guidelines. A free-text search was conducted of medication incident reports (2016-2021) using search terms related to common guidelines. All identified reports linked to moderate-severe harm or death, and a random sample of 5100 no/low-harm reports were coded to describe deviations from the HTA. A random sample of 500 cases were independently double-coded. RESULTS: In total, 28,217 reports were identified, with 608 relating to moderate-severe harm or death. Fleiss' kappa for interrater reliability was 0.46. Of the 5708 reports coded, 642 described an HTA step discrepancy (including four linked to a death), suggesting over 3200 discrepancies in the entire dataset of 28,217 reports. Discrepancies related to finding guidelines (n = 300 reports), finding information within guidelines (n = 166) and using information (n = 176). Discrepancies were most frequently identified for guidelines produced by a local organisation (n = 405), and most occurred during prescribing (n = 277) or medication administration (n = 241). CONCLUSION: Difficulties finding and using information from clinical guidelines contribute to thousands of prescribing and medication administration incidents, some of which are associated with substantial patient harm.

A Qualitative Study Identifying Barriers and Enablers to Exercise Adherence in People with Chronic Low Back Pain. "It's a personal journey".

Exercise leads to clinically meaningful pain reductions in people with chronic low back pain and is recommended as a first line treatment. The benefits of exercise for chronic low back pain decrease over time with a lack of long-term exercise adherence as a potential reason for this decreasing effect. We aimed to identify the barriers and enablers to exercise adherence from the perspective of people with chronic low back pain. This qualitative study was underpinned by a constructivist epistemology and used a critical realist ontological perspective. Adults (18-65 years) with chronic low back pain who had exercised since the onset of their back pain were recruited to participate in focus groups and individual interviews. Audio data were transcribed and then analysed in 2 stages 1) inductive coding using reflexive thematic analysis, followed by 2) deductive analysis through mapping codes onto the Theoretical Domains Framework. Five enablers and 3 barriers were identified across 6 of the 14 Theoretical Domain Framework domains. Exercise identity and confidence in deciding to self-manage pain were enablers, whereas beliefs about the consequences of exercise, exercise context, and relationships could function as either barriers or enablers. These barriers and enablers were complex and fluid, with participants reporting conflicting barriers and enablers that varied, depending on context. These findings improve our understanding of the barriers and enablers to exercise adherence from the individual perspective of people with chronic low back pain and can be utilised for more effective exercise treatment in this population. PERSPECTIVE: This article presents the barriers and enablers to exercise adherence from the perspective of people with chronic low back pain. These perspectives may aid to individualise and optimise exercise treatment, improve its long-term adherence and therefore its effectiveness for chronic low back pain.

Exercise Snacks and Other Forms of Intermittent Physical Activity for Improving Health in Adults and Older Adults: A Scoping Review of Epidemiological, Experimental and Qualitative Studies.

Exercise snacks, including other variants of brief intermittent bouts, are an emerging approach for increasing physical activity, although their operationalisation is unstandardised and their health benefits remain unclear. This scoping review aimed to explore characterisations of exercise snacks and summarise their effects on health in adults and older adults. Clinical trial registers (clinicaltrials.gov and ANZCTR) and electronic databases (PubMed, CINAHL, CENTRAL, PsycINFO) were searched from inception to 1 June 2023, for ongoing and published studies of exercise snacks. Backwards and forwards citation tracking was also conducted to identify additional eligible studies. Studies were included if they investigated exercise snacks-brief intermittent bouts of physical activity spread across the day-in adults or older adults. We included epidemiological, experimental, quasi-experimental and qualitative studies that examined the effect of exercise snacks on any health outcomes or described barriers to and enablers of these approaches. Thirty-two studies were included (7 trial registers, 1 published protocol, 3 epidemiological studies and 20 trials reported across 21 studies). Three main terms were used to describe exercise snacks: exercise snack(ing), snacktivity and vigorous intermittent lifestyle physical activity (VILPA). Participants were predominantly physically inactive but otherwise healthy adults or older adults. Exercise snacks were feasible and appeared safe. Epidemiological studies showed steep, near-linear associations of VILPA with reduced all-cause, cardiovascular and cancer mortality as well as reduced incidence of major adverse cardiovascular events and cancer. The limited trial evidence showed exercise snacks had modest effects on improving cardiorespiratory fitness, whereas effects on physical function, mood, quality of life and other health outcomes were equivocal. In conclusion, exercise snacks appear feasible and safe for adults and older adults and may have promising health benefits, but this is mostly based on findings from a limited number of small quasi-experimental studies, small randomised trials or qualitative studies. More studies are needed in individuals with chronic disease. This emerging physical activity approach may have appeal for individuals who find structured exercise unfeasible.Registration https://osf.io/qhu24/.

Pharmacy users' perceptions, awareness and future expectations of community pharmacy in England: a focus group study.

OBJECTIVE: To explore pharmacy users' perceptions of current and future provision of community pharmacy services in England. METHODS: Qualitative, reconvened focus groups were conducted with community pharmacy users. An initial focus group explored preliminary views. Participants were then given an evidence brief describing community pharmacy before a reconvened focus group two weeks later. Transcripts were analysed using inductive thematic analysis. KEY FINDINGS: Eleven individuals participated across two reconvened focus groups. Participants valued community pharmacies and staff, but lacked awareness of their services and roles: '… I don't think the general public is aware of all of this … it gives you a very different perspective'. Urgent care and long-term conditions management were identified as suitable for future development, facilitated by training, closer collaboration with general practices, shared access to health records, and premises with more space and confidentiality: 'I still think of it as a retail space more than as a health service'. Concerns were expressed about working conditions in community pharmacy and unplanned closures: 'doesn't sound like a great place to work'. Participants anticipated greater use of technology but did not want this to replace face-to-face contact with pharmacy staff: 'I am not saying it's inaccurate, it is so remote and impersonal'. CONCLUSIONS: Pharmacy users would value a greater role for community pharmacy in addressing the challenges currently faced by the health service in England, provided that their concerns on a range of issues are addressed.

Are Exercise Interventions in Clinical Trials for Chronic Low Back Pain Dosed Appropriately to Meet the World Health Organization's Physical Activity Guidelines?

OBJECTIVE: This study aimed to estimate the proportion of exercise interventions tested in clinical trials of people with chronic low back pain (CLBP) that meet the World Health Organization's (WHO) physical activity guidelines. METHODS: A secondary analysis of the 2021 Cochrane review of exercise therapy for CLBP was performed. Data from each study were extracted by 1 reviewer and were checked by a second reviewer. Data extracted related to the frequency, duration and intensity of each exercise intervention, and the proportion of exercise interventions that met the WHO's physical activity guidelines (aerobic, muscle strengthening, or both) were determined. RESULTS: The 249 included trials comprised 426 exercise interventions. Few interventions reported an exercise type and dose consistent with the WHO guidelines (aerobic: 1.6%, muscle strengthening: 5.6%, both: 1.6%). Poor reporting of exercise intensity limited our ability to determine whether interventions met the guidelines. CONCLUSION: Few interventions tested in clinical trials for people with CLBP prescribe an exercise type and dose consistent with the WHO guidelines. Therefore, they do not appear sufficiently dosed to achieve broader health outcomes. Future trials should investigate the effect of WHO guideline-recommended exercise interventions on patient-reported outcomes (pain and disability) as well as health-related outcomes in people with CLBP. IMPACT: This exploratory analysis showed the lack of exercise interventions in the CLBP literature that meet the WHO's physical activity guidelines. With people in chronic pain groups, such as people with CLBP, being at higher risk for noncommunicable disease, it appears this is a key consideration for exercise practitioners when designing interventions for people with CLBP.

Barriers and Enablers to Using Intervention Reporting Guidelines in Sports and Exercise Medicine Trials: A Mixed-Methods Study.

OBJECTIVE: To identify barriers and facilitators for using intervention reporting guidelines (CERT and TIDieR) from authors of randomized controlled trials in sports and exercise medicine journals. DESIGN: Mixed-methods cross-sectional online survey. METHODS: We recruited authors of randomized controlled trials published from June 2, 2018, to June 2, 2022, in the 10 leading sports and exercise medicine journals. We invited authors of eligible trials to complete an online survey that included multiple-choice and Likert-scale questions, as well as open-ended free-text questions on the barriers and facilitators to using intervention reporting guidelines. We used descriptive analysis to summarize the quantitative data and a hybrid deductive-inductive thematic analysis to identify barriers and facilitators from the qualitative data. We conducted a subgroup analysis to explore differences in barriers and facilitators between early-mid career researchers and senior researchers. RESULTS: Eighty-four participants from 21 countries completed the survey (44 early-mid-career researchers, 40 senior researchers). We identified 8 themes relating to using intervention reporting guidelines. Themes classified as barriers related to publication constraints (word count limits), low awareness of intervention reporting guidelines, unclear benefits of the guidelines, and the increased burden imposed upon the researcher. Themes classified as facilitators related to journal requirements for guidelines use, the desire to accurately describe interventions, recommendations from other researchers, and reporting guideline use indicating "quality" of work. CONCLUSION: Barriers to using intervention reporting guidelines are largely modifiable and could be addressed by journals mandating their use, and educational initiatives. J Orthop Sports Phys Ther 2024;54(2):1-11. Epub 16 November 2023. doi:10.2519/jospt.2023.12110.

Unexpected Periodicity in Cationic Group 5 Initiators for the Ring-Opening Polymerization of Lactones.

ε-Caprolactone (ε-CL) adducts of cationic, amine tris(phenolate)-supported niobium(V) and tantalum(V) ethoxides initiate the ring-opening polymerization of lactones. The Ta(V) species prepared and applied catalytically herein exhibits higher activity in the ring-opening polymerization (ROP) of ε-caprolactone than the previously reported, isostructural Nb(V) complex, contradicting literature comparisons of Nb(V)- and Ta(V)-based protocols. Both systems also initiate the ROP of δ-valerolactone and rac-ß-butyrolactone, kinetic studies confirming retention of higher activity by the Ta congener. Polymerizations of rac-ß-butyrolactone and δ-valerolactone were previously unrealized under Group V- or Ta-mediated conditions, respectively, although the former has afforded only low molecular weight, cyclic poly-3-hydroxybutyrate. Cationic ethoxo-Nb(V) and -Ta(V) δ-valerolactone adducts are also reported, demonstrating the facility of δ-valerolactone as a ligand and the generality of the synthetic method. Both δ-valerolactone-bearing complexes initiate the ROP of ε-caprolactone, δ-valerolactone, and rac-ß-butyrolactone. Accordingly, we have elucidated trends in reactivity and investigated the initiation mechanism for such systems, the insertion event being predicated upon intramolecular nucleophilic attack on the coordinated lactone by the adjacent alkoxide moiety. This mechanism enables quantitative, stoichiometric installation of a single monomer residue distinct from the bulk of the polymer chain, and permits modification of polymer properties via both manipulation of the molecular architecture and tuning of the polymerization kinetics, and thus dispersity, through hitherto inaccessible independent control of the initiation event.

Are the attitudes and beliefs of Australian exercise-based practitioners associated with their use of, and confidence in, treatment modalities for people with chronic low back pain?

BACKGROUND: Practitioners' attitudes and beliefs towards chronic low back pain (CLBP) influence their clinical decision making, but few studies have investigated decision making outside the context of patient vignettes for a range of first- and second-line treatment options for CLBP, or in accredited exercise physiologists (AEPs). METHODS: Using an online survey, Australian AEPs and physiotherapists rated their use of different treatments for CLBP (exercise, education, manual therapy, cognitive behavioural therapy) and their confidence in these treatments for reducing pain and disability. Their biomedical and biopsychosocial beliefs were also assessed using the Pain and Attitudes Beliefs Scale for Physiotherapists. Differences between disciplines in treatment use and confidence were analysed using Mann-Whitney U tests and independent t-tests, respectively. Multiple linear regression was used to explore factors associated with treatment choices. RESULTS: Two-hundred thirty-three practitioners (n = 143 physiotherapists, n = 90 AEPs) completed the survey. Most practitioners were confident in treating CLBP, had a moderate-high level of confidence in the different treatments, and regularly used them in practice. Practitioners with higher biomedical beliefs had greater use of, and confidence in, specific exercise, manual therapy, and combined exercise and manual therapy. Practitioners with higher biopsychosocial beliefs were more confident in general exercise, cognitive behavioural therapy, pain education and combined exercise and pain education. CONCLUSION: Practitioner beliefs influence their use of, and confidence in different treatments for CLBP. These findings suggest a need for strategies to enhance biopsychosocial beliefs/reduce biomedical beliefs in Australian exercise-based practitioners.

Elementary effects for models with dimensional inputs of arbitrary type and range: Scaling and trajectory generation.

The Elementary Effects method is a global sensitivity analysis approach for identifying (un)important parameters in a model. However, it has almost exclusively been used where inputs are dimensionless and take values on [0, 1]. Here, we consider models with dimensional inputs, inputs taking values on arbitrary intervals or discrete inputs. In such cases scaling effects by a function of the input range is essential for correct ranking results. We propose two alternative dimensionless sensitivity indices by normalizing the scaled mean or median of absolute effects. Testing these indices with 9 trajectory generation methods on 4 test functions (including the Penman-Monteith equation for evapotranspiration) reveals that: i) scaled elementary effects are necessary to obtain correct parameter importance rankings; ii) small step-size methods typically produce more accurate rankings; iii) it is beneficial to compute and compare both sensitivity indices; and iv) spread and discrepancy of the simulation points are poor proxies for trajectory generation method performance.

Professional stakeholders' expectations for the future of community pharmacy practice in England: a qualitative study.

OBJECTIVES: To explore the views of professional stakeholders on the future of community pharmacy services in England. Specific objectives related to expectations of how community pharmacy services will be provided by 2030 and factors that will influence this. DESIGN: Qualitative, using semistructured interviews in person or via telephone/Skype. The topic guide was informed by a recent policy review that used the Walt and Gilson policy framework. Transcripts were analysed using inductive thematic analysis. SETTING: England. PARTICIPANTS: External stakeholders were representatives of non-pharmacy organisations, including policy-makers, commissioners and representatives of healthcare professions. Internal stakeholders were community pharmacists or pharmacy organisation representatives. Interviewees were identified using stakeholder mapping RESULTS: In total, 25 interviews were completed (7 external stakeholders and 18 internal stakeholders, of which 10 were community pharmacists). Community pharmacy was recognised as having a key role in expanding health system capacity ('…pharmacy is the obvious person to take on those roles…'), particularly for long-term condition management (eg, adherence, reducing polypharmacy, monitoring), urgent care (eg, minor illnesses) and public health (including mental health). For these contributions to be developed and optimised, greater integration and collaboration with general practices will be needed ('…there is no room for isolationism in pharmacy anymore…'), as well as use of technology in a patient-centred way and full access to health records. These changes will require workforce development together with appropriate commissioning and contractual arrangements. Community pharmacy is currently undervalued ('…the complete misunderstanding by senior Government officials is very scary') and recent investment in general practice pharmacists rather than community pharmacy was seen as a missed opportunity. CONCLUSIONS: Community pharmacy as a sector could and should be developed to increase health service capacity to address its current challenges. Numerous modifications are required from a range of stakeholders to create the environment in which these changes can occur.

Characterisation of former manufactured gas plant soils using parent and alkylated polycyclic aromatic hydrocarbons and Rock-Eval(6) pyrolysis.

Soils sampled from 10 former manufactured gas plants (MGP) in the UK were investigated using gas chromatography mass spectrometry (GC-MS/MS) and Rock-Eval (6) Pyrolysis (RE). RE is a screening tool used to characterise bulk organic matter in soils via the release of carbon compounds during pyrolysis and oxidation. Both the distributions and concentrations of 30 parent and 21 alkylated polycyclic aromatic hydrocarbons (PAHs) and the parameters of RE were analysed to establish relationships between soils and the MGP processes history. Principal component analysis (PCA) using the PAHs distributions and RE parameters can assist with differentiating between MGP processes. MGP processes utilizing oil provided the clearest results, attributed to petrogenic signatures with high proportions of low molecular weight PAHs. Processes using lower temperature processes were distinguished by higher proportions of high molecular weight PAHs. RE parameters alone were unable to distinguish MGP processes but showed potential in estimating the lability and thus the amount of PAH that could be released from soils. This research provides new insights that may be useful in understanding and characterising the risks posed to human health from PAHs in soils.

Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.

Importance: Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice. Objective: To assess the reporting of observational studies that explicitly aimed to emulate a target trial. Evidence Review: We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation. Findings: A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation. Conclusion and Relevance: In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.

Nonpharmacological approaches for pain and symptoms of depression in people with osteoarthritis: systematic review and meta-analyses.

People with osteoarthritis often experience pain and depression. These meta-analyses examined and compared nonpharmacological randomized controlled trials (RCTs) for pain and symptoms of depression in people living with osteoarthritis. RCTs published up until April 2022 were sourced by searching electronic databases EMBASE, PUBMED & MEDLINE, Web of Science, CINAHL and PEDro. Random-effects meta-analyses were performed to calculate pooled effect sizes (ES) and 95% confidence intervals (CI) for pain and depression. Subgroup analyses examined intervention subtypes. For pain, 29 interventions (n = 4382; 65 ± 6.9 years; 70% female), revealed a significant effect on reducing pain (ES = 0.43, 95% CI [0.25, 0.61], p < 0.001). Effect sizes were significant (p < 0.001) for movement meditation (ES = 0.52; 95% CI [0.35, 0.69]), multimodal approaches (ES = 0.37; 95% CI [0.22, 0.51]), and psychological therapy (ES = 0.21; 95% CI [0.11, 0.31]), and significant (p = 0.046) for resistance exercise (ES = 0.43, 95% CI [- 0.07, 0.94]. Aerobic exercise alone did not improve pain. For depression, 28 interventions (n = 3377; 63 ± 7.0 years; 69% female), revealed a significant effect on reducing depressive symptoms (ES = 0.29, 95% CI [0.08, 0.49], p < 0.001). Effect sizes were significant for movement meditation (ES = 0.30; 95% CI [0.06, 0.55], p = 0.008) and multimodal interventions (ES = 0.12; 95% CI [0.07, 0.18], p < 0.001). Resistance/aerobic exercise or therapy alone did not improve depressive symptoms. Mind-body approaches were more effective than aerobic/resistance exercise or therapy alone for reducing pain and depression in people with osteoarthritis.Systematic review registration: PROSPERO CRD42022338051.

The smallest worthwhile effect on pain intensity of nonsteroidal anti-inflammatory drugs and exercise therapy for acute and chronic low back pain: a benefit-harm trade-off study.

QUESTION: What are the smallest worthwhile effects of nonsteroidal anti-inflammatory drugs (NSAIDs) for people with acute and chronic low back pain (LBP)? What is the smallest worthwhile effect of individualised exercise for people with chronic LBP compared with no intervention? DESIGN: Benefit-harm trade-off study. PARTICIPANTS: Participants were recruited by advertisement on social media and included if they were English-speaking adults in Australia who had non-specific LBP. OUTCOME MEASURE: Pain intensity. RESULTS: A total of 116 people with acute LBP and 230 people with chronic LBP were recruited. For acute LBP, the smallest worthwhile effect of NSAIDs additional to no intervention was a 30% (IQR 10 to 40%) reduction in pain intensity. For chronic LBP, the smallest worthwhile effect of NSAIDs additional to no intervention was a 27.5% (IQR 10 to 50%) reduction in pain intensity. For chronic LBP, the smallest worthwhile effect of exercise additional to no intervention was a 20% (IQR 10 to 40%) reduction in pain intensity. There were small associations between baseline pain, duration of pain and level of exercise and the smallest worthwhile effect of NSAIDs for acute LBP. There were no other clear associations. CONCLUSIONS: For people with LBP, the smallest worthwhile effect of exercise and NSAIDs additional to no intervention is approximately a 20 to 30% reduction in pain. These results can inform the interpretation of the effects of NSAIDs and exercise in randomised trials and meta-analyses, incorporating consumers' perspectives. Further research on comparisons between different interventions and on other core LBP outcomes may inform decision-making. REGISTRATION: OSF osf.io/3erjx/.

Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.

BACKGROUND: Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline. METHODS/DESIGN: The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses. ETHICS AND DISSEMINATION: Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.

Coordination of ε-Caprolactone to a Cationic Niobium(V) Alkoxide Complex: Fundamental Insight into Ring-Opening Polymerization via Coordination-Insertion.

We report three niobium-based initiators for the catalytic ring-opening polymerization (ROP) of ε-caprolactone, exhibiting good activity and molecular weight control. In particular, we have prepared on the gram-scale and fully characterized a monometallic cationic alkoxo-Nb(V) ε-caprolactone adduct representing, to the best of our knowledge, an unprecedented example of a metal complex with an intact lactone monomer and a functional ROP-initiating group simultaneously coordinated at the metal center. At 80 °C, all three systems initiate the immortal solution-state ROP of ε-caprolactone via a coordination-insertion mechanism, which has been confirmed through experimental studies, and is supported by computational data. Natural bond orbital calculations further indicate that polymerization may necessitate isomerization about the metal center between the alkoxide chain and the coordinated monomer. The observations made in this work are expected to inform mechanistic understanding both of amine tris(phenolate)-supported metal alkoxide ROP initiators, including various highly stereoselective systems for the polymerization of lactides and of coordination-insertion-type ROP protocols more broadly.

eLearning improves allied health professionals' knowledge and confidence to manage medically unexplained chronic fatigue states: A randomized controlled trial.

OBJECTIVES: To evaluate the impact of eLearning by allied health professionals on improving the knowledge and confidence to manage people with medically unexplained chronic fatigue states (FS). METHODS: Using a parallel randomized controlled trial design, participants were randomized 1:1 to a 4-week eLearning or wait-list control group. Knowledge and self-reported confidence in clinical skills to implement a therapeutic intervention for patients with FS were assessed at baseline, post-intervention and follow-up. Secondary outcomes (adherence and satisfaction with online education, knowledge retention) were also assessed. Data was analyzed using intention-to-treat. RESULTS: There were 239 participants were randomized (eLearning n = 119, control n = 120), of whom 101 (85%) eLearning and 107 (89%) control participants completed baseline assessments and were included in the analysis. Knowledge (out of 100) improved significantly more in the eLearning group compared to the control group [mean difference (95% CI) 8.6 (5.9 to 11.4), p < 0.001]. Knowledge was reduced in the eLearning group at follow-up but was still significantly higher than baseline [6.0 (3.7 to 8.3), p < 0.001]. Median change (out of 5) in confidence in clinical skills to implement the FS intervention was also significantly greater in the eLearning group compared to the control group [knowledge: eLearning (1.2), control (0); clinical skills: eLearning (1), control (0.1); both p < 0.001)]. Average time spent on the eLearning program was 8.8 h. Most participants (80%) rated the lesson difficulty as at the "right level", and 91% would recommend it to others. CONCLUSIONS: eLearning increased knowledge and confidence to manage FS amongst allied health professionals and was well-accepted. REGISTRATION: ACTRN12616000296437 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370222&isReview=true.