The impact of sport on the physical, psychological and social wellbeing of people with chronic breathlessness: A mixed-methods systematic review.

OBJECTIVE: Sport participation may have quality-of-life benefits for people with chronic breathlessness; however, its feasibility and impact on health are unknown. We aimed to synthesise the scientific literature concerning the impact of sport for people with chronic breathlessness. DATA SOURCES: Searches of MEDLINE, CINAHL, PsycINFO, Embase, SPORTDiscus and Google Scholar were conducted (May 2023). REVIEW METHODS: Studies were included if they assessed the impact of sport with participants who were likely to suffer from chronic breathlessness due to an underlying condition (e.g. severe asthma, heart failure). A convergent-segregated approach to synthesis in accordance with the JBI methodology for mixed-methods reviews was utilised, including meta-analytic and meta-aggregation analyses. RESULTS: A total of 22 studies met the inclusion criteria. Studies sampled 1017 participants from 13 different countries, with sample sizes ranging from 5 to 185. Causes of breathlessness consisted of chronic respiratory diseases (9 studies) and coronary heart disease (13 studies). Design-wise, 18 reported quantitative methods, 3 qualitative, and 1 mixed-methods. CONCLUSIONS: Sports were well-adhered to with only minor/unrelated adverse events reported. Improvements in exercise capacity were observed although there was no impact on health-related quality of life. Other quantitative outcomes extracted varied widely across studies, making it difficult to draw firm conclusions. Participation in sports was reliably recorded at intensity consistent with moderate-to-vigorous activity despite being self-paced. Qualitative themes emphasised the positive elements of sport participation, namely, social cohesion, the capacity to incorporate culture, and the idea that participation is enjoyable rather than a necessary chore to maintain one's health.

An exploration of primary care healthcare professionals' understanding of pain and pain management following a brief pain science education.

BACKGROUND: Persistent pain is a leading cause of disability worldwide yet implementation of clinical guidelines that recommend a biopsychosocial approach remains a challenge in clinical practise. Limited pain understanding amongst clinicians may be partly responsible for this. PURPOSE OF THE STUDY: 1) Qualitatively explore the experience of receiving PSE, understanding of PSE and operationalisation of PSE-related principles in routine clinical practice. 2) Quantitatively explore pain knowledge, attitudes, and behaviours of general practitioners (GPs) and nurse practitioners (NPs) before and after pain science education (PSE). METHODS: An exploratory, single-site, mixed-methods study in north-east England. Fifteen NPs/GPs completed questionnaires and a case-vignette before and after a 70-min face-to-face PSE lecture. Qualitative data were thematically analysed from two focus groups after the intervention. RESULTS: Clinicians' relatively high prior levels of knowledge, attitudes, and behaviour were similar after PSE. Qualitative themes described facilitation of self-reflection on pain management behaviours, and difficulties in operationalising PSE principles in practise including: limited patient rapport; short appointment times; patients' passive and often oppositional biomedical treatment expectations; and clinicians' lack of readily understandable language to communicate with patients. CONCLUSION: The findings highlight the value of PSE perceived by these clinicians who were already favourably inclined towards biopsychosocial pain management. They sought more resources for their personal learning and for communication with patients. Even with such favourable disposition, the practicalities and environment of clinical practice impeded the operationalisation of PSE-related principles. TRIAL REGISTRATION: This study was prospectively registered at ClinicalTrials.Gov ( NCT04587596 ) in October 2020.

International, multi-disciplinary, cross-section study of pain knowledge and attitudes in nursing, midwifery and allied health professions students.

BACKGROUND: Persistent pain is a highly prevalent, global cause of disability. Research suggests that many healthcare professionals are not well equipped to manage pain, and this may be attributable at least in part to undergraduate education. The primary aim of this study was to quantify and compare first and final year nursing, midwifery and allied health professional (NMAHP) students' pain related knowledge and attitudes. The secondary aim was to explore what factors influence students' pain related knowledge and attitudes. METHODS: In this cross-sectional study, 1154 first and final year healthcare students, from 12 universities in five different countries completed the Revised Neurophysiology of Pain Quiz (RNPQ) [knowledge] and the Health Care Providers Pain and Impairment Relationship Scale (HC-PAIRS) [attitudes]. RESULTS: Physiotherapy was the only student group with statistically and clinically improved pain related knowledge [mean difference, 95% CI] (3.4, 3.0 to 3.9, p = 0.01) and attitudes (-17.2, -19.2 to 15.2, p = 0.01) between first and final year. Pain education teaching varied considerably from course to course (0 to 40 h), with greater levels of pain related knowledge and attitudes associated with higher volumes of pain specific teaching. CONCLUSIONS: There was little difference in pain knowledge and attitudes between all first and final year NMAHP students other than physiotherapy. This suggests that for most NMAHP disciplines, undergraduate teaching has little or no impact on students' understanding of pain. There is an urgent need to enhance pain education provision at the undergraduate level in NMAHPs. TRIAL REGISTRATION: The study protocol was prospectively registered at ClinicalTrials.Gov NCT03522857 .

Balance impairment in individuals with COPD: a systematic review with meta-analysis.

BACKGROUND: People with chronic obstructive pulmonary disease (COPD) are four times more likely to fall than healthy peers, leading to increased morbidity and mortality. Poor balance is a major risk factor for falls. This review aims to quantify the extent of balance impairment in COPD, and establish contributing clinical factors, which at present are sparse. METHODS: Five electronic databases were searched, in July 2017 and updated searches were performed in March 2019, for studies comparing balance in COPD with healthy controls. Meta-analyses were conducted on sample mean differences (MD) and reported correlations between balance and clinical factors. Meta-regression was used to quantify the association between mean difference in percentage predicted forced expiratory volume in 1 s (FEV1) and mean balance impairment. Narrative summaries were provided where data were insufficient for meta-analysis. RESULTS: Twenty-three studies were included (n=2751). Meta-analysis indicated COPD patients performed worse than healthy controls on timed up and go (MD=2.77 s, 95% CI 1.46 s to 4.089 s, p=<0.005), single leg stance (MD=-11.75 s, 95% CI -15.12 s to -8.38 s, p=<0.005) and berg balance scale (MD=-6.66, 95% CI -8.95 to -4.37, p=<0.005). The pooled correlation coefficient between balance and reduced quadriceps strength was weak-moderate (r=0.37, 95% CI 0.23 to 0.45, p=<0.005). The relationship between differences in percentage predicted FEV1 and balance were negligible (r2 =<0.04). CONCLUSIONS: Compared with healthy controls, people with COPD have a clinically meaningful balance reduction, which may be related to reduced muscle strength, physical activity and exercise capacity. Our findings support a need to expand the focus of pulmonary rehabilitation to include balance assessment and training, and further exploration of balance impairment in COPD. PROSPERO registration number CRD4201769041.

Design and Characterization of Protein E-PilA, a Candidate Fusion Antigen for Nontypeable Haemophilus influenzae Vaccine.

Nontypeable Haemophilus influenzae (NTHi) is a pathogen known for being a frequent cause of acute otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In the present study, a vaccine antigen based on the fusion of two known NTHi adhesive proteins, protein E (PE) and a pilin subunit (PilA), was developed. The quality of the combined antigen was investigated through functional, biophysical, and structural analyses. It was shown that the PE and PilA individual structures are not modified in the PE-PilA fusion and that PE-PilA assembles as a dimer in solution, reflecting PE dimerization. PE-PilA was found to bind vitronectin by enzyme-linked immunosorbent assay, as isolated PE does. Disulfide bridges were conserved and homogeneous, which was determined by peptide mapping and top-down analysis of PE, PilA, and PE-PilA molecules. Finally, the PE-PilA crystal showed a PE entity with a three-dimensional (3D) structure similar to that of the recently published isolated PE, while the structure of the PilA entity was similar to that of a 3D model elaborated from two other type 4 pilin subunits. Taken together, our observations suggest that the two tethered proteins behave independently within the chimeric molecule and display structures similar to those of the respective isolated antigens, which are important characteristics for eliciting optimal antibody-mediated immunity. PE and PilA can thus be further developed as a single fusion protein in a vaccine perspective, in the knowledge that tethering the two antigens does not perceptibly compromise the structural attributes offered by the individual antigens.

An Exploration of the Experiences and Educational Needs of Patients With Failed Back Surgery Syndrome Receiving Spinal Cord Stimulation.

OBJECTIVE: To explore the experience of spinal cord stimulation (SCS) for patients with failed back surgery syndrome (FBSS). METHODS: Adults with FBSS referred for SCS underwent semistructured interviews at three time points: before their SCS trial, after the trial, and three months after receiving the SCS implant. The face-to-face interviews were audio recorded, transcribed verbatim and analyzed thematically. RESULTS: Twelve adults (8 male, 4 female, aged 38-80 years, pain duration 1-26 years) were recruited. Six themes were identified; 1) What should I expect? 2) Varied outcomes, 3) Understanding pain and this new treatment, 4) Experiences of the SCS journey, 5) Getting used to the device, and 6) Finding out what I need to know. Participants' expectations were varied and the procedures were broadly viewed as minor surgery. Participants' expectations about SCS were not limited to pain relief and included reductions in medication, better sleep, and increased physical activity. Participants' understanding of pain and how SCS purports to work was limited. Throughout the process, practical challenges were identified such as the surgical wound management and battery recharging. Participants received information from multiple sources and identified a range of key information needs including a quick-start guide on how to operate the device and a list of dos and don'ts. CONCLUSIONS: Overall, participants' understanding of SCS was limited. The value participants placed on understanding of the process varied markedly. A list of practical informational needs has been identified. Bespoke, user-friendly, informational tools should be developed from this list to enhance the patient experience of SCS.

Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus Fusion Protein Stabilized in a Noncleaved Prefusion Conformation.

The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state is a superior target for neutralizing antibodies compared to the post-F state. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F conformation, it was compared with a recombinant post-F molecule, called Post-F-XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational stability different from that of Post-F-XC, as shown by chemical denaturation. Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like structure. In contrast, Post-F-XC had a typical elongated conical shape. Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules had common rigid folding core and dynamic regions and provided structural insight for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was shown to deplete hRSV-neutralizing antibodies from human serum more efficiently than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly potent monoclonal antibody specific for the pre-F conformation. In conclusion, this construct presents several pre-F characteristics, does not switch to the post-F conformation, and presents antigenic features required for a protective neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a promising candidate vaccine antigen.IMPORTANCE Human respiratory syncytial virus (RSV) is a global leading cause of infant mortality and adult morbidity. The development of a safe and efficacious RSV vaccine remains an important goal. The RSV class I fusion (F) glycoprotein is considered one of the most promising vaccine candidates, and recent evidences suggest that the prefusion (pre-F) state is a superior target for neutralizing antibodies. Our study presents the physicochemical characterization of Pre-F-GCN4t, a molecule designed to be stabilized in the pre-F conformation. To confirm its pre-F conformation, Pre-F-GCN4t was analyzed in parallel with Post-F-XC, a molecule in the post-F conformation. Our results show that Pre-F-GCN4t presents characteristics of a stabilized pre-F conformation and support its use as an RSV vaccine antigen. Such an antigen may represent a significant advance in the development of an RSV vaccine.

Perceptions of adults with overweight/obesity and chronic musculoskeletal pain: An interpretative phenomenological analysis.

AIMS AND OBJECTIVES: To gain insight into the lived experience of adults with overweight/obesity and chronic musculoskeletal pain. Knowledge gained will inform healthcare professionals about the complexity of the weight-pain relationship and enable more effective engagement with this population. BACKGROUND: Quantitative studies show links between weight and pain. Adults with overweight/obesity are more likely to experience comorbidity; however, qualitative research describing the complexities of the relationship is limited. METHODS: A purposive sample of adults with overweight/obesity and chronic musculoskeletal pain participated in face-to-face interviews. Interviews were audio-recorded, transcribed verbatim and analysed using interpretive phenomenological analysis. RESULTS: Eighteen adults (16 female) aged 29-71, body mass index ≥25-46, participated in this study. Three superordinate themes emerged: "pain as a motivator and barrier to weight loss"; "fear of weight causing more damage"; and "activity is positive." Pain motivates some individuals to lose weight while simultaneously inhibiting weight loss efforts. Participants' perception that extra pressure caused by their weight further damaged joints contributed to fear and catastrophising. Fear is often exacerbated by healthcare professionals' descriptions of musculoskeletal damage, or participants' perception of healthcare professionals' attitude towards people with overweight/obesity. Conversely, individuals acknowledged the benefits of increased activity. CONCLUSION: Adults with overweight/obesity and chronic musculoskeletal pain in this study identified a bidirectional relationship between their weight and pain that challenged their weight loss efforts. Overweight/obesity contributed to fear and catastrophising, which resulted in avoidance of exercise that would have assisted their weight loss. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals need to understand the complex relationship between weight and pain, and their patients' understanding of that relationship. Healthcare professionals should use therapeutic communication to reduce the fear of weight causing damage, and thus promote physical activities that will contribute to weight loss. It is also important to ensure that the language used with this patient group does not stigmatise individuals, or cause or exacerbate fear of normal movement.

Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews.

BACKGROUND: Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning.Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure. OBJECTIVES: To provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions. METHODS: We searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence.We extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death.Due to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively. MAIN RESULTS: We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis.Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi.Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance. AUTHORS' CONCLUSIONS: The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews.There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life.The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.

Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews.

BACKGROUND: Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning.Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure. OBJECTIVES: To provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions. METHODS: We searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence.We extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death.Due to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively. MAIN RESULTS: We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis.Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi.Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance. AUTHORS' CONCLUSIONS: The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews.There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life.The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.

Are there three main subgroups within the patellofemoral pain population? A detailed characterisation study of 127 patients to help develop targeted intervention (TIPPs).

BACKGROUND: Current multimodal approaches for the management of non-specific patellofemoral pain are not optimal, however, targeted intervention for subgroups could improve patient outcomes. This study explores whether subgrouping of non-specific patellofemoral pain patients, using a series of low cost simple clinical tests, is possible. METHOD: The exclusivity and clinical importance of potential subgroups was assessed by applying à priori test thresholds (1 SD) from seven clinical tests in a sample of adult patients with non-specific patellofemoral pain. Hierarchical clustering and latent profile analysis, were used to gain additional insights into subgroups using data from the same clinical tests. RESULTS: 130 participants were recruited, 127 had complete data: 84 (66%) female, mean age 26 years (SD 5.7) and mean body mass index 25.4 (SD 5.83), median (IQR) time between onset of pain and assessment was 24 (7-60) months. Potential subgroups defined by the à priori test thresholds were not mutually exclusive and patients frequently fell into multiple subgroups. Using hierarchical clustering and latent profile analysis three subgroups were identified using 6 of the 7 clinical tests. These subgroups were given the following nomenclature: (1) 'strong', (2) 'weak and tighter' and (3) 'weak and pronated foot'. CONCLUSIONS: We conclude that three subgroups of patellofemoral patients may exist based on the results of six clinical tests which are feasible to perform in routine clinical practice. Further research is needed to validate these findings in other data sets and, if supported by external validation, to see if targeted interventions for these subgroups improve patient outcomes.

Nitroimidazo-oxazole compound DNDI-VL-2098: an orally effective preclinical drug candidate for the treatment of visceral leishmaniasis.

OBJECTIVES: The objective of this study was to identify a nitroimidazo-oxazole lead molecule for the treatment of visceral leishmaniasis (VL). METHODS: A library of 72 nitroimidazo-oxazoles was evaluated in vitro for their antileishmanial activity against luciferase-transfected DD8 amastigotes of Leishmania donovani. On the basis of their in vitro potency and pharmacokinetic properties, the promising compounds were tested in acute BALB/c mouse and chronic hamster models of VL via oral administration and efficacy was evaluated by microscopic counting of amastigotes after Giemsa staining. The best antileishmanial candidates (racemate DNDI-VL-2001) and its R enantiomer (DNDI-VL-2098) were evaluated in vitro against a range of Leishmania strains. These candidates were further studied in a hamster model using various dose regimens. Cytokine and inducible nitric oxide synthase estimations by real-time PCR and nitric oxide generation by Griess assay were also carried out for DNDI-VL-2098. RESULTS: In vitro screening of nitroimidazo-oxazole compounds identified the racemate DNDI-VL-2001 (6-nitroimidazo-oxazole derivative) and its enantiomers as candidates for further evaluation in in vivo models of VL. DNDI-VL-2098 (IC50 of 0.03 µM for the DD8 strain) showed excellent in vivo activity in both mouse and hamster models, with an ED90 value of 3.7 and <25 mg/kg, respectively, and was also found to be very effective against high-grade infection in the hamster model. Our studies revealed that, along with leishmanicidal activity, DNDI-VL-2098 was also capable of inducing host-protective immune cells to suppress Leishmania parasites in hamsters. CONCLUSIONS: These studies led to the identification of compound DNDI-VL-2098 as a preclinical candidate for further drug development as an oral treatment for VL.

Design, synthesis, ADME characterization and antileishmanial evaluation of novel substituted quinoline analogs.

In vitro ADME characterization of the lead compound 1 identified for visceral leishmaniasis was undertaken and further structural analogs were synthesized for antileishmanial screening. Compound 1 was highly permeable in intestinal PAMPA model (31 × 10(-6)cm/s) and was moderately bound to mouse and human plasma proteins (% bound 85-95%), its blood to plasma concentration ratio was less than 1, but the compound was unstable in blood. Compound 1 was found to have no CYP450 liability with CYP2C9, 2C19, 2D6 and 3A4. It showed inhibition with CYP1A2 with an IC50 value of 0.50 µM. Analogs of 1 were synthesized and subsequently characterized for in vitro activity against the intracellular form of Leishmania donovani. Resulting quinolines were found to have similar efficacy as 1 against the parasite. Compounds 8b and 8f were found to be the most active with IC50 values of 0.84 µM and 0.17 µM, respectively compared to 0.22 µM for compound 1. Of all the analogs tested, 8d was stable in hamster, mouse and human liver microsomes but lost the efficacy with an IC50 of 6.42 µM. Based on the in vitro efficacy and DMPK profile, compounds 8b and 8f seem the best candidates to be screened in further assays.

Systematically searching for and assessing the literature for self-management of chronic pain: a lay users' perspective.

BACKGROUND: The Engaging with older adults in the development of strategies for the self management of chronic pain (EOPIC) study aims to design and develop self management strategies to enable older adults to manage their own pain. Involving older adults in research into chronic pain management will better enable the identification and development of strategies that are more appropriate for their use, but how can perspectives really be utilised to the best possible outcomes? METHOD: Seven older adults were recruited through a local advertising campaign to take part. We also invited participants from the local pain services, individuals who had been involved in earlier phase of the EOPIC study and a previous ESRC funded project. The group undertook library training and research skills training to facilitate searching of the literature and identified sources of material. A grading tool was developed using perceived essential criteria identified by the older adults and material was graded according to the criteria within this scale. RESULTS: Fifty-seven resources from over twenty-eight sources were identified. These materials were identified as being easily accessible, readable and relevant. Many of the web based materials were not always easy to find or readily available so they were excluded by the participants. All but one were UK based. Forty-four items were identified as meeting the key criteria for inclusion in the study. This included five key categories as follows; books, internet, magazines, leaflets, CD's/Tapes. CONCLUSION: This project was able to identify a number of exemplars of self management material along with some general rules regarding the categories identified. We must point out that the materials identified were not age specific, were often locally developed and would need to be adapted to older adults with chronic pain. For copyright issues we have not included them in this paper. The key message is really related to the format rather than the content. However, the group acknowledge that these may vary according to the requirements of each individual older adult and therefore recommend the development of a leaflet to help others in their search for resources. This leaflet has been developed as part of Phase IV of the EOPIC study.

Tactile acuity training for patients with chronic low back pain: a pilot randomised controlled trial.

BACKGROUND: Chronic pain can disrupt the cortical representation of a painful body part. This disruption may play a role in maintaining the individual's pain. Tactile acuity training has been used to normalise cortical representation and reduce pain in certain pain conditions. However, there is little evidence for the effectiveness of this intervention for chronic low back pain (CLBP). The primary aim of this study was to inform the development of a fully powered randomised controlled trial (RCT) by providing preliminary data on the effect of tactile acuity training on pain and function in individuals with CLBP. The secondary aim was to obtain qualitative feedback about the intervention. METHODS: In this mixed-methods pilot RCT 15 individuals were randomised to either an intervention (tactile acuity training) or a placebo group (sham tactile acuity training). All participants received 3 sessions of acuity training (intervention or sham) from a physiotherapist and were requested to undertake daily acuity home training facilitated by an informal carer (friend/relative). All participants also received usual care physiotherapy. The primary outcome measures were pain (0-100visual analogue scale (VAS)) and function (Roland Morris Disability Questionnaire (RMDQ)). Participants and their informal carers were invited to a focus group to provide feedback on the intervention. RESULTS: The placebo group improved by the greatest magnitude for both outcome measures, but there was no statistically significant difference (Mean difference (95%CI), p-value) between groups for change in pain (25.6 (-0.7 to 51.9), p = 0.056) or function (2.2 (-1.6 to 6.0), p = 0.237). Comparing the number of individuals achieving a minimally clinically significant improvement, the placebo group had better outcomes for pain with all participants achieving ≥30% improvement compared to only a third of the intervention group (6/6 vs. 3/9, p = 0.036). Qualitatively, participants reported that needing an informal carer was a considerable barrier to the home training component of the study. CONCLUSIONS: This pilot RCT found tactile acuity training to be no more effective than sham tactile acuity training for function and less effective for pain in individuals with CLBP. That the intervention could not be self-applied was a considerable barrier to its use. TRIAL REGISTRATION ISRCTN: ISRCTN98118082.

Utilisation and experience of emergency medical services by patients with back pain: A scoping review.

BACKGROUND: Back pain is recognised as a common reason for people to access emergency medical services (EMS). EMS focus on identifying and treating serious and life-threatening conditions. Back pain frequently has a non-specific cause, however back pain is also a symptom for potentially serious pathology best suited for management by EMS. OBJECTIVES: This scoping review explores how and why patients with back pain access EMS, the care provided, and patients' and clinicians' perceptions of EMS. METHODS: The established methodology advocated by the Joanna Briggs Institute was followed. Literature was identified via a comprehensive search of six databases as well as grey literature searching. Data was extracted to form a narrative review supported by summary tables and figures. RESULTS: The review included 144 papers across the last 36 years, with half the papers published since 2018, the majority from the USA and Australia. Rates of back pain presentation range from 1 to 9% depending on the definition used, with the rate of serious pathology higher than in primary care. Patients present due to concerns about their condition, positive perceptions of the care provided by EMS and difficulty in accessing primary care. Imaging and opioids are widely used, blood markers may aid diagnosis of serious pathology, whilst physiotherapists in Emergency Departments may support management of patients without serious pathology. CONCLUSIONS: Back pain is a common reason for EMS presentation. Whilst non-specific back pain is the most common diagnosis further research to support the recognition and care of serious cases would be beneficial.

Acceptability and feasibility of virtual reality to promote health literacy in primary care from the health professional's view: A qualitative study.

OBJECTIVE: The development of health literacy is important in the management of chronic pain and virtual reality may be an effective medium for its development. This study aims to understand the usability and acceptability of a virtual reality-based pain education system for the facilitation of health literacy. METHODS: Semi-structured interviews were conducted with health professionals who had used a VR-based pain education system within their clinical practice, to explore perceptions of feasibility. Data collection and analyses were informed by the Unified Theory of Acceptance and Use of Technology and the Integrated Model of Health Literacy. RESULTS: From 10 participants, the VR-based system was considered feasible in providing immersive experiential learning which addressed patient understanding and health-related communication. CONCLUSION: VR appears to be perceived as an acceptable and feasible technology to support the development of health literacy in people with chronic pain. Its largest perceived benefit was its capacity to provide an immersive and entertaining alternative to conventional methods of pain education. PRACTICE IMPLICATIONS: Virtual reality is considered as a feasible method of facilitating patient understanding and health-related communication related to chronic pain. Feasibility of such a tool relies clinically on time available, social expectations of VR, and the role of immersive and experiential learning within the management of chronic pain.

The Test-Retest Reliability of Pain Outcome Measures in People With Phantom Limb Pain.

OBJECTIVES: To quantify the test-retest reliability of 3 patient-reported outcome measures of pain for people living with phantom limb pain (PLP) and assess the impact of test-retest errors on future research and clinical decisions. METHODS: Thirty-nine participants (30 males), mean (SD) age: 55 (16), mean (SD) years postamputation: 6.8 (8.3), reported their PLP levels on a visual analogue scale (VAS) for pain intensity, the revised short-form McGill Pain Questionnaire (SF-MPQ-2), and a pain diary, on 2 occasions 7 to 14 days apart. Mean systematic change, within-subjects SD, limits of agreement (LOA), coefficient of variation, and the intraclass correlation coefficient (ICC) were quantified alongside their respective 95% confidence intervals (95% CIs). RESULTS: Systematic learning effects (mean changes) were not clinically relevant across the VAS, SF-MPQ-2, and pain diary. Within-subject SDs (95% CI) were 11.8 (9.6-15.3), 0.9 (0.7-1.2), and 8.6 (6.9-11.5), respectively. LOA (95% CI) were 32.6 (26.5-42.4), 2.5 (2-3.3), and 23.9 (19.2-31.8), respectively. ICCs (95% CI) were 0.8 (0.6-0.9), 0.8 (0.7-0.9), and 0.9 (0.8-0.9), respectively, but may have been inflated by sample heterogeneity. The test-retest errors allowed detection of clinically relevant effect sizes with feasible sample sizes in future studies, but individual errors were large. DISCUSSION: For people with PLP, a pain intensity VAS, the SF-MPQ-2, and a pain diary show an acceptable level of intersession reliability for use in future clinical trials with feasible sample sizes. Nevertheless, the random error observed for all 3 of the pain outcome measures suggests they should be interpreted with caution in case studies and when monitoring individuals' clinical status and progress.

Exercise-based interventions targeting balance and falls in people with COPD: a systematic review and meta-analysis.

INTRODUCTION: This review quantifies the mean treatment effect of exercise-based interventions on balance and falls risk in people with COPD. METHODS: A structured search strategy (2000-2023) was applied to eight databases to identify studies evaluating the impact of exercise-based interventions (≥14 days in duration) on balance or falls in people with COPD. Pooled mean treatment effects (95% confidence intervals (CIs), 95% prediction intervals (PIs)) were calculated for outcomes reported in five or more studies. Inter-individual response variance and the promise of behaviour change techniques (BCTs) were explored. RESULTS: 34 studies (n=1712) were included. There were greater improvements in balance post intervention compared to controls for the Berg Balance Scale (BBS) (mean 2.51, 95% CI 0.22-4.80, 95% PI -4.60-9.63), Timed Up and Go (TUG) test (mean -1.12 s, 95% CI -1.69- -0.55 s, 95% PI -2.78-0.54 s), Single-Leg Stance (SLS) test (mean 3.25 s, 95% CI 2.72-3.77 s, 95% PI 2.64-3.86 s) and Activities-specific Balance Confidence (ABC) scale (mean 8.50%, 95% CI 2.41-14.58%, 95% PI -8.92-25.92%). Effect on falls remains unknown. Treatment effects were larger in male versus mixed-sex groups for the ABC scale and SLS test, and in balance training versus other exercise-based interventions for the BBS and TUG test. Falls history was not associated with changes in balance. Meta-analysis of individual response variance was not possible and study-level results were inconclusive. Eleven promising BCTs were identified (promise ratio ≥2). CONCLUSION: Evidence for the effect of exercise-based interventions eliciting clinically important improvements in balance for people with COPD is weak, but targeted balance training produces the greatest benefits. Future exercise interventions may benefit from inclusion of the identified promising BCTs.

Guidance on the management of pain in older people.

This guidance document reviews the epidemiology and management of pain in older people via a literature review of published research. The aim of this document is to inform health professionals in any care setting who work with older adults on best practice for the management of pain and to identify where there are gaps in the evidence that require further research. The assessment of pain in older people has not been covered within this guidance and can be found in a separate document (http://www.britishpainsociety.org/pub_professional.htm#assessmentpop). Substantial differences in the population, methods and definitions used in published research makes it difficult to compare across studies and impossible to determine the definitive prevalence of pain in older people. There are inconsistencies within the literature as to whether or not pain increases or decreases in this age group, and whether this is influenced by gender. There is, however, some evidence that the prevalence of pain is higher within residential care settings. The three most common sites of pain in older people are the back; leg/knee or hip and 'other' joints. In common with the working-age population, the attitudes and beliefs of older people influence all aspects of their pain experience. Stoicism is particularly evident within this cohort of people. Evidence from the literature search suggests that paracetamol should be considered as first-line treatment for the management of both acute and persistent pain, particularly that which is of musculoskeletal origin, due to its demonstrated efficacy and good safety profile. There are few absolute contraindications and relative cautions to prescribing paracetamol. It is, however, important that the maximum daily dose (4 g/24 h) is not exceeded. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution in older people after other safer treatments have not provided sufficient pain relief. The lowest dose should be provided, for the shortest duration. For older adults, an NSAID or cyclooxygenase-2 (COX-2) selective inhibitor should be co-prescribed with a proton pump inhibitor (PPI), and the one with the lowest acquisition cost should be chosen. All older people taking NSAIDs should be routinely monitored for gastrointestinal, renal and cardiovascular side effects, and drug­drug and drug­disease interactions. Opioid therapy may be considered for patients with moderate or severe pain, particularly if the pain is causing functional impairment or is reducing their quality of life. However, this must be individualised and carefully monitored. Opioid side effects including nausea and vomiting should be anticipated and suitable prophylaxis considered. Appropriate laxative therapy, such as the combination of a stool softener and a stimulant laxative, should be prescribed throughout treatment for all older people who are prescribed opioid therapy. Tricyclic antidepressants and anti-epileptic drugs have demonstrated efficacy in several types of neuropathic pain. But, tolerability and adverse effects limit their use in an older population. Intra-articular corticosteroid injections in osteoarthritis of the knee are effective in relieving pain in the short term, with little risk of complications and/or joint damage. Intra-articular hyaluronic acid is effective and free of systemic adverse effects. It should be considered in patients who are intolerant to systemic therapy. Intra-articular hyaluronic acid appears to have a slower onset of action than intra-articular steroids, but the effects seem to last longer. The current evidence for the use of epidural steroid injections in the management of sciatica is conflicting and, until further larger studies become available, no firm recommendations can be made. There is, however, a limited body of evidence to support the use of epidural injections in spinal stenosis. The literature review suggests that assistive devices are widely used and that the ownership of devices increases with age. Such devices enable older people with chronic pain to live in the community. However, they do not necessarily reduce pain and can increase pain if used incorrectly. Increasing activity by way of exercise should be considered. This should involve strengthening, flexibility, endurance and balance, along with a programme of education. Patient preference should be given serious consideration. A number of complementary therapies have been found to have some efficacy among the older population, including acupuncture, transcutaneous electrical nerve stimulation (TENS) and massage. Such approaches can affect pain and anxiety and are worth further investigation. Some psychological approaches have been found to be useful for the older population, including guided imagery, biofeedback training and relaxation. There is also some evidence supporting the use of cognitive behavioural therapy (CBT) among nursing home populations, but of course these approaches require training and time. There are many areas that require further research, including pharmacological management where approaches are often tested in younger populations and then translated across. Prevalence studies need consistency in terms of age, diagnosis and terminology, and further work needs to be done on evaluating non-pharmacological approaches.