New initiation of opioids, benzodiazepines and antipsychotics following hospitalization for COVID-19.

BACKGROUND: Patients newly initiated on opioids (OP), benzodiazepines (BZD), and antipsychotics (AP) during hospitalization are often prescribed these on discharge. Implications of this practice on outcomes remains unexplored. OBJECTIVE: To explore the prevalence and risk factors of new initiation of select OP, BZD and AP among patients requiring in-patient stays. Test the hypothesis that new prescriptions are associated with higher odds of readmission or death within 28 days of discharge. DESIGN: Single center retrospective cohort study. SETTING AND PARTICIPANTS: Patients admitted to a tertiary-level medical center with either a primary diagnosis of RT-PCR positive for COVID-19 or high index of clinical suspicion thereof. INTERVENTION: None. MAIN OUTCOME AND MEASURES: Exposure was the new initiation of select common OP, BZD, and AP which were continued on hospital discharge. Outcome was a composite of 28-day readmission or death following index admission. Multivariable logistic regression was used to assess patient mortality or readmission within 28 days of discharge associated with new prescriptions at discharge. RESULTS: One thousand three hundred and nineteen patients were included in the analysis. 11.3% (149/1319) were discharged with a new prescription of select OP, BZD, or AP either alone or in combination. OP (110/149) were most prescribed followed by BZD (41/149) and AP (22/149). After adjusting for unbalanced confounders, new prescriptions (adjusted odds ratio: 2.44, 95% confidence interval: 1.42-4.12; p = .001) were associated with readmission or death within 28 days of discharge. One in nine patients admitted with a diagnosis of COVID-19 or high clinical suspicion thereof were discharged with a new prescription of either OP, BZD or AP. New prescriptions were associated with higher odds of 28-day readmission or death. Strengthening medication reconciliation processes focused on these classes may reduce avoidable harm.

Swedish translation and psychometric testing of the Self-Conscious Emotions in COPD Questionnaire.

Assessment of self-conscious emotions is important to develop tailored interventions for people with chronic obstructive pulmonary disease (COPD). Previous instruments have largely been developed for mental health populations. The Self-Conscious Emotions in COPD Questionnaire was the first instrument to assess self-conscious emotions in people with COPD, but it was only available in English. The aim was to translate the Self-Conscious Emotions in COPD Questionnaire into Swedish and to evaluate its psychometric properties and internal structure in a Swedish context. The translation process included forward and backward translation, a multidisciplinary meeting, assessment of content validity, and cognitive interviews. The translated instrument was tested in a sample of 173 people with COPD between September 2021 and September 2022. Parallel analysis (PA), exploratory factor analysis (EFA), and test-retest reliability was performed. The content validity index (CVI) for the instrument was 0.88. Based on the PA, an EFA with a two-factor solution was conducted, with a high Cronbach's alpha (0.786-0.821), and one item about self-blame was excluded. The two factors were labelled: The burden of living with a disability and The desire to hide vulnerability. Test-retest reliability showed no difference between scale scores on factor or item level, except for one item. The Swedish Self-Conscious Emotions in COPD showed good validity and reliability. One item was excluded from the two subscales, indicating that the instrument needs to be further developed to cover the concept of self-blame. The instrument is expected to be a valuable tool for assessing self-conscious emotions in people with COPD.

Investigating mother-child inter-brain synchrony in a naturalistic paradigm: A functional near infrared spectroscopy (fNIRS) hyperscanning study.

Successful social interactions between mothers and children are hypothesised to play a significant role in a child's social, cognitive and language development. Earlier research has confirmed, through structured experimental paradigms, that these interactions could be underpinned by coordinated neural activity. Nevertheless, the extent of neural synchrony during real-life, ecologically valid interactions between mothers and their children remains largely unexplored. In this study, we investigated mother-child inter-brain synchrony using a naturalistic free-play paradigm. We also examined the relationship between neural synchrony, verbal communication patterns and personality traits to further understand the underpinnings of brain synchrony. Twelve children aged between 3 and 5 years old and their mothers participated in this study. Neural synchrony in mother-child dyads were measured bilaterally over frontal and temporal areas using functional Near Infra-red Spectroscopy (fNIRS) whilst the dyads were asked to play with child-friendly toys together (interactive condition) and separately (independent condition). Communication patterns were captured via video recordings and conversational turns were coded. Compared to the independent condition, mother-child dyads showed increased neural synchrony in the interactive condition across the prefrontal cortex and temporo-parietal junction. There was no significant relationship found between neural synchrony and turn-taking and between neural synchrony and the personality traits of each member of the dyad. Overall, we demonstrate the feasibility of measuring inter-brain synchrony between mothers and children in a naturalistic environment. These findings can inform future study designs to assess inter-brain synchrony between parents and pre-lingual children and/or children with communication needs.

Lack of detection of SARS-CoV-2 in British wildlife 2020-21 and first description of a stoat (Mustela erminea) Minacovirus.

Repeat spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into new hosts has highlighted the critical role of cross-species transmission of coronaviruses and establishment of new reservoirs of virus in pandemic and epizootic spread of coronaviruses. Species particularly susceptible to SARS-CoV-2 spillover include Mustelidae (mink, ferrets and related animals), cricetid rodents (hamsters and related animals), felids (domestic cats and related animals) and white-tailed deer. These predispositions led us to screen British wildlife with sarbecovirus-specific quantitative PCR and pan coronavirus PCR assays for SARS-CoV-2 using samples collected during the human pandemic to establish if widespread spillover was occurring. Fourteen wildlife species (n=402) were tested, including: two red foxes (Vulpes vulpes), 101 badgers (Meles meles), two wild American mink (Neogale vison), 41 pine marten (Martes martes), two weasels (Mustela nivalis), seven stoats (Mustela erminea), 108 water voles (Arvicola amphibius), 39 bank voles (Myodes glareolous), 10 field voles (Microtus agrestis), 15 wood mice (Apodemus sylvaticus), one common shrew (Sorex aranaeus), two pygmy shrews (Sorex minutus), two hedgehogs (Erinaceus europaeus) and 75 Eurasian otters (Lutra lutra). No cases of SARS-CoV-2 were detected in any animals, but a novel minacovirus related to mink and ferret alphacoronaviruses was detected in stoats recently introduced to the Orkney Islands. This group of viruses is of interest due to pathogenicity in ferrets. The impact of this virus on the health of stoat populations remains to be established.

Influences of COVID-19 vaccination policy on students' vaccine acceptance.

Background: Higher education institutions (HEIs) developed and implemented a mandatory COVID-19 vaccination policy to facilitate vaccine acceptance and vaccination among universities' staff and students. However, little is known about influences of the mandatory vaccination policy on health science students at a university and they tend to result in vaccine hesitancy. Aim: To explore the influences of the mandatory COVID-19 vaccine policy on health sciences students' vaccine acceptance at HEIs in South Africa. Setting: The study was conducted in one of the universities in the Western Cape Province, South Africa. Methods: An interpretive qualitative exploratory-descriptive research was conducted with 10 participants who were selected using the purposive sampling method to participate in semi-structured interviews. Data were audio-recorded, transcribed verbatim and thematically analysed. Results: Two themes and 12 sub-themes were identified during the data analysis, namely individual and group influencing factors, as well as contextual influencing factors. Conclusion: This study revealed that the COVID-19 vaccination mandatory policy influenced the students' quality of life, academic performance and well-being. The findings from this study indicate that there were perceived barriers related to personal and contextual influencing factors than benefits of COVID-19 vaccination. Contribution: The understanding of and insight into the influences of the mandatory vaccination policy provided a basis for further strategies that may be developed to address COVID-19 vaccine infodemic, vaccine hesitancy and its risk effects. This can be done through collaboration with different stakeholders to educate health science students about the perceived benefits of COVID-19 vaccination.

Estimating surgery, radiotherapy and systemic anti-cancer therapy treatment costs for cancer patients by stage at diagnosis.

BACKGROUND: The increasing burden of cancer has economic implications for the healthcare system in England. However, there is limited evidence on the cost of cancer treatment. We calculated the costs of initial cancer treatment (resection, radiotherapy, systemic anti-cancer therapy [SACT]) based on stage at diagnosis. METHODS: Data from England's National Cancer Registration Dataset were matched to English Hospital, Radiotherapy and SACT data for breast, lung, prostate, colon and rectal cancers diagnosed between 2016 and 2018. Treatment data were matched to National Schedule of Reference Costs data to calculate the cost of each treatment event. RESULTS: Breast, colon and rectal cancers treated with resection, radiotherapy or SACT had increasing costs with later stage at diagnosis; costs for lung and prostate cancers were lower at stages 1 and 4 compared to stages 2 and 3. In general, surgery and SACT were the most expensive treatments. Radiotherapy and SACT costs showed little change across stages 1-3; radiotherapy costs decreased in stage 4, while SACT costs increased. CONCLUSIONS: This analysis estimates initial treatment costs by stage based on observed data. Future research can build on this to provide more comprehensive costings associated with cancer; this is important for future planning of cancer services.

Meningeal P2X7 Signaling Mediates Migraine-Related Intracranial Mechanical Hypersensitivity.

Cortical spreading depolarization (CSD) is a key pathophysiological event that underlies visual and sensory auras in migraine. CSD is also thought to drive the headache phase in migraine by promoting the activation and mechanical sensitization of trigeminal primary afferent nociceptive neurons that innervate the cranial meninges. The factors underlying meningeal nociception in the wake of CSD remain poorly understood but potentially involve the parenchymal release of algesic mediators and damage-associated molecular patterns, particularly ATP. Here, we explored the role of ATP-P2X purinergic receptor signaling in mediating CSD-evoked meningeal afferent activation and mechanical sensitization. Male rats were subjected to a single CSD episode. In vivo, extracellular single-unit recording was used to measure meningeal afferent ongoing activity changes. Quantitative mechanical stimuli using a servomotor force-controlled stimulator assessed changes in the afferent's mechanosensitivity. Manipulation of meningeal P2X receptors was achieved via local administration of pharmacological agents. Broad-spectrum P2X receptor inhibition, selective blockade of the P2X7 receptor, and its related Pannexin 1 channel suppressed CSD-evoked afferent mechanical sensitization but did not affect the accompanying afferent activation response. Surprisingly, inhibition of the pronociceptive P2X2/3 receptor did not affect the activation or sensitization of meningeal afferents post-CSD. P2X7 signaling underlying afferent mechanosensitization was localized to the meninges and did not affect CSD susceptibility. We propose that meningeal P2X7 and Pannexin 1 signaling, potentially in meningeal macrophages or neutrophils, mediates the mechanical sensitization of meningeal afferents, which contributes to migraine pain by exacerbating the headache during normally innocuous physical activities.SIGNIFICANCE STATEMENT Activation and sensitization of meningeal afferents play a key role in migraine headache, but the underlying mechanisms remain unclear. Here, using a rat model of migraine with aura involving cortical spreading depolarization (CSD), we demonstrate that meningeal purinergic P2X7 signaling and its related Pannexin 1 pore, but not nociceptive P2X2/3 receptors, mediate prolonged meningeal afferent sensitization. Additionally, we show that meningeal P2X signaling does not contribute to the increased afferent ongoing activity in the wake of CSD. Our finding points to meningeal P2X7 signaling as a critical mechanism underlying meningeal nociception in migraine, the presence of distinct mechanisms underlying the activation and sensitization of meningeal afferents in migraine, and highlight the need to target both processes for effective migraine therapy.

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.

The Association of Pain with Incident Falls in People with Chronic Obstructive Pulmonary Disease: Evidence from the English Longitudinal Study of Ageing.

People with chronic obstructive pulmonary disease (COPD) have a higher prevalence of pain and a greater risk of falls than their healthy peers. As pain has been associated with an increased risk of falls in older adults, this study investigated the association between pain and falls in people with COPD compared to healthy controls. Data from the English Longitudinal Study of Ageing were used to establish an association between pain and falls when modelled with a generalised ordinal logistic regression and adjusted for sex, age, wealth, and education (complete case analysis only; n = 806 COPD, n = 3898 healthy controls). The odds were then converted to the predicted probabilities of falling. The predicted probability of falling for people with COPD was greater across all pain categories than for healthy controls; for COPD with (predicted probability % [95%CI]), no pain was 20% [17 to 25], with mild pain was 28% [18 to 38], with moderate pain was 28% [22 to 34] with severe pain was 39% [30 to 47] and for healthy controls with no pain was 17% [16 to 18], mild pain 22% [18 to 27], moderate pain 25% [20 to 29] and severe pain 27% [20 to 35]. The probability of falling increased across pain categories in individuals with COPD, with the most severe pain category at a nearly 40% probability of falling, indicating a potential interaction between COPD and pain.

Rehabilitation for People with Respiratory Disease and Frailty: An Official American Thoracic Society Workshop Report.

People with respiratory disease have increased risk of developing frailty, which is associated with worse health outcomes. There is growing evidence of the role of rehabilitation in managing frailty in people with respiratory disease. However, several challenges remain regarding optimal methods of identifying frailty and delivering rehabilitation for this population. The aims of this American Thoracic Society workshop were to outline key definitions and concepts around rehabilitation for people with respiratory disease and frailty, synthesize available evidence, and explore how programs may be adapted to align to the needs and experiences of this population. Across two half-day virtual workshops, 20 professionals from diverse disciplines, professions, and countries discussed key developments and identified opportunities for future research, with additional input via online correspondence. Participants highlighted a "frailty rehabilitation paradox" whereby pulmonary rehabilitation can effectively reduce frailty, but programs are challenging for some individuals with frailty to complete. Frailty should not limit access to rehabilitation; instead, the identification of frailty should prompt comprehensive assessment and tailored support, including onward referral for additional specialist input. Exercise prescriptions that explicitly consider symptom burden and comorbidities, integration of additional geriatric or palliative care expertise, and/or preemptive planning for disruptions to participation may support engagement and outcomes. To identify and measure frailty in people with respiratory disease, tools should be selected on the basis of sensitivity, specificity, responsiveness, and feasibility for their intended purpose. Research is required to expand understanding beyond the physical dimensions of frailty and to explore the merits and limitations of telerehabilitation or home-based pulmonary rehabilitation for people with chronic respiratory disease and frailty.

Sarbecoviruses of British horseshoe bats; sequence variation and epidemiology.

Horseshoe bats are the natural hosts of the Sarbecovirus subgenus that includes SARS-CoV and SARS-CoV- 2. Despite the devastating impact of the COVID-19 pandemic, there is still little known about the underlying epidemiology and virology of sarbecoviruses in their natural hosts, leaving large gaps in our pandemic preparedness. Here we describe the results of PCR testing for sarbecoviruses in the two horseshoe bat species (Rhinolophus hipposideros and R. ferrumequinum) present in Great Britain, collected in 2021-22 during the peak of COVID-19 pandemic. One hundred and ninety seven R. hipposideros samples from 33 roost sites and 277 R. ferrumequinum samples from 20 roost sites were tested. No coronaviruses were detected in any samples from R. ferrumequinum whereas 44 and 56 % of individual and pooled (respectively) faecal samples from R. hipposideros across multiple roost sites tested positive in a sarbecovirus-specific qPCR. Full genome sequences were generated from three of the positive samples (and partial genomes from two more) using Illumina RNAseq on unenriched samples. Phylogenetic analyses showed that the obtained sequences belong to the same monophyletic clade, with >95 % similarity to previously-reported European isolates from R. hipposideros. The sequences differed in the presence or absence of accessory genes ORF 7b, 9b and 10. All lacked the furin cleavage site of SARS-CoV-2 spike gene and are therefore unlikely to be infective for humans. These results demonstrate a lack, or at least low incidence, of SARS-CoV-2 spill over from humans to susceptible GB bats, and confirm that sarbecovirus infection is widespread in R. hipposideros. Despite frequently sharing roost sites with R. ferrumequinum, no evidence of cross-species transmission was found.

Non-pharmacological and non-invasive interventions for chronic pain in people with chronic obstructive pulmonary disease: A systematic review without meta-analysis.

OBJECTIVES: Chronic Obstructive Pulmonary Disease (COPD) is complicated by chronic pain. People with COPD report higher pain prevalence than the general population. Despite this, chronic pain management is not reflected in current COPD clinical guidelines and pharmacological treatments are often ineffective. We conducted a systematic review that aimed to establish the efficacy of existing non-pharmacological and non-invasive interventions on pain and identify behaviour change techniques (BCTs) associated with effective pain management. METHODS: A systematic review was conducted with reference to Preferred Reporting Items for Systematic Review (PRISMA) [1], Systematic review without Meta analysis (SWIM) standards [2] and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines [3]. We searched 14 electronic databases for controlled trials of non-pharmacological and non-invasive interventions where the outcome measure assessed pain or contained a pain subscale. RESULTS: Twenty-nine studies were identified involving 3,228 participants. Seven interventions reported a minimally important clinical difference in pain outcomes, although only two of these reached statistical significance (p < 0.05). A third study reported statistically significant outcomes, but this was not clinically significant (p = 0.0273). Issues with intervention reporting prevented identification of active intervention ingredients (i.e., BCTs). CONCLUSIONS: Pain appears to be a meaningful issue for many individuals with COPD. However, intervention heterogeneity and issues with methodological quality limit certainty about the effectiveness of currently available non-pharmacological interventions. An improvement in reporting is required to enable identification of active intervention ingredients associated with effective pain management.

Online comic-based art workshops as an innovative patient and public involvement and engagement approach for people with chronic breathlessness.

BACKGROUND: Talking about breathlessness can be emotionally challenging. People can feel a sense of illegitimacy and discomfort in some research contexts. Comic-based illustration (cartooning) offers an opportunity to communicate in a more creative and inclusive way. We used cartooning in patient and public involvement and engagement (PPIE) work to explore symptoms of breathlessness and their impact on peoples' everyday lives. MAIN BODY: Five, 90-min cartooning workshops were delivered online to members of Breathe Easy Darlington (UK). The workshop series involved 5-10 Breathe Easy members and were facilitated by a professional cartoonist supported by three researchers. The experience of living with breathlessness was represented via illustrations of cartoon characters and ideas explored in subsequent conversations. Cartooning was fun and the majority found it a nostalgic experience. Sharing the experience helped the research team develop new understandings of breathlessness and fostered relationships with the Breathe Easy members. The illustrations showed characters leaning against objects, sweating and sitting down, demonstrating living with the sensation of not being in control. CONCLUSION: Comic-based art, as a fun and innovative PPIE approach. It facilitated the research team becoming embedded in an existing group who will act as PPIE members on a long-term research programme. Illustrations enabled storytelling and fostered novel insights into the lived experiences of people with breathlessness including sensations of a loss of control, disorientation, and unsteadiness. This will impact on work investigating balance in people with chronic obstructive pulmonary disease. This model has potential to be applied in a range of PPIE and research contexts.

Talking about breathlessness can be difficult and cause feelings of anxiety. Involving people with breathlessness in research activities can also be challenging. Research contexts can make people feel uncomfortable as they may struggle to understand and feel like they don't belong. Comic-based illustration (cartooning) offers an opportunity to communicate in a different way. Cartooning was used with members of Breathe Easy Darlington, a support group for people with breathlessness, as a way of helping the research team understand how breathlessness impacts daily lives. Five 90-min cartooning workshops were delivered online and involved 5­10 Breathe Easy members per session. The sessions were led by a professional cartoonist whilst the research team facilitated discussions about breathlessness and related issues. The experience of living with breathlessness was illustrated via cartoon characters and ideas were explored through conversations about the illustrations. People found cartooning fun and sharing the experience with the research team helped them to become part of an existing group who will support a long-term research project directly impacting research investigating balance in people with lung disease. The Breathe Easy members were able to tell their stories via illustrations allowing the research team an insight into different aspects of living with breathlessness. The illustrations showed characters leaning against trees and chairs, sweating and sitting down. The need for physical support caused embarrassment, while people struggled to appear "normal". Conversations about the illustrations revealed that the idea of "balance" aligns with a loss of control, disorientation, and unsteadiness which causes intense fear and shame.

Meningeal P2X7 signaling mediates migraine-related intracranial mechanical hypersensitivity.

Cortical spreading depolarization (CSD) is a key pathophysiological event that underlies visual and sensory auras in migraine. CSD is also thought to drive the headache phase in migraine by promoting the activation and mechanical sensitization of trigeminal primary afferent nociceptive neurons that innervate the cranial meninges. The factors underlying meningeal nociception in the wake of CSD remain poorly understood but potentially involve the parenchymal release of algesic mediators and damage-associated molecular patterns, particularly ATP. Here, we explored the role of ATP-P2X purinergic receptor signaling in mediating CSD-evoked meningeal afferent activation and mechanical sensitization. Male rats were subjected to a single CSD episode. In vivo, extracellular single-unit recording was used to measure meningeal afferent ongoing activity changes. Quantitative mechanical stimuli using a servomotor force-controlled stimulator assessed changes in the afferent's mechanosensitivity. Manipulation of meningeal P2X receptors was achieved via local administration of pharmacological agents. Broad-spectrum P2X receptor inhibition, selective blockade of the P2X7 receptor, and its related pannexin 1 channel suppressed CSD-evoked afferent mechanical sensitization but did not affect the accompanying afferent activation response. Surprisingly, inhibition of the pronociceptive P2X2/3 receptor did not affect the activation or sensitization of meningeal afferents post-CSD. P2X7 signaling underlying afferent mechanosensitization was localized to the meninges and did not affect CSD susceptibility. We propose that meningeal P2X7 and Pannexin 1 signaling, potentially in meningeal macrophages or neutrophils, mediates the mechanical sensitization of meningeal afferents, which contributes to migraine pain by exacerbating the headache during normally innocuous physical activities. Significance Statement: Activation and sensitization of meningeal afferents play a key role in migraine headache, but the underlying mechanisms remain unclear. Here, using a rat model of migraine with aura involving cortical spreading depolarization (CSD), we demonstrate that meningeal purinergic P2X7 signaling and its related Pannexin 1 pore, but not nociceptive P2X2/3 receptors, mediate prolonged meningeal afferent sensitization. Additionally, we show that meningeal P2X signaling does not contribute to the increased afferent ongoing activity in the wake of CSD. Our finding points to meningeal P2X7 signaling as a critical mechanism underlying meningeal nociception in migraine, the presence of distinct mechanisms underlying the activation and sensitization of meningeal afferents in migraine, and highlight the need to target both processes for effective migraine therapy.

Prehabilitation in elective patients undergoing cardiac surgery: a randomised control trial (THE PrEPS TRIAL) - a study protocol.

INTRODUCTION: Prehabilitation prior to surgery has been shown to reduce postoperative complications, reduce length of hospital stay and improve quality of life after cancer and limb reconstruction surgery. However, there are minimal data on the impact of prehabilitation in patients undergoing cardiac surgery, despite the fact these patients are generally older and have more comorbidities and frailty. This trial will assess the feasibility and impact of a prehabilitation intervention consisting of exercise and inspiratory muscle training on preoperative functional exercise capacity in adult patients awaiting elective cardiac surgery, and determine any impact on clinical outcomes after surgery. METHODS AND ANALYSIS: PrEPS is a randomised controlled single-centre trial recruiting 180 participants undergoing elective cardiac surgery. Participants will be randomised in a 1:1 ratio to standard presurgical care or standard care plus a prehabilitation intervention. The primary outcome will be change in functional exercise capacity measured as change in the 6 min walk test distance from baseline. Secondary outcomes will evaluate the impact of prehabilitation on preoperative and postoperative outcomes including; respiratory function, health-related quality of life, anxiety and depression, frailty, and postoperative complications and resource use. This trial will evaluate if a prehabilitation intervention can improve preoperative physical function, inspiratory muscle function, frailty and quality of life prior to surgery in elective patients awaiting cardiac surgery, and impact postoperative outcomes. ETHICS AND DISSEMINATION: A favourable opinion was given by the Sheffield Research Ethics Committee in 2019. Trial findings will be disseminated to patients, clinicians, commissioning groups and through peer-reviewed publication. TRIAL REGISTRATION NUMBER: ISRCTN13860094.

Variation in suspected cancer referral pathways in primary care: comparative analysis across the International Benchmarking Cancer Partnership.

BACKGROUND: International variations in cancer outcomes persist and may be influenced by differences in the accessibility and organisation of cancer patient pathways. More evidence is needed to understand to what extent variations in the structure of primary care referral pathways for cancer investigation contribute to differences in the timeliness of diagnoses and cancer outcomes in different countries. AIM: To explore the variation in primary care referral pathways for the management of suspected cancer across different countries. DESIGN AND SETTING: Descriptive comparative analysis using mixed methods across the International Cancer Benchmarking Partnership (ICBP) countries. METHOD: Schematics of primary care referral pathways were developed across 10 ICBP jurisdictions. The schematics were initially developed using the Aarhus statement (a resource providing greater insight and precision into early cancer diagnosis research) and were further supplemented with expert insights through consulting leading experts in primary care and cancer, existing ICBP data, a focused review of existing evidence on the management of suspected cancer, published primary care cancer guidelines, and evaluations of referral tools and initiatives in primary care. RESULTS: Referral pathway schematics for 10 ICBP jurisdictions were presented alongside a descriptive comparison of the organisation of primary care management of suspected cancer. Several key areas of variation across countries were identified: inflexibility of referral pathways, lack of a managed route for non-specific symptoms, primary care practitioner decision-making autonomy, direct access to investigations, and use of emergency routes. CONCLUSION: Analysing the differences in referral processes can prompt further research to better understand the impact of variation on the timeliness of diagnoses and cancer outcomes. Studying these schematics in local contexts may help to identify opportunities to improve care and facilitate discussions on what may constitute best referral practice.

Diagnostic pathways for breast cancer in 10 International Cancer Benchmarking Partnership (ICBP) jurisdictions: an international comparative cohort study based on questionnaire and registry data.

OBJECTIVES: A growing body of evidence suggests longer time between symptom onset and start of treatment affects breast cancer prognosis. To explore this association, the International Cancer Benchmarking Partnership Module 4 examined differences in breast cancer diagnostic pathways in 10 jurisdictions across Australia, Canada, Denmark, Norway, Sweden and the UK. SETTING: Primary care in 10 jurisdictions. PARTICIPANT: Data were collated from 3471 women aged >40 diagnosed for the first time with breast cancer and surveyed between 2013 and 2015. Data were supplemented by feedback from their primary care physicians (PCPs), cancer treatment specialists and available registry data. PRIMARY AND SECONDARY OUTCOME MEASURES: Patient, primary care, diagnostic and treatment intervals. RESULTS: Overall, 56% of women reported symptoms to primary care, with 66% first noticing lumps or breast changes. PCPs reported 77% presented with symptoms, of whom 81% were urgently referred with suspicion of cancer (ranging from 62% to 92%; Norway and Victoria). Ranges for median patient, primary care and diagnostic intervals (days) for symptomatic patients were 3-29 (Denmark and Sweden), 0-20 (seven jurisdictions and Ontario) and 8-29 (Denmark and Wales). Ranges for median treatment and total intervals (days) for all patients were 15-39 (Norway, Victoria and Manitoba) and 4-78 days (Sweden, Victoria and Ontario). The 10% longest waits ranged between 101 and 209 days (Sweden and Ontario). CONCLUSIONS: Large international differences in breast cancer diagnostic pathways exist, suggesting some jurisdictions develop more effective strategies to optimise pathways and reduce time intervals. Targeted awareness interventions could also facilitate more timely diagnosis of breast cancer.