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.

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.

Pulmonary rehabilitation with balance training for fall reduction in chronic obstructive pulmonary disease: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Available evidence suggests that adults with chronic obstructive pulmonary disease (COPD) performed substantially worse than healthy controls on many balance measures and balance training can improve the balance measures in this population. We conducted this study to determine the effects of incorporating balance training into pulmonary rehabilitation (PR) on the incidence of falls at 12 months follow-up in high fall risk adults with COPD. METHODS: We conducted a prospective international multi-center randomized controlled trial. Eligible participants were adults with COPD at a high risk of future falls and were randomly assigned (1:1) to the intervention or control group. The intervention included personalized balance training for a targeted total of 90 min per week. Both the intervention and control groups received usual PR (2-3 times per week for 8-12 weeks). The primary outcome was the incidence of falls at 12-month follow-up using monthly fall diary calendars. Negative binomial regression or recurrent events models were used to examine the effects of the intervention on fall events. Multiple imputations were performed to deal with missing values. RESULTS: Of 258 participants who were enrolled in the trial, 178 provided falls information (intervention group = 91, control group = 87) and were included in the main analysis. Forty-one participants (45%) experienced at least one fall event in the intervention group and 33 (38%) in the control group (p = 0.34). The mean incidence of falls at 12 months was similar between the two groups (128 versus 128 per 100 person-years; mean difference: 0.30, 95% CI: -0.76 to 1.36 per 100 person-years). The results are robust after multiple imputations for missing data (n = 67). CONCLUSIONS: PR incorporating balance training compared to PR alone did not reduce the incidence of falls over the 12-month period in high fall risk adults with COPD. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (NCT02995681) on 14/12/2016.

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.

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.

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.

International variation in oesophageal and gastric cancer survival 2012-2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study).

OBJECTIVE: To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare. METHODS: As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012-2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country. RESULTS: Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes. CONCLUSION: Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future.

Diagnostic routes and time intervals for ovarian cancer in nine international jurisdictions; findings from the International Cancer Benchmarking Partnership (ICBP).

BACKGROUND: International Cancer Benchmarking Partnership Module 4 reports the first international comparison of ovarian cancer (OC) diagnosis routes and intervals (symptom onset to treatment start), which may inform previously reported variations in survival and stage. METHODS: Data were collated from 1110 newly diagnosed OC patients aged >40 surveyed between 2013 and 2015 across five countries (51-272 per jurisdiction), their primary-care physicians (PCPs) and cancer treatment specialists, supplement by treatment records or clinical databases. Diagnosis routes and time interval differences using quantile regression with reference to Denmark (largest survey response) were calculated. RESULTS: There were no significant jurisdictional differences in the proportion diagnosed with symptoms on the Goff Symptom Index (53%; P = 0.179) or National Institute for Health and Care Excellence NG12 guidelines (62%; P = 0.946). Though the main diagnosis route consistently involved primary-care presentation (63-86%; P = 0.068), onward urgent referral rates varied significantly (29-79%; P < 0.001). In most jurisdictions, diagnostic intervals were generally shorter and other intervals, in particular, treatment longer compared to Denmark. CONCLUSION: This study highlights key intervals in the diagnostic pathway where improvements could be made. It provides the opportunity to consider the systems and approaches across different jurisdictions that might allow for more timely ovarian cancer diagnosis and treatment.

The variant-specific burden of SARS-CoV-2 in Michigan: March 2020 through November 2021.

Accurate estimates of the total burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to inform policy, planning, and response. We sought to quantify SARS-CoV-2 cases, hospitalizations, and deaths by age in Michigan. Coronavirus disease 2019 cases reported to the Michigan Disease Surveillance System were multiplied by age and time-specific adjustment factors to correct for under-detection. Adjustment factors were estimated in a model fit to incidence data and seroprevalence estimates. Age-specific incidence of SARS-CoV-2 hospitalization, death, vaccination, and variant proportions were estimated from publicly available data. We estimated substantial under-detection of infection that varied by age and time. Accounting for under-detection, we estimate the cumulative incidence of infection in Michigan reached 75% by mid-November 2021, and over 87% of Michigan residents were estimated to have had ≥1 vaccination dose and/or previous infection. Comparing pandemic waves, the relative burden among children increased over time. In general, the proportion of cases who were hospitalized or who died decreased over time. Our results highlight the ongoing risk of periods of high SARS-CoV-2 incidence despite widespread prior infection and vaccination. This underscores the need for long-term planning for surveillance, vaccination, and other mitigation measures amidst continued response to the acute pandemic.

An International Consensus on Actions to Improve Lung Cancer Survival: A Modified Delphi Method Among Clinical Experts in the International Cancer Benchmarking Partnership.

BACKGROUND: Research from the International Cancer Benchmarking Partnership (ICBP) demonstrates that international variation in lung cancer survival persists, particularly within early stage disease. There is a lack of international consensus on the critical contributing components to variation in lung cancer outcomes and the steps needed to optimise lung cancer services. These are needed to improve the quality of options for and equitable access to treatment, and ultimately improve survival. METHODS: Semi-structured interviews were conducted with 9 key informants from ICBP countries. An international clinical network representing 6 ICBP countries (Australia, Canada, Denmark, England, Ireland, New Zealand, Northern Ireland, Scotland & Wales) was established to share local clinical insights and examples of best practice. Using a modified Delphi consensus model, network members suggested and rated recommendations to optimise the management of lung cancer. Calls to Action were developed via Delphi voting as the most crucial recommendations, with Good Practice Points included to support their implementation. RESULTS: Five Calls to Action and thirteen Good Practice Points applicable to high income, comparable countries were developed and achieved 100% consensus. Calls to Action include (1) Implement cost-effective, clinically efficacious, and equitable lung cancer screening initiatives; (2) Ensure diagnosis of lung cancer within 30 days of referral; (3) Develop Thoracic Centres of Excellence; (4) Undertake an international audit of lung cancer care; and (5) Recognise improvements in lung cancer care and outcomes as a priority in cancer policy. CONCLUSION: The recommendations presented are the voice of an expert international lung cancer clinical network, and signpost key considerations for policymakers in countries within the ICBP but also in other comparable high-income countries. These define a roadmap to help align and focus efforts in improving outcomes and management of lung cancer patients globally.

Age and Sex Differences in Balance Outcomes among Individuals with Chronic Obstructive Pulmonary Disease (COPD) at Risk of Falls.

No previous research has examined age and sex differences in balance outcomes in individuals with chronic obstructive pulmonary disease (COPD) at risk of falls. A secondary analysis of baseline data from an ongoing trial of fall prevention in COPD was conducted. Age and sex differences were analyzed for the Berg Balance scale (BBS), Balance Evaluation System Test (BEST test) and Activities-specific Balance Confidence Scale (ABC). Overall, 223 individuals with COPD were included. Females had higher balance impairments than males [BBS: mean (SD) = 47 (8) vs. 49 (6) points; BEST test: 73 (16) vs. 80 (16) points], and a lower confidence to perform functional activities [ABC = 66 (21) vs. 77 (19)]. Compared to a younger age (50-65 years) group, age >65 years was moderately associated with poor balance control [BBS (r = - 0.37), BEST test (r = - 0.33)] and weakly with the ABC scale (r = - 0.13). After controlling for the effect of balance risk factors, age, baseline dyspnea index (BDI), and the 6-min walk test (6-MWT) explained 38% of the variability in the BBS; age, sex, BDI, and 6-MWT explained 40% of the variability in the BEST test; And BDI and the 6-MWT explained 44% of the variability in the ABC scale. This study highlights age and sex differences in balance outcomes among individuals with COPD at risk of falls. Recognition of these differences has implications for pulmonary rehabilitation and fall prevention in COPD, particularly among females and older adults.

The CKD Stress Scale: Development and identification of patients at risk.

AIMS: Develop a novel chronic kidney disease (CKD)-specific stress scale and examine associations with patient characteristics. MATERIALS AND METHODS: Adults with CKD stages 1 - 5 enrolled in a cross-sectional survey. Eight questions assessed patients' thoughts and feelings of stress related to CKD (CKD Stress Scale). Patients also reported their knowledge of CKD, barriers to CKD health, and demographics. The scale was evaluated using exploratory factor analysis and Cronbach's alpha. Associations were examined via linear regression. RESULTS: 245 participant enrolled with a mean age of 60 years and a mean estimated glomerular filtration rate (eGFR) of 34 mL/min/1.73m2; 49% were women (match percentage in Table 1), 74% White, 14% African American. A one-factor model of CKD Stress exhibited high internal consistency (α = 0.89). In bivariate analyses, higher CKD Stress was associated with lower eGFR, younger age, African American race (compared to White), and having a high school education or some college (compared to college degree or higher). Adjusting for these characteristics, as well as income and knowledge about CKD, only lower eGFR (b = -0.01; 95% CI [-0.01, -0.001]), younger age (b = -0.01; 95% CI [-0.01, -0.003]), African American race (b = 0.35, 95% CI [0.10, 0.60]), and receiving a high school education or some college (b = 0.20, 95% CI [0.01, 0.39]) were independently associated with more CKD-specific stress. Concurrent validity was supported by associations between stress and perceived barriers to care. CONCLUSION: Our CKD Stress Scale exhibits excellent internal reliability and identified where future educational interventions may benefit from tailoring for at-risk patients.

Tailored or adapted interventions for adults with chronic obstructive pulmonary disease and at least one other long-term condition: a mixed methods review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by shortness of breath, cough and recurrent exacerbations. People with COPD often live with one or more co-existing long-term health conditions (comorbidities). People with more severe COPD often have a higher number of comorbidities, putting them at greater risk of morbidity and mortality. OBJECTIVES: To assess the effectiveness of any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention for people with COPD and one or more common comorbidities (quantitative data, RCTs) in terms of the following outcomes: Quality of life, exacerbations, functional status, all-cause and respiratory-related hospital admissions, mortality, pain, and depression and anxiety. To assess the effectiveness of an adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more common comorbidities (quantitative data, RCTs) compared to usual care in terms of the following outcomes: Quality of life, exacerbations, functional status, all-cause and respiratory-related hospital admissions, mortality, pain, and depression and anxiety. To identify emerging themes that describe the views and experiences of patients, carers and healthcare professionals when receiving or providing care to manage multimorbidities (qualitative data). SEARCH METHODS: We searched multiple databases including the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, and CINAHL, to identify relevant randomised and qualitative studies. We also searched trial registries and conducted citation searches. The latest search was conducted in January 2021. SELECTION CRITERIA: Eligible randomised controlled trials (RCTs) compared a) any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention, or b) any adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more comorbidities, compared to usual care. We included qualitative studies or mixed-methods studies to identify themes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for analysis of the RCTs. We used Cochrane's risk of bias tool for the RCTs and the CASP checklist for the qualitative studies. We planned to use the Mixed Methods Appraisal tool (MMAT) to assess the risk of bias in mixed-methods studies, but we found none. We used GRADE and CERQual to assess the quality of the quantitative and qualitative evidence respectively. The primary outcome measures for this review were quality of life and exacerbations. MAIN RESULTS: Quantitative studies We included seven studies (1197 participants) in the quantitative analyses, with interventions including telemonitoring, pulmonary rehabilitation, treatment optimisation, water-based exercise training and case management. Interventions were either compared with usual care or with an active comparator (such as land-based exercise training). Duration of trials ranged from 4 to 52 weeks. Mean age of participants ranged from 64 to 72 years and COPD severity ranged from mild to very severe. Trials included either people with COPD and a specific comorbidity (including cardiovascular disease, metabolic syndrome, lung cancer, head or neck cancer, and musculoskeletal conditions), or with one or more comorbidities of any type. Overall, we judged the evidence presented to be of moderate to very low certainty (GRADE), mainly due to the methodological quality of included trials and imprecision of effect estimates. Intervention versus usual care Quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) total score may improve with tailored pulmonary rehabilitation compared to usual care at 52 weeks (mean difference (MD) -10.85, 95% confidence interval (CI) -12.66 to -9.04; 1 study, 70 participants; low-certainty evidence). Tailored pulmonary rehabilitation is likely to improve COPD assessment test (CAT) scores compared with usual care at 52 weeks (MD -8.02, 95% CI -9.44 to -6.60; 1 study, 70 participants, moderate-certainty evidence) and with a multicomponent telehealth intervention at 52 weeks (MD -6.90, 95% CI -9.56 to -4.24; moderate-certainty evidence). Evidence is uncertain about effects of pharmacotherapy optimisation or telemonitoring interventions on CAT improvement compared with usual care. There may be little to no difference in the number of people experiencing exacerbations, or mean exacerbations with case management compared with usual care (OR 1.09, 95% CI 0.75 to 1.57; 1 study, 470 participants; very low-certainty evidence). For secondary outcomes, six-minute walk distance (6MWD) may improve with pulmonary rehabilitation, water-based exercise or multicomponent interventions at 38 to 52 weeks (low-certainty evidence). A multicomponent intervention may result in fewer people being admitted to hospital at 17 weeks, although there may be little to no difference in a telemonitoring intervention. There may be little to no difference between intervention and usual care for mortality. Intervention versus active comparator We included one study comparing water-based and land-based exercise (30 participants). We found no evidence for quality of life or exacerbations. There may be little to no difference between water- and land-based exercise for 6MWD (MD 5 metres, 95% CI -22 to 32; 38 participants; very low-certainty evidence). Qualitative studies One nested qualitative study (21 participants) explored perceptions and experiences of people with COPD and long-term conditions, and of researchers and health professionals who were involved in an RCT of telemonitoring equipment. Several themes were identified, including health status, beliefs and concerns, reliability of equipment, self-efficacy, perceived ease of use, factors affecting usefulness and perceived usefulness, attitudes and intention, self-management and changes in healthcare use. We judged the qualitative evidence presented as of very low certainty overall. AUTHORS' CONCLUSIONS: Owing to a paucity of eligible trials, as well as diversity in the intervention type, comorbidities and the outcome measures reported, we were unable to provide a robust synthesis of data. Pulmonary rehabilitation or multicomponent interventions may improve quality of life and functional status (6MWD), but the evidence is too limited to draw a robust conclusion. The key take-home message from this review is the lack of data from RCTs on treatments for people living with COPD and comorbidities. Given the variation in number and type of comorbidity(s) an individual may have, and severity of COPD, larger studies reporting individual patient data are required to determine these effects.

A comparative analysis: international variation in PET-CT service provision in oncology-an International Cancer Benchmarking Partnership study.

OBJECTIVE: To explore differences in position emission tomography-computed tomography (PET-CT) service provision internationally to further understand the impact variation may have upon cancer services. To identify areas of further exploration for researchers and policymakers to optimize PET-CT services and improve the quality of cancer services. DESIGN: Comparative analysis using data based on pre-defined PET-CT service metrics from PET-CT stakeholders across seven countries. This was further informed via document analysis of clinical indication guidance and expert consensus through round-table discussions of relevant PET-CT stakeholders. Descriptive comparative analyses were produced on use, capacity and indication guidance for PET-CT services between jurisdictions. SETTING: PET-CT services across 21 jurisdictions in seven countries (Australia, Denmark, Canada, Ireland, New Zealand, Norway and the UK). PARTICIPANTS: None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULTS: PET-CT service provision has grown over the period 2006-2017, but scale of increase in capacity and demand is variable. Clinical indication guidance varied across countries, particularly for small-cell lung cancer staging and the specific acknowledgement of gastric cancer within oesophagogastric cancers. There is limited and inconsistent data capture, coding, accessibility and availability of PET-CT activity across countries studied. CONCLUSIONS: Variation in PET-CT scanner quantity, acquisition over time and guidance upon use exists internationally. There is a lack of routinely captured and accessible PET-CT data across the International Cancer Benchmarking Partnership countries due to inconsistent data definitions, data linkage issues, uncertain coverage of data and lack of specific coding. This is a barrier in improving the quality of PET-CT services globally. There needs to be greater, richer data capture of diagnostic and staging tools to facilitate learning of best practice and optimize cancer services.

Investigating balance, gait, and physical function in people who have undergone thoracic surgery for a diagnosis of lung cancer: A mixed-methods study.

OBJECTIVES: Symptoms associated with lung cancer and thoracic surgery might increase fall risk. We aimed to investigate: 1) balance, gait and functional status in people post-thoracic surgery compared to healthy controls; 2) perceptions of balance, gait and functional status. METHODS: Recruitment targeted older adults (≥50 years) who had undergone thoracic surgery for a diagnosis of lung cancer in the previous 3 months, and healthy age-matched controls. Dynamic and static balance, gait velocity, knee-extension strength and physical activity levels were assessed using the BESTest, Kistler force plate, GAITRite system, Biodex System 3 and CHAMPS questionnaire, respectively. Two-part semi-structured interviews were conducted post-surgery. RESULTS: Individuals post-surgery (n = 15) had worse dynamic balance and gait, and lower levels of moderate/vigorous physical activity (MVPA) (all p<0.05) versus healthy controls (n = 15). Strength did not differ between groups (p > 0.05). No associations between BESTest and strength or physical activity existed post-surgery (p > 0.05). Three themes were identified: 1) Symptoms affect daily activities; 2) Functional assessments alter perceptions of balance ability and 3) Open to supervised rehabilitation. CONCLUSION: Balance, gait and MVPA are impaired post-thoracic surgery, yet balance was not viewed to be important in enabling activities of daily living. However, supervised rehabilitation was considered acceptable.

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.

Exploring variations in ovarian cancer survival by age and stage (ICBP SurvMark-2): A population-based study.

OBJECTIVE: The study aims to evaluate the differences in ovarian cancer survival by age and stage at diagnosis within and across seven high-income countries. METHODS: We analyzed data from 58,161 women diagnosed with ovarian cancer during 2010-2014, followed until 31 December 2015, from 21 population-based cancer registries in Australia, Canada, Denmark, Ireland, New Zealand, Norway, and United Kingdom. Comparisons of 1-year and 3-year age- and stage-specific net survival (NS) between countries were performed using the period analysis approach. RESULTS: Minor variation in the stage distribution was observed between countries, with most women being diagnosed with 'distant' stage (ranging between 64% in Canada and 71% in Norway). The 3-year all-ages NS ranged from 45 to 57% with Australia (56%) and Norway (57%) demonstrating the highest survival. The proportion of women with 'distant' stage was highest for those aged 65-74 and 75-99 years and varied markedly between countries (range:72-80% and 77-87%, respectively). The oldest age group had the lowest 3-year age-specific survival (20-34%), and women aged 65-74 exhibited the widest variation across countries (3-year NS range: 40-60%). Differences in survival between countries were particularly stark for the oldest age group with 'distant' stage (3-year NS range: 12% in Ireland to 24% in Norway). CONCLUSIONS: International variations in ovarian cancer survival by stage exist with the largest differences observed in the oldest age group with advanced disease. This finding endorses further research investigating international differences in access to and quality of treatment, and prevalence of comorbid conditions particularly in older women with advanced disease.

Exploring international differences in ovarian cancer treatment: a comparison of clinical practice guidelines and patterns of care.

INTRODUCTION: The International Cancer Benchmarking Partnership demonstrated international differences in ovarian cancer survival, particularly for women aged 65-74 with advanced disease. These findings suggest differences in treatment could be contributing to survival disparities. OBJECTIVE: To compare clinical practice guidelines and patterns of care across seven high-income countries. METHODS: A comparison of guidelines was performed and validated by a clinical working group. To explore clinical practice, a patterns of care survey was developed. A questionnaire regarding management and potential health system-related barriers to providing treatment was emailed to gynecological specialists. Guideline and survey results were crudely compared with 3-year survival by 'distant' stage using Spearman's rho. RESULTS: Twenty-seven guidelines were compared, and 119 clinicians completed the survey. Guideline-related measures varied between countries but did not correlate with survival internationally. Guidelines were consistent for surgical recommendations of either primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery with the aim of complete cytoreduction. Reported patterns of surgical care varied internationally, including for rates of primary versus interval debulking, extensive/'ultra-radical' surgery, and perceived barriers to optimal cytoreduction. Comparison showed that willingness to undertake extensive surgery correlated with survival across countries (rs=0.94, p=0.017). For systemic/radiation therapies, guideline differences were more pronounced, particularly for bevacizumab and PARP (poly (ADP-ribose) polymerase) inhibitors. Reported health system-related barriers also varied internationally and included a lack of adequate hospital staffing and treatment monitoring via local and national audits. DISCUSSION: Findings suggest international variations in ovarian cancer treatment. Characteristics relating to countries with higher stage-specific survival included higher reported rates of primary surgery; willingness to undertake extensive/ultra-radical procedures; greater access to high-cost drugs; and auditing.

The meaning of the name of 'pulmonary rehabilitation' and its influence on engagement with individuals with chronic lung disease.

Pulmonary rehabilitation (PR) is recommended for all individuals living with a lung condition and chronic breathlessness. This article considers how adopting an interdisciplinary, medical humanities approach to the term 'pulmonary rehabilitation' might unpack some of the misconceptions, misrepresentations or negative connotations surrounding it, which have been largely overlooked in explanations of the low uptake of this programme. Taking key insights from Wellcome Trust-funded Life of Breath project, including ethnographic research in community fitness groups in North East England and the 'Breath Lab' special interest group, this article outlines how the whole-body approach of PR is not easily understood by those with lung conditions; how experience can inform breath perception through the pacing of everyday life; and how stigma can impact rehabilitation. This article highlights the value of medical humanities in working through communicative challenges evident in the translation of PR between patient and clinical contexts and sets out two arts-based approaches (Singing for Lung Health and dance movement) as potential options that could be included in the PR referral. Finally, the article outlines the need for collaborative research exploring the communication and meaning of healthcare strategies and experiences at the interface of the arts, humanities and medical practice.