Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group.

INTRODUCTION: In 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care. METHODS: We conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the "ACT" component of VBA. Participants were aged ≥ 35 years, smoked ≥ 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation. RESULTS: There was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses. CONCLUSION: Overall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists. TRIAL REGISTRATION: The trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.

Histone 3 lysine 4 monomethylation supports activation of transcription in S. cerevisiae during nutrient stress.

Mono-methylation of the fourth lysine on the N-terminal tail of histone H3 was found to support the induction of RNA polymerase II transcription in S. cerevisiae during nutrient stress. In S. cerevisiae, the mono-, di- and tri-methylation of lysine 4 on histone H3 (H3K4) is catalyzed by the protein methyltransferase, Set1. The three distinct methyl marks on H3K4 act in discrete ways to regulate transcription. Nucleosomes enriched with tri-methylated H3K4 are usually associated with active transcription whereas di-methylated H3K4 is associated with gene repression. Mono-methylated H3K4 has been shown to repress gene expression in S. cerevisiae and is detected at enhancers and promoters in eukaryotes. S. cerevisiae set1Δ mutants unable to methylate H3K4 exhibit growth defects during histidine starvation. The growth defects are rescued by either a wild-type allele of SET1 or partial-function alleles of set1, including a mutant that predominantly generates H3K4me1 and not H3K4me3. Rescue of the growth defect is associated with induction of the HIS3 gene. Growth defects observed when set1Δ cultures were starved for isoleucine and valine were also rescued by wild-type SET1 or partial-function set1 alleles. The results show that H3K4me1, in the absence of H3K4me3, supports transcription of the HIS3 gene and expression of one or more of the genes required for biosynthesis of isoleucine and valine during nutrient stress. Set1-like methyltransferases are evolutionarily conserved, and research has linked their functions to developmental gene regulation and several cancers in higher eukaryotes. Identification of mechanisms of H3K4me1-mediated activation of transcription in budding yeast will provide insight into gene regulation in all eukaryotes.

Understanding the impact of systemic lupus erythematosus on work amongst South Asian people in the UK: An explorative qualitative study.

SLE has a range of fluctuating symptoms affecting individuals and their ability to work. Although South Asian (SA) patients are at increased risk of developing SLE there is limited knowledge of the impact on employment for these patients in the UK. Understanding ethnicity and disease-specific issues are important to ensure patients are adequately supported at work. Semi-structured interviews were conducted with patients of SA origin to explore how SLE impacted on their employment. Thematic analysis was used to analyse the data which are reported following COREQ guidelines. Ten patients (8 female; 2 male) were recruited from three rheumatology centres in the UK and interviewed between November 2019 and March 2020. Patients were from Indian (n = 8) or Pakistani (n = 2) origin and worked in a range of employment sectors. Four themes emerged from the data: (1) Disease related factors; (2) Employment related factors; (3) Cultural and interpersonal factors impacting on work ability; (4) Recommendations for improvement. Patients' ability to work was affected by variable work-related support from their hospital clinicians, low awareness of SLE and variable support from their employers, and cultural barriers in their communities that could affect levels of family support received. These findings highlight the need for additional support for SA patients with SLE in the workplace.

Performance of the EQ-5D-5L Plus Respiratory Bolt-On in the Birmingham Chronic Obstructive Pulmonary Disease Cohort Study.

OBJECTIVES: A respiratory bolt-on dimension for the EQ-5D-5L has recently been developed and valued by the general public. This study aimed to validate the EQ-5D-5L plus respiratory dimension (EQ-5D-5L+R) in a large group of patients with chronic obstructive pulmonary disease (COPD). METHODS: Validation was undertaken with data from the Birmingham COPD Cohort Study, a longitudinal UK study of COPD primary care patients. Data on the EQ-5D-5L+R were collected from 1008 responding participants during a follow-up questionnaire in 2017 and combined with (previously collected) data on patient and disease characteristics. Descriptive and correlation analyses were performed on the EQ-5D-5L+R dimensions and utilities, in relation to COPD characteristics and compared with the EQ-5D-5L without respiratory dimension. Multivariate regression models were estimated to test whether regression coefficients of clinical characteristics differed between the EQ-5D-5L+R utility and the EQ-5D-5L utility. RESULTS: Correlation coefficients for the EQ-5D-5L+R utility with COPD parameters were slightly higher than the EQ-5D-5L utility. Both instruments displayed discriminant validity but analyses in clinical subgroups of patients showed larger absolute differences in utilities for the EQ-5D-5L+R. In the multivariate analyses, only the coefficient for the COPD Assessment Test score was higher for the model using the EQ-5D-5L+R utility as outcome. CONCLUSIONS: This study showed that the addition of a respiratory domain to the EQ-5D-5L led to small improvements in the instrument's performance. Comparability of the EQ-5D across diseases, currently considered one of its strengths, would have to be traded off against a modest improvement in utility difference when adding the respiratory dimension.

Model-based evaluation of the long-term cost-effectiveness of systematic case-finding for COPD in primary care.

INTRODUCTION: 'One-off' systematic case-finding for COPD using a respiratory screening questionnaire is more effective and cost-effective than routine care at identifying new cases. However, it is not known whether early diagnosis and treatment is beneficial in the longer term. We estimated the long-term cost-effectiveness of a regular case-finding programme in primary care. METHODS: A Markov decision analytic model was developed to compare the cost-effectiveness of a 3-yearly systematic case-finding programme targeted to ever smokers aged ≥50 years with the current routine diagnostic process in UK primary care. Patient-level data on case-finding pathways was obtained from a large randomised controlled trial. Information on the natural history of COPD and treatment effects was obtained from a linked COPD cohort, UK primary care database and published literature. The discounted lifetime cost per quality-adjusted life-year (QALY) gained was calculated from a health service perspective. RESULTS: The incremental cost-effectiveness ratio of systematic case-finding versus current care was £16 596 per additional QALY gained, with a 78% probability of cost-effectiveness at a £20 000 per QALY willingness-to-pay threshold. The base case result was robust to multiple one-way sensitivity analyses. The main drivers were response rate to the initial screening questionnaire and attendance rate for the confirmatory spirometry test. DISCUSSION: Regular systematic case-finding for COPD using a screening questionnaire in primary care is likely to be cost-effective in the long-term despite uncertainties in treatment effectiveness. Further knowledge of the natural history of case-found patients and the effectiveness of their management will improve confidence to implement such an approach.

Predicting risk of undiagnosed COPD: development and validation of the TargetCOPD score.

Chronic obstructive pulmonary disease (COPD) is greatly underdiagnosed worldwide and more efficient methods of case-finding are required. We developed and externally validated a risk score to identify undiagnosed COPD using primary care records.We conducted a retrospective cohort analysis of a pragmatic cluster randomised controlled case-finding trial in the West Midlands, UK. Participants aged 40-79 years with no prior diagnosis of COPD received a postal or opportunistic screening questionnaire. Those reporting chronic respiratory symptoms were assessed with spirometry. COPD was defined as presence of relevant symptoms with a post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal. A risk score was developed using logistic regression with variables available from electronic health records for 2398 participants who returned a postal questionnaire. This was externally validated among 1097 participants who returned an opportunistic questionnaire to derive the c-statistic, and the sensitivity and specificity of cut-points.A risk score containing age, smoking status, dyspnoea, prescriptions of salbutamol and prescriptions of antibiotics discriminated between patients with and without undiagnosed COPD (c-statistic 0.74, 95% CI 0.68-0.80). A cut-point of ≥7.5% predicted risk had a sensitivity of 68.8% (95% CI 57.3-78.9%) and a specificity of 68.8% (95% CI 65.8.1-71.6%).A novel risk score using routine data from primary care electronic health records can identify patients at high risk for undiagnosed symptomatic COPD. This score could be integrated with clinical information systems to help primary care clinicians target patients for case-finding.

Factors associated with work productivity among people with COPD: Birmingham COPD Cohort.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are more likely to take time off work (absenteeism) and report poor performance at work (presenteeism) compared to those without COPD. Little is known about the modifiable factors associated with these work productivity outcomes. AIM: To assess the factors associated with work productivity among COPD patients. METHODS: Cross-sectional analysis of baseline data from a subsample (those in paid employment) of the Birmingham COPD Cohort study. Absenteeism was defined by self-report over the previous 12 months. Presenteeism was assessed using the Stanford Presenteeism Scale. Logistic regression analysis was used to assess the effects of sociodemographic, clinical and occupational characteristics on work productivity. RESULTS: Among 348 included participants, increasing dyspnoea was the only factor associated with both absenteeism and presenteeism (p for trend<0.01). Additionally, increasing history of occupational exposure to vapours, gases, dusts or fumes (VGDF) was independently associated with presenteeism (p for trend<0.01). CONCLUSIONS: This is the first study to identify important factors associated with poor work productivity among patients with COPD. Future studies should evaluate interventions aimed at managing breathlessness and reducing occupational exposures to VGDF on work productivity among patients with COPD.

Patient self-management in primary care patients with mild COPD - protocol of a randomised controlled trial of telephone health coaching.

BACKGROUND: The prevalence of diagnosed chronic obstructive pulmonary disease (COPD) in the UK is 1.8%, although it is estimated that this represents less than half of the total disease in the population as much remains undiagnosed. Case finding initiatives in primary care will identify people with mild disease and symptoms. The majority of self-management trials have identified patients from secondary care clinics or following a hospital admission for exacerbation of their condition. This trial will recruit a primary care population with mild symptoms of COPD and use telephone health coaching to encourage self-management. METHODS/DESIGN: In this study, using a multi-centred randomised controlled trial (RCT) across at least 70 general practices in England, we plan to establish the effectiveness of nurse-led telephone health coaching to support self-management in primary care for people who report only mild symptoms of their COPD (MRC grade 1 and 2) compared to usual care. The intervention focuses on taking up smoking cessation services, increasing physical activity, medication management and action planning and is underpinned by behavioural change theory. In total, we aim to recruit 556 patients with COPD confirmed by spirometry with follow up at six and 12 months. The primary outcome is health related quality of life using the St Georges Respiratory Questionnaire (SGRQ). Spirometry and BMI are measured at baseline. Secondary outcomes include self-reported health behaviours (smoking and physical activity), physical activity measured by accelerometery (at 12 months), psychological morbidity, self-efficacy and cost-effectiveness of the intervention. Longitudinal qualitative interviews will explore how engaged participants were with the intervention and how embedded behaviour change was in every day practices. DISCUSSION: This trial will provide robust evidence about the effectiveness of a novel telephone health coaching intervention to promote behaviour change and prevent disease progression in patients with mild symptoms of dyspnoea in primary care. TRIAL REGISTRATION: Current controlled trials ISRCTN06710391 .

TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol.

BACKGROUND: Many people with clinically significant chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. There are a number of small studies which have examined possible methods of case finding through primary care, but no large RCTs that have adequately assessed the most cost-effective approach. METHODS/DESIGN: In this study, using a cluster randomised controlled trial (RCT) in 56 general practices in the West Midlands, we plan to investigate the effectiveness and cost-effectiveness of a Targeted approach to case finding for COPD compared with routine practice. Using an individual patient RCT nested in the Targeted arm, we plan also to compare the effectiveness and cost-effectiveness of Active case finding using a postal questionnaire (with supplementary opportunistic questionnaires), and Opportunistic-only case finding during routine surgery consultations.All ever-smoking patients aged 40-79 years, without a current diagnosis of COPD and registered with participating practices will be eligible. Patients in the Targeted arm who report positive respiratory symptoms (chronic cough or phlegm, wheeze or dyspnoea) using a brief questionnaire will be invited for further spirometric assessment to ascertain whether they have COPD or not. Post-bronchodilator spirometry will be conducted to ATS standards using an Easy One spirometer by trained research assistants.The primary outcomes will be new cases of COPD and cost per new case identified, comparing targeted case finding with routine care, and two types of targeted case finding (active versus opportunistic). A multilevel logistic regression model will be used to model the probability of detecting a new case of COPD for each treatment arm, with clustering of patients (by practice and household) accounted for using a multi-level structure.A trial-based analysis will be undertaken using costs and outcomes collected during the trial. Secondary outcomes include the feasibility, efficiency, long-term cost-effectiveness, patient and primary care staff views of each approach. DISCUSSION: This will be the largest RCT of its kind, and should inform how best to identify undiagnosed patients with COPD in the UK and other similar healthcare systems. Sensitivity analyses will help local policy-makers decide which sub-groups of the population to target first. TRIAL REGISTRATION: Current controlled trials ISRCTN14930255.

Arm Health in Elite Collegiate Summer League Baseball Players Assessed by the Kerlan-Jobe Orthopaedic Clinic Score.

CONTEXT: Collegiate baseball players with professional aspirations often participate in summer leagues; foremost among them is the Cape Cod Baseball League (CCBL). Injuries acquired during the collegiate baseball season can be carried into the CCBL season and vice versa. OBJECTIVE: To assess the history of throwing arm injury and current functionality in midseason CCBL players. DESIGN: Cross-sectional study. SETTING: Online questionnaire. PATIENTS OR OTHER PARTICIPANTS: A total of 123 CCBL players participated. Qualifying athletes were ≥18 years old and were rostered CCBL players with remaining collegiate eligibility. MAIN OUTCOME MEASURE(S): After collecting background information, we used the Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow questionnaire to assess the history of throwing arm injury and current functionality. The maximum KJOC score is 100.0; higher scores correspond with greater functionality. RESULTS: The mean KJOC score was 86.6 ± 14.5 (n = 92); 24.5% (23/94) of players reported a prior diagnosis of throwing arm injury other than a strain or sprain. A total of 49 (49/96, 51.0%) players had undergone rehabilitation for a throwing arm injury, and 7 (7/96, 7.3%) had experienced a medical procedure. Players with no previous treatment (n = 41, mean KJOC score = 88.9 ± 19.0) more frequently demonstrated KJOC scores of ≥90 than players with such treatment (n = 55, 80.9 ± 17.1; P < .001). The 18 players with time-loss arm injury in the last year had lower mean KJOC scores (71.3 ± 20.0) than players with no injury or time loss (90.3 ± 9.8; P < .001). Similarly, players who reported current arm trouble (n = 15) had lower KJOC scores (71.6 ± 17.5) than players with healthy arms (89.5 ± 11.9; P < .001). CONCLUSIONS: The average KJOC score of the CCBL players was <90, with particularly low scores in athletes with prior arm injury and treatment.

Implementation of a diagnostic stewardship intervention to improve blood-culture utilization in 2 surgical ICUs: Time for a blood-culture change.

OBJECTIVE: We compared the number of blood-culture events before and after the introduction of a blood-culture algorithm and provider feedback. Secondary objectives were the comparison of blood-culture positivity and negative safety signals before and after the intervention. DESIGN: Prospective cohort design. SETTING: Two surgical intensive care units (ICUs): general and trauma surgery and cardiothoracic surgery. PATIENTS: Patients aged ≥18 years and admitted to the ICU at the time of the blood-culture event. METHODS: We used an interrupted time series to compare rates of blood-culture events (ie, blood-culture events per 1,000 patient days) before and after the algorithm implementation with weekly provider feedback. RESULTS: The blood-culture event rate decreased from 100 to 55 blood-culture events per 1,000 patient days in the general surgery and trauma ICU (72% reduction; incidence rate ratio [IRR], 0.38; 95% confidence interval [CI], 0.32-0.46; P < .01) and from 102 to 77 blood-culture events per 1,000 patient days in the cardiothoracic surgery ICU (55% reduction; IRR, 0.45; 95% CI, 0.39-0.52; P < .01). We did not observe any differences in average monthly antibiotic days of therapy, mortality, or readmissions between the pre- and postintervention periods. CONCLUSIONS: We implemented a blood-culture algorithm with data feedback in 2 surgical ICUs, and we observed significant decreases in the rates of blood-culture events without an increase in negative safety signals, including ICU length of stay, mortality, antibiotic use, or readmissions.

Australian Cerebral Palsy Child Study: protocol of a prospective population based study of motor and brain development of preschool aged children with cerebral palsy.

BACKGROUND: Cerebral palsy (CP) results from a static brain lesion during pregnancy or early life and remains the most common cause of physical disability in children (1 in 500). While the brain lesion is static, the physical manifestations and medical issues may progress resulting in altered motor patterns. To date, there are no prospective longitudinal studies of CP that follow a birth cohort to track early gross and fine motor development and use Magnetic Resonance Imaging (MRI) to determine the anatomical pattern and likely timing of the brain lesion. Existing studies do not consider treatment costs and outcomes. This study aims to determine the pathway(s) to motor outcome from diagnosis at 18 months corrected age (c.a.) to outcome at 5 years in relation to the nature of the brain lesion (using structural MRI). METHODS: This prospective cohort study aims to recruit a total of 240 children diagnosed with CP born in Victoria (birth years 2004 and 2005) and Queensland (birth years 2006-2009). Children can enter the study at any time between 18 months to 5 years of age and will be assessed at 18, 24, 30, 36, 48 and 60 months c.a. Outcomes include gross motor function (GMFM-66 & GMFM-88), Gross Motor Function Classification System (GMFCS); musculoskeletal development (hip displacement, spasticity, muscle contracture), upper limb function (Manual Ability Classification System), communication difficulties using Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP), participation using the Paediatric Evaluation of Disability Inventory (PEDI), parent reported quality of life and classification of medical and allied health resource use and determination of the aetiology of CP using clinical evaluation combined with MRI. The relationship between the pathways to motor outcome and the nature of the brain lesion will be analysed using multiple methods including non-linear modelling, multilevel mixed-effects models and generalised estimating equations. DISCUSSION: This protocol describes a large population-based study of early motor development and brain structure in a representative sample of preschool aged children with CP, using direct clinical assessment. The results of this study will be published in peer reviewed journals and presented at relevant international conferences. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ACTRN1261200169820).

A Systematic Review of the Effectiveness of Interventions to Promote Referral; Adherence; and Uptake of Pulmonary Rehabilitation for Patients with Chronic Obstructive Pulmonary Disease.

Background: Pulmonary rehabilitation (PR) is an effective treatment for patients with chronic obstructive pulmonary disease (COPD). However, referral, uptake, and adherence remain low. Objective: To determine effectiveness of interventions to increase patient referral, uptake, and adherence to PR programs for patients with COPD. Methods: Randomized controlled trials (RCTs), non-randomized controlled trials, pre-post studies, and uncontrolled studies were sought from 7 databases and 3 clinical trial registries, to end August 2021. Full articles/conference abstracts were included if a coordinated set of activities was targeted to healthcare professionals (HCPs) caring for COPD patients, adults with COPD or their carers, to increase referral, uptake or adherence to any type of PR program. Two review authors independently screened titles, abstracts and full texts, extracted data and critically appraised studies using standard risk of bias tools. Results: From 11,272 records, 30 studies (23 full-text; 7 abstracts) met inclusion criteria: study interventions and designs were varied and generally low quality, targeting patients (n=13), HCPs (n=14) or both (n=3 studies). A CCT of patient held evidence score cards increased referral by 7.3% compared to 1.3% for usual care (p-0.03). A cluster RCT involving COPD nurse home visits with individualized care plans increased uptake to 31% compared to 10% in usual care (p=0.002). For people with anxiety or depression, one RCT of cognitive behavioral therapy alongside PR increased adherence (mean sessions 14.0 (sd 1.7) compared to 12.4 (sd 2.6)). Conclusion: Although a small number of studies, the weight of evidence suggested that interventions incorporating partnership working between patients and HCPs appeared to increase referral, uptake, and adherence with greater effectiveness than those targeting single populations. Increasing knowledge and empowering HCPs and patients may be important strategies. Concerns about study design and risk of bias suggest clear need for well-designed trials of interventions to report full pathway outcomes.

At least it is a dry cold: the global distribution of freeze-thaw and drought stress and the traits that may impart poly-tolerance in conifers.

Conifers inhabit some of the most challenging landscapes where multiple abiotic stressors (e.g., aridity, freezing temperatures) often co-occur. Physiological tolerance to multiple stressors ('poly-tolerance') is thought to be rare because exposure to one stress generally limits responses to another through functional trade-offs. However, the capacity to exhibit poly-tolerance may be greater when combined abiotic stressors have similar physiological impacts, such as the disruption of hydraulic function imposed by drought or freezing. Here, we reviewed empirical data in light of theoretical expectations for conifer adaptations to drought and freeze-thaw cycles with particular attention to hydraulic traits of the stem and leaf. Additionally, we examined the commonality and spatial distribution of poly-stress along indices of these combined stressors. We found that locations with the highest values of our poly-stress index (PSi) are characterized by moderate drought and moderate freeze-thaw, and most of the global conifer distribution occupies areas of moderate poly-stress. Among traits examined, we found diverse responses to the stressors. Turgor loss point did not correlate with freeze-thaw or drought stress individually, but did with the PSi, albeit inverse to what was hypothesized. Leaf mass per area was more strongly linked with drought stress than the poly-stress and not at all with freeze-thaw stress. In stems, the water potential causing 50% loss of hydraulic conductivity became more negative with increasing drought stress and poly-stress but did not correlate with freeze-thaw stress. For these traits, we identified a striking lack of coverage for substantial portions of species ranges, particularly at the upper boundaries of their respective PSis, demonstrating a critical gap in our understanding of trait prevalence and plasticity along these stress gradients. Future research should investigate traits that confer tolerance to both freeze-thaw and drought stress in a wide range of species across broad geographic scales.

Sex, susceptibility to smoking and chronic obstructive pulmonary disease: the effect of different diagnostic criteria. Analysis of the Health Survey for England.

BACKGROUND: Some previous studies suggest there are sex differences in susceptibility to, and prevalence of, chronic obstructive pulmonary disease (COPD) but findings are inconsistent. In this study, whether different diagnostic criteria for COPD may contribute to these conflicting findings was examined. METHODS: Cross sectional analysis of data from the 1995, 1996 and 2001 Health Survey for England was undertaken, including participants of white ethnicity, aged 40+ years with a valid smoking history and lung function data. COPD was defined using Global Initiative for Chronic Obstructive Lung Disease (GOLD), National Institute for Health and Clinical Excellence (NICE) and lower limit of normal (LLN) spirometric criteria, in the absence of a diagnosis of asthma. RESULTS: COPD was present in 3035 (16.1%), 1304 (7.0%) and 1684 (9.0%) people, according to the GOLD, NICE and LLN criteria, respectively. With both the GOLD and NICE definitions, men had significant independent increased risks of COPD compared with women (OR 1.46 (95% CI 1.34 to 1.59) and 1.30 (1.15 to 1.48), respectively). With the LLN definition, this effect was removed (OR 0.96 (0.87 to 1.07). With the use of both the GOLD and NICE criteria, women had significantly greater susceptibility to COPD (25-30% higher risk) for the same level of pack years of exposure. This was not observed with the LLN criteria. CONCLUSIONS: The study indicates that sex differences in risk of COPD reported in previous studies are influenced by the definition used for COPD. When using a statistically driven definition (LLN), no independent sex difference was found and there was no evidence of an increased susceptibility to COPD among female compared with male smokers.

Factors associated with uptake of pandemic influenza vaccine among general practitioners and practice nurses in Shropshire, UK.

BACKGROUND: At the time of the 2009-10 influenza pandemic there was considerable unease about vaccination. Early surveys suggested that the intention to be vaccinated amongst healthcare workers was low. AIMS: To determine what influenced vaccination uptake among general practice healthcare workers in Shropshire County Primary Care Trust in the UK. METHODS: A cross-sectional survey was distributed to all frontline healthcare workers in Shropshire County's general practices in June 2010. All 45 practices participated. Questionnaires were distributed by practice managers to frontline staff and returned by post. Practices with the lowest return rates were reminded by telephone after 3 months. RESULTS: 205 valid replies were received, giving a response rate of 48.0%. 10.0% reported being infected with the pandemic H1N1 strain by the time they received the questionnaire. 172 (83.9%) respondents reported that they had been vaccinated against H1N1. Influenza infection prior to vaccination had a negative impact on uptake (adjusted OR 0.17, 95% CI 0.05 to 0.56) and previous vaccination against seasonal influenza was associated with increased uptake (adjusted OR 4.07, 95% CI 1.62 to 10.24). Those who received the pandemic vaccine were seven times more likely to accept future vaccines (adjusted OR 7.04, 95% CI 2.70 to 18.37). CONCLUSIONS: Vaccination uptake was significantly higher than the national (40.3%), regional (40.9%), and county averages (49.3%). Motivation for and against vaccination was very similar to that for seasonal vaccination, with previous vaccination having the greatest influence. Ensuring healthcare workers receive vaccination early in their career is likely to set a precedent for future vaccination. This is the first detailed study purely in general practice in England.

Screening tools for work-related asthma and their diagnostic accuracy: a systematic review protocol.

INTRODUCTION: Work-related asthma (WRA) refers to asthma caused by exposures at work (occupational asthma) and asthma made worse by work conditions (work-exacerbated asthma). WRA is common among working-age adults with asthma and impacts individual health, work-life and income but is often not detected by healthcare services. Earlier identification can lead to better health and employment outcomes. However, the optimal tool for screening and its effectiveness in practice is not well established. Screening tools may include whole questionnaires, questionnaire items, physiological measurements and/or immunological tests. Since the publication of the most contemporary WRA or occupational asthma-specific guidelines, further studies evaluating tools for identifying WRA have been performed. Our systematic review aims to summarise and compare the performance of screening tools for identifying WRA in both clinical and workplace settings. METHODS AND ANALYSIS: We will conduct a systematic review of observational and experimental studies (1975-2021) using MEDLINE, EMBASE, CINAHL Plus, Web of Science, CDSR, DARE, HTA, CISDOC databases and grey literature. Two independent reviewers will screen the studies using predetermined criteria, extract data according to a schedule and assess study quality using the Quality Assessment of Diagnostic Test Accuracy 2 tool. Screening tools and test accuracy measures will be summarised. Paired forest plots and summary receiver operating characteristic curves of sensitivities and specificities will be evaluated for heterogeneity between studies, using subgroup analyses, where possible. If the studies are sufficiently homogenous, we will use a bivariate random effect model for meta-analysis. A narrative summary and interpretation will be provided if meta-analysis is not appropriate. ETHICS AND DISSEMINATION: As this is a systematic review and does not involve primary data collection, formal ethical review is not required. We will disseminate our findings through open access peer-reviewed publication as well as through other academic and social media. PROSPERO REGISTRATION NUMBER: CRD42021246031.

Investigating primary healthcare practitioners' barriers and enablers to referral of patients with COPD to pulmonary rehabilitation: a mixed-methods study using the Theoretical Domains Framework.

OBJECTIVES: Pulmonary rehabilitation (PR) is a highly effective, recommended intervention for patients with chronic obstructive pulmonary disease (COPD). Using behavioural theory within mixed-methods research to understand why referral remains low enables the development of targeted interventions in order to improve future PR referral. DESIGN: A multiphase sequential mixed-methods study. SETTING: United Kingdom (UK). PARTICIPANTS: 252 multiprofessional primary healthcare practitioners (PHCPs). MEASURES: Phase 1: semistructured interviews. Phase 2: a 54-item paper and online questionnaire, based on the Theoretical Domains Framework (TDF). Content and descriptive analysis utilised. Data mixed at two points: instrument design and interpretation. RESULTS: 19 PHCPs took part in interviews and 233 responded to the survey. Integrated results revealed that PHCPs with a post qualifying respiratory qualification (154/241; 63.9%) referred more frequently (91/154; 59.1%) than those without (28/87; 32.2%). There were more barriers than enablers for referral in all 13 TDF domains. Key barriers included: infrequent engagement from PR provider to referrer, concern around patient's physical ability and access to PR (particularly for those in work), assumed poor patient motivation, no clear practice referrer and few referral opportunities. These mapped to domains: belief about capabilities, social influences, environment, optimism, skills and social and professional role. Enablers to referral were observed in knowledge, social influences memory and environment domains. Many PHCPs believed in the physical and psychological value of PR. Helpful enablers were out-of-practice support from respiratory interested colleagues, dedicated referral time (annual review) and on-screen referral prompts. CONCLUSIONS: Referral to PR is complex. Barriers outweighed enablers. Aligning these findings to behaviour change techniques will identify interventions to overcome barriers and strengthen enablers, thereby increasing referral of patients with COPD to PR.