Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease at High Risk of Exacerbation: The BICS Randomized Clinical Trial.

Importance: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Observational studies report that ß-blocker use may be associated with reduced risk of COPD exacerbations. However, a recent trial reported that metoprolol did not reduce COPD exacerbations and increased COPD exacerbations requiring hospital admission. Objective: To test whether bisoprolol decreased COPD exacerbations in people with COPD at high risk of exacerbations. Design, Setting, and Participants: The Bisoprolol in COPD Study (BICS) was a double-blind placebo-controlled randomized clinical trial conducted in 76 UK sites (45 primary care clinics and 31 secondary clinics). Patients with COPD who had at least moderate airflow obstruction on spirometry (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity <0.7; FEV1 <80% predicted) and at least 2 COPD exacerbations treated with oral corticosteroids, antibiotics, or both in the prior 12 months were enrolled from October 17, 2018, to May 31, 2022. Follow-up concluded on April 18, 2023. Interventions: Patients were randomly assigned to bisoprolol (n = 261) or placebo (n = 258). Bisoprolol was started at 1.25 mg orally daily and was titrated as tolerated during 4 sessions to a maximum dose of 5 mg/d, using a standardized protocol. Main Outcomes and Measures: The primary clinical outcome was the number of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both during the 1-year treatment period. Safety outcomes included serious adverse events and adverse reactions. Results: Although the trial planned to enroll 1574 patients, recruitment was suspended from March 16, 2020, to July 31, 2021, due to the COVID-19 pandemic. Two patients in each group were excluded postrandomization. Among the 515 patients (mean [SD] age, 68 [7.9] years; 274 men [53%]; mean FEV1, 50.1%), primary outcome data were available for 514 patients (99.8%) and 371 (72.0%) continued taking the study drug. The primary outcome of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both was 526 in the bisoprolol group, with a mean exacerbation rate of 2.03/y, vs 513 exacerbations in the placebo group, with a mean exacerbation rate of 2.01/y. The adjusted incidence rate ratio was 0.97 (95% CI, 0.84-1.13; P = .72). Serious adverse events occurred in 37 of 255 patients in the bisoprolol group (14.5%) vs 36 of 251 in the placebo group (14.3%; relative risk, 1.01; 95% CI, 0.62-1.66; P = .96). Conclusions and Relevance: Among people with COPD at high risk of exacerbation, treatment with bisoprolol did not reduce the number of self-reported COPD exacerbations requiring treatment with oral corticosteroids, antibiotics, or both. Trial Registration: isrctn.org Identifier: ISRCTN10497306.

Could paramedics use the HEART Pathway to identify patients at low-risk of myocardial infarction in the prehospital setting?

In the Emergency Department, patients with suspected myocardial infarction can be risk stratified using the HEART pathway, which has recently been amended for prehospital use and modified for the incorporation of a high-sensitivity cardiac troponin test. In a prospective analysis, the performance of both HEART pathways in the prehospital setting, with a high-sensitivity cardiac troponin test using 3 different thresholds, was evaluated for major adverse cardiac events at 30 days. We found that both low-risk HEART pathways, when using the most conservative cardiac troponin thresholds, approached but did not reach accepted rule-out performance in the Emergency Department.

Cost and Affordability of Habitual and Recommended Diets in Welfare-Dependent Households in Australia.

It is crucial to ensure healthy diets are affordable in low socioeconomic groups, such as welfare-dependent households, who experience higher rates of diet-related disease than others. This study assessed the cost of habitual (unhealthy) and recommended (healthy) diets in six welfare-dependent and six other, comparable Australian households, using either popular branded products or the cheapest available alternatives. It also assessed diet affordability in welfare-dependent households, before and after modest increases in government welfare payments introduced in early September 2023. Results confirmed that recommended diets were less expensive than habitual diets in all households unless the cheapest available products were included. This strategy reduced habitual diet costs by 35-37% and recommended diet costs by 30-32%. The lower cost differential could aid perceptions that healthy foods are more expensive than unhealthy foods. In April 2023, 23-37% of the income of welfare-dependent households with children was required to purchase recommended diets; this reduced only to 20-35% in September 2023. Hence, the increases in welfare payments were insufficient to meaningfully improve the affordability of healthy diets in the most vulnerable Australians. In the current cost-of-living crisis, there is an urgent need for more welfare support to help purchase healthy diets. Monitoring of diet cost and affordability is also required.

Improving economic access to healthy diets in first nations communities in high-income, colonised countries: a systematic scoping review.

BACKGROUND: Affordability of healthy food is a key determinant of the diet-related health of First Nations Peoples. This systematic scoping review was commissioned by the Ngaanyatjarra Pitjantjatjara Yankunytjatjara Women's Council (NPYWC) in Central Australia to identify interventions to improve economic access to healthy food in First Nations communities in selected high-income, colonised countries. METHODS: Eight databases and 22 websites were searched to identify studies of interventions and policies to improve economic access to healthy food in First Nations communities in Australia, Canada, the United States or New Zealand from 1996 to May 2022. Data from full text of articles meeting inclusion criteria were extracted to a spreadsheet. Results were collated by descriptive synthesis. Findings were examined with members of the NPYWC Anangu research team at a co-design workshop. RESULTS: Thirty-five publications met criteria for inclusion, mostly set in Australia (37%) or the US (31%). Interventions (n = 21) were broadly categorised as price discounts on healthy food sold in communities (n = 7); direct subsidies to retail stores, suppliers and producers (n = 2); free healthy food and/or food vouchers provided to community members (n = 7); increased financial support to community members (n = 1); and other government strategies (n = 4). Promising initiatives were: providing a box of food and vouchers for fresh produce; prescriptions for fresh produce; provision/promotion of subsidised healthy meals and snacks in community stores; direct funds transfer for food for children; offering discounted healthy foods from a mobile van; and programs increasing access to traditional foods. Providing subsidies directly to retail stores, suppliers and producers was least effective. Identified enablers of effective programs included community co-design and empowerment; optimal promotion of the program; and targeting a wide range of healthy foods, particularly traditional foods where possible. Common barriers in the least successful programs included inadequate study duration; inadequate subsidies; lack of supporting resources and infrastructure for cooking, food preparation and storage; and imposition of the program on communities. CONCLUSIONS: The review identified 21 initiatives aimed at increasing affordability of healthy foods in First Nations communities, of which six were deemed promising. Five reflected the voices and experiences of members of the NPYWC Anangu research team and will be considered by communities for trial in Central Australia. Findings also highlight potential approaches to improve economic access to healthy foods in First Nations communities in other high-income colonised countries. TRIAL REGISTRATION: PROSPERO CRD42022328326.

Habitual Diets Are More Expensive than Recommended Healthy Diets.

Understanding food prices and affordability is crucial for promoting healthy dietary habits and informing policy actions. We assessed changes in the cost and affordability of habitual and recommended healthy diets in Northwest Tasmania from 2021 to 2023. The recommended diet was 16-22% less expensive than the habitual diet during the period. Notably, 60% of the total cost of the habitual diet was spent on discretionary items. The cost of the habitual diet increased by 9% in this period, whereas the cost of the recommended diet increased by only 2%. The habitual diet was unaffordable for households with median gross, minimum wage disposable or welfare-dependent incomes. The recommended diet, however, was affordable for some groups but posed a risk of food stress for those with median gross and minimum wage disposable income and remained unaffordable for those who were welfare dependent. Our findings reveal that adhering to a healthy Australian Dietary Guidelines-recommended diet can be more cost-effective than following a habitual unhealthy diet. However, adopting a healthy diet can be challenging for low-income families. Interventions such as financial support, nutrition education, community gardens and food hubs, as well as price regulation and subsidies for farmers, can help address food insecurity in Northwest Tasmania.

Establishing the predictive validity of the intercollegiate membership of the Royal Colleges of surgeons written examination: MRCS Part A.

Successful completion of the Intercollegiate Membership of the Royal Colleges of Surgeons (MRCS) examination is mandatory for surgical trainees entering higher specialist training in the United Kingdom. Despite its international reputation, and the value placed on the examination in surgical training, there has been little evidence of its predictive validity until recently. In this review, we present a summary of findings of four recent Intercollegiate studies assessing the predictive validity of the MRCS Part A (written) examination. Data from all four studies showed statistically significant positive correlations between the MRCS Part A and other written examinations taken by surgical trainees over the course of their education. The studies summarised in this review provide compelling evidence for the predictive validity of this gatekeeping examination. This review will be of interest to trainees, training institutions and the Royal Colleges given the value placed on the examination by surgical training programmes.

Establishing the predictive validity of the intercollegiate membership of the Royal Colleges of surgeons written examination: MRCS part B.

The Intercollegiate Membership of the Royal Colleges of Surgeons (MRCS) is a high-stakes postgraduate examination taken by thousands of surgical trainees worldwide every year. The MRCS is a challenging assessment, highly regarded by surgical training programmes and valued as a gatekeeper to the surgical profession. The examination is taken at considerable personal, social and financial cost to surgical trainees, and failure has significant implications for career progression. Given the value placed on MRCS, it must be a reliable and valid assessment of the knowledge and skills of early-career surgeons. Our first article 'Establishing the Predictive Validity of the Intercollegiate Membership of the Royal Colleges of Surgeons Written Examination: MRCS Part A' discussed the principles of assessment reliability and validity and outlined the mounting evidence supporting the predictive validity of the MRCS Part A (the multiple-choice questionnaire component of the examination). This, the second article in the series discusses six recently published studies investigating the predictive validity of the MRCS Part B (the clinical component of the examination). All national longitudinal cohort studies reviewed have demonstrated significant correlations between MRCS Part B and other assessments taken during the UK surgical training pathway, supporting the predictive validity of MRCS Part B. This review will be of interest to trainees, trainers and Royal Colleges given the value placed on the examination by surgical training programmes.

Performance of a prehospital HEART score in patients with possible myocardial infarction: a prospective evaluation.

INTRODUCTION: The History, Electrocardiogram (ECG), Age, Risk Factors and Troponin (HEART) score is commonly used to risk stratify patients with possible myocardial infarction as low risk or high risk in the Emergency Department (ED). Whether the HEART score can be used by paramedics to guide care were high-sensitivity cardiac troponin testing available in a prehospital setting is uncertain. METHODS: In a prespecified secondary analysis of a prospective cohort study where paramedics enrolled patients with suspected myocardial infarction, a paramedic Heart, ECG, Age, Risk Factors (HEAR) score was recorded contemporaneously, and a prehospital blood sample was obtained for subsequent cardiac troponin testing. HEART and modified HEART scores were derived using laboratory contemporary and high-sensitivity cardiac troponin I assays. HEART and modified HEART scores of ≤3 and ≥7 were applied to define low-risk and high-risk patients, and performance was evaluated for an outcome of major adverse cardiac events (MACEs) at 30 days. RESULTS: Between November 2014 and April 2018, 1054 patients were recruited, of whom 960 (mean 64 (SD 15) years, 42% women) were eligible for analysis and 255 (26%) experienced a MACE at 30 days. A HEART score of ≤3 identified 279 (29%) as low risk with a negative predictive value of 93.5% (95% CI 90.0% to 95.9%) for the contemporary assay and 91.4% (95% CI 87.5% to 94.2%) for the high-sensitivity assay. A modified HEART score of ≤3 using the limit of detection of the high-sensitivity assay identified 194 (20%) patients as low risk with a negative predictive value of 95.9% (95% CI 92.1% to 97.9%). A HEART score of ≥7 using either assay gave a lower positive predictive value than using the upper reference limit of either cardiac troponin assay alone. CONCLUSIONS: A HEART score derived by paramedics in the prehospital setting, even when modified to harness the precision of a high-sensitivity assay, does not allow safe rule-out of myocardial infarction or enhanced rule-in compared with cardiac troponin testing alone.

Examining the diversity of MRCS examiners.

BACKGROUND: MRCS examiners are the face of the Royal College of Surgeons for early-career surgeons and should therefore represent the workforce they are examining as not to marginalise or negatively impact on the assessment experience of candidates from minoritised groups. This study aimed to explore the diversity of MRCS examiners and whether they represent the demographics of the MRCS candidates. METHODS: A retrospective observational study including all active examiners and examination candidates who attempted MRCS Part A or Part B between January 2020 and July 2021. Self-declared demographic data collected by the Intercollegiate Committee for Basic Surgical Examinations (ICBSE) included gender, sexual orientation, disability status and ethnicity. Following data anonymisation, total group response frequencies were made available to the research team for statistical analysis. RESULTS: Chi-squared analyses showed statistically significant differences in the representation of gender, disability and ethnicity between candidates and examiners (all p < 0.001). Men (83.9% (n = 1121) vs 70.9% (n = 6017) respectively), individuals without disability (98.7% (n = 917) vs 96.1% (n = 6847)) and individuals of White ethnicity (36.6% (n = 346) vs 20.4% (n = 1223)) were significantly overrepresented in the examiners compared to the examination candidates. There was no statistically significant difference in sexual orientation between examiners and candidates (p = 0.712). CONCLUSIONS: Broadly speaking, the socio-demographic profile of MRCS examiners reflects that seen in senior and leadership positions in surgery in the UK - that is, predominantly male and White - but not that seen in early-career surgeons. Positive action is now required in examiner recruitment by the Royal Colleges to ensure that the cohort of MRCS examiners reflects the modern surgical workforce.

Healthy Food Prices Increased More Than the Prices of Unhealthy Options during the COVID-19 Pandemic and Concurrent Challenges to the Food System.

Food prices have escalated due to impacts of the COVID-19 pandemic on global food systems, and other regional shocks and stressors including climate change and war. Few studies have applied a health lens to identify the most affected foods. This study aimed to assess costs and affordability of habitual (unhealthy) diets and recommended (healthy, equitable and more sustainable) diets and their components in Greater Brisbane, Queensland, Australia from 2019 to 2022 using the Healthy Diets Australian Standardised Affordability and Pricing protocol. Affordability was determined for reference households at three levels of income: median, minimum wage, and welfare-dependent. The recommended diet cost increased 17.9%; mostly in the last year when the prices of healthy foods, such as fruit, vegetables and legumes, healthy fats/oils, grains, and meats/alternatives, increased by 12.8%. In contrast, the cost of the unhealthy foods and drinks in the habitual diet 'only' increased 9.0% from 2019 to 2022, and 7.0% from 2021 to 2022. An exception was the cost of unhealthy take-away foods which increased by 14.7% over 2019-2022. With government COVID-19-related payments, for the first time recommended diets were affordable for all and food security and diets improved in 2020. However, the special payments were withdrawn in 2021, and recommended diets became 11.5% less affordable. Permanently increasing welfare support and providing an adequate minimum wage, while keeping basic, healthy foods GST-free and increasing GST to 20% on unhealthy foods, would improve food security and diet-related health inequities. Development of a Consumer Price Index specifically for healthy food would help highlight health risks during economic downturns.

Short- and Long-Term Impact of Prior Chronic Obstructive Pulmonary Disease Exacerbations on Healthcare Resource Utilization and Related Costs: An Observational Study (SHERLOCK).

The observational retrospective cohort Study on HEalthcare Resource utiLization (HCRU) related to exacerbatiOns in patients with COPD (SHERLOCK; D5980R00014) evaluated exacerbation-related HCRU and costs using the U.K. National Health Service Greater Glasgow and Clyde Health Board data. Patients (≥40 years) with COPD were stratified by exacerbations one year before the index date: Group A (none), B (1 moderate), C (1 severe) and D (≥2 moderate and/or severe). All-cause and COPD-related HCRU and costs were assessed over 36 months. Adjusted rate ratios (RRs) or relative costs versus Group A were estimated using generalized linear models with appropriate distributions and link functions. The study included 22 462 patients (Group A, n = 7788; B, n = 5151; C, n = 250 and D, n = 9273). At 12 months, RRs (95% CI) versus Group A for all-cause and COPD-related HCRU, respectively, were highest in Groups C (1.28 [1.18, 1.39] and 1.18 [1.09, 1.29]) and D (1.26 [1.23, 1.28] and 1.29 [1.26, 1.31]). General practitioner and outpatient visits, and general ward stays/days accounted for the greatest COPD-related HCRU. All-cause and COPD-related relative costs (95% CI) versus Group A at 12 months, respectively, were 1.03 (0.94, 1.12) and 1.06 (0.99, 1.13) in Group B; 1.47 (1.07, 2.01) and 1.54 (1.20, 1.97) in Group C; 1.47 (1.36, 1.58) and 1.63 (1.54, 1.73) in Group D. Increased HCRU and costs in patients with exacerbation histories persisted at 36 months, demonstrating the sustained impact of exacerbations. The study suggests the importance of management and prevention of exacerbations through intervention optimization and budgeting by payers for exacerbation-related costs.

Polysubstance Use in Adults With Opioid Use Disorder Receiving Buprenorphine Maintenance.

INTRODUCTION: Studying polysubstance use is a public health recommendation. In the United Arab Emirates, more than 80% of adults with opioid use disorder (OUD) use 2 or more nonopioid substances. This secondary analysis contrasts the characteristics of polysubstance users (OUD + ≥1 nonopioid) with OUD, explores the correlates and predictors of nonfatal overdose, and examines the impact of polysubstance use on OUD treatment outcomes using buprenorphine (BUP). METHODS: This analysis uses data from a 16-week outpatient randomized controlled trial of 141 adults with OUD allocated to BUP + incentivized adherence and abstinence monitoring (n = 70) and BUP in usual care (control, n = 71). Outcomes were nonfatal overdose events over the preceding 12 months, positive drug screens, and treatment retention. Participant characteristics were contrasted, and bivariate statistical tests were conducted for simple associations followed by logistic regression. RESULTS: Polysubstance use was reported by 117 participants (82.9%), the majority of whom used pregabalin 72.1% (n = 75). Compared with OUD, polysubstance users observed higher arrests (median, 1.0 [interquartile range, 0.0-3.0] vs 0.5 [interquartile range, 0.0-2.0]; P = 0.04]) and nonfatal overdose events (n = 33 [31.8%] vs 2 [10.8%], P = 0.003). Carisoprodol and injecting drug use independently predicted nonfatal overdose (adjusted odds ratio, 4.519 [95% confidence interval, 1.81-11.22] and 2.74 [95% confidence interval, 1.15-6.51], respectively). No significant difference was observed in opioid use and retention in treatment outcomes between groups. CONCLUSION: Carisoprodol and injecting drug use increase the likelihood of nonfatal overdose in adults with OUD. Polysubstance use does not impact response to BUP treatment compared with OUD.

Environmental sustainability in national food-based dietary guidelines: a global review.

Food-based dietary guidelines (FBDGs) provide country-specific guidance on what constitutes a healthy diet. With increasing evidence for the synergy between human and planetary health, FBDGs have started to consider the environmental sustainability of food choices. However, the number of countries that discuss environmental sustainability in their guidelines is unknown. The purpose of this Review was to identify countries with government-endorsed FBDGs that made explicit mention of environmental sustainability and to examine the breadth and depth of the inclusion of sustainability in FBDGs. The Food and Agriculture Organization of the UN identified 95 countries with FBDGs. We assessed 83 countries against our inclusion criteria, of which 37 mentioned environmental sustainability. Relevant content was assessed against a set of criteria based on the Food and Agriculture Organization's guiding principles for sustainable healthy diets. The depth to which environmental sustainability was discussed varied and it was often restricted to general explanations of what a sustainable diet is. Few FBDGs addressed why sustainability is important, how dietary changes can be made, or provided quantified advice for implementing sustainable diets.

Lower buprenorphine elimination rate constant is associated with lower opioid use.

BACKGROUND: Opioid craving is suggested to correlate with the rate of reduction in buprenorphine (BUP) plasma levels. No studies explored Buprenorphine elimination rate constant (BUP EL.R) as a predictor of opioid use or retention in BUP treatment. METHODS: Analysis was performed using data from a randomized controlled trial of 141 adults with opioid use disorder (OUD) randomized to Incentivized Adherence and Abstinence monitoring (I-AAM; experimental (n = 70) and treatment-as-usual; control (n = 71). In the I-AAM, structured access to unsupervised BUP doses was provided up to 28 days contingent of adherence measured by Therapeutic Drug Monitoring and abstinence by Urinary Drug Screens (UDS). In contrast, the treatment-as-usual (control) provided unstructured access to unsupervised doses was provided for up to 14 days considering UDS results. The primary outcome was percentage negative UDS. The secondary outcome, retention in treatment, was continuous enrollment in the study and analysis was via intention-to-treat. Significant bivariate correlations with the outcomes were adjusted for group allocation. RESULTS: A significant negative correlation between BUP EL.R and percentage negative opioid screens (Pearson correlation coefficient - 0.57, p < 0.01) was found. After adjusting for trial group, BUP EL.R was shown to be an independent predictor of percentage negative opioid screens (Standardized Beta Coefficient - 0.57, 95% CI - 221.57 to - 97.44, R2 0.322). CONCLUSION: BUP EL.R predicted 32.2% of the variation in percentage negative opioid UDS and may serve as a potential promising tool in precision medicine of BUP treatment. Higher buprenorphine elimination is associated with higher positive opioid urine screens during treatment. TRIAL REGISTRATION: ISRCTN41645723 retrospectively registered on 15/11/2015.

Exocyst inactivation in urothelial cells disrupts autophagy and activates non-canonical NF-κB signaling.

Ureter obstruction is a highly prevalent event during embryonic development and is a major cause of pediatric kidney disease. We have previously reported that ureteric bud-specific ablation of the gene expressing the exocyst subunit EXOC5 in late murine gestation results in failure of urothelial stratification, cell death and complete ureter obstruction. However, the mechanistic connection between disrupted exocyst activity, urothelial cell death and subsequent ureter obstruction was unclear. Here, we report that inhibited urothelial stratification does not drive cell death during ureter development. Instead, we demonstrate that the exocyst plays a critical role in autophagy in urothelial cells, and that disruption of autophagy activates a urothelial NF-κB stress response. Impaired autophagy first provokes canonical NF-κB activity, which is progressively followed by increasing levels of non-canonical NF-κB activity and cell death if the stress remains unresolved. Furthermore, we demonstrate that ureter obstructions can be completely rescued in Exoc5 conditional knockout mice by administering a single dose of the pan-caspase inhibitor z-VAD-FMK at embryonic day 16.5 prior to urothelial cell death. Taken together, ablation of Exoc5 disrupts autophagic stress response and activates progressive NF-κB signaling, which promotes obstructive uropathy.

Type I interferon regulates proteolysis by macrophages to prevent immunopathology following viral infection.

The ability to treat severe viral infections is limited by our understanding of the mechanisms behind virus-induced immunopathology. While the role of type I interferons (IFNs) in early control of viral replication is clear, less is known about how IFNs can regulate the development of immunopathology and affect disease outcomes. Here, we report that absence of type I IFN receptor (IFNAR) is associated with extensive immunopathology following mucosal viral infection. This pathology occurred independent of viral load or type II immunity but required the presence of macrophages and IL-6. The depletion of macrophages and inhibition of IL-6 signaling significantly abrogated immunopathology. Tissue destruction was mediated by macrophage-derived matrix metalloproteinases (MMPs), as MMP inhibition by doxycycline and Ro 28-2653 reduced the severity of tissue pathology. Analysis of post-mortem COVID-19 patient lungs also displayed significant upregulation of the expression of MMPs and accumulation of macrophages. Overall, we demonstrate that IFNs inhibit macrophage-mediated MMP production to prevent virus-induced immunopathology and uncover MMPs as a therapeutic target towards viral infections.

Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial (BICS).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease. METHODS: BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1 < 80% predicted, FEV1/FVC < 0.7), a self-reported history of ≥ 2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥ 40 years and a smoking history ≥ 10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5 mg bisoprolol) over 4-7 weeks depending on tolerance to up-dosing of bisoprolol/placebo-these titration assessments are completed by telephone or video call. Participants complete the remainder of the 52-week treatment period on the final titrated dose (1, 2, 3, 4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography and measurement of blood biomarkers. DISCUSSION: The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally. TRIAL REGISTRATION: Current controlled trials ISRCTN10497306 . Registered on 16 August 2018.

Cost and affordability of healthy, equitable and more sustainable diets in the Torres Strait Islands.

OBJECTIVES: To assess the cost, cost differential and affordability of current and recommended (healthy, equitable, culturally acceptable and more sustainable) diets in the Torres Strait Islands and compare with other Queensland locations. METHODS: The Aboriginal and Torres Strait Islander Healthy Diets ASAP (Australian Standardised Affordability and Pricing) methods protocol was applied in five randomly selected communities in the Torres Strait Islands. RESULTS: The current diet was 32% more expensive than that recommended; 'discretionary' foods comprised 64% of the current diet cost. Families could save at least A$281.38 a fortnight by switching to recommended diets. However, these cost 35-40% more than elsewhere in Queensland. Recommended diets would cost 35% of median and 48% of welfare household income in the Torres Straits. CONCLUSIONS: While less expensive than the current diet, recommended diets are unaffordable for most households. Consequently, many Torres Strait Islander families are at high risk of food insecurity and diet-related disease. IMPLICATIONS FOR PUBLIC HEALTH: Urgent policy action is required to further lower the relative price of recommended diets, and also increase household incomes and welfare supplements to equitably improve food security and diet-related health, and contribute to environmental sustainability in the Torres Strait Islands.

The long-term clinical impact of COPD exacerbations: a 3-year observational study (SHERLOCK).

BACKGROUND AND AIMS: Exacerbations of chronic obstructive pulmonary disease (COPD) drive disease progression and can lead to an accelerated decline in lung function and a burden on healthcare systems. The retrospective, observational cohort Study on HEalthcare Resource utiLization related to exacerbatiOns in patients with COPD (SHERLOCK; D5980R00014) evaluated the associations between exacerbation history and rates of subsequent COPD exacerbations in primary care patients from the National Health Service in Greater Glasgow and Clyde, United Kingdom. METHODS: Patients were stratified into four groups according to exacerbation history in the year before the index date: Group A (no exacerbations), Group B (1 moderate exacerbation only), Group C (1 severe exacerbation only), and Group D (⩾2 moderate or severe exacerbations). The frequencies of moderate and/or severe exacerbations were recorded over 36 months of follow-up and compared with reference Group A, using generalized linear models. RESULTS: Over 36 months of follow-up, the adjusted rate ratios (RRs, 95% confidence interval) of moderate or severe exacerbations relative to Group A were 1.60 (1.53, 1.67), 1.75 (1.50, 2.04), 1.61 (1.54, 1.68), and 3.61 (3.48, 3.74) for Groups B, C, B + C, and D, respectively. Compared with Group A, patients in Group C exhibited an increased rate of moderate (RR, 1.58 (1.35, 1.85)) and severe exacerbations (RR, 3.13 (2.20, 4.46)). CONCLUSION: SHERLOCK highlights that even one moderate exacerbation increases the risk for subsequent exacerbations compared with having no recent prior exacerbations. Reviewing recent exacerbation history to ascertain future exacerbation risk and inform COPD management may reduce hospitalizations and improve patient outcomes.

Differential attainment at MRCS according to gender, ethnicity, age and socioeconomic factors: a retrospective cohort study.

OBJECTIVE: A recent independent review on diversity and inclusivity highlighted concerns that barriers to surgical career progression exist for some groups of individuals and not others. Group-level differences in performance at the Intercollegiate Membership of the Royal Colleges of Surgeons (MRCS) examinations have been identified but are yet to be investigated. We aimed to characterise the relationship between sociodemographic differences and performance at MRCS. DESIGN: Retrospective cohort study. SETTING: Secondary care. PARTICIPANTS: All UK MRCS candidates attempting Part A (n = 5780) and Part B (n = 2600) between 2013 and 2019 with linked sociodemographic data in the UK Medical Education Database (https://www.ukmed.ac.uk). MAIN OUTCOME MEASURES: Chi-square tests established univariate associations with MRCS performance. Multiple logistic regression identified independent predictors of success, adjusted for medical school performance. RESULTS: Statistically significant differences in MRCS pass rates were found according to gender, ethnicity, age, graduate status, educational background and socioeconomic status (all p < 0.05). After adjusting for prior academic attainment, being male (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.87-2.92) or a non-graduate (OR 1.98, 95% CI 1.44-2.74) were independent predictors of MRCS Part A success and being a non-graduate (OR 1.77, 95% CI 1.15-2.71) and having attended a fee-paying school (OR 1.51, 95% CI 1.08-2.10) were independent predictors of Part B success. Black and minority ethnic groups were significantly less likely to pass MRCS Part B at their first attempt (OR 0.41, 95% CI 0.18-0.92 for Black candidates and OR 0.49, 95% CI 0.35-0.69 for Asian candidates) compared to White candidates. CONCLUSIONS: There is significant group-level differential attainment at MRCS, likely to represent the accumulation of privilege and disadvantage experienced by individuals throughout their education and training. Those leading surgical education now have a responsibility to identify and address the causes of these attainment differences.