The role of sodium glucose cotransporter-2 inhibitors in atherosclerotic cardiovascular disease: A narrative review of potential mechanisms

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of medication with broad cardiovascular benefits in those with type 2 diabetes, chronic kidney disease, and heart failure. These include reductions in major adverse cardiac events and cardiovascular death. The mechanisms that underlie their benefits in atherosclerotic cardiovascular disease (ASCVD) are not well understood, but they extend beyond glucose lowering. This narrative review summarises the ASCVD benefits of SGLT2 inhibitors seen in large human outcome trials, as well as the mechanisms of action explored in rodent and small human studies. Potential pathways include favourable alterations in lipid metabolism, inflammation, and endothelial function. These all require further investigation in large human clinical trials with mechanistic endpoints, to further elucidate the disease modifying benefits of this drug class and those who will benefit most from it

Falling Incapacity Benefit claims in a former industrial city: policy impacts or labour market improvement?

This article provides an in-depth study of Incapacity Benefit (IB) claims in a major city and of the factors behind their changing level. It relates to the regime prior to the introduction of the Employment and Support Allowance (ESA) in 2008. Glasgow has had one of the highest levels of IB in Britain with a peak of almost one fifth of the working age population on IB or Severe Disablement Allowance (SDA). However, over the past decade the number of IB claimants in Glasgow, as in other high claiming areas, has fallen at a faster rate than elsewhere, and Glasgow now has twice the national proportion of working-age people on IB/SDA rather than its peak of three times. The rise in IB in Glasgow can be attributed primarily to deindustrialisation; between 1971 and 1991, over 100,000 manufacturing jobs were lost in the city. Policy response was belated. Lack of local statistics on IB led to a lengthy delay in official recognition of the scale of the issue, and targeted programmes to divert or return IB claimants to work did not begin on any scale until around 2004. Evidence presented in the article suggests that the reduction in claims, which has mainly occurred since about 2003, has been due more to a strengthening labour market than to national policy changes or local programmes. This gives strong support to the view that excess IB claims are a form of disguised unemployment. Further detailed evaluation of ongoing programmes is required to develop the evidence base for this complex area. However, the study casts some doubt on the need for the post-2006 round of IB reforms in high-claim areas, since rapid decline in the number of claimants was already occurring in these areas. The article also indicates the importance of close joint working between national and local agencies, and further development of local level statistics on IB claimants

Estimating the Economic Value of Australian Stock Herding Dogs

This study aimed to estimate the value of the typical Australian herding dog in terms of predicted return on investment. This required an assessment of the costs associated with owning herding dogs and estimation of the work they typically perform. Data on a total of 4,027 dogs were acquired through The Farm Dog Survey which gathered information from 812 herding dog owners around Australia. The median cost involved in owning a herding dog was estimated to be a total of AU$7,763 over the period of its working life. The work performed by the dog throughout this time was estimated to have a median value of AU$40,000. So, herding dogs typically provided their owners with a 5.2-fold return on investment. When respondents were asked to nominate the maximal, one-off, veterinary expenditure they would consider to remedy an illness or injury for an especially valued dog, the median response was AU$1,001–2,000 which is not concordant with the dogs’ calculated median lifetime value. The current findings equip working dog owners with useful information to make financially appropriate expenditure decisions related to their working dogs. This is expected to increase farm profitability and improve welfare for farm dogs

Valuable Behavioural Phenotypes in Australian Farm Dogs

This report presents findings regarding the ways to optimise the performance of livestock working dogs in Australia. The methods available to optimise dog performance include both environmental and genetic factors. The objectives of this study were to identify objective measures of desirable behavioural phenotypes in Australian livestock working dogs and explore genetic parameters of these \u27quality of working life\u27 traits within the Kelpie breed. The document reports on genotyping that reveals gene-behaviour associations and describes heritability estimates that underpin a database for potential estimated breeding value (EBV) calculations

Valuable Behavioural Phenotypes in Australian Farm Dogs

This report presents findings regarding the ways to optimise the performance of livestock working dogs in Australia. The methods available to optimise dog performance include both environmental and genetic factors. The objectives of this study were to identify objective measures of desirable behavioural phenotypes in Australian livestock working dogs and explore genetic parameters of these \u27quality of working life\u27 traits within the Kelpie breed. The document reports on genotyping that reveals gene-behaviour associations and describes heritability estimates that underpin a database for potential estimated breeding value (EBV) calculations

Estimating the Economic Value of Australian Stock Herding Dogs

This study aimed to estimate the value of the typical Australian herding dog in terms of predicted return on investment. This required an assessment of the costs associated with owning herding dogs and estimation of the work they typically perform. Data on a total of 4,027 dogs were acquired through The Farm Dog Survey which gathered information from 812 herding dog owners around Australia. The median cost involved in owning a herding dog was estimated to be a total of AU$7,763 over the period of its working life. The work performed by the dog throughout this time was estimated to have a median value of AU$40,000. So, herding dogs typically provided their owners with a 5.2-fold return on investment. When respondents were asked to nominate the maximal, one-off, veterinary expenditure they would consider to remedy an illness or injury for an especially valued dog, the median response was AU$1,001–2,000 which is not concordant with the dogs’ calculated median lifetime value. The current findings equip working dog owners with useful information to make financially appropriate expenditure decisions related to their working dogs. This is expected to increase farm profitability and improve welfare for farm dogs

ADRIC: Adverse Drug Reactions In Children - a programme of research using mixed methods

Aims To comprehensively investigate the incidence, nature and risk factors of adverse drug reactions (ADRs) in a hospital-based population of children, with rigorous assessment of causality, severity and avoidability, and to assess the consequent impact on children and families. We aimed to improve the assessment of ADRs by development of new tools to assess causality and avoidability, and to minimise the impact on families by developing better strategies for communication. Review methods Two prospective observational studies, each over 1 year, were conducted to assess ADRs in children associated with admission to hospital, and those occurring in children who were in hospital for longer than 48 hours. We conducted a comprehensive systematic review of ADRs in children. We used the findings from these studies to develop and validate tools to assess causality and avoidability of ADRs, and conducted interviews with parents and children who had experienced ADRs, using these findings to develop a leaflet for parents to inform a communication strategy about ADRs. Results The estimated incidence of ADRs detected in children on admission to hospital was 2.9% [95% confidence interval (CI) 2.5% to 3.3%]. Of the reactions, 22.1% (95% CI 17% to 28%) were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44 out of 249 (17.7%) of ADRs, the remainder originating from hospital. A total of 120 out of 249 (48.2%) reactions resulted from treatment for malignancies. Off-label and/or unlicensed (OLUL) medicines were more likely to be implicated in an ADR than authorised medicines [relative risk (RR) 1.67, 95% CI 1.38 to 2.02; p  48 hours, the overall incidence of definite and probable ADRs based on all admissions was 15.9% (95% CI 15.0 to 16.8). Opiate analgesic drugs and drugs used in general anaesthesia (GA) accounted for > 50% of all drugs implicated in ADRs. The odds ratio of an OLUL drug being implicated in an ADR compared with an authorised drug was 2.25 (95% CI 1.95 to 2.59; p < 0.001). Risk factors identified were exposure to a GA, age, oncology treatment and number of medicines. The systematic review estimated that the incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children [pooled estimate of 2.9% (95% CI 2.6% to 3.1%)] and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. New tools to assess causality and avoidability of ADRs have been developed and validated. Many parents described being dissatisfied with clinician communication about ADRs, whereas parents of children with cancer emphasised confidence in clinician management of ADRs and the way clinicians communicated about medicines. The accounts of children and young people largely reflected parents’ accounts. Clinicians described using all of the features of communication that parents wanted to see, but made active decisions about when and what to communicate to families about suspected ADRs, which meant that communication may not always match families’ needs and expectations. We developed a leaflet to assist clinicians in communicating ADRs to parents. Conclusion The Adverse Drug Reactions In Children (ADRIC) programme has provided the most comprehensive assessment, to date, of the size and nature of ADRs in children presenting to, and cared for in, hospital, and the outputs that have resulted will improve the management and understanding of ADRs in children and adults within the NHS. Recommendations for future research: assess the values that parents and children place on the use of different medicines and the risks that they will find acceptable within these contexts; focusing on high-risk drugs identified in ADRIC, determine the optimum drug dose for children through the development of a gold standard practice for the extrapolation of adult drug doses, alongside targeted pharmacokinetic/pharmacodynamic studies; assess the research and clinical applications of the Liverpool Causality Assessment Tool and the Liverpool Avoidability Assessment Tool; evaluate, in more detail, morbidities associated with anaesthesia and surgery in children, including follow-up in the community and in the home setting and an assessment of the most appropriate treatment regimens to prevent pain, vomiting and other postoperative complications; further evaluate strategies for communication with families, children and young people about ADRs; and quantify ADRs in other settings, for example critical care and neonatology

Holding back the genes: limitations of research into canine behavioural genetics

Canine behaviours that are both desirable and undesirable to owners have a demonstrable genetic component. Some behaviours are breed-specific, such as the livestock guarding by maremmas and flank sucking seen in Dobermanns. While the identification of genes responsible for common canine diseases is rapidly advancing, those genes underlying behaviours remain elusive. The challenges of accurately defining and measuring behavioural phenotypes remain an obstacle, and the use of variable phenotyping methods has prevented meta-analysis of behavioural studies. International standardised testing protocols and terminology in canine behavioural evaluations should facilitate selection against behavioural disorders in the modern dog and optimise breeding success and performance in working dogs. This review examines the common hurdles faced by researchers of behavioural genetics and the current state of knowledge

Enhancing Communication about Paediatric Medicines: Lessons from a Qualitative Study of Parents' Experiences of Their Child's Suspected Adverse Drug Reaction

Background: There is little research on parents’ experiences of suspected adverse drug reactions in their children and hence little evidence to guide clinicians when communicating with families about problems associated with medicines. Objective: To identify any unmet information and communication needs described by parents whose child had a suspected adverse drug reaction. Methods: Semi-structured qualitative interviews with parents of 44 children who had a suspected adverse drug reaction identified on hospital admission, during in-patient treatment or reported by parents using the Yellow Card Scheme (the UK system for collecting spontaneous reports of adverse drug reactions). Interviews were conducted face-to-face or by telephone; most interviews were audiorecorded and transcribed. Analysis was informed by the principles of the constant comparative method. Results: Many parents described being dissatisfied with how clinicians communicated about adverse drug reactions and unclear about the implications for their child’s future use of medicines. A few parents felt that clinicians had abandoned their child and reported refusing the use of further medicines because they feared a repeated adverse drug reaction. The accounts of parents of children with cancer were different. They emphasised their confidence in clinicians’ management of adverse drug reactions and described how clinicians prospectively explained the risks associated with medicines. Parents linked symptoms to medicines in ways that resembled the established reasoning that clinicians use to evaluate the possibility that a medicine has caused an adverse drug reaction. Conclusion: Clinicians’ communication about adverse drug reactions was poor from the perspective of parents, indicating that improvements are needed. The accounts of parents of children with cancer indicate that prospective explanation about adverse drug reactions at the time of prescription can be effective. Convergence between parents and clinicians in their reasoning for linking children’s symptoms to medicines could be a starting point for improved communication