The application of pulsed wave Doppler tissue imaging in the evaluation of cardiac function in cats with primary cardiomyopathy and disease states linked to specific cardiomyopathies in human-beings

Cardiac dysfunction is commonly identified in geriatric cats. Disease may be primary, typically hypertrophic cardiomyopathy (HCM), or may occur in association with a number of specific diseases, such as hyperthyroidism or hypertension.Doppler Tissue Imaging (DTI) techniques allow for the non-invasive assessment of myocardial dynamics. These techniques have previously demonstrated regional and global diastolic impairment in various forms of human cardiomyopathy and in cats with HCM.The aim of this study was to characterise the echocardiographic findings in healthy geriatric cats and to compare these to the changes seen in geriatric cats with primary cardiomyopathy and disease states linked to specific cardiomyopathies in human beings. It was predicted that from this it might be possible to derive disease specific cardiac changes. In addition, it may be possible to elucidate the affect of medication on disease processes.A total of 134 cats, aged eight years or above, were studied. Each cat underwent a conventional echocardiographic examination (two-dimensional, spectral Doppler, and M-mode) and a more advanced assessment of diastolic function (pulsed-wave Doppler tissue imaging [pw-DTI], colour M-mode propagation velocity and spectral Doppler assessment of the isovolumetric relaxation time). The cats were grouped according to either the disease process, or the diastolic filling pattern, and groups were then compared.Pulsed-wave DTI tracings (of both radial and longitudinal velocity) were successfully recorded from the feline myocardium. The repeatability of these measurements was assessed, and generally found to be comparable to the variability reported in human beings. There was no evidence that pw-DTI velocities are affected by age in a normal geriatric cat population. Furthermore, there was no significant difference in the relationship between pw-DTI velocities and age in cats within any of the disease groups studied, although there was some variation with heart rate (as assessed by the R-R interval). In addition, it was demonstrated that when grouped according to the transmitral diastolic flow pattern and the ratio of transmitral A-wave duration to pulmonary venous atrial reversal duration, the pwDTI flow pattern recorded from the apical four chamber view (at either the lateral aspect of the mitral annulus, or mid-lateral wall) was able to differentiate normal from impaired relaxation and pseudonormal flow patterns.Analysis of echocardiographic data demonstrated that there was an increase in the thickness of the basilar interventricular septum in the majority of cats studied. Compared to unaffected cats, cats with HCM had a decrease in the E' velocity (recorded by pw-DTI at the interventricular septum) and a tendency towards a decrease at the lateral aspect of the mitral annulus (recorded from the left apical fourchamber view). A similar decrease in the E' velocity in cats and people with HCM has been reported previously, and is thought to suggest diastolic dysfunction in affected individuals. Cats with chronic renal failure demonstrated some mild 2- dimensional and spectral Doppler abnormalities; however, no pw-DTI changes were detected in this group. The hyperthyroid cats demonstrated increased S' velocities, suggesting an increased inotropic state. In addition, the hyperthyroid cats demonstrated increased A' velocities, the cause of which was undetermined, but which may suggest mild diastolic dysfunction or an increase in atrial systolic function. A comparison of treated and untreated hyperthyroid cats was performed. This found that the treated hyperthyroid cats generally demonstrated less variation from the normal cats, compared to the untreated hyperthyroid cats, this may suggest that the use of carbimazole improves the function of the feline myocardium in thyrotoxic cardiomyopathy.This work, for the first time, uses novel ultrasound techniques to investigate the myocardial dynamics in normal geriatric cats, cats with primary hypertrophy and cats with a range of disease states linked to specific cardiomypathies in human beings. The use of these techniques has provided us with a new insight into these disease processes and has evaluated the use of this clinically applicable tool for the evaluation of feline myocardial dynamics

Community hubs: Ten strategies for sustainability - Learning from the experience of Safe Regeneration

The study explores the factors affecting sustainability within Safe Regeneration (Safe) – a community hub organisation in Sefton, Liverpool city region – that has been operating with steady growth for 20 years, working within some of the most disadvantaged communities in England1. We set out to understand what has helped the organisation and what can be learnt from its experiences that might prove valuable to other community hubs. We want to help other community hub leaders in their journey towards sustainability by sharing the experiences of those involved in the success of Safe Regeneration. Key findings We identified ten characteristics that have helped make Safe Regeneration sustainable: 1. Operating as a business: commercially-minded with social values There is a shared understanding that operating a community hub is a business operation integrating strong social values into commercial activities. 2. Adhering to lean principles Organisational growth has been constrained. The core staff team has been kept small and overheads have been kept low. 3. Operating a hub-and-spoke framework A network of interdependent organisations work together like the parts of a wheel. The hub organisation leads project development and subcontracts to the spokes, a consortium of complementary partner organisations. 4. Focusing on asset acquisition and management Acquiring assets has created turning points, prompting new phases of sustainability. 5.Diversified and entrepreneurial More than 20 services are offered on site, serving the complex and varied needs of the local community. 6. Community-led Strategy is developed through a constant two-way flow through three tiers of governance – community, consortia and trustees. 7. Focusing on impact External impact is prioritised over organisational development. 8. Communicating directly Social media and engaging online video enable broad reach and control over message and delivery. 9. Practising generous leadership Members are enabled to take ownership of their role, work and professional development. 10. Supporting the sector Ideas and knowledge are shared freely with others in the sector. We took an ethnographic, participant-observation approach, involving interviews with 27 participants including eight employees and trustees of Safe Regeneration, seven consortium members and eight community hub leaders from elsewhere in the region. We observed events and day-to-day practice over a period of six months between March and August 2019. Conclusions and recommendations In conclusion, we encourage you to consider whether the characteristics we’ve identified for Safe’s journey towards sustainability could help your organisation on its own journey. We are interested in exploring the extent to which these characteristics apply in other settings and contexts. We recommend creating a community hub leadership development programme that can support a new generation of community hub leaders to work together to grow the sector. We also recommend that anchor institutions consider the leadership role that community hubs can play within the rich and diverse community business sector, and the role that community hub-led consortia could play in the delivery of public sector services. Finally, we suggest that further research addresses current gaps in the literature on community hubs, particularly in relation to leadership and acquiring and managing assets. 1 According to the Indices of Deprivation (gov.uk, 2019) the area in which Safe Regeneration is based is amongst the 0.2% most deprived communities in England

Parents' and clinicians' views of an interactive booklet about respiratory tract infections in children: a qualitative process evaluation of the EQUIP randomised controlled trial

Background: ‘When should I worry?’ is an interactive booklet for parents of children presenting with respiratory tract infections (RTIs) in primary care and associated training for clinicians. A randomised controlled trial (the EQUIP study) demonstrated that this intervention reduced antibiotic prescribing and future consulting intentions. The aims of this qualitative process evaluation were to understand how acceptable the intervention was to clinicians and parents, how it was implemented, the mechanisms for any observed effects, and contextual factors that could have influenced its effects.<p></p> Methods: Semi-structured interviews were conducted with 20 parents and 13 clinicians who participated in the trial. Interviews were audio-recorded and transcribed verbatim. Data were analysed using a framework approach, which involved five stages; familiarisation, development of a thematic framework, indexing, charting, and interpretation.<p></p> Results: Most parents and clinicians reported that the ‘When should I worry’ interactive booklet (and online training for clinicians) was easy to use and valuable. Information on recognising signs of serious illness and the usual duration of illness were most valued. The interactive use of the booklet during consultations was considered to be important, but this did not always happen. Clinicians reported lack of time, lack of familiarity with using the booklet, and difficulty in modifying their treatment plan/style of consultation as barriers to use. Increased knowledge and confidence amongst clinicians and patients were seen as key components that contributed to the reductions in antibiotic prescribing and intention to consult seen in the trial. This was particularly pertinent in a context where decisions about the safe and appropriate management of childhood RTIs were viewed as complex and parents reported frequently receiving inconsistent messages. Conclusions: The ‘When should I worry’ booklet, which is effective in reducing antibiotic prescribing, has high acceptability for clinicians and parents, helps address gaps in knowledge, increases confidence, and provides a consistent message. However, it is not always implemented as intended. Plans for wider implementation of the intervention in health care settings would need to address clinician-related barriers to implementation

Making for Change: an independent evaluation of Making for Change: skills in a fashion training & manufacturing workshop

Making for Change Fashion Training and Manufacturing Workshop is a partnership between HM Prison Service and London College of Fashion, UAL (LCF). Making for Change takes an innovative approach in prison, linked to improving the engagement of women offenders in prison industries by providing training in fashion production skills and accrediting participants with industry-recognised qualifications; offering a route away from re-offending whilst simultaneously addressing the skills shortage within the UK fashion manufacturing industry

Cluster randomised trials in the medical literature: two bibliometric surveys

Background: Several reviews of published cluster randomised trials have reported that about half did not take clustering into account in the analysis, which was thus incorrect and potentially misleading. In this paper I ask whether cluster randomised trials are increasing in both number and quality of reporting. Methods: Computer search for papers on cluster randomised trials since 1980, hand search of trial reports published in selected volumes of the British Medical Journal over 20 years. Results: There has been a large increase in the numbers of methodological papers and of trial reports using the term 'cluster random' in recent years, with about equal numbers of each type of paper. The British Medical Journal contained more such reports than any other journal. In this journal there was a corresponding increase over time in the number of trials where subjects were randomised in clusters. In 2003 all reports showed awareness of the need to allow for clustering in the analysis. In 1993 and before clustering was ignored in most such trials. Conclusion: Cluster trials are becoming more frequent and reporting is of higher quality. Perhaps statistician pressure works

Calcitriol-mediated modulation of urokinase-type plasminogen activator and plasminogen activator inhibitor-2

Calcitriol-induced differentiation of U937 mononuclear phagocytes is known to have divergent effects on the synthesis of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-2 (PAI-2). In this study, we sought to determine whether calcitriol affects the expression of these proteins by modulating intermediate signal trasduction involving intracellular calcium and protein kinase C (PKC). U937 cells were stimulated with calcitriol (50 nM) for 6-72 hr, inducing a transient increase in specific binding of [3H]phorbol dibutyrate ([3H]PDBu), seen only after 24 hr. Staurosporine (2 nM), a PKC inhibitor, had no effect on calcitriol-induced secretion of plasminogen activator (PA) activity. However, staurosporine significantly (P < 0.05) inhibited the ability of calcitriol to enhance phorbol myristate acetate (PMA)-induced secretion of PA inhibitor activity, indicating that this priming effect of calcitriol requires expression of PKC. The calcium ionophore A23187 (0.1 [mu]M) induced a modest increase in secreted PA inhibitor activity, in contrast to the secretion of PA activity which is consistently seen in response to calcitriol. Northern blot analysis demonstrated that A23187 induced an increase in PAI-2 mRNA and a marked reduction in uPA mRNA, while calcitriol induced opposite changes in both mRNA species. We conclude that calcitriol modulates uPA and PAI-2 expression by multiple mechanisms that are both PKC dependent and PKC independent. Our studies also demonstrated that increased intracellular calcium alters the synthesis of both uPA and PAI-2 in a manner which favors expression of PA inhibitor activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29456/1/0000538.pd

How are patients with rare diseases and their carers in the UK impacted by the way care is coordinated? An exploratory qualitative interview study.

BACKGROUND: Care coordination is considered important for patients with rare conditions, yet research addressing the impact of care coordination is limited. This study aimed to explore how care coordination (or lack of) impacts on patients and carers. Semi-structured interviews were conducted with 15 patients and carers/parents in the UK, representing a range of rare conditions (including undiagnosed conditions). Transcripts were analysed thematically in an iterative process. RESULTS: Participants described a range of experiences and views in relation to care coordination. Reports of uncoordinated care emerged: appointments were uncoordinated, communication between key stakeholders was ineffective, patients and carers were required to coordinate their own care, and care was not coordinated to meet the changing needs of patients in different scenarios. As a result, participants experienced an additional burden and barriers/delays to accessing care. The impacts described by patients and carers, either attributed to or exacerbated by uncoordinated care, included: impact on physical health (including fatigue), financial impact (including loss of earnings and travel costs), and psychosocial impact (including disruption to school, work and emotional burden). Overall data highlight the importance of flexible care, which meets individual needs throughout patients'/carers' journeys. Specifically, study participants suggested that the impacts may be addressed by: having support from a professional to coordinate care, changing the approach of clinics and appointments (where they take place, which professionals/services are available and how they are scheduled), and improving communication through the use of technology, care plans, accessible points of contact and multi-disciplinary team working. CONCLUSION: This study provides further evidence of impacts of uncoordinated care; these may be complex and influenced by a number of factors. Approaches to coordination which improve access to care and lessen the time and burden placed on patients and carers may be particularly beneficial. Findings should influence future service developments (and the evaluation of such developments). This will be achieved, in the first instance, by informing the CONCORD Study in the UK

Limb lengthening and peripheral nerve function—factors associated with deterioration of conduction

Background and purpose Limb lengthening is performed for a diverse range of orthopedic problems. A high rate of complications has been reported in these patients, which include motor and sensory loss as a result of nerve damage. We investigated the effect of limb lengthening on peripheral nerve function.Patients and methods 36 patients underwent electrophysiological testing at 3 points: (1) preoperatively, (2) after application of external fixator/corticotomy but before lengthening, and (3) after lengthening. The limb-length discrepancy was due to a congenital etiology (n = 19), a growth disturbance (n = 9), or a traumatic etiology (n = 8).Results 2 of the traumatic etiology patients had significant changes evident on electrophysiological testing preoperatively. They both deteriorated further with lengthening. 7 of the 21 patients studied showed deterioration in nerve function after lengthening, but not postoperatively, indicating that this was due to the lengthening process and not to the surgical procedure. All of these patients had a congenital etiology for their leg-length discrepancy.Interpretation As detailed electrophysiological tests were carried out before surgery, after surgery but before lengthening, and finally after completion of lengthening, it was possible to distinguish between the effects of the operation and the effects of lengthening on nerve function. The results indicate that the etiology, site (femur or tibia), and nerve (common peroneal or tibial) had a bearing on the risk of nerve injury and that these factors had a far greater effect than the total amount of lengthening