Evaluation of the North West London Diabetes Foot Care Transformation Project: A Mixed-Methods Evaluation.

Introduction: Diabetes foot ulceration (DFU) presents an enormous burden to those living with diabetes and to the local health systems and economies. There is an increasing interest in implementing integrated care models to enhance the quality of care for people living with diabetes and related complications and the value of co-production approaches to achieve sustainable change. This paper aims to describe the evaluation methodology for the North West London (NWL) Diabetes Foot Care Transformation project. Description: A mixed methods design including: i) a quasi-experimental quantitative analysis assessing the impact of the implementation of the local secondary care multi-disciplinary diabetes foot team clinics on service utilisation and clinical outcomes (amputations and number of healed patients); ii) a phenomenological, qualitative study to explore patient and staff experience; and iii) a within-trial cost-effectiveness analysis (pre and post 2017) to evaluate the programme cost-effectiveness. Discussion and Conclusion: Demonstrating the impact of multidisciplinary, integrated care models and the value of co-production approaches is important for health providers and commissioners trying to improve health outcome. Evaluation is also needed to identify strategies to overcome barriers which might have reduced the impact of the programme and key elements for improvement.

Bridging the education-action gap: a near-peer case-based undergraduate ethics teaching programme.

Undergraduate ethics teaching has made significant progress in the past decade, with evidence showing that students and trainee doctors feel more confident in identifying and analysing ethical issues. There is general consensus that ethics education should enable students and doctors to take ethically appropriate actions, and nurture moral integrity. However, the literature reports that doctors continue to find it difficult to take action when faced with perceived unethical behaviour. This has been evident in recent healthcare scandals, in which care has fallen below acceptable ethical standards, despite the presence of professional ethical guidelines and competencies. The National Foundation Training Programme forms the first 2 years of training for new UK doctors. We designed a Foundation Doctor (FD)-led teaching programme in which medical students were invited to bring cases and experiences from clinical placements for small group discussion facilitated by FDs. The aim was to enable students to act ethically in practice through developing moral sensitivity and moral identity, together with skills in ethical reasoning and tools to address barriers to taking ethical action. FDs were chosen as facilitators, based on the evidence that near-peer is an effective form of teaching in medicine and may provide positive role models for students. This article reviews the background rationale for the programme and its design. Important themes emerging from the case discussions are explored. Student and FD facilitator feedbacks are evaluated, and practical challenges to the implementation of this type of programme are discussed.

What is good medical ethics? A clinician's perspective.

Speaking from the perspective of a clinician and teacher, good medical ethics needs to make medicine better. Over the past 50 years medical ethics has helped shape the culture in medicine and medical practice for the better. However, recent healthcare scandals in the UK suggest more needs to be done to translate ethical reasoning into ethical practice. Focusing on clinical practice and individual patient care, I will argue that, to be good, medical ethics needs to become integral to the activities of health professionals and healthcare organisations. Ethics is like a language which brings a way of thinking and responding to the world. For ethics to become embedded in clinical practice, health professionals need to progress from classroom learners to fluent social speakers through ethical dialogue, ethical reflection and ethical actions. I will end by discussing three areas that need to be addressed to enable medical ethics to flourish and bring about change in everyday clinical care.

Harnessing the LMG legacy: the IME's vision for the future.

London Medical Group was founded in 1963. It was student-led, spawned Medical Groups in almost every UK medical school and met a need for non-partisan debate and dialogue in medical ethics. It became a victim of its own success as the Institute of Medical Ethics published the Pond Report in 1987, which recommended that medical ethics be incorporated into the undergraduate curriculum. Medical schools began to teach medical ethics and the General Medical Council demanded this in 1993's Tomorrow's Doctors. The Institute of Medical Ethics had grown out of the LMG. After running a number of successful conferences for medical ethics teachers, the Institute of Medical Ethics is recapturing the natural innovative tendencies of students and junior doctors that the LMG and related Medical Groups had fostered. It is now launching itself as a membership organisation: the recommendations of the Francis report and responses to it have emphasised the need to support individuals with the ability, freedom and confidence to question the status quo from a reasoned ethical basis. The Institute of Medical Ethics aims to develop a robust medical ethics community ready to face the challenges of 21st Century healthcare.

Dialysis or conservative care for frail older patients: ethics of shared decision-making.

Increasing numbers of frail elderly with end-stage renal disease (ESRD) and multiple comorbidities are undertaking dialysis treatment. This has been accompanied by increasing dialysis withdrawal, thus warranting investigation into why this is occurring and whether a different approach to choosing treatment should be implemented. Despite being a potentially life-saving treatment, the physical and psychosocial burdens associated with dialysis in the frail elderly usually outweigh the benefits of correcting uraemia. Conservative management is less invasive and avoids the adverse effects associated with dialysis, but unfortunately it is often not properly considered until patients withdraw from dialysis. Shared decision-making has been proposed to allow patients active participation in healthcare decisions. Through this approach, patients will focus on their personal values to receive appropriate treatment, and perhaps opt for conservative management. This may help address the issue of dialysis withdrawal. Moreover, shared decision-making attempts to resolve the conflict between autonomy and other ethical principles, including physician paternalism. Here, we explore the ethical background behind shared decision-making, and whether it is genuinely in the patient's best interests or whether it is a cynical solution to encourage more patients to consider conservative care, thus saving limited resources.

Readiness for legally literate medical practice? Student perceptions of their undergraduate medico-legal education.

Medical councils increasingly require graduates to understand law and to practise medicine mindful of the legal rules. In the UK a revised curriculum for medical law and ethics has been published. However, coverage of law in medical education remains variable and doubts exist about how far students acquire legal knowledge and skills in its implementation. This survey of students in two UK medical schools measured their law learning and their confidence in using this knowledge. Concept maps and a self-audit questionnaire were used to capture students' understanding and perceptions of this knowledge domain and self-assessments of their legal knowledge and skills. A large sample was achieved across first, second and final year students. Students agree that a sound understanding of law is essential to being a good doctor. Their perceptions of law are generally positive but the interface between the legal rules and codes of medical ethics creates difficulty. In some areas students offer relatively confident self-assessments of their legal knowledge and skills for practising law. However, levels of confidence in other areas of their law learning raise doubts about the degree to which they can advocate for and protect their patients. Conclusions are drawn about the effectiveness of students' law learning and recommendations made for further research.

Type 2 diabetes: follow up.

CASE HISTORY: A 41 year old accountant recently registered with your practice. His registration health check indicates: BMI 31, BP 150/95, urine 1 + of glucose, no protein, smoker of 15 cigarettes daily. He has had diabetes for seven years and is taking Metformin 500 mg four times daily. It has been over a year since he last saw a doctor and he has now come to see you to obtain a prescription for medication.

Hypothalamic cocaine- and amphetamine-regulated transcript (CART) and agouti-related protein (AgRP) neurons coexpress the NOP1 receptor and nociceptin alters CART and AgRP release.

Nociceptin or orphanin FQ (N/OFQ) and its receptor NOP1 are expressed in hypothalamic nuclei involved in energy homeostasis. N/OFQ administered by intracerebroventricular or arcuate nucleus (ARC) injection increases food intake in satiated rats. The mechanisms by which N/OFQ increases food intake are unknown. We hypothesized that N/OFQ may regulate hypothalamic neurons containing peptides involved in the control of food intake such as cocaine- and amphetamine-regulated transcript (CART), alphaMSH, neuropeptide Y (NPY), and agouti-related protein (AgRP). We investigated the ability of N/OFQ to alter the release of CART, alphaMSH, NPY, and AgRP using ex vivo medial basal hypothalamic explants. Incubation of hypothalamic explants with N/OFQ (1, 10, 100 nM) resulted in significant changes in CART and AgRP release. One hundred nanomoles N/OFQ caused a 33% decrease in release of CART (55-102) immunoreactivity (IR) and increased release of AgRP-IR to 163% but produced no change in either alphaMSH-IR or NPY-IR. Double immunocytochemistry/in situ hybridization demonstrated that CART-IR and NOP1 mRNA are colocalized throughout the hypothalamus, in particular in the paraventricular nucleus, lateral hypothalamus, zona incerta, and ARC, providing an anatomical basis for N/OFQ action on CART release. Dual in situ hybridization demonstrated that AgRP neurons in the ARC also express the NOP1 receptor. Our data suggest that nociceptin via the NOP1 receptor may increase food intake by decreasing the release of the anorectic peptide CART and increasing the release of the orexigenic peptide AgRP.

Triiodothyronine stimulates food intake via the hypothalamic ventromedial nucleus independent of changes in energy expenditure.

Increased food intake is characteristic of hyperthyroidism, although this is presumed to compensate for a state of negative energy balance. However, here we show that the thyroid hormone T(3) directly stimulates feeding at the level of the hypothalamus. Peripheral administration of T(3) doubled food intake in ad libitum-fed rats over 2 h and induced expression of the immediate early gene, early growth response-1, in the hypothalamic ventromedial nucleus (VMN), whereas maintaining plasma-free T(3) levels within the normal range. T(3)-induced feeding occurred without altering energy expenditure or locomotion. Injection of T(3) directly into the VMN produced a 4-fold increase in food intake in the first hour. The majority of T(3) in the brain is reported to be produced by tissue-specific conversion of T(4) to T(3) by the enzyme type 2 iodothyronine deiodinase (D2). Hypothalamic D2 mRNA expression showed a diurnal variation, with a peak in the nocturnal feeding phase. Hypothalamic D2 mRNA levels also increased after a 12- and 24-h fast, suggesting that local production of T(3) may play a role in this T(3) feeding circuit. Thus, we propose a novel hypothalamic feeding circuit in which T(3), from the peripheral circulation or produced by local conversion, stimulates food intake via the VMN.

A role for arcuate cocaine and amphetamine-regulated transcript in hyperphagia, thermogenesis, and cold adaptation.

We have recently shown that injection of the hypothalamic peptide cocaine and amphetamine regulated transcript (CART) into discrete hypothalamic nuclei stimulates food intake. This stimulation was particularly marked in the arcuate nucleus. Here we show that twice daily intra-arcuate injection of 0.2 nmole CART peptide for 7 days was associated with a 60% higher daytime food intake, an 85% higher thermogenic response to the beta3 agonist BRL 35135, and a 60% increase in brown adipose tissue UCP-1 mRNA. In a separate study, using stereotactically targeted gene transfer, a CART transgene was delivered by using polyethylenimine to the arcuate nucleus of adult rats. Food intake was increased significantly during ad libitum feeding and following periods of food withdrawal and food restriction in CART over-expressing animals. CART over-expressing animals lost 12% more weight than controls following a 24-h fast. Brown adipose tissue uncoupling protein-1 (UCP-1) mRNA levels (collected Day 25) were 80% higher in CART over-expressing animals. Finally, by using quantitative in situ hybridization, we found that chronic cold exposure (20 days at 4oC) increased arcuate nucleus CART mRNA by 124%. Together with the orexigenic and thermogenic effects of CART, this finding suggests a role for arcuate nucleus CART in cold adaptation.

Distribution of fluorescence following injection of recombinant adeno-associated virus encoding green fluorescent protein into the paraventricular nucleus.

We have used recombinant type 2 adeno-associated virus to deliver the gene encoding green fluorescent protein into the central nervous system of adult rats. Gene expression, determined by fluorescent microscopy, was observed not only at the site of injection but also in axons following known neuroanatomical pathways. We have demonstrated a spread of enhanced green fluorescent protein from the paraventricular nucleus of the hypothalamus into the median eminence and neurohypophysis. Cell bodies containing enhanced green fluorescent protein were also visualized in the paraventricular nucleus contralateral to the side of injection. These findings suggest that gene transfer by recombinant adeno-associated virus could be used as a tool to investigate hypothalamic-pituitary interactions and, elsewhere in the central nervous system, to trace axonal pathways.

Free cortisol index as a surrogate marker for serum free cortisol.

BACKGROUND: The biologically active component of a hormone is the unbound or free fraction. Changes in cortisol-binding protein could give misleading results if only total cortisol is measured for the interpretation of dynamic function tests. METHODS: This study aimed to measure serum free cortisol using a steady-state gel-filtration method and then to evaluate the correlation between the serum free cortisol and the free cortisol index (FCI), defined as serum total cortisol/cortisol-binding globulin (CBG). RESULTS: Forty-eight serum samples from healthy volunteers undergoing a short Synacthen test were analysed for total cortisol, free cortisol and CBG. The FCI correlated well with a previously established, but more complex, calculation of serum free cortisol (R = 0.98, P <0.001) and with measured serum free cortisol (R = 0.90, P < 0.001). CONCLUSION: Free cortisol index is a reliable and user-friendly measure of serum free cortisol.

A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism.

PURPOSE: The role of thyroxine replacement in subclinical hypothyroidism remains unclear. We performed a 6-month randomized, double-blind, placebo-controlled trial to evaluate the effects of thyroxine treatment for mild subclinical hypothyroidism, defined as a serum thyroid-stimulating hormone level between 5 to 10 microU/mL with a normal serum free thyroxine level (0.8-16 ng/dL). SUBJECTS AND METHODS: We randomly assigned 40 women with mild subclinical hypothyroidism who had presented to their family practitioners to either thyroxine treatment (n = 23; 50 to 100 microg daily) or placebo (n = 17). Health-related quality of life (Hospital Anxiety and Depression scale, 30-item General Health Questionnaire), fasting lipid profiles, body weight, and resting energy expenditure were measured at baseline and 6 months. RESULTS: The most common presenting symptoms were fatigue (n = 33 [83%]) and weight gain (n = 32 [80%]). At presentation, 20 women (50%) had elevated anxiety scores and 22 (56%) had elevated scores on the General Health Questionnaire. Thirty-five women completed the study. There were no significant differences in the changes from baseline to 6 months between women in the thyroxine group and the placebo group for any of the metabolic, lipid, or anthropometric variables measured, expressed as the mean change in the thyroxine group minus the mean change in the placebo group: body mass index, -0.3 kg/m(2) (95% confidence interval [CI]: -0.9 to 0.4 kg/m(2)); resting energy expenditure, -0.2 kcal/kg/24 h (95% CI: -1.3 to 1.0 kcal/kg/24 h); and low-density lipoprotein cholesterol, -4 mg/dL (95% CI: -23 to 15 mg/dL). There was a significant worsening in anxiety scores in the thyroxine group (scores increased in 8 of 20 women and were unchanged in 2 of 20) compared with the placebo group (scores increased in 1 of 14 women and were unchanged in 6 of 14; P = 0.03). CONCLUSIONS; We observed no clinically relevant benefits from 6 months of thyroxine treatment in women with mild subclinical hypothyroidism.