Scotland's GP Rural Fellowship: an initiative that has impacted on rural recruitment and retention.

CONTEXT: In Scotland 20% of the population live in a remote or rural area spread across 94% of the land mass that is defined as remote and rural. NHS Education for Scotland (NES), NHS Scotland's training and education body, works in partnership with territorial health boards and medical schools to address rural recruitment and retention through a variety of initiatives. The longest established of these is the GP Rural Fellowship, which has been in place since 2002. This article describes this program and reports on a survey of the output of the Fellowship from 2002 to 2013. THE RURAL FELLOWSHIP PROGRAM: The Fellowship is aimed at newly qualified GPs, who are offered a further year of training in and exposure to rural medicine. The Fellowship has grown and undergone several modifications since its inception. The current model involves co-funding arrangements between NES and participating boards, supporting a maximum of 12 fellows per year. The Health Boards' investment in the Fellowship is returned through the service commitment that the Fellows provide, and the funding share from NES allows Fellows to have protected educational time to meet their educational needs in relation to rural medicine. Given this level of funding support it is important that the outcome of the Fellowship experience is understood, in particular its influence on recruitment to and retention in general practice in rural Scotland. To address this need a survey of all previous rural Fellows was undertaken in the first quarter of 2014, including all Fellows that had undertaken the Fellowship between 2002-03 and 2012-13. A total of 69 GPs were recruited to the Fellowship in this period, of which 66 were able to be included in the survey. There was a response rate of 98% to the survey and 63 of those that responded (97%) were working currently in general practice, 53 of whom were doing so in Scotland. A total of 46 graduates of the Fellowship in the period surveyed (71%) were working in rural areas or accessible small towns in Scotland, 39 in substantive general practice roles (60%). LESSONS LEARNED: Scotland's GP Rural Fellowship program represents a successful collaboration between education and service, and the results of the survey reported in this article underline previously unpublished data that suggest that approximately three-quarters of graduates are retained in important roles in rural Scotland. It is unclear however whether the Fellowship confirms a prior intention to work in rural practice, or whether it provides a new opportunity through protected exposure. This will form the basis of further evaluation.

An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist.

BACKGROUND: Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T cells. We report a disorder caused by mutations of IL1RN, which encodes the interleukin-1-receptor antagonist, with prominent involvement of skin and bone. METHODS: We studied nine children from six families who had neonatal onset of sterile multifocal osteomyelitis, periostitis, and pustulosis. Response to empirical treatment with the recombinant interleukin-1-receptor antagonist anakinra in the first patient prompted us to test for the presence of mutations and changes in proteins and their function in interleukin-1-pathway genes including IL1RN. RESULTS: We identified homozygous mutations of IL1RN in nine affected children, from one family from Newfoundland, Canada, three families from The Netherlands, and one consanguineous family from Lebanon. A nonconsanguineous patient from Puerto Rico was homozygous for a genomic deletion that includes IL1RN and five other interleukin-1-family members. At least three of the mutations are founder mutations; heterozygous carriers were asymptomatic, with no cytokine abnormalities in vitro. The IL1RN mutations resulted in a truncated protein that is not secreted, thereby rendering cells hyperresponsive to interleukin-1beta stimulation. Patients treated with anakinra responded rapidly. CONCLUSIONS: We propose the term deficiency of the interleukin-1-receptor antagonist, or DIRA, to denote this autosomal recessive autoinflammatory disease caused by mutations affecting IL1RN. The absence of interleukin-1-receptor antagonist allows unopposed action of interleukin-1, resulting in life-threatening systemic inflammation with skin and bone involvement. (ClinicalTrials.gov number, NCT00059748.)

Evaluation of the antidiabetic activity of DPP IV resistant N-terminally modified versus mid-chain acylated analogues of glucose-dependent insulinotropic polypeptide.

Glucose dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with therapeutic potential for type 2 diabetes due to its insulin-releasing and antihyperglycaemic actions. However, development of GIP-based therapies is limited by N-terminal degradation by DPP IV resulting in a very short circulating half-life. Numerous GIP analogues have now been generated exhibiting DPP IV resistance and extended bioactivity profiles. In this study, we report a direct comparison of the long-term antidiabetic actions of three such GIP molecules, N-AcGIP, GIP(Lys(37)PAL) and N-AcGIP(Lys(37)PAL) in obese diabetic (ob/ob) mice. An extended duration of action of each GIP analogue was demonstrated prior to examining the effects of once daily injections (25nmolkg(-1) body weight) over a 14-day period. Administration of either N-AcGIP, GIP(Lys(37)PAL) or N-AcGIP(Lys(37)PAL) significantly decreased non-fasting plasma glucose and improved glucose tolerance compared to saline treated controls. All three analogues significantly enhanced glucose and nutrient-induced insulin release, and improved insulin sensitivity. The metabolic and insulin secretory responses to native GIP were also enhanced in 14-day analogue treated mice, revealing no evidence of GIP-receptor desensitization. These effects were accompanied by significantly enhanced pancreatic insulin following N-AcGIP(Lys(37)PAL) and increased islet number and islet size in all three groups. Body weight, food intake and circulating glucagon were unchanged. These data demonstrate the therapeutic potential of once daily injection of enzyme resistant GIP analogues and indicate that N-AcGIP is equally as effective as related palmitate derivatised analogues of GIP.