Endodiabology 2006; Issue 2 (June)
ENDODIABOLOGY
endodiabology.blogspot.com
NORTHEAST NEWSLETTER FOR SPRs AND BOSSES TRAPPED IN THE NORTHERN DEANERY
JUNE 2006
Editors: Shaz Wahid and Petros Perros
Associate Editors: Freda Razvi, Akheel Syed and Ebaa Al-Ozairi
SpR PLACEMENTS (NTN year of training from 1st October 2005)
RVI: Arun(5), Salman Razvi (4), Akheel Syed (4), Andrew Advani (3/4), Ebaa Al-Ozairi (3/4), Suresh Vaikkakara (visiting SpR)
Freeman: Eelin Lim(3), Reena Thomas (4), Vishmawitra Sharma
North Tyneside/Wansbeck: Muthu Jayapaul (3) /Chandima Idampitiya (1)
South Tyneside: Ibrahim M Ibrahim (4)
Gateshead: Ravi Erukalapati(1)
Sunderland: Isha Malik(1), Subir Ray (2)
North Tees/Hartlepool: Sony Anthony(4)/ Peter Carey(3)
Middlesbrough: Sukesh Chandran(2), Asgar Madathil (2), A Asim (LAS)
Carlisle: Khaled Mansur-Dukhan (2)
Bishop Auckland/Durham: Beas Bhatacharya (3)/Jeevan Metayil (1)
NGH/QEH: Ravikumar Balasubramanian (2)
Research with numbers (supervisor): Latika Sibal (Prof Home), Arutchelvan Vijayaraman (Prof Home)
Acting up: David Woods (5), Simon Ashwell (5)
MEETINGS / LECTURES / ANNOUNCEMENTS
1st June 2006 Northern Endocrine & Diabetes Summer CME, Freeman Hospital. Contact Simon Ashwell.
6th June 2006 Joint Trainers and Trainees meeting, Board room, 1730-1900, Medical School. Contact Shaz Wahid
24th-27th June 2006 ENDO 2006, Boston, USA. Contact ENDO email or ENDO website.
9th-13th June 2006 American Diabetes Association 66th Annual Scientific Sessions, Washington DC, USA. Contact ADA email.
6th-7th July 2006 Middlesbrough Insulin Infusion Pump Course, James Cook University Hospital. Contact Zoe Halland
11th-14th July 2006 The Society For Endocrinology Summer School, Cambridge. Contact Ann Lloyd
12th July 2006 GIM training ½ day. Contact Lorraine Waugh 0191 223 1247
14th September 2006 GIM training ½. Contact Lorraine Waugh 0191 223 1247
14th-17th September 2006 42nd EASD Annual Meeting 2006, Copenhagen-Malmoe, EASD website
21st September 2006 PCOS UK Conference 2006, Manchester Conference Centre. Contact Holly Small 01483 243336 or PCOS-UK website.
11th October 2006 Northern Endocrine & Diabetes Autumn CME, James Cook University Hospital. Contact Reena Thomas and/or Arutchelvam Vijayaraman
1st November 2006 British Thyroid Association Annual meeting, London, BTA website.
3rd November 2006 Closing date for abstract submission to DUK for APC in Glasgow 2007.
1st-2nd November 2006 ABCD Autumn Meeting, London, ABCD website
6th-7th November 2006 197th Meeting of the Society for Endocrinology Diamond Jubilee Kensington Town Hall, London, Contact SFE website
8th November 2006 RCP Updates in Medicine, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
29th November 2006 Northern Endocrine Region Research and Audit Group annual meeting, Lumley Castle, Durham 2pm-8pm. Contact Shaz Wahid
3-7th December 2006 IDF World Diabetes Congress, Cape Town SA. IDF website
TRAINING ISSUES
Training E-mails: From 1st June 2006 any e-mails related to training matters will be sent to Endodiabology email. This will provide an archive for future reference on Endodiabology website.
Registering with JCHMT/PMETB: It is essential that all new SpRs (even LATs) register with the PMETB (used to be JCHMT). Not doing so means your training is not counted and you cannot have a RITA.
Log Book/Portfolio Documentation: It is a trainees responsibility to make sure their portfolio/log book is prospectively completed and the necessary signatures obtained. Any experience that is not signed off by your educational supervisor at the time cannot be counted towards training.
Assessment tools: Please see the JCHMT website. As of October 2005 Multisource feedback (MSF) and Directly Observed Procedural Skills (DOPS) have been formally introduced and Mini Clinical Evaluation Exercise (Mini-CEX) will go live from October 2006.
Trainee Representative: With Simon Ashwell moving on from July 2006 a 2nd Trainee Representative is needed on the STC. If you wish to undertake this role please forward a 500 word application to Shaz Wahid, outlining what you believe this role entails and your personal qualities that you believe will fit in with this role. The STC will announce a replacement in June 2006.
Consultant Interview preparation: By popular demand we have updated this previously run article. Questions to which you should have an answer at your fingertips are:
Outline your training so far?
Why do you want this job?
Are there any gaps in your training and if there are will this hinder you as a Consultant?
What attributes do you possess that you will bring to the department and Trust?
Do you have any weaknesses?
What are the strengths and weaknesses of this department?
What is Clinical Governance?
How would you enthuse your colleagues with Clinical Governance?
How would you introduce Clinical Governance in an in-patient and out-patient setting?
What is appraisal and revalidation?
Please summarise the GMCs “Good Medical Practice Guide”?
Please present a balanced view on the Diabetes NSF? Please summarise the Diabetes Information Strategy?
What do you know about the National Clinical Audit support Programme?
What do you know about UKDIABS and QUIDS?
What are your feelings about the new Consultant Contract?
What do you understand by the term “core clinical skills”?
What do you know about the document “unfinished business”?
What are your thoughts on Education programmes for Diabetic patients?
How would you improve the Endocrine service provided by this trust?
Can any Endocrinology be delivered primarily in the Community and if so how would you aid this?
Which papers have had a significant impact on your GIM, Diabetes and Endocrine practice in the last 18-months?
What is the role of a Community Diabetologist?
What is the role of the National Clinical Director for the Diabetes NSF?
How would you approach the Trust board with an idea for service development?
Using an example, describe a business case?
How do you see GIM moving forward, and how would you deal with the ever increasing GIM work-load?
How do you see the interface between A&E and GIM?
How would you handle a complaint made against you personally and practically?
How would you handle an under performing Consultant colleague?
How would you handle an under performing HO, SHO or SpR?
How do you feel about the NHS plan?
Do you ration health care?
How do you see the GMC developing from it’s current role?
What do you know about Health action Zones?
What do you know about NHS beacon sites?
What problems with service delivery do you anticipate with the European Working Time Directive?
Define Management?
What are the roles of an NHS Manager?
How has your research benefited you?
How would you appraise an SHO?
What skills are needed when dealing with patients or relatives who are complaining?
Have you completed a critical incident form?
What is the purpose of a critical incident form?
How do feel about Nurse prescribing?
What are your thoughts on Foundation Hospitals?
What do you understand by the terms Payment by Results and Practice Based Commissioning?
What impact has the new GMS contract had on Diabetes and Endocrine Care?
How has/will MMC effect(ed) future training in Diabetes & Endocrinology?
How would you define “professionalism”?
What do you understand about the Long-term Conditions NSF?
What impact has the Renal NSF had on Diabetes care?
Would you prescribe statin therapy to a 25-yr old Type 1 Diabetic lady?
How do you see Academic Training developing in the era of MMC?
Out of Programme experience: Any SpR wishing to take leave from the rotation (research, travel, etc) from any time after 1st October 2006 must notify the Programme Director by the 1st September 2006 and follow the procedure outlined at PIMD website. An advert date is planned end of September 2006 with interviews in November 2006. Any one missing this deadline runs the risk of having no replacement available until the interviews in June 2007.
SpR Training Survey: The regional SpR training survey conducted by Shaz Wahid is now complete and a summary of the results will be presented at the Trainers & Trainees meeting on 6th June 2006.
International Medical Graduates: The recent Foreign Office guidance on the new regulations related to work-permits and medical training will have no effect on those IMGs already holding a training number. If your current period of permit-free training elapses during your SpR training a work-permit will be issued to cover the remainder of your training. But, plan ahead and do not leave matters until the last minute. Contact Human Resources at the PIMD and the Foreign Office well before your permit-free period elapses. As of 1st July 2006 those IMGs applying for future posts (LATs included) will be advised in the advert that the chances of being appointed are unlikely if there is a UK National or EEA National at interview. Now impartiality goes out of the window, this @*#>&s! (Also see letters section)
Mini-CEX documentation: Mini-CEXs are compulsory from 1st October 2006. When undertaking a Mini-CEX retain 1 copy for yourself, give 1 copy to your Mini-CEX supervisor and have 1 copy available for the RITA panel. The Programme Director will retain this copy for the PIMD. Make sure that a Mini-CEX RITA summary is also completed for your RITA in May 2007.
MSF documentation: It is essential that the SpR does not see any original MSF forms from individuals as it is an anonymous exercise. Make sure that the official MSF RITA summary form is completed and 1 copy made available for the RITA panel. This will be retained by the Programme Director for the PIMD.
Training Committee: Committee Chair: Jola Weaver; Regional Speciality Advisor: Richard Quinton; Programme Director: Shaz Wahid; Consultant members: Jean Macleod, Simon Pearce (Research Advisor), Simon Eaton & Ronan Canavan; SpR representatives: Simon Ashwell & Andrew Advani
OLD FACES ON THE GO
Simon Ashwell is currently acting up at James Cook University hospital and will have his CCT on 31st July 2006.
David Woods has obtained his CCT-congratulations.
A blast from the not too distant past: congratulations to Alison Gallagher on obtaining a Consultant post in Leicester.
NEWS FROM THE NORTHEAST
Congratulations to Stuart Bennett on his marriage to Fiona who is a teacher of the deaf on the regional children’s cochlear implant team.
Reena Thomas and Arutchelvam Vijayaraman are the SpR contacts for issues related to the Northern Endocrine and Diabetes CME meetings.
Congratulations to all SpRs and Trainers who had poster and/or oral presentations at ECE and DUK 2006. I saw a strong presence from the North East at ECE 2006 and looking at the abstract book the same can be said for DUK 2006.
Freda Razvi will be undertaking a session at Newcastle Diabetes Centre to keep her hand in during her period of flexible careers leave.
Bill Kelly’s Festschrift is planned for Friday 1st September 2006, 1430 at James Cook University Hospital. Contact Rudy Bilous.
Professor Roy Taylor is on the look out for a research fellow (see letters section). Congratulations to Arun on obtaining his MD.
LETTERS
Contributions for this section can include meeting reports, research experiences, book reviews, experiences abroad, and anything else you feel may benefit trainees and trainers around the region. The success of this section really does depend on YOU.
Book Review - Shaz Wahid
Transitions In Care: meeting the challenges of Type1 Diabetes in young adults. Wolpert HA, Anderson BJ, Weissberg-Benchell J. American Diabetes Association 2006. ISBN 1-58040-172-4. This is an excellent little book that is split into 3 parts. Part 1 sets the scene and parts 2 & 3 explore adolescent diabetes care from the perspective of the patient and health professional, respectively. It is full of little “gems” and provides sound practical advice on managing patients in this challenging area. This book should be standard reading for trainees. Very importantly it can be easily read whilst on the exercise bike as it only measures 10x14cm and is 85 pages in length. Happy reading.
The Future for Diabetes Care - Shaz Wahid
The words of a famous comedian come to mind “..another fine mess you have got us into..” when I think of the recent directives from government and market forces having a detrimental effect on planning future diabetes care. There is an air of despondency when speaking to most Diabetologists and even those colleagues practicing Endocrinology alone look upon a Clinical Diabetologist with sympathy. Clearly the “specialist” role seems threatened with the drive to move 85% of diabetes care into the community. Trainees are cottoning onto this fact and are concerned that the job content of future posts will not be what they envisaged when entering the specialty. However it is important to remember that it is essential to define specialist roles in each locality as there is no way GPs will take on the pregnancy/adolescents/renal disease/post any transplant/ CF / complex 2DM and nor should they. Since starting at South Tyneside our unit’s strategic vision has been to move towards developing specialist clinics. This has served us well as we now have numerous specialist clinics that can’t be decanted into primary care. Between both myself and John Parr 3 clinic sessions of “standard” diabetes clinics could be undertaken in the community, which should satisfy Government and PCT targets and indeed our educational and strategic role can flourish and remain enormously rewarding. The future also remains rosy in that there's a big hump of existing DM which will run into trouble before any of our long term health promotion strategies kick in and with the rising incidence predicted I think there will be a place for specialists for the next 20 years and more. With other drugs heading our way specialist combination regimens will be needed and GPs won't take that on even in intermediate care (of which there is truly none in the North East). Writing this article was a good pep talk and I hope you felt this way as well.
New immigration rules for overseas doctors - Salman Razvi & Akheel Syed
The Immigration and Nationality Directorate, in conjunction with the Department of Health, has introduced changes to the visa laws with respect to overseas (non-UK/non-EU) postgraduate doctors in training. Permit-Free Training (PFT), a special visa category for postgraduate doctors, has been discontinued and overseas doctors will now need to meet the requirements of an employment category of the Immigration Rules, such as the Work Permit (WP). Doctors who are undertaking training programmes as a Specialist Registrar which are due to continue beyond their current leave to remain as a Postgraduate Doctor can switch to WP without the need to re-advertise their post and applications for WPs have to be submitted by the employer by 31 December 2006.
In light of these changes, a survey of overseas trainees in Diabetes & Endocrinology in the region has indicated that the vast majority (14 out of 17 respondents) perceive themselves as affected. Nine of the affected trainees are on PFT, 4 on Highly Skilled Migrant Programme and one on Dependent status. The current visas are due for renewal this year for two, but not up to 2009 for others.
“I fully understand the government’s reasoning behind the new rules, but it has been done abruptly,” commented one affected trainee. Several trainees have raised concerns about the implications of the new rules not only for themselves but also their families as many have spouses whose career prospects have also been affected. Some trainees are anticipating that the Postgraduate Institute for Medicine and Dentistry (PIMD) will be organising WPs on their behalf before the deadline. Telephonic enquiries at the PIMD, however, have elicited the standard reply, “We are still in the process of studying the new rules and will advise affected doctors in due course.”
“I find it surprising that our employers (PIMD) have not been in touch with anyone regarding these important developments,” remarked one trainee. “Trainees may not be able to plan ahead if things are left to the last minute.”
Further information
Immigration and Nationality Directorate website
NHS Employers website
Smith J. A very British muddle. BMJ 2006 Apr 22;332(7547):0
Eaton L. Tossed aside. BMJ. 2006 Apr 22;332(7547):932
Research Fellowship in Human Metabolism - Professor Roy Taylor
The handling of glucose and lipids after meals is central to understanding type 2 diabetes, especially in the early stages of the condition. We know that excess triglyceride uptake into muscle and liver is associated with relative failure to store glucose as glycogen. This one year clinical research post will involve magnetic resonance spectroscopy and associated metabolic investigations on subjects with diabetes and matched controls. The work would be based largely at the Newcastle Magnetic Resonance Centre with some studies on the 7T magnet in Nottingham. It is funded by a Wellcome Programme grant and could allow registration for an M Phil degree (and possible extension for a 2 year MD degree depending upon career choices and funding). Applicants may be enrolled for training in Endocrinology and Diabetes or be considering such training. (MRCP essential). Probable start date 1st Jan 2007. Contact Roy Taylor for informal discussion and further details.
Two New Genes Controlling Human Puberty: GPR54 and KISS1 - Eelin Lim
This year’s Clinical Endocrinology Trust Visiting Lecturer is Professor William Crowley who is the Professor of Medicine at Harvard Medical School, Director of the Harvard Medical School’s Centre of Reproductive Endocrine Sciences Centre & Director of Clinical Research at the Massachusetts General Hospital. His work over the last two and a half decades has been to improve the understanding and treatment of reproductive disorders in humans such as pioneering the use of GnRH analogues in the treatment of children with central precocious puberty, use of pulsatile GnRh for use in puberty induction in men with idiopathic hypogonadotrophic hypogonadism as well as ovulation induction in Kallman’s syndrome amongst many others.
A great mystery of human biology is in the understanding of the neuroendocrine and genetic control of sexual maturity. What switches puberty on? This was the focus of his lecture. Using genetic and molecular approaches in humans and in mice, his group identified two new genes, GPR54 and KISS1, which have offered new light in trying to understand normal reproduction and disorders of puberty. Investigations into a consanguineous family with members who lacked pubertal development (idiopathic hypogonadotrophic hypogonadism) were found to have mutations in GPR54, which is a member of the rhodopsin family of G protein-coupled receptors. Another endogenous peptide derived from a precursor protein, kisspeptin-1 which is encoded by KISS1 gene, has also been recently identified to display agonist activity to GPR54 receptors suggesting perhaps a role in the downstream signalling pathways.
The morning was preceded by interesting case presentations from some of our Endocrine SpRs as well as our Paediatric Endocrine colleagues which generated plenty of discussions and views from our expert visitor. All in all it was an enjoyable and educating morning in midst of the venue change due to fire outside the Copthorne! Many thanks to Andy James for chairing the morning!
RECENT PUBLICATIONS FROM THE NORTHEAST
Please send us your recent publication for inclusion in the next newsletter.
Ashwell SG, Amiel SA, Bilous RW, Dashora U, Heller SR, Hepburn DA, Shutler SD, Stephens JW, Home PD. Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetes. Diabet Med. 2006 Mar;23(3):285-92.
McIntyre EA, Parker L, Pearce MS, Gerrard J, Sattar N, Craft AW, Walker M. Relation between birth weight and soluble markers of endothelial function in middle aged subjects. Heart. 2006 May;92(5):679-80.
McMillan C, Bradley C, Razvi S, Weaver J. Psychometric evaluation of a new questionnaire measuring treatment satisfaction in hypothyroidism: the ThyTSQ. Value Health. 2006 Mar-Apr;9(2):132-9.
Patel S, Minton JA, Weedon MN, Frayling TM, Ricketts C, Hitman GA, McCarthy MI, Hattersley AT, Walker M, Barrett TG. Common variations in the ALMS1 gene do not contribute to susceptibility to type 2 diabetes in a large white UK population. Diabetologia. 2006 Jun;49(6):1209-13.
Salman Razvi, Bijay Vaidya, Petros Perros and Simon H S Pearce. What is the evidence behind the evidence-base? The premature death of block-replace antithyroid drug regimens for Graves’disease. Eur J Endocrinol ; 154: 783-786.
Woods DR, Arun CS, Corris PA, Perros P. Cushing's syndrome without excess cortisol. BMJ. 2006 Feb 25;332(7539):469-70.
RECENT PUBLICATIONS IN DIABETES & ENDOCRINOLOGY THAT HIT THE NEWS OR THAT MAY HAVE A SIGNIFICANT IMPACT ON MANAGEMENT
Denosumab in postmenopausal women with low bone mineral density. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ; AMG 162 Bone Loss Study Group. N Engl J Med. 2006 Feb 23;354(8):821-31.
Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action. This study investigated the efficacy and safety of subcutaneous denosumab over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 10 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. Denosumab treatment resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 % (as compared with an increase of 4.6 % with alendronate and a loss of 0.8 % with placebo), at the total hip of 1.9 to 3.6 % (as compared with an increase of 2.1 % with alendronate and a loss of 0.6 % with placebo), and at the distal third of the radius of 0.4 to 1.3 % (as compared with decreases of 0.5 % with alendronate and 2.0 % with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. In conclusion, the authors have shown that in postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption suggesting that that denosumab might be an effective treatment for osteoporosis. I would highly recommend the accompanying editorial.
Feasibility of treating prehypertension with an angiotensin-receptor blocker. Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, Black HR, Grimm RH Jr, Messerli FH, Oparil S, Schork MA; Trial of Preventing Hypertension (TROPHY) Study Investigators. N Engl J Med. 2006 Apr 20;354(16):1685-97.
Prehypertension is considered a precursor of stage 1 hypertension (systolic 140-149 and/or diastolic 90-99) and a predictor of excessive cardiovascular risk. This study investigated whether pharmacological treatment of prehypertension prevents or postpones stage 1 hypertension. Participants with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower, or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg, were randomly assigned to receive two years of candesartan or placebo, followed by two years of placebo for all. When a participant reached the study end point of stage 1 hypertension, treatment with antihypertensive agents was initiated. Both the candesartan group and the placebo group were instructed to make changes in lifestyle to reduce blood pressure throughout the trial. A total of 409 participants were randomly assigned to candesartan, and 400 to placebo. Data on 772 participants (391 in the candesartan group and 381 in the placebo group; mean age, 48.5 years; 59.6 % male) were available for analysis. During the first two years, hypertension developed in 154 participants in the placebo group and 53 of those in the candesartan group (relative risk reduction, 66.3 %; P<0.001). After four years, hypertension had developed in 240 participants in the placebo group and 208 of those in the candesartan group (relative risk reduction, 15.6 percent; P<0.007). Serious adverse events occurred in 3.5 % of the participants assigned to candesartan and 5.9 % of those receiving placebo. In conclusion, over a period of four years, stage 1 hypertension developed in nearly two thirds of patients with untreated prehypertension (the placebo group). Treatment of prehypertension with candesartan appeared to be well tolerated and reduced the risk of incident hypertension during the study period. Thus, treatment of prehypertension appears to be feasible. However, whether this results in reductions in hard end-points requires further study. A personal take home message is that the target blood pressure of <130/80 for all diabetic patients should be utilised by health professionals given the results of this study when extrapolating to diabetic patients.
Thyroxine in goitre, Helicobacter pylori infection, and chronic gastritis. Centanni M, Gargano L, Canettieri G, Viceconti N, Franchi A, Delle Fave G, Annibale B. N Engl J Med. 2006 Apr 27;354(17):1787-95.
Malabsorption of thyroxine has been described in patients treated with drugs that modify an acidic environment. The authors studied whether there is an increased need for thyroxine in patients with euthyroid multinodular goitre and impaired secretion of gastric acid by assessing the dose of thyroxine required to obtain a low level of TSH (0.05 to 0.20 mU/l) in 248 patients with multinodular goitre. Of these 248 patients, 53 also had Helicobacter pylori-related gastritis and 60 had atrophic gastritis of the body of the stomach (31 with evidence of H. pylori infection and 29 without such evidence). The reference group comprised 135 patients with multinodular goitre and no gastric disorders. In addition, variation in the level of serum TSH was prospectively studied in 11 patients treated with thyroxine before and after H. pylori infection and both before and during treatment with omeprazole in 10 patients treated with thyroxine who had gastroesophageal reflux. The daily requirement of thyroxine was higher (by 22 to 34 %) in patients with H. pylori-related gastritis, atrophic gastritis, or both conditions than in the reference group. In prospective studies, the occurrence of H. pylori infection in the 11 patients treated with thyroxine led to an increase in the level of serum TSH (P=0.002), an effect that was nearly reversed on eradication of H. pylori infection. In a similar way, omeprazole treatment was associated with an increase in the level of serum TSH in all 10 patients treated with thyroxine, an effect that was reversed by an increase in the thyroxine dose by 37 %. In conclusion, patients with impaired acid secretion require an increased dose of thyroxine, suggesting that normal gastric acid secretion is necessary for effective absorption of oral thyroxine. Acid reflux disease is another factor to be wary of before invoking non-compliance as a cause of raised TSH in patients on thyroxine replacement therapy.
Seven years of feast, seven years of famine: boom to bust in the NHS? Alan Maynard, Andrew Street. BMJ 2006;332:906-908.
An excellent article that outlines the problems as a result of recent directives and service targets and what may happen in the future.
Xiang AH et al. Effect of pioglitazone on pancreatic β-cell function and diabetes risk in Hispanic women with prior gestational diabetes. The PIPOD Study. Diabetes. 2006;55:517-522.
The TRIPOD and subsequent PIPOD studies have provided important information regarding the progression of β-cell failure from impaired glucose tolerance to diabetes in a select group of Latino women with a history of gestational diabetes. Although the final sample size in the PIPOD study is fairly small, it still provides interesting observations on the possibility of arresting the deterioration of glucose tolerance in these women. The three main findings from this study were that thiazolidinediones (TZDs) stabilize β-cell function; that a strong relationship exists between reduction in insulin secretion and prevention of progression of diabetes; and that there was no consistent effect on insulin sensitivity after TZDs were discontinued. This is because of a non-linear relationship between insulin sensitivity and reduction in endogenous insulin requirements. Hopefully, larger studies such as the DREAM and ACT-NOW trials will confirm that TZDs can prevent progression of diabetes. From these studies basic clinical guidelines will need to be developed for who to treat with TZDs, at what point in their disease process, and how to follow response. Another important issue will be the cost of preventing diabetes compared to the cost of treating diabetes and its complications.
Ding EL et al. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and misanalysis. JAMA. 2006;295:1288-1299.
Type 2 diabetes increases the risk of coronary heart disease mortality in both men and women, but the risk is more pronounced in women. Through a systematic review and meta analysis, Ding and associates evaluated the association of plasma levels of testosterone, sex hormone-binding globulin (SHBG), and estradiol with the risk of type 2 diabetes. A search of EMBASE and MEDLINE (1966-June 2005), identified 43 prospective and cross-sectional studies involving type 2 diabetes. These studies included a total of 6,974 women and 6,427 men. This analysis pooled data using random effects and meta-regressions. In cross-sectional studies, testosterone level was significantly lower in men with type 2 diabetes and higher in women with type 2 diabetes compared with controls (P<0.001>60 vs ≤60 nmol/L) had an 80% lower risk of type 2 diabetes , whereas men with higher SHBG levels had a 52% lower risk of type 2 diabetes (P=0.003 for sex difference). In cross-sectional studies, estradiol levels were elevated in both men and postmenopausal women with type 2 diabetes compared with controls. The results of this systematic review indicate that endogenous levels of testosterone influence the risk of developing type 2 diabetes in opposite directions in men and women and that SHBG is associated inversely with diabetes risk in both genders, although somewhat more strongly in women. The investigators speculate on mechanisms for the gender-specific effects of testosterone on diabetes risk (mostly via different effects on insulin resistance). They also suggest sex hormone levels might be useful for predicting type 2 diabetes, albeit after additional studies to identify important levels for risk stratification. Study limitations included the use of observational data, lack of reliable data on free hormone levels, and the confounding effects of polycystic ovarian syndrome. Large prospective studies are needed to fully determine the predictive value of sex hormones in the development of type 2 diabetes.
NEXT NEWSLETTER Due out beginning of October 2006, so keep the gossip coming.
endodiabology.blogspot.com
NORTHEAST NEWSLETTER FOR SPRs AND BOSSES TRAPPED IN THE NORTHERN DEANERY
JUNE 2006
Editors: Shaz Wahid and Petros Perros
Associate Editors: Freda Razvi, Akheel Syed and Ebaa Al-Ozairi
SpR PLACEMENTS (NTN year of training from 1st October 2005)
RVI: Arun(5), Salman Razvi (4), Akheel Syed (4), Andrew Advani (3/4), Ebaa Al-Ozairi (3/4), Suresh Vaikkakara (visiting SpR)
Freeman: Eelin Lim(3), Reena Thomas (4), Vishmawitra Sharma
North Tyneside/Wansbeck: Muthu Jayapaul (3) /Chandima Idampitiya (1)
South Tyneside: Ibrahim M Ibrahim (4)
Gateshead: Ravi Erukalapati(1)
Sunderland: Isha Malik(1), Subir Ray (2)
North Tees/Hartlepool: Sony Anthony(4)/ Peter Carey(3)
Middlesbrough: Sukesh Chandran(2), Asgar Madathil (2), A Asim (LAS)
Carlisle: Khaled Mansur-Dukhan (2)
Bishop Auckland/Durham: Beas Bhatacharya (3)/Jeevan Metayil (1)
NGH/QEH: Ravikumar Balasubramanian (2)
Research with numbers (supervisor): Latika Sibal (Prof Home), Arutchelvan Vijayaraman (Prof Home)
Acting up: David Woods (5), Simon Ashwell (5)
MEETINGS / LECTURES / ANNOUNCEMENTS
1st June 2006 Northern Endocrine & Diabetes Summer CME, Freeman Hospital. Contact Simon Ashwell.
6th June 2006 Joint Trainers and Trainees meeting, Board room, 1730-1900, Medical School. Contact Shaz Wahid
24th-27th June 2006 ENDO 2006, Boston, USA. Contact ENDO email or ENDO website.
9th-13th June 2006 American Diabetes Association 66th Annual Scientific Sessions, Washington DC, USA. Contact ADA email.
6th-7th July 2006 Middlesbrough Insulin Infusion Pump Course, James Cook University Hospital. Contact Zoe Halland
11th-14th July 2006 The Society For Endocrinology Summer School, Cambridge. Contact Ann Lloyd
12th July 2006 GIM training ½ day. Contact Lorraine Waugh 0191 223 1247
14th September 2006 GIM training ½. Contact Lorraine Waugh 0191 223 1247
14th-17th September 2006 42nd EASD Annual Meeting 2006, Copenhagen-Malmoe, EASD website
21st September 2006 PCOS UK Conference 2006, Manchester Conference Centre. Contact Holly Small 01483 243336 or PCOS-UK website.
11th October 2006 Northern Endocrine & Diabetes Autumn CME, James Cook University Hospital. Contact Reena Thomas and/or Arutchelvam Vijayaraman
1st November 2006 British Thyroid Association Annual meeting, London, BTA website.
3rd November 2006 Closing date for abstract submission to DUK for APC in Glasgow 2007.
1st-2nd November 2006 ABCD Autumn Meeting, London, ABCD website
6th-7th November 2006 197th Meeting of the Society for Endocrinology Diamond Jubilee Kensington Town Hall, London, Contact SFE website
8th November 2006 RCP Updates in Medicine, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
29th November 2006 Northern Endocrine Region Research and Audit Group annual meeting, Lumley Castle, Durham 2pm-8pm. Contact Shaz Wahid
3-7th December 2006 IDF World Diabetes Congress, Cape Town SA. IDF website
TRAINING ISSUES
Training E-mails: From 1st June 2006 any e-mails related to training matters will be sent to Endodiabology email. This will provide an archive for future reference on Endodiabology website.
Registering with JCHMT/PMETB: It is essential that all new SpRs (even LATs) register with the PMETB (used to be JCHMT). Not doing so means your training is not counted and you cannot have a RITA.
Log Book/Portfolio Documentation: It is a trainees responsibility to make sure their portfolio/log book is prospectively completed and the necessary signatures obtained. Any experience that is not signed off by your educational supervisor at the time cannot be counted towards training.
Assessment tools: Please see the JCHMT website. As of October 2005 Multisource feedback (MSF) and Directly Observed Procedural Skills (DOPS) have been formally introduced and Mini Clinical Evaluation Exercise (Mini-CEX) will go live from October 2006.
Trainee Representative: With Simon Ashwell moving on from July 2006 a 2nd Trainee Representative is needed on the STC. If you wish to undertake this role please forward a 500 word application to Shaz Wahid, outlining what you believe this role entails and your personal qualities that you believe will fit in with this role. The STC will announce a replacement in June 2006.
Consultant Interview preparation: By popular demand we have updated this previously run article. Questions to which you should have an answer at your fingertips are:
Outline your training so far?
Why do you want this job?
Are there any gaps in your training and if there are will this hinder you as a Consultant?
What attributes do you possess that you will bring to the department and Trust?
Do you have any weaknesses?
What are the strengths and weaknesses of this department?
What is Clinical Governance?
How would you enthuse your colleagues with Clinical Governance?
How would you introduce Clinical Governance in an in-patient and out-patient setting?
What is appraisal and revalidation?
Please summarise the GMCs “Good Medical Practice Guide”?
Please present a balanced view on the Diabetes NSF? Please summarise the Diabetes Information Strategy?
What do you know about the National Clinical Audit support Programme?
What do you know about UKDIABS and QUIDS?
What are your feelings about the new Consultant Contract?
What do you understand by the term “core clinical skills”?
What do you know about the document “unfinished business”?
What are your thoughts on Education programmes for Diabetic patients?
How would you improve the Endocrine service provided by this trust?
Can any Endocrinology be delivered primarily in the Community and if so how would you aid this?
Which papers have had a significant impact on your GIM, Diabetes and Endocrine practice in the last 18-months?
What is the role of a Community Diabetologist?
What is the role of the National Clinical Director for the Diabetes NSF?
How would you approach the Trust board with an idea for service development?
Using an example, describe a business case?
How do you see GIM moving forward, and how would you deal with the ever increasing GIM work-load?
How do you see the interface between A&E and GIM?
How would you handle a complaint made against you personally and practically?
How would you handle an under performing Consultant colleague?
How would you handle an under performing HO, SHO or SpR?
How do you feel about the NHS plan?
Do you ration health care?
How do you see the GMC developing from it’s current role?
What do you know about Health action Zones?
What do you know about NHS beacon sites?
What problems with service delivery do you anticipate with the European Working Time Directive?
Define Management?
What are the roles of an NHS Manager?
How has your research benefited you?
How would you appraise an SHO?
What skills are needed when dealing with patients or relatives who are complaining?
Have you completed a critical incident form?
What is the purpose of a critical incident form?
How do feel about Nurse prescribing?
What are your thoughts on Foundation Hospitals?
What do you understand by the terms Payment by Results and Practice Based Commissioning?
What impact has the new GMS contract had on Diabetes and Endocrine Care?
How has/will MMC effect(ed) future training in Diabetes & Endocrinology?
How would you define “professionalism”?
What do you understand about the Long-term Conditions NSF?
What impact has the Renal NSF had on Diabetes care?
Would you prescribe statin therapy to a 25-yr old Type 1 Diabetic lady?
How do you see Academic Training developing in the era of MMC?
Out of Programme experience: Any SpR wishing to take leave from the rotation (research, travel, etc) from any time after 1st October 2006 must notify the Programme Director by the 1st September 2006 and follow the procedure outlined at PIMD website. An advert date is planned end of September 2006 with interviews in November 2006. Any one missing this deadline runs the risk of having no replacement available until the interviews in June 2007.
SpR Training Survey: The regional SpR training survey conducted by Shaz Wahid is now complete and a summary of the results will be presented at the Trainers & Trainees meeting on 6th June 2006.
International Medical Graduates: The recent Foreign Office guidance on the new regulations related to work-permits and medical training will have no effect on those IMGs already holding a training number. If your current period of permit-free training elapses during your SpR training a work-permit will be issued to cover the remainder of your training. But, plan ahead and do not leave matters until the last minute. Contact Human Resources at the PIMD and the Foreign Office well before your permit-free period elapses. As of 1st July 2006 those IMGs applying for future posts (LATs included) will be advised in the advert that the chances of being appointed are unlikely if there is a UK National or EEA National at interview. Now impartiality goes out of the window, this @*#>&s! (Also see letters section)
Mini-CEX documentation: Mini-CEXs are compulsory from 1st October 2006. When undertaking a Mini-CEX retain 1 copy for yourself, give 1 copy to your Mini-CEX supervisor and have 1 copy available for the RITA panel. The Programme Director will retain this copy for the PIMD. Make sure that a Mini-CEX RITA summary is also completed for your RITA in May 2007.
MSF documentation: It is essential that the SpR does not see any original MSF forms from individuals as it is an anonymous exercise. Make sure that the official MSF RITA summary form is completed and 1 copy made available for the RITA panel. This will be retained by the Programme Director for the PIMD.
Training Committee: Committee Chair: Jola Weaver; Regional Speciality Advisor: Richard Quinton; Programme Director: Shaz Wahid; Consultant members: Jean Macleod, Simon Pearce (Research Advisor), Simon Eaton & Ronan Canavan; SpR representatives: Simon Ashwell & Andrew Advani
OLD FACES ON THE GO
Simon Ashwell is currently acting up at James Cook University hospital and will have his CCT on 31st July 2006.
David Woods has obtained his CCT-congratulations.
A blast from the not too distant past: congratulations to Alison Gallagher on obtaining a Consultant post in Leicester.
NEWS FROM THE NORTHEAST
Congratulations to Stuart Bennett on his marriage to Fiona who is a teacher of the deaf on the regional children’s cochlear implant team.
Reena Thomas and Arutchelvam Vijayaraman are the SpR contacts for issues related to the Northern Endocrine and Diabetes CME meetings.
Congratulations to all SpRs and Trainers who had poster and/or oral presentations at ECE and DUK 2006. I saw a strong presence from the North East at ECE 2006 and looking at the abstract book the same can be said for DUK 2006.
Freda Razvi will be undertaking a session at Newcastle Diabetes Centre to keep her hand in during her period of flexible careers leave.
Bill Kelly’s Festschrift is planned for Friday 1st September 2006, 1430 at James Cook University Hospital. Contact Rudy Bilous.
Professor Roy Taylor is on the look out for a research fellow (see letters section). Congratulations to Arun on obtaining his MD.
LETTERS
Contributions for this section can include meeting reports, research experiences, book reviews, experiences abroad, and anything else you feel may benefit trainees and trainers around the region. The success of this section really does depend on YOU.
Book Review - Shaz Wahid
Transitions In Care: meeting the challenges of Type1 Diabetes in young adults. Wolpert HA, Anderson BJ, Weissberg-Benchell J. American Diabetes Association 2006. ISBN 1-58040-172-4. This is an excellent little book that is split into 3 parts. Part 1 sets the scene and parts 2 & 3 explore adolescent diabetes care from the perspective of the patient and health professional, respectively. It is full of little “gems” and provides sound practical advice on managing patients in this challenging area. This book should be standard reading for trainees. Very importantly it can be easily read whilst on the exercise bike as it only measures 10x14cm and is 85 pages in length. Happy reading.
The Future for Diabetes Care - Shaz Wahid
The words of a famous comedian come to mind “..another fine mess you have got us into..” when I think of the recent directives from government and market forces having a detrimental effect on planning future diabetes care. There is an air of despondency when speaking to most Diabetologists and even those colleagues practicing Endocrinology alone look upon a Clinical Diabetologist with sympathy. Clearly the “specialist” role seems threatened with the drive to move 85% of diabetes care into the community. Trainees are cottoning onto this fact and are concerned that the job content of future posts will not be what they envisaged when entering the specialty. However it is important to remember that it is essential to define specialist roles in each locality as there is no way GPs will take on the pregnancy/adolescents/renal disease/post any transplant/ CF / complex 2DM and nor should they. Since starting at South Tyneside our unit’s strategic vision has been to move towards developing specialist clinics. This has served us well as we now have numerous specialist clinics that can’t be decanted into primary care. Between both myself and John Parr 3 clinic sessions of “standard” diabetes clinics could be undertaken in the community, which should satisfy Government and PCT targets and indeed our educational and strategic role can flourish and remain enormously rewarding. The future also remains rosy in that there's a big hump of existing DM which will run into trouble before any of our long term health promotion strategies kick in and with the rising incidence predicted I think there will be a place for specialists for the next 20 years and more. With other drugs heading our way specialist combination regimens will be needed and GPs won't take that on even in intermediate care (of which there is truly none in the North East). Writing this article was a good pep talk and I hope you felt this way as well.
New immigration rules for overseas doctors - Salman Razvi & Akheel Syed
The Immigration and Nationality Directorate, in conjunction with the Department of Health, has introduced changes to the visa laws with respect to overseas (non-UK/non-EU) postgraduate doctors in training. Permit-Free Training (PFT), a special visa category for postgraduate doctors, has been discontinued and overseas doctors will now need to meet the requirements of an employment category of the Immigration Rules, such as the Work Permit (WP). Doctors who are undertaking training programmes as a Specialist Registrar which are due to continue beyond their current leave to remain as a Postgraduate Doctor can switch to WP without the need to re-advertise their post and applications for WPs have to be submitted by the employer by 31 December 2006.
In light of these changes, a survey of overseas trainees in Diabetes & Endocrinology in the region has indicated that the vast majority (14 out of 17 respondents) perceive themselves as affected. Nine of the affected trainees are on PFT, 4 on Highly Skilled Migrant Programme and one on Dependent status. The current visas are due for renewal this year for two, but not up to 2009 for others.
“I fully understand the government’s reasoning behind the new rules, but it has been done abruptly,” commented one affected trainee. Several trainees have raised concerns about the implications of the new rules not only for themselves but also their families as many have spouses whose career prospects have also been affected. Some trainees are anticipating that the Postgraduate Institute for Medicine and Dentistry (PIMD) will be organising WPs on their behalf before the deadline. Telephonic enquiries at the PIMD, however, have elicited the standard reply, “We are still in the process of studying the new rules and will advise affected doctors in due course.”
“I find it surprising that our employers (PIMD) have not been in touch with anyone regarding these important developments,” remarked one trainee. “Trainees may not be able to plan ahead if things are left to the last minute.”
Further information
Immigration and Nationality Directorate website
NHS Employers website
Smith J. A very British muddle. BMJ 2006 Apr 22;332(7547):0
Eaton L. Tossed aside. BMJ. 2006 Apr 22;332(7547):932
Research Fellowship in Human Metabolism - Professor Roy Taylor
The handling of glucose and lipids after meals is central to understanding type 2 diabetes, especially in the early stages of the condition. We know that excess triglyceride uptake into muscle and liver is associated with relative failure to store glucose as glycogen. This one year clinical research post will involve magnetic resonance spectroscopy and associated metabolic investigations on subjects with diabetes and matched controls. The work would be based largely at the Newcastle Magnetic Resonance Centre with some studies on the 7T magnet in Nottingham. It is funded by a Wellcome Programme grant and could allow registration for an M Phil degree (and possible extension for a 2 year MD degree depending upon career choices and funding). Applicants may be enrolled for training in Endocrinology and Diabetes or be considering such training. (MRCP essential). Probable start date 1st Jan 2007. Contact Roy Taylor for informal discussion and further details.
Two New Genes Controlling Human Puberty: GPR54 and KISS1 - Eelin Lim
This year’s Clinical Endocrinology Trust Visiting Lecturer is Professor William Crowley who is the Professor of Medicine at Harvard Medical School, Director of the Harvard Medical School’s Centre of Reproductive Endocrine Sciences Centre & Director of Clinical Research at the Massachusetts General Hospital. His work over the last two and a half decades has been to improve the understanding and treatment of reproductive disorders in humans such as pioneering the use of GnRH analogues in the treatment of children with central precocious puberty, use of pulsatile GnRh for use in puberty induction in men with idiopathic hypogonadotrophic hypogonadism as well as ovulation induction in Kallman’s syndrome amongst many others.
A great mystery of human biology is in the understanding of the neuroendocrine and genetic control of sexual maturity. What switches puberty on? This was the focus of his lecture. Using genetic and molecular approaches in humans and in mice, his group identified two new genes, GPR54 and KISS1, which have offered new light in trying to understand normal reproduction and disorders of puberty. Investigations into a consanguineous family with members who lacked pubertal development (idiopathic hypogonadotrophic hypogonadism) were found to have mutations in GPR54, which is a member of the rhodopsin family of G protein-coupled receptors. Another endogenous peptide derived from a precursor protein, kisspeptin-1 which is encoded by KISS1 gene, has also been recently identified to display agonist activity to GPR54 receptors suggesting perhaps a role in the downstream signalling pathways.
The morning was preceded by interesting case presentations from some of our Endocrine SpRs as well as our Paediatric Endocrine colleagues which generated plenty of discussions and views from our expert visitor. All in all it was an enjoyable and educating morning in midst of the venue change due to fire outside the Copthorne! Many thanks to Andy James for chairing the morning!
RECENT PUBLICATIONS FROM THE NORTHEAST
Please send us your recent publication for inclusion in the next newsletter.
Ashwell SG, Amiel SA, Bilous RW, Dashora U, Heller SR, Hepburn DA, Shutler SD, Stephens JW, Home PD. Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetes. Diabet Med. 2006 Mar;23(3):285-92.
McIntyre EA, Parker L, Pearce MS, Gerrard J, Sattar N, Craft AW, Walker M. Relation between birth weight and soluble markers of endothelial function in middle aged subjects. Heart. 2006 May;92(5):679-80.
McMillan C, Bradley C, Razvi S, Weaver J. Psychometric evaluation of a new questionnaire measuring treatment satisfaction in hypothyroidism: the ThyTSQ. Value Health. 2006 Mar-Apr;9(2):132-9.
Patel S, Minton JA, Weedon MN, Frayling TM, Ricketts C, Hitman GA, McCarthy MI, Hattersley AT, Walker M, Barrett TG. Common variations in the ALMS1 gene do not contribute to susceptibility to type 2 diabetes in a large white UK population. Diabetologia. 2006 Jun;49(6):1209-13.
Salman Razvi, Bijay Vaidya, Petros Perros and Simon H S Pearce. What is the evidence behind the evidence-base? The premature death of block-replace antithyroid drug regimens for Graves’disease. Eur J Endocrinol ; 154: 783-786.
Woods DR, Arun CS, Corris PA, Perros P. Cushing's syndrome without excess cortisol. BMJ. 2006 Feb 25;332(7539):469-70.
RECENT PUBLICATIONS IN DIABETES & ENDOCRINOLOGY THAT HIT THE NEWS OR THAT MAY HAVE A SIGNIFICANT IMPACT ON MANAGEMENT
Denosumab in postmenopausal women with low bone mineral density. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ; AMG 162 Bone Loss Study Group. N Engl J Med. 2006 Feb 23;354(8):821-31.
Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action. This study investigated the efficacy and safety of subcutaneous denosumab over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 10 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. Denosumab treatment resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 % (as compared with an increase of 4.6 % with alendronate and a loss of 0.8 % with placebo), at the total hip of 1.9 to 3.6 % (as compared with an increase of 2.1 % with alendronate and a loss of 0.6 % with placebo), and at the distal third of the radius of 0.4 to 1.3 % (as compared with decreases of 0.5 % with alendronate and 2.0 % with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. In conclusion, the authors have shown that in postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption suggesting that that denosumab might be an effective treatment for osteoporosis. I would highly recommend the accompanying editorial.
Feasibility of treating prehypertension with an angiotensin-receptor blocker. Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, Black HR, Grimm RH Jr, Messerli FH, Oparil S, Schork MA; Trial of Preventing Hypertension (TROPHY) Study Investigators. N Engl J Med. 2006 Apr 20;354(16):1685-97.
Prehypertension is considered a precursor of stage 1 hypertension (systolic 140-149 and/or diastolic 90-99) and a predictor of excessive cardiovascular risk. This study investigated whether pharmacological treatment of prehypertension prevents or postpones stage 1 hypertension. Participants with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower, or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg, were randomly assigned to receive two years of candesartan or placebo, followed by two years of placebo for all. When a participant reached the study end point of stage 1 hypertension, treatment with antihypertensive agents was initiated. Both the candesartan group and the placebo group were instructed to make changes in lifestyle to reduce blood pressure throughout the trial. A total of 409 participants were randomly assigned to candesartan, and 400 to placebo. Data on 772 participants (391 in the candesartan group and 381 in the placebo group; mean age, 48.5 years; 59.6 % male) were available for analysis. During the first two years, hypertension developed in 154 participants in the placebo group and 53 of those in the candesartan group (relative risk reduction, 66.3 %; P<0.001). After four years, hypertension had developed in 240 participants in the placebo group and 208 of those in the candesartan group (relative risk reduction, 15.6 percent; P<0.007). Serious adverse events occurred in 3.5 % of the participants assigned to candesartan and 5.9 % of those receiving placebo. In conclusion, over a period of four years, stage 1 hypertension developed in nearly two thirds of patients with untreated prehypertension (the placebo group). Treatment of prehypertension with candesartan appeared to be well tolerated and reduced the risk of incident hypertension during the study period. Thus, treatment of prehypertension appears to be feasible. However, whether this results in reductions in hard end-points requires further study. A personal take home message is that the target blood pressure of <130/80 for all diabetic patients should be utilised by health professionals given the results of this study when extrapolating to diabetic patients.
Thyroxine in goitre, Helicobacter pylori infection, and chronic gastritis. Centanni M, Gargano L, Canettieri G, Viceconti N, Franchi A, Delle Fave G, Annibale B. N Engl J Med. 2006 Apr 27;354(17):1787-95.
Malabsorption of thyroxine has been described in patients treated with drugs that modify an acidic environment. The authors studied whether there is an increased need for thyroxine in patients with euthyroid multinodular goitre and impaired secretion of gastric acid by assessing the dose of thyroxine required to obtain a low level of TSH (0.05 to 0.20 mU/l) in 248 patients with multinodular goitre. Of these 248 patients, 53 also had Helicobacter pylori-related gastritis and 60 had atrophic gastritis of the body of the stomach (31 with evidence of H. pylori infection and 29 without such evidence). The reference group comprised 135 patients with multinodular goitre and no gastric disorders. In addition, variation in the level of serum TSH was prospectively studied in 11 patients treated with thyroxine before and after H. pylori infection and both before and during treatment with omeprazole in 10 patients treated with thyroxine who had gastroesophageal reflux. The daily requirement of thyroxine was higher (by 22 to 34 %) in patients with H. pylori-related gastritis, atrophic gastritis, or both conditions than in the reference group. In prospective studies, the occurrence of H. pylori infection in the 11 patients treated with thyroxine led to an increase in the level of serum TSH (P=0.002), an effect that was nearly reversed on eradication of H. pylori infection. In a similar way, omeprazole treatment was associated with an increase in the level of serum TSH in all 10 patients treated with thyroxine, an effect that was reversed by an increase in the thyroxine dose by 37 %. In conclusion, patients with impaired acid secretion require an increased dose of thyroxine, suggesting that normal gastric acid secretion is necessary for effective absorption of oral thyroxine. Acid reflux disease is another factor to be wary of before invoking non-compliance as a cause of raised TSH in patients on thyroxine replacement therapy.
Seven years of feast, seven years of famine: boom to bust in the NHS? Alan Maynard, Andrew Street. BMJ 2006;332:906-908.
An excellent article that outlines the problems as a result of recent directives and service targets and what may happen in the future.
Xiang AH et al. Effect of pioglitazone on pancreatic β-cell function and diabetes risk in Hispanic women with prior gestational diabetes. The PIPOD Study. Diabetes. 2006;55:517-522.
The TRIPOD and subsequent PIPOD studies have provided important information regarding the progression of β-cell failure from impaired glucose tolerance to diabetes in a select group of Latino women with a history of gestational diabetes. Although the final sample size in the PIPOD study is fairly small, it still provides interesting observations on the possibility of arresting the deterioration of glucose tolerance in these women. The three main findings from this study were that thiazolidinediones (TZDs) stabilize β-cell function; that a strong relationship exists between reduction in insulin secretion and prevention of progression of diabetes; and that there was no consistent effect on insulin sensitivity after TZDs were discontinued. This is because of a non-linear relationship between insulin sensitivity and reduction in endogenous insulin requirements. Hopefully, larger studies such as the DREAM and ACT-NOW trials will confirm that TZDs can prevent progression of diabetes. From these studies basic clinical guidelines will need to be developed for who to treat with TZDs, at what point in their disease process, and how to follow response. Another important issue will be the cost of preventing diabetes compared to the cost of treating diabetes and its complications.
Ding EL et al. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and misanalysis. JAMA. 2006;295:1288-1299.
Type 2 diabetes increases the risk of coronary heart disease mortality in both men and women, but the risk is more pronounced in women. Through a systematic review and meta analysis, Ding and associates evaluated the association of plasma levels of testosterone, sex hormone-binding globulin (SHBG), and estradiol with the risk of type 2 diabetes. A search of EMBASE and MEDLINE (1966-June 2005), identified 43 prospective and cross-sectional studies involving type 2 diabetes. These studies included a total of 6,974 women and 6,427 men. This analysis pooled data using random effects and meta-regressions. In cross-sectional studies, testosterone level was significantly lower in men with type 2 diabetes and higher in women with type 2 diabetes compared with controls (P<0.001>60 vs ≤60 nmol/L) had an 80% lower risk of type 2 diabetes , whereas men with higher SHBG levels had a 52% lower risk of type 2 diabetes (P=0.003 for sex difference). In cross-sectional studies, estradiol levels were elevated in both men and postmenopausal women with type 2 diabetes compared with controls. The results of this systematic review indicate that endogenous levels of testosterone influence the risk of developing type 2 diabetes in opposite directions in men and women and that SHBG is associated inversely with diabetes risk in both genders, although somewhat more strongly in women. The investigators speculate on mechanisms for the gender-specific effects of testosterone on diabetes risk (mostly via different effects on insulin resistance). They also suggest sex hormone levels might be useful for predicting type 2 diabetes, albeit after additional studies to identify important levels for risk stratification. Study limitations included the use of observational data, lack of reliable data on free hormone levels, and the confounding effects of polycystic ovarian syndrome. Large prospective studies are needed to fully determine the predictive value of sex hormones in the development of type 2 diabetes.
NEXT NEWSLETTER Due out beginning of October 2006, so keep the gossip coming.
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