52 Rapid Responses published for 38 different articles.

Articles			Rapid Responses
	EDITORIALS: Prostate specific antigen for detecting early prostate cancer Ilic and Green (24 September 2009) [Full text]		The PSA screening editorial defies the evidence Charles J. Wright   (27 November 2009) Read every Rapid Response to this article
	PRACTICE: Metformin associated lactic acidosis Fitzgerald et al. (16 September 2009) [Full text]		D-lactate acidosis due to metformin Heikki Savolainen   (27 November 2009) Read every Rapid Response to this article
	PRACTICE: Tennis elbow Mallen et al. (2 September 2009) [Full text]		Exorcise your tennis elbow Gary Stack   (27 November 2009) Read every Rapid Response to this article
	RESEARCH: Effect of tailored practice and patient care plans on secondary prevention of heart disease in general practice: cluster randomised controlled trial Murphy et al. (29 October 2009) [Abstract] [Full text] [PDF]		Hawthorne Effect L Sam Lewis   (27 November 2009) Treatment of coronary heart disease should begin with lowering blood viscosity. Les.O Simpson   (26 November 2009) Read every Rapid Response to this article
	CLINICAL REVIEW: Cryptosporidiosis Davies and Chalmers (19 October 2009) [Full text]		A case of Cryptosporidium infection leading to IBD suggests a role for common disease pathways Katie Adair, et al.   (26 November 2009) Read every Rapid Response to this article
	EDITORIALS: Panton-Valentine leucocidin associated Staphylococcus aureus infections Etienne and Dumitrescu (16 October 2009) [Full text]		PVL in contact sports and need for Rapid screening especially with Pandemic swine flu. Murugesh Jagadeesan   (25 November 2009) Read every Rapid Response to this article
	RESEARCH: The PRaCTICaL study of nurse led, intensive care follow-up programmes for improving long term outcomes from critical illness: a pragmatic randomised controlled trial Cuthbertson et al. (16 October 2009) [Abstract] [Full text] [PDF]		Re: Cognitive Function assessment might improve the quality of life in intensive care survivors Judith C Wright, et al.   (25 November 2009) Read every Rapid Response to this article
	PRACTICE: Chest radiographs in pregnancy O’Connor et al. (9 October 2009) [Full text]		Re: Chest Radiographs in Pregnancy - why not? Sally J O'Connor   (27 November 2009) Re: To be less invasive and less irrational. Sally J O'Connor   (27 November 2009) Read every Rapid Response to this article
	RESEARCH: Cervical collar or physiotherapy versus wait and see policy for recent onset cervical radiculopathy: randomised trial Kuijper et al. (7 October 2009) [Abstract] [Full text] [PDF]		author's reply Barbara Kuijper, et al.   (27 November 2009) Read every Rapid Response to this article
	NEWS: Giving homoeopathy on the NHS is unethical and unreliable, MPs are told O’Dowd (27 November 2009) [Full text]		The Evidence is Sufficient Stephen J Gordon   (27 November 2009) Read every Rapid Response to this article
	NEWS: Series of studies highlights health benefits of action on climate change Kmietowicz (25 November 2009) [Full text]		The global warming lobby will damage our ability to improve health stephen black   (27 November 2009) Read every Rapid Response to this article
	OBSERVATIONS: Wonder in medicine Sokol (25 November 2009) [Full text]		Words of wisdom Jon Arne Søreide   (26 November 2009) Read every Rapid Response to this article
	LETTERS: Selection bias explains seasonal vaccine’s protection Janjua et al. (24 November 2009) [Full text]		Selection bias explains seasonal vaccine’s protection Danuta M Skowronski   (25 November 2009) Read every Rapid Response to this article
	LETTERS: Sedating unfasted children may be dangerous Crawford and Kapoor (24 November 2009) [Full text]		Sedating fasted children may also be dangerous Alan J Grayson   (26 November 2009) Read every Rapid Response to this article
	VIEWS & REVIEWS: Letting go Paton (24 November 2009) [Full text]		Letting Go Mick A Leach   (26 November 2009) Read every Rapid Response to this article
	RESEARCH: Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies Strazzullo et al. (24 November 2009) [Abstract] [Full text] [PDF]		Fast food and stroke Rizaldy Pinzon   (27 November 2009) Re: Mammalian salt requirement Les.O Simpson   (27 November 2009) Competing Interests Morton Satin   (26 November 2009) Salt and water Tom H Hughes-Davies   (26 November 2009) Mammalian salt requirement Alastair R Michell   (25 November 2009) Read every Rapid Response to this article
	NEWS: Admissions from emergency departments rise as four hour target approaches Mooney (20 November 2009) [Full text]		Curbing the rising tide of short stay admissions in children Sonia K Saxena, et al.   (25 November 2009) Read every Rapid Response to this article
	HEAD TO HEAD: Should the NHS strive to eradicate all unexplained variation? Yes Richards (19 November 2009) [Full text]		Unexplained ? L Sam Lewis   (26 November 2009) Read every Rapid Response to this article
	PRACTICE: A woman with acute myelopathy in pregnancy: case progression Reuß et al. (20 November 2009) [Full text]		Autoimmune diseases in pregnancy Muhammad K Rafiq   (26 November 2009) Read every Rapid Response to this article
	CLINICAL REVIEW: Diagnosis and management of dengue Teixeira and Barreto (18 November 2009) [Full text]		Prevention of vector breeding through community engagement Biji T Kurien   (27 November 2009) Dengue fever: Vector control is important! Fook Chang Lam   (25 November 2009) Read every Rapid Response to this article
	EDITORIALS: Is primary care research a lost cause? Mar (18 November 2009) [Full text]		-not if it returns to its roots john howie   (26 November 2009) Read every Rapid Response to this article
	VIEWS & REVIEWS: An inside story Dalrymple (17 November 2009) [Full text]		Doctors in literature Alan J O'Rourke   (26 November 2009) Read every Rapid Response to this article
	VIEWS & REVIEWS: Rhyme and reason Moore (17 November 2009) [Full text]		Re: Oliver Wendell Holmes and puerperal fever Wendy Moore   (27 November 2009) Oliver Wendell Holmes and puerperal fever Peter N Bennett   (26 November 2009) Read every Rapid Response to this article
	RESEARCH: Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study Levine et al. (17 November 2009) [Abstract] [Full text] [PDF]		Can Thyroid function tests predict preeclampsia and what proportion of hypothyroid women have a history of preclampsia in their pregnancies ? Neeru Gupta, et al.   (27 November 2009) Read every Rapid Response to this article
	NEWS: Poor service provision is blamed for overuse of antipsychotics in dementia patients Mashta (17 November 2009) [Full text]		Both conventional and atypical anti- psychotics are dangerous Zekria Ibrahimi   (27 November 2009) Considering the alternatives Wiiliam R Jones, et al.   (27 November 2009) Please don't waste more resources Thomas A Groves   (26 November 2009) Read every Rapid Response to this article
	FEATURE: Doctors in management Stephenson (17 November 2009) [Full text]		Health management education for UK medical students Timothy D Heymann, et al.   (27 November 2009) Read every Rapid Response to this article
	NEWS: Australia operates "closed shop" to restrict doctors from overseas, say critics Sweet (16 November 2009) [Full text]		Something worth Protecting Peter A West   (27 November 2009) Read every Rapid Response to this article
	NEWS: Chlamydia screening in young people fails to reduce prevalence Mayor (13 November 2009) [Full text]		Yet more problems with chlamydia screening Trevor G Stammers   (26 November 2009) Read every Rapid Response to this article
	RESEARCH: Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study Dumurgier et al. (10 November 2009) [Abstract] [Full text] [PDF]		Validity of the results Edward M Absoud   (27 November 2009) Read every Rapid Response to this article
	EDITORIALS: Greater equality and better health Pickett and Wilkinson (10 November 2009) [Full text]		A pardigm shifting hypothesis and Dr Johnson's swallows Seth Jenkinson   (25 November 2009) Read every Rapid Response to this article
	EDITORIALS: Slow walking speed in elderly people Harwood and Conroy (10 November 2009) [Full text]		Fast walking and the mind Evan L Lloyd   (27 November 2009) Read every Rapid Response to this article
	LETTERS: Never mind the treatment, what about the tests? Bamji (10 November 2009) [Full text]		Cervical radiculopathy, never mind the tests what about the treatment? Laurie Allan   (27 November 2009) Read every Rapid Response to this article
	RESEARCH: Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial Lund et al. (9 November 2009) [Abstract] [Full text] [PDF]		Re: Is repaglinide really suitable for combination therapy with insulin? Søren S. Lund, et al.   (27 November 2009) Is repaglinide really suitable for combination therapy with insulin? Stefano Malinverni   (25 November 2009) Read every Rapid Response to this article
	ANALYSIS: How long does it take to train a surgeon? Purcell Jackson and Tarpley (5 November 2009) [Full text]		How long does it take to train non-surgeons to perform surgery? Kathryn M Chu, et al.   (25 November 2009) What is the Aim? M Felix Freshwater   (25 November 2009) Read every Rapid Response to this article
	RESEARCH: Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial Hoff et al. (29 May 2009) [Abstract] [Full text] [PDF]		Re: Complications due to sigmoidoscopy and colonoscopy? Geir Hoff   (26 November 2009) Complications due to sigmoidoscopy and colonoscopy? Hans-Hermann Dubben   (25 November 2009) Read every Rapid Response to this article
	NEWS: Journal retracts article about age of transfused blood three years after publication Lenzer (20 May 2009) [Full text]		Muddy Waters: "Fraud" Vs. "Lost Data" And An Editor's Conflict Of Interest Shailendra Joshi   (25 November 2009) Read every Rapid Response to this article
	VIEWS & REVIEWS: Shiny happy people? Spence (20 May 2009) [Full text]		a modest proposal for a melanoma trial Stephen F Hayes   (26 November 2009) Read every Rapid Response to this article
	EDITORIALS: Treatment of enteric fever Parry and Beeching (3 June 2009) [Full text]		Chronic carriage and mucosal health. Richard G Fiddian-Green   (27 November 2009) Carrier state is a major risk for emergence of antimicrobial resistance to typhoidal salmonellae Hendrik K van Saene, et al.   (25 November 2009) Read every Rapid Response to this article

EDITORIALS: Prostate specific antigen for detecting early prostate cancer Ilic and Green (24 September 2009) [Full text] Prostate specific antigen for detecting early prostate cancer The PSA screening editorial defies the evidence 27 November 2009 Charles J. Wright, consultant Toronto, Canada, M5T2Y9 Send response to journal: Re: The PSA screening editorial defies the evidence Dear Sir, The papers on pages 784 and 793 of the October 3rd BMJ, and also the first column of Dr Ilic's editorial in the same journal were very interesting, but his conclusions are incongruous. It is as if, having summarised all the evidence to date on the validity of PSA screening, it was decided to ignore most of it and basically state that what we need is more research. The more time we spend conducting more research the more men will continue to be subjected to major interventions with the accompanying high risks of serious complications including incontinence, impotence and even death (I must admit to some bias here in view of the death of a close friend from a massive pulmonary embolus on day 7 following radical prostatectomy, recommended to him because of a raised PSA level - the pathology in retrospect showed a prostate problem that would almost certainly never have bothered him if left alone). How could an editorial on this subject possibly avoid the conclusion that seems now very clear from the evidence, namely that PSA screening should be abandoned. It may continue to be useful in managing symptomatic patients but surely it is now clear that it leads to substantially more harm than benefit as a screening test for normal healthy men. We have known for decades that prostate "cancer" can be found at autopsy in up to 80% of elderly men who have died of unrelated causes. In other words, pathologists are currently incapable of predicting the prognosis for clinical disease from microscopic appearances (again, not news). We now know also from the large published trials that the "benefit" from PSA screening lies somewhere between vanishingly small and non-existent Yes, we certainly need the research focus to turn towards the molecular biology of prostate "cancer" wherein a solution to this problem may lie, but until then it is doing a serious disservice to men to state the kind of timid and insipid conclusion of this editorial, rather than a clear cease and desist recommendation on PSA screening. Yours sincerely, Charles J. Wright, MD,MSc,FRCS(C,E,Ed) Consultant in medical and academic affairs, program planning and evaluation Suite 704, 211 St Patrick Street, Toronto, Ontario, Canada, M5T 2Y9 email: cjwright@rogers.com Competing interests: None declared

PRACTICE: Metformin associated lactic acidosis Fitzgerald et al. (16 September 2009) [Full text] Metformin associated lactic acidosis D-lactate acidosis due to metformin 27 November 2009 Heikki Savolainen, Prof. Dept. of Occup. Safety & Hlth., POB 536, FIN-33101 Tampere, Finland Send response to journal: Re: D-lactate acidosis due to metformin Dear Editor, The article describing metformin-induced lactate acidosis (1) contains a figure which might be amended for clarity. The case is that metformin increases the D-lactate formation from the methylglyoxal, a glucose break-down product, through the methylglyoxalase system (2). The increase can be demonstrated even in clinically stable diabetes patients receiving the drug. This distinction is important as D-lactate is slowly metabolized by a high Km mitochonrial D-lactate oxidase contributing thus to the duration of acidosis. Propylene glycol in IV drugs also gives rise to D-lactate so that this could also be its source in critically ill patients. 1 Fitzgerald E, Mathieu S, Ball A. Metformin associated lactic acidosis. BMJ 2009; 339: b3660 2 Talasniemi JP, Pennanen S, Savolainen H, et al. Assay of D-lactate in diabetic plasma and urine. Clin Biochem 2008; 41: 1099-1103 Competing interests: None declared

PRACTICE: Tennis elbow Mallen et al. (2 September 2009) [Full text] Tennis elbow Exorcise your tennis elbow 27 November 2009 Gary Stack, GP Park Medical Practice, Killarney, Co Kerry Send response to journal: Re: Exorcise your tennis elbow I totally agree with Dr O'Connor, I have been extremely disappointed with the results of injection. I advise the patient of same and suggest the following exercises learnt from a sports physician many years ago: 1. WRIST ON WRIST, FLEX & EXTEND x 25 (Place the wrist of the painful forearm on top of the other wrist & move it up & down 25 times) 2. = 1. UPSIDE DOWN x 25 (Turn turn "bad" wrist in the opposite direction and again move it up & down 25 times) 3. = 1. and 2. HOLDING CAN OF BEANS x 25 (Do 1 & 2 holding a weight) 4. WRING A TEA TOWEL x 25 5. SQUEEZE A TENNIS BALL x 25 6. APPLY AN ANTI-INFLAMMATORY GEL (May well be the massage of the area rather than the medication that helps!) Do all of the above 3 times a day until resolution To my financial detriment I have had excellent results. Competing interests: None declared

RESEARCH: Effect of tailored practice and patient care plans on secondary prevention of heart disease in general practice: cluster randomised controlled trial Murphy et al. (29 October 2009) [Abstract] [Full text] [PDF] Effect of tailored practice and patient care plans on secondary prevention of heart... Hawthorne Effect 27 November 2009 L Sam Lewis, GP Trainer Surgery, Newport, Pembrokeshire, SA42 0TJ Send response to journal: Re: Hawthorne Effect Perhaps this study should be re-titled "Effect of Academia taking an interest in General Practice, with regular pep-talks", and subtitled "Subliminal messaging re: managing Hospital Admission Rates" ? It is interesting that this effect did not depend on the putative interventions; there was no measurable difference in effect on cholesterol or BP process measures, yet hospital admissions declined. That's benefit enough, you might think.. until you ask " What happened to patient well-being, morbidity and mortality ? " Perhaps people who needed hospital admission didn't get it ?? One could focus further study on CHD morbidity. Such advice and keen interest as was shown in this study , also pertains under the QOF incentive scheme. Yet Des Spence is unimpressed with any outcomes change.. Perhaps this is a new "Toyota Way" ? Give me academic "personalised interest" anytime ( and some away-days !), instead of blanket overburden with muda, mura, and muri ? References Grimshaw et al. "Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations." The Lancet, Volume 342, Issue 8883, Pages 1317-1322 Parsons HM: What caused the Hawthorne effect? A scientific detective story. Adm Soc 1978, 10:259-283. Publisher Full Text Des Spence: Dr Doom BMJ 2009;339:b4663, doi: 10.1136/bmj.b4663 (Published 12 November 2009) Jeffrey Liker (2003), The Toyota Way: 14 Management Principles from the World's Greatest Manufacturer, First edition, McGraw-Hill, ISBN 0-07- 139231-9. Competing interests: None declared Effect of tailored practice and patient care plans on secondary prevention of heart... Treatment of coronary heart disease should begin with lowering blood viscosity. 26 November 2009 Les.O Simpson, retired experimental pathologist Dunedin New Zealand 9077 Send response to journal: Re: Treatment of coronary heart disease should begin with lowering blood viscosity. The sheer size of the published literature dealing with coronary heart disease (CHD) makes it unlikely that any investigator is familiar with all that information. A PubMed search listed 209695 titles. Hidden within that mass is 604 titles dealing with CHD and blood viscosity and 565 titles dealing with CHD and blood rheology. The lack of any mention by Murphy et al of either of the last 2 topics, makes it likely that they are unaware that there is a role for impaired blood flow in the pathogenesis of CHD. Although the paper concerned patient care and secondary prevention of CHD, the paper provided no insights into the group's concept of the pathophysiology of the disorder they were investigating. Cholesterol levels were assessed, but elevated cholesterol as a cause of increased blood viscosity and of reduced red cell deformability was not recognised. Nor was there any recognition of the published reports which show blood viscosity as a causal factor in hypertension. At least since the 1980s it has been shown that smoking increases blood viscosity, but it was unclear just what was meant by the statement, "For all measurements of blood pressure we also considered smoking status." As early as 1964, Mayer had reported the results of a study of blood viscosity in healthy subjects and in those, "...with unequivocable evidence of coronary heart disease." He concluded, "It is suggested that the higher viscosity of whole blood and plasma is a contributory factor in the development of the clinical symptoms of coronary heart disease and possibly of atherosclerosis itself." Many other investigators have reached similar conclusions. There was early interest in the fact that natives with a diet rich in fish had a low incidence of heart disease. In 1985 Kromhout et al reported that a daily intake of 35 grams of oily fish reduced the incidence of coronary heart disease by 50% in a 20 year long follow up study. Simons et al (1988) reported that 16 grams daily of fish oil as MaxEPA, reduced triglycerides by 58% and plasma cholesterol by 34%. Others have reported similar findings. Therefore, is it reasonable to make recommendations about patient care when a major factor is not recognised or considered ? As the first objective should be to lower blood viscosity, patients should be advised to stop smoking; to reduce their dietary intake of saturated fats; to increase their dietary intake of oily fish and to include a session of low intensity activity during each day. All four recommendations will lower blood viscosity. Competing interests: None declared

CLINICAL REVIEW: Cryptosporidiosis Davies and Chalmers (19 October 2009) [Full text] Cryptosporidiosis A case of Cryptosporidium infection leading to IBD suggests a role for common disease pathways 26 November 2009 Katie Adair, FY2 Paediatrics Royal Hospital for Sick Children, Dalnair Street, Glasgow, G3 8SJ, Lawrence Armstrong, Jonathan Bishop, Richard K Russell Send response to journal: Re: A case of Cryptosporidium infection leading to IBD suggests a role for common disease pathways Davies and Chalmers provide a useful and comprehensive account of cryptosporidiosis in immunocompetent and immunocompromised individuals (1). The article references data which suggest that Cryptosporidium infection may cause relapse of inflammatory bowel disease (IBD)(2). We have recently seen a de novo case of IBD occurring after acute cryptosporidium infection. A 13 year old previously well female developed acute gastroenteritis, with stools positive for Cryptosporidium parvum. Her symptoms persisted despite subsequent negative stool cultures and 4 months after initial presentation a diagnosis of Ulcerative Colitis was confirmed by endoscopic examination together with characteristic findings on mucosal biopsy. The biopsies did not demonstrate persistence of Cryptosporidium. She had an aggressive disease course that resulted in the development of an acute severe colitis with toxic megacolon necessitating colectomy within weeks of presentation. The colectomy specimen had macroscopic and microscopic features consistent with Ulcerative Colitis. IBD arises in a genetically susceptible individual when a dysregulated immune response to gut bacteria leads to chronic intestinal inflammation(3). The genetic susceptibility to IBD has become more fully understood with the completion of genome wide association studies (GWAS) in patients with IBD that have implicated genes involved in both the adaptive and innate immune response(4). Infectious gastroenteritis has long been implicated with the onset of IBD with a recent study demonstrating the increased risk of IBD following infection with specific bacterial pathogens (Salmonella, Campylobacter)(5). While cryptosporidiosis is known to cause acute relapse of IBD symptoms in patients with established disease(6), we do not know of any other published reports where Cryptosporidium is implicated in de novo disease. In disease models, IBD-type lesions have been induced by infecting immunocompromised mice with Cryptosporidium parvum (7). Interferon gamma (IFN-gamma)is one of the key cytokines produced by Cryptosporidium parvum infection. Mice developed to have absent IFN-gamma activity (Gamma Interferon Knockout mice) develop severe fatal small bowel disease after infection with Cryptosporidium parvum(8). Regulation of IFN- gamma is controlled by IL-12/IL-23, one of the key regulatory pathways in IBD patients identified from the GWAS(9,10). This case therefore further illustrates how immune dysregulation resulting from a complex interaction between the host and the environment can trigger chronic and debilitating inflammatory illnesses that may result from common aetiological pathways in a seemingly immunocompetent individual. 1. Davies AP, Chalmers RM. Cryptosporidiosis. BMJ 2009;339:b4168 2.Manthey MW, Ross AB, Soergel KH. Cryptosporidiosis and inflammatory bowel disease. Experience from the Milwaukee outbreak. Dig Dis Sci 1997;42:1580-6 3.Van Limbergen J, Russell RK, Nimmo ER, Satsangi J. The Genetics of Inflammatory Bowel Disease. The American Journal of Gastroenterology 2007; 102(12):2820-2831 4.Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nature Genetics 2008; 40(8):955-962. 5.Gradel KO, Nielsen HL, Schlonheyder HC, Ejlertsen T, Kristensen B, Nielsen H. Increased short- and long-term risk of inflammatory bowel disease after salmonella or campylobacter gastroenteritis. Gastroenterology 2009;137:495-501 6.Manthey MW, Ross AB, Soergel KH. Crytptosporidiosis and inflammatory bowel disease. Experience from the Milwaukee outbreak. Dig Dis Sci1997;42:1580-6 7.Waters WR, Wannemuehler MJ, Sacco RE, Palmer MV, Haynes JS, Pesch BA, Harp JA. Cryptosporidium parvum- induced inflammatory bowel disease of TCR-beta- x TCR-delta-deficient mice. J Parasitol 1999;85:1100-5 8.Griffiths JK, Theodos C, Paris M, Tzipori S. The gamma interferon gene knockout mouse: a highly sensitive model for evaluation of therapeutic agents against Cryptosporidium parvum. J Clin Microbiol 1998; 36(9):2503-2508. 9.Gomez Morales MA, La RG, Ludovisi A, Onori AM, Pozio E. Cytokine profile induced by Cryptosporidium antigen in peripheral blood mononuclear cells from immunocompetent and immunosuppressed persons with cryptosporidiosis. J Infect Dis 1999; 179(4):967-973. 10.Wang K, Zhang H, Kugathasan S, Annese V, Bradfield JP, Russell RK et al. Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn Disease. American Journal of Human Genetics 2009; 84(3):399-405. Competing interests: None declared Editorial note Patient consent obtained.

EDITORIALS: Panton-Valentine leucocidin associated Staphylococcus aureus infections Etienne and Dumitrescu (16 October 2009) [Full text] Panton-Valentine leucocidin associated Staphylococcus aureus infections PVL in contact sports and need for Rapid screening especially with Pandemic swine flu. 25 November 2009 Murugesh Jagadeesan, SpR in Microbiology Blackpool Victoria Hospital,Whinney Heys Road,Blackpool.FY3 8NR Send response to journal: Re: PVL in contact sports and need for Rapid screening especially with Pandemic swine flu. The Authors have righly pointed out in the article more Prevalence of Methicillin Sensitive Staphylococcus aureus with PVL in the UK,which is classically noted in clinical presentation. In addition it may be also worth considering Staphylococcus aureus with PVL in Athletes involved in Contact sports like Rugby,Wrestling with recurrent boil and skin infection infections ,especially if involving more than one athlete. Like the authors pointed out for household contacts, personnel hygiene and decolonisation would help in this setting as well,with avoidance of sharing fomites like contaminated towel. In UK the turn-around time for results from SRU in suspected PVL infections is from 48hrs to 7days (in rare delay due to transportation).It may be worth introducing in house testing for PVL genes lukS-PV and lukF- PV as additional cards in laboratories already using Molecular Diagnostic testing methods for MRSA and others PCR systems which allow for this addition.This would shorten turnaround time and would also be saving lives especially with expected aggressive infections following Primary Pandemic influenza infection. Competing interests: None declared

RESEARCH: The PRaCTICaL study of nurse led, intensive care follow-up programmes for improving long term outcomes from critical illness: a pragmatic randomised controlled trial Cuthbertson et al. (16 October 2009) [Abstract] [Full text] [PDF] The PRaCTICaL study of nurse led, intensive care follow-up programmes for improving... Re: Cognitive Function assessment might improve the quality of life in intensive care survivors 25 November 2009 Judith C Wright, consultant in critical care and anaesthesia James Cook University Hospital Middlesbrough TS4 3BW, Gerry Danjoux, Alan Batterham, and Simon Howell Send response to journal: Re: Re: Cognitive Function assessment might improve the quality of life in intensive care survivors Rehabilitation following intensive care admission Dear Editor, We read with interest Prof Cuthbertson and colleagues’ results from their PRaCTICaL study.1 We believe that the lack of any positive or cost effective result may be due to the unsupervised approach and the lack of any specific target. Given the high prevalence of anxiety and depression following intensive care admission it would not be surprising to find that patients issued with a manual do not then feel able or motivated to follow it.2,3,4 In addition the study utilised no objective measure of fitness improvement; this is a clear limitation as self-report methods are prone to bias. We are currently performing an exploratory trial (PIX study) looking at the effects of a targeted supervised exercise programme in patients discharged from intensive care. Our treatment group have baseline cardiopulmonary exercise testing and quality of life questionnaires completed prior to a supervised targeted exercise programme. It is supervised by a senior physiotherapist from critical care and targeted by using the Borg scale of exertion. Following completion, cardiopulmonary exercise testing is repeated and further quality of life indices are measured. This therefore enables formal objective changes in fitness to be assessed, which we believe to be critical in assessing change in physical fitness status. The study was designed in this way as we believe that the key to any rehabilitation is that it is supervised and targeted. In short although the results of the PRacTICAL study are disappointing they do not mean that the 80 plus hospitals across the UK that have follow-up services have wasted their money. We agree with Prof Cuthbertson et al. that a review of what follow-up services provide should be performed but that this is in conjunction with a targeted approach to rehabilitation. Our study is due to complete in 2011. Yours, JC Wright - Consultant in critical care and anaesthesia James Cook University Hospital Middlesbrough, G Danjoux - Consultant in anaesthesia James Cook University Hospital Middlesbrough , AM Batterham – Professor in Exercise Science University of Teesside, S Howell – Senior Lecturer and Honorary Consultant in anaesthesia University of Leeds. On behalf on the PIX study investigators References 1. Cuthbertson BH, Rattray J, Campbell MK, Gager M, Roughton S, Smith A, etal. The PRaCTICaL study of nurse led, intensive care follow-up programmes for improving long term outcomes from critical illness: a pragmatic randomised controlled trial. British Medical Journal 2009;339 (Oct 16 – 1 );b3723 2. Eddleston J, White P, Guthrie E. Survival, morbidity and quality of life after discharge from intensive care. Crit Care Med 200;28:2293-9. 3. Kapfhammer HP, Rothenhausler HB, Krausenneck T, Stoll C, Scelling G. Posttraumatic stress disorder and health-related quality of life in long- term survivors of acute respiratory distress syndrome. Am J Psychiatry 2004;161:45-52. 4. Cuthbertson B, Hull A, Strachan A, Scott J. Post-traumatic stress disorder after critical illness requiring general intensive care. Intensive care medicine 2004;30:450-5 Competing interests: None declared

PRACTICE: Chest radiographs in pregnancy O’Connor et al. (9 October 2009) [Full text] Chest radiographs in pregnancy Re: Chest Radiographs in Pregnancy - why not? 27 November 2009 Sally J O'Connor, Respiratory SpR Kingston Hospital, Surrey, KT2 7QB Send response to journal: Re: Re: Chest Radiographs in Pregnancy - why not? The points made by Dr McCann et al are valid and welcomed. The criteria mentioned in the article are those from the BTS guidelines: Recommendations for the management of cough in adults. These guidelines state that a chest radiograph should be performed in all adults with a chronic cough (greater than 8 weeks duration), or with atypical symptoms including haemoptysis, breathlessness, fever, chest pain or weight loss. The article aimed to highlight that pregnancy itself should not affect a clinician's decision to perform a chest radiograph. We agree that pregnant women should be assessed as if they were not pregnant. However, the understanding of the low foetal risk posed by chest radiographs is not yet common knowledge amongst patients. Concern regarding any radiation in pregnancy is prevalent. Until patients are better informed, it remains prudent to discuss and document the decision to perform a chest radiograph. In the process it is possible to educate patients and facilitate informed decision-making. Competing interests: None declared Chest radiographs in pregnancy Re: To be less invasive and less irrational. 27 November 2009 Sally J O'Connor, Respiratory SpR Kingston Hospital, Surrey, KT2 7QB Send response to journal: Re: Re: To be less invasive and less irrational. Dr Ali's comments are welcomed. In hindsight the neck swelling should have been actively investigated - biopsy may have allowed an earlier and/or less invasive diagnosis. Nonetheless, the chest radiograph aided staging and choice of further imaging - it should have been performed on admission. The inclusion of fever in the BTS Cough Guidelines allows serious conditions such as pneumonia, tuberculosis and lymphoma to be diagnosed early. The chest radiograph is a highly effective screening tool in these cases, although admittedly patients with simple upper respiratory tract infections and persistent fever may end up being unnecessarily radiographed. Competing interests: None declared

RESEARCH: Cervical collar or physiotherapy versus wait and see policy for recent onset cervical radiculopathy: randomised trial Kuijper et al. (7 October 2009) [Abstract] [Full text] [PDF] Cervical collar or physiotherapy versus wait and see policy for recent onset cervical... author's reply 27 November 2009 Barbara Kuijper, neurologist Rotterdam, The Netherlands, 3078 HT, Barbara Kuijper, Jos Tans, Anita Beelen, Frans Nollet and Marianne de Visser Send response to journal: Re: author's reply We very much appreciate Dr Jacks’ comments regarding our article 1. His main concern is that we studied patients with other conditions than cervical radiculopathy. The patients in our study were referred by their general physician to the neurology outpatient clinic of the participating hospital because a cervical radicular syndrome was suspected. The diagnosis cervical radiculopathy was confirmed by a neurologist, who subsequently verified that the patients satisfied our inclusion and exclusion criteria. All patients had arm pain radiating distal to the elbow with an average VAS-score of 70 mm on the 0-100 mm scale, indicating quite severe pain. Sensory disturbances with a dermatomal irradiation pattern were found in 80 to 90 percent of cases, hyporeflexia and muscle weakness in corresponding myotomes were present in lower percentages, as is usually the case in this medical condition 2-4 . We are confident that the combination of the typical clinical picture and the imaging findings showing root compression in 74-82 % of the cases, are compatible with cervical radiculopathy only. For a comprehensive description of the clinical signs of cervical radiculopathy we refer to our review article 4. 1. Kuijper B, Tans JT, Beelen A, Nollet F, de Visser M. Cervical collar or physiotherapy versus wait and see policy for recent onset cervical radiculopathy: randomised trial. Bmj 2009;339:b3883. 2. Radhakrishnan K, Litchy WJ, O'Fallon WM, Kurland LT. Epidemiology of cervical radiculopathy. A population-based study from Rochester, Minnesota, 1976 through 1990. Brain 1994;117 ( Pt 2):325-35. 3. Yoss RE, Corbin KB, Maccarty CS, Love JG. Significance of symptoms and signs in localization of involved root in cervical disk protrusion. Neurology 1957;7(10):673-83. 4. Kuijper B, Tans JT, Schimsheimer RJ, van der Kallen BF, Beelen A, Nollet F, et al. Degenerative cervical radiculopathy: diagnosis and conservative treatment. A review. Eur J Neurol 2009;16(1):15-20. Competing interests: None declared

NEWS: Giving homoeopathy on the NHS is unethical and unreliable, MPs are told O’Dowd (27 November 2009) [Full text] Giving homoeopathy on the NHS is unethical and unreliable, MPs are told The Evidence is Sufficient 27 November 2009 Stephen J Gordon, A practising homeopath and General Secretary of the European Central Council of Homeopaths Norfolk Clinic NR3 4AG Send response to journal: Re: The Evidence is Sufficient The evidence base for homeopathy is easily sufficient for it to remain in the NHS. Taking a range of evidence including systematic reviews, RCTs, outcome studies and trials comparing its effectiveness with conventional treatments gives homeopathy an evidence profile that matches or surpasses those of a whole range of interventions currently practised in the NHS. If homeopathy is to go, then the so-called experts who gave opposing evidence at this highly unbalanced hearing must, by their own criteria, have the integrity to raise their hands and admit that there is a whole raft of other interventions used daily in the NHS that must go too. http://clinicalevidence.bmj.com/ceweb/about/knowledge.jsp Competing interests: A practising homeopath and General Secretary of the European Central Council of Homeopaths

NEWS: Series of studies highlights health benefits of action on climate change Kmietowicz (25 November 2009) [Full text] Series of studies highlights health benefits of action on climate change The global warming lobby will damage our ability to improve health 27 November 2009 stephen black, management consultant london sw1w 9sr Send response to journal: Re: The global warming lobby will damage our ability to improve health There is something extremely sad about the world when genuinely good ideas for improving public health need to be bundled with the global warming bandwagon in order to gain attention. In fact, we face a significant risk that the attention spent on global warming will damage world health. Even if I believed the world was about to enter another ice age, I would regard the replacement of indian wood-burning stoves as a good public health intervention. Even the skeptics who don't believe in global warming would agree that London's health would improve if the population did more exercise. Pretending that either have much if anything at all to do with climate change is both nonsense and an outrageous distraction from the actual public health case for the ideas (and this is probably true for the other interventions: i've just picked the easiest to ridicule). But there is a worse effect. The current case for the health impact of warming itself is far far more tenuous than the case for the existence of warming. The case for avoiding warming rather than adapting to it is also pretty poor. In both cases we are urged by the lobby to spend extraordinary amounts of money for small and highly uncertain gains. If we spent a fraction of the proposed sums on intervention where we are certain health and quality of life could be improved, we could guarantee to achieve much larger benefits. The risk of attaching such good projects to the warming bandwagon is that they will be squeezed out of the portfolio by the vast expenditure on warming avoidance projects of dubious benefit. In addition, urging health professionals to campaign specifically on climate change will take time away from the pursuit of easily reachable health gains. Hitching good public health projects to the climate bandwagon will ultimately damage public health. Competing interests: None declared

OBSERVATIONS: Wonder in medicine Sokol (25 November 2009) [Full text] Wonder in medicine Words of wisdom 26 November 2009 Jon Arne Søreide, Professor of Surgery Stavanger University Hospital, 4022 Stavanger, NORWAY Send response to journal: Re: Words of wisdom Dear Dr. Sokol. I thank you so much for your very thoughtful and well written article on wonders in medicine. While there might be a lot more to say, there is little more to add to your short note, which indeed is a to-the-point piece of excellent writing and communication with the society of professionals in the medical community. Thanks a lot. Competing interests: None declared

LETTERS: Selection bias explains seasonal vaccine’s protection Janjua et al. (24 November 2009) [Full text] Selection bias explains seasonal vaccine’s protection Selection bias explains seasonal vaccine’s protection 25 November 2009 Danuta M Skowronski, Epidemiologist BC Centre for Disease Control, Vancouver, British Columbia, Canada Send response to journal: Re: Selection bias explains seasonal vaccine’s protection Please note that in the second paragraph of our Letter to the Editor of BMJ, the final parenthesis of sentence seven should read "(~15%)" rather than "(9%)" and the order of references 5 and 6 should be sequentially reversed. Competing interests: DMS has previously (>3 years ago) received research grant funding from GSK and Sanofi-Pasteur.

LETTERS: Sedating unfasted children may be dangerous Crawford and Kapoor (24 November 2009) [Full text] Sedating unfasted children may be dangerous Sedating fasted children may also be dangerous 26 November 2009 Alan J Grayson, Speciality Registrar, Emergency Medicine Royal Blackburn Hospital, Haslingden Road, Blackburn, BB22EE Send response to journal: Re: Sedating fasted children may also be dangerous Dear Editor, The contention by Drs Crawford and Kapoor that general anaesthesia with a protected airway in a fasted child is the safest option is not in doubt.(1) That it is necessary for many minor procedures is, as is their belief that ketamine is any inherently more unsafe than propofol, thiopental, fentanyl or any other agent that they may choose to use in their anaesthetic room. Most trauma or emergency operating lists include children, especially in district general hospitals, and they are not always supervised by consultant anaesthetists with an interest in paediatrics. The College of Emergency Medicine guidelines on the safe sedation of children are quite clear.(2) The dismissal of the paper by Treston (3) as a "ten year old paper in which no child suffered aspiration pneumonitis" is erroneous with a trend towards increased vomiting in fasted children and I would invite them to reread that, along with the paper by Agrawal, cited in the CEM guidelines in which there were no significant differences between those meeting fasting guidelines and those not. Emergency Medicine trainees undergo a year of training in the Acute Care Common Stem in Anaesthesia and ICU. Most deaneries specify 6 months at ST3 in Paediatric Emergency Medicine where available. Their concern that any doctor may be administering ketamine is unfounded; again the guidelines are quite clear "Ketamine should be only used by clinicians experienced in its use and capable of managing any complications, particularly airway obstruction, apnoea and laryngospasm. The doctor managing the ketamine sedation and airway should be suitably trained and experienced in ketamine use, with a full range of advanced airway skills." Whilst I believe that there will always be disagreement between some emergency physicians and some anaesthetists over sedation in the emergency department, one thing is certain, either safe sedation, delivered by trained specialists in the ED, or safe general anaesthesia, delivered by specialists in the operating theatre, is significantly more acceptable and humane than the traditional "brutacaine" approach. Yours Alan Grayson 1. Crawford, DC and Kapoor, A. Sedating unfasted children may be dangerous. BMJ 2009;339:b4959. 2. The College of Emergency Medicine. Guideline for ketamine sedation in emergency departments. secure.collemergencymed.ac.uk/asp/document.asp?ID=4880. 3. Treston G. Prolonged pre-procedure fasting time is unnecessary when using titrated intravenous ketamine for paediatric procedural sedation. Emerg Med Aust 2004;16:145-50. 4. Agrawal D, et al. Preprocedural Fasting State and Adverse Events in Children Undergoing Procedural Sedation and Analgesia in a Pediatric Emergency Department. Ann Emerg Med. 2003;42:636-646. Competing interests: None declared

VIEWS & REVIEWS: Letting go Paton (24 November 2009) [Full text] Letting go Letting Go 26 November 2009 Mick A Leach, GP principal Harrogate, HG1 4QD Send response to journal: Re: Letting Go In his piece "Letting Go" Dr Paton gives us his Personal View of the need that we should in Britain accept euthanasia. We are all members of our society and have to live within the limits agreed by people of many and varied beliefs and values. In offering any response I tread warily but I'd like respectfully to make three observations of my own. He poignantly describes his own experiences: of his wife letting go, of her life, of her relationships; of his letting go of his wife. She'd lived life to the full, but modern medicine (which is, after all, largely a reflection of society as a whole) refused to accept that her time on earth was coming to an end and help guide her through the transition period. And then, mercifully, there was her last fortnight, surrounded by her husband, children and grandchildren, "able to talk and laugh and share in the gossip till near the end". Isn't it time that society started to recognise that death is a normal life event, one that we don't have to, at all times, strive to postpone with increasingly futile medical intervention? Once it was recognised that she was within her time of dying what a precious two weeks his wife and all the family had together, unique to those moments in time and their life experience (that could not have been the same at any other time). So isn't it time that society stopped trying to userp God's role, accepted that we can never fully understand life, and accepted that the best time to die is not actually ours to determine? Competing interests: Dr Leach is a committed Christian who supports the umbrella organisation "Care not Killing"

RESEARCH: Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies Strazzullo et al. (24 November 2009) [Abstract] [Full text] [PDF] Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies Fast food and stroke 27 November 2009 Rizaldy Pinzon, Neurologist Bethesda hospital Yogyakarta Indonesia 55224 Send response to journal: Re: Fast food and stroke There is changing way of life in many developing countries. There is a trend of changing diet pattern also. There is a rapid growth of fast food consumption. The fast food contains relatively higher salt compared with home made food. Some of the the quick and easy option foods were loaded with salt and incur harmful consequences. This study showed clearly that a difference of 5 g a day in habitual salt intake is associated with a 23 percent difference in the rate of stroke and a 17 percent difference in the rate of total cardiovascular disease.Based on the evidence, the authors estimate that reducing daily salt intake by 5 g at the population level could prevent one and a quarter million deaths from stroke and almost three million deaths from cardiovascular disease each year.Previous study showed that people who consumed more than 4 grams of sodium per day had an 84 percent greater likelihood of having such a stroke than did people consuming 2.4 grams or less sodium daily. The American Heart Association recommends 2.4 grams as the upper daily limit for sodium intake. Most sodium is consumed in the form of salt.These results support the role of a substantial population reduction in salt intake for the prevention of cardiovascular disease. Competing interests: None declared Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies Re: Mammalian salt requirement 27 November 2009 Les.O Simpson, retired experimental pathologist Dunedin New Zealand 9077 Send response to journal: Re: Re: Mammalian salt requirement Professor Mitchell stated, "Meanwhile the key question is what level of sodium intake is necessary to avoid the age-related rise in blood pressure which is regarded as normal, but is avoided at lower intakes consistent with nutritional requirement." According to Ajmani and Rifkind (1998) blood viscosity increases as a part of the aging process, mainly due to rising levels of fibrogen. Many studies have shown a relationship between blood pressure and blood viscosity. Before a sodium effect on blood pressure can be confirmed it would be necessary to eliminate the contribution of blood viscosity. Competing interests: None declared Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies Competing Interests 26 November 2009 Morton Satin, Technical Director 700 N. Fairfax St, Alexandria, VA 22314 USA Send response to journal: Re: Competing Interests I am employed by the salt industry. That is the competing interest which I am pleased to declare. For the sake of an open and honest debate it seems only fair that readers know where my interests lie. However, I find it of great interest that members of WASH (World Action on Salt and Health), a global advocacy group whose singular goal is to 'achieve a gradual reduction in salt intake' have the temerity to declare that they have no competing interests. Is this a reflection of their inability to concede their own declared biases? If they are bold enough to publicly declare their membership in this advocacy group on the WASH website, why hide it from the BMJ audience? And while members of WASH have openly declared their mission, they refuse to acknowledge that this may have removed their objectivity in all matters related to salt and health. This was aptly captured by C. S. Lewis “Of all tyrannies, a tyranny sincerely exercised for the good of its victims may be the most oppressive……those who torment us for our own good will torment us without end for they do so with the approval of their own conscience.” I note that two authors, Strazzullo and Cappuccio are members of WASH as is A. R. Mitchell, your first rapid response. All have declared ‘No Competing Interest’ as if their biases transcend the definition of subjectivity. No doubt, more members of WASH will weigh in as they always have, under the pretense of objectivity. The debate around salt and health has been of a near bankrupt scientific quality – it has been far more a reflection of bias than science. This poverty was best captured by one statement in this most recent publication, “Validation of these predictions by a randomised controlled trial of the effects of long term reduction in dietary salt on morbidity and mortality from cardiovascular disease would provide definite proof. At present, a study of this kind is not available and, in fact, it is extremely unlikely that it will ever be performed because of practical difficulties, the long duration required, and high costs.” Rather than demand that such a study be carried out, as the Salt Institute has demanded for more than a decade, it appears that all the salt-reduction advocates, including the authors of this paper prefer that their own opinions carry the day, so that entire populations can (without their knowledge) be the subjects of a massive clinical trial - unintended consequences be damned. It is also the reason that every salt-reduction initiative around the world, including that of the FSA in the UK has never been accompanied by a program to determine the effect of salt reduction on health metrics (BP, cardiovascular disease, aldosterone, metabolic syndrome indicators, etc.) - no health metrics at all have been engineered into these programs - what a travestry of science and of trust. In the meantime, it should do all who read BMJ some good to compare the salt intakes of all countries cited in the INTERSALT study with the cardiovascular metrics in the Global Cardiovascular Infobase, a WHO Collaborating Center (http://www.cvdinfobase.ca/) . As a final note, Mr Mitchell may wish to read Weiss et al, Yearbook Phys. Anthropol, 27, 153- 178, (1984) as well as Mitchell et al Am. J. Epidemlol, 131, 423-433, (1990) to learn of the impact of the absence of the D/D genotype amongst many of the very low salt consuming human beings before concluding that the age-related rise in blood pressure is, without exception, entirely the result of salt. Competing interests: Member of the salt industry Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies Salt and water 26 November 2009 Tom H Hughes-Davies, Retired paediatrician Breamore Marsh SP6 2EJ Send response to journal: Re: Salt and water The kidney's work in disposing of salt varies with the water available. Any survey of salt and health should include drink or urine volume - few do. Competing interests: None declared Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies Mammalian salt requirement 25 November 2009 Alastair R Michell, Professor of Comparative Medicine [Univ of London] Dept. Biochem. Pharmacology, Harvey Institute, Bart's Hospital, Charterhouse Sq.,London EC1M 6BG Send response to journal: Re: Mammalian salt requirement Humans were not uniquely created: they evolved and evidence concerning Paleolithic salt intake suggests it was probably below 0.4 mmol/kg/d. Evidence concerning nutritional maintenance requirement for sodium in a range of mammals indicates that it is unlikely to exceed 0.5- 0.7 mmol/kg/d [and is probably considerably less]; that is roughly 2.5 g/d for an average adult human. Those who believe that humans require significantly more sodium should reveal the unique defect in renal sodium conservation, or the route of obligatory non-renal salt loss to justify these higher intakes. Meanwhile the key question is what level of sodium intake is necessary to avoid the age-related rise in blood pressure which is regarded as normal, but is avoided at lower intakes consistent with nutritional requirement. There is no exception to the rule that human beings from low salt cultures avoid this rise. Reference: Michell AR: The Clinical Biology of Sodium Pergamon,1995 Competing interests: None declared

NEWS: Admissions from emergency departments rise as four hour target approaches Mooney (20 November 2009) [Full text] Admissions from emergency departments rise as four hour target approaches Curbing the rising tide of short stay admissions in children 25 November 2009 Sonia K Saxena, Consultant senior lecturer Imperial College London W6 8RF, Mike Sharland Alex Bottle Ruth GIlbert Send response to journal: Re: Curbing the rising tide of short stay admissions in children The four hour wait is only one of many potential factors fuelling the year on year rise in hospital admission rates.(1) The highest rises are in young children, many of whom are admitted through emergency departments (AEDs).(2;3) Children account for 30% of AED contacts and in up to 60% of cases, their parents have not sought advice from a GP prior to attending.(4) This year, we reported substantial (20%) increases in unplanned hospital admission rates in England among children aged< 10 years from a period (1996 to 2007) spanning these changes.(5) The majority of admissions were due to short stay isolated minor infectious illness episodes. The increases in admissions are not explained by greater efficiency from trusts since the proportion of children admitted for greater than 2 days has fallen by only 12%, hence the 41% expansion in short stay admissions lasting less than 2 days suggests a true increase. We would argue that many of these episodes could have been more appropriately dealt with in primary and community settings and a crude estimate of the costs of potentially avoidable admissions is in excess of £60 million per year. Simply increasing resources in emergency departments is not going to stem this rising tide. A number of emerging models of care may provide possible solutions including traditional GP led care, polyclinics and dedicated paediatric assessment units, which have been estimated to reduce up to 15% of admissions.(6) In all but the most urgent cases it should be possible to stream minor illness and injury in children away from hospital AEDs they reach A and E. Reference List (1) Mooney H. Admissions from emergency departments rise as four hour target approaches. BMJ 2009; 339(nov19_2):b4931. (2) NHS Institute for Innovation and Improvement. Focus on: emergency and urgent care pathway for children and young people. 2008. Coventry, NHS Institute for Innovation and Improvement. 1-3-2009. (3) Chief Nursing Officer's Directorate CF&MA. Trends in children and young people's care: Emergency admission statistics, 1996/97 - 2006/07, England. 2008. England, TSO. (4) Tadros S, Wallis D, Sharland M. Lack of use for advice by parents results in increasing attendance to the paediatric emergency department. Arch Dis Child 2009; 94(6):483. (5) Saxena S, Bottle A, Gilbert R, Sharland M. Increasing Short-Stay Unplanned Hospital Admissions among Children in England; Time Trends Analysis. PLoS ONE 2009; 4(10):e7484. (6) Healthcare for London, Commissioning Support for London. Meeting the needs of children and young people; guide for commissioners. 2009. London. Competing interests: None declared

HEAD TO HEAD: Should the NHS strive to eradicate all unexplained variation? Yes Richards (19 November 2009) [Full text] Should the NHS strive to eradicate all unexplained variation? Yes Unexplained ? 26 November 2009 L Sam Lewis, GP Surgery, Newport, Pembrokeshire, SA42 0TJ Send response to journal: Re: Unexplained ? Neither Richards nor Lilford make a worthy case, since both fail to address the relevance of the term "unexplained". Richards suggests that deviation from evidenced practice should be detected as 'special variation' and rooted out. And 'Common variation' is a term that begs so many questions. He has a touching faith in "statistical process control". For example, he homes in on variation in QOF exception rates, and ( typically ) turns his attention to High- excepters - "PCTs have a mechanism for investigating practices with unusually high rates of exception reporting and they should use it." He does not explain why low-excepters, or indeed 'average-excpeters' should not also be investigated. Statistical deviation of practice rates has no demonstrated relevance. Either this patient should be excepted or should not, and no other patients are relevant. An acceptable EXPLANATION for variation is all that matters. The same is true for prescribing rates. I regularly enjoy taking my prescribing advisers to task, by pointing out my Simvastatin rates are easily the highest in the county. I contest that I am prescribing evidence-based medicine, and other GPs are not keeping up with my pace. Why is it that 'prescribing quality' advisers pay such scant attention to low-rate prescribers? Could it be that they have not triggered the 'Cost' statistical process control ?? Similarly, a quoted statistical norm suggests a preventer-inhaler rate should be half the reliever-rate. But the only real questions are " have my patients got Asthma, and are their treatments working ? ". Lilford began well by presuming that patient choice and evidence- based differences constituted a sufficient explanation. But where evidence was lacking, he argued that various opinions and actions were acceptable. Isn't such variation therefore 'explained' ? Nobody has actually addressed 'unexplained variation'. I venture to suggest it is not desirable, without first explaining why it is harmful.. Acceptable explanation is what counts ! Competing interests: None declared

PRACTICE: A woman with acute myelopathy in pregnancy: case progression Reuß et al. (20 November 2009) [Full text] A woman with acute myelopathy in pregnancy: case progression Autoimmune diseases in pregnancy 26 November 2009 Muhammad K Rafiq, Specialist Registrar in Neurology Sheffield S10 2JF Send response to journal: Re: Autoimmune diseases in pregnancy Presence of oligoclonal bands in CSF simple indicate inflammation within the CNS and can be due to any inflammatory cause e.g. viruses, bacterial infections or autoimmune condtions. They are non-specfic. Autoimmune conditions can be treated in a stepwise approach guided by the response with steroids (plus steroid sparing drugs), then immunoglobulins and finally plasmapheresis. It is well known that autoimmune conditions tend to flare up in pregnancy and that may well be the case in this patient. If the patient does not respond to above measures, then sometimes termination of pregnancy may be considered as a last resort (ofcourse with patient's consent). As far as future pregnancies are concerned, she should be advised against given the serious risk to her nervous system and iatrogenic complications in the baby. She should be advised about a permanent method of contraception. But, its her choice what she likes to choice. Competing interests: None declared

CLINICAL REVIEW: Diagnosis and management of dengue Teixeira and Barreto (18 November 2009) [Full text] Diagnosis and management of dengue Prevention of vector breeding through community engagement 27 November 2009 Biji T Kurien, Senior Research Scientist OMRF, Oklahoma City, OK 73104, USA Send response to journal: Re: Prevention of vector breeding through community engagement The article ‘Diagnosis and management of dengue’ gives a comprehensive review of dengue, detailing cause, transmission, clinical features, treatment and prevention (1). With respect to prevention, the authors discuss about vaccine development, community involvement strategy, vector control using chemicals, biologicals and traps. According to the authors, the strategy to control vector population is centred mainly on the use of chemicals, a counterproductive measure. Therefore, efforts should focus on community involvement to control Aedes aegypti, the principal vector, which breeds in discarded containers (that collect rainwater) and in other water storage containers. When DDT had been widely in use about 41 years ago (2) Aedes aegypti had almost disappeared from many countries. With diminished use of DDT, the menace of DHF has now returned (2). The problem has become more pronounced with urban expansion, increased use of non-biodegradable products (that can hold rain water and allow mosquitoes to lay eggs), lack of water supply via pipes (this makes water storage in containers and tanks a necessity) among other factors (2). A community involved environmental management for dengue prevention study carried out in Guantanamo, Cuba showed Aedes infestation reduction by 50-75% (3). However, as the authors suggest (1), this study did not investigate the effect of the intervention on dengue virus transmission (1). Notwithstanding this, persistent reduction in vector infestation is bound to reduce dengue virus transmission. Cans, plastic bottles, tires, car batteries (4) and flower containers in cemeteries have been found to be good breeding places. Latex collection cups, in rubber growing countries, cocoa pods, coconut shells, tree holes, plant stumps, mud pots, flower pots, grinding stones, water tanks etc are good breeding ground for mosquitoes (5). Care needs to be taken to turn latex collection cups upside down during rainy season to prevent vector breeding. Use of flower holding vases with drain holes or bronze vases, in cemeteries, has been suggested to limit mosquito spread (6). Community participation programme focusing on eradicating or reducing breeding containers at homes, weekly emptying of storage containers (weekly emptying can disrupt mosquito life cycles, since newly hatched larvae require 9 days under favorable conditions to develop into the adult stage or complete the cycle), encouraging larval control by using larvicide (temephos or Abate 1% sand granules), introducing larvivorous fish into water containers, covering larger containers with lids to prevent egg laying by mosquitoes and encouraging the use of predacious copephods of the genus Mesocyclops as a biological control agent will help stop the spread of dengue and DHF (7,8). A novel insecticide delivery instrument named the Mossie-Buster has been developed to control mosquito larvae from urban breeding places in Townsville, Australia (9). References 1. Teixeira GM, Barreto ML. Diagnosis and management of dengue. BMJ 2009;339:b4338 2. Vu SN, Nguyen TY, Kay BH, Marten GG, Reid JW. Eradication of Aedes aegypti from a village in Vietnam, using copepods and community participation. Am J Trop Med Hyg. 1998; 59:657-60. 3. Vanlerberghe V, Toledo ME, Rodríguez M, Gomez D, Baly A, Benitez 33 JR, et al. Community involvement in dengue vector control: cluster randomised. BMJ 2009;338:1959b. 4. Mazine CA, Macoris ML, Andrighetti MT, Yasumaro S, Silva ME, Nelson MJ, Winch PJ. Disposable containers as larval habitats for Aedes aegypti in a city with regular refuse collection: a study in Marilia, Sao Paulo State, Brazil. Acta Trop. 1996; 62:1-13. 5 Thenmozhi V, Hiriyan JG, Tewari SC, Philip Samuel P, Paramasivan R, Rajendran R, Mani TR, Tyagi BK. Natural vertical transmission of dengue virus in Aedes albopictus (Diptera: Culicidae) in Kerala, a southern Indian state. Jpn J Infect Dis. 2007;60:245-9. 6. O'Meara GF, Gettman AD, Evans LF Jr, Scheel FD. Invasion of cemeteries in Florida by Aedes albopictus. J Am Mosq Control Assoc. 1992 ;8:1-10. 7. Effectiveness of dengue control practices in household water containers in Northeast Thailand.Trop Med Int Health. 2005;10:755-63. 8. Vu SN, Nguyen TY, Tran VP, Truong UN, Le QM, Le VL, Le TN, Bektas A, Briscombe A, Aaskov JG, Ryan PA, Kay BH. Elimination of dengue by community programs using Mesocyclops(Copepoda) against Aedes aegypti in central Vietnam. Am J Trop Med Hyg. 2005;72:67-73. 9. Canyon DV, Hii JL. The Mossie-Buster: a hose-driven insecticide delivery tool for the control of container-breeding mosquitoes. J Am Mosq Control Assoc. 1997 ;13:389-94. Competing interests: None declared Diagnosis and management of dengue Dengue fever: Vector control is important! 25 November 2009 Fook Chang Lam, Specialist Registrar Gartnavel General Hospital, 1053 Great Western Road, Glasgow G12 0YN Send response to journal: Re: Dengue fever: Vector control is important! I read with interest Teixeira et al’s recent excellent clinical review on the 'Diagnosis and management of dengue'. [1] However, when Texeira et al under the subheading of ‘How might dengue be prevented?’ state that the reduction of the vector population has ‘low or no effectiveness in reducing levels of dengue transmission’, they perhaps leave the impression that vector control measures- that are aimed at keeping the mosquito population at a low level- are ineffective in reducing the incidence of dengue infections. Indeed, the Aedes aegypti mosquito, the main vector for dengue, is well adapted to living in urban environments and natural breeding habitats are created as quickly as they are eliminated, and there is no evidence that the use of chemical insecticides in an area after cases have already been detected are effective. However, the experience in Singapore shows that a well-conducted vector control system based on entolomogic surveillance and larval source reduction aiming to control the mosquito population before disease is detected in an area can be successful. [2] In this instance, this strategy of keeping the vector population low was successful in bringing about a 15-year period of low dengue incidence. Dengue infections are currently on a rapid rise globally. This has been attributed to population growth, a proliferation of breeding sites for mosquitos with uncontrolled urbanization, difficulties in implementing successful vector control and a rapid increase in international travel. [3] In fact, the recent resurgence in Singapore itself has been partly attributed to the shift in the emphasis in prevention from vector surveillance towards responding to detected cases of dengue, and increasing travel. [2} With treatment for dengue fever and dengue haemorrhagic fever being at best supportive and an effective vaccine still at the stage of phase III trials, [4] then continued diligence towards holistic and effective vector control measures aimed at keeping the Aedes aegypti population low cannot and should not be neglected. References 1. Teixeira MG, Barreto ML. Diagnosis and management of dengue. BMJ 2009; 39: b4338. 2. Ooi EE, Goh KT, Gubler DJ. Dengue prevention and 35 ears of vector control in Singapore. Emerg infect Dis 2006; 12(6): 887-93. 3. Kyle JL, Harris E. Global spread and persistence of dengue. Annu Rev Microbiol 2008; 62: 71–92. 4. Webster DP, Farrar J, Rowland-Jones S. Progress towards a dengue vaccine. Lancet Infect Dis. 2009 Nov;9(11):678-87. Competing interests: None declared

EDITORIALS: Is primary care research a lost cause? Mar (18 November 2009) [Full text] Is primary care research a lost cause? -not if it returns to its roots 26 November 2009 john howie, emeritus professor of general practicce university of edinburgh eh89dx Send response to journal: Re: -not if it returns to its roots In his thoughtful editorial on the Report of the Academy of Medical Sciences into general practice research, del Mar asks if primary care research is a lost cause. Two institutional realities have contributed to the problem. First, universities and their medical schools have become imprisoned in the search for large sums of research money to survive, resulting in restructuring of research activity and the pursuit of high earning high technology activities, neither of which are helpful to the preferred agendas of academic general practice. Second, the re-ordering of community clinical services (at least in the UK) to promote incentivised public health interventions combined with the opportunity for general practitioners to opt out of out-of-hours care has seriously compromised the core values of continuity and the primacy of patient agendas at general practice consultations. Academic general practice has perhaps had no option but to go along with these realities, but in so doing it has risked losing its intellectual and research identities. In research terms, the effect has been an almost exclusive move into evidence-based research approaches to the exclusion of the work on the consultation, patient-centredness and holism which del Mar dates as belonging to a passing generation. Too many of the questions now being asked and of the papers being published lack either or both of interest or relevance to the individual patient in consultation with the individual doctor. del Mar kindly referred to my work on prescribing for respiratory illness in the 1970s(1). My first study(2) was a double-blind clinical trial which showed no benefit to antibiotic takers in a normally healthy working-age male population. I spent the next thirty plus years trying to explain why these findings had made so little change to standard clinical practice. In the end it was the work on the consultation and on patient- centredness that seemed to make most sense to the realities of the consulting room. I have recently had the opportunity to revisit one of my studies of the early 1970s, and to comment on its relevance to modern clinical practice(3). This has confirmed for me that if general practice research is to contribute to the future of medicine in the way patients most need to-day, it will only be through a combination of medical and social science approaches. del Mar says that 'primary care research is in the doldrums'. If that is indeed true, the way ahead must surely be for the original discipline of general practice (whether or not delivered solely by doctors) to re-assert its core values both in the medical school and in the consulting room. The discipline so many worked to develop in the second half of the 20th century was about much more important aspects of patient care than simply 'primary care' on its own. references 1. del Mar. Is primary care research a lost cause? BMJ 2009:339:b4810. 2. Howie J G R, Clark G A. Double-blind trial of early demethylchlortetracycline in minor illness in general practice. Lancet,1970;ii:1099-1102. 3.Howie J. Diagnosis in general practice and its implications for quality of care. J Health Serv Res Policy. doi:jhsrp.2009.009109. Competing interests: None declared

VIEWS & REVIEWS: An inside story Dalrymple (17 November 2009) [Full text] An inside story Doctors in literature 26 November 2009 Alan J O'Rourke, lecturer ScHARR, Sheffielld University Send response to journal: Re: Doctors in literature Dear Theodore: Enjoy your column in the BMJ. Wondered if you had come across the following novel which has a medical hero: Arnold Bennett's "The Ghost," first published 1907. It is a ripping yarn, but quite "sensationalist" and not really in the same class of writing as his Potteries sagas Basically, the book is an excuse for a newly-qualified young doctor, Carl Foster, to have all sorts of adventures, picking up a small fortune, a mansion in Brughes and the love of a world-famous opera singer along the way. Right in the middle of the book, he has rather adventurous night time trip from London-Paris, surviving both a train crash , and a serious maritime accident. Carl is taking a break after his finals, and thinking about joining his brother’s practice in Totnes (the abbreviation “GP” is used at least once), when a chance meeting with a cousin leads to an invitation to the opera. Answering an “is there a doctor in the house?” call, Carl finds himself attending the leading tenor, Alresca, who has fallen back stage. Based on clinical signs (including crepitus!) he diagnoses “the left thigh was broken near the knee joint.” Carl shows enough judgement to advise that a surgeon would be more useful than a physician, and just then a suitable Scottish one, Toddy MacWhirter (by co-incidence, recently one of Carl’s examiners), presents himself and sets the leg in plaster. Mr MacWhirter seems to believe in the minimum of orthopaedic follow up (one house call) and then discharges Alresca into Carl’s care, as personal physician and companion, for convalescence at his Brughes home. Alresca’s fracture heals, but his health declines in a mysterious, psychological way. He then seems to recover, but on being visited by Rosa Rosetta, the famous young soprano, Aresca’s co-star and as it transpires, object of desire, he suffers a fatal relapse. Carl discovers that Alresca has made him his heir, to the Brughes house, a modest fortune and a strange letter. Despite the periodic intrusion of the “Ghost” ( the malign spirit of a deceased lover of Rosa), by the strength of Rosa’s character and love, Carl finally wins her hand as well. His medical expertise is however only needed twice more in the book: once when he detects that Rosa’s maid is attempting to poison her with Atropine in a milk drink, and once to provide first aid to a stab victim…who takes several days to die! Also, as one stage we have to believe that a man moribund with “brain fever” (??meningitis) can rise from his death bed, don full evening wear, make a valedictory speech and then expire! Rgds Alan Competing interests: None declared

VIEWS & REVIEWS: Rhyme and reason Moore (17 November 2009) [Full text] Rhyme and reason Re: Oliver Wendell Holmes and puerperal fever 27 November 2009 Wendy Moore, author London Send response to journal: Re: Re: Oliver Wendell Holmes and puerperal fever I'm grateful to Peter Bennett for reminding us of Alexander Gordon's pioneering research on puerperal fever. Space prohibited my mentioning him but I did detail his role in an earlier column 'Now wash your hands', on 25 August 2007 (BMJ 2007;335:402 (25 August), doi:10.1136/bmj.39314.598854.59). Anyone interested in more information on Gordon should read the excellent novel 'Touching Distance' by Rebecca Abrams. Wendy Moore Competing interests: None declared Rhyme and reason Oliver Wendell Holmes and puerperal fever 26 November 2009 Peter N Bennett, consultant physician [ret'd] Denmede, Southstoke road, Bath BA2 5SL Send response to journal: Re: Oliver Wendell Holmes and puerperal fever Dear Letters Editor, Wendy Moore[BMJ2009;339:b4890] correctly states that Oliver Wendell Holmes recognised that puerperal fever was carried between patients by the medical attendants before Ignaz Semmelweis did, but let us remember Alexander Gordon provided compelling evidence of this mode of transmission 48 years earlier than Holmes {Alexnder Gordon, A treatise on the epidemic puerperal fever of Aberdeen. London: GG & J Robinson, 1795]. Yours etc Dr Peter N Bennett Competing interests: None declared

RESEARCH: Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study Levine et al. (17 November 2009) [Abstract] [Full text] [PDF] Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid... Can Thyroid function tests predict preeclampsia and what proportion of hypothyroid women have a history of preclampsia in their pregnancies ? 27 November 2009 Neeru Gupta, Deputy Director General and scientist E Indian Council of Medical Research, Ansari Nagar, New Delhi-110029, Nivedita Gupta, Manjula Singh and KK Jani Send response to journal: Re: Can Thyroid function tests predict preeclampsia and what proportion of hypothyroid women have a history of preclampsia in their pregnancies ? Soluble fms like tyrosine kinase, an antiangiogenic factor is associated with subclinical hypothyroidis in pregnancy. It remains to be determined that at what levels the risk of hypothyrodism occurs. For determining the cut-off values a Reciever Operating characteristic curve (ROC curve) should have been plotted (sensitivity vs false positivity/1- specificity. Pre-eclampsia is also associated with many circulating biomarkers (VEGF, calcitonin gene-related peptide, parathyroid hormone related peptide etc). The study tells an association but not causation. It is not clear that fms-like soluble tyrosine kinase is cause or an effect of the hypothyroidism and whether hypothyroidism is also associated with changed levels of other circulating biomarkers of preeclamsia or not. It is also observed in the study that preeclampsia in the pregnancy (population based part of the study) can lead to hypothyroidism in later life. A complimentary study should be planned to study whether hypothyroid women had a history of pre-eclampsia. Alternatively, all women with pre- eclamsia/soluble fms like tyrosine kinase positive women should be followed to see whether hypothyroidism develops, which will be able to prove causation. Competing interests: None declared

NEWS: Poor service provision is blamed for overuse of antipsychotics in dementia patients Mashta (17 November 2009) [Full text] Poor service provision is blamed for overuse of antipsychotics in dementia patients Both conventional and atypical anti- psychotics are dangerous 27 November 2009 Zekria Ibrahimi, psychiatric patient Coombs Library, Southall, UB13EU Send response to journal: Re: Both conventional and atypical anti- psychotics are dangerous The atypical anti- psychotics such as olanzapine and risperidone were condemned by the FDA as being involved in a higher death rate for those with dementia. But the conventional first generation anti psychotics, particularly haloperidol, are implicated in even larger hazard ratios (HR) (1). All anti- psychotics, old or new, are unsafe for the elderly. Anti- psychotics were designed for schizophrenia and have no appropriate receptor profile for Alzheimer's. Schizophrenics may be worried meanwhile that they are being given drugs damaging those who are weak and vulnerable. It is part of schizophrenia that its sufferers are less likely to look after themselves and are in bad health. Anti- psychotics are not so benign as aspirin and to overprescribe them is dangerous for the old in nursing homes- or indeed for schizophrenics in psychiatric units. REFERENCES: (1) All- cause mortality associated with atypical and conventional antipsychotcis among nursing home residenst with dementia: a retrospective cohort study. Rosa Liperoti et al. J. Clin Psychiatry. 2009:70 (10):1340- 1347 Competing interests: None declared Poor service provision is blamed for overuse of antipsychotics in dementia patients Considering the alternatives 27 November 2009 Wiiliam R Jones, ST4 in Psychiatry Yorkshire Centre for Eating Disorders, Newsam Centre, Leeds LS14 6UH, John F Morgan, Katherine Murphy Send response to journal: Re: Considering the alternatives The report led by Professor Banerjee is welcome and timely given the widespread off-label use of antipsychotics to treat behavioural and psychotic symptoms due to dementia (BPSD).[1] Commissioning specialist older people’s mental health services to support primary care and care homes and developing a curriculum to train GPs will go some way to meeting the proposed targets. However, given the current economic climate and lack of realistic evidence-based alternatives it seems unlikely that antipsychotic use will drop to the extent predicted by Professor Banerjee. The report recommends that “the Improving Access to Psychological Therapies (IAPT) programme should ensure that resources are made available for the delivery of therapies to people with dementia and their carers”. This seems unrealistic given the lack of evidence-based non- pharmacological methods of treating BPSD. The National Institute for Health and Clinical Excellence (NICE) guidance on the use of antipsychotics for BPSD has been heavily criticised for the inclusion of non-pharmacological measures such as animal-assisted therapy and massage which lack an evidence base.[2] More emphasis should be placed on the need for further research in assessing the clinical and cost-effectiveness of non-pharmacological methods of treating BPSD and of other pharmacological approaches as an alternative to antipsychotic medication. Similarly, there is only a strand of the IAPT initiative that focuses on older people and it has been more focused on adults of a working age. It seems that the lion's share of the £173m budget for IAPT will not be ring-fenced as mental health experts had originally believed. Instead the remaining £100m yet to be allocated will be spent at the discretion of individual PCTs. Few older people and even fewer people with dementia and their carers are likely to benefit from the programme as it is currently designed and delivered. Furthermore, the report recommends “the need to develop a curriculum for the development of appropriate skills for care home staff in the non- pharmacological treatment of behavioural disorder in dementia, including the deployment of specific therapies with positive impact.” Like many of us, care home owners have felt the financial strain of the current economic recession. It is unlikely that they will invest scarce resources into such developments anytime soon. Finally, we can learn from the United States where concern about the overuse of antipsychotics was highlighted over twenty years ago. This led to the introduction of legislation (Omnibus Reconciliation Act 1987) requiring all nursing facilities to have a medical director and each resident having an attending doctor who visits them at specified intervals. This had a considerable impact on the prescribing of antipsychotics to residents of nursing homes[3,4] and the government should consider how these policies could be adopted in the United Kingdom. References 1. Banerjee S (2009) The use of antipsychotic medication for people with dementia: Time for action. A report for the Minister of State for Care Services Department of Health: London 2. Haw C, Yorston G, & Stubbs J (2009) Guidelines on antipsychotics for dementia: are we losing our mind? Psychiatric Bulletin; 33: 57-60 3. Shorr RI, Fought RL, & Ray WA (1994) Changes in antipsychotic drug use in nursing homes during implementation of the OBRA-87 regulations. JAMA; 271: 358-62. 4. Semla TP, Palla K, Poddig B, & Brauner DJ (1994) Effect of the Omnibus Reconciliation Act 1987 on antipsychotic prescribing in nursing home residents. J Am Geriatr Soc; 42: 648-52. Competing interests: None declared Poor service provision is blamed for overuse of antipsychotics in dementia patients Please don't waste more resources 26 November 2009 Thomas A Groves, ST3 GP registrar B80 7QU Send response to journal: Re: Please don't waste more resources Dear Sir I have been following with great interest the recent revelations in both medical and non medical publications that anti-psychotic medications are leading to excess mortality secondary to cardiovascular disease in patients with dementia. I also read with great interest the fact that this excess use is being blamed on primary care and General Practitioners. In june long before these revelations were made widely known, i was in my second year of GP training and i undertook an audit of drug use in patients with dementia. Clearly the numbers involved were small but it was interesting to find that over 90% of patients with dementia on anti- psychotic medications had been started in secondary care by our local elderly care psychiatry team NOT by their GP. The vast majority of these patients remained under secondary care follow up and the majority had been on these medications for well over 1 year (well beyond the 6 weeks currently being recommended). Is is right that primary care services are receiving all the blame? Can i be accountable for a drug i didn't prescribe? As a ST3 GP Registrar i do not need more training about how to look after patients with dementia. I have done my time as an Elderly care and Psychiatry SHO and most importantly i have spent plenty of time in GP training. I know that anti-psychotics increase stroke risk but i also know that nursing home staff and resources, and families are stretched to the limit. If i could prescribe 1:1 nursing care with overnight sitters, i would, if i could prescribe cats and dogs for animal therapy, i would, if i could ensure that the same nurse would be looking after the same patient everyday, i would.... but i can't. So instead, after careful consideration, looking at the patient as a whole, taking into account the likelihood of harm verses benefit for the patient and those around them i might prescribe anti-psychotic medication. This is not a decision that is made easily i can assure you. Please don't waste more money and resources teaching hard working GPs how to look after patients with dementia, please tackle the problem and use resources where they will have the biggest impact. Competing interests: None declared

FEATURE: Doctors in management Stephenson (17 November 2009) [Full text] Doctors in management Health management education for UK medical students 27 November 2009 Timothy D Heymann, Reader in Health Management Imperial College London, London SW7 2AZ, Jenny Higham Send response to journal: Re: Health management education for UK medical students We read with interest Jo Stephenson’s review [1] of approaches to management training for clinicians. She describes in detail initiatives in continental Europe, the United States and Australasia. She quotes Professor Ham in observing that we need to invest in training and support for those who want to take on clinical leadership roles. Here at Imperial College London we have been offering an intercalated year in heath management since 2002 [2]. For the last two years we have introduced all 320 final year students to some of the management challenges they may face in the National Health Service as part of a ‘practical medicine’ module. Our health management BSc is one of Imperial medics’ most popular choices for their intercalated year. The course also attracts many talented intercalating students from other medical schools. Whilst we agree with Professor Ham that “[the development of more clinical leaders] is not going to happen through spontaneous combustion”, many of the doctors of tomorrow already appear to sense that management skills and knowledge will help them in their careers and want to seize the opportunity to develop them. [1] BMJ 2009;339:b4595 [2] http://www3.imperial.ac.uk/ugprospectus/facultiesanddepartments/businessschool/undergraduatecourses/bscprogramme Competing interests: The authors both work at Imperial College London

NEWS: Australia operates "closed shop" to restrict doctors from overseas, say critics Sweet (16 November 2009) [Full text] Australia operates "closed shop" to restrict doctors from overseas, say critics Something worth Protecting 27 November 2009 Peter A West, Senior Research Associate York Health Economics Consortium Send response to journal: Re: Something worth Protecting Readers of the article on restricted doctor entry to Australia should bear in mind that GPs and hospital doctors are paid fees for every patient (not in all cases for hospital but consistently for GPs). More doctors means one of two things, less fees for current doctors, which the doctors would not like, or more fees paid by the health system, which tax payers and government will not like. A free market in doctors' services could see incomes fall and perhaps lead to more competition on fees. But it is hard to see turkeys voting for Christmas, even in Australia's warmer Christmas climes! Competing interests: None declared

NEWS: Chlamydia screening in young people fails to reduce prevalence Mayor (13 November 2009) [Full text] Chlamydia screening in young people fails to reduce prevalence Yet more problems with chlamydia screening 26 November 2009 Trevor G Stammers, GP 2, Church Lane, Merton Park, SW19 3NY Send response to journal: Re: Yet more problems with chlamydia screening It is not only those failings of the UK chamydia screening programme highlighted by Mayor (1) that have given rise to its predictable failure. Even with adequate screening uptake rates, the 3 month re-infection rate after treatment is 30% in those who don’t use condoms consistently and 15% in those who do (2). Research in the US suggests that women who have had a chlamydia infection should be re-screened within 4 to 6 months of their initial positive test since this would identify more than half of women re -infected, and could prevent infertility and other sequelae commonly associated with repeated infections. (3) This needs to become nationwide UK policy along with advice on condom use for those who don’t use them and accurate information about the limitations of condoms in preventing chlamydia (and other non-HIV STIs) for those who do (4). A further problem is with programmes virtually guaranteed to increase the incidence of chlamydia. Despite the National Screening Programme’s own website indicating that financial incentives sometimes increase uptake but there is no evidence at all that they improve relevant outcomes such as reduction of incidence (5), many PCTs are still running such schemes and some groups like the NUS are even promoting vouchers for cheap alcohol as incentives (6). Given the known associations with alcohol and sexual risk- taking, it is no wonder chlamydia rates in the UK are not declining. 1. Mayor S 2009 Chlamydia screening in young people fails to reduce prevalence BMJ 339 b4736 2.Paz-Bailey G, Koumans EH, Sternberg M et al 2005 The effect or correct and consistent condom use on chlamydial and gonoccocal infection among urban adolescents Arch Ped and Adol Med 159 536-542 3. Kang M, Chow J, Dunn T et al 2002 Re-infection With Chlamydia trachomatis in a Large Northern California HMO: Implications for Screening www.cdc.gov/stdconference/2002/2002ConfAbOralD.htm#D6C 4. Genuis S 2008 Are condoms the answer to rising rates of non-HIV sexually transmitted infections: No. BMJ 336 185 5.www.chlamydiascreening.nhs.uk/ps/assets/ppt/sharing/incentives08- 09.ppt#269,2,Background 6. www.dailymail.co.uk/news/article-1219351/The-booze-bribe-students- agree-sexual-health-tests-rewarded--free-alcohol.html Competing interests: None declared

RESEARCH: Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study Dumurgier et al. (10 November 2009) [Abstract] [Full text] [PDF] Slow walking speed and cardiovascular death in well functioning older adults: prospective... Validity of the results 27 November 2009 Edward M Absoud, Retired Consultant Surgeon Pilgrim Hospital, PE21 9QS Send response to journal: Re: Validity of the results This research is fundamentally flawed. As the walking speed equals: length of pace multiplied by number of paces per unit time, but the length of pace is determined only by the length of lower limbs in fit persons. Therefore, a more accurate assessment of speed and mobility, would be the number of paces per unit time. Competing interests: None declared

EDITORIALS: Greater equality and better health Pickett and Wilkinson (10 November 2009) [Full text] Greater equality and better health A pardigm shifting hypothesis and Dr Johnson's swallows 25 November 2009 Seth Jenkinson, retired BD9 5BE Send response to journal: Re: A pardigm shifting hypothesis and Dr Johnson's swallows Equality, health and other social ills Pickett and Wilkinson BMJ 2009;339:1154-1155 This is a very remarkable hypothesis. If the underlying science is true, it is a paradigm shifting thesis, like evolution or germ theory. In essence Wilkinson and Pickett assert that they have evidence that many of the ills of modern prosperous societies, from obesity and drug abuse through teenage pregnancies to violence and bulging jails all have a common cause; income inequality. This is a ground breaking assertion because it renders large areas of political discourse irrelevant. Almost every day on the Radio 4 Today programme topics are discussed which are importantly affected by this hypothesis. Cameron's broken society and Brown's suggestion of hostels for teenage mothers both need the same solution, a more equal society. Indeed the evidence is so powerful that it implies that unless we can achieve more equal societies other action will not work, thus the redundancy of much present political discussion. I have known about Wilkinson's work on inequality and health for at least 20 years but the thesis is now enlarged into other measures namely; levels of trust, mental illness (including drug and alcohol abuse), life expectancy and infant mortality, obesity, children's educational performance, teenage births, homicides, imprisonment rates and social mobility. Clearly, in unequal societies the poor suffer the most, but another intriguing assertion, with evidence, is that there is a fine stratification of disadvantage which permeates society to the very top. This also has been known for many years in the narrower field of medicine from Marmot's well known Whitehall study. This present book broadens the canvas dramatically and shows that rich people in unequal societies are less healthy and happy than the top layers of more equal countries. In the 19th century, cholera and typhoid came roaring out of the slums to affect the middle classes and even Prince Albert, so once the germ theory was understood, clean water and good sewage disposal became a benefit for all. The poor benefited the most, because they died the most but everyone benefited. The analogy today is that as criminality, anti-social behaviour and dependency costs bubble up out of the poorest areas of cities, everyone's life would be improved by more equality. This is a rich country analysis. No-one doubts that the lives of people in poor countries can only be improved by economic advance. There is however a turning point (maybe $20000 per head per year) after which further increases in wealth are not accompanied by improved social statistics. The richest and most unequal country of all, the USA, passed this turning point decades ago and further increases in its wealth have only produced a violent society with a huge jail population where the middle classes hide behind security locks in gated communities. The book is a devastating critique of the failure of the US version of market democracy which has dominated the world since 1945. There are other ways to ride the capitalist beast. The Scandinavian countries and Japan, at the egalitarian end of the spectrum, exemplify two very different ways. The researchers are also able to show the effects of inequality between different US states. This is extraordinary because it shows how powerful the effect must be if it can be detected between states whose culture and wealth vary so little. The differences between New York and New Hampshire are far fewer than the differences between Portugal and Sweden yet the parameter of inequality still predicts all its malign effects. This book deserves the widest discussion. In a nod towards the illustrious predecessor of 1859 I think it could be subtitled “Origin of Stresses” by means of unnatural inequality. The authors also speculate in a very interesting way at the end of the book on the biological plausibility of human beings functioning better in more equal societies. This book is nothing less than the scientific underpinning of centre left politics. Therein lies its weakness because the conclusions have been asserted by liberal lefties for more than a century, and this could be thoughtlessly dismissed as more of the same. But it isn't. The important thing is that here is EVIDENCE. Once you have evidence that swallows migrate to Africa in the winter, you no longer have to speculate, as Doctor Johnson did, about them hibernating at the bottom of lakes. The old discourse is dead. Doubters may find it hard to accept that the only ASBO we need is more equality. It may seem as improbable to them as a tiny bird flying to Africa, it just happens to be true. Seth Jenkinson Nov 09 PS a powerful characteristic of scientific truth is that it is true even before it is known or accepted. eg Cigarettes caused lung cancer long before it was known that they did. If inequality causes social ills because of the nature of human beings, it remains true, even if we never act upon the truth. Competing interests: None declared

EDITORIALS: Slow walking speed in elderly people Harwood and Conroy (10 November 2009) [Full text] Slow walking speed in elderly people Fast walking and the mind 27 November 2009 Evan L Lloyd, Retired 72 Belgrave Road Edinburgh EH12 6NQ Send response to journal: Re: Fast walking and the mind Dear Sir In this review the authors have omitted one major factor involved in fast walking. Fast walking speed certainly involves good cardiorespiratory condition and good musculoskeletal status. However it is also associated with good psychological/cerebral function. If a person is depressed, lonely or bored he/she is likely to walk slowly. Those who walk fast usually do so because they have something to do which is important to them. This is likely to keep them healthy. It is a similar situation to assessing the risk of developing hypothermia in an elderly person alone at home. The standard question is "When last did someone come to see you?" A much more valid question is "When last did you go to see someone?" This second question differentiates between those who still have the mental capacity to think about someone else, as well as indicating a reasonable physical and physiological function level, from those who are selfish and expect other people to run to them. These latter are at a much higher risk of developing hypothermia. Evan L Lloyd FRCPE, FRCA Competing interests: None declared

LETTERS: Never mind the treatment, what about the tests? Bamji (10 November 2009) [Full text] Never mind the treatment, what about the tests? Cervical radiculopathy, never mind the tests what about the treatment? 27 November 2009 Laurie Allan, Consultant Anaesthetist Northwick Park Hospital, Watford Road, Harrow, MIDDX, HA1 3UJ Send response to journal: Re: Cervical radiculopathy, never mind the tests what about the treatment? Andrew Bamji raises the real dilemma of expensive and unnecessary tests emerging with the introduction of open access magnetic resonance imaging to primary care in some areas1. He correctly states that persistent symptoms for six weeks or four weeks with motor signs require investigation, but scanning all cases is pointless when only 1% require surgery. However this leaves the unanswered question of what to do for all these symptomatic patients. In primary care, application of the World Health Organisation analgesic stepladder is helpful and indeed many patients are helped, if not optimally, by oral anti-inflammatory drugs2. This may predict a more useful response to targeted anti-inflammatory therapy by cervical steroid epidural. There is systematic review evidence of efficacy for this 3 and evidence-based practice guidelines 4 and a Cochrane review of medicinal and injection therapies for mechanical neck disorders5.This approach should be known by healthcare staff and more available to patients as in skilled hands this technique is carried out under local anaesthetic as a daycase with few problems6. Unfortunately the full spectrum of multidisciplinary pain services are too frequently forgotten and primary care commissioning teams would do well to balance diagnostics and therapies within care plans that deliver not just the diagnosis but all the options for symptom control which ultimately is what we would all want as patients. Similarly, the apparent failure to consider all the evidence for injection therapies as well as other options has resulted in the President resigning from the Pain Society and the National Institute for Clinical Excellence reconsidering its recommendations for back pain. 1. Andrew N. Bamji. Never mind the treatment, what about the tests? BMJ 2009; 339: b4619. 2. World Health Organisation. Cancer pain relief, 2nd ed. Geneva: WHO, 1996. 3. Benyamin RM, Singh V, Parr AT, Conn A, Diwan S, Abdi S. Systematic review of the effectiveness of cervical epidurals in the management of chronic neck pain. Pain Physician. 2009 Jan-Feb;12(1):137-57. 4. Boswell MV, Trescot AM, Datta S, Schultz DM, Hansen HC, Abdi S, Sehgal N,Shah RV. Singh V, Benyamin RM, Patel VB, Buenaventura RM, ColsonJD, Cordner HJ, Epter RS, Jasper JF, Dunbar EE, Atluri SL, Bowman RC, Deer TR, Swicegood JR, Staats PS, Smith HS, Burton AW, Kloth DS, Giordano J, Manchikanti L. Interventional techniques: Evidence-based practice guidelines in the management of chronic spinal pain. Pain Physician 2007:10:7-111. 5. Peloso PMJ, Gross A, Haines T, Trinh K, Goldsmith CH, Burnie SJ, Cervical Overview Group. Medicinal and injection therapies for mechanical neck disorders. Cochrane Database Syst Rev 2007; 3:CD000319. 6. Derby R, Lee SH, Kim BJ, Chen Y, Seo KS. Complications following cervical epidural steroid injections by expert interventionalists in 2003. Pain Physician 2004;7:445-449 Competing interests: None declared

RESEARCH: Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial Lund et al. (9 November 2009) [Abstract] [Full text] [PDF] Combining insulin with metformin or an insulin secretagogue in non-obese patients... Re: Is repaglinide really suitable for combination therapy with insulin? 27 November 2009 Søren S. Lund, MD Steno Diabetes Center, 2820 Gentofte, Denmark, Allan A. Vaag Send response to journal: Re: Re: Is repaglinide really suitable for combination therapy with insulin? We welcome the discussion raised by Dr. Malinverni. We believe that achieving good glycaemic control is not a natural consequence of aiming for it. Factors, such as hypoglycaemia might prevent achieving good glycaemic control also when it has been aimed for. Hence, aiming for and achieving good glycaemic control as in our study supports the conclusion that treatments, including insulin and repaglinide, can be used succesfully. We agree with Dr. Malinverni that other factors such as beta- cell failure, weight-gain or dosage schedules could be of clinical importance. We believe that hard endpoint studies will be needed to address these issues appropriately. Competing interests: SSL and AAV have reported equity in Novo Nordisk A/S. AAV have received funds from Novo Nordisk A/S for research. SSL and AAV have received fees from Novo Nordisk A/S for speaking and AAV has received fees from Novo Nordisk A/S for organising education. SSL and AAV are employees at Steno Diabetes Center, Gentofte, Denmark. Steno Diabetes Center is an independent academic institution owned by Novo Nordisk A/S and the Novo Nordisk Foundation. Combining insulin with metformin or an insulin secretagogue in non-obese patients... Is repaglinide really suitable for combination therapy with insulin? 25 November 2009 Stefano Malinverni, Consultant Ospedale San Raffaele del Monte Tabor, Milano, via Olgettina 60, 20132 Milano, Italy Send response to journal: Re: Is repaglinide really suitable for combination therapy with insulin? Lund and colleagues after comparing regimens of insulin plus either metformin or an insulin secretagogue affirm in their conclusions that both treatments might be used favorably in non-obese patients. This conclusion is founded on the good HbA1c achieved in both arms of their study. However this conclusion cannot be inferred from this study since both arms of treatment were aimed to achieve optimal glicemic target self adjusting their insulin. Moreover the significant weight gain observed in the repaglinide group together with the concerns on the possible β cell exhaustion caused by insulin secretagogues cast doubts on the long term efficacy of insulin secretagogues combined with insulin in non-obese patients. Finally, in the case of repaglinide, the burden of an additional drug in a patient already taking insulin, is not justified by any possible advantage on monotherapy with insulin. Metformin on the other hand offers, when used together with insulin, a better insulin sensitivity and weight reduction making it a much more appealing drug for combination therapy in type 2 diabetes. Competing interests: None declared

ANALYSIS: How long does it take to train a surgeon? Purcell Jackson and Tarpley (5 November 2009) [Full text] How long does it take to train a surgeon? How long does it take to train non-surgeons to perform surgery? 25 November 2009 Kathryn M Chu, Surgeon Medecins Sans Frontieres, Cape Town, South Africa 8005 Send response to journal: Re: How long does it take to train non-surgeons to perform surgery? In their Analysis (Nov 5 2009) Drs. Purcell Jackson and Tarpley highlight the challenges of training surgeons in a formal training program. They purport a minimum number of training hours (10,000 t0 20,000) are needed to reach surgical expertise. The majority of surgical procedures in developing countries are performed by non-surgeons, mostly general practitioners (GPs) with surgical skills. Doctors are rare in many resource-limited countries, and surgeons even rarer. For example, in East Africa, there are 0.25 fully trained surgeons per 100,000 persons compared to 5.69 per 100,000 in the United States.1, 2 The surgical training of GPs is often informal and non-regulated. GPs in South Africa for example, frequently learn their surgical skills after medical school by practicing in a rural hospital during obligatory “community service” years.3 Similarly, many doctors in East Africa gain surgical competency at their first post-graduate district hospital post. A fully qualified surgeon trainer is an exception in these settings. GPs with surgical skills perform essential life-saving surgery mostly at the district hospital level. Procedures are basic and include Cesarean section, incision and drainage of abscesses, hernia repair, bowel resection, circumcision, and closed reduction of extremity fractures. More complicated cases are referred to a tertiary hospital and a fully trained surgeon if available. Surgical training programs for GPs are on the rise. In Niger, the Ministry of Health and the University of Niamey School of Medicine co- sponsor a 12 month training program for GPs. Graduates receive certificate in “Capacity of District Surgery”.4 For most of the 1990s, Médecins Sans Frontières offered GPs in Chad in surgical training for 6-12 months prior to working in district hospitals where they were expected to perform surgery independently.5 However, the majority of GPs in resource-limited settings still receive no formal surgical training. How many hours does it take to train a non-surgeon to perform basic surgery? More relevant than counting hours of training, is to ask how to best evaluate the competency of these GPs. Their surgical training is varied and a theoretical curriculum is not always available. Safe surgery requires knowing when as well as how to operate. GPs worldwide provide invaluable surgical services. However, competency varies greatly because training is unregulated. The formal evaluation system and minimum case requirements of Western surgical residency programs can be adapted to ensure that these practitioners working at the district hospital receive adequate training to care for surgical patients safely. References 1. Derbew M, Beveridge M, Howard A, Byrne N. Building surgical research capacity in Africa: the Ptolemy Project. PLoS Med. Jul 2006;3(7):e305. 2. Lynge DC, Larson EH, Thompson MJ, Rosenblatt RA, Hart LG. A longitudinal analysis of the general surgery workforce in the United States, 1981-2005. Arch Surg. Apr 2008;143(4):345-350; discussion 351. 3. Bornman PC, Krige JE. Perspectives on surgery in the new South Africa. World J Surg. Aug 2005;29(8):949-952. 4. Sani R, Nameoua B, Yahaya A, et al. The impact of launching surgery at the district level in niger. World J Surg. Oct 2009;33(10):2063-2068. 5. Chu K, Rosseel P, Gielis P, Ford N. Surgical task shifting in Sub- Saharan Africa. PLoS Med. May 19 2009;6(5):e1000078. Competing interests: None declared How long does it take to train a surgeon? What is the Aim? 25 November 2009 M Felix Freshwater, Voluntary Professor of Surgery University of Miami School of Medicne Send response to journal: Re: What is the Aim? Days to train a surgeon - subject to debate Days to educate a surgeon - a lifetime Competing interests: None declared

RESEARCH: Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial Hoff et al. (29 May 2009) [Abstract] [Full text] [PDF] Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised... Re: Complications due to sigmoidoscopy and colonoscopy? 26 November 2009 Geir Hoff, professor Cancer Registry of Norway, 0304 Oslo, Norway Send response to journal: Re: Re: Complications due to sigmoidoscopy and colonoscopy? Dear Professor Dubben, Thank you for asking these questions. We agree that complications, harms and risks should be clearly weighted against benefits of screening. This is particularly important once (or if) the expected benefit of endoscopy screening may become evident after a longer follow-up period. At this interim analysis we did not want to repeat too much information from the already published baseline data referred to in the present BMJ paper. In this publication (1) complications are described in detail. These baseline results also include the 50-54-year old add-on age cohort not yet included in our follow-up analyses. Briefly, there were no perforations, bleeding or other complications requiring hospitalization after flexible sigmoidoscopy. Out of 38 events not requiring hospitalization (0.2%), there were 26 cases of vasovagal reaction due to the on-site administration of enema or the flexible sigmoidoscopy examination itself. During colonoscopy work-up of screen-positives there were six perforations – one in 336 therapeutic colonoscopies and none in the 803 purely diagnostic colonoscopies. Additionally, four patients were admitted to hospital due to post-polypectomy bleeding, but none of them required transfusions or surgical intervention. There were 41 minor events not requiring hospitalization during the 2524 colonoscopies – including 24 cases of vasovagal reactions. For patients requiring surgery for screen-detected cancer (n=37) or complications at work-up colonoscopy (n=6) there was no post-surgical mortality, but two severe complications – one case of pulmonary embolism and one case of anastomotic leakage after resection. Yours sincerely, Geir Hoff 1. Gondal G, Grotmol T, Hofstad B, Bretthauer M, Eide TJ, Hoff G. The Norwegian colorectal cancer prevention (NORCCAP) screening study: baseline findings and implications for clinical work-up in age groups 50-64 years. Scand J Gastroenterol 2003;38:635-42 Competing interests: None declared Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised... Complications due to sigmoidoscopy and colonoscopy? 25 November 2009 Hans-Hermann Dubben, Associate professor University of Hamburg, Institute of Primary Medical Care, Martinistrasse 52, 20246 Hamburg, Germany Send response to journal: Re: Complications due to sigmoidoscopy and colonoscopy? In the interesting and important study on colorectal cancer screening by Hoff et al. it was reported that “no severe complications occurred during flexible sigmoidoscopy.” How were “severe complications” defined? What kind of complications occurred due to sigmoidoscopy and colonoscopy and how frequent were they? Yours sincerely, Hans-Hermann Dubben Competing interests: None declared

NEWS: Journal retracts article about age of transfused blood three years after publication Lenzer (20 May 2009) [Full text] Journal retracts article about age of transfused blood three years after publication Muddy Waters: "Fraud" Vs. "Lost Data" And An Editor's Conflict Of Interest 25 November 2009 Shailendra Joshi, Assistant Professor Columbia University, NY10032 Send response to journal: Re: Muddy Waters: "Fraud" Vs. "Lost Data" And An Editor's Conflict Of Interest To The Editor, The BMJ, Far from clarifying the situation, Dr. Shafer’s response to Ms. Lenzer’s article (1,2) raises more scientific and editorial questions about the editorial handling of the Basran paper particularly when there seems to be an apparent conflict of interest.(3) • An important question it raises is regarding the significance of the loss of data while defending a scientific paper? The Basran paper was questioned by Rothmann et al. soon after publication, well within the Office of Research Integrity (ORI) guidelines that recommend data and techniques to be preserved for at least three years, or longer if they are considered significant.(4,5) When the Anesthesia and Analgesia (A&A) decided not to retract the paper Dr. Shafer wrote, “How embarrassing!”(6) More recently in his comments to the Anesthesiology News he considered retraction of the Ruben papers to be a case of fraud but the Basran paper he said was different, a case of lost data that ‘“did not involve fraud”.(7) Dr. Shafer is correct that loss of data by itself does not amount to fraud or scientific misconduct. The current definition of scientific misconduct (42 CFR 93.103) does not specifically include loss of data even when there is a challenge immediately after publication, while "falsification" and "fabrication" are clearly defined (http://law.justia.com/us/cfr/title 42/42- 1.0.1.8.71.1.29). If we accept the loss of data as a valid excuse for not defending the results, then it will be virtually impossible to subsequently investigate any allegations of falsification or fabrication. The lack of penalty for not archiving data for any length of time seems to provide a loophole in the definition of scientific misconduct that needs to be addressed by the ORI. • Dr. Shafer says, “the era of written laboratory notebooks has passed. This problem will likely recur because investigators archive data on spreadsheets hosted on their laptop computers.” Dr. Shafer’s excuse that the data were lost because they were on missing laptops does not apply to the Basran paper. The Basran paper was a retrospective analysis of clinical data that are still available through hospital, blood bank and US social security death index databases, page 16.(3) The original data is not experimental data that was archived on a notebook or a laptop. With some effort it should possible to replicate the data set from the very same databases that were used by the authors. Furthermore, it is impossible to accept that all key authors, such as the research coordinator, statistician, first author and the corresponding author, all those who should have had copies of this large data set, had the files on missing laptops. The Bennett-Guerrero/Frumento team published several papers, many of them in the A&A, and should have been familiar with the importance of preserving data. Dr. Shafer’s explanation for the lost data to the BMJ, is slightly different from that in his editorial the Occam’s razor.(6) In the editorial he had asserted that the data were lost as the authors moved. Although at the time when Rothmann et al. questioned the study, five of the nine authors, including the first author, were at their respective institutions. • Dr. Shafer says that “Retraction sends a strong message about authorship responsibility for archiving data” but he makes an exception in this case because the publication did not describe a new drug, device or a procedure so he let it stand "albeit" weakly. Not true! In 2007, the range of penalties that the A&A could impose on an author for "academic misconduct" could be, "Sanctions against authors range from requesting a Letter to the Editor acknowledging the error and voluntarily withdrawing a manuscript, to a lifetime ban on publication in Anesthesia & Analgesia." (14) When it came to the Basran paper the journal applied the least possible penalty for not archiving data, by merely requesting a “letter acknowledging the error”. In the letter the authors did not even have to disclose how the data were lost within days of publication. The penalty imposed for the loss of data then was more was in line with the “How embarrassing!” comment than it was to send any strong message. The message “Occam’s razor” sent was contrary to the commitment to data archiving that Dr. Shafer now apparently supports.(6) In addition, Dr. Shafer seems to be arguing for a two-tier system for peer- review based on the contents of the publication (devices, drugs and procedures vs. others, such as basic science papers) that is fundamentally unfair and potentially dangerous in the long run. Be as it may, the publication by Basran et al. was not an insignificant one for the A&A. The paper’s findings could have huge impact on the operations of (procedures at) the blood banks and it could also increase liability of medical professionals. The New York Times (15), Science Now (16), the Red Cross (17), and the FDA (18) quoted this paper! How many papers in the A&A achieve such recognition? If this paper did not merit scrutiny, will any other paper ever will? • Dr. Shafer says the findings of this study have been “verified” by the Koch’s paper(19). The significance of the Basran paper is not just in pointing to the hazards of blood transfusion but when they are likely to occur. The Basran paper draws that line at >30 days while the Koch paper draws it at >14 days.(3,19) Not the same results. The difference in the results could have a huge impact on the operations of the blood banks.(20,21) In May 2008, a joint statement by the American Association of Blood Banks (AABB), American Red Cross (ARC) and America’s Blood Centers (ABC), pointed to the problems with the Koch’s study and recommended no changes in blood transfusion practices based on these publications.(17) • Dr. Shafer says that, “Journals have neither the authority nor the resources to investigate questions that arise regarding the conduct of research. That responsibility lies with the academic institution." Certainly true, however, the readership of the journal and the larger society expects the editors to do their job, to ask pertinent questions and to demonstrate some curiosity as 'how" and "why" did something happen not just report the "what". If the criteria for accepting a publication is the belief that the finding can be trusted (6), sooner or later A&A will permit fraudulent research to get by its review process.(22) Note that contrary to what the authors repeatedly emphasize that there is “an error in our paper”, suggesting a single error, (13,23) there are many errors in the paper beyond those that Rothmann et al. were concerned with.(24) There are unusually strong P-values such as "P = 0.000" (page 18) or "P < 0.000" (Page 17), the data in text and tables are internally inconsistent in several places, whether this is poor editing, sloppy rounding, or statistical errors is hard to determine.(3) Although disturbing, these are not the major problems with the paper. • The major problems with the Basran study are that data presented in the final manuscript are incompatible with the preliminary data presented as earlier in abstracts.(3,9,10) While the underlying data are missing, we do have access to preliminary results published as abstracts from the same cohort. (9,10) In their retraction letter (13) the authors have acknowledged, the paper was retracted because the number of patients with acute renal dysfunction (ARD, 58 cases) was the same for the 392 patients reported in the abstract (9) as it was for the 321 patients that were reported in the final analysis.(3) There was not a single case of ARD in the 71 patients that were excluded from the final analysis. Exclusions in the final analysis were mostly due to the patients receiving "irradiated blood".(3) With 18% overall incidence of ARD (3) the chances of this happening is exceedingly remote, less than 1:1000,000. Alternately, if we accept the data in the abstract and the paper, then we will come to the stunning and improbable conclusion that “irradiated blood” provides absolute protection against renal failure during repeat cardiac surgery! Furthermore, there were a total of 434 patients with cardiac re- operations in the abstract and the paper. According to the abstracts, 42 patients were excluded because they were not transfused.(9,10) Of the remaining 392 that were transfused, "Ninety-two patients were excluded because they received ≥1 U of irradiated RBCs." (3) Therefore, there could be no more than 300 eligible patients in this cohort, even if we ignore the other exclusion criterions. Yet, the study describes results from 321 patients! Where did these 21 additional patients come from? The apparent incompatibility between the data presented in the abstract and the final manuscript is not some simple error as the authors (13,23), and Dr. Shafer (6), refer to but they raise the possibility of a compromised data set. Either the inclusion and exclusion criteria were not properly applied, or there were serious data entry errors, or there was "cherry picking" of the data particularly with regards to patients with renal failure. The absence of any effort on the part of the authors' to replicate their results - when they could apparently have done so – under these circumstances, also challenges one's imagination. • What has really made the Basran paper unique is the editorial handling of the issues. One thing Dr. Shafer does not categorically state is whether he has/had any conflict of interest in the defending the Basran paper although he has commented on the paper several times by now.(1,6,7,25) An unambiguous statement in the matter will help us understand what he and the journal consider to be a conflict of interest?(26) A recent article and accompanying editorial in the Proceedings of the Mayo Clinic points to complex bidirectional issues regarding the conflicts of interest pertaining to medical journal editors.(27,28) Under the usual circumstances, if Dr. Shafer was seeking a job or transitioning into one, at the department of origin of the paper (2) he should have at least declared his conflicts of interest and ideally should have excused himself from intervening in the process.(29) In his closing comments Dr. Shafer certainly wants to put all this behind. However, Dr. Shafer’s comments and actions are deeply concerning whether he is providing changing reasons for data loss,(1,6) applying a rhetorical argument “Occum’s razor” to correct statistical errors,(6) or "apparently" ignoring his conflicts of interest.(2) Instead of proposing new rules, the A&A under Dr. Shafer should be more alert and less gullible, and it should follow the existing rules. A good starting point for Dr. Shafer will be to follow the lead of the Basran paper and retract his editorial “Occam’s razor” that in my opinion undermines the significance of data loss. (6) For the rest of us, and for the regulatory authorities, we should address the deficiencies in the definition of research misconduct and find methods to enforce at least some over-sight of medical editors from the ground up and top down. Sincerely, Shailendra Joshi, MD References: 1. Shafer SL. Editorial Responsibilities. The BMJ 2009;Rapid Response:b 2057. 2. Lenzer J. Journal retracts article about age of transfused blood three years after publication. The BMJ 2009;338:b 2057. 3. Basran S, Frumento RJ, Cohen A et al. The association between duration of storage of transfused red blood cells and morbidity and mortality after reoperative cardiac surgery. Anesth Analg 2006;103:15-20. 4. Steneck NH. ORI Introduction to the Responsible Conduct of Research: US Government Printing Office, 2007. 5. Coulehan MB, Wells JF. Guidelines for Responsible data management in Scientific Research. Clinical Tools:http://ori.dhhs.gov/education/products/clinicaltools/data.pdf. 6. Shafer SL. Occam's razor. Anesth Analg 2007;104:1597-8. 7. Editorial. Burned by Fraud, Anesthesia Journal Grids Author Rules. Anesthesiology News 2009; 35 :1 and 70. 8. Lenzer J, Brownlee S. Government Orders Columbia to Tell Patients 'True Nature" of Drug Study. Huffington Post 2009:http://www.huffingtonpost.com/2009/10/07/ government-orders columbi_n_312536.html. 9. Basran S, Frumento R, Cohen A et al. Association between Length of Storage of Erythrocytes and Postoperative Acute Renal Dysfunction in Patients Undergoing Reoperative Cardiac Surgery. Anesthesiology 2004;Proceedings of the Annual Meeting of the American Society of Anesthesiologists 2004:A205 http://www.asaabstracts.com/strands/asaabstracts/search. 10. Frumento R, Basran S, Cohen A et al. Association between the Length of Storage of Transfused Red Cells and Length of Stay in Patients Undergoing Reoperative Cardiac Surgery. Anesthesiology 2004;Proceeding of the Annual Meeting of the American Society of Anesthesiologists 2004:A-179 http://www.asaabstracts.com/strands/asaabstracts/search. 11. Girshin M, Frumento RJ. Pediatric Mortality Related to Anesthesia outside of the Operating Room. ASA abstract (A-1408) 2007;American Society of Anesthesiologists Annual Meeting Abstracts (abstract index) (index):http://www.asaabstracts.com/strands/asaabstracts/abstractList.htm;j sessionid=2C938BC55238FF8149087F60BCB77BDD?year=2007&index=16. 12. Jindal M, Frumento R. Can ASA Grade Predict QA Respiratory Events in Bariatric Surgery? An Analysis of 1,625 Patients (A-925). Annual meeting of the American Society of Anesthesiologists (abstract index) 2007:http://www.asaabstracts.com/strands/asaabstracts/abstractList.htm;js essionid=F5C6B1F8B6AFE9AFE0271CAF9AC52A68?year=2007&index=15. 13. Basran S, Frumento R, Cohen A et al. Request for Retraction. Anesth Analg 2009;108:1991. 14. Editorial. Guide of Authors 2006-07. Anesth Analg 2007;105:187-99. 15. Balakar N. Age of Trasfused Blood May Play Part in Recovery New York Times. New York, 2006:http://www.nytimes.com/2006/06/27/health/27blood.html. 16. Gray B. Blood Gone Bad? Science 2006;Science Now:http://sciencenow.sciencemag.org/cgi/content/full/2006/622/2. 17. Triulzi D. Clinical Significance of Red Cell Age in Transfusions. Statement Before the Advisory Committee on Blood Safety and Availability 2008;May 30, 2008 :http://www.aabb.org/Content/News_and_Media/Statements/jointstatement0 53008.html 18. He P. FDA's Criteria for Evaluation of Red Blood Cell Products. Proceedings of the Blood Products Advisory Committee (91st) Meeting, Rockville MD 2008:http://www.fda.gov/ohrms/dockets/AC/08/slides/2008- 4355S1-12_files/frame.htm. 19. Koch CG, Li L, Sessler DI et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med 2008;358:1229-39. 20. Pereira A. Blood inventory management in the type and screen era. Vox Sang 2005;89:245-50. 21. Owens W, Tokessy M, Rock G. Age of blood in inventory at a large tertiary care hospital. Vox Sang 2001;81:21-3. 22. Shafer SL. Tattered threads. Anesth Analg 2009;108:1361-3. 23. Basran S, Frumento R, Cohen A et al. Author reply. Anesth Analg 2007;104:1597. 24. Rothmann M, Braun MM, Ng TH. On the hazard ratios and corresponding confidence intervals that appear in Basran et al. (2006). Anesth Analg 2007;104:1597; author reply. 25. Shafer SL. Notice of Retraction. Anesth Analg 2009;108:1953. 26. Shafer SL. Full disclosure matters! Anesth Analg 2008;106:1017. 27. Lanier WL. Bidirectional conflicts of interest involving industry and medical journals: who will champion integrity? Mayo Clin Proc 2009;84:771- 5. 28. Hirsch LJ. Conflicts of interest, authorship, and disclosures in industry- related scientific publications: the tort bar and editorial oversight of medical journals. Mayo Clin Proc 2009;84:811-21. 29. Editorial. International Committee for Medical Journal Editors: Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication. 2008 :http://www.icmje.org/icmje. Competing interests: none

VIEWS & REVIEWS: Shiny happy people? Spence (20 May 2009) [Full text] Shiny happy people? a modest proposal for a melanoma trial 26 November 2009 Stephen F Hayes, GP, GPwSI in dermatology TheCanute Surgery, 6A Portsmouth road, Southampton SO19 9AL Send response to journal: Re: a modest proposal for a melanoma trial Sir Dr Spence rightly says that there are things we don't know about melanoma. Dermatologists believe that removing lesions at a thinner stage, due to better diagnosis and earlier surgery, prevents progress to invasive disease, which is one explanation for the mortality figures rising more slowly than the incidence. It is assumed from 5 year survival figures based on Breslow thickness that these thinner lesions would have progressed if left. However, there has never been a proper randomised controlled clinical trial to prove that thin melanomas progress to invasive disease, so possibly those of us who labour to diagnose ever thinner melanomas through education are wasting our time. We need evidence. A trial would be easily designed, and perhaps could begin as early as the first of April next year. Patients with clinically diagnosed thin melanomas could be randomised to treatment or observation groups. The progress of their melanomas could be observed and in time we would have proper evidence as to what proportion of thin melanomas advance to invasive and metastatic disease, and over what time span. In the absence of such an RCT, how can we be sure that we are doing any good by excising thin melanomas? On the other hand, if the above trial fails to recruit sufficient volunteers or is declined ethical approval, we'll have to fall back on common sense and profesional judgment. Not so good as an RCT of course, but sometimes the best we can do. Competing interests: worker in skin cancer clinic, PCDS trustee and dermoscopy educator

EDITORIALS: Treatment of enteric fever Parry and Beeching (3 June 2009) [Full text] Treatment of enteric fever Chronic carriage and mucosal health. 27 November 2009 Richard G Fiddian-Green, FRCS, FACS None Send response to journal: Re: Chronic carriage and mucosal health. Resistence to infection to gut organisms depends upon antigen presentation, the secretion of IgA, and T cell competence. All are impaired when there is a chronic energy deficit for they are highly energy dependent. Inf Crohn's disease, for example, "lazy" T cells are implicated it the pathogenesis. A chronic energy defict is accompanied by alterations in the gaseous milieu in the lumen of the gut, a potentially important variable in the case of microaerophilic and anaerobic organisms such as H pylori and C difficile (1). The energy deficit could be due to mucosal ischaemia induced, for example, by dehydration in an hot climate. It could also be due to a nutritional deficit particularly in regard to those nutrients necessary for the de novo resynthesis of ATP. Prolonged carriage may, therefore, be partially or wholly the product of a mucosal energy deficit. 1. Richard G Fiddian-Green. Chronic intestinal ischaemia and Hirschsprung’s disease. Archives of Disease in Childhood 2007;92:185. 2. Virchow's cell theory in action? Richard G Fiddian-Green (23 March 2009) rapid response re: Jo C Dumville, Gill Worthy, J Martin Bland, Nicky Cullum, Christopher Dowson, Cynthia Iglesias, Joanne L Mitchell, E Andrea Nelson, Marta O Soares, David J Torgerson on behalf of the VenUS II team. Larval therapy for leg ulcers (VenUS II): randomised controlled trial. BMJ 2009; 338: b773 Competing interests: None declared Treatment of enteric fever Carrier state is a major risk for emergence of antimicrobial resistance to typhoidal salmonellae 25 November 2009 Hendrik K van Saene, Consultant/Reader University of Liverpool L693GA, Nia Taylor, Vladimir Damjanovic Send response to journal: Re: Carrier state is a major risk for emergence of antimicrobial resistance to typhoidal salmonellae We read with interest the editorial entitled ‘Treatment of enteric fever’ by Drs Parry and Beeching1. We agree that ’fluoroquinolones remain the first option in areas where resistance is uncommon’. The authors rightly highlight the need to understand the factors that determine the emergence of isolates with decreased susceptibility to ciprofloxacin (DSC) in many parts of Asia. They query whether this may be because ciprofloxacin dose is too low, the duration of treatment is too short, or because ciprofloxacin is used indiscriminately in all patients with fever. There is no doubt that any of these or all of them may contribute to the selection of resistant mutants, however the question remains what factor determines the emergence of resistant mutants in the first place. We suggest that the understanding the carrier state of the typhoidal Salmonellae may offer an explanation. A number of facts can substantiate the crucial role of the faecal carriage of typhoidal Salmonellae in the emergence of DSC. First, typhoidal Salmonellae are well adapted human parasites with the ability to invade, persist .and in some individuals establish a chronic carrier state with persistent excretion of the organism for months or years2. Second, although the intensity of excretion by carriers may vary widely, figures as high as 450x106 organisms per gram of faeces in a paratyphoid carrier have been quoted, and between 1x106 and 10000x106 for typhoid carriers3. We would suggest that such high microbial gut concentration guarantees increased spontaneous mutation leading to polyclonality and antibiotic resistance in typhoid and paratyphoid carriers, in a similar manner as it occurs in the critically ill with gut overgrowth of potentially pathogenic organisms4,5. Third, it has also been reported that high level quinolone resistance was induced through the long carrier state of S.paratyphi A under selective pressure of frequent quinolone administration6. Fourth, the emergence of isolates with DSC occurs in parts of Asia with a high level of carriage in endemic areas7. Fifth, most chronic carriers are asymptomatic and a quarter may have had no history of typhoid fever8, a fact which further contributes to transmission of DSC mutants. Sixth, although clonal spread of particular quinolone resistant strains was reported in some areas9, the evidence that resistance has emerged de novo in different strains is also published10. Seventh, resistance to ciprofloxacin has been described in cases of gut overgrowth of other gram-negative organisms, such as Acinetobacter, by similar mutation mechanism as in Salmonella11. Eighth, and finally, one of the authors of the editorial in the discussion (CMP) concludes together with Threlfall9 in their extensive review on the same subject that ‘patterns of resistance in Salmonella are constantly changing’. However finding and treating chronic carriers will remain a daunting task. We believe that surveillance of the abnormal carrier state for resistant bacteria will become an essential part of managing typhoid fever in the future era of antimicrobial resistance9. The addition of enteral antimicrobials polymyxin/tobramycin to eradicate abnormal carriage may be part of that management of resistance against fluoroquinolones and/or macrolides12. HKF van Saene N Taylor V Damjanovic 1. Parry CM, Beeching NJ. Treatment of enteric fever. BMJ 2009; 338: 1340-1341. 2. Wain J, Hien TT, Connerton P, Ali T, Parry CM, Chinh NT, Vinh H, Phuong CX, Ho VA, Diep TS, Farrar JJ, White NJ, Dougan G. Molecular typing of multiple-antibiotic-resistant Salmonella enterica serovar typhi from Vietnam: application to acute and relapse cases of typhoid fever. J Clin Microbiol 1999; 37: 2466-2472. 3. Christie AB. Typhoid and paratyphoid fevers. In Infectious Diseases: Epidemiology and Clinical Practice. Eds AB Christie Churchill Livingstone New York, 1987; pp 100-164. 4. van Saene HK, Taylor N, Damjanovic V, Sarginson RE. Microbial gut overgrowth guarantees increased spontaneous mutation leading to polyclonality and antibiotic resistance in the critically ill. Curr Drug Targets 2008; 9: 419-421. 5. Damjanovic V, Taylor N, van Saene HK. Origin of epidemic clones of Acinetobacter in the critically ill. J Hosp Infect 2009; 73: 285-286. 6. Adachi T, Sagara H, Hirose K, Watanabe H. Fluoroquinolone-resistant Salmonella paratyphi A. Emerg Infect Dis 2005; 11: 172-174. 7. Roumagnac P, Weill FX, Dolecek C, Baker S, Brisse S, Chinh NT, Le TA, Acosta CJ, Farrar J, Dougan G, Achtman M. Evolutionary history of Salmonella typhi. Science 2006; 314: 1301-1304. 8. Bhan MK, Bahl R, Bhatnagar S. Typhoid and paratyphoid fever. Lancet 2005; 366: 749-762. 9. Parry CM, Threlfall EJ. Antimicrobial resistance in typhoidal and nontyphoidal salmonellae. Curr Opin Infect Dis 2008; 21: 531-538. 10. Hasan R, Cooke FJ, Nair S, Harish BN, Wain J. Typhoid and paratyphoid fever. Lancet 2005; 366: 1603-1604. 11. Riley TV, Webb SA, Cadwallader H, Briggs BD, Christiansen L, Bowman RA. Outbreak of gentamicin-resistant Acinetobacter baumanii in an intensive care unit: clinical, epidemiological and microbiological features. Pathology 1996; 28: 359-363. 12. Taylor N, van Saene HK, Abella A, Silvestri L, Vucic M, Peric M. Selective digestive decontamination. Why don't we apply the evidence in the clinical practice? Med Intensiva 2007; 31: 136-145. Competing interests: None declared