76 Rapid Responses published for 53 different articles.

Articles			Rapid Responses
	NEWS: Doctors’ view of care pathway for dying patients clashes with audit findings Kmietowicz (16 September 2009) [Full text]		End of Life Care Using the Liverpool Care Pathway Hilary Speller   (23 November 2009) Read every Rapid Response to this article
	OBSERVATIONS: No power for the people Heath (14 September 2009) [Full text]		No Triumph for 'the people' still susanne stevens mccabe   (23 November 2009) Read every Rapid Response to this article
	PRACTICE: Tennis elbow Mallen et al. (2 September 2009) [Full text]		decorator's elbow Geraldine R lindley   (23 November 2009) Family practice & specialism - the difference peter mahaffey   (23 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]		Treatment of coronary heart disease should begin with lowering blood viscosity. Les.O Simpson   (26 November 2009) Read every Rapid Response to this article
	OBSERVATIONS: The chilling effect of English libel law Hurley (28 October 2009) [Full text]		Libel makes our legal system look foolish Neville W Goodman   (24 November 2009) Read every Rapid Response to this article
	RESEARCH: Differences in atherosclerosis according to area level socioeconomic deprivation: cross sectional, population based study Deans et al. (27 October 2009) [Abstract] [Full text] [PDF]		Atherosclerosis cannot be understood without knowledge of blood viscosity. Les.O Simpson   (23 November 2009) Read every Rapid Response to this article
	FEATURE: The price of silence Gornall (27 October 2009) [Full text]		Re. ‘The price of silence’ (Vol.339 31 October) Helen Gavin   (23 November 2009) Read every Rapid Response to this article
	PRACTICE: Depression in adults, including those with a chronic physical health problem: summary of NICE guidance Pilling et al. (27 October 2009) [Full text]		Depression: its pathophysiology and treatment. Les.O Simpson   (20 November 2009) Read every Rapid Response to this article
	CLINICAL REVIEW: Hyperkalaemia Nyirenda et al. (23 October 2009) [Full text]		Re: Salbutamol unsafe in hyperkalaemia Moffat J Nyirenda, et al.   (23 November 2009) Read every Rapid Response to this article
	EDITORIALS: Use of erythropoietins in patients with renal transplants Treleaven and Clase (23 October 2009) [Full text]		‘Normalisation of haemoglobin is hazardous, ineffective and costly.’ Eric J Will   (23 November 2009) Read every Rapid Response to this article
	NEWS: Only 12% of Germans say they will have H1N1 vaccine after row blows up over safety of adjuvants Stafford (21 October 2009) [Full text]		A/H1N1 vaccine in Germany: Analyzing the reasons for a low acceptability David A. Groneberg, et al.   (24 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
	NEWS: Public health messages that invoke disgust work best for men, study finds Kmietowicz (16 October 2009) [Full text]		On the causes of poor sanitation in the public lavatories of the former Soviet Union Sergei V. Jargin   (24 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) Panton Valentine Leucocidin (PVL) Staphylococcus Aureus Osteomyelitis Matthew J Hall, et al.   (24 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
	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]		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
	EDITORIALS: Health research in developing countries Barreto (20 November 2009) [Full text]		Health research in developing countries: Ideas, collaboration, resources. Prof. Enrique J. Sánchez Delgado, MD   (23 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
	EDITOR'S CHOICE: The power of stories Groves (20 November 2009) [Full text]		The power of stories. David R Warriner   (23 November 2009) Once upon a time... Hugh Mann   (23 November 2009) Telling stories through statistics Dr.Indranil Banerjee   (23 November 2009) Read every Rapid Response to this article
	VIEWS & REVIEWS: The health department and the NHS: time to separate? Crisp (20 November 2009) [Full text]		Remedial and generative health services Peter G Davies   (24 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) Why are we so surprised by variation? Peter G Davies   (24 November 2009) Read every Rapid Response to this article
	PRACTICE: Avoiding midazolam overdose: summary of a safety report from the National Patient Safety Agency Lamont et al. (19 November 2009) [Full text]		Time for a more serious attitude to Midazolam John H Wake   (24 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) The importance of Oligomeric bands Ben D Butler-Reid   (23 November 2009) Recurrent myelopathy Mike Boggild   (23 November 2009) Read every Rapid Response to this article
	EDITORIALS: The economic impact of pandemic influenza Maynard and Bloor (19 November 2009) [Full text]		Flu Bedside Diagnosis and Differential Diagnosis Sergio Stagnaro   (23 November 2009) Read every Rapid Response to this article
	CLINICAL REVIEW: Diagnosis and management of dengue Teixeira and Barreto (18 November 2009) [Full text]		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]		Oliver Wendell Holmes and puerperal fever Peter N Bennett   (26 November 2009) Read every Rapid Response to this article
	VIEWS & REVIEWS: Politics, science, and the White House Smith (17 November 2009) [Full text]		Politics & Religion Hugh Mann   (24 November 2009) Read every Rapid Response to this article
	LETTERS: Avoiding spurious hyperkalaemia Gama et al. (17 November 2009) [Full text]		Re: spurious hyperkalemia Paul M. Verheecke   (24 November 2009) Read every Rapid Response to this article
	NEWS: First official citywide electronic record system for patients is launched in London O’Dowd (17 November 2009) [Full text]		Where is the evidence of benefit? Peter A West   (23 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]		Please don't waste more resources Thomas A Groves   (26 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
	VIEWS & REVIEWS: Learning to teach Jackson (12 November 2009) [Full text]		Learning to Teach David R. Gibson   (24 November 2009) Re: Practical Teaching Tips [Correction] Avtar Singh   (23 November 2009) Practical Teaching Tips Avtar Singh   (20 November 2009) Read every Rapid Response to this article
	PRACTICE: Investigating recurrent respiratory infections in primary care Wood and Peckham (12 November 2009) [Full text]		Re: A clear indication for HIV testing Dr Viera Scheibner   (24 November 2009) A clear indication for HIV testing. Morgan Evans   (23 November 2009) Read every Rapid Response to this article
	EDITORIALS: Capping earnings from private patients in NHS foundation trusts Appleby (11 November 2009) [Full text]		Profit not Income Peter A West   (23 November 2009) Read every Rapid Response to this article
	OBSERVATIONS: The years of magical thinking Delamothe (11 November 2009) [Full text]		Magical thinking on sex as well as drugs Trevor G Stammers, et al.   (23 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]		Age-related increased blood viscosity, walking speed and risk of cardiovascular death. Les.O Simpson   (24 November 2009) Info. regarding Speed to be maintained Revan pujari   (24 November 2009) Slow walking speed and cardiovascular risk john zacharias   (23 November 2009) Good study; few questions DR.Indranil Banerjee, et al.   (20 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) A Third Explanation for the Link Between Inequality and Health Harry F. Tibbals   (23 November 2009) Read every Rapid Response to this article
	EDITORIALS: Slow walking speed in elderly people Harwood and Conroy (10 November 2009) [Full text]		Achilles and the Tortoise. Richard G Fiddian-Green   (24 November 2009) Mortality rate Janet E Shackleton   (23 November 2009) Sprint your way to immortality Michael O'Donnell   (20 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]		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) Surgical trainees need to work smarter not harder Lucy A Radmore   (23 November 2009) Read every Rapid Response to this article
	VIEWS & REVIEWS: The highs and lows of policy based evidence Colquhoun (4 November 2009) [Full text]		Independent? John Stone   (23 November 2009) Read every Rapid Response to this article
	EDITORIALS: Who should receive Tamiflu for swine flu? Ellis and McEwen (6 July 2009) [Full text]		Experience in Sri Lanka Kamal Abdul Naser   (24 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) Over Diagnosis Bias of Melanoma Des Spence   (24 November 2009) Primary Care Dermatology Society recommendation on Sun Bed use Stephen Kownacki, et al.   (23 November 2009) Read every Rapid Response to this article
	EDITORIALS: Treatment of enteric fever Parry and Beeching (3 June 2009) [Full text]		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
	RESEARCH: Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups Madsen et al. (27 January 2009) [Abstract] [Full text] [PDF]		A doubt about the interpretation of the findings Adrian White   (24 November 2009) Read every Rapid Response to this article

NEWS: Doctors’ view of care pathway for dying patients clashes with audit findings Kmietowicz (16 September 2009) [Full text] Doctors’ view of care pathway for dying patients clashes with audit findings End of Life Care Using the Liverpool Care Pathway 23 November 2009 Hilary Speller, Former carer N/A Home Address:SE11 4TJ Send response to journal: Re: End of Life Care Using the Liverpool Care Pathway I would like to comment on the experience of my father’s death which was managed using the Liverpool Care Pathway. He was in a dementia nursing home and could not communicate using words. After a series of strokes my father developed a chest infection. We took the difficult decision that he should be made comfortable, remain in the nursing home and not receive treatment to prolong his life. We were unaware of the practice of withdrawing fluids to a dying person, but it was explained that it was in his interests not to prolong the process of dying. My father survived for 11 days from the first ‘nil by mouth instruction’. His death certificate states that he died from a stroke and bronchial pneumonia, but we feel we witnessed a harrowing death from dehydration. We were at his bedside 24/7 for the final seven days. The LCP was introduced to us several days after the initial decision was taken about his care We had not heard of it before; my interpretation of the document and our need to sign it was simply that it ensured all parties involved with my father’s care understood that he was dying. Having previously never faced the dying process, we did not know what to expect and we felt very poorly supported. We feel there was a lack of continuity in monitoring him; perhaps that is inherent in a nursing home environment. During those eleven days he was seen by five different general practice doctors. We explained to every person involved with his care that his left shoulder was clearly causing him a great deal of pain, especially when moved, although this was not investigated. It was in the last 24 hours of his life when my sister who is a physiotherapist arrived that we realised that my father had a dislocated shoulder. What have we learnt? The LCP must be used by people with good experience and understanding of it as a tool in palliative care. More training is needed, especially for staff in care homes where the majority of residents do indeed end their lives. There must be access to expert palliative care on a 24/7 basis, beyond hospice and hospital settings. The dying person needs continuity of care; the LCP guidelines are meaningless if applied as a box ticking exercise. In addition, there are specific issues about end of life care for those with dementia which need to be considered. And relatives need more than kind words and cups of tea. We are in no doubt that my father had a bad death. We hope that the painful process of recounting aspects his death mean that lessons are learnt. Hilary and Rosemary Speller 22 November 2009 Competing interests: None declared

OBSERVATIONS: No power for the people Heath (14 September 2009) [Full text] No power for the people No Triumph for 'the people' still 23 November 2009 susanne stevens mccabe, retired cf5 6su Send response to journal: Re: No Triumph for 'the people' still It is not pleasant to feel powerless but maybe demonising those with opposing strongly held views is not very useful. What should not happen is that residents of local communities become used as pawns in the sort of power games they are largely unaware of. As it turns out Rosa Curling, Solicitor for Leigh Day and Co. representing campaigners against the proposal to introduce a Polyclinic,has won a challenge to the legality of the Trust's proposal. They consulted only on locality and services without consulting as to whether it was wanted by the community in the first place. This could be described as a successful curb on the power of NHS Camden but it was achievable only with the help of large amounts of funding and the assistance of networks of people in influential positions. People in general in the community had very little information or knowledge, were mainly informed if at all, by those who opposed the introduction of the Polyclinics. It is not easy to weigh up information and come to an autonomous decision in this way.The ability of residents to seriously influence policy, as usual, is pretty negligible. Massive efforts have been put into this campaign against the Polyclinics but it has not been matched historically by any group from either side, practitioners of managers, by an interest in bringing people into a democratic process - whereby all with a stake could work together. 'The people' mainly get what coalitions of those in powerful positions, decide. Reference: article by Gareth Iacobucci in 'Pulse' November 18th 2009 Competing interests: ex long term resident of Camden. Have been involved in NHS consultation and implementation processes

PRACTICE: Tennis elbow Mallen et al. (2 September 2009) [Full text] Tennis elbow decorator's elbow 23 November 2009 Geraldine R lindley, retired homoeopath N/a Send response to journal: Re: decorator's elbow The grip tension may be the source of the problem if no other cause is obvious. Has your patient tried increasing the circumference of his brush handles with the use of padding( or changing the make of his brushes)? This will frquently give some relief as it may help relax his habitual grip and thus help resolve the problem Competing interests: None declared Tennis elbow Family practice & specialism - the difference 23 November 2009 peter mahaffey, consultant (plastic & hand surgery) bedford hospital mk42 9dj Send response to journal: Re: Family practice & specialism - the difference We in the hospital service are constantly told that its more efficient to retain patients in primary care, but honestly, most of that 'consultation' was flannel. And what did the patient get out of it at the end......nothing really. Tennis elbow is diagnosed following a complaint of persistent pain at the lateral epicondyle and is confirmed by focal tenderness 1 cm distal to the bony prominence. There is no proven treatment and the condition settles after about 1 year. Usually its fatuous to tell patients to "avoid" certain actions because they have to get on with their lives and pain will dictate what they can and cant do. Steroids achieve nothing (Stahl, S., Journal of Bone and Joint Surgery 79:1648-52 (1997). Indeed if one believes the microtrauma theory, then to subject patients to "pepperpot" injections at the site is nonsense because anyone who's done appreciable amounts of minor surgery will be well familiar with the degree of bruising and bleeding one gets in local tissues from injections. 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... 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

OBSERVATIONS: The chilling effect of English libel law Hurley (28 October 2009) [Full text] The chilling effect of English libel law Libel makes our legal system look foolish 24 November 2009 Neville W Goodman, Retired Anaesthetist Bristol, BS9 3LW, UK Send response to journal: Re: Libel makes our legal system look foolish I am pleased that this issue is being discussed. Sadly, it is not the first time that real concern has been raised - I am thinking of what happened immediately after Robert Maxwell's death - and I fear that discussion is all that will happen. I am surprised that, 6 days after this article appeared in print, there are still no responses to it? Is that because everyone agrees, or because no one thinks that it will ever happen to them? Some years ago, I was threatened with libel. When it seemed all had died down (simply because letters ceased to arrive and threaten me), I wrote a Personal View for the BMJ, making the plea that the English libel laws be changed and that medical journals be left alone. Although I wrote generally, not specifically, and repeated absolutely no details of the accusation that had been made against me that could have identified the claimant, the Personal View was rejected on the advice of the BMJ's lawyers that the claimant could try again. The case was ridiculous, but to say anything about it might well resurrect it even now. I await with interest to see how many paragraphs of this Eletter appear on- line. Competing interests: None declared

RESEARCH: Differences in atherosclerosis according to area level socioeconomic deprivation: cross sectional, population based study Deans et al. (27 October 2009) [Abstract] [Full text] [PDF] Differences in atherosclerosis according to area level socioeconomic deprivation:... Atherosclerosis cannot be understood without knowledge of blood viscosity. 23 November 2009 Les.O Simpson, retired experimental pathologist Dunedin New Zealand 9077 Send response to journal: Re: Atherosclerosis cannot be understood without knowledge of blood viscosity. Deans et al have reported the results of a high-tech assessment of vascular changes which occur in both deprived and in non-deprived participants. It is noteworthy that although the blood levels of cholesterol and smoking history were recorded, there was no recognition of the effects of such variables on the physical properties of the blood, or on blood flow in the presence of plaques. As plaques reduce the lumenal diameter, the rate of blood flow distal to the plaque will be reduced, resulting in thixotropic amplification of blood viscosity. This is because blood is a thixotropic system in which viscosity is related directly to rate of blood flow. Blood viscosity is minimal at the highest rates of blood flow. A PubMed search for "atherosclerosis and blood viscosity" produced 316 titles, so it is not an unresearched topic. The significance of blood viscosity is that it is a determinant of intravascular pressure. The relevance of this was explained by JE French writing on atherosclerosis in Florey's "General Pathology," 1958. French drew attention to the fact that, "There are no capillary vessels in the tunica intima of normal arteries.In general, the vasa vasorum do not penetrate further than the middle of the tunica media and the nutrition of the intima and the inner part of the media is maintained by filtration from the arterial lumen." It seems reasonable to consider that the nature of the filtrate entering the intima will be determined by the blood pressure. If this is so then an elevation of blood pressure would produce a different filtrate possibly with larger molecules. This could explain the vascular changes seen in healthy subjects, as French had noted, "...the so-called fatty streaks may be seen in the posterior wall of the aorta in children, and by the age of 20, some evidence of atherosclerosis can always be found on careful inspection of the aorta." It is possible that such deposits represent non-metabolised substances which had been filtered from the vessel lumen. So what do the observations of French imply for the results of the Deans et al study ? Firstly, because of the absence of any measures of blood rheology, they were unable to explain some of the similarities which linked the deprived and nondeprived data. For example, blood viscosity could be increased in both groups, but due to different mechanisms. Stress, smoking, alcohol intake and dietary factors in different mixes would increase blood viscosity in both groups. Secondly, in circumstances where blood viscosity was increased, plaque score and intima-media thickness measurements could be good predictors of adverse events. Thirdly, the recognition of blood viscosity as an important factor, indicates that lowering of blood viscosity could have beneficial effects. Dietary changes which lowered the intake of saturated fats, and increased the intake of oily fish would be beneficial. As 6 grams daily of fish oil has been found to be effective in hypertension, it is possible that the effects of 6 grams of fish oil daily on blood viscosity could reduce the significance of atherosclerosis. Competing interests: None declared

FEATURE: The price of silence Gornall (27 October 2009) [Full text] The price of silence Re. ‘The price of silence’ (Vol.339 31 October) 23 November 2009 Helen Gavin, Communications Officer L8 7SS Send response to journal: Re: Re. ‘The price of silence’ (Vol.339 31 October) I am writing to voice my concern regarding the way in which the article by Jonathan Gornall, originally researched back in July of this year, was eventually published and also the disgraceful editorial comment that accompanied it. Despite earlier contact during July, the Trust was not afforded the courtesy of being informed that you intended to publish after a lapse of some three months. Had you chosen to inform us that you were going to print we could have perhaps corrected some of the factual inaccuracies in the piece. An example of this is the assertion that all of the compromise agreements entered into by the Trust were with doctors in order to ‘gag’ them. Accurately reported the article could have referred to the fact that agreements were with a range of staff who left the Trust for a variety of reasons, only two of whom were doctors. It would also have been accurate and balanced to have reported that there is a specific clause within such agreements which states that “nothing…prevents the employee making disclosures to the National Patient Safety Agency or any NHS regulatory body.” Apart from being guilty of taking the same biased approach as the main article, the editorial is also written in the most insulting, inflammatory and unprofessional terms about an organisation that has a long track record of success and an excellent reputation locally, nationally and internationally. The slapdash and biased treatment of what is undoubtedly a serious issue does little to further a mature debate and in the process brings the standing of the BMJ into disrepute. Fortunately your discerning readers will recognise that this was an error of judgement on the Editorial department’s part. Yours faithfully, Ken Morris, Chairman, Liverpool Women's NHS Foundation Trust Competing interests: None declared

PRACTICE: Depression in adults, including those with a chronic physical health problem: summary of NICE guidance Pilling et al. (27 October 2009) [Full text] Depression in adults, including those with a chronic physical health problem: summary... Depression: its pathophysiology and treatment. 20 November 2009 Les.O Simpson, retired experimental pathologist Dunedin New Zealand 9077 Send response to journal: Re: Depression: its pathophysiology and treatment. The article by Pilling et al discusses treatment of depression without reference to the pathophysiology. However, there are a number of published reports which raise the possibility that depression is a consequence of impaired cerebral blood flow. Possibly such studies have been rejected because of their small size. But a PubMed search for "Depression and impaired cerebral blood flow," produced 60 titles. Even though many of such studies involve animals, they show a common thought pattern. In 1995, Bench et al reported a study in which patients underwent brain scans while depressed, and were rescanned on remission. The report concluded, "Thus, recovery from depression is associated with increases in regional cerebral blood flow in the same area in which focal decreases in regional cerebral blood flow are described in the depressed state, in comparison with normal subjects." It is difficult to ignore such direct observations as they imply that depression has a blood flow-related cause. While there is general acceptance that stressful events are triggers for episodes of depression, it seems not to be recognised that the stress hormones stiffen the red blood cells. The resulting reduction in cell deformability will increase blood viscosity. For example, the English translation of a paper in Italian (Psychological stress and sudden death, 2002) included the statement, "...the second mechanism acts through adverse health behaviours, such as poor diet, alcohol consumption or smoking in case of acute psychological stress, the mechanisms involved are mainly the ability to trigger myocardial ischemia, to promote arrhythmogenesis, to stimulate platelet function and to increase blood viscosity." It seemed not to be recognised that the increased blood viscosity was the primary agent. As similar statements have been made by other authors, it is not surprising that a PubMed search for "Depression and blood viscosity," should produce 83 titles. This raises the pertinent question, "Could treatments aimed at reducing blood viscosity be helpful for those suffering from depression?" As Stoll has reported that fish oil was an excellent mood stabiliser in bipolar disorder, and 6 grams of fish oil daily has been found to be an effective treatment for hypertension, would 6 gams of fish oil daily help those suffering from major depressive disorder ? Competing interests: None declared

CLINICAL REVIEW: Hyperkalaemia Nyirenda et al. (23 October 2009) [Full text] Hyperkalaemia Re: Salbutamol unsafe in hyperkalaemia 23 November 2009 Moffat J Nyirenda, MRC clinician scientist/honorary consultant physician The Queen's Medical Research Institute, University of Edinburgh, EH16 4TJ, Justin I. Tang, Paul L. Padfield, Jonathan R. Seckl Send response to journal: Re: Re: Salbutamol unsafe in hyperkalaemia We agree with Prof Dimmitt1 that tachycardia is an adverse effect of β-agonist therapy, and we would advise that sulbutamol should be used with caution in patients with significant coronary artery disease or unstable heart rhythms. There have been no robust controlled clinical trials on management of severe hyperkalaemia, but most studies (including a recent Cochrane review)2 have shown that β-agonists are effective at lowering serum potassium levels. Unfortunately, most reports have only focused on serum potassium levels, but not on mortality or cardiac arrhythmias. Indeed, in studies cited by Prof Dimmitt, β-agonists were not used for management of hyperkalaemia, but to treat COPD in normokalaemic patients.3,4 It is true that β-agonists, like insulin, only promote intracellular potassium shift, but this is thought to be an important early temporizing measure to prevent potential adverse effects of hyperkalaemia – before definitive strategies to remove excess potassium from the body take effect. The use of resonium resins remains controversial, with some authorities not recommending their use for treatment of acute hyperkalaemia.5 1. Dimmitt SB. Salbutamol unsafe in hyperkalaemia. Bmj.com, 19 Nov 2009. 2. Mahoney BA, Smith WA, Lo DS, Tsoi K, Tonelli M, Clase CM. Emergency interventions for hyperkalaemia. Cochrane Database Syst Rev 2005;cd003235. 3. Kallergis EM, Manios EG, Kanoupakis EM, Schiza SE, Mavrakis HE, Klapsinos NK, Vardas PE. Acute electrophysiologic effects of inhaled salbutamol in humans. Chest (2005) 127:2057-2063. 4. Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of β-agonists in patients with asthma and COPD. Chest (2004)125:2309- 2321. 5. Kamel KS, Wei C. Controversial issues in the treatment of hyperkalaemia. Nephrol Dial Transplant (2003) 18: 2215-2218. Competing interests: None declared

EDITORIALS: Use of erythropoietins in patients with renal transplants Treleaven and Clase (23 October 2009) [Full text] Use of erythropoietins in patients with renal transplants ‘Normalisation of haemoglobin is hazardous, ineffective and costly.’ 23 November 2009 Eric J Will, Retired Nephrologist St James's University Hospital, Beckett Street, Leeds LS9 7TF Send response to journal: Re: ‘Normalisation of haemoglobin is hazardous, ineffective and costly.’ The editorial commentary on the paper by Heinze et al rehearsed all the solecisms that careless terminology has visited on this area of clinical research. The catch-phrase metaphors of targeting and normalisation have confused the scientific discussion to the point of utterly misleading statements, like their sub-title above. As they rather awkwardly concede, any putative mischief in Erythropoietin (ESA) treated renal anaemia relates to the intention to reach ‘normal’ haemoglobin (Hb) values (‘treated to a high haemoglobin target)’ through the application of feed-back algorithms to determine ESA dose and intervention thresholds. It should not be concluded that ‘raising haemoglobin to normal concentrations, ...., seems harmful’, since those subjects that did achieve normal values in the index studies did perfectly well (their ref 8 and 10). The Heinze paper, in which neither the criterion of the nominated ‘Haemoglobin’ nor the anticipated intentions of treating clinicians were given, serves to confuse again (their ref 5). It appears to relate outcome to achieved haemoglobin, rather than the intended, unknowable ‘target’ values, a significant change in emphasis of possible causation. The editorialists then succumb to conflate the achieved Hb results with intention by assuming that achieved values were related to ‘the effect of various haemoglobin targets’. In practice, most ‘normal’ Hb values in renal disease probably occur either in patients who do not require ESA at all or are the inadvertent consequence of poorly predictable ESA sensitivity during management. It is the failure to discriminate deliberate from incidental ‘normal’ Hb values in clinical practice that bedevil the development of sensible treatment principles. A super-structure of possible pathopysiological mechanisms is only too easy for clinician scientists to erect and repeat, which further establishes a more readily understood, mechanistic, but potentially erroneous, interpretation of the studies. It would matter less if it were not likely that misguided attempts to avoid ‘high’ Hb levels would result in many lower values, for which there is evidence of avoidable symptomatology and adverse outcome. This sequence of events parallels the probable disbenefit of deliberately reduced haemodialysis hours after the quantification of dialysis dose in the early 1980s, both phenomena being of especial relevance to the private dialysis sector in the US. It would be helpful for the Heinze data to be analysed to give the absolute number of events in each ‘Hb’ category. It seems more likely that any consequence of ESA treatment in transplantation is related to unknown confounding clinical factors that lead to the use of the drugs in the first place, the Hb response being a token of ESA management but in no way causative. Because of the difficulties of ESA management in patient groups the ‘optimal target’ for Hb is an aspirational value towards which clinical effort might be directed by whatever means, in the same sense that optimal Systolic Blood Pressure is a poorly defined ‘less than XXX mmHg’ value. The ‘optimal target’ is also the desirable achieved Hb, but ‘target’ and achievement are qualitatively different components of a treatment vocabulary for which we use only the one word in discourse. So, what may be hazardous, of limited effectiveness and costly are the processes of deliberately attempting to ‘normalise’ Hb in patient cohorts, which few clinicians were anyway pursuing but which cannot be distinguished from inadvertent ESA reactions. The convenient, punchy, publication shorthand of ‘Normalisation’, like ‘tight’ control, is flattering to researchers but ultimately misleading. For the citizen it was fortunate that these semantic confusions allowed governments and payers to move in on the costs of ESA management. It is perhaps less creditable that the scientific academic community have not unpacked the issues, but then it is a Kuhnian universe and they have their own considerations. It is all rather subtle. Competing interests: None declared

NEWS: Only 12% of Germans say they will have H1N1 vaccine after row blows up over safety of adjuvants Stafford (21 October 2009) [Full text] Only 12% of Germans say they will have H1N1 vaccine after row blows up over safety... A/H1N1 vaccine in Germany: Analyzing the reasons for a low acceptability 24 November 2009 David A. Groneberg, Full professor of medicine and director Berlin, David Quarcoo, Cristian Scutaru, Albert Nienhaus, and Andrés de Roux Send response to journal: Re: A/H1N1 vaccine in Germany: Analyzing the reasons for a low acceptability A/H1N1 vaccine in Germany: Analyzing the reasons for a low acceptability N. Stafford recently stated that only 12% of Germans say they will have H1N1 vaccine after row blows up over safety of adjuvants. 1 As one reason for this low acceptability, it is stated that concerns were growing in Germany after news was leaked that government employees and politicians will be given an alternative vaccine. For the public, the state and federal health departments ordered 50 million doses of Pandemrix which is the adjuvanted A/H1N1 vaccine that is produced by GlaxoSmithKline. This vaccine includes adjuvants that may cause side effects. For government employees and politicians, an alternative vaccine without the questioned adjuvants was ordered. In the article, a number of media releases citing scientists, politicians and physicians with controversal opinions is cited and polls that show that only 12% of Germans definitely plan to be vaccinated against H1N1. 1 This is in striking contrast to i.e. the results of Lau et al who reported that about 45% of the Hong Kong general population would be highly likely take up vaccination if it was free. 2 We assessed potential reasons of the extreme low acceptability and conducted a survey among outpatient physicians in the German capital Berlin that was supported by the State department of health, the statuary accident insurance and the State chamber of physicians.3 Analysing the responses of 469 physicians we found that 73,8% (346/469) are of the opinion that the media discussion is unobjective, while only 23,9% (112/469) believe that the discussion is objective (2,3% gave no answer, 11/469) (Fig. 1). In the light of the extremely low acceptability and the discussion on mandatory vaccinations,4 we believe that improved information politics have to be evaluated against the background of future pandemics. David A. Groneberg, director and professor, 1 David Quarcoo, associate director and head physician,1 Cristian Scutaru, research associate, 1 Albert Nienhaus, associate professor and department head, 2 and Andrés de Roux, research associate and physician 1 1 Charité - Institute of Occupational Medicine, Free University Berlin and Humboldt-University Berlin, Berlin, Germany; 2 Institution for Statutory Accident Insurance and Prevention in the Health and Welfare Services, Hamburg, Germany No competing interests. 1 Stafford N. Only 12% of Germans say they will have H1N1 vaccine after row blows up over safety of adjuvants.BMJ 2009;339:b4335 2 Lau JT, Yeung NC, Choi KC, Cheng MY, Tsui HY, Griffiths S. Acceptability of A/H1N1 vaccination during pandemic phase of influenza A/H1N1 in Hong Kong: population based cross sectional survey. BMJ 2009;339:b4164 3 Berlin State Chamber of Physicians: http://www.aerztekammer- berlin.de/40presse/15_meldungen/00659_FOBI_Neue_Grippe/index.htm (last update: 2009-11-19) 4 Stewart AM. Mandatory Vaccination of Health Care Workers. N Engl J Med. 2009 Nov 4. [Epub ahead of print] PMID: 19890107 Legend figure 1: Opinion of Berlin physicians towards A/H1N1 discussion in the German media. 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.

NEWS: Public health messages that invoke disgust work best for men, study finds Kmietowicz (16 October 2009) [Full text] Public health messages that invoke disgust work best for men, study finds On the causes of poor sanitation in the public lavatories of the former Soviet Union 24 November 2009 Sergei V. Jargin, Pathology Clementovski per 6-82; 115184 Moscow, Russia Send response to journal: Re: On the causes of poor sanitation in the public lavatories of the former Soviet Union It is known that sanitary standards in the lavatories in public places of the former Soviet Union are, on average, far from perfect. One of the psychological mechanisms is, obviously, the following. In the Soviet Army, cleaning of the toilet, as well as other kinds of cleaning work, were used as a punishment for small misdemeanors. The work in the toilet was the most humiliating one. Therefore majority of men, especially those who had served in the army, have strong aversion against cleaning the toilet rooms. Therefore, public lavatories in Russia are usually cleaned by female personnel. In Moscow, Saint Petersburg and other large cities, sanitary conditions in lavatories are, on average, more satisfactory. In some more distant places, such as Dushanbe, Grozny or Vladikavkaz, the author of this letter observed extremely contaminated toilets in public places, where deposits of excrements accumulated around the apertures or lavatory pans, as well as elsewhere on the floor, were up to 1 meter in depth or more. Nonetheless, the lavatories were further in use. One of the reasons thereof is obviously related to the fact that in the army, many soldiers from the corresponding areas refused cleaning lavatories, referring to their customs and traditions. Competing interests: None declared

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 Panton-Valentine leucocidin associated Staphylococcus aureus infections Panton Valentine Leucocidin (PVL) Staphylococcus Aureus Osteomyelitis 24 November 2009 Matthew J Hall, Specialist Registrar, Trauma + Orthopaedics Derriford Hospital, Plymouth, PL6 8DH, Jane Steer, Jonathan Keenan Send response to journal: Re: Panton Valentine Leucocidin (PVL) Staphylococcus Aureus Osteomyelitis We would like to commend the authors of this editorial for raising awareness of disease related to Panton Valentine Leucocidin Staphylococcus Aureus (PVLSA) infection within the world wide community along with the potentially destructive nature of the infection. Early diagnosis with targeted surgical and microbiological treatment combined with screening of close family relatives for the presence of the disease being the clear recommendations. In the UK looking specifically at the disease monitoring by the Health Protection Agency, it can be clearly seen that the numbers of PVLSA infections has risen steadily since 2005, with a two fold increase from 2005 to 2006 (1). Disease surveillance studies have also shown that PVL related disease occurs primarily in clusters within the community as opposed to the hospital environment (1). The editorial by Etienne and Dumitrescu comments on the potential for rapidly progressing musculoskeletal infection however we would like to emphasise the problems of PVL osteomyelitis based on our experience in the Orthopaedic Department in this centre. We have seen several musculoskeletal PVL infections both soft tissue based as well as osteomyelitis. Within the orthopaedic literature there have been several case reports of PVL osteomyelitis reported in children and from these cases it has been noted that the infection is more aggressive and difficult to treat compared to convential osteomyelitis (2, 3). From our experience of a case of PVL osteomyelitis of the proximal tibia we found that an aggressive bone and soft tissue debridement and antibiotics alone were inadequate to treat the infection and that transposition of a well vascularised muscle flap early in the treatment course would have been advisable. The literature and Health Protection Agency figures show that PVLSA infection remains a rare diagnosis in the UK possibly due to the lack of awareness. We completely concur with the original editorial highlighting the emerging danger of PVL strains especially in musculoskeletal infections. Based on our experience of PVL osteomyelitis and its potentially destructive nature we would recommend clinical awareness and testing, early aggressive debridement and use of a muscle flap together with antibiotic therapy and seeking the advice of a specialist microbiologist along with an infection control team in the management of these aggressive infections. Matthew Hall – Orthopaedic Specialist Registrar, Derriford Hospital, Plymouth Jane Steer – Consultant Microbiologist, Derriford Hospital, Plymouth Jonathan Keenan – Consultant Orthopaedic Surgeon, Derriford Hospital, Plymouth 1. Guidance on the diagnosis and management of PVL-associated Staphylococcus aureus infections (PVL SA) in England. August 2008. Lewis D, Campbell R, Cookson B, Day C, Duerden B, Duckworth G, Hawkey P, Howe R, Jeffries D, Kearns A, Morgan M, McCartney C, Nathwani D, Pearson A, Steer J. Health Protection Agency. www.hpa.org.uk. 2. Gillet Y, Dohin B, Dumitresco O, Lina G, Vandenesch F, Etienne, J, Floret D. Osteoarticular infections with Staphylococcus aureus secreting Panton-Valentine leucocidin. Arch Pediatr 2007; Oct 14 Suppl 2: S102-7. 3. Dohin B, Gillet Y, Kohler R, Lina G, Vandenesch F, Vanhems P, Floret D, Etienne J. Pediatric bone and joint infections caused by Panton- Valentine leukocidin-positive Staphylococcus aureus. Pediatr Infect Dis J 2007; Nov 26(11): 1042-8. 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

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 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

EDITORIALS: Health research in developing countries Barreto (20 November 2009) [Full text] Health research in developing countries Health research in developing countries: Ideas, collaboration, resources. 23 November 2009 Prof. Enrique J. Sánchez Delgado, MD, Internist-Clinical Pharmacologist, Director of Medical Education Hospital Metropolitano Vivan Pellas, Managua, Nicaragua Send response to journal: Re: Health research in developing countries: Ideas, collaboration, resources. Health research in developing countries: Ideas, collaboration, resources. In Latin America there are many needs for the health of the population, but also many physicians with good ideas that could contribute to affordable solutions and improvements in prevention, and education of the patients to help themselves. The limited resources for research should not discourage dedicated doctors and scientists to continue searching for the development of practical ideas and collaborate in their respective fields of expertise. The international journals, like the BMJ, in the era of internet, are open to contribute to these efforts, and we should take advantage of this opportunity. For example, ten years ago we published in The Lancet (13 March 1999), that the correlation between pulse or resting heart rate-RHR, and body mass index-BMI, in the PULSE MASS INDEX, permits an easy and inexpensive, not laboratory or technology dependant, evaluation of the global cardiovascular risk. This index can be especially useful in the developing countries, where 80 percent of cardiovascular diseases occur. The PULSE MASS INDEX has a high correlation with the Framingham Risk Score. In the last few years, almost a decade after our original publication, several other studies have confirmed the importance of the pulse or resting heart rate, as well as of the body mass index, the two components of the PULSE MASS INDEX, as cardiovascular risk factors of first range. Among others the studies: BEAUTIFUL, EUROPA, QRISK, Women Health Initiative (WHI), the Framingham Heart Study and the Framingham Offspring Study. Both RHR and BMI reflect the basal oxidative metabolic rate, vascular inflammation, endothelial dysfunction, hyperinsulinemia and insulin resistance, sympathetic stimulation, effects of stress, smoking, and other factors that have impact on the cardiovascular risk. The PULSE MASS INDEX and its elements improve with a balanced diet or caloric restriction (eg, avoiding junk food or empty, useless calories), weight reduction, exercise, stress control, non smoking, and improvement on other risk factors, as also with drugs like beta blockers, ivabradine or metformin, some of them affordable at low cost in the developing countries. The PULSE MASS INDEX can be a good help for preventive medicine and education, at a very low cost, that any doctor, and patients, in the developing countries can easily use. Similar ideas and concepts can be investigated in other areas of health research in the developing countries. Prof. Enrique Sánchez Delgado, MD Internal Medicine-Clinical Pharmacology Director of Medical Education Hospital Metropolitano Vivian Pellas Managua, Nicaragua 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

EDITOR'S CHOICE: The power of stories Groves (20 November 2009) [Full text] The power of stories The power of stories. 23 November 2009 David R Warriner, ST2 Gastroenterology Barnsley Hospital, South Yorkshire, S70 2JW Send response to journal: Re: The power of stories. The power of the narrative to influence both doctors and patients behaviour is well known, but what of its power to support a diagnosis? A patient was suffering from panic attacks, but my explanation and their negative test results failed to reassure that this was physical manifestation of a psychological condition. When a fellow patient witnessed this paroxysm of dyspnoea and discussed the similarities to their own disorder, the patient accepted the diagnosis. We may have the title and the knowledge but a fellow patient may have more credibility. This patient-patient interaction is, to my knowledge, unprecedented and whilst respecting patient confidentiality, it should not be overlooked. Competing interests: None declared The power of stories Once upon a time... 23 November 2009 Hugh Mann, Physician Eagle Rock, MO 65641 USA Send response to journal: Re: Once upon a time... Storytelling is a timeless, universal form of entertainment, education, and inspiration. Scripture, myth, legend, fable, and fairytale are fantastic, unforgettable stories that magically blend fact and fiction with logic and illogic. So let’s rediscover our love of bedtime stories and apply the magic of childhood to our drab, dull, adult lives. Competing interests: None declared The power of stories Telling stories through statistics 23 November 2009 Dr.Indranil Banerjee, M.D.(P. G. T) B.M.C.H 713104 Send response to journal: Re: Telling stories through statistics Respected editor, Thank you for your nice editorial. Today in the era of evidence based medicine most of the published research articles appear to be a jargon of statistics undermining the importance of stories behind the incept of those research thoughts. The power of stories as described by Thomas B Newman (1) is immense. I can share a personal experience. While working as a junior resident in a tertiary care hospital we were repeatedly sensitized with charts and figures regarding prevention of needle stick injury. I was never interested in remembering them all. One day my senior described the trauma which one of his peers suffered after sustaining needle stick injury while performing intravenous catheterization in an unscreened patient. After hearing the story I became serious about seminars dealing with facts and figures of needle stick injury. Thus stories have a great impact on us since we are habituated to receive this input right from childhood. Again as Dr. Tara Lamont pointed out'without statistics story becomes mere anecdotes.'(2) A handshake of story and statistics is welcome. It will really be a pleasure to read the 'Safety alerts ‘in BMJ if one can tell story through statistics in that section. With regards. (1) Newman T. The power of stories over statistics. BMJ 2003;327:1424 -1427 (2 Lamont Tara. National Patient safety agency: combining stories with statistics to minimize harms.BMJ 2009; 339: b 4489. Competing interests: None declared

VIEWS & REVIEWS: The health department and the NHS: time to separate? Crisp (20 November 2009) [Full text] The health department and the NHS: time to separate? Remedial and generative health services 24 November 2009 Peter G Davies, General Practitioner Keighley Road Surgery, Illingworth, Halifax. HX2 9LL Send response to journal: Re: Remedial and generative health services As a doctor I welcome Crisp's proposal (1) and would suggest he might draw the distinction he suggests even more sharply. The NHS has long been misnamed being really an illness treatment service rather than a health service. None of the NHS, the profession or the government has ever committed itself to a coherent view of health (2) or its achievement. We currently have a UK health discourse that focuses on costs, risk, stress, pathology and treatment, and which regards absence of disease as a sufficiently good health outcome. We have little discourse about what a healthy life is, or how to cheerfully boost resilience (3), rather than dutifully putting up with stress. We have little idea of what a good death (4) might be, and how it fits in as a necessary part of life. We have not yet made the full use of the concept of salutogenesis. (health generation) (5) Perhaps the separation we need to make is between remedial medical work which treats disease, and salutogenesis (health generation) which tries to nudge (6) people towards greater health. The remedial task is important task for reasons of basic humanity- we need to relieve each other’s suffering. Medicine is actually focused on this task, and it is what medicine is really about. There is no shortage of work under this rubric. An illness treatment service of some sort will always be necessary. Perhaps what we need is a Department of Illness that deals specifically with pathology working alongside a Department of Salutogenesis that deals with health generation and aiming towards health individuals in healthy life contexts. I am not sure that the two functions sit well under one department as they try to do currently in the DH. As individuals and as a society we would need different inputs from each department over our life course, and both departments would have much useful work to do. 1. Crisp, N (2009) BMJ 2009; 339:b4881 The health department and the NHS: time to separate? 2. Davies, P (2007) Between health and Illness Perspectives in Biology and Medicine, volume 50, number 3 (summer 2007):444–52 3. Siebert, A. 2005. The resiliency advantage. San Fransisco: Berrett- Koehler 4. Smith, R (2000) A good death BMJ ;320:129-130 ( 15 January ) 5. Antonovsky, A. 1987. Unravelling the mystery of health: How people manage stress and stay well. San Francisco: Jossey-Bass. 6. Thaler, R. H. and Sunstein, C. R. (2008) Nudge:Improving Decisions About Health, Wealth, and Happiness 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 Should the NHS strive to eradicate all unexplained variation? Yes Why are we so surprised by variation? 24 November 2009 Peter G Davies, General Practitioner Keighley Road Surgery, Illingworth, Halifax. HX2 9LL Send response to journal: Re: Why are we so surprised by variation? When I hear "variation" discussed in relation to the quality of medical care I nearly always hear the adjectives, "unwarranted", "unexplained" and "unacceptable" echoing in the background. And yet biological and medical sciences are very much about analysis of variations, and of knowing what is a normal variant and what is pathological. In medicine we know that our patients are variable, not standard. The better we get to know our patients the more idiosyncratic and particular they become. The skilled doctor knows how to vary his approach depending on which particular patient he is treating. We also know that doctors vary in their knowledge, skills, experiences and attitudes. We know that they may well treat what appear to be similar cases in divergent ways. This is sometimes a question or "right" or "wrong" , but more often the divergence reflects the doctor dealing with each patient as an individual, worthy of treatment and care in his or her own right. With variation in both the lay and medical inputs into consultations, and variation in the interaction of doctors and patients why are we surprised that the outputs are so variable? Why would they be anything else? Competing interests: None declared

PRACTICE: Avoiding midazolam overdose: summary of a safety report from the National Patient Safety Agency Lamont et al. (19 November 2009) [Full text] Avoiding midazolam overdose: summary of a safety report from the National Patient... Time for a more serious attitude to Midazolam 24 November 2009 John H Wake, GP VTS ST1 Northampon General Hospital, NN1 BD Send response to journal: Re: Time for a more serious attitude to Midazolam Both your article and the NPSA on avoiding Midazolam overdoses were timely. Sedation by non-anaesthetists is increasing at a relatively rapid rate. As an SHO working in an Emergency Department (ED) I found myself performing supervised sedations of patients for manipulations on a regular basis. We audited our practice and that of other local EDs and found that there were a number of areas that would have benefitted from improvement. We found that EDs often did not have clear formal policies on sedation. There was no formal training for SHOs in ED sedation despite that fact that they were performing it in all the Trusts monitored. Proformas used did not meet the recommended guidelines. Doctors were frequently unaware of the advice that they should be giving patients after sedation, such as avoiding driving and alcohol and did not tend to give written advice despite the effects of Midazolam on short-term memory. The NPSA guidelines are extremely useful and will hopefully lead to positive changes in reducing incidents. An attitude change is required among non-anaesthetists using Midazolam that matches the seriousness of the drug. 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 A woman with acute myelopathy in pregnancy: case progression The importance of Oligomeric bands 23 November 2009 Ben D Butler-Reid, Final Year Medical Student University of Bristol, BS8 1TH Send response to journal: Re: The importance of Oligomeric bands In response to the interactive case report: A woman with acute myelopathy in pregnancy: case progression BMJ 2009;339:b4025 I offer the following as a response to the first question posed. What is the diagnostic importance of oligoclonal bands? Oligoclonal bands are collections of immunoglobulins that can be observed when samples of plasma or cerebrospinal fluid (CSF) are examined via protein electrophoresis. The relevance to this case is that oligoclonal bands can be found peripherally in plasma or locally in CSF. In order to differentiate their source, samples of both serum and CSF need to be taken. Electrophoresis is undertaken and the bands that are found in both the serum and CSF are subtracted from one another thus leaving only the oligoclonal bands that originated within the Central nervous system so called intrathecal immunoglobulins. A nice explanation is given here: http://www.clinlabnavigator.com/Tests/OligoclonalBandsinCSF.html While monoclonal oligoclonal bands are yet to be associated with significant pathologies; it is known that oligoclonal bands can be found in a variety of CNS pathologies including Multiple Sclerosis, Syphilis, Subarachnoid Haemorrhage and Primary CNS lymphoma. The concentration of oligoclonal bands in the CSF correlates well with disease progression and they ultimately fade as the disease resolves. Consequently they can be used as a proxy for disease activity in conditions such as MS. From a diagnostic perspective up to 90% of patients with MS may have permenantly raised oligoclonal bands. Competing interests: None declared A woman with acute myelopathy in pregnancy: case progression Recurrent myelopathy 23 November 2009 Mike Boggild, Consultant Neurologist The Walton Centre, Liverpool, L9 7LJ Send response to journal: Re: Recurrent myelopathy Oligoclonal bands are a marker of intra-thecal immunogobulin synthesis, common (>90%) in MS (for which this MRI appearance would be highly unusual). They are much less frequently seen in recurrent longitudinally extensive myelitis (rLETM) or neuromyelitis optica (~10- 15%). Positive aquaporin-4 antibodies, found in ~50% of patients with rLTEM, would suggest this is 'NMO spectrum disorder' - the antibody appears highly specific, if somewhat less sensitive, for these disorders. A variety of other organ specific and non-specific auto-antibodies are often seen in such cases, as is the case here. Possibly representing disordered humoral immunity. Acute treatment would be with high dose IV and oral steroids with therapeutic plasma exchange reserved for patients failing to respond over the next 1-2 weeks. There is no class I evidence to guide long-term treatment but azathioprine (2.5-3.0mg/kg) or Rituximab would probably be considered. In pregnancy a case could perhaps also be made for use of Intravenous Immunoglobulin. There is precious little data on pregnancy in this setting to allow any specific advice to be given. Competing interests: None declared

EDITORIALS: The economic impact of pandemic influenza Maynard and Bloor (19 November 2009) [Full text] The economic impact of pandemic influenza Flu Bedside Diagnosis and Differential Diagnosis 23 November 2009 Sergio Stagnaro, Researcher in Quantum Biophysical Semeiotics Quantum Biophysical Semeiotics Research Laboratory Send response to journal: Re: Flu Bedside Diagnosis and Differential Diagnosis Flu Bedside Diagnosis and Differential Diagnosis. from: Sergio Stagnaro MD Via Erasmo Piaggio 23/8 16039 Riva Trigoso (Genoa) Italy Founder of Quantum Biophysical Semeiotics Who's Who in the World (and America) since 1996 to 2009 Ph 0039-0185-42315 Cell. 3338631439 www.semeioticabiofisica.it dottsergio@semeioticabiofisica.it Sirs, in a number of Arch.Intern.Med. Authors have suprisingly stated that flu diverse type can be diagnosed with sophisticated semeiotics, certainly not apllicable on very large scale (Impact of Rapid Diagnosis on Management of Adults Hospitalized With Influenza. Ann R. Falsey, MD; Yoshihiko Murata, MD, PhD; Edward E. Walsh, MD Arch Intern Med. 2007;167,doi:10.1001/archinte.167.4.ioi60207). In my opinion, intriguing articles, like that just mentioned, are not updated, since authors unfortunately either ignore or overlook Quantum Biophysical Semeiotics (www.semeioticabiofisica.it). In fact, nowadays it is very difficult to know the real nature of an infectious disorder at both the bed-side and ER or hospital, as well as to recognize a lot of cases such as those described in the article, not to speak of disorders recognizable by means of the academic, orthodox, physical semeiotics, as allows me to state a 53-year-long clinical experience. In fact, I am filled with wonder at reading that there are doctors who are sharing the uncertainty of the value of antibiotics for acute tonsillitis, pharingitis, bronchitis in the form of written and verbal advice, although I do not know if these physicians are skill at performing the advancement in the field of physical examination (1). For space reasons, I underscore here merely the possibility of recognizing easily and quickly the “chronic” antibodies synthesis in the spleen during flu, as well as the spleen “small” antibody production, in case of Gram- negative bacteria (Esch.coli, HP, a.s.o.), which play a pivotal role in bed-side diagnosis of virus or Gram-negative infections (1). Moreover, interestingly doctor can now-a-day observe clinically, and in a “quantitative”way, the so-called Reticulo- Endothelial-System-Hperfunction Syndrome (RESH), which parallels with ESR and Proteins Electrophoresis, but it is “more” sensitive and specific than both (2-3). Certainly, most adults, and childrens, of course, with acute bronchitis who consult their general practitioner (as well as University Professors...) will receive antibiotics, although in many cases antibiotics do not modify the natural course of the disorder, at all. In my mind, the real problem is to recognize “clinically” both the nature of infectious disorder and the actual patient's defence , including antibody and PCR synthesis (in above- cited website): first, the “ethyological” , complete diagnose, starting from bedside recognizing all constitutions (ibidem; 4) and, then, the proper therapy. Nowadays, we can solve such as problem, and a lot of others…if we are determined to be “open-minded” physicians, Referees and peer-review's Editors. As regards differential diagnosis between different types of flu, parameters values play a central role. In fact, e.g., in the seasonal flu, latency time of BALT-Gastric Aspecific Reflex is 4-5 sec. (NN = 6 sec.), intensity less than 3 cm., duration 4 sec. followed by characteristic tonic Gastric Contraction. On the contrary, in A flu, intensity is greatest (5 cm,) as well as duration. 1) Stagnaro Sergio, Stagnaro-Neri Marina. Introduzione alla Semeiotica Biofisica. Il Terreno oncologico”. Ed. Travel Factory SRL., Roma, 2004. www.travelfactory.it 2) Stagnaro-Neri M., Stagnaro S., Appendicite. Min. Med. 87, 183, 1996[MEDLINE] 3) Stagnaro S., Sindrome percusso-ascoltatoria di Iperfunzione del Sistema Reticolo-Istiocitario Min. Med. 74, 479, 1983 [MEDLINE]. 4) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico- Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. 5) Stagnaro S., Stagnaro-Neri M. Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Ed. Travel Factory, Roma, 2005. 6) Stagnaro Sergio. Bedside Diagnosis of Flu. October, 2009. http://doc2doc.bmj.com/forums.html LINK 7) . Stagnaro Sergio. Subjects at Inherited Real Risk of A/H1N1 broncho- pneumonitis. MedicalPage, 4 November, 2009 http://www.medpagetoday.com/tbindex.cfm?tbid=16786#ayk 8) Stagnaro Sergio. Quantum-Biophysical-Semeiotic Bedside Diagnosis of Flu, since its earliest stage. 30 October, 2009. CMAJ 2009; 181: E195- 196E. http://www.cmaj.ca/cgi/eletters/181/9/E195#228652 Competing interests: None declared

CLINICAL REVIEW: Diagnosis and management of dengue Teixeira and Barreto (18 November 2009) [Full text] 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 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

VIEWS & REVIEWS: Politics, science, and the White House Smith (17 November 2009) [Full text] Politics, science, and the White House Politics & Religion 24 November 2009 Hugh Mann, Physician Eagle Rock, MO 65641 USA Send response to journal: Re: Politics & Religion Politics and religion are philosophies that function as software for the hardware of our nervous system. Liberalism is read-and-write software that promotes progress; while conservatism and fundamentalism are read-only software that protects the status quo. Competing interests: None declared

LETTERS: Avoiding spurious hyperkalaemia Gama et al. (17 November 2009) [Full text] Avoiding spurious hyperkalaemia Re: spurious hyperkalemia 24 November 2009 Paul M. Verheecke, Chemical pathologist Centrum voor Medische Analyse, Elfde Liniestraat 27; B-3500 Hasselt, Belgium Send response to journal: Re: Re: spurious hyperkalemia In our experience, by far the most frequent reason for spurious hyperkalemia is the cooling of blood samples before or after clotting. Competing interests: None declared

NEWS: First official citywide electronic record system for patients is launched in London O’Dowd (17 November 2009) [Full text] First official citywide electronic record system for patients is launched in London Where is the evidence of benefit? 23 November 2009 Peter A West, Senior Research Associate York Health Economics Consortium Send response to journal: Re: Where is the evidence of benefit? In hailing the arrival of a pan-London electronic record, Ruth Carnall is quoted as saying "Getting hold of health records for London’s highly mobile population often presents real challenges to doctors and nurses when patients need out of hours and emergency care. The summary care record has demonstrated clear benefits elsewhere in the country, and NHS London is keen to bring these to the capital". Where is this demonstration of benefits in an emergency, where has it been published? I am not aware of it. The assumption that electronic records will offer fast access in an emergency overlooks factors such as the lack of ID carried by some individuals, the lack of a consistent address on medical records for a highly mobile population and the lack of detail on name or date of birth when an individual is unconscious. How will the system find a single J Smith or B Davies in London without detailed ID? But if we all carry detailed ID to help find our medical records, why not carry a summary record too, particularly if suffering from a serious illness. This would offer fast access to information of the kind offered by medical alert bracelets and other very simple technology. I would rather a paramedic treating me in an emergency got on with the job, using the signs and symptoms available, rather than having to surf the web to find me among all the other P Wests in London. If there are benefits, let us see the studies. If there are not, let us stop making bogus claims. 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 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

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

VIEWS & REVIEWS: Learning to teach Jackson (12 November 2009) [Full text] Learning to teach Learning to Teach 24 November 2009 David R. Gibson, Retired GP & Medical Educator Belfast, BT55 7JA Send response to journal: Re: Learning to Teach I was very interested to read Philippa Jackson's experiences. Something that I, and most of us, have experienced from early SHO days and, for me, led to much time in medical education. Doctors have this time-honoured requisite to teach their followers, but not all want to. Those that do require educational training - but at what time should this begin? With such a crowded curriculum, limited time and resources, it is difficult to start early in one's career but there is a strong case for such training to be made available from SHO level onwards and mandatory for those involved in training doctors and medical students once they have reached higher levels in their speciality. The Colleges and regions have made a good effort in this area but unfortunately the necessary levels are not being reached. Competing interests: None declared Learning to teach Re: Practical Teaching Tips [Correction] 23 November 2009 Avtar Singh, 4th year medical student College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT Send response to journal: Re: Re: Practical Teaching Tips [Correction] Jackson’s article (1), highlighting the difficulties in teaching from the junior doctor’s perspective, certainly made for an interesting read. Perhaps ironic then that this reply comes from a student (especially one located round the corner at Birmingham Medical School!). I would like to respond to the queries raised by Jackson regarding practical ways of improving one’s teaching and the necessity of formal teacher training within medical education. We can all recall personal examples of outstanding medical teaching that we have received in a variety of different clinical settings; from the patient’s bedside on a ward round to standing next to the surgeon in theatre, and from the outpatient clinic to primary care. So, as Jackson mentions, one could utilise the knowledge gained from these past experiences to guide us in our own teaching roles (1). However, applying educational theory in the clinical arena is often easier said than done. Outlined below are some practical tips that may assist the newly qualified junior doctor in helping his students get the most out of their teaching session: • Time devoted to clinical educational activity in hospitals is often variable or even absent, ranging from 0 – 25% of students’ time spent on the wards (2). So junior doctors would greatly improve the learning experiences of their students simply by trying to find more time to teach them. Realistically, however, not all the material may be covered in a time-constraint teaching session, so providing a summary handout or pointing to areas of further reading would be useful. • Failure to utilise the assets of the clinical environment is commonplace. Many doctors revert towards didactic impartment of factual knowledge best left in the lecture theatre or seminar room, thereby losing the clinical context for teaching skills of history taking and examination. This is reflected in a study on teaching rounds, where only 11% of the time was spent at the patient’s bedside, the rest of the time being spent in the conference room or discussing in hallways (3). This is particularly surprising when bedside teaching and medical clerking are considered the most valuable teaching methods amongst both students and practicing doctors (4). • Interruptions on the ward (e.g. being bleeped when on-call, restricted times for patients at mealtimes and during visiting hours) should be taken into account so as to minimise the disruption to bedside teaching arrangements. • Be prepared to be opportunistic in clinical teaching, since cases never occur in a logical order. • Set clear learning goals. Discuss objectives with learners to avoid covering topics they have already met; especially since medical students, even within the same medical school, will have had completely different learning experiences (5). This also enables learners to point out areas of weakness and to help them focus on the salient points of the lesson. At the end, review the aims, clarify any misunderstandings and summarise the key information. • The motivation of learners can be difficult to maintain at times. Simple ways of achieving this include varying the teaching stimulus (e.g. mixing up the teaching of practical skills with recall of medical knowledge) and utilising tasks that are more engaging and interactive (e.g. bedside detective work and games for teaching physical examination (6)). Moreover, it has been shown that one of the features of good clinical teaching is enabling the student to be an active participant (7); so a good teacher would involve the students on the ward round by getting them to write in the patient notes, take a patient’s blood and getting them to listen to the heart sounds before the consultant does. • A good teacher would frequently ask relevant open questions, avoid answering his own questions, and question the answers of his students (8). • Giving personal feedback is an important factor in student satisfaction (9). So spend time supervising their physical examinations and reviewing their histories. Medicine is different to other professions, in that teaching, whether it be to students, fellow doctors or other healthcare professionals, is an expectation. Furthermore, the General Medical Council state that those involved in teaching should “develop the skills, attitudes and practices of a competent teacher” (10). However, few doctors have had any formal training in educational method, though many express an interest in receiving it (11). Thus, there is a need for recognised training on how to teach within the medical curriculum. This has been acknowledged in recent years with some medical schools offering Special Study Modules in teaching, as well as assessing medical students on a given teaching performance to peers; therefore helping them to be more confident in teaching when they qualify. Postgraduate qualifications in medical education and teacher training courses also exist for those wishing to further their skills; however, only 6% of actively teaching doctors have ever attended masters or other short courses on teaching (12). Patient-centred medicine to student-centred teaching seems a simple enough transition to make, but many find it a daunting prospect. So adequate training in educational methods should be in place for anyone who takes a keen interest in their teaching roles. However, being a good clinical teacher often goes beyond the theoretical teaching methods, and is characterised by being enthusiastic, inspiring and supportive (13). References: (1) Jackson P. Learning to Teach. BMJ 2009;339:b4554 (2) Jolly B, Rees L. Medical education in the millennium. Oxford: Oxford Medical Publications; 1998 (3) Miller M, Johnson B, Greene HL, Baier M, Nowlin S. An observational study of attending rounds. J Gen Intern Med 1992;7:646-8 (4) Ward B, Moody G, Mayberry JF. The views of medical students and junior doctors on pre-graduate clinical teaching. Postgrad Med J 1997;73:723-5 (5) Kowlowitz V, Curtis P, Sloane PD. The procedural skills of medical students: expectations and experiences. Acad Med 1990;65:656-8 (6) Ramani S. Twelve tips for excellent physical examination teaching. Med Teach 2008;30:851-6 (7) Stritter FT, Hain JD, Grimes MD. Clinical teaching re-examined. J Med Educ 1975;50:876-82 (8) Spencer J. Learning and teaching in the clinical environment. BMJ 2003;326:591-4 (9) Chesser A, Brett M. Clinical teaching in context: a factor analysis of student ratings. Research in Medical Education, Proceedings of the twenty-eighth annual conference. Washington: Association of American Medical Colleges; 1989. p49-54 (10) General Medical Council. Good Medical Practice [online]. 2006 [cited 2009 Nov 18]. Available from URL: http://www.gmc- uk.org/guidance/good_medical_practice/index.asp (11) Wilson DH. Education and training of preregistration house officers: the consultants’ viewpoint. BMJ 1993;306:194-6 (12) Lawson M, Seabrook M, Jolly BC, Pettingale KW. Teachers at King’s: who teaches and how? Paper presented at the annual conference of the Association for the Study of Medical Education. Med Educ 1996;30:71-2 (13) Sutkin G, Wagner E, Harris I, Schiffer R. What makes a good clinical teacher in medicine? A review of the literature. Acad Med 2008;83:452-66 Competing interests: None declared Learning to teach Practical Teaching Tips 20 November 2009 Avtar Singh, 4th year medical student College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT Send response to journal: Re: Practical Teaching Tips Jackson’s article (1), highlighting the difficulties in teaching from the junior doctor’s perspective, certainly made for an interesting read. Perhaps ironic then that this reply comes from a student (especially one located around the corner at Birmingham Medical School!). We can all recall personal examples of outstanding medical teaching that we have received in a variety of different clinical settings; from the patient’s bedside on a ward round to standing next to the surgeon in theatre, and from the outpatient clinic to primary care. So, as Jackson mentions, one could utilise the knowledge gained from these past experiences to guide us in our own teaching roles (1). However, applying educational theory in the clinical arena is often easier said than done. Outlined below are some practical tips that may assist the newly qualified junior doctor in helping his students get the most out of their teaching session: • Time devoted to clinical educational activity in hospitals is often variable or even absent, ranging from 0 – 25% of students’ time spent on the wards (2). So junior doctors would greatly improve the learning experiences of their students simply by trying to find more time to teach them. However, if not all the material can be covered in a time-constraint teaching session, providing a summary handout or pointing to areas of further reading is also useful. • Failure to utilise the assets of the clinical environment is commonplace. Many doctors revert towards didactic impartment of factual knowledge best left in the lecture theatre or seminar room, thereby losing the clinical context for teaching skills of history taking and examination. This is reflected in a study on teaching rounds, where only 11% of the time was spent at the patient’s bedside, the rest of the time being spent in the conference room or discussing in hallways (3). This is particularly surprising when bedside teaching and medical clerking are considered the most valuable teaching methods amongst both students and practicing doctors (4). • Interruptions on the ward (e.g. being bleeped when on-call, restricted times for patients at mealtimes and during visiting hours) should be taken into account so as to minimise the disruption to bedside teaching arrangements. • Be prepared to be opportunistic in clinical teaching, since cases never occur in a logical order. • Set clear learning goals. Discuss objectives with learners to avoid covering topics they have already met; especially since medical students, even within the same medical school, will have had completely different learning experiences (5). This also enables learners to point out areas of weakness and to help them focus on the salient points of the lesson. At the end, review the aims, clarify any misunderstandings and summarise the key information. • The motivation of learners can be difficult to maintain at times. Simple ways of achieving this include varying the teaching stimulus (e.g. mixing up the teaching of practical skills with recall of medical knowledge) and utilising tasks that are more engaging and interactive (e.g. bedside detective work and games for teaching physical examination (6)). Moreover, it has been shown that one of the features of good clinical teaching is enabling the student to be an active participant (7); so a good teacher would involve the students on the ward round by getting them to write in the patient notes, take a patient’s blood and getting them to listen to the heart sounds before the consultant does. • A good teacher would frequently ask relevant open questions, avoid answering his own questions, and question the answers of his students (8). • Giving personal feedback is an important factor in student satisfaction (9). So spend time supervising their physical examinations and reviewing their histories. Medicine is different to other professions, in that teaching, whether it be to students, fellow doctors or other healthcare professionals, is an expectation. Furthermore, the General Medical Council state that those involved in teaching should “develop the skills, attitudes and practices of a competent teacher” (10). However, few doctors have had any formal training in educational method, though many express an interest in receiving it (11). Thus, there is a need for recognised training on how to teach within the medical curriculum. This has been acknowledged in recent years with some medical schools offering Special Study Modules in teaching, as well as assessing medical students on a given teaching performance to peers. Postgraduate qualifications in medical education and teacher training courses also exist for those wishing to further their skills; however, only 6% of actively teaching doctors have ever attended masters or other short courses on teaching (12). Patient-centred medicine to student-centred teaching seems a simple enough transition to make, but many find it a daunting prospect. So adequate training in educational methods should be in place for anyone who takes a keen interest in their teaching roles. However, being a good clinical teacher often goes beyond the theoretical teaching methods, and is characterised by being enthusiastic, inspiring and supportive (13). References: (1) Jackson P. Learning to Teach. BMJ 2009;339:b4554 (2) Jolly B, Rees L. Medical education in the millennium. Oxford: Oxford Medical Publications; 1998 (3) Miller M, Johnson B, Greene HL, Baier M, Nowlin S. An observational study of attending rounds. J Gen Intern Med 1992;7:646-8 (4) Ward B, Moody G, Mayberry JF. The views of medical students and junior doctors on pre-graduate clinical teaching. Postgrad Med J 1997;73:723-5 (5) Kowlowitz V, Curtis P, Sloane PD. The procedural skills of medical students: expectations and experiences. Acad Med 1990;65:656-8 (6) Ramani S. Twelve tips for excellent physical examination teaching. Med Teach 2008;30:851-6 (7) Stritter FT, Hain JD, Grimes MD. Clinical teaching re-examined. J Med Educ 1975;50:876-82 (8) Spencer J. Learning and teaching in the clinical environment. BMJ 2003;326:591-4 (9) Chesser A, Brett M. Clinical teaching in context: a factor analysis of student ratings. Research in Medical Education, Proceedings of the twenty-eighth annual conference. Washington: Association of American Medical Colleges; 1989. p49-54 (10) General Medical Council. Good Medical Practice [online]. 2006 [cited 2009 Nov 18]. Available from URL: http://www.gmc- uk.org/guidance/good_medical_practice/index.asp (11) Wilson DH. Education and training of preregistration house officers: the consultants’ viewpoint. BMJ 1993;306:194-6 (12) Lawson M, Seabrook M, Jolly BC, Pettingale KW. Teachers at King’s: who teaches and how? Paper presented at the annual conference of the Association for the Study of Medical Education. Med Educ 1996;30:71-2 (13) Sutkin G, Wagner E, Harris I, Schiffer R. What makes a good clinical teacher in medicine? A review of the literature. Acad Med 2008;83:452-66 Competing interests: None declared

PRACTICE: Investigating recurrent respiratory infections in primary care Wood and Peckham (12 November 2009) [Full text] Investigating recurrent respiratory infections in primary care Re: A clear indication for HIV testing 24 November 2009 Dr Viera Scheibner, Scientist (Retired)/Author Blackheath NSW Australia Send response to journal: Re: Re: A clear indication for HIV testing What causes recurrent respiratory bacterial (and viral) infections in young persons? The key words in this debate are “primary and secondary immunodeficiency”. HIV infection is only one of at least two causes of immunodeficiency. The most prevalent cause is vaccination. According to orthodox immunological research since the turn of the twentieth century, vaccines sensitise, make the recipients more susceptible to the diseases which the vaccines are supposed to prevent and also to a host of related and unrelated bacterial and viral infections. Craighead (1975) documented this phenomenon in his “Report of a workshop: Disease accentuation after immunization with inactivated microbial vaccines” (J Infect Dis; 131 (6): 749-754). Quoting first the animal research, he wrote: “…animals immunized with several low-potency, inactivated viral and rickettsial vaccines responded to challenge with an infection of increased severity. A few years later, Grayston and his associates noted an accentuated pattern of disease in previously immunized subjects who were experimentally given inoculations of live trachoma agent in the eye. Subsequently, several groups of investigators documented the sporadic occurrence of an atypical pattern of disease of naturally acquired measles several years after the administration of an inactivated virus vaccine to children. In 1967 Smith et al. described a febrile illness accompanied by pneumonia in experimentally infected recipients of a killed Mycoplasma pneumoniae vaccine who failed to produce detectable antibody. Two years later, Kapikian et al.[7], Kim et al.[8], Fulginiti et al.[9] and Chin et al.[10] simultaneously reported an unusually severe respiratory disease in infants and young children developing natural infections with respiratory syncytial virus after immunization with formaldehyde-treated vaccine. These observations, although limited in scope, suggested that immunization with inactivated vaccines could ‘sensitize’ the recipient and result in an accentuated pattern of disease upon natural or experimental exposure.” Craighead (1975) also described a [post-vaccination] fall of circulating antibodies to rubeola virus often down to undetectable levels. Eibl et al. (1984) described “Abnormal T-lymphocyte subpopulations in healthy subjects after tetanus booster immunizations” (NEJM; 310 (3): 198- 199), as seen in AIDS patients. More recently, Sabath et al. (1987. “Antigen-induced transient hypersusceptibility (H): a cause of sporadic and fulminant infection (INF) in normals.” Clin Research; 35 (3): 617a) wrote that in infants hospitalised for purulent meningitis (PM) there was a clustering of time intervals between routine IMZ [=immunization] and date of admission [11 to 14 days (ds) 5 of 24 aged 2 to 6 months] …compared to 93 age and sex- matched controls (AS-MC) admitted for non-infectious causes…Others have documented profound alterations in T-cell ratios and decreased responsiveness in 2nd week PI [=postinfection], coinciding with period of H [=hypersusceptibility] noted here in humans. We conclude that many Ags [=antigens] induce global changes in hosts’ immunological response; this transient effect is an important cause of infections in normals. Huge doses [of] Ag cause narrow spectrum H at about 2ds PI.” Perhaps here I should comment on the use of the term “transient”: other researchers documented the entity of the “negative phase of lowered bactericidal power of the blood” caused by vaccine injections which may last for up to several months and even years (Wright 1901. “On the changes effected by antityphoid inoculation in the bacterial power of the blood. With remarks on the probable significance of these changes.” Lancet: 14 September: 715-723). Daum et al. (1989) described “Decline in serum antibody to the capsule of Haemophilus influenza type b in the immediate post-immunization period.” (J Pediatrics; 114: 742-747) resulting in invasive infections. Jefferys (2001. T cells and vaccination. Lancet; 357: 1451) wrote “Accumulating evidence suggests that the mechanisms underlying the maintenance of homeostasis are intimately involved in preventing the undesired expansion of self-reactive T cells and resultant autoimmune disease. Most importantly, the continuous export of naive T cells from the thymus seems to be the key in controlling the number of self-reactive peripheral T cells, according to Tanchot and Rocha...Before any immunization is declared safe, the potential dysruption in normal T cell homeostasis – and any resultant adverse outcomes – must be fully addressed. For infants whose immune system is still maturing, such ill- understood issues should be a public health priority.” One does not have to jump to conclusions about a possible AIDS infection; the answer is much closer to home. Competing interests: None declared Investigating recurrent respiratory infections in primary care A clear indication for HIV testing. 23 November 2009 Morgan Evans, Specialist Registrar in Infectious Diseases City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, Hucknall Road, NG5 1PB Send response to journal: Re: A clear indication for HIV testing. Dear Editor, I was disappointment to read that the clinical scenario of recurrent respiratory tract infections [1] is not seen as an indication for HIV testing. The description of a young patient with recurrent lower respiratory tract infections with proven pneumococcal pneumonia on one occasion should highlight as rightly pointed out a problem with the humoural immune system. It is because of this defect in the humoural immune system that pneumococcal diseases is 150-300 times more common in patients with HIV. The activation of B cells with the dysregulation manifest as polyclonal gammopathy is well recognised in HIV. The acronym SPUR suggested by the authors could probably be associated with HIV more than any other single condition. The 2008 guidance from BHIVA sets bacterial pneumonia as an indicator for consideration for HIV testing [2]. Unfortunately risk assessments, particularly defining and questioning around "high risk sex", lack the sensitivity to detect all those at risk of HIV. HIV testing should have been recommended as a routine investigation in this scenario. Without increasing HIV testing in primary care we will not reduce the morbidity and mortality associated with late presentation of patients with HIV. 1. Wood P, Peckham D. Rational Testing: Investigating recurrent respiratory infections in primary care. BMJ 2009;339:b4118 2. UK National Guidelines for HIV Testing 2008, British HIV Association & British Association of Sexual Health and HIV & British Infection Society, http://www.bhiva.org/files/file1031097.pdf Competing interests: None declared

EDITORIALS: Capping earnings from private patients in NHS foundation trusts Appleby (11 November 2009) [Full text] Capping earnings from private patients in NHS foundation trusts Profit not Income 23 November 2009 Peter A West, Senior Research Associate York Health Economics Consortium Send response to journal: Re: Profit not Income The debate about private patient income in the NHS is almost always conducted around the wrong figures - it is the profit to the NHS that matters, not the total income, because, of course, services for the private patient have a cost and are not "free", unless the NHS is seen as offering a 100 per cent subsidy. I have never found an NHS trust which has a good handle on the costs of services to private patients though developments in service line costing may change this. If, as seems likely, private patients tie up capacity in the NHS without making much of a profit, there may not be much to gain from having a bit more or less private activity. One key development that should come out of the current debate about the cap on private patient income is a reliable estimate of profit and not just income. Competing interests: None declared

OBSERVATIONS: The years of magical thinking Delamothe (11 November 2009) [Full text] The years of magical thinking Magical thinking on sex as well as drugs 23 November 2009 Trevor G Stammers, GP The Church Lane Practice,, Merton Park, SW19 3NY Send response to journal: Re: Magical thinking on sex as well as drugs Delamothe’s (1) cogent and pithy essay is the second article (2) to appear in the BMJ commenting on the triumph of ideology over evidence in UK health policy in the wake of the sacking of Prof David Nutt. Neither article has however mentioned the area in which this is most apparent in virtually all current policy– namely sexual health. To take just two examples:- 1) The vast majority of studies show that in those US states which have introduced laws making parental notification (not consent) mandatory before abortions are performed in underage girls, there are significant decreases in overall conception rates(3), in underage abortion rates (4), and in rates of teenage STIs(5). This evidence however is totally ignored by UK government who are determined to promote children’s rights over parental responsibility in the education and healthcare of underage young people for sexual behavour. 2) The gross failings of the chamydia screeing programme in UK were recently highlighted (6) including the waste of £17m and poor uptake rates. Even with adequate uptake however, the 3 month reinfection rate after treatment is 30% in those who don’t use condoms consistently and 15% in those who do (7). Without primary prevention programmes, all efforts being channeled into screening for chlamydia are destined to remain fruitless in reducing the incidence of the disease. With the latest UK figues showing an increase of a third in underage teenage abortions (8) and continuing rises in underage STIs, there is surely much more evidence to call for the sacking of the head of the incompetent Advisory Group on Sexual Health than for the sacking of the unfortunate Professor Nutt. 1.Delamothe T 2009 The years of magical thinking BMJ 339 1117 2.Colquhoun D 2009 The highs and lows of policy based evidence BMJ 339 1087 3.Levine P 2003 Parental involvement laws and fertility behavior. Journal of Health Economics 22 861-78 4.Joyce T et al 2006 Changes in abortions and births and the Texas Parental Notification Law. New EnglandJournal of Medicine 354 10 1031-38 5.Klick J, Stratmann T 2008 Abortion access and risky sex among teens: parental involvement laws and sexually transmitted diseases. Journal of Law, Economics and Organization 24 2-21 6.Mayor S 2009 Chlamydia screening in young people fails to reduce prevalence BMJ 339 b4736 7.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 8.Institute for Family Policies 2009 Evolution of the Family in Europe http://www.ipfe.org/Report_evolution_on_the_family_in_Europe_2009.pdf 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... Age-related increased blood viscosity, walking speed and risk of cardiovascular death. 24 November 2009 Les.O Simpson, retired experimental pathologist Dunedin New Zealand 9077 Send response to journal: Re: Age-related increased blood viscosity, walking speed and risk of cardiovascular death. When Greenberg introduced the term "citation bias", his paper also drew attention to the selective use of the published literature, with relative segments being ignored. To a major extent the paper by Dumurgier et al is an example of this, as there is no mention of the possible role of increased blood viscosity. After all, the published literature is by no means trivial. A PubMed search for "Cardiovascular disorders and blood viscosity," produced 4305 titles. In 1998, Ajmani and Rifkind, from the Institute for Aging, reported that increased blood viscosity and reduced red cell deformability were parts of the aging process. As a result, the rate of capillary blood flow would be reduced and may reach levels which resulted in an inadequate rate of oxygen delivery to sustain normal tissue function. It would be reasonable to consider this a possible cause of muscle dysfunction manifested as slow walking. As the Dumurgier et al study involved people over 65 years of age it is very likely that they would share the common feature of increased blood viscosity,but at differing levels. So if those who manifested impaired blood flow as slow walking had higher levels of hyperviscosity then it would not be surprising if such changes in the physical properties of the blood led to cardiovascular death. And there are published reports of such associations. It is also relevant that when PubMed searched for "Diabetes and blood viscosity," 764 titles were obtained. Therefore, it is not surprising that, "Those who died during follow-up were older, taller, more often men,and had a higher prevalence of cardiovascular risk factors (diabetes mellitus,hypertension, smoking) compared with survivors." It should be noted that diabetes, hypertension and smoking are all assoiated with increased blood viscosity. So it seems reasonable to suggest that those who died may have had more viscous blood which adversely affected their walking ability. It seems strange that a study which involved walking should have overlooked the work of Professor Edzard Ernst. One of his papers titled, "Influence of regular physical activity on blood rheology," was published in 1987. He stated, "This suggests that an improvement in blood fluidity can be induced by regular physical exercise." Thus walking was shown to lower blood viscosity. It is important that the exercise be of low intensity (such as walking, dancing, gardening) as heavy competitive activity has an adverse effect on the flow properties of the blood. An Australian study showed that pram walking was effective in the treatment of post natal depression. In concluding that, "Slow walking speed in older people is strongly associated with an increased risk of cardiovascular mortality," it seems that the authors have inadvertedly drawn attention to the blood viscosity problems of the elderly. What this implies is that treatments which lowered blood viscosity could be beneficial. There is much published information which shows what can be accomplished by dietary changes and lifestyle modifications. Competing interests: None declared Slow walking speed and cardiovascular death in well functioning older adults: prospective... Info. regarding Speed to be maintained 24 November 2009 Revan pujari, Medical affairs 560040 Send response to journal: Re: Info. regarding Speed to be maintained Very good study. It would have been better if they provide the details like what speed to be maintained/min or /sec. for a healthy CV health in elderly/cardiac patients. Competing interests: None declared Slow walking speed and cardiovascular death in well functioning older adults: prospective... Slow walking speed and cardiovascular risk 23 November 2009 john zacharias, retd GP scunthorpe DN17 2 XB Send response to journal: Re: Slow walking speed and cardiovascular risk I am sceptical about the above mentioned research being applicable universally. I think the premise on which it is based is not valid. The people who live in the tropical, humid and arid regions do not walk fast, whatever their age. If they do, excessive loss of salt in the sweat will lead to exhaustion rapidly. Have you noticed the nomads who live in the Sahara rushing with their camels? Perhaps this premise is applicable to overfed, mostly overweight individuals in the cooler climes of the world who are prone to CVD in any case Competing interests: None declared Slow walking speed and cardiovascular death in well functioning older adults: prospective... Good study; few questions 20 November 2009 DR.Indranil Banerjee, MD(P.G.T) B.M.C.H,, 713104 Send response to journal: Re: Good study; few questions At first I would like to thank the entire team of researchers for conducting study on this much needed yet neglected topic. This study has surpassed the limits of previous studies (e.g. Study to find relation between low walking speed and stroke) by performing careful baseline assessment. However certain points in the method and conclusion section deserve more clarification. The present study considered walking velocity over a short distance (6m) which indicates motor control, strength, balance and adaptation in gait pattern.(1) Timed walking distance (e.g. distance walked in 6 minutes) provides a better measure of endurance, fatigability and cardiovascular fitness.(2))The study did not mention the rationale of choosing walking velocity instead of timed walking distance. The title and conclusion of the research article repeatedly mentions the words “Slow walking speed” which drags controversies. It appears that the message of the study is the persons who walk slowly than their usual pace are at increased risk of cardiovascular mortality. A careful reading of the text informs us that it is actually “low walking speed “which is a simple yet reliable indicator of increased cardiovascular mortality as chronic exposure to vascular risk factors is associated with both increased cardiovascular mortality and reduced speed of walking.With regards (1)J.Dumurgier et al.Slow walking speed and cardiovascular death in well functioning older adults:prospective cohort study.BMJ 2009;339:b4460 (2)Dobkin B.Short distance walking speed and timed walking distance:Redundant measures for clinical trials? Neurology 2006;66:584-586 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 Greater equality and better health A Third Explanation for the Link Between Inequality and Health 23 November 2009 Harry F. Tibbals, Director, Bioinstrumentation, Office of Technology Development UTSouthwestern BioCenter EB2.220, 5323 Harry Hines Blvd, Dallas, Texas 75390-9025 USA Send response to journal: Re: A Third Explanation for the Link Between Inequality and Health As pointed out by Professors Pickett and Wilkinson, and illustrated in the references cited and analysed, recent proposed explanations for the link between inequality and health fall into two categories: "compositional" and "contextual". Compositional explanations focus on demographics - unequal societies have worse health simply because they have more poor people. Contextual explanations posit that negative health outcomes arise from divisive and socially corrosive psychosocial aspects of inequality. Stress and behaviour originating from negative deficits in social status, friendship, social capital, and sense of control make contextual explanations at least as plausible as demographic effects such as lack of economic access to healthcare in a large portion of a population. There are several indirect contributing effects of inequality to negative health, including the role of poverty in maintaining resevoirs of infection, and increased negative impacts from crime on health (both direct by violence and indirect by stress factors). Another indirect effect is the association between development associated with wealth as conventionally measured by economic outputs and increased concentration of disease causing pollution in the environment. None of these indirect effects necessarily correlate directly with inequality, as opposed to increasing development and urbanization. But a potential significant contributor has been overlooked in recent analyses of the relation between inequality and population health, namely the negative impacts of wealth itself. Increased wealth tends to be associated with increased access to remedial and crisis interventional healthcare, but not necessarily with good preventive care and practices. Wealthier lifestyles are associated with less exercise, overconsumption, and other negative environmental and behavioural risks, making excessive wealth itself a plausible negative factor for health outcomes and health expenditures. In the wealthiest economies, inequal distributions of incomes is associated with differential quality of diet and exercise at the two extremes, and a generally negative impact on quality of diet, exercise, and environmental factors in the middle. The result is a very complex set of influences which requires much careful study and analysis for any conclusive evaluation. However, in any analysis, the negative influences of excessive leisure and consumption associated with increased wealth, and found particularly in societies with large wealth disparities, which tend to value conspicuous consumption, need to be considered along with the health benefits accruing to wealthier populations. 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 Achilles and the Tortoise. 24 November 2009 Richard G Fiddian-Green, FRCS, FACS None Send response to journal: Re: Achilles and the Tortoise. The tortoise on the cover of this week's BMJ and accompanying article reminded me of Zeno's paradox and Aesop's fable. "In the paradox of Achilles and the Tortoise, Achilles is in a footrace with the tortoise. Achilles allows the tortoise a head start of 100 metres. If we suppose that each racer starts running at some constant speed (one very fast and one very slow), then after some finite time, Achilles will have run 100 metres, bringing him to the tortoise's starting point. During this time, the tortoise has run a much shorter distance, say, 10 metres. It will then take Achilles some further time to run that distance, by which time the tortoise will have advanced farther; and then more time still to reach this third point, while the tortoise moves ahead. Thus, whenever Achilles reaches somewhere the tortoise has been, he still has farther to go. Therefore, because there are an infinite number of points Achilles must reach where the tortoise has already been, he can never overtake the tortoise" (Wikipedia). "The Tortoise and the Hare is a fable attributed to Aesop. The story concerns a hare who ridicules a slow-moving tortoise. In response, the tortoise challenges his swift mocker to a race. The hare soon leaves the tortoise far behind and, confident of winning, he decides to take a nap midway through the course. When he awakes, however, he finds that his competitor, crawling slowly but steadily, has already won the race" (Wikipedia). Slow and steady wins the race. An important determinant of walking speed is the condition of peoples feet and the quality of the shoes they wear. As anyone who has had the misfortune to run a vascular clinic knows very well, patients with peripheral vascular disease and/or diabetes can have terrible feet and can be very restricted not only by pathology in their feet but also by the cost of having to have shoes specially made to accommodate their ailments. If a slower walking speed is associated with a poorer outcome it may simple be due to walking speed being a measure of pedal health. Competing interests: None declared Slow walking speed in elderly people Mortality rate 23 November 2009 Janet E Shackleton, GP Lyngford Park Surgery, Taunton, TA2 8SQ Send response to journal: Re: Mortality rate In response to the opening sentence 'People who walk faster are less likely to die' can I remind the editors that mortality is 100%, however fast you walk. Competing interests: None declared Slow walking speed in elderly people Sprint your way to immortality 20 November 2009 Michael O'Donnell, Journeyman writer Loxhill GU8 4BD Send response to journal: Re: Sprint your way to immortality Language is a way of communicating thought and sloppy language is an expression of sloppy thinking. So what are we to make of the first sentence of this editorial? “People who walk faster are less likely to die than slow walkers, especially from vascular disease.“ One one way to write clear and interesting prose is to think carefully about the meaning of each word you use. Clearly the authors had neither the time nor inclination to do this but surely someone on the editorial staff could have offered them a helpful hint. Michael O'Donnell FRCGP mod@doctors.org.uk 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... 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 How long does it take to train a surgeon? Surgical trainees need to work smarter not harder 23 November 2009 Lucy A Radmore, F2 General Surgery Department of GI Surgery, Cheltenham General Hospital, Sandford Road, Cheltenham, GL53 7AN Send response to journal: Re: Surgical trainees need to work smarter not harder I felt compelled to respond to the recent article by Jackson and Tarpley, as it was very relevant to me as a junior doctor planning on a future career in surgery. Undoubtedly the change brought by the European Working Time Directive has brought about issues regarding surgical training and there has been an almost simultaneous decrease in the time to train to be a surgeon. I have been reflecting on my future career and asking surgical trainees and consultants the impact they feel this is having and I have also presented this article at our Surgical Journal club. It seems to me that concerns are rife but feasible solutions are lacking. The surgical community is concerned about the issues brought up in this article such as lack of continuity of care, reduced experience in managing complications and complicated cases. Juniors often exceed their working hours to provide adequate care. This article called for a flexible approach with respect to the application of working time restrictions. However I feel that this will be difficult to encourage all trainees to work longer than the 48 hour week because as this article states there has been an associated improvement in the happiness of trainees with the reduction in working hours. Rather than work harder; trainees, and those responsible for their training, need to find ways to work smarter. There needs to be a more efficient and effective training pathway. This may involve increased training using surgical simulation with laparoscopic simulators for example in addition to clinical work. Operating lists should include planned training cases that are allocated to a specific trainee to meet their particular learning needs. We also need to change working patterns; if junior doctors all worked 12 hour days for 4 days in a row there would be better continuity of care and less handovers. I sincerely hope that things improve as I go through my surgical training. Competing interests: None declared

VIEWS & REVIEWS: The highs and lows of policy based evidence Colquhoun (4 November 2009) [Full text] The highs and lows of policy based evidence Independent? 23 November 2009 John Stone, Contributing editor: Age of Autism London N22 Send response to journal: Re: Independent? David Colquhoun writes [1]: "In the House of Commons Mr Johnson said, "I asked Professor Nutt to resign as my principal drugs adviser, not because of the work of the council but because of his failure to recognise that, as chair of ACMD, his role is to advise rather than to criticise government policy on drugs." But Mr Johnson had it wrong. Nutt, unlike, for example, the chief scientific adviser, is not a civil servant. He is an academic. It is his job to be independent. He is paid nothing for all his hard work on the ACMD. He has a day job to do as well. It is his job to criticise whatever he thinks it right to criticise." In this post Blairite era it may seem strange to point out that Civil Servants are paid to be independent. On the other hand academics are expected as things are to seek out the direct patronage of industry. In the case of David Nutt he states in a article [2]: "The author has received grants, speaker’s honoraria or consulting fees from all of the pharmaceutical companies that have developed and marketed the antidepressants discussed in Cipriani et al. (2009)." The article reproduces a chart from Cipriani et al which includes in alphabetical order (I have added the names of associated manufacturers): Bupropion (GlaxoSmithKline), Citalopram (Forest Laboratories), Duloxetine (Eli Lilly) Escitalopram (Lundbeck and Forest Laboratories),Fluoxetine (Eli Lilly), Fluvoxamine (Solvay), Milnacipran (Cypress Bioscience), Mirtazapine (Organon International), Paroxetine (GlaxoSmithKline)),Reboxetine (Pfizer) andVenlafaxine (Wyeth) In his controversial lecture (Eve Saville Lecture, for Centre of Crime and Justice Studies at King's College, London', as recalled by Colquhoun, Nutt spoke favourably of the safety of the recreational drugs cannabis and ecstasy: "This furore arose simply because Nutt said that cannabis was less dangerous than tobacco and alcohol (true) and that more people were killed and brain damaged from riding accidents than from ecstasy (also true)." But it should also be pointed out that the use of these drugs, particularly cannabis, has been linked with depression. For instance, the Royal College of Psychiatry website tells us [3]: "A study following 1600 Australian school-children, aged 14 to 15 for seven years, found that while children who use cannabis regularly have a significantly higher risk of depression, the opposite was not the case - children who already suffered from depression were not more likely than anyone else to use cannabis. However, adolescents who used cannabis daily were five times more likely to develop depression and anxiety in later life." Another relevant question might be, in the event of these recreational drugs ever being legalised, who might manufacture them for the mass market? [1] David Colquhoun, 'The highs and lows of policy based evidence', BMJ 4 November 2009 http://www.bmj.com/cgi/content/full/339/nov04_1/b4564 [2] David J Nutt, 'Prescribing anti-depressants post Cipriani et al' Journal Psychopharmacology 2009, http://jop.sagepub.com/cgi/reprint/23/8/865 [3] Royal College of Psychiatrists, 'Cannabis and mental health', http://www.rcpsych.ac.uk/mentalhealthinformation/mentalhealthproblems/alcoholanddrugs/cannabisandmentalhealth.aspx Competing interests: Autistic son - distrust of pharmaceutical companies

EDITORIALS: Who should receive Tamiflu for swine flu? Ellis and McEwen (6 July 2009) [Full text] Who should receive Tamiflu for swine flu? Experience in Sri Lanka 24 November 2009 Kamal Abdul Naser, Consultant Physician Teaching Hospital, Peradeniya, Sri Lanka Send response to journal: Re: Experience in Sri Lanka I am in charge of a sentinal unit for H1N1 influenza in Sri Lanka where we have treated about seventy in patients with suspected and confirmed H1N1 influenza patients over a period of a month. When we start treating patients,there is always a panic amongst the health care workers. I get several requests for Ostelamir prophylaxis. Indications for requests vary from high risk exposure to just being working in a hospital. I have been maintaining a strict policy of not prescribing prophylaxis, except in high risk exposure for a high risk patient like pregnancy, asthma,immunosuppressed patients etc. Of course we have taken out all pregnant nurses out of medical, paediatric and emergency units. 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 Shiny happy people? Over Diagnosis Bias of Melanoma 24 November 2009 Des Spence, GP Glasgow G20 9DR Send response to journal: Re: Over Diagnosis Bias of Melanoma I wasn’t sure that I was supporting the use of sunbeds ! But the issues here are worthy of debate. The incidence of melanoma has tripled in the 45 -64 age group but the death rate in remains unchanged. Melanoma is difficult to treat and not sensitive to chemotherapy nor radiotherapy, so we have a situation where a three fold increase has not resulted in a three fold increase in death rate. Also the incidence in men is lower but their death rate is higher. The incidence is highest in social class 1, but they are the least likely to use Sunbeds. The melanoma data is riddled with confounding and conflicting anomalies. The more we look the more we find. There can be only one conclusion, there is large over diagnosis bias of malignant melanoma. The health anxious – social class 1 are more likely to request moles to be removed and women more likely to present to doctors. The diagnosis on biopsy is in the end is a human judgement – humanity in these risk averse days errs the side of caution. Interestingly , I was sent evidence looking at the role of Vitamin D ( the Northern European pale skin being an adaptation to allowing easy Vitamin D synthesis ) and it seems clear that Vitamin D is important to our general well being not merely our bones– we need the sun. Using current sunbeds is not a good idea. But exposing ourselves to natural sunlight is no bad thing. So in the dark November I still look forward to the summer sun, a more balanced debate and some research into the clear and evident over diagnosis bias of malignant melanoma. Competing interests: None declared Shiny happy people? Primary Care Dermatology Society recommendation on Sun Bed use 23 November 2009 Stephen Kownacki, Executive Chair PCDS and GP Primary Care Dermatology Society 2nd Floor Titan Court 3 Bishop Square Hatfield AL10 9NA, The trustees and committee of the Primary Care Dermatology Society (PCDS) Send response to journal: Re: Primary Care Dermatology Society recommendation on Sun Bed use The doubts about the harm due to sun bed exposure have now been resolved by clinical research and the PCDS is now convinced by the evidence that a proportion of avoidable melanoma deaths are due to sun bed use. It is well established that UV damage to the skin of children and teenagers increases the risk of melanoma more than exposure in adulthood. We do not wish or seek to prevent informed adults from all risk taking behaviour, but as with alcohol, tobacco and gambling, society has a responsibility to protect vulnerable young people. The PCDS therefore adds our support to calls for a ban on sun bed use for under 18s and unsupervised cash or card operated tanning machines. We suggest a minimal degree of suitable health advice, perhaps in the form of a leaflet advising on the risks and early signs of skin cancer, for adults choosing to indulge in recreational or cosmetic UV light. In the light of the skin cancer epidemic, we call on the government to introduce a short bill, or an administrative amendment to existing health and safety legislation, to achieve these limited and reasonable measures. pcds@pcds.org.uk Competing interests: None declared

EDITORIALS: Treatment of enteric fever Parry and Beeching (3 June 2009) [Full text] 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

RESEARCH: Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups Madsen et al. (27 January 2009) [Abstract] [Full text] [PDF] Acupuncture treatment for pain: systematic review of randomised clinical trials... A doubt about the interpretation of the findings 24 November 2009 Adrian White, Senior researcher NAFKAM The National Research Center in Complementary and Alternative Medicine, Univ of Tromsø Send response to journal: Re: A doubt about the interpretation of the findings Madsen et al found a significant difference between acupuncture and ‘placebo’ acupuncture. This difference was robust, remaining significant in subgroup analyses of different outcome measures and of high quality studies. In interpreting this finding, the authors state that this effect ‘cannot be clearly distinguished from bias’. They state that these biases arise because patients may distinguish real acupuncture from ‘placebo’ acupuncture, and because patients interact with practitioners who cannot be blinded so may subconsciously influence the outcome. These inherent biases presumably apply to all placebo controlled studies of acupuncture, in any condition that can respond to non-specific influences. It is noteworthy, therefore, that a meta-analysis of RCTs of acupuncture for migraine shows no difference between acupuncture and ‘placebo’ acupuncture. This was a robust finding which applied both immediately after treatment (seven studies, 1091 patients) and after 3-4 months (11 studies, 1225 patients).[1] It is known that migraine does respond to non-specific influences.[2] The fact that these biases, which these authors claim are inherent in acupuncture, have no effect in studies of acupuncture for migraine argues against their existence in studies of acupuncture for other painful conditions. Thus it appears that the inherent bias that Madsen et al refer to in these studies is either very small or non-existent. And so it seems more logical to interpret their findings as showing that acupuncture has a significant analgesic effect that is small but robust. Competing interest The author is paid as the editor in chief of Acupuncture in Medicine. References 1. Linde K, Allais G, Brinkhaus B, et al. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev 2009(1):CD001218. 2. Macedo A, Banos JE, Farre M. Placebo response in the prophylaxis of migraine: a meta-analysis. Eur J Pain 2008;12(1):68-75. Competing interests: The author is paid as the editor in chief of Acupuncture in Medicine