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RESEARCH: Sandra Hollinghurst, Niamh Redmond, Céire Costelloe, Alan Montgomery, Margaret Fletcher, Tim J Peters, and Alastair D Hay Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): economic evaluation of a randomised controlled trial BMJ 2008; 337: a1490 [Abstract] [Full text]

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Beyond costs

Carlos A Calderon Ospina, Alejandra Salcedo Monsalve   (11 September 2008)

Flawed economic evaluation of PITCH

Wouter Havinga   (29 September 2008)

Beyond costs 11 September 2008
Carlos A Calderon Ospina, Assistant Professor Pharmacology Unit. Faculty of Medicine. Universidad del Rosario. Bogota. Colombia., Alejandra Salcedo Monsalve Send response to journal: Re: Beyond costs	Recently, the BMJ published a clinical study according to which the combination of ibuprofen and paracetamol is more effective in going temperature down in children with fever (1). In turn, ibuprofen is more effective as monotherapy than paracetanol in controlling this symptom; that is why the authors conclude that for discomfort feverish children; first it should be administrate ibuprofen and then consider adding paracetamol for 24 hours in case of do not obtain the expected recovery. However, there are a few reports that suggest an association between the intake of ibuprofen or ibuprofen and paracetamol and an increased risk to suffer from soft-tissue infections, some of them very serious such as necrotizing fasciitis (2,3,4,5,6). Some of these studies shown an increase of the risk arose from the intake of ibuprofen as monotherapy (2,3,5,6), or the combination between ibuprofen and paracetamol (3,4); but at the same time a few of them are very emphatic showing that there is not an increase in the risk associated to the intake of paracetamol alone (3,4,7). The main risk factors for suffering from necrotizing fasciitis associated to nonsteroideal anti-inflammatory drugs (NSAIDs) include age (children) and a viral disease during the treatment. In fact, a French, case (patients with soft tissue necrotizante infection)-control study, published recently (6), documented that among 38 cases that were reported to the National System of Pharmacovigilance between 2000 and 2004, 25 patients were exposed to ibuprofen and 24 patients had have chickenpox. In the same study patients had a median age of 4 years old, and the adjusted odds ratios for exposure to NSAIDs and for viral infection were 31,38 (IC 95% 6,40 – 153,84) and 17,55 (IC 95% 3,47 – 88,65) respectively. It is quite interesting that in Hay´s et. al. study (1), 57 children with viral diseases were included (36,5%), and although it says that 5 children were hospitalized due to adverse serious events, it is not clear how these events happened or none extra information besides the medication taken is given. To conclude, I think that is not possible to ignore the available evidence, and although the combination of ibuprofen and paracetamol could be more effective for treating fever in children, precautions have to be taken when administrating this combination in children with viral infections, especially in children with chickenpox, and in this population the administration of paracetamol should be considered as monotherapy, decreasing the risk of suffering from soft tissue infections such as necrotizing fasciitis. References 1. Hay A, Costelloe C, Redmond N, Montgomery A, Fletcher M, Hollinghurst S, Peters T. Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial. BMJ. 2008; 337: a1302. 2. Zerr DM, Alexander ER, Duchin JS, Koutsky LA, Rubens CE. A case- control study of necrotizing fasciitis during primary varicella. Pediatrics. 1999; 103: 783 - 790. 3. Lesko SM, O'Brien KL, Schwartz B, Vezina R, Mitchell AA. Invasive group A streptococcal infection and nonsteroidal antiinflammatory drug use among children with primary varicella. Pediatrics. 2001; 107:1108 -1115. 4. Lesko SM. The safety of ibuprofen suspension in children. Int J Clin Pract Suppl. 2003; 135: 50 - 53. 5. Leroy S, Mosca A, Landre-Peigne C, Cosson MA, Pons G. Ibuprofen in childhood: evidence-based review of efficacy and safety. Arch Pediatr. 2007; 14: 477 - 484. 6. Souyri C, Olivier P, Grolleau S, Lapeyre-Mestre M; French Network of Pharmacovigilance Centres. Severe necrotizing soft-tissue infections and nonsteroidal anti-inflammatory drugs. Clin Exp Dermatol. 2008; 33: 249 -255. 7. Mikaeloff Y, Kezouh A, Suissa S. Nonsteroidal anti-inflammatory drug use and the risk of severe skin and soft tissue complications in patients with varicella or zoster disease. Br J Clin Pharmacol. 2008; 65: 203 - 209. Competing interests: None declared
Flawed economic evaluation of PITCH 29 September 2008
Wouter Havinga, GP locum GL6 6JL Send response to journal: Re: Flawed economic evaluation of PITCH	The authors spell out under the heading 'study design' that it takes the perspective of the NHS, parents and carers. (1)   As such the study design didn't make the study group a priority: the children. PITCH is based on outdated, institutionalised behaviour, not taking into account indications from decades of medical literature that document that the natural fever process is just as good (if not better?) than suppressing the natural healing with anti-inflammatory products. (2)   Furthermore, the authors are aware of the daily re-occurring overdoses, adverse events, inappropriate use and hospitalisations due to paracetamol and ibuprofen but did not value it in the study. PITCH didn't use a placebo in the study. These issues also makes the economic evaluation of PITCH flawed. (3/4)   The cost consequences of a doctor or nurse ritualistic advising administration of analgesics, resulting in fever phobia and recurring consultations, yearly casualties and possible long term side effects are incomparable to the simple effort of health professionals taking the time to inform parents about the natural fever process.   Parents, but doctors in particular, need to be informed about the natural process of fever. (5) This information will help them to deal with confidence with the feverish child. As such the work pressure and the cost on primary and secondary care will reduce.   The authors, most of whom appear to be not medical, have been misinformed by the doctor's paradigm, that fever is bad and collusion with parents is best. The emotional cost for the medical profession to admit to this is of course a stumble block but can be overcome with compassion, for oneself, and foremost for each child and their parents.   It follows that the BMJ needs to retract the conclusions of the PITCH studies and the misleading headlines on the front cover and the index page of the printed issue of 27 September 2008.     Sandra Hollinghurst, Niamh Redmond, Céire Costelloe, Alan Montgomery, Margaret Fletcher, Tim J Peters, and Alastair D Hay. Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): economic evaluation of a randomised controlled trial BMJ, Sep 2008; 337: a1490 http://www.bmj.com/cgi/content/full/337/sep09_3/a1490 Drug and Therapeutics Bulletin 2008;46:17-21 http://dtb.bmj.com/cgi/content/full/46/3/17  Wouter Havinga. PITCH: an indication of the level of emotion in relation to childhood fevers. http://www.bmj.com/cgi/eletters/337/sep02_2/a1302#201799 Wouter Havinga. In the interest of the public. http://www.bmj.com/cgi/eletters/337/sep02_2/a1409#202312 Child Adolesc Psychiatry Ment Health. 2007; 1: 7. Managing childhood fever and pain – the comfort loop Jacqui Clinch and Stephen Dale http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1971248   Competing interests: see http://www.bmj.com/cgi/eletters/337/sep02_2/a1409#202312