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Background:Dual-energy computed tomography (DECT) detects urate depositions, and is included in the ACR/EULAR classification criteria for gout. There is lack of longitudinal studies in large patient populations for changes in urate deposition measured by DECT during urate lowering therapy (ULT).Objectives:To explore by DECT the longitudinal changes urate depositions during a treat-to-target approach in gout with ULT.Methods:In a prospective observational study, patients with crystal-proven gout were included if they presented after a recent gout flare and with increased serum urate levels (>360 μmol/L/>6 mg/dl). In a treat-to-target approach they received ULT with escalating drug doses with monthly follow-up during the first year until the treatment target was met with serum urate A DECT scanner (General Electric Discovery CT750 HD) acquired data from bilateral forefeet and ankles at 80 KW and 140 KV, processed with a software with a 2-material decomposition algorithm which colour codes urate. Follow-up DECT was performed after one and two years.Images were scored with a semiquantitative method (Bayat et al. 2015) by one experienced radiologist in known order and blinded to serum urate and clinical data. Each scan assessed four regions: the first metatarsophalangeal (MTP1) joint, the other joints of the toes, the ankles and midfeet, and all visible tendons in the feet and ankles. Each region was then scored according to the maximum amount of urate deposition observed on visual inspection (0=no deposits, 1=dots, 2=single deposit, 3=more than one deposit). A total DECT sum score was derived by adding all values from the four regions, with a maximum score of 12.Results:DECT was at baseline measured in 187 of 211 patients. 95.2% were males, mean (SD) age was 56.7 (13.7) years, disease duration 8.1 (7.9) years), and 17% had clinical tophi.The total DECT scores and all subscores decreased from baseline to 2 years (pThe mean (SD) serum urate level (μmol/L) decreased from 501 (80) at baseline to 311 (48) at 12 months and 322 (67) at 24 months. Reaching the treatment target Conclusion:During a treat-to-target approach urate deposition visualised by DECT were clearly reduced in ankles and feet after 1 year with further reduction after 2 years.Table 1.Baseline (n=187) Mean (SD)1 year (n=157) Mean (SD)2 years (n=166) Mean (SD)MTP1 (0-3)1.4 (2.0)1.0 (1.7)0.6 (1.3)Toes (0-3)1.0 (1.8)0.6 (1.4)0.3 (1.0)Ankle/Midfoot (0-3)1.2 (2.1)0.7 (1.60.3 (1.0)Tendons (0-3)1.0 (1.7)0.5 (1.2)0.3 (0.8)Sum score (0-12)4.6 (6.4)2.8 (4.7)1.5 (3.2)Disclosure of Interests:Till Uhlig Speakers bureau: Grünenthal, Novartis, Consultant of: Grünenthal, Novartis, Tron Eskild: None declared, Lars Fridtjof Karoliussen: None declared, Tore K. Kvien Consultant of: AbbVie, MSD, UCB, Hospira/Pfizer, Eli-Lilly, Roche, Hikma, Orion, Sanofi, Celltrion, Sandoz, Biogen, Amgen, Egis, Ewopharma, Mylan, Grant/research support from: BMS, AbbVie, MSD, UCB, Hospira/Pfizer, Eli-Lilly, Espen A Haavardsholm Consultant of: Pfizer, UCB, Eli Lilly, Celgene, Janssen-Cilag, AbbVie and Gilead, Nicola Dalbeth Speakers bureau: Menarini, AstraZeneca, Takeda, S. Nicolaou, Consultant of: AstraZeneca, Fonterra, Takeda, Pfizer, Cymabay, Crealta, Grant/research support from: AstraZeneca, Siemens Healthcare, Hilde Berner Hammer Consultant of: AbbVie, Lilly and Novartis

AimCurrently, majority of prescribed medication doses are calculated according to a child’s body weight without considering the available drug products for administration or the therapeutic range of the drug. This can lead to lack of consistency in dosing and drug administration errors, which affects many children of all ages treated with medicines.1 There are no established standards for dose-banding in national or international healthcare systems. This project aimed to establish dose-banding limits for paediatric medicines, to be used for prescribing and administering accurate, safe, and effective drug doses.MethodA list of the most common oral prescribed medications was established from the medication dispensing database of four hospitals in the UK. Then the evidence for safe and effective dose ranges for each drug on the list was identified from paediatric reference books, Summary of Product Characteristics (SPC) and published literature. After using these data to develop dose bands based on body weight, we used a Delphi process to achieve healthcare professionals’ consensus about the suggested dose bands for each drug on the list.ResultsA total of 45 drugs for 45 specific indications were included. Four categories of dose-banding limits were established; drugs with 2-weight bands; 3-weight bands; 4-weight bands and 5-weight bands. Overall, for 53.3% (24/45) of the included drug, all their suggested dose-banding limits reached consensus after two rounds of Delphi. For 92% (22/24) of them, consensus was achieved on all their suggested bands in the first round. Only for 2 drugs the agreement was achieved after the second round. For the drugs included in 2-weight band and 5-weight band categories, all their suggested dose-banding limits received total consensus after round 1 of the Delphi process. For 9 drugs included in the 4-weight bands category, the agreement was achieved only on either one or two of their suggested dose bands. For 12 drugs, no agreement was reached on any of their suggested bands.ConclusionThe study results provide healthcare professionals with a set of recommended dose-banding limits for commonly prescribed drugs in the UK. These recommended limits could establish the basis for change in clinical practice to improve health care provided for children.AcknowledgementThis work is part of a larger project funded by the Neonatal and Paediatric Pharmacists Group.ReferenceRashed AN, Tomlin S, Arenas-Lópes S, et al. Evaluation of the practice of dose-rounding in paediatrics. Int J Pharm Pract 2019 May 29. doi:10.1111/ijpp.12549. [Epub ahead of print]

Objectives Vial sharing practices introduce risk to aseptic compounding. This review aims to quantify the financial gain that can be achieved from taking on this additional risk. Method By looking at all drug doses compounded over a 2-year period at a general district hospital, it has been possible to calculate the number of vials used along with the amount of each drug that was wasted. From there it was possible to use the drug doses compounded and model this data against four different options around vial sharing. Option 1 was for no vial sharing, option 2 was for vial sharing on a single day, option 3 was for vial sharing Monday to Friday and option 4 was for vial sharing on a rolling 7-day basis. Options 3 and 4 allowed for an added consumable cost per vial. Results Over the 2-year period, a rolling 7-day vial sharing practice showed considerable cost savings. This saving was not uniform across all drugs compounded, with some high-cost low-volume drugs resulting in additional cost from a rolling 7-day vial sharing practice. Conclusions Vial sharing is cost effective against increased consumable costs and can be further enhanced by selecting the drugs to use vial sharing for.

Background: Many drugs are unlicensed in children and consequently their doses have been scaled down from those used in adults. Objective: To compare the performance of three scaling models in predicting maintenance doses for children from those used in adults. Methods: Three scaling models based on body weight (BW), body surface area (BSA) and BW 0.75 were used to predict maintenance doses across the paediatric age band from the equivalent adult doses for 30 different drugs. The predicted doses were compared with those in the British National Formulary for children 2006 (BNFc). Percentage error and mean squared prediction error were used as a measure of precision, and mean prediction error was used as a measure of bias. Results: In the 1-month and 12-month age groups, the different approaches ranked on their bias (least bias first) were BW 0.75 BW 0.75 >BSA. The BSA and BW 0.75 methods predicted doses up to 2.86-fold higher than the BNFc in the 1-month and 1-year age group. In the 7-year and 12-year age groups, BW 0.75 and BSA performed better than BW for precision and bias, and no predictions were more than 1.8-fold higher than the BNFc. The BW method tended to also under-predict dose across the paediatric age range. Conclusions: Dose scaling should only be used as a last resort for determining a suitable dose in children. No single method was suitable across the entire paediatric age range.

Childhood obesity is increasing nationally and worldwide. Using the child's total body weight to calculate drug doses for certain medications could result in incorrect dosing. The aim of this study was to assess whether paediatric doctors have knowledge about prescribing correct doses of medications for obese children by using methods to calculate the ‘ideal body weight’ (IBW). A questionnaire was sent to paediatric doctors asking whether they understand IBW and how to calculate it using the McLaren method. The results suggested that most paediatric doctors did not determine whether a child was obese when calculating drug doses. There was relatively poor understanding about the concept of IBW and only 9% of paediatricians in this study knew how to calculate it. There should be more training and guidance about calculating IBW in obese children to avoid potentially toxic errors.

Aims—To establish the extent and type of premedication used before intubation in neonatal units in the United Kingdom. Methods—A structured telephone survey was conducted of 241 eligible units. Units were subdivided into those that routinely intubated and ventilated babies (routine group) and those that transferred intubated and ventilated babies (transfer group). Results—Of the units contacted,239 (99%) participated. Only 88/239 (37%) gave any sedation before intubating on the unit and only 34/239 (14%) had a written policy covering this. Morphine was used most commonly (66%), with other opioids and benzodiazepines used less frequently. Of the 88 units using sedation, 19 (22%) also used paralysis. Suxamethonium was given by 10/19 (53%) but only half of these combined it with atropine. Drug doses varied by factors of up to 200, even for commonly used drugs. Conclusion—Most UK neonatal units do not sedate babies before intubating, despite evidence of physiological and practical benefits. Only a minority have written guidelines, which prohibits auditing of practice. (Arch Dis Child Fetal Neonatal Ed 2000;82:F38‐F41)

Aims Childhood obesity is increasing in the UK and worldwide. Recent Public Health England data confirms that in England 19.1% of year-6 school children are obese and 14.4% are overweight. It is also recognised that increased fat and lean masses in obese children affect pharmacokinetics and the distribution of drugs in tissues. Using the child’s Total Body Weight (TBW) to calculate doses could result in incorrect dosing. This study was prompted by an incident of drug toxicity in an obese child where a very large dose was administered based on TBW. We aim to assess whether paediatric doctors have knowledge about prescribing correct doses of medications for obese children by using methods to calculate the ‘Ideal Body Weight’ (IBW). Method A questionnaire was sent to all paediatric trainees and consultants in the region asking whether they take into account the patient’s weight when prescribing for obese children, whether they understand ‘IBW’ and how to calculate it using the McLaren method. Results Of the respondents, only 3% (3/109) calculated BMI and determined if the child was obese for its age when prescribing medications. Conclusion The findings suggested that most paediatric prescribers did not ascertain if a child was obese when calculating drug doses. There was relatively poor understanding about the concept of IBW, which is the recommended weight to be used for dose calculations for certain drugs. We noted that although the British National Formulary for Children (BNFC) highlighted which drugs need IBW estimation, it did not provide a method for calculating it. These deficiencies should be addressed at the medical student and junior doctor level with appropriate prescribing training. In addition, the BNFC should include more guidance about calculating IBW in obese children to avoid potentially toxic errors.

Background Paediatric patients receive drug dosages based on their body weights. Consequently only part of a vial with medicine for intravenous (i.v.) administration is often required for a child, contrary to an adult, for whom one vial normally equals one dosage. This does not present a problem when preparing an i.v. drug dosage from an i.v. concentrate or solution. However the problem arises when the drug is formulated as a powder requiring reconstitution. The displacement values of the drug powders can be of negligible or significant sizes. Neglecting to take into account significant displacement values can result in under-dosing. A literature search revealed guidelines highlighting the importance of accounting for displacement values. No recent studies regarding the size of underdosing resulting from ignored displacement values were found. Purpose To investigate whether displacement values of powders for reconstitution are taken into account in the preparation and administration guide for i.v. drugs at the paediatric ward. If not, then categorising these drugs and calculating the percentage of the resulting underdosing. Material and methods The preparation and administration guide for i.v. drugs at the paediatric ward was studied to see whether displacement values were actually stated and to establish how the specified drug concentrations of reconstituted powders had been calculated. For the drugs where displacement values were not stated a description of the drug type was carried out and the size of the deviation between the estimated concentration (where the displacement value was addressed) and the specified concentration was calculated. Displacement values were obtained through a literature search and by contacting the marketing authorisation holders. Results Displacement values were taken into account in only 1 in 7 drug powders in the guide, all of them antibiotics, resulting in potential under-dosing ranging from 4–12%. Conclusion Ignoring displacement values of i.v. antibiotic drug powders for reconstitution can result in under-dosing of children. References and/or acknowledgements None. No conflict of interest.

Background The kind of patients we can find in a geriatric centre have various comorbidities, which implies that they usually have more than one medicine. It is common to have drug interactions. Purpose To evaluate the rational use of proton pump inhibitors (PPIs) in a geriatric centre with 300 beds attached to a second-level hospital. Material and methods We performed a cross descriptive study in all patients of a geriatric centre with PPI treatment in July 2014. Medical histories were reviewed and a database was designed: PPI, drug dose, diagnosis and concomitant NSAID treatment. PPI criteria for use were based on the current evidence available. Esomeprazole was limited to patients with a nasogastric tube, as it´s the only one that can be administered in this way. Results PPIs were prescribed in 80% of patients. Omeprazole was prescribed in 197 patients: 39% (77/197) had a gastrointestinal diagnosis and 61% (120/197) had no indication recorded, of which 57.5% (69/120) were on chronic NSAID treatment. Drug dosages were: 52.3% (103/197) 20 mg/24 h, 20 mg/12 h in 46.7% (92/197) and 0.5% (1/197) with 20 mg/8 h or 40 mg/8 h. The 42.5% (51/120) of patients whose treatment indication was unknown were re-evaluated: In 19.6% (10/51) the drug was suspended, in 58.8% (30/51) doses were changed to 20 mg/24 h. The remaining 21.6 (11%) patients were not changed without a clear medical reason. Esomeprazole was prescribed in 45 patients: 24% (11/45) had digestive diseases and 76% (34/45) had no indication recorded, of whom 61.7% (21/34) were on chronic NSAID treatment. Drug doses were: 66.7% (30/45) 20 mg/24 h and 40 mg/24 h in 33.3% (15/45). The 38.2% (13/34) patients whose treatment indication was unknown were re-evaluated: in 69.2% (9/13) the drug was suspended, 30.8% (4/13) were switched to omeprazole 20 mg/24 h. Only 28.9% (13/45) were carriers of a nasogastric tube. Conclusion Inappropriate use of PPIs was observed in terms of indication and drug dose. Prophylaxis of gastropathy in patients on NSAIDs was the most common correct indication. It is important to incorporate clinical pharmacists in geriatric centre teams to ensure and promote the rational use of medicines. Reference http://dx.doi.org/10.4321/S1130-01082008000200003 No conflict of interest.

Polytherapy is increasingly common because of the large number of new Anti Epileptic Drugs (AED). We carried out a study to determine if polytherapy has more adverse effects (AE) than monotherapy. Methods We compared three groups: monotherapy (n=186), polytherapy (n=325) and control subjects no taking AED (n=65). We used the Liverpool Adverse Event Profile (LAEP) to ascertain AE and to calculate the total AE score. We also recorded the frequency of refractory epilepsy, depression subscores on the LAEP and drug doses. Results The mean LAEP scores were significantly higher in polytherapy (45.56, CI=44.36 to 46.76) than in monotherapy (42.29, CI=40.65 to 44.02) and controls (33.25, CI=31.05 to 35.44). Tiredness, memory problems and difficulty concentrating were the most common symptoms in patients taking AED. The frequencies of symptoms reported as always or sometimes a problem were as follows: tiredness (polytherapy/monotherapy/controls) 82.5%/75.6%/64.6%, memory problems 76%/63.2%/29.2% and difficulty concentrating 68%/63.9%/30.8%. The proportion of seizure free patients was significantly lower in the polytherapy group (17%) than in the monotherapy group (55%). Depression rates between the monotherapy and polytherapy groups were similar. Drug dosages were higher in polytherapy, however this was not statistically significant. Conclusion Patients on polytherapy had significantly higher LAEP scores than patients on monotherapy. This should be carefully discussed with the patient before a second AED is added.

The popular show Your Life in Their Hands follows some foundation trainees at work and at home and has been much discussed by colleagues. Having heard negative comments from seniors about the show, I wondered whether exposing yourself to the media when you are very junior is dangerous. What makes good television probably isn’t best for the junior and might not show the rest of us in a great light. It has become almost impossible for those of us who watch television to avoid the ubiquitous reality show. Our appetite must be insatiable, for they seem to crop up more and more. Between fat clubbing, grand designing, and master chef-ing, you might have thought there was little space on the airwaves for a new band of brave, fresh faced young people armed with stethoscopes. Alas, some newly qualified foundation trainees have found their way on to the BBC in the second series of Your Life in Their Hands , their minds bursting with incorrect drug doses and an eagerness to prescribe them. In the days after the initial episodes I was struck by how many colleagues and friends brought the programme up in conversation …

There is now a great deal of evidence that doctors experience great difficulties when calculating drug doses. Six questionnaire studies published over the past 20 years have shown that when determining the correct volume of a drug solution to administer, doctors struggle when converting ratios and percentages.1–5 Despite recent evidence that these ways of expressing the concentration of drug solutions result in …

Higher dose chemotherapy reduces overall risk of relapse after breast cancer by 22% compared with less aggressive regimens. Similar benefits were seen in older and younger women, results from a meta-analysis show ( JAMA 2005;293:1073-81). The study retrospectively analysed data from four randomised clinical trials of treatments for lymph node positive breast cancer in 1975-99. Each trial compared more aggressive with less aggressive chemotherapy regimens, including a treatment arm using drug doses or schedules that were regarded as being high. A total of 6487 women with lymph node positive breast cancer were included, with 542 …

EDITOR,—David Wilks and colleagues defend their book vigorously—and so they should, as it has much to commend it, as I pointed out in my review. The drug doses they quote are based on the British National Formulary and manufacturers' datasheets, but unfortunately some of these are out of date or simply incorrect. Take the recommendation that a patient with a creatinine …

The contents of most drug ampoules are given as their mass concentration (mg or μg/ml), but a few drugs are traditionally given as a dilution or percentage concentration—for example, 1:1000 or 1% respectively. Many drugs used in resuscitation and acute medical emergencies are labelled in this way—for example, adrenaline 1:1000 and sodium bicarbonate 8.4% solution. A survey showed that many junior doctors could not calculate the mass of lignocaine in ampoules of different concentrations.1 We investigated further the ability of hospital doctors to convert between mass concentrations, dilutions, and percentage concentrations. We also asked which convention they preferred and the adequacy of their teaching on calculating drug doses. View this table: Answers to questions on drug doses. Values are numbers (percentages) of hospital doctors We asked 150 teaching hospital doctors of all grades and from a representative …

Three episodes on BBC Radio 4, 6 to 20 August at 9 pm Producer Beth Eastwood Programmes also available to download at www.bbc.co.uk/radio4/science/onemansmedicine.shtml Rating: ![Graphic][1] ;![Graphic][2] ![Graphic][3] ;![Graphic][4] ![Graphic][5] ![Graphic][6] The title of Gerald Carson's book about patent medicines, One for a Man, Two for a Horse (Doubleday, 1961), did not tell us what its author thought about drug doses in women and children, but it did at least intimate that there is variability in responsiveness to medicines, the theme of these three half-hour radio programmes. Men and women, blacks and whites, old and young–we all differ in the ways in which we respond to medicines. And the sources of variability are legion: differences between pharmaceutical formulations; in understanding and compliance; in drug disposition (pharmacokinetics) and pharmacological responses (pharmacodynamics); in the ways in which variable kinetics and dynamics are translated into therapeutic and adverse outcomes; … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif [5]: /embed/inline-graphic-5.gif [6]: /embed/inline-graphic-6.gif

Editor—Shere writes that not reading and signing letters you have dictated may be dangerous, but I disagree with most of most of what he says.1 Perhaps some other doctors do not have as many letters to sign as I do: to scrutinise and sign every routine clinic letter would mean that I would no longer be able to keep my head above the paperwork. Dreary work is bearable if it is useful, but what is the return for checking routine letters for the odd spelling mistake? Shere mentions a mistyped drug dose error that could have been lethal. No doctor should base his or her drug doses solely on another doctor's letter, signed or not. A signed letter is certainly more courteous than an unsigned one, but I hope that general practitioners in my area realise that an unsigned letter was dictated with just as much courtesy, that my stress levels are kept in check by sending unsigned letters, and that unsigned letters will arrive more quickly. I would postulate that what general practitioners really do not like are long and unstructured letters in which it is difficult to pick out essential information such as diagnosis, treatment (lethal or otherwise), and when the next appointment is. I started adding “Please accept unsigned to avoid delay” to my letters five years ago. That was some economy of the truth, I admit. But “Please accept this unsigned to avoid delay and because the prospect of unnecessarily signing 2000 or 3000 letters a year fills me with nausea and will bring on my early departure from the NHS” would not have struck the right tone.

Child Health: A Manual for Medical and Health Workers in Health Centres and Rural Hospitals. 2nd ed. Edited by P Stanfield, B Balldion, Z Versluys. (Pp 525; KSh360.) African Medical and Research Foundation, 1997. ISBN 9-966-87407-0. Rural hospitals in Africa sometimes have a small library, often in the senior doctor’s office, where the books are not accessible to the staff who would benefit from reading them. They are usually old editions of standard British or American textbooks, long winded, with drug doses in minims and guidance for making tincture of belladonna. Occasionally, there would be a paperback edition of Clayton’s Ten …

EDITOR,--I have always found it curious that the drugs whose concentrations are most likely to be expressed as per cent or as 1 in x thousand are also the most important drugs used in resuscitation. One can speculate on the reluctance of the appropriate authorities to tamper with the presentation of such important drugs, yet it comes as no surprise to find that most doctors …

About 70-80% of undergraduates entering medical training in Britain have passed mathematics at A level, and virtually all will have passed the subject at O level. Yet, as Rolfe and Harper show, among a representative sample of 150 doctors asked to perform simple calculations converting drug doses from a percentage or dilution to mass per volume the success rate was as low as 16% (p 1173).1 The results showed that senior doctors (consultants and senior registrars) were better at calculating the correct answer, and anaesthetists were notably better. While these data seem to suggest a hierarchy in numerical skill among doctors, in terms of both age and specialty, clearly there are …