The manipulation of dosage forms of medications, with the aim of achieving the required dose, for administration to children

Background: There is a lack of commercially-available, age-appropriate formulations designed for administration to babies and children. This means that medicines may need to be manipulated to achieve the dose that is required in paediatric practice. This raises concerns about the dose accuracy and safety of the manipulated product. Though this is known and accepted as necessary, to date there has been no assessment of the evidence relating to these manipulations, the extent and nature of manipulations or of any associated practice issues. Objective: This thesis aimed to determine whether there is an evidence base for drug manipulations, to investigate the nature of manipulations, at the point of administration, in current clinical practice in neonatal and paediatric settings in the UK and to explore drug manipulations in the context of long-term medication administration by parents. Methods: Several methods were used to explore drug manipulations: a wide-ranging systematic review, an observation based study of drug manipulations in in-patient neonatal and paediatric areas, a UK wide survey of paediatric nurses and an interview based study with parents of children taking long-term medications. Outcomes: Manipulations to administer the required dose occur throughout practice and are not supported by evidence. Drug manipulation is intrinsic in neonatal and paediatric practice. Manipulations were identified more often in high dependency areas but were found throughout all clinical areas. Manipulations occurred more commonly with certain dosage forms, notably with tablets, but were found involving many dosage forms. Manipulations were identified involving drugs that are commonly prescribed and for prescriptions that had been written for babies and children of all ages and with a wide variety of diagnoses. Concerns relating to drug manipulations have been raised by those working in these areas. Parents described undertaking manipulations prior to administering medications to children, though undertaking these manipulations did not appear to cause undue concern. Conclusions: This thesis has reviewed the limited evidence, scoped out the nature of manipulations used in practice and by parents and suggested areas where future work would be appropriate. In exploring drug manipulation this thesis has added to ongoing discussion about the need for appropriate medication for paediatric use

A randomised, patient-assessor blinded, sham-controlled trial of external noninvasive peripheral nerve stimulation for chronic neuropathic pain following peripheral nerve injury (EN-PENS trial):study protocol for a randomised controlled trial

BACKGROUND: Eight percent of people in the UK are estimated to have persistent (chronic) neuropathic pain, and for many there is no effective treatment. Medications are the most common first-line treatment but often have limited benefit or adverse events. Surgical treatments, such as spinal cord stimulation, are then often considered. External non-invasive peripheral nerve stimulation (EN-PENS) is a form of electrical stimulation that involves placing a pen-shaped electrode onto the skin, which can be easily self-administered by patients. Observational studies suggest that EN-PENS may relieve pain for people with localised neuropathic pain; however, there is currently no evidence from controlled trials to confirm the efficacy and confidently determine the effect size for patients with longstanding neuropathic pain. METHODS: EN-PENS is a single-site, blinded, randomised controlled parallel-group superiority add-on trial with a 1:1 allocation ratio, designed to evaluate the efficacy of treatment versus control treatment in 76 patients with longstanding neuropathic pain following peripheral nerve injury. Patients with moderate to -severe neuropathic pain following peripheral nerve injury will be randomised to receive either the active or control treatment, followed by an optional treatment extension or treatment switch to the alternative treatment arm. The primary outcome is average 24-h pain intensity recorded on an 11-point (0–10) numerical rating scale, averaged over the last 7 days of treatment. DISCUSSION: Study results will be used to inform potential treatment efficacy and cost-effectiveness of EN-PENS for this population group. TRIAL REGISTRATION: ISRCTN53432663. Registered on 7 July 2016

Fibromyalgia in Behçet's disease: a narrative review.

IntroductionFibromyalgia is characterised by chronic widespread pain and tenderness. It has often been reported to occur concomitantly with chronic rheumatological conditions. Behçet's disease is a chronic relapsing, multisystem, autoinflammatory disease. There is only limited understanding of a potential relationship between fibromyalgia and Behçet's disease.AimGiven the potential detrimental influence of pain on the outcome of chronic disease, the aim of this narrative review is to gain an understanding of the incidence and presentation of fibromyalgia in Behçet's disease.MethodsElectronic databases Scopus, Medline, PubMed and UpToDate were searched.ResultsA total of 269 studies were identified, and limitations and exclusion/inclusion criteria were applied to ensure accurate and comparable selection of studies; four studies were selected. All cases were assessed for the presence of fibromyalgia according to the 1990 or 2010 diagnostic criteria of the American College of Rheumatology, with Behçet's disease diagnosed according to the International Study Group (ISG) for Behçet's disease criteria. A higher prevalence of fibromyalgia (5.7-37.1%) was reported in Behçet's disease compared to that of the general population (2.9-4.7%).DiscussionWhile an increased prevalence of fibromyalgia was found in patients with Behçet's disease, this needs to be considered within the context of limited available evidence. The potential impact of these conditions on the disease activity of each other is not clear and may require a prospective study.ConclusionFibromyalgia appears to be more prevalent in those with Behçet's disease than would be expected in the overall population. Significance: This review provides some evidence that fibromyalgia is more prevalent in those with Behçet's disease. To ensure appropriate patient treatment choices, it is important that both conditions are diagnosed where they co-exist

Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence

Background: A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice.Method: A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses' experiences and views.Results: The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance.Conclusion: Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children

A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice

This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug

Prophylaxis against infective endocarditis: summary of NICE guidance

Infective endocarditis is a rare condition with an incidence of less than 10 per 100 000 population/year. It is, however, associated with a high mortality and morbidity. Accepted clinical practice has been to use antibiotic prophylaxis in those at risk of infective endocarditis undergoing dental and certain non-dental interventional procedures, in the belief that this may prevent its development. The effectiveness of such antibiotic prophylaxis in humans is, however, not proved1 and the recent American Heart Association guideline2 recommends a much more limited role for antibiotic prophylaxis against infective endocarditis. This article summarises the most recent guidance from the National Institute for Health and Clinical Excellence (NICE) on antibiotic prophylaxis against infective endocarditis.