Jean V. Craig

A European consensus for the evaluation and management of infants with an equivocal diagnosis following newborn screening for cystic fibrosis

Screening newborns for cystic fibrosis (CF) is considered to be an ethical undertaking in regions with a significant incidence of the condition. Current screening protocols result in recognition of infants with an equivocal diagnosis. A survey of European practice suggested inconsistencies in the evaluation and management of these infants. We have undertaken a consensus process using a modified Delphi method. This has enabled input of CF specialists from a wide geographical area to a rigorous process that has provided a clear pathway to a consensus statement. A core group produced 21 statements, which were modified over a series of three rounds (including a meeting arranged at the European CF Conference). A final document of 19 statements was produced, all of which achieved a satisfactory level of consensus. The statements cover four themes; sweat testing, further assessments and investigations, review arrangements and database. This consensus document will provide guidance to CF specialists with established screening programmes and those who are in the process of implementing newborn screening in their region.

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

BackgroundA 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.MethodA 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.ResultsThe 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.ConclusionManipulations 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.

Postpartum smoking relapse--a thematic synthesis of qualitative studies.

BACKGROUND AND AIMS Many women quit smoking during pregnancy, but relapse after the baby is born. To understand why and identify ways of preventing this, this study reviewed the qualitative literature on womens experience of postpartum smoking relapse. METHODS A systematic review of qualitative studies and process evaluations of trials. We undertook a thematic synthesis of published qualitative data. RESULTS We screened 1336 papers. Twenty-two papers reporting on 16 studies were included, reporting on the views of 1031 postpartum women. Factors affecting relapse and barriers and facilitators to relapse prevention were identified around the key themes of beliefs, social influences, motivation, physiological factors and identity. Womens beliefs about smoking as a means of coping with stress and the need for social support, especially from a partner, emerged as important. Extrinsic motivation to quit during the pregnancy (for the health of the fetus) appeared to be a factor in prompting relapse after the baby was born. During the immediate postpartum period women believed that physiological changes influence cigarette cravings. The stress of caring for a newborn, sleeplessness and adjusting to a new mothering identity were also reported to be important. CONCLUSIONS Among women who quit smoking during pregnancy, those who relapse postpartum talk commonly about no longer needing to protect the baby and the effects of stress. Partner support and a sense of changed identity are cited as factors preventing relapse.

The manipulation of drugs to obtain the required dose: systematic review

AIM To describe the development of a systematic review protocol that maps the evidence relating to drug manipulations conducted to obtain the required dose. This process included defining a search strategy and methods to assess the quality and to synthesize the evidence retrieved. BACKGROUND Economic constraints mean that marketed formulations may not meet the needs of all patients. Consequently, it is sometimes necessary to manipulate marketed products with the aim of obtaining the required dose. Most clinical practice appears to be guided by ad hoc approaches and informal literature reviews. METHODS This systematic review protocol has been designed to identify the evidence available on drug manipulation. The review aims to identify what evidence is available and where the gaps appear in the current evidence. This report describes the challenges of developing a systematic review in an area that potentially involves many drugs and considers outcomes other than effectiveness. In particular, searches required the use of non-specific terms and the iterative development of a complex search strategy. The development of quality assessment criteria is also described. Funding commenced in April 2009. DISCUSSION The systematic review described here will capture a broad selection of research about drug manipulations and may also be of interest to those conducting reviews in broad remit subject areas that are not easy to define using accepted terminology.

Estimating the requirement for manipulation of medicines to provide accurate doses for children

Objective To determine the type and frequency of manipulations of drug dosage forms required to administer smaller doses for children and the drugs involved. Methods An experienced paediatric clinical pharmacist estimated the requirement to manipulate a medicine to achieve accurate dose administration from prescription data in all neonatal and paediatric inpatients collected over 5-day periods and information on drug dosage form availability in a regional childrens hospital (RCH) and regional paediatric intensive care unit (RPICU), a regional neonatal intensive care unit (RNICU) and paediatric and neonatal wards of a district general hospital (DGH) using paper-based prescribing systems. Doses were expressed by weight. Ward stock supply with some intravenous drugs ready-to-administer was provided. The main outcome measures were the estimated requirement for dosage form manipulation, nature of the manipulation and drug name. Results Of 5375 evaluated drug administrations, 542 (10.1%) were judged to require manipulation or measurement of a small volume (<0.2 ml). The most frequent manipulation was measurement of oral dose in volumes of 0.1 to <0.2 ml in the DGH. Requirement to measure doses of <0.1 ml (oral and intravenous) accounted for 25.2% of all manipulations, with the need to measure intravenous doses of <0.1 ml being most frequent in the RNICU and RPICU (60.4% and 31.9% of manipulations, respectively). Hydrocortisone was the drug most frequently judged to require manipulation with both measurement of small volumes for intravenous injection (RPICU and RNICU) and segmentation of tablets (RCH). Conclusions Manipulation of medicines (including measurement of very small volumes) to provide accurate smaller doses for children is common in the hospital setting.

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.

Audit to monitor the uptake of national mouth care guidelines for children and young people being treated for cancer

PurposeThe aim of this study is to review current oral care practices in children being treated for cancer against audit criteria derived from national guidelines, and to compare findings with data from a baseline survey carried out in 2002 prior to implementation of the national guidelines.MethodsA telephone survey was carried out of all 21 haematology–oncology (HO) centres and seven bone marrow transplant (BMT) units within the UK Children’s Cancer Study Group focusing on key audit themes of: availability of evidence-based guidelines, oral and dental care prior to and during cancer treatment, oral assessment, prevention and treatment of oral complications.ResultsThe national guidelines were used in 19/25 (76%) settings that employed written guidelines. There was little variation in advice given to patients/parents on basic oral hygiene, and this advice was commensurate with guideline recommendations. Inconsistencies in oral care assessment, reported at baseline, remained commonplace across the majority of settings. In only 10/21 HO centres, it was usual practice for children to undergo dental assessment prior to commencing cancer treatment, indicating no improvement since baseline survey. Few therapies outside of the guideline recommendations were being used. The routine use of preventive nystatin, not recommended in the guideline, had significantly decreased from baseline (by 40%).ConclusionsUptake of national guidelines by HO/BMT settings was good however certain oral care practices fell short of the guideline recommendations. Routine dental checks need to be embedded in practice. Further consideration is needed as to how oral assessment might be used more effectively in informing treatment.

Relationship between the Mediterranean dietary pattern and musculoskeletal health in children, adolescents, and adults: systematic review and evidence map

Context: An understanding of the modifiable effects of diet on bone and skeletal muscle mass and strength over the life course will help inform strategies to reduce age‐related fracture risk. The Mediterranean diet is rich in nutrients that may be important for optimal musculoskeletal health. Objective: The aim of this systematic review was to investigate the relationship between a Mediterranean diet and musculoskeletal outcomes (fracture, bone density, osteoporosis, sarcopenia) in any age group. Data Sources: Ten electronic databases were searched. Study Selection: Randomized controlled trials and prospective cohort studies that investigated a traditional Mediterranean diet, published in any language, were eligible. Studies using other designs or other definitions of the Mediterranean diet were collated separately in an evidence map. Data Extraction: Details on study design, methods, population, dietary intervention or exposure, length of follow‐up, and effect on or association with musculoskeletal outcomes were extracted. Results: The search yielded 1738 references. Data from eligible randomized controlled trials (n = 0) and prospective cohort studies (n = 3) were synthesized narratively by outcome for the systematic review. Two of these studies reported on hip fracture incidence, but results were contradictory. A third study found no association between the Mediterranean diet and sarcopenia incidence. Conclusions: Overall, the systematic review and evidence map demonstrate a lack of research to understand the relationship between the Mediterranean diet and musculoskeletal health in all ages. Systematic Review Registration: PROSPERO registration number IDCRD42016037038.

MODRIC - Manipulation of drugs in children.

European Medicines Agency Committee for Medicinal Products for Human Use & Paediatric Committee & Committee on Herbal Medicinal Products (concept paper only). Guideline on the pharmaceutical development of medicines for paediatric use. Concept paper, first draft, comments, revised draft and overview of comments. Available at: http://www.ema.europa.eu/ema/ index.jsp?curl=pages/regulation/general/general content 000362.jsp&mid= WC0b01ac0580028eb2 (accessed 05.01.13). European Paediatric Formulation Initiative, 2013. EUPFI 3rd conference “Formulating better medicines for children”, Available at: http://www.eupfi.org/ new%20website%20template/index1.html (accessed 01.09.12, accessed 02.01.13). International Conference on Harmonization, 2013. Guideline ICH Q8(R2) on Pharmaceutical Development, Available at: http://www. ich. org/products/guidelines/quality/article/quality-guidelines.html (accessed 02.01.13). European Commission, 2013. Directive 2001/83 of the European Parliament and of the Council of 6 November 2011 on the community code relating to medicinal products for human use, Available at: http://ec.europa. eu/health/documents/eudralex/vol-1/index en.htm (accessed 02.01.13). European Pharmacopoeia, 2013. Monograph 0478 on Tablets, Available at: http://online6.edqm.eu/ep708/#doc 15 of 532 (accessed 05.01.13). European Commission DG Sanco, 2012. A guideline on summary of product characteristics (SmPC), Available at: http://ec.europa.eu/health/files/ eudralex/vol-2/c/smpc guideline rev2 en.pdf (accessed 13.11.12). European Commission Enterprise Directorate General, 2013. Notice to Applicants, Volume 3B. Guidelines Medicinal Products for human use. Safety of environment and information. Excipients in the label and package leaflet of medicinal products for human use, Available at: http://www. ema.europa.eu/docs/ en GB/document library/Scientific guideline/2009/09/WC500003412.pdf (accessed 02.01.13).

The relationship between pre-defined Mediterranean dietary patterns and musculoskeletal health in all age groups: a systematic review.

Bone accretion in childhood and adolescence, and loss of bone occurring with ageing, are major determinants of fracture risk in later life(3) . Skeletal muscle mass is closely inter-related with bone mass throughout the lifespan(4) , and sarcopenia, defined as the presence of low skeletal muscle mass and low muscle strength or physical function(5) is significantly associated with fracture occurrence(6) . Both bone and skeletal muscle health are potentially modifiable through nutrition. The Mediterranean diet, characterised by high intake of plant foods (fruits, vegetables, legumes, nuts and cereals); moderate-high intake of fish, low-to-moderate intake of dairy products; low intake of meat, poultry, and saturated lipids; high intake of olive oil; and a moderate intake of ethanol(7) , is rich in nutrients that may be important for optimal musculoskeletal health.