On-call hospital pharmacy services in NHS England: service provision and documentation of medicines advice calls

Objectives UK hospital pharmacy services have historically been delivered during typical ‘office’ hours, which include the provision of medicines advice via the pharmacy's medicines information department. Outside office hours, an on-call service operates whereby pharmacists handle requests for medicine supply and advice. It is not known how this out-of-hours service operates. The aim of this study was to quantify the extent and scope of its provision across England. Methods A piloted self-administered survey was sent to every chief pharmacist in England representing acute hospitals and mental health trusts (n=218). Key findings Just over half (n=116/218, 53.2%) of chief pharmacists returned a completed survey. Most hospitals provided an on-call pharmacy service (87.1%, n=101/116). Nearly all on-call pharmacy services (91.1%, n=92/101) provided both supply of medication and medicines advice. Two-thirds (66.2%) of pharmacists who provided on-call services were junior. The majority of trusts (83.1%, n=74/89) receive <20 calls for medicines advice per week. Hospital nurses/midwives were seen as the most common users of the on-call pharmacy service. Medicines advice was documented by on-call pharmacists all (49.5%, n=47/95) or some of the time (49.5%, n=47/95). Just under half of trusts (41.1%, n=39/95) had a standard policy for the documentation of medicines advice. Two-thirds (66.7%, n=62/93) of respondents stated that advice was documented using paper-based forms. Most trusts (81.1%, n=77/95) provided training prior to pharmacists being on-call, with medicines information pharmacists involved in nearly 80% of cases (n=61/77) (respondents could select more than one option). Conclusions Medicines advice is an integral part of the pharmacy on-call service, which was provided by junior staff. Variability existed in resourcing the service across trusts. In addition to existing standards for documentation of medicines advice, professional standards should be developed for on-call hospital pharmacy service provision and training

Medicines advice out of hours: exploring the opinions of healthcare professionals on the use and provision of on-call pharmacy services in England

Provision of NHS hospital pharmacy services has historically been delivered during typical ‘office’ hours. During these hours most pharmacy departments provide a medicines information (MI) service where any healthcare professional can ask for medicines advice. Outside of these hours questions are handled by an on-call pharmacist. This study aimed to investigate the provision of pharmacy services and medicines advice out of hours, from the perspective of pharmacists and other healthcare professionals, in NHS England. A mixed methods approach was used: an online survey of all Chief Pharmacists in England (2012: n=220) and semi-structured interviews of on-call pharmacists (2014: n=8) and doctors and nurses (2015: n=3 & n=4 respectively) in the East of England. The online survey provided information about the provision of on-call pharmacy services in England, documentation of calls handled, and provision of relevant training. Semi-structured interviews generated 19 themes, grouped into 5 meta themes: documentation, individual’s knowledge and experience, information accessibility, use of service, and awareness of service. On-call pharmacy services were provided by most hospitals, predominantly by less senior staff with limited years’ experience. Documentation of questions was variable, and less than half of Trusts had a documentation policy. Documentation by on-call pharmacists was found to be affected by their knowledge and experience, if they had any concerns about the enquirer’s understanding, the time the call was received, and remuneration and Information Technology (IT) issues. Both Chief Pharmacists and on-call pharmacists identified that training mainly consisted of operational issues, with on-call pharmacists believing a greater role could be played by MI staff in this training. Drug administration and ‘medication safety check’ were the main types of medicines advice questions sought out of hours. Chief Pharmacists stated on-call pharmacy services were well advertised but doctors and nurses seemed unaware of its provision and means of access; on-call pharmacists perceived this to be due to a lack of promotion. Access to information out of hours, particularly patients’ drug and clinical information, by on-call pharmacists was a barrier to providing medicines advice. This is the first insight into the national landscape of on-call pharmacy services. There is a clear role for MI services to support on-call pharmacy services, and national standards should be developed for provision, information accessibility, documentation and training. National pharmacy policy makers could also consider structured training, repeated on a regular basis, for all on-call pharmacists

Development of reverse-transcription PCR techniques to analyse the density and sex ratio of gametocytes in genetically diverse Plasmodium chabaudi infections

We have developed cross-genotype and genotype-specific quantitative reverse-transcription PCR (qRT-PCR) assays to detect and quantify the number of parasites, transmission stages (gametocytes) and male gametocytes in blood stage Plasmodium chabaudi infections. Our cross-genotype assays are reliable, repeatable and generate counts that correlate strongly (R(2)s > 90%) with counts expected from blood smears. Our genotype-specific assays can distinguish and quantify different stages of genetically distinct parasite clones (genotypes) in mixed infections and are as sensitive as our cross-genotype assays. Using these assays we show that gametocyte density and gametocyte sex ratios vary during infections for two genetically distinct parasite lines (genotypes) and present the first data to reveal how sex ratio is affected when each genotype experiences competition in mixed-genotype infections. Successful infection of mosquito vectors depends on both gametocyte density and their sex ratio and we discuss the implications of competition in genetically diverse infections for transmission success

Culling-Induced Changes in Badger (Meles meles) Behaviour, Social Organisation and the Epidemiology of Bovine Tuberculosis

In the UK, attempts since the 1970s to control the incidence of bovine tuberculosis (bTB) in cattle by culling a wildlife host, the European badger (Meles meles), have produced equivocal results. Culling-induced social perturbation of badger populations may lead to unexpected outcomes. We test predictions from the ‘perturbation hypothesis’, determining the impact of culling operations on badger populations, movement of surviving individuals and the influence on the epidemiology of bTB in badgers using data dervied from two study areas within the UK Government's Randomised Badger Culling Trial (RBCT). Culling operations did not remove all individuals from setts, with between 34–43% of badgers removed from targeted social groups. After culling, bTB prevalence increased in badger social groups neighbouring removals, particularly amongst cubs. Seventy individual adult badgers were fitted with radio-collars, yielding 8,311 locational fixes from both sites between November 2001 and December 2003. Home range areas of animals surviving within removed groups increased by 43.5% in response to culling. Overlap between summer ranges of individuals from Neighbouring social groups in the treatment population increased by 73.3% in response to culling. The movement rate of individuals between social groups was low, but increased after culling, in Removed and Neighbouring social groups. Increased bTB prevalence in Neighbouring groups was associated with badger movements both into and out of these groups, although none of the moving individuals themselves tested positive for bTB. Significant increases in both the frequency of individual badger movements between groups and the emergence of bTB were observed in response to culling. However, no direct evidence was found to link the two phenomena. We hypothesise that the social disruption caused by culling may not only increase direct contact and thus disease transmission between surviving badgers, but may also increase social stress within the surviving population, causing immunosuppression and enhancing the expression of disease

ENU Mutagenesis Reveals a Novel Phenotype of Reduced Limb Strength in Mice Lacking Fibrillin 2

Background: Fibrillins 1 (FBN1) and 2 (FBN2) are components of microfibrils, microfilaments that are present in many connective tissues, either alone or in association with elastin. Marfan's syndrome and congenital contractural arachnodactyly (CCA) result from dominant mutations in the genes FBN1 and FBN2 respectively. Patients with both conditions often present with specific muscle atrophy or weakness, yet this has not been reported in the mouse models. In the case of Fbn1, this is due to perinatal lethality of the homozygous null mice making measurements of strength difficult. In the case of Fbn2, four different mutant alleles have been described in the mouse and in all cases syndactyly was reported as the defining phenotypic feature of homozygotes.Methodology/Principal Findings: As part of a large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified a mouse mutant, Mariusz, which exhibited muscle weakness along with hindlimb syndactyly. We identified an amber nonsense mutation in Fbn2 in this mouse mutant. Examination of a previously characterised Fbn2-null mutant, Fbn2(fp), identified a similar muscle weakness phenotype. The two Fbn2 mutant alleles complement each other confirming that the weakness is the result of a lack of Fbn2 activity. Skeletal muscle from mutants proved to be abnormal with higher than average numbers of fibres with centrally placed nuclei, an indicator that there are some regenerating muscle fibres. Physiological tests indicated that the mutant muscle produces significantly less maximal force, possibly as a result of the muscles being relatively smaller in Mariusz mice.Conclusions: These findings indicate that Fbn2 is involved in integrity of structures required for strength in limb movement. As human patients with mutations in the fibrillin genes FBN1 and FBN2 often present with muscle weakness and atrophy as a symptom, Fbn2-null mice will be a useful model for examining this aspect of the disease process further

Population Structure Shapes Copy Number Variation in Malaria Parasites.

If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size (Ne) than from populations with a small Ne. Malaria parasites (Plasmodium falciparum) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in seven countries in Africa, South East Asia and South America using a high-density single-nucleotide polymorphism/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from <500 bp to 59 kb, as well as 10,107 flanking, biallelic single-nucleotide polymorphisms. Overall, CNVs were rare, small, and skewed toward low frequency variants, consistent with the deleterious model. Relative to African and South East Asian populations, CNVs were significantly more common in South America, showed significantly less skew in allele frequencies, and were significantly larger. On this background of low frequency CNV, we also identified several high-frequency CNVs under putative positive selection using an FST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1, and several other CNVs (e.g., DNA helicase and three conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen

A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy

Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l) gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease

Smoking Cessation Intervention for Severe Mental Ill Health Trial (SCIMITAR+) : study protocol for a randomised controlled trial

BACKGROUND: Smoking is highly prevalent among people who have experience of severe mental ill health, contributing to their poor physical health. Despite the 'culture' of smoking in mental health services, people with severe mental ill health often express a desire to quit smoking; however, the services currently available to aid quitting are those which are widely available to the general population and may not be suitable or effective for people with severe mental ill health. The aim of this study is to explore the effectiveness and cost-effectiveness of a bespoke smoking-cessation intervention specifically targeted at people with severe mental ill health. METHODS/DESIGN: SCIMITAR+ is a multicentre, pragmatic, two-arm, parallel-group, individually randomised controlled trial. We aim to recruit 400 participants aged 18 years and above with a documented diagnosis of bipolar disorder, schizophrenia or schizoaffective disorder who smoke. Potentially eligible participants identified in primary or secondary care will be screened, and baseline data collected. Eligible, consenting participants will be randomly allocated to one of two groups. In the intervention arm, the participant will be assigned a mental health professional trained to deliver smoking-cessation interventions who will work with the participant and participant's GP or mental health specialist to provide an individually tailored smoking-cessation service. The comparator arm will be usual care - following current NICE guidelines for smoking cessation, in line with general guidance that is offered to all smokers, with no specific adaptation or enhancement in relation to severe mental ill health. The primary outcome will be self-reported smoking cessation at 12 months verified by expired carbon monoxide (CO) measurement. Secondary outcome measures include Body Mass Index at 12 months, the Fagerström Test for Nicotine Dependence, Motivation to Quit questionnaire, SF-12, PHQ-9, GAD-7, EQ-5D-5 L, and health service utilisation at 6 and 12 months. The economic evaluation at 12 months will be conducted in the form of an incremental cost-effectiveness analysis. DISCUSSION: SCIMITAR+ trial is the largest trial to our knowledge to investigate the effectiveness of a bespoke smoking-cessation service for people with severe mental ill health. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number, ISRCTN72955454 . Registered on 16 January 2015

SLC2A9 Is a High-Capacity Urate Transporter in Humans

Serum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man