Drug administration guides in dysphagia

Aim: The aim of this evaluation was to evaluate the use of Individualised Medication Administration Guides (IMAGs) for patients with dysphagia on one stroke ward over a 6month period. Background: Patients with dysphagia (PWD) are more likely to suffer an administration error than patients without swallowing difficulties. To both standardise and improve medicines administration to patients with dysphagia I-MAGs were introduced on one stroke ward over a 6 month period. Methods: A software package supported with data on current national guidelines on the administration of medicines to PWD was designed by a specialised pharmacist in dysphagia to enable him to create individualised medication administration guides for patients with dysphagia which stated how each medicine should be optimally prepared and administered. On completion of the pilot service a questionnaire was given to all nurses, pharmacist and speech and language therapists who had experienced the I-MAGs. All the professionals received the same questionnaire but questions relevant only to their practice were added to the nurse’s questionnaire. Results: Of 26 Healthcare professionals (HCPs) approached, 19 returned completed questionnaires. Higher variability was found in the 13 responses from the nurse respondents than in the ones from the 3 pharmacist and the 3 SALTs. 8 (61%) of the nurses felt more confident in their practice when I-MAGs were in place. 10 (76%) of the nurses admitted that the guides could sometimes increase the time of the administration, but saw that it made practice safer. All the pharmacists considered the recommendations in the guides useful and all the respondents with the exception of one nurse (12:13) would like this service to continue. Conclusion: I-MAGs were well received on the ward and they support individualised care for patients with dysphagia. But the guides needed additional pharmacist input and greater nursing time. Research to determine the cost effectiveness of I-MAGs is needed.

Implementation of individualised medication administration guides for patients with dysphagia: Results from a pilot controlled trial

Introduction Patients with dysphagia (PWDs) have been shown to be four times more likely to suffer medication administration errors (MAEs).1 2 Individualised medication administration guides (I-MAGs) which outline how each formulation should be administered, have been developed to standardise medication administration by nurses on the ward and reduce the likelihood of errors. This pilot study aimed to determine the recruitment rates, estimate effect on errors and develop the intervention to design a future full scale randomised controlled trial to determine the costs and effects of I-MAG implementation. Ethical approval was granted by local ethics committee. Method Software was developed to enable I-MAG production (based on current best practice)3 4 for all PWDs on two care of the older person wards admitted during a six month period from January to July 2011. I-MAGs were attached to the medication administration record charts to be utilised by nurses when administering medicines. Staff training was provided for all staff on the intervention wards. Two care of the older person wards in the same hospital were used for control purposes. All patients with dysphagia were recruited for follow up purposes at discharge. Four ward rounds at each intervention and control ward were observed pre and post I-MAG implementation to determine the level of medication administration errors. NHS ethical approval for the study was obtained. Results 164 I-MAGs were provided for 75 patients with dysphagia (PWDs) in the two intervention wards. At discharge, 23 patients in the intervention wards and 7 patients in the control wards were approached for recruitment of which 17 (74%) & 5 (71.5%) respectively consented. Discussion Recruitment rates were low on discharge due to the dysphagia remitting during hospitalisation. The introduction of the I-MAG demonstrated no effect on the quality of administration on the intervention ward and interestingly practice improved on the control ward. The observation of medication rounds at least one month post I-MAG removal may have identified a reversal to normal practice and ideally observations should have been undertaken with I-MAGs in place. Identification of the reason for the improvement in the control ward is warranted.

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10−14, odds ratio = 0.86, 95% confidence interval = 0.82–0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.

Inability to swallow tablets is common and cause for concern

We naturally chew food before swallowing, but tablets and capsules require a complicated, conscious mechanism to over-ride the need to chew and the gag reflex, designed to eject foodstuffs that are not adequately chewed...

Inappropriate formulation choices in the administration of medication to elderly patients with dysphagia in nursing homes

Inappropriate food or medication texture in patients with dysphagia is the most significant risk factor for pneumonia. Dysphagia is prevalent within care homes for the older person as it is largely found in conditions associated with ageing. This study was designed to determine the appropriateness of medication formulation choices in elderly patients with dysphagia in care homes.

Nurses’ views on the implementation of Individualised Medication Administration Guides in patients with dysphagia in care homes

As conditions such as stroke, cancer, Parkinson's disease and Huntingdon's chorea are commonly found in care homes between 15% and 30% of residents in care homes have been found to have difficulties in swallowing their medicines.To address the difficulties associated with administering medicines to patients who cannot swallow (with dysphagia), Individualised Medication Administration Guides (I-MAGs) were introduced by a specialised pharmacist in Care for Elderly wards in a general hospital in East Anglia. The guides contained detailed information about how to administer each medication and they were individualised to the needs of the patient. The I-MAGs were printed in green forms and attached to the medication chart in order to be used in conjunction with it. The ward nurses reported an increase in their confidence when administering medication when I-MAGs were present in the ward. Some patients with I-MAG were discharged to care homes where the I-MAG might have been equally useful. However, the design of such guides is not known to be suitable for care homes environment where they have never been used before. This study aims to explore the opinions of nurses and carers within care homes on the relevance and acceptability of individualised medication administration guides for patients with dysphagia (PWD).

Medicines related dysphagia in primary care: The prevalence of and impact on community pharmacists

Dysphagia is a common and problematic symptom characterised by varying degrees of difficulty swallowing food, fluids and medicines of differing consistencies. International primary care based studies have identified that between 1 in 4 and 1 in 5 patients have some form of dysphagia, it can affect medicines taking behaviour and healthcare professionals are largely unaware of this1,2. Similar research has not been undertaken in the UK. Adherence related pharmacy based services in the UK provide an opportunity for community pharmacists to identify the problem and facilitate better medicines use. The aim of this pilot study was to estimate the level of patient reported dysphagia in older persons using community pharmacies in the UK, describe how it affects their medicine taking behaviour and identify whether advanced pharmacy services are related to improved awareness of this.

ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients

The association of endoplasmic reticulum aminopeptidase 2 (ERAP2) with ankylosing spondylitis (AS) was recently described in the large International Genetics of AS Consortium Immunochip study...

Ectopic calcification among families in the Azores: Clinical and radiologic manifestations in families with diffuse idiopathic skeletal hyperostosis and chondrocalcinosis

Objective. Twelve families that were multiply affected with diffuse idiopathic skeletal hyperostosis (DISH) and/or chondrocalcinosis, were identified on the island of Terceira, The Azores, potentially supporting the hypothesis that the 2 disorders share common etiopathogenic factors. The present study was undertaken to investigate this hypothesis. Methods. One hundred three individuals from 12 unrelated families were assessed. Probands were identified from patients attending the Rheumatic Diseases Clinic, Hospital de Santo Espirito, in The Azores. Family members were assessed by rheumatologists and radiologists. Radiographs of all family members were obtained, including radiographs of the dorsolumbar spine, pelvis, knees, elbows, and wrists, and all cases were screened for known features of chondrocalcinosis. Results. Ectopic calcifications were identified in 70 patients. The most frequent symptoms or findings were as follows: axial pain, elbow, knee and metacarpophalangeal (MCP) joint pain, swelling, and/or deformity, and radiographic enthesopathic changes. Elbow and MCP joint periarticular calcifications were observed in 35 and 5 patients, respectively, and chondrocalcinosis was identified in 12 patients. Fifteen patients had sacroiliac disease (ankylosis or sclerosis) on computed tomography scans. Fifty-two patients could be classified as having definite (17%), probable (26%), or possible (31%) DISH. Concomitant DISH and chondrocalcinosis was diagnosed in 12 patients. Pyrophosphate crystals were identified from knee effusions in 13 patients. The pattern of disease transmission was compatible with an autosomal-dominant monogenic disease. The mean age at which symptoms developed was 38 years. Conclusion. These families may represent a familial type of pyrophosphate arthropathy with a phenotype that includes peripheral and axial enthesopathic calcifications. The concurrence of DISH and chondrocalcinosis suggests a shared pathogenic mechanism in the 2 conditions.

Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects

Introduction: A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort. Methods: A total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs). Results: A total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism. Conclusions: We have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease.

Association of IL23R and ERAP1 genes with ankylosing spondylitis in a Portuguese population

Objective: Association between ankylosing spondylitis (AS) and two genes, ERAP1 and IL23R, has recently been reported in North American and British populations. The population attributable risk fraction for ERAP1 in this study was 25%, and for IL23R, 9%. Confirmation of these findings to ERAP1 in other ethnic groups has not yet been demonstrated. We sought to test the association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to AS among a Portuguese population. We also investigated the role of these genes in clinical manifestations of AS, including age of symptom onset, the Bath Ankylosing Spondylitis Disease Activity, Metrology and Functional Indices, and the modified Stoke Ankylosing Spondylitis Spinal Score. Methods: The study was conducted on 358 AS cases and 285 ethnically matched Portuguese healthy controls. AS was defined according to the modified New York Criteria. Genotyping of IL23R and ERAP1 allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests of genotypes as implemented in PLINK for dichotomous and quantitative variables respectively. A meta-analysis for Portuguese and previously published Spanish IL23R data was performed using the StatsDirect® Statistical tools, by fixed and random effects models. Results: A total of 14 nsSNPs markers (8 for IL23R, 5 for ERAPl, 1 for LN-PEP) were analysed. Three markers (2 for IL23R and 1 for ERAP1) showed significant single-locus disease associations, confirming that the association of these genes with AS in the Portuguese population. The strongest associated SNP in IL23R was rs1004819 (OR=1.4, p=0.0049), and in ERAP1 was rs30187 (OR=1.26, p=0.035). The population attributable risk fractions in the Portuguese population for these SNPs are 11% and 9.7% respectively. No association was seen with any SNP in LN-PEP, which flanks ERAP1 and was associated with AS in the British population. No association was seen with clinical manifestations of AS. Conclusions: These results show that IL23R and ERAP1 genes are also associated with susceptibility to AS in the Portuguese population, and that they contribute a significant proportion of the population risk for this disease.

Spectrum of ankylosing spondylitis in Portugal. Development of BASDAI, BASFI, BASMI and mSASSS reference centile charts

The availability of population-specific normative data regarding disease severity measures is essential for patient assessment. The goals of the current study were to characterize the pattern of ankylosing spondylitis (AS) in Portuguese patients and to develop reference centile charts for BASDAI, BASFI, BASMI and mSASSS, the most widely used assessment tools in AS. AS cases were recruited from hospital outpatient clinics, with AS defined according to the modified New York criteria. Demographic and clinical data were recorded. All radiographs were evaluated by two independent experienced readers. Centile charts for BASDAI, BASFI, BASMI and mSASSS were constructed for both genders, using generalized linear models and regression models with duration of disease as independent variable. A total of 369 patients (62.3% male, mean ± (SD) age 45.4 ± 13.2 years, mean ± (SD) disease duration 11.4 ± 10.5 years, 70.7% B27-positive) were included. Family history of AS in a first-degree relative was reported in 17.6% of the cases. Regarding clinical disease pattern, at the time of assessment 42.3% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopatic disease. Anterior uveitis (33.6%) was the most common extra-articular manifestation. The centile charts suggest that females reported greater disease activity and more functional impairment than males but had lower BASMI and mSASSS scores. Data collected through this study provided a demographic and clinical profile of patients with AS in Portugal. The development of centile charts constitutes a useful tool to assess the change of disease pattern over time and in response to therapeutic interventions.

Postglacial Early Permian (late Sakmarian-early Artinskian) shallow-marine carbonate deposition along a 2000 km transect from Timor to west Australia

Late Sakmarian to early Artinskian (Early Permian) carbonate deposition was widespread in the marine intracratonic rift basins that extended into the interior of Eastern Gondwana from Timor in the north to the northern Perth Basin in the south. These basins spanned about 20° of paleolatitude (approximately 35°S to 55°S). This study describes the type section of the Maubisse Limestone in Timor-Leste, and compares this unit with carbonate sections in the Canning Basin (Nura Nura Member of the Poole Sandstone), the Southern Carnarvon Basin (Callytharra Formation) and the northern Perth Basin (Fossil Cliff Member of the Holmwood Shale). The carbonate units have no glacial influence and formed part of a major depositional cycle that, in the southern basins, overlies glacially influenced strata and lies a short distance below mudstone containing marine fossils and scattered dropstones (perhaps indicative of sea ice). In the south marine conditions became more restricted and were replaced by coal measures at the top of the depositional sequence. In the north, the carbonate deposits are possibly bryozoan–crinoidal mounds; whereas in the southern basins they form laterally continuous relatively thin beds, deposited on a very low-gradient seafloor, at the tops of shale–limestone parasequences that thicken upward in parasequence sets. All marine deposition within the sequence took place under very shallow (inner neritic) conditions, and the limestones have similar grain composition. Bryozoan and crinoidal debris dominate the grain assemblages and brachiopod shell fragments, foraminifera and ostracod valves are usually common. Tubiphytes ranged as far south as the Southern Carnarvon Basin, albeit rarely, but is more common to the north. Gastropod and bivalve shell debris, echinoid spines, solitary rugose corals and trilobite carapace elements are rare. The uniformity of the grain assemblage and the lack of tropical elements such as larger fusulinid foraminifera, colonial corals or dasycladacean algae indicate temperate marine conditions with only a small increase in temperature to the north. The depositional cycle containing the studied carbonate deposits represents a warmer phase than the preceding glacially influenced Asselian to early Sakmarian interval and the subsequent cool phase of the “mid” Artinskian that is followed by significant warming during the late Artinskian–early Kungurian. The timing of cooler and warmer intervals in the west Australian basins seems out-of-phase with the eastern Australian succession, but this may be a problem of chronostratigraphic miscorrelation due to endemic faunas and palynofloras.

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.

Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.