Predictors of adherence to treatment in bronchiestasis

Objectives

We aimed to determine if beliefs about treatment, clinical factors and quality of life predicted adherence to treatment in patients with bronchiectasis.

Methods

We recruited participants with confirmed bronchiectasis to a one-year study. We calculated adherence to treatment using medication possession ratios and self-report. Baseline Beliefs about Medicines, clinical, demographic and Quality of Life Questionnaire-Bronchiectasis data were collected. We used logistic regression to determine predictors of adherence to treatment during the subsequent year.

Results

Seventy-five participants were recruited. Beliefs about harm, age and total number of prescribed medications were predictors of adherence to inhaled antibiotics. Concerns about medication, age and Quality of Life Questionnaire-Bronchiectasis Treatment Burden were predictors of adherence to other respiratory medicines. Beliefs about necessity of airway clearance and age were predictors of adherence to airway clearance.

Conclusion

Beliefs about treatment, age, number of prescribed medications and perceived treatment burden predicted subsequent adherence in bronchiectasis, thereby, providing potential targets for future interventions in this population. Clinicians can use these data to identify patients with bronchiectasis who might be at risk of non-adherence i.e. those who are younger, have concerns about medications, who do not think airway clearance is necessary or who are prescribed numerous medications.

Developed turbulence and nonlinear amplification of magnetic fields in laboratory and astrophysical plasmas

The visible matter in the universe is turbulent and magnetized. Turbulence in galaxy clusters is produced by mergers and by jets of the central galaxies and believed responsible for the amplification of magnetic fields. We report on experiments looking at the collision of two laser-produced plasma clouds, mimicking, in the laboratory, a cluster merger event. By measuring the spectrum of the density fluctuations, we infer developed, Kolmogorov-like turbulence. From spectral line broadening, we estimate a level of turbulence consistent with turbulent heating balancing radiative cooling, as it likely does in galaxy clusters. We show that the magnetic field is amplified by turbulent motions, reaching a nonlinear regime that is a precursor to turbulent dynamo. Thus, our experiment provides a promising platform for understanding the structure of turbulence and the amplification of magnetic fields in the universe.

Explaining variation in cancer survival between 11 jurisdictions in the International Cancer Benchmarking Partnership: a primary care vignette survey

OBJECTIVES: The International Cancer Benchmarking Partnership (ICBP) is a collaboration between 6 countries and 12 jurisdictions with similar primary care-led health services. This study investigates primary care physician (PCP) behaviour and systems that may contribute to the timeliness of investigating for cancer and subsequently, international survival differences.

DESIGN: A validated survey administered to PCPs via the internet set out in two parts: direct questions on primary care structure and practice relating to cancer diagnosis, and clinical vignettes, assessing management of scenarios relating to the diagnosis of lung, colorectal or ovarian cancer.

PARTICIPANTS: 2795 PCPs in 11 jurisdictions: New South Wales and Victoria (Australia), British Columbia, Manitoba, Ontario (Canada), England, Northern Ireland, Wales (UK), Denmark, Norway and Sweden.

PRIMARY AND SECONDARY OUTCOME MEASURES: Analysis compared the cumulative proportion of PCPs in each jurisdiction opting to investigate or refer at each phase for each vignette with 1-year survival, and conditional 5-year survival rates for the relevant cancer and jurisdiction. Logistic regression was used to explore whether PCP characteristics or system differences in each jurisdiction affected the readiness to investigate.

RESULTS: 4 of 5 vignettes showed a statistically significant correlation (p<0.05 or better) between readiness to investigate or refer to secondary care at the first phase of each vignette and cancer survival rates for that jurisdiction. No consistent associations were found between readiness to investigate and selected PCP demographics, practice or health system variables.

CONCLUSIONS: We demonstrate a correlation between the readiness of PCPs to investigate symptoms indicative of cancer and cancer survival rates, one of the first possible explanations for the variation in cancer survival between ICBP countries. No specific health system features consistently explained these findings. Some jurisdictions may consider lowering thresholds for PCPs to investigate for cancer-either directly, or by specialist referral, to improve outcomes.

Relationships between Religion and Two Forms of Homonegativity in Europe—A Multilevel Analysis of Effects of Believing, Belonging and Religious Practice

This paper examines relationships between religion and two forms of homonegativity
across 43 European countries using a bivariate response binary logistic multilevel model. The model analyzes effects of religious believing, belonging and practice on two response variables: a) a moral rejection of homosexuality as a practice and b) intolerance toward homosexuals as a group. The findings indicate that both forms of homonegativity are prevalent in Europe. Traditional doctrinal religious believing (belief in a personal God) is positively related to a moral rejection of homosexuality but to a much lesser extent associated with intolerance toward homosexuals as a group. Members of religious denominations are more likely than non-members to reject homosexuality as morally wrong and to reject homosexuals as neighbors. The analysis found significant differences between denominations that are likely context-dependent. Attendance at religious services is positively related to homonegativity in a majority of countries. The findings vary considerably across countries: Religion is more strongly related to homonegativity in Western than in Eastern Europe. In the post-soviet countries homonegativity appears to be largely a secular phenomenon. National contexts of high religiosity, high perceived government corruption, high income inequality and shortcomings in the implementation of gay rights in the countries’ legislations are statistically related to higher levels of both moralistic homonegativity and intolerance toward homosexuals as a group.

Biosecurity and Emerging Plant Health Problems in Turf Production and Maintenance

Recent research has supported the view that the distributions of many pests and diseases have extended towards higher latitudes over the last 50 years. Probably driven by a combination of climate change and trade, this extension to the ranges of hundreds of plant pathogens may have serious implications not only for agriculture, horticulture and forestry, but also for turf production &maintenance. Here we review our data relating to the current status of three emerging pest and disease problems across North West Europe (rapid blight, Labyrinthula sp. , the root knot nematode, Meloidogyne minor and the pacific stem gall nematode, Anguina pacificae ) and discuss the factors which may be involved in their spread and increasing impact on the turf industry. With turf production and maintenance becoming an increasingly international business, we ask if biosecurity and the promotion of plant health in turf production fields and associated sport facilities should be a greater priority for the industry. We also examine if a lack of effective biosecurity measures in the materials supply chain has led to increased plant health problems.

Symposium - Organisational transformation in policing: Leadership and change in extreme contexts

Nearly 4000 people died in Northern Ireland’s long running conflict, 314 of them police officers (Brewer and Magee 1991, Brewer 1996, Hennessey 1999, Guelke and Milton-Edwards 2000). The republican and loyalist ceasefires of 1994 were the first significant signal that NI society was moving beyond the ‘troubles’ and towards a normalised political environment. The Belfast (Good Friday) Agreement of 1998 cemented that movement (Hennessey 1999). Policing was a key and seemingly unresolvable element of the conflict, seen as unrepresentative and partisan. Its reform or ‘recasting’ in a new dispensation was an integral part of the conflict transformation endeavour(Ellison 2010). As one of the most controversial elements of the conflicted past, it had remained outside the Agreement and was subject to a specific commission of interest (1999), generally known as the Patten Commission. The Commission’s far reaching proposals included a change of name, badge and uniform, the introduction of 50/50 recruitment (50% Roman Catholic and 50% other), a new focus on human rights, a new district command and headquarter structure, a review of ‘Special Branch’ and covert techniques, a concern for ‘policing with the community’ and a significant voluntary severance process to make room for new recruits, unconnected with the past history of the organisation(Murphy 2013).

This paper reflects upon the first data collection phase of a long term processual study of organisational change within the Royal Ulster Constabulary / Police Service of Northern Ireland. This phase (1996-2002) covers early organisational change initiation (including the pre-change period) and implementation including the instigation of symbolic changes (name, badge, and crest) and structural changes (new HQ structure and District Command structure). It utilises internal documentation including messages from the organisations leaders, interviews with forty key informants (identified through a combination of snow-balling from referrals by initial contacts, and key interviews with significant individuals), as well as external documentation and commentary on public perceptions of the change. Using a processual lens (Langley, Smallman et al. 2013) it seeks to understand this initial change phase and its relative success in a highly politicised environment.

By engaging key individuals internally and externally, setting up a dedicated change team, adopting a non normative, non urgent, calming approach to dissent, communicating in orthodox and unorthodox ways with members, acknowledging the huge emotional strain of letting go of the organisation’s name and all it embodied, and re-emphasising the role of officers as ‘police first’, rather than ‘RUC first’, the organisations leadership remained in control of a volatile and unhappy organisational body and succeeded in moving it on through this initial phase, even while much of the political establishment lambasted them externally. Three years into this change process the organisation had a new name, a new crest, new structures, procedures and was deeply engaged in embedding the joint principles of human rights and community policing within its re-woven fabric. While significant problems remained, the new Police Service of Northern Ireland had successfully begun a long journey to full community acceptance in a post conflict context.

This case illustrates the significant challenges of leading change under political pressure, with external oversight and no space for failure(Hannah, Uhl-Bien et al. 2009). It empirically reflects the reality of change implementation as messy, disruptive and unpredictable and highlights the significance of political skill and contextual understanding to success in the early stages(Buchanan and Boddy 1992). The implications of this for change theory and the practice of change implementation are explored (Eisenhardt and Graebner 2007) and some conclusions drawn about what such an extreme case tells us about change generally and change implementation under pressure.

Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations

Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled 'reservoir' host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers. © 2012 Biek et al.

Prevalence, Nature, Severity and Risk Factors for Prescribing Errors in Hospital Inpatients: Prospective Study in 20 UK Hospitals

Introduction: It has been suggested that doctors in their first year of post-graduate training make a disproportionate number of prescribing errors.

Obkective: This study aimed to compare the prevalence of prescribing errors made by first-year post-graduate doctors with that of errors by senior doctors and non-medical prescribers and to investigate the predictors of potentially serious prescribing errors.

Methods: Pharmacists in 20 hospitals over 7 prospectively selected days collected data on the number of medication orders checked, the grade of prescriber and details of any prescribing errors. Logistic regression models (adjusted for clustering by hospital) identified factors predicting the likelihood of prescribing erroneously and the severity of prescribing errors.

Results: Pharmacists reviewed 26,019 patients and 124,260 medication orders; 11,235 prescribing errors were detected in 10,986 orders. The mean error rate was 8.8 % (95 % confidence interval [CI] 8.6-9.1) errors per 100 medication orders. Rates of errors for all doctors in training were significantly higher than rates for medical consultants. Doctors who were 1 year (odds ratio [OR] 2.13; 95 % CI 1.80-2.52) or 2 years in training (OR 2.23; 95 % CI 1.89-2.65) were more than twice as likely to prescribe erroneously. Prescribing errors were 70 % (OR 1.70; 95 % CI 1.61-1.80) more likely to occur at the time of hospital admission than when medication orders were issued during the hospital stay. No significant differences in severity of error were observed between grades of prescriber. Potentially serious errors were more likely to be associated with prescriptions for parenteral administration, especially for cardiovascular or endocrine disorders.

Conclusions: The problem of prescribing errors in hospitals is substantial and not solely a problem of the most junior medical prescribers, particularly for those errors most likely to cause significant patient harm. Interventions are needed to target these high-risk errors by all grades of staff and hence improve patient safety.

The Cyclin D1 (CCND1) A870G polymorphism predicts clinical outcome to lapatinib and capecitabine in HER2-positive metastatic breast cancer

BACKGROUND: Lapatinib plus capecitabine emerged as an efficacious therapy in metastatic breast cancer (mBC). We aimed to identify germline single-nucleotide polymorphisms (SNPs) in genes involved in capecitabine catabolism and human epidermal receptor signaling that were associated with clinical outcome to assist in selecting patients likely to benefit from this combination.

PATIENTS AND METHODS: DNA was extracted from 240 of 399 patients enrolled in EGF100151 clinical trial (NCT00078572; clinicaltrials.gov) and SNPs were successfully evaluated in 234 patients. The associations between SNPs and clinical outcome were analyzed using Fisher's exact test, Kaplan-Meier curves, log-rank tests, likelihood ratio test within logistic or Cox regression model, as appropriate.

RESULTS: There were significant interactions between CCND1 A870G and clinical outcome. Patients carrying the A-allele were more likely to benefit from lapatinib plus capecitabine versus capecitabine when compared with patients harboring G/G (P = 0.022, 0.024 and 0.04, respectively). In patients with the A-allele, the response rate (RR) was significantly higher with lapatinib plus capecitabine (35%) compared with capecitabine (11%; P = 0.001) but not between treatments in patients with G/G (RR = 24% and 32%, respectively; P = 0.85). Time to tumor progression (TTP) was longer in patients with the A-allele treated with lapatinib plus capecitabine compared with capecitabine (median TTP = 7.9 and 3.4 months; P < 0.001), but not in patients with G/G (median TTP = 6.1 and 6.6 months; P = 0.92).

CONCLUSION: Our findings suggest that CCND1A870G may be useful in predicting clinical outcome in HER2-positive mBC patients treated with lapatinib plus capecitabine.

Agriculture, settlement and society in Early Medieval Ireland

During the early medieval period, Ireland was politically organised into a large number of very small kingdoms. Unlike much of Western Europe, it had not been incorporated into the Roman Empire, and as a consequence, settlement remained exclusively rural in character until the Viking period. Extensive documentary, archaeological, zooarchaeological and macro-plant evidence provides a detailed reconstruction of the livestock and arable economy of the period. Cattle ownership formed the basis of wealth as well as being an indicator of status in society, and this is reflected in its clear dominance of the livestock economy during this period. From the eighth century onwards, however, cereal production appears to grow in importance as subsistence farming gave way to the production of agricultural surplus. This is reflected in cereal diversification and in the construction of watermills and more efficient grain-drying kilns. At the same time, settlement underwent significant changes and the relative importance of cattle in some areas began to decline.

Single nucleotide polymorphisms in the APCS gene influence geographic atrophy secondary to VEGF inhibition therapy in neovascular macular degeneration.

Introduction: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly mostly due to the development of neovascular AMD (nAMD) or geographic atrophy (GA). Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are an effective therapeutic option for nAMD. Following anti-VEGF treatments, increased atrophy of the retinal pigment epithelium (RPE) and choriocapillaries that resembles GA has been reported. We sought to evaluate the underlying genetic influences that may contribute to this process. Methods: We selected 68 single nucleotide polymorphisms (SNPs) from genes previously identified as susceptibility factors in AMD, along with 43 SNPs from genes encoding the VEGF protein and its cognate receptors as this pathway is targeted by treatment. We enrolled 467 consecutive patients (Feb 2009 to October 2011) with nAMD who received anti-VEGF therapy. The acutely presenting eye was designated as the study eye and retinal tomograms graded for macular atrophy at study exit. Statistical analysis was performed using PLINK to identify SNPs with a P value < 0.01. Logistic regression models with macular atrophy as dependent variable were fitted with age, gender, smoking status, common genetic risk factors and the identified SNPs as explanatory variables. Results: Grading for macular atrophy was available in 304 study eyes and 70% (214) were classified as showing macular atrophy. In the unadjusted analysis we observed significant associations between macular atrophy and two independent SNPs in the APCS gene: rs6695377: odds ratio (OR) = 1.98; 95% confidence intervals (CI): 1.23, 3.19; P = 0.004; rs1446965: OR = 2.49, CI: 1.29, 4.82; P = 0.006 and these associations remained significant after adjustment for covariates. Conclusions: VEGF is a mitogen and growth factor for choroidal blood vessels and the RPE and its inhibition could lead to atrophy of these key tissues. Anti-VEGF treatment can interfere with ocular vascular maintenance and may be associated with RPE and choroidal atrophy. As such, these medications, which block the effects of VEGF, may influence the development of GA. The top associated SNPs are found in the APCS gene, a highly conserved glycoprotein that encodes Serum amyloid P (SAP) which opsonizes apoptotic cells. SAP can bind to and activate complement components via binding to C1q, a mechanism by which SAP may remove cellular debris, affecting regulation of the three complement pathways.

Use of bacterial whole-genome sequencing to investigate local persistence and spread in bovine tuberculosis

Mycobacterium bovis is the causal agent of bovine tuberculosis, one of the most important diseases currently facing the UK cattle industry. Here, we use high-density whole genome sequencing (WGS) in a defined sub-population of M. bovis in 145 cattle across 66 herd breakdowns to gain insights into local spread and persistence. We show that despite low divergence among isolates, WGS can in principle expose contributions of under-sampled host populations to M. bovis transmission. However, we demonstrate that in our data such a signal is due to molecular type switching, which had been previously undocumented for M. bovis. Isolates from farms with a known history of direct cattle movement between them did not show a statistical signal of higher genetic similarity. Despite an overall signal of genetic isolation by distance, genetic distances also showed no apparent relationship with spatial distance among affected farms over distances <5 km. Using simulations, we find that even over the brief evolutionary timescale covered by our data, Bayesian phylogeographic approaches are feasible. Applying such approaches showed that M. bovis dispersal in this system is heterogeneous but slow overall, averaging 2 km/year. These results confirm that widespread application of WGS to M. bovis will bring novel and important insights into the dynamics of M. bovis spread and persistence, but that the current questions most pertinent to control will be best addressed using approaches that more directly integrate WGS with additional epidemiological data.

Development of a new welfare assessment protocol for practical application in long-term dog shelters

In many European shelters, dogs may spend many years confined. A poor environment and inappropriate management may lead to a low quality of life. The absence of harmonised European regulatory frameworks defining the minimum requirements for shelter facilities makes the definition of welfare standards for kennelled dogs challenging. Here, a new protocol was developed and tested to help identify the main welfare issues for shelter dogs. Twenty-six indicators were identified including management, resource and animal based measures. Accuracy and interobserver reliability were checked between four assessors. The protocol was applied in 29 shelters (n=1308 dogs) in six European countries. Overall prevalence of poor health conditions was below 10%. Test-retest reliability and validity of the protocol were investigated with encouraging results. A logistic regression was carried out to assess the potential of the protocol as a tool to identify welfare hazards in shelter environments. Inappropriate space allowance, for example, was found to be a risk factor potentially affecting the animal's cleanliness, skin condition and body condition. The protocol was designed to be concise and easy to implement. Systematic data collection could help identify welfare problems that are likely to arise in certain shelter designs and thus determine improvement in animal care standards.