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"Busby, John"
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bioclim: the first species distribution modelling package, its early applications and relevance to most current MaxEnt studies
Aim Interest in species distribution models (SDMs) and related niche studies has increased dramatically in recent years, with several books and reviews being prepared since 2000. The earliest SDM studies are dealt with only briefly even in the books. Consequently, many researchers are unaware of when the first SDM software package (bioclim) was developed and how a broad range of applications using the package was explored within the first 8 years following its release. The purpose of this study is to clarify these early developments and initial applications, as well as to highlight bioclim's continuing relevance to current studies. Location Mainly Australia and New Zealand, but also some global applications. Methods We outline the development of the bioclim package, early applications (1984–1991) and its current relevance. Results bioclim was the first SDM package to be widely used. Early applications explored many of the possible uses of SDMs in conservation biogeography, such as quantifying the environmental niche of species, identifying areas where a species might be invasive, assisting conservation planning and assessing the likely impacts of climate change on species distributions. Main conclusions Understanding this pioneering work is worthwhile as bioclim was for many years one of the leading SDM packages and remains widely used. Climate interpolation methods developed for bioclim were used to create the WorldClim database, the most common source of climate data for SDM studies, and bioclim variables are used in about 76% of recent published MaxEnt analyses of terrestrial ecosystems. Also, some of the bioclim studies from the late 1980s, such as measuring niche (both realized and fundamental) and assessing possible impacts of climate change, are still highly relevant to key conservation biogeography issues.
Journal Article
Remotely Monitored Therapy and Nitric Oxide Suppression Identifies Nonadherence in Severe Asthma
Poor adherence is common in difficult-to-control asthma. Distinguishing patients with difficult-to-control asthma who respond to inhaled corticosteroids (ICS) from refractory asthma is an important clinical challenge.
Suppression of fractional exhaled nitric oxide (Fe
) with directly observed ICS therapy over 7 days can identify nonadherence to ICS treatment in difficult-to-control asthma. We examined the feasibility and utility of Fe
suppression testing in routine clinical care within UK severe asthma centers using remote monitoring technologies.
A web-based interface with integrated remote monitoring technology was developed to deliver Fe
suppression testing. We examined the utility of Fe
suppression testing to demonstrate ICS responsiveness and clinical benefit on electronically monitored treatment with standard high-dose ICS and long-acting β
-agonist treatment.
Clinical response was assessed using the Asthma Control Questionnaire-5, spirometry, and biomarker measurements (Fe
and peripheral blood eosinophil count). Of 250 subjects, 201 completed the test with 130 positive suppression tests. Compared with a negative suppression test, a positive test identified a Fe
-low population when adherent with ICS/long-acting β
-agonist (median, 26 ppb [interquartile range, 16-36 ppb] vs. 43 ppb [interquartile range, 38-73 ppb]) with significantly greater FEV
% (mean, 88.2 ± 16.4 vs. 74.1 ± 20.9; P < 0.01). Asthma Control Questionnaire-5 improved significantly in both groups (positive test: mean difference, -1.2; 95% confidence interval, -0.9 to -1.5; negative test: mean difference, -0.9; 95% confidence interval, -0.4 to -1.3).
Remote Fe
suppression testing is an effective means of identifying nonadherence to ICS in subjects with difficult-to-control asthma and the substantial population of subjects who derive important clinical benefits from optimized ICS/long-acting β
-agonist treatment.
Journal Article
The idea of a human rights museum
\"The Idea of a Human Rights Museum is the first book to examine the formation of the Canadian Museum for Human Rights and to situate the museum within the context of the international proliferation of such institutions. Sixteen essays consider the wider political, cultural and architectural contexts within which the museum physically and conceptually evolved drawing comparisons between the CMHR and institutions elsewhere in the world that emphasize human rights and social justice. This collection brings together authors from diverse fields--law, cultural studies, museum studies, sociology, history, political science, and literature--to critically assess the potentials and pitfalls of human rights education through \"ideas\" museums. Accessible, engaging, and informative, the collection's essays will encourage museum-goers to think more deeply about the content of human rights exhibits.\"-- Provided by publisher.
Book
Selective serotonin reuptake inhibitor use and breast cancer survival: a population-based cohort study
Background
Nearly 50% of breast cancer patients suffer from depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for depression, have been implicated in breast cancer development through increased prolactin levels and tamoxifen metabolism inhibition. Previous studies of breast cancer progression have focused on tamoxifen users, or have been limited by their small sample size and methodology. Therefore, we used UK population-based data to more robustly investigate the association between SSRI use and cancer-specific mortality.
Methods
A cohort of patients with newly-diagnosed breast cancer between 1998 and 2012 was selected from English cancer registries and linked to prescription records from the Clinical Practice Research Datalink, and to death records from the Office for National Statistics. We used Cox regression models to calculate hazard ratios (HRs) comparing mortality between post-diagnostic SSRI users and non-users (using time-dependant covariates), after adjusting for demographics, comorbidities and pre-diagnosis use of hormone replacement therapy or oral contraceptives. We conducted several additional analyses to assess causality.
Results
Our cohort included 23,669 breast cancer patients, of which 2672 used SSRIs and 3053 died due to their breast cancer during follow-up. After adjustment, SSRI users had higher breast cancer-specific mortality than non-users (HR = 1.27; 95% confidence interval (CI) 1.16, 1.40). However, this association was attenuated when restricting to patients with a prior history of depression (HR = 1.14; 95% CI 0.98, 1.33), and when comparing to users of other antidepressant medications (HR = 1.06; 95% CI 0.93, 1.20). There was some evidence of higher mortality among long-term SSRI users, even when restricting to patients with prior depression (HR = 1.54; 95% CI 1.03, 2.29).
Conclusions
In this large breast cancer cohort, SSRI use was associated with a 27% increase in breast cancer mortality. The cause of this is unknown; however, confounding by indication seems likely as it was largely attenuated when restricting to patients with prior depression, or when comparing SSRIs to other antidepressant medications. Clinicians should not be unduly concerned when prescribing SSRIs to breast cancer patients, but the increase in mortality among long-term SSRI users warrants further investigation.
Journal Article
Calculating hospital length of stay using the Hospital Episode Statistics; a comparison of methodologies
Background
Accurate calculation of hospital length of stay (LOS) from the English Hospital Episode Statistics (HES) is important for a wide range of audit and research purposes. The two methodologies which are commonly used to achieve this differ in their accuracy and complexity. We compare these methods and make recommendations on when each is most appropriate.
Methods
We calculated LOS using continuous inpatient spells (CIPS), which link care spanning across multiple hospitals, and spells, which do not, for six conditions with short (dyspepsia or other stomach function, ENT infection), medium (dehydration and gastroenteritis, perforated or bleeding ulcer), and long (stroke, fractured proximal femur) average LOS. We examined how inter-area comparisons (i.e. benchmarking) and temporal trends differed. We defined a classification system for spells and explored the causes of differences.
Results
Stroke LOS was 16.5 days using CIPS but 24% (95% CI: 23, 24) lower, at 12.6 days, using spells. Smaller differences existed for shorter-LOS conditions including dehydration and gastroenteritis (4.5 vs. 4.2 days) and ENT infection (0.9 vs. 0.8 days). Typical patient pathways differed markedly between areas and have evolved over time. One area had the third shortest stroke LOS (out of 151) using spells but the fourth longest using CIPS. These issues were most profound for stroke and fractured proximal femur, as patients were frequently transferred to a separate hospital for rehabilitation, however important disparities also existed for conditions with simpler secondary care pathways (e.g. ENT infections, dehydration and gastroenteritis).
Conclusions
Spell-based LOS is widely used by researchers and national reporting organisations, including the Health and Social Care Information Centre, however it can substantially underestimate the time patients spend in hospital. A widespread shift to a CIPS methodology is required to improve the quality of LOS estimates and the robustness of research and benchmarking findings. This is vital when investigating clinical areas with typically long, complex patient pathways. Researchers should ensure that their LOS calculation methodology is fully described and explicitly acknowledge weaknesses when appropriate.
Journal Article
Real World Biologic Use and Switch Patterns in Severe Asthma: Data from the International Severe Asthma Registry and the US CHRONICLE Study
International registries provide opportunities to describe use of biologics for treating severe asthma in current clinical practice. Our aims were to describe real-life global patterns of biologic use (continuation, switches, and discontinuations) for severe asthma, elucidate reasons underlying these patterns, and examine associated patient-level factors.
This was a historical cohort study including adults with severe asthma enrolled into the International Severe Asthma Registry (ISAR; http://isaregistries.org, 2015-2020) or the CHRONICLE Study (2018-2020) and treated with a biologic. Eleven countries were included (Bulgaria, Canada, Denmark, Greece, Italy, Japan, Kuwait, South Korea, Spain, UK, and USA). Biologic utilization patterns were defined: 1) continuing initial biologic; 2) stopping biologic treatment; or 3) switching to another biologic. Reasons for discontinuation/switching were recorded and comparisons drawn between groups.
A total of 3531 patients were included. Omalizumab was the most common initial biologic in 2015 (88.2%) and benralizumab in 2019 (29.6%). Most patients (79%; 2791/3531) continued their first biologic; 10.2% (356/3531) stopped; 10.8% (384/3531) switched. The most frequent first switch was from omalizumab to an anti-IL-5/5R (49.6%; 187/377). The most common subsequent switch was from one anti-IL-5/5R to another (44.4%; 20/45). Insufficient efficacy and/or adverse effects were the most frequent reasons for stopping/switching. Patients who stopped/switched were more likely to have a higher baseline blood eosinophil count and exacerbation rate, lower lung function, and greater health care resource utilization.
The description of real-life patterns of continuing, stopping, or switching biologics enhances our understanding of global biologic use. Prospective studies involving structured switching criteria could ascertain optimal strategies to identify patients who may benefit from switching.
Journal Article
An examination of factorial invariance of the Asthma Control Questionnaire among adults with severe asthma
The Asthma Control Questionnaire (ACQ) is used to assess asthma symptom control. The relationship between the questionnaire items and symptom control has not been fully studied in severe asthmatic patients, and its validity for making comparisons between subgroups of patients is unknown.
Data was obtained from patients in the United Kingdom Severe Asthma Registry whose symptom control was assessed using the five-item ACQ (ACQ5) (n = 2,951). Confirmatory factor analysis determined whether a latent factor for asthma symptom control, as measured by the ACQ5, was consistent with the data. Measurement invariance was examined in relation to ethnicity, sex and age; this included testing for approximate measurement invariance using Bayesian Structural Equation Modelling (BSEM). The fitted models were used to estimate the internal consistency reliability of the ACQ5. Invariance of factor means across subgroups was assessed.
A one-factor construct with residual correlations for the ACQ5 was an excellent fit to the data in all subgroups (Root Mean Square Error Approximation 0.03 [90%CI 0.02,0.05], p-close fit 0.93, Comparative Fit Index 1.00, Tucker Lewis Index 1.00}. Expected item responses were consistent for Caucasian and non-Caucasian patients with the same absolute level of symptom control. There was some evidence that females and younger adults reported wakening more frequently during the night than males and older adults respectively with the same absolute level of symptom control (p<0.001). However approximate measurement invariance was tenable and any failure to observe strong measurement invariance had minimal impact when comparing mean levels of asthma symptom control between patients of different sexes or ages. Average levels of asthma symptom control were lower for non-Caucasians (p = 0.001), females (p<0.01)and increased with age (p<0.01). Reliability of the instrument was high (over 88%) in all subgroups studied.
The ACQ5 is informative in comparing levels of symptom control between severe asthmatic patients of different ethnicities, sexes and ages. It is important that analyses are replicated in other severe asthma registries to determine whether measurement invariance is observed.
Journal Article
International severe asthma registry (ISAR): protocol for a global registry
Background
Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour.
Methods
ISAR is a multi-disciplinary initiative benefitting from the combined experience of the ISAR Steering Committee (ISC; comprising 47 clinicians and researchers across 29 countries, who have a special interest and/or experience in severe asthma management or establishment and maintenance of severe asthma registries) in collaboration with scientists and experts in database management and communication. Patients (≥18 years old) receiving treatment according to the 2018 definitions of the Global Initiative for Asthma (GINA) Step 5 or uncontrolled on GINA Step 4 treatment will be included. Data will be collected on a core set of 95 variables identified using the Delphi method. Participating registries will agree to provide access to and share standardised anonymous patient-level data with ISAR. ISAR is a registered data source on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. ISAR’s collaborators include Optimum Patient Care, the Respiratory Effectiveness Group (REG) and AstraZeneca. ISAR is overseen by the ISC, REG, the Anonymised Data Ethics & Protocol Transparency Committee and the ISAR operational committee, ensuring the conduct of ethical, clinically relevant research that brings value to all key stakeholders.
Conclusions
ISAR aims to offer a rich source of real-life data for scientific research to understand and improve disease burden, treatment patterns and patient outcomes in severe asthma. Furthermore, the registry will provide an international platform for research collaboration in respiratory medicine, with the overarching aim of improving primary and secondary care of adults with severe asthma globally.
Journal Article