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author:("exworthy, S")
1.  Lymphoma risk in systemic lupus: effects of disease activity versus treatment 
Annals of the rheumatic diseases  2013;73(1):10.1136/annrheumdis-2012-202099.
Objective
To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE).
Methods
We performed case–cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren’s syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses.
Results
We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls.
Conclusions
In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.
doi:10.1136/annrheumdis-2012-202099
PMCID: PMC3855611  PMID: 23303389
3.  Medical audible alarms: a review 
Objectives
This paper summarizes much of the research that is applicable to the design of auditory alarms in a medical context. It also summarizes research that demonstrates that false alarm rates are unacceptably high, meaning that the proper application of auditory alarm design principles are compromised.
Target audience
Designers, users, and manufacturers of medical information and monitoring systems that indicate when medical or other parameters are exceeded and that are indicated by an auditory signal or signals.
Scope
The emergence of alarms as a ‘hot topic’; an outline of the issues and design principles, including IEC 60601-1-8; the high incidence of false alarms and its impact on alarm design and alarm fatigue; approaches to reducing alarm fatigue; alarm philosophy explained; urgency in audible alarms; different classes of sound as alarms; heterogeneity in alarm set design; problems with IEC 60601-1-8 and ways of approaching this design problem.
doi:10.1136/amiajnl-2012-001061
PMCID: PMC3628049  PMID: 23100127
audible alarms; alarms; decision support
4.  Cancer risk in systemic lupus: An updated international multi-centre cohort study 
Journal of autoimmunity  2013;42:130-135.
OBJECTIVE
To update estimates of cancer risk in SLE relative to the general population.
METHODS
A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers.
RESULTS
Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin’s lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61–0.88), endometrial (SIR 0.44, 95% CI 0.23–0.77), and possibly ovarian cancers (0.64, 95% CI 0.34–1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23).
CONCLUSION
These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.
doi:10.1016/j.jaut.2012.12.009
PMCID: PMC3646904  PMID: 23410586
Systemic Lupus Erythematosus; Epidemiology; Treatment; Disease Activity
5.  The Trajectory of Dispersal Research in Conservation Biology. Systematic Review 
PLoS ONE  2014;9(4):e95053.
Dispersal knowledge is essential for conservation management, and demand is growing. But are we accumulating dispersal knowledge at a pace that can meet the demand? To answer this question we tested for changes in dispersal data collection and use over time. Our systematic review of 655 conservation-related publications compared five topics: climate change, habitat restoration, population viability analysis, land planning (systematic conservation planning) and invasive species. We analysed temporal changes in the: (i) questions asked by dispersal-related research; (ii) methods used to study dispersal; (iii) the quality of dispersal data; (iv) extent that dispersal knowledge is lacking, and; (v) likely consequences of limited dispersal knowledge. Research questions have changed little over time; the same problems examined in the 1990s are still being addressed. The most common methods used to study dispersal were occupancy data, expert opinion and modelling, which often provided indirect, low quality information about dispersal. Although use of genetics for estimating dispersal has increased, new ecological and genetic methods for measuring dispersal are not yet widely adopted. Almost half of the papers identified knowledge gaps related to dispersal. Limited dispersal knowledge often made it impossible to discover ecological processes or compromised conservation outcomes. The quality of dispersal data used in climate change research has increased since the 1990s. In comparison, restoration ecology inadequately addresses large-scale process, whilst the gap between knowledge accumulation and growth in applications may be increasing in land planning. To overcome apparent stagnation in collection and use of dispersal knowledge, researchers need to: (i) improve the quality of available data using new approaches; (ii) understand the complementarities of different methods and; (iii) define the value of different kinds of dispersal information for supporting management decisions. Ambitious, multi-disciplinary research programs studying many species are critical for advancing dispersal research.
doi:10.1371/journal.pone.0095053
PMCID: PMC3990620  PMID: 24743447
6.  Breast Cancer in Systemic Lupus Erythematosus 
Oncology  2013;85(2):117-121.
Objective
Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries.
Methods
Information on age, SLE duration, cancer date, and histology was available. We analyzed information on histological type and performed multivariate logistic regression analyses of histological types according to age, SLE duration, and calendar year.
Results
We studied 180 breast cancers in the SLE cohort. Of the 155 cases with histology information, 11 were referred to simply as ‘carcinoma not otherwise specified’. In the remaining 144 breast cancers, the most common histological type was ductal carcinoma (n = 95; 66%) followed by lobular adenocarcinoma (n = 11; 8%), 15 cancers were of mixed histology, and the remaining ones were special types. In our regression analyses, the independent risk factors for lobular versus ductal carcinoma was age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01–1.14] and for the ‘special’ subtypes it was age (OR 1.06, 95% CI 1.01–1.10) and SLE duration (OR 1.05, 95% CI 1.00–1.11).
Conclusions
Generally, up to 80% of breast cancers are ductal carcinomas. Though our results are not definitive, in the breast cancers that occur in SLE, there may be a slight decrease in the ductal histological type. In our analyses, age and SLE duration were independent predictors of histological status.
doi:10.1159/000353138
PMCID: PMC3934367  PMID: 23887245
Breast cancer; Systemic lupus erythematosus; Histopathology; Epidemiology
9.  A novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic H1N1 influenza viruses in mice 
Virology  2011;417(2):379-384.
The HA protein of the 2009 pandemic H1N1viruses (H1N1pdm) is antigenically closely related to the HA of classical North American swine H1N1 influenza viruses (cH1N1). Since 1998, through mutation and reassortment of HA genes from human H3N2 and H1N1 influenza viruses, swine influenza strains are undergoing substantial antigenic drift and shift. In this report we describe the development of a novel monoclonal antibody (S-OIV-3B2) that shows high hemagglutination inhibition (HI) and neutralization titers against not only H1N1pdm, but also against representatives of the α, β, and γ clusters of swine-lineage H1 influenza viruses. Mice that received a single intranasal dose of S-OIV-3B2 were protected against lethal challenge with either H1N1pdm or cH1N1 virus. These studies highlight the potential use of S-OIV-3B2 as effective intranasal prophylactic or therapeutic antiviral treatment for swine-lineage H1 influenza virus infections.
doi:10.1016/j.virol.2011.06.021
PMCID: PMC3180849  PMID: 21774955
monoclonal antibody; H1N1pdm; protection; treatment; swine; influenza
10.  A review of human factors principles for the design and implementation of medication safety alerts in clinical information systems 
The objective of this review is to describe the implementation of human factors principles for the design of alerts in clinical information systems. First, we conduct a review of alarm systems to identify human factors principles that are employed in the design and implementation of alerts. Second, we review the medical informatics literature to provide examples of the implementation of human factors principles in current clinical information systems using alerts to provide medication decision support. Last, we suggest actionable recommendations for delivering effective clinical decision support using alerts. A review of studies from the medical informatics literature suggests that many basic human factors principles are not followed, possibly contributing to the lack of acceptance of alerts in clinical information systems. We evaluate the limitations of current alerting philosophies and provide recommendations for improving acceptance of alerts by incorporating human factors principles in their design.
doi:10.1136/jamia.2010.005264
PMCID: PMC2995688  PMID: 20819851
Alerts; human factors; medication alerting; patient safety
11.  The development of participatory health research among incarcerated women in a Canadian prison 
This paper describes the development of a unique prison participatory research project, in which incarcerated women formed a research team, the research activities and the lessons learned. The participatory action research project was conducted in the main short sentence minimum/medium security women's prison located in a Western Canadian province. An ethnographic multi-method approach was used for data collection and analysis. Quantitative data was collected by surveys and analysed using descriptive statistics. Qualitative data was collected from orientation package entries, audio recordings, and written archives of research team discussions, forums and debriefings, and presentations. These data and ethnographic observations were transcribed and analysed using iterative and interpretative qualitative methods and NVivo 7 software. Up to 15 women worked each day as prison research team members; a total of 190 women participated at some time in the project between November 2005 and August 2007. Incarcerated women peer researchers developed the research processes including opportunities for them to develop leadership and technical skills. Through these processes, including data collection and analysis, nine health goals emerged. Lessons learned from the research processes were confirmed by the common themes that emerged from thematic analysis of the research activity data. Incarceration provides a unique opportunity for engagement of women as expert partners alongside academic researchers and primary care workers in participatory research processes to improve their health.
doi:10.1080/17449200902884021
PMCID: PMC2704626
Health; incarceration; participatory; prison; research; women
12.  Effects of an enhanced secondary prevention program for patients with heart disease: A prospective randomized trial 
The Canadian Journal of Cardiology  2007;23(13):1066-1072.
BACKGROUND:
Secondary prevention medications in cardiac patients improve outcomes. However, prescription rates for these drugs and long-term adherence are suboptimal.
OBJECTIVE:
To determine whether an enhanced secondary prevention program improves outcomes.
METHODS:
Hospitalized patients with indications for secondary prevention medications were randomly assigned to either usual care or an intervention arm, in which an intensive program was used to optimize prescription rates and long-term adherence. Follow-up was 19 months.
RESULTS:
A total of 2643 patients were randomly assigned in the study; 1342 patients were assigned to usual care and 1301 patients were assigned to the intervention arm. Prescription rates were near optimal except for lipid-lowering medications. Rehospitalization rates per 100 patients were 136.2 and 132.6 over 19 months in the usual care and intervention groups, respectively (P=0.59). Total days in hospital per patient were similar (10.9 days in the usual care group versus 10.2 days in the intervention group; P not significant). Crude mortality was 6.2% and 5.5% in the usual care and intervention groups, respectively, with no significant difference (P=0.15) in overall survival. Post hoc analysis suggested that after the study team became experienced, days in hospital per patient were reduced by the program (11.1±0.91 and 8.9±0.61 in the usual care and intervention groups, respectively; P<0.05).
CONCLUSIONS:
The intervention program failed to improve outcomes in the present study. One explanation for these results is the near optimal physician compliance with guidelines in both groups. It is also possible that a substantial learning curve for the staff was involved, as suggested by the reduction in total days in hospital in the intervention patients during the second part of the study.
PMCID: PMC2651931  PMID: 17985009
Guideline adherence; Secondary prevention
13.  Non-Hodgkin's lymphoma in systemic lupus erythematosus 
Annals of the Rheumatic Diseases  2005;64(10):1507-1509.
Objectives: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL.
Methods: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined.
Results: 42 cases of NHL occurred in the patients with SLE during the 76 948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis.
Conclusions: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.
doi:10.1136/ard.2004.034504
PMCID: PMC1755239  PMID: 16162903
14.  Fewer but better auditory alarms will improve patient safety 
Quality & safety in health care  2005;14(3):212-215.


 Auditory warnings and alarms are used throughout the medical environment but often fall short of ideal. In some instances they can be a hindrance rather than a help to medical practice. The main reasons why alarms are less than ideal are: (1) they are used too often and people's hearing as the primary warning sense is overused; (2) false alarm rates are often exceedingly high because trigger points are inappropriately set; and (3) their design is often poor. However, enough is now known about auditory warning design and implementation to overcome many of the traditional problems associated with them. A new draft international standard incorporates many of these measures, and increasing pressure from safety organisations such as the Joint Commission on the Accreditation of Healthcare Organisations in the USA and the National Patient Safety in the UK can help to improve the way that auditory warnings are used in medical care by implementing what is known from research into practice.
doi:10.1136/qshc.2004.013052
PMCID: PMC1744044  PMID: 15933320
15.  Internet hand x-rays: A comparison of joint space narrowing and erosion scores (Sharp/Genant) of plain versus digitized x-rays in rheumatoid arthritis patients 
Background
The objective of the study is to examine the reliability of erosion and joint space narrowing scores derived from hand x-rays posted on the Internet compared to scores derived from original plain x-rays.
Methods
Left and right x-rays of the hands of 36 patients were first digitized and then posted in standard fashion to a secure Internet website. Both the plain and Internet x-rays were scored for erosions and joint space narrowing using the Sharp/Genant method. All scoring was completed in a blind and randomized manner. Agreement between plain and Internet x-ray scores was calculated using Lin's concordance correlations and Bland-Altman graphical representation.
Results
Erosion scores for plain x-rays showed almost perfect concordance with x-rays read on the Internet (concordance 0.887). However, joint space narrowing scores were only "fair" (concordance 0.365). Global scores demonstrated substantial concordance between plain and Internet readings (concordance 0.769). Hand x-rays with less disease involvement showed a tendency to be scored higher on the Internet versions than those with greater disease involvement. This was primarily evident in the joint space narrowing scores.
Conclusions
The Internet represents a valid medium for displaying and scoring hand x-rays of patients with RA. Higher scores from the Internet version may be related to better viewing conditions on the computer screen relative to the plain x-ray viewing, which did not include magnifying lens or bright light. The capability to view high quality x-rays on the Internet has the potential to facilitate information sharing, education, and encourage collaborative studies.
doi:10.1186/1471-2474-3-13
PMCID: PMC113251  PMID: 11980582
16.  Telemedicine in developing countries  
BMJ : British Medical Journal  2001;323(7312):524-525.
PMCID: PMC1121115  PMID: 11546681

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