Publications by authors named "Catherine Armstrong"

25 Publications

  • Page 1 of 1

Severe refractory Kawasaki disease in seven infants in the COVID-19 era.

Lancet Rheumatol 2020 Sep 10;2(9):e520. Epub 2020 Jul 10.

Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Bristol BS2 8BJ, UK.

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http://dx.doi.org/10.1016/S2665-9913(20)30231-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351415PMC
September 2020

Osteoporotic Vertebral Fractures are Common in Hip Fracture Patients and are Under-recognized.

J Clin Densitom 2020 May 21. Epub 2020 May 21.

Department of Rheumatology, Galway University Hospitals, Ireland; School of Medicine, National University of Ireland, Galway, Ireland.

Introduction: The vertebrae are the most common site for osteoporotic fracture. While they can result in disability and increased mortality, only one-third present clinically. People with multiple fractures are at greater risk of future fractures. Most hip fracture patients are neither diagnosed nor treated for their underlying osteoporosis. Computed tomography (CT) studies are often performed on hospitalised patients, can be used to diagnose osteoporosis and are gaining popularity for opportunistic osteoporosis screening by measuring BMD and other bone strength indices. The aim of this study was to assess the prevalence of vertebral fractures on CT pulmonary angiograms (CTPA) in a cohort of hip fracture patients and whether this increased their diagnosis and treatment rates.

Methods: We retrospectively identified all hip fractures admitted to our institution between 2010 and 2017 to identify those who underwent CTPA scans. An independent, blinded consultant musculoskeletal radiologist reviewed the images for vertebral fractures and quantified severity using Genant criteria. Results were compared to the original radiology report, discharge diagnoses and treatment rates for osteoporosis.

Results: Eleven percent (225/2122) of patients had CTPA images available. Seventy percent (158) were female with a mean age of 78 years (SD: 11). The median length of stay for all patients was 16 days (1-301). Forty percent (90) of patients had at least one vertebral fracture present and 20% (46) had more than one fracture. Only one in 5 radiology reports noted the fractures. 24% of subjects had osteoporosis treatment recorded at hospital discharge and there was no difference between those with vertebral fractures to those without.

Conclusion: Many hip fracture patients have undiagnosed spine fractures. A screening strategy which evaluates CT scans for fractures has potential to increase diagnosis and treatment rates of osteoporosis. However, more work is needed to increase awareness.
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http://dx.doi.org/10.1016/j.jocd.2020.05.007DOI Listing
May 2020

A systematic review of the Irish osteoporotic vertebral fracture literature.

Arch Osteoporos 2020 03 2;15(1):34. Epub 2020 Mar 2.

School of Medicine, National University of Ireland, Galway, Ireland.

Introduction: Vertebral fractures (VF) are the most common osteoporotic fracture. They are associated with significant morbidity and mortality and are an important predictor of future fractures. The epidemiology of VF in Ireland is limited and a greater understanding of their scale and impact is needed. Therefore, we conducted a systematic review of publications on osteoporotic VF in Ireland.

Methods: Systematic searches were conducted using PubMed, Medline, Embase, Scopus and Cochrane electronic databases to identify eligible publications from Ireland addressing osteoporotic VF.

Results: Twenty studies met the inclusion criteria out of 1558 citations. All studies were published since 2000. Data was obtained on 182,771 patients with fractures. Nine studies included more than 100 subjects and three included more than 1000. Females accounted for 70% with an overall mean age of 65.2 years (30-94). There was significant heterogeneity in study design, methods and outcome measures including the following: use of administrative claims data on public hospital admissions, surgical and medical interventions, the impact of a fracture liaison service and the osteoporosis economic burden. The prevalence of VF was difficult to ascertain due to definitions used and differences in the study populations. Only two studies systematically reviewed spine imaging using blinded assessors and validated diagnostic criteria to assess the prevalence of fractures in patient cohorts.

Conclusions: Several studies show that VF are common when addressed systematically and the prevalence may be rising. However, there is a deficit of large studies systematically addressing the epidemiology and their importance in Ireland.
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http://dx.doi.org/10.1007/s11657-020-0704-0DOI Listing
March 2020

Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.

Am J Hum Genet 2020 02 30;106(2):272-279. Epub 2020 Jan 30.

Exeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter EX2 5DW, UK; Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter EX2 5DW, UK. Electronic address:

Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data.
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http://dx.doi.org/10.1016/j.ajhg.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010973PMC
February 2020

Introducing pharmacy students to the structure and function of general practice through undergraduate placements.

Curr Pharm Teach Learn 2019 Oct 28;11(10):1055-1064. Epub 2019 Jun 28.

School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences and Wellbeing, University of Sunderland, Dale Building, Pasteur 153, Sciences Complex, Wharncliffe Street, Sunderland SR1 3SD, United Kingdom. Electronic address:

Background And Purpose: The aim of this study was to design and evaluate the introduction of a sustainable and feasible structure of placements in general practice for third-year pharmacy students at the University of Sunderland. The national agenda in the United Kingdom (UK) calls for an increased presence of pharmacists within general practice; therefore, development of placements in this is setting is aligned to the development of these new roles.

Educational Activity And Setting: The placements were located in general practice surgeries in the North East of England in the UK. Students engaged in activities which introduced them to the structure and function of general practice and familiarise them with the role of pharmacists and other practice staff. Two cohorts undertook the education activity during the development process. The first cohort was comprised of 213 students, with 193 students the following year.

Findings: An action research approach was taken to evaluate and revise the design of the placement. The final design and delivery have been shown to have a positive impact on student learning experience, be feasible and sustainable. The placement was also successful at introducing students to potential future roles in general practice for pharmacists.

Summary: This model of general practice placement provision was found to be a feasible and sustainable delivery model, which was well received by undergraduate students.
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http://dx.doi.org/10.1016/j.cptl.2019.06.013DOI Listing
October 2019

High-performing physicians are more likely to participate in a research study: findings from a quality improvement study.

BMC Med Res Methodol 2019 08 7;19(1):171. Epub 2019 Aug 7.

CT Lamont Primary Health Care Research Centre, Bruyère Research Institute, 113-43, rue Bruyère St, K1N 5C7, Annex E, Ottawa, ON, Canada.

Background: Participants in voluntary research present a different demographic profile than those who choose not to participate, affecting the generalizability of many studies. Efforts to evaluate these differences have faced challenges, as little information is available from non-participants. Leveraging data from a recent randomized controlled trial that used health administrative databases in a jurisdiction with universal medical coverage, we sought to compare the quality of care provided by participating and non-participating physicians prior to the program's implementation in order to assess whether participating physicians provided a higher baseline quality of care.

Methods: We conducted clustered regression analyses of baseline data from provincial health administrative databases. Participants included all family physicians who were eligible to participate in the Improved Delivery of Cardiovascular Care (IDOCC) project, a quality improvement project rolled out in a geographically defined region in Ontario (Canada) between 2008 and 2011. We assessed 14 performance indicators representing measures of access, continuity, and recommended care for cancer screening and chronic disease management.

Results: In unadjusted and patient-adjusted models, patients of IDOCC-participating physicians had higher continuity scores at the provider (Odds Ratio (OR) [95% confidence interval]: 1.06 [1.03-1.09]) and practice (1.06 [1.04-1.08]) level, lower risk of emergency room visits (Rate Ratio (RR): 0.93 [0.88-0.97]) and hospitalizations (RR:0.87 [0.77-0.99]), and were more likely to have received recommended diabetes tests (OR: 1.25 [1.06-1.49]) and cancer screening for cervical cancer (OR: 1.32 [1.08-1.61] and breast cancer (OR: 1.32 [1.19-1.46]) than patients of non-participating physicians. Some indicators remained statistically significant in the model after adjusting for provider factors.

Conclusions: Our study demonstrated a participation bias for several quality indicators. Physician characteristics can explain some of these differences. Other underlying physician or practice attributes also influence interest in participating in quality improvement initiatives and existing quality levels. The standard for addressing participation bias by controlling for basic physician and practice level variables is inadequate for ensuring that results are generalizable to primary care providers and practices.
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http://dx.doi.org/10.1186/s12874-019-0809-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685269PMC
August 2019

A unique triadin exon deletion causing a null phenotype.

HeartRhythm Case Rep 2018 Nov 4;4(11):514-518. Epub 2018 Aug 4.

Bristol Royal Hospital for Children, Bristol, United Kingdom.

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http://dx.doi.org/10.1016/j.hrcr.2018.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241331PMC
November 2018

Withdrawn: A Randomized Controlled Trial Comparing Modular and Nonmodular Neck Versions of a Titanium Stem.

J Arthroplasty 2018 Sep 21. Epub 2018 Sep 21.

Department of Trauma and Orthopaedics, Royal Liverpool and Broadgreen Hospital, Liverpool, United Kingdom.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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http://dx.doi.org/10.1016/j.arth.2018.09.039DOI Listing
September 2018

Blood Metal Ion Levels Have Limited Utility in the Surveillance of Asymptomatic Large-Head Metal-on-Metal Total Hip Arthroplasties.

J Arthroplasty 2017 12 20;32(12):3685-3688. Epub 2017 Jul 20.

Department of Trauma and Orthopaedics, Royal Liverpool and Broadgreen Hospital, Liverpool, United Kingdom.

Background: Blood cobalt (Co) and chromium (Cr) ion levels have been used as surveillance tools for adverse reaction to metal debris (ARMD) in metal-on-metal (MoM) articulations with varying thresholds in different countries. The aim of our study is to present the serial 12-year blood Co and Cr levels in a cohort of MoM total hip arthroplasties (THAs) with femoral head size ≥36 mm and analyze their utility in asymptomatic patients at current thresholds.

Methods: A total of 256 patients with unilateral MoM THA with femoral head size ≥36 mm were included in this study with data collected prospectively. The implants used were Birmingham hip resurfacing cup-Freeman stem (BHR-F) or an Articular Surface Resurfacing cup-Corail/S-ROM stem. Annual follow-up with blood Co and Cr measurements was done as per Medicines and Healthcare Products Regulatory Agency (MHRA) of the United Kingdom guidelines. Receiver operating characteristic curve was plotted based on the sensitivity and specificity of blood metal ion values to detect ARMD. The metal ion levels in asymptomatic patients were analyzed separately.

Results: Receiver operating characteristic curves showed poor discriminatory ability for both Co and Cr values in predicting ARMD at 7 μg/L. The sensitivity of Co and Cr was 82.1% and 53.5%, respectively, and their positive predictive values were 43.8% and 67.6%, respectively. After 7 years, there was no significant change in Co values, and there was a decline in Cr value after 9 years in asymptomatic patients.

Conclusion: To the best of our knowledge, this is the first study to describe the behavior of serial blood metal ion levels in asymptomatic large-diameter MoM THA. We suggest that annual blood Co and Cr have limited discriminant capacity in diagnosing the occurrence of metallosis and their measurement beyond 7 years is of limited utility in asymptomatic patients.
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http://dx.doi.org/10.1016/j.arth.2017.07.015DOI Listing
December 2017

Improving access to specialists in remote communities: a cross-sectional study and cost analysis of the use of eConsult in Nunavut.

Int J Circumpolar Health 2017 ;76(1):1323493

f Department of Medicine , University of Ottawa , Ottawa , Ontario , Canada.

Background: Residents of remote communities face inequities in access to specialists, excessive wait times, and poorly coordinated care. The Champlain BASE (Building Access to Specialists through eConsultation) service facilitates asynchronous communication between primary care providers (PCP) and specialists. The service was extended to several PCPs in Nunavut in 2014.

Objective: To (1) describe the use of eConsult services in Nunavut, and (2) conduct a costing evaluation.

Design: A cross-sectional study and cost analysis of all eConsult cases submitted between August 2014 and April 2016.

Results: PCPs from Nunavut submitted 165 eConsult cases. The most popular specialties were dermatology (16%), cardiology (8%), endocrinology (7%), otolaryngology (7%), and obstetrics/gynaecology (7%). Specialists provided a response in a median of 0.9 days (IQR=0.3-3.0, range=0.01-15.02). In 35% of cases, PCPs were able to avoid the face-to-face specialist visits they had originally planned for their patients. Total savings associated with eConsult in Nunavut are estimated at $180,552.73 or $1,100.93 per eConsult.

Conclusions: The eConsult service provided patients in Nunavut's remote communities with prompt access to specialist advice. The service's chief advantage in Canada's northern communities is its ability to offer electronic access to a breadth of specialties far greater than could be supported locally. Our findings suggest that a territory-wide adoption of eConsult would generate enormous savings.
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http://dx.doi.org/10.1080/22423982.2017.1323493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497548PMC
April 2018

Cardiac involvement as a presenting feature of eosinophilic granulomatosis with polyangiitis in childhood.

Clin Exp Rheumatol 2017 Mar-Apr;35 Suppl 103(1):225. Epub 2017 Mar 15.

Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Bristol & Royal National Hospital for Rheumatic Diseases NHS Foundation Trust, Bath, UK.

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July 2017

Finding covert fluid: methods for detecting volume overload in children on dialysis.

Pediatr Nephrol 2016 12 10;31(12):2327-2335. Epub 2016 Jun 10.

Bristol Children's Renal Unit, Bristol Royal Hospital for Children, Upper Maudlin Street, Bristol, BS2 8BJ, UK.

Background: Lung ultrasound is a novel technique for detecting generalized fluid overload in children and adults with end-stage renal disease (ESRD). Echocardiography and bioimpedance spectroscopy are established methods, albeit variably adopted in clinical practice. We compared the practicality and accuracy of lung ultrasound with current objective techniques for detecting fluid overload in children with ESRD.

Methods: A prospective observational study was performed to compare lung ultrasound B-lines, echocardiographic measurement of inferior vena cava parameters and bioimpedance spectroscopy in the assessment of fluid overload in children with ESRD on dialysis. The utility of each technique in predicting fluid overload, based on short-term weight gain, was assessed. Multiple linear regression models to predict fluid overload by weight were explored.

Results: A total of 22 fluid assessments were performed in 13 children (8 on peritoneal dialysis, 5 on haemodialysis) with a median age of 4.0 (range 0.8-14.0) years. A significant linear correlation was observed between the number of B-lines detected by lung ultrasound and fluid overload by weight (r = 0.57, p = 0.005). A non-significant positive linear correlation was observed between fluid overload by weight and bioimpedance spectroscopy (r = 0.43, p = 0.2), systolic blood pressure (r = 0.19, p = 0.4) and physical examination measurements (r = 0.19, p = 0.4), while a non-significant negative linear relationship was found between the inferior vena cava collapsibility index and fluid overload by weight (r = -0.24, p = 0.3). In multiple linear regression models, a combination of three fluid parameters, namely lung ultrasound B-lines, clinical examination and systolic blood pressure, best predicted fluid overload (R  = 0.46, p = 0.05).

Conclusions: Lung ultrasound may be superior to echocardiographic methods and bioimpedance spectroscopy in detecting volume overload in children with ESRD. Given the practicality and sensitivity of this new technique, it can be adopted alongside clinical examination and blood pressure in the routine assessment of fluid status in children with ESRD.
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http://dx.doi.org/10.1007/s00467-016-3431-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118410PMC
December 2016

A mixed-methods study of the causes and impact of poor teamwork between junior doctors and nurses.

Int J Qual Health Care 2016 Jun 18;28(3):339-45. Epub 2016 Apr 18.

Saolta Healthcare Group, Galway, Ireland.

Objectives: This study aimed to collect and analyse examples of poor teamwork between junior doctors and nurses; identify the teamwork failures contributing to poor team function; and ascertain if particular teamwork failures are associated with higher levels of risk to patients.

Design: Critical Incident Technique interviews were carried out with junior doctors and nurses.

Setting: Two teaching hospitals in the Republic of Ireland.

Participants: Junior doctors (n = 28) and nurses (n = 8) provided descriptions of scenarios of poor teamwork. The interviews were coded against a theoretical framework of healthcare team function by three psychologists and were also rated for risk to patients by four doctors and three nurses.

Results: A total of 33 of the scenarios met the inclusion criteria for analysis. A total of 63.6% (21/33) of the scenarios were attributed to 'poor quality of collaboration', 42.4% (14/33) to 'poor leadership' and 48.5% (16/33) to a 'lack of coordination'. A total of 16 scenarios were classified as high risk and 17 scenarios were classified as medium risk. Significantly more of the high-risk scenarios were associated with a 'lack of a shared mental model' (62.5%, 10/16) and 'poor communication' (50.0%, 8/16) than the medium-risk scenarios (17.6%, 3/17 and 11.8%, 2/17, respectively).

Conclusion: Poor teamwork between junior doctors and nurses is common and places patients at considerable risk. Addressing this problem requires a well-designed complex intervention to develop the team skills of doctors and nurses and foster a clinical environment in which teamwork is supported.
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http://dx.doi.org/10.1093/intqhc/mzw036DOI Listing
June 2016

Medium-term results following large diameter metal-on-metal total hip arthroplasty: increasing failure after 6 years.

Hip Int 2016 May 20;26(3):226-32. Epub 2016 Mar 20.

Trauma and Orthopaedics Department, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool - UK.

Purpose: The main aim of our study is to report the medium-term survivorship of Birmingham Hip Resurfacing (BHR) cup and a large modular metal head (MMT) on an uncemented Freeman femoral stem. No results have been reported till date with these implants combinations.

Methods: A total of 205 metal-on-metal total hip replacements (MoM THRs) were performed on 190 patients from October 2002 to November 2004. Prior to the Medicines and Healthcare Products Regulatory Agency (MHRA) guidelines, the patients were followed up at 3, 6 and 12 months postoperatively and annually thereafter. Following the MHRA alert in 2010, the patients were followed-up as per the MHRA guidelines.All statistical analyses were conducted using Stata 13.

Results: At a mean follow-up of 10.5 years, a total of 42 out of 205 hips were revised for reasons related to ALTR. The failure rates increased significantly over time (7% at 6 years and 29% at 10-year follow-up). The analysis showed no statistically significant association to age, gender, side, BMI or component size or position (p<0.05). Blood metal ions showed a poor discriminant ability to separate failed from well-functioning MoM hip replacements.

Conclusions: Large head MoM BHR on an uncemented stem has extremely high failure rate. The authors do not recommend the use of large head MoM articulation in total hip arthroplasty in the wake of this report and similar findings across the world. Continued surveillance of these implants is required as the failure rates increase with time.
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http://dx.doi.org/10.5301/hipint.5000344DOI Listing
May 2016

Staged interventional and surgical management for complex low birthweight tetralogy of Fallot: another imperfect but legitimate strategy.

BMJ Case Rep 2013 Sep 30;2013. Epub 2013 Sep 30.

Bristol Royal Infirmary, Bristol, UK.

Management of spelling low weight infants with complex tetralogy of Fallot is often fraught. We present a 2.8-kg infant with DiGeorge syndrome and spelling tetralogy with non-confluent pulmonary arteries, the left pulmonary artery being supplied by an aberrant ductus arteriosus from the left common carotid artery. We performed stenting of the outflow tract and the ductus to allow this patient to achieve a successful elective surgical correction.
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http://dx.doi.org/10.1136/bcr-2013-201085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794286PMC
September 2013

Differential distribution of cobalt, chromium, and nickel between whole blood, plasma and urine in patients after metal-on-metal (MoM) hip arthroplasty.

J Orthop Res 2012 Oct 23;30(10):1640-6. Epub 2012 Mar 23.

Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, University of Liverpool, Prescot Street, Liverpool L7 8XP, United Kingdom.

Evidence shows that raised cobalt (Co), chromium (Cr), and nickel (Ni) whole blood concentrations correlate with poor device outcome in patients following metal-on-metal (MoM) hip arthroplasty. To understand the local and systemic pathological effects of these raised metal concentrations it is important to define their distribution between whole blood, plasma, and urine. The metals were measured by Inductively Coupled Plasma Mass Spectrometry (ICPMS). Two hundred and five plasma, 199 whole blood, and 24 sets of urine samples were analyzed from 202 patients with Co-Cr alloy MoM hip prostheses implanted between 8 months to 12 years (mean 6.0 years) prior to analysis. Plasma Co (median 39.1 nmol/L) showed significantly positive 1:1 correlation with whole blood Co (median 45.9 nmol/L; R(2)  = 0.98, p < 0.001, slope = 1.0). Plasma Cr (median 53.8 nmol/L) and whole blood Cr (median 40.3 nmol/L) were also correlated; however, concentrations were significantly higher in plasma indicating relatively little blood cell uptake (R(2)  = 0.96, p < 0.001, slope = 1.6). Urinary Co was up to threefold higher than Cr (median 334.0 vs. 97.3 nmol/L respectively). Nickel concentrations in whole blood, plasma, and urine were low relative to Co and Cr. The analysis shows fundamental differences in the physiological handling of these metals: Co is distributed approximately equally between blood cells and plasma, whereas Cr is mainly in plasma, despite which, Cr had far less renal excretion than Co.
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http://dx.doi.org/10.1002/jor.22107DOI Listing
October 2012

Metal ion levels decrease after revision for metallosis arising from large-diameter metal-on-metal hip arthroplasty.

Acta Orthop Belg 2011 Dec;77(6):777-81

Royal Liverpool and Broadgreen University Hospital, Liverpool, United Kingdom.

Concerns have been renewed regarding the possible long-term effects of elevated circulating levels of cobalt and chromium as a direct result of implantation of large femoral head diameter metal-on-metal bearings. In order to establish whether metal ion levels remain persistently elevated, we compared metal ion levels before and after revision surgery in patients with large head diameter (greater than 38 mm) metal-on-metal total hip arthroplasty or hip resurfacing arthroplasty. At greater than one year post removal of a large-diameter metal-on-metal hip implant for the indication of symptomatic metallosis, metal ion levels were found to fall to almost normal levels.
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December 2011

A high throughput in vitro mrp2 assay to predict in vivo biliary excretion.

Xenobiotica 2012 Feb 2;42(2):157-63. Epub 2011 Oct 2.

Biological Sciences, Boehringer Ingelheim (Canada) Ltd., Laval, Québec, Canada.

Prediction of biliary excretion is a challenge for drug discovery scientists due to the lack of in vitro assays. This study explores the possibility of establishing a simple assay to predict in vivo biliary excretion via the mrp2 transport system. In vitro mrp2 activity was determined by measuring the ATP-dependent uptake of 5(6)-carboxy-2',7'-dichlorofluorescein (CDCF) in canalicular plasma membrane vesicles (cLPM) from rat livers. The CDCF uptake was time- and concentration-dependent (K(m) of 2.2 ± 0.3 µM and V(max) of 115 ± 26 pmol/mg/min) and strongly inhibited by the mrp2 inhibitors, benzbromarone, MK-571, and cyclosporine A, with IC(50) values ≤ 1.1 µM. Low inhibition of CDCF uptake by taurocholate (BSEP inhibitor; 57 µM) and digoxin (P-gp inhibitor; 101 µM) demonstrated assay specificity towards mrp2. A highly significant correlation (r(2) = 0.959) between the in vitro IC(50) values from the described mrp2 assay and in vivo biliary excretion in rats was observed using 10 literature compounds. This study demonstrated, for the first time, that a high throughput assay could be established with the capability of predicting biliary excretion in the rat using CDCF as a substrate.
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http://dx.doi.org/10.3109/00498254.2011.614021DOI Listing
February 2012

Improved delivery of cardiovascular care (IDOCC) through outreach facilitation: study protocol and implementation details of a cluster randomized controlled trial in primary care.

Implement Sci 2011 Sep 27;6:110. Epub 2011 Sep 27.

C. T. Lamont Primary Health Care Research Centre, Elisabeth Bruyère Research Institute, Ottawa, Ontario, Canada.

Background: There is a need to find innovative approaches for translating best practices for chronic disease care into daily primary care practice routines. Primary care plays a crucial role in the prevention and management of cardiovascular disease. There is, however, a substantive care gap, and many challenges exist in implementing evidence-based care. The Improved Delivery of Cardiovascular Care (IDOCC) project is a pragmatic trial designed to improve the delivery of evidence-based care for the prevention and management of cardiovascular disease in primary care practices using practice outreach facilitation.

Methods: The IDOCC project is a stepped-wedge cluster randomized control trial in which Practice Outreach Facilitators work with primary care practices to improve cardiovascular disease prevention and management for patients at highest risk. Primary care practices in a large health region in Eastern Ontario, Canada, were eligible to participate. The intervention consists of regular monthly meetings with the Practice Outreach Facilitator over a one- to two-year period. Starting with audit and feedback, consensus building, and goal setting, the practices are supported in changing practice behavior by incorporating chronic care model elements. These elements include (a) evidence-based decision support for providers, (b) delivery system redesign for practices, (c) enhanced self-management support tools provided to practices to help them engage patients, and (d) increased community resource linkages for practices to enhance referral of patients. The primary outcome is a composite score measured at the level of the patient to represent each practice's adherence to evidence-based guidelines for cardiovascular care. Qualitative analysis of the Practice Outreach Facilitators' written narratives of their ongoing practice interactions will be done. These textual analyses will add further insight into understanding critical factors impacting project implementation.

Discussion: This pragmatic, stepped-wedge randomized controlled trial with both quantitative and process evaluations demonstrates innovative methods of implementing large-scale quality improvement and evidence-based approaches to care delivery. This is the first Canadian study to examine the impact of a large-scale multifaceted cardiovascular quality-improvement program in primary care. It is anticipated that through the evaluation of IDOCC, we will demonstrate an effective, practical, and sustainable means of improving the cardiovascular health of patients across Canada.

Trial Registration: ClinicalTrials.gov: NCT00574808.
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http://dx.doi.org/10.1186/1748-5908-6-110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197547PMC
September 2011

Anaesthetic considerations for intrabronchial valves.

Eur J Anaesthesiol 2010 May;27(5):491-2

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http://dx.doi.org/10.1097/EJA.0b013e328330ece5DOI Listing
May 2010

Cost-effectiveness of Anticipatory and Preventive multidisciplinary Team Care for complex patients: evidence from a randomized controlled trial.

Can Fam Physician 2010 Jan;56(1):e20-9

C.T. Lamont Primary Health Care Research Centre, Elisabeth Bruyère Research Institute, Ottawa, Ontario.

Objective: To evaluate the cost-effectiveness of Anticipatory and Preventive Team Care (APTCare).

Design: Analysis of data drawn from a randomized controlled trial.

Setting: A family health network in a rural area near Ottawa, Ont.

Participants: Patients 50 years of age or older at risk of experiencing adverse health outcomes. Analysis of cost-effectiveness was performed for a subsample of participants with at least 1 of the chronic diseases used in the quality of care (QOC) measure (74 intervention and 78 control patients).

Interventions: At-risk patients were randomly assigned to receive usual care from their family physicians or APTCare from a collaborative team.

Main Outcome Measures: Cost-effectiveness and the net benefit to society of the APTCare intervention.

Results: Costs not directly associated with delivery of the intervention were similar in the 2 arms: $9121 and $9222 for the APTCare and control arms, respectively. Costs directly associated with the program were $3802 per patient for a total cost per patient of $12,923 and $9222, respectively (P=.033). A 1% improvement in QOC was estimated to cost $407 per patient. Analysis of the net benefit to society in absolute dollars found a breakeven threshold of $750 when statistical significance was required. This implies that society must place a value of at least $750 on a 1% improvement in QOC in order for the intervention to be socially worthwhile. By any of the metrics used, the APTCare intervention was not cost-effective, at least not in a population for which baseline QOC was high.

Conclusion: Although our calculations suggest that the APTCare intervention was not cost-effective, our results need the following caveats. The costs of such a newly introduced intervention are bound to be higher than those for an established, up-and-running program. Furthermore, it is possible that some benefits of the secondary preventive measures were not captured in this limited 12- to 18-month study or were simply not measured. TRIAL REGISTRATION NUMBER NCT00238836 (CONSORT).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2809192PMC
January 2010

Randomized controlled trial of anticipatory and preventive multidisciplinary team care: for complex patients in a community-based primary care setting.

Can Fam Physician 2009 Dec;55(12):e76-85

University of Ottawa, Department of Family Medicine, 43 Bruyère St, Ottawa, ON K1N 5C8.

Objective: T o examine whether quality of care (QOC) improves when nurse practitioners and pharmacists work with family physicians in community practice and focus their work on patients who are 50 years of age and older and considered to be at risk of experiencing adverse health outcomes.

Design: Randomized controlled trial.

Setting: A family health network with 8 family physicians, 5 nurses, and 11 administrative personnel serving 10 000 patients in a rural area near Ottawa, Ont.

Participants: Patients 50 years of age and older at risk of experiencing adverse health outcomes (N = 241).

Interventions: At-risk patients were randomly assigned to receive usual care from their family physicians or Anticipatory and Preventive Team Care (APTCare) from a collaborative team composed of their physicians, 1 of 3 nurse practitioners, and a pharmacist.

Main Outcome Measures: Quality of care for chronic disease management (CDM) for diabetes, coronary artery disease, congestive heart failure, and chronic obstructive pulmonary disease.

Results: Controlling for baseline demographic characteristics, the APTCare approach improved CDM QOC by 9.2% (P < .001) compared with traditional care. The APTCare intervention also improved preventive care by 16.5% (P < .001). We did not observe significant differences in other secondary outcome measures (intermediate clinical outcomes, quality of life [Short-Form 36 and health-related quality of life scales], functional status [instrumental activities of daily living scale] and service usage).

Conclusion: Additional resources in the form of collaborative multidisciplinary care teams with intensive interventions in primary care can improve QOC for CDM in a population of older at-risk patients. The appropriateness of this intervention will depend on its cost-effectiveness. TRIAL REGISTRATION NUMBER NCT00238836 (CONSORT).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793206PMC
December 2009

Home-based intermediate care program vs hospitalization: Cost comparison study.

Can Fam Physician 2008 Jan;54(1):66-73

Department of Economics at the University of Ottawa in Ontario.

Objective: To explore whether a home-based intermediate care program in a large Canadian city lowers the cost of care and to look at whether such home-based programs could be a solution to the increasing demands on Canadian hospitals.

Design: Single-arm study with historical controls.

Setting: Department of Family Medicine at the Ottawa Hospital (Civic campus) in Ontario.

Participants: Patients requiring hospitalization for acute care. Participants were matched with historical controls based on case-mix, most responsible diagnosis, and level of complexity.

Interventions: Placement in the home-based intermediate care program. Daily home visits from the nurse practitioner and 24-hour access to care by telephone.

Main Outcome Measures: Multivariate regression models were used to estimate the effect of the program on 5 outcomes: length of stay in hospital, cost of care substituted for hospitalization (Canadian dollars), readmission for a related diagnosis, readmission for any diagnosis, and costs incurred by community home-care services for patients following discharge from hospital.

Results: The outcomes of 43 hospital admissions were matched with those of 363 controls. Patients enrolled in the program stayed longer in hospital (coefficient 3.3 days, P < .001), used more community care services following discharge (coefficient $729, P = .007), and were more likely to be readmitted to hospital within 3 months of discharge (coefficient 17%, P = .012) than patients treated in hospital. Total substituted costs of home-based care were not significantly different from the costs of hospitalization (coefficient -$501, P = .11).

Conclusion: While estimated cost savings were not statistically significant, the limitations of our study suggest that we underestimated these savings. In particular, the economic inefficiencies of a small immature program and the inability to control for certain factors when selecting historical controls affected our results. Further research is needed to determine the economic effect of mature home-based programs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2293319PMC
January 2008

Patient, informal caregiver and care provider acceptance of a hospital in the home program in Ontario, Canada.

BMC Health Serv Res 2007 Aug 17;7:130. Epub 2007 Aug 17.

C.T. Lamont Primary Health Care Research Centre, Elisabeth Bruyère Research Institute, Rue Bruyère St,, Ottawa, Canada.

Background: Hospital in the home programs have been implemented in several countries and have been shown to be safe substitutions (alternatives) to in-patient hospitalization. These programs may offer a solution to the increasing demands made on tertiary care facilities and to surge capacity. We investigated the acceptance of this type of care provision with nurse practitioners as the designated principal home care providers in a family medicine program in a large Canadian urban setting.

Methods: Patients requiring hospitalization to the family medicine service ward, for any diagnosis, who met selection criteria, were invited to enter the hospital in the home program as an alternative to admission. Participants in the hospital in the home program, their caregivers, and the physicians responsible for their care were surveyed about their perceptions of the program. Nurse practitioners, who provided care, were surveyed and interviewed.

Results: Ten percent (104) of admissions to the ward were screened, and 37 patients participated in 44 home hospital admissions. Twenty nine patient, 17 caregiver and 38 provider surveys were completed. Most patients (88%-100%) and caregivers (92%-100%) reported high satisfaction levels with various aspects of health service delivery. However, a significant proportion in both groups stated that they would select to be treated in-hospital should the need arise again. This was usually due to fears about the safety of the program. Physicians (98%-100%) and nurse practitioners also rated the program highly. The program had virtually no negative impact on the physician workload. However nurse practitioners felt that the program did not utilize their full expertise.

Conclusion: Provision of hospital level care in the home is well received by patients, their caregivers and health care providers. As a new program, investment in patient education about program safety may be necessary to ensure its long term success. A small proportion of hospital admissions were screened for this program. Appropriate dissemination of program information to family physicians should help buy-in and participation. Nurse practitioners' skills may not be optimally utilized in this setting.
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http://dx.doi.org/10.1186/1472-6963-7-130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2020484PMC
August 2007

Duodenal perforation after ibuprofen overdose.

J Toxicol Clin Toxicol 2004 ;42(7):983-5

Emergency Department, South Manchester University Hospital, Wythenshawe, Manchester, UK.

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http://dx.doi.org/10.1081/clt-200041767DOI Listing
January 2005