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1.  Transient ischaemic attack: a qualitative study of the long term consequences for patients 
BMC Family Practice  2014;15(1):174.
Transient ischaemic attack (TIA) is characterised by its transient nature with symptoms of neurological dysfunction resolving within 24 hours. The occurrence of TIA is a major risk factor for stroke with 10–15% of TIA patients going on to have ischaemic stroke. Internationally, recommendations for the management of TIA focus on the need for early diagnosis and medical management of the acute increased risk of ischaemic stroke. However there is a limited amount of evidence that some patients suffer enduring consequences as a result of this ‘transient’ event. This paper focusses on patients’ long term lived experience following a TIA.
Semi structured interviews were carried out with patients who had a TIA between two and 24 months previously. Participants were asked about their TIA, the advice and management received and any changes made as a result of the TIA. Interviews were recorded and transcribed verbatim. Thematic content analysis involved scrutinising transcripts to look for links and associations within and between accounts in a process similar to the grounded theory approach of open coding. The category of transience emerged and was explored in more detail to examine the enduring consequences of TIA.
Thirty nine patients aged between 31 and 89 years were interviewed. Accounts detailed the long term impact of the TIA and the subsequent ‘at risk’ status, on the physical and psychosocial wellbeing of participants. Some participants sought to proactively manage the consequences of their TIA but found it difficult to obtain the information and support they needed, whereas others felt that no further action was needed to prevent future stroke.
Current definitions conceptualise TIA as a transient event however our study suggests that some patients experienced long term consequences as a result of their TIA. These included anxiety and uncertainty in the light of their increased stroke risk. TIA patients need access to detailed, evidence based stroke prevention information from a credible source, and support to help them understand and apply the information over time, if they are to effectively self-manage the long term consequences of TIA and reduce their risk of future stroke.
PMCID: PMC4221669  PMID: 25359664
Transient ischaemic attack; Qualitative; Patient experience; Self-management; Secondary prevention; Stroke
2.  iCanCope with Pain™: User-centred design of a web- and mobile-based self-management program for youth with chronic pain based on identified health care needs 
Chronic pain self-management involves providing patients with knowledge, coping strategies and social support that help them to manage their pain. This type of intervention has been shown to be useful in treating chronic pain; however, many eligible chronic pain patients never receive such treatment due to limited accessibility and high cost. The use of Internet-based cognitive behavioural therapy has the potential to change this. In this study, the authors report their progress in the development of an Internet- and smartphone-based application for chronic pain self-management.
While there are emerging web-based self-management programs for children and adolescents with chronic pain, there is currently not an integrated web- and smartphone-based app that specifically addresses the needs of adolescents with chronic pain.
To conduct a needs assessment to inform the development of an online chronic pain self-management program for adolescents, called iCanCope with Pain™.
A purposive sample of adolescents (n=23; 14 to 18 years of age) was recruited from two pediatric chronic pain clinics in Ontario. Interdisciplinary health care providers were also recruited from these sites. Three focus groups were conducted with adolescents (n=16) and one with pediatric health care providers (n=7). Individual adolescent interviews were also conducted (n=7).
Qualitative analysis uncovered four major themes: pain impact; barriers to care; pain management strategies; and transition to adult care. Pain impacted social, emotional, physical and role functioning, as well as future goals. Barriers to care were revealed at the health care system, patient and societal levels. Pain management strategies included support systems, and pharmacological, physical and psychological approaches. Transition subthemes were: disconnect between pediatric and adult systems; skills development; parental role; and fear/anxiety. Based on these identified needs, the iCanCope with Pain™ architecture will include the core theory-based functionalities of: symptom self-monitoring; personalized goal setting; pain coping skills training; peer-based social support; and chronic pain education.
The proposed iCanCope with Pain™ program aims to address the self-management needs of adolescents with chronic pain by improving access to disease information, strategies to manage symptoms and social support.
PMCID: PMC4197753  PMID: 25000507
Adolescent; Chronic pain; E-health; Mobile-health; Needs assessment; Self-management
3.  The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases 
PLoS ONE  2014;9(8):e106159.
High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.
PMCID: PMC4149520  PMID: 25170916
4.  Low‐dose maternal alcohol consumption: effects in the hearts of offspring in early life and adulthood 
Physiological Reports  2014;2(7):e12087.
High alcohol consumption during pregnancy leads to deleterious effects on fetal cardiac structure and it also affects cardiomyocyte growth and maturation. This study aimed to determine whether low levels of maternal alcohol consumption are also detrimental to cardiomyocyte and cardiac growth in the early life of offspring and whether cardiac structure and function in adulthood is affected. Pregnant Sprague–Dawley rat dams were fed a control or 6% (volume/volume) liquid‐based ethanol supplemented (isocaloric) diet throughout gestation. At embryonic day 20, the expression of genes involved in cardiac development was analyzed using Real‐time PCR. At postnatal day 30, cardiomyocyte number, size, and nuclearity in the left ventricle (LV) were determined stereologically. In 8‐month‐old offspring, LV fibrosis and cardiac function (by echocardiography) were examined. Maternal ethanol consumption did not alter gene expression of the cardiac growth factors in the fetus or cardiomyocyte number in weanling offspring. However, at 8 months, there were significant increases in LV anterior and posterior wall thickness during diastole in ethanol‐exposed offspring (P = 0.037 and P = 0.024, respectively), indicative of left ventricular hypertrophy; this was accompanied by a significant increase in fibrosis. Additionally, maximal aortic flow velocity was significantly decreased in ethanol‐exposed offspring (P = 0.035). In conclusion, although there were no detectable early‐life differences in cardiac and cardiomyocyte growth in animals exposed to a chronic low dose of ethanol during gestation, there were clearly deleterious outcomes by adulthood. This suggests that even relatively low doses of alcohol consumed during pregnancy can be detrimental to long‐term cardiac health in the offspring.
Low dose alcohol consumption during gestation in rats illustrated no differences in cardiomyocyte and cardiac growth in the offspring in early life. However, in adulthood, induction of left ventricular hypertrophy was observed suggesting low doses of alcohol during pregnancy can be detrimental to long‐term cardiac health in offspring.
PMCID: PMC4187541  PMID: 25077510
Cardiomyocyte; ethanol; heart; prenatal; rat
5.  Assessing pain intensity in children with chronic pain: Convergent and discriminant validity of the 0 to 10 numerical rating scale in clinical practice 
Assessment of children’s self-reported pain is essential for pain management, and must be conducted using a measure that is simple, valid and easy to administer. The numerical analogue scale, on which individuals rate their pain on a scale of 0 to 10, is validated and widely used in adults experiencing both acute and chronic pain. The scale is also often used in children and is believed to be an appropriate tool, although this has not been formally assessed among children experiencing chronic pain. Accordingly, the authors of this article conducted a retrospective analysis of the numerical rating scale using data obtained during assessment at a pediatric chronic pain clinic in Toronto, Ontario
In clinical practice, children are often asked to rate their pain intensity on a simple 0 to 10 numerical rating scale (NRS). Although the NRS is a well-established measure for adults, no study has yet evaluated its validity for children with chronic pain.
To examine the convergent and discriminant validity of the NRS as it is used within regular clinical practice to document pain intensity for children with chronic pain. Interchangeability between the NRS and an analogue pain measure was also assessed.
A cohort of 143 children (mean [± SD] age 14.1±2.4 years; 72% female) rated their pain intensity (current, usual, lowest and strongest levels) on a verbally administered 0 to 10 NRS during their first appointment at a specialized pain clinic. In a separate session that occurred either immediately before or after their appointment, children also rated their pain using the validated 0 to 10 coloured analogue scale (CAS).
NRS ratings met a priori criteria for convergent validity (r>0.3 to 0.5), correlating with CAS ratings at all four pain levels (r=0.58 to 0.68; all P<0.001). NRS for usual pain intensity differed significantly from an affective pain rating, as hypothesized (Z=2.84; P=0.005), demonstrating discriminant validity. The absolute differences between NRS and CAS pain scores were small (range 0.98±1.4 to 1.75±1.9); however, the two scales were not interchangeable.
The present study provides preliminary evidence that the NRS is a valid measure for assessing pain intensity in children with chronic pain.
PMCID: PMC4158959  PMID: 24712019
Children; Chronic pain; Clinical pain assessment; Numerical rating scale; Pain intensity scales
7.  Netazepide, a Gastrin Receptor Antagonist, Normalises Tumour Biomarkers and Causes Regression of Type 1 Gastric Neuroendocrine Tumours in a Nonrandomised Trial of Patients with Chronic Atrophic Gastritis 
PLoS ONE  2013;8(10):e76462.
Autoimmune chronic atrophic gastritis (CAG) causes hypochlorhydria and hypergastrinaemia, which can lead to enterochromaffin-like (ECL) cell hyperplasia and gastric neuroendocrine tumours (type 1 gastric NETs). Most behave indolently, but some larger tumours metastasise. Antrectomy, which removes the source of the hypergastrinaemia, usually causes tumour regression. Non-clinical and healthy-subject studies have shown that netazepide (YF476) is a potent, highly selective and orally-active gastrin/CCK-2 receptor antagonist. Also, it is effective in animal models of ECL-cell tumours induced by hypergastrinaemia.
To assess the effect of netazepide on tumour biomarkers, number and size in patients with type I gastric NETs.
We studied 8 patients with multiple tumours and raised circulating gastrin and chromogranin A (CgA) concentrations in an open trial of oral netazepide for 12 weeks, with follow-up 12 weeks later. At 0, 6, 12 and 24 weeks, we carried out gastroscopy, counted and measured tumours, and took biopsies to assess abundances of several ECL-cell constituents. At 0, 3, 6, 9, 12 and 24 weeks, we measured circulating gastrin and CgA and assessed safety and tolerability.
Netazepide was safe and well tolerated. Abundances of CgA (p<0.05), histidine decarboxylase (p<0.05) and matrix metalloproteinase-7(p<0.10) were reduced at 6 and 12 weeks, but were raised again at follow-up. Likewise, plasma CgA was reduced at 3 weeks (p<0.01), remained so until 12 weeks, but was raised again at follow-up. Tumours were fewer and the size of the largest one was smaller (p<0.05) at 12 weeks, and remained so at follow-up. Serum gastrin was unaffected.
The reduction in abundances, plasma CgA, and tumour number and size by netazepide show that type 1 NETs are gastrin-dependent tumours. Failure of netazepide to increase serum gastrin further is consistent with achlorhydria. Netazepide is a potential new treatment for type 1 NETs. Longer, controlled trials are justified.
Trial Registration
European Union EudraCT database 2007-002916-24 NCT01339169
PMCID: PMC3788129  PMID: 24098507
8.  Parental risk factors for the development of pediatric acute and chronic postsurgical pain: a longitudinal study 
Journal of Pain Research  2013;6:727-741.
The goal of this longitudinal study was to examine the associations among psychological factors and pain reports of children and their parents over the 12 month period after pediatric surgery.
Materials and methods
Included in the study were 83 children aged 8–18 years undergoing major surgery. In each case, the child and one of their parents completed measures of pain intensity and unpleasantness, psychological function, and functional disability at 48–72 hours, 2 weeks (child only), 6 months, and 12 months after surgery.
The strength of the correlation coefficients between the psychological measures of the parent and their child increased significantly over time. There was a fair level of agreement between parent ratings of child acute and chronic pain (6 months after surgery) and the child’s actual ratings. Parent and child pain anxiety scores 48–72 hours after surgery interacted significantly to predict pain intensity, pain unpleasantness, and functional disability levels 2 weeks after discharge from hospital. Parent pain catastrophizing scores 48–72 hours after surgery predicted child pain intensity reports 12 months later.
These results raise the possibility that as time from surgery increases, parents exert greater and greater influence over the pain response of their children, so that by 12 months postsurgery mark, parent pain catastrophizing (measured in the days after surgery) is the main risk factor for the development of postsurgical pain chronicity.
PMCID: PMC3792832  PMID: 24109194
pain anxiety; pain catastrophizing; children; parental risk factors; postsurgical pain
9.  Towards a methodology for cluster searching to provide conceptual and contextual “richness” for systematic reviews of complex interventions: case study (CLUSTER) 
Systematic review methodologies can be harnessed to help researchers to understand and explain how complex interventions may work. Typically, when reviewing complex interventions, a review team will seek to understand the theories that underpin an intervention and the specific context for that intervention. A single published report from a research project does not typically contain this required level of detail. A review team may find it more useful to examine a “study cluster”; a group of related papers that explore and explain various features of a single project and thus supply necessary detail relating to theory and/or context.
We sought to conduct a preliminary investigation, from a single case study review, of techniques required to identify a cluster of related research reports, to document the yield from such methods, and to outline a systematic methodology for cluster searching.
In a systematic review of community engagement we identified a relevant project – the Gay Men’s Task Force. From a single “key pearl citation” we conducted a series of related searches to find contextually or theoretically proximate documents. We followed up Citations, traced Lead authors, identified Unpublished materials, searched Google Scholar, tracked Theories, undertook ancestry searching for Early examples and followed up Related projects (embodied in the CLUSTER mnemonic).
Our structured, formalised procedure for cluster searching identified useful reports that are not typically identified from topic-based searches on bibliographic databases. Items previously rejected by an initial sift were subsequently found to inform our understanding of underpinning theory (for example Diffusion of Innovations Theory), context or both. Relevant material included book chapters, a Web-based process evaluation, and peer reviewed reports of projects sharing a common ancestry. We used these reports to understand the context for the intervention and to explore explanations for its relative lack of success. Additional data helped us to challenge simplistic assumptions on the homogeneity of the target population.
A single case study suggests the potential utility of cluster searching, particularly for reviews that depend on an understanding of context, e.g. realist synthesis. The methodology is transparent, explicit and reproducible. There is no reason to believe that cluster searching is not generalizable to other review topics. Further research should examine the contribution of the methodology beyond improved yield, to the final synthesis and interpretation, possibly by utilizing qualitative sensitivity analysis.
PMCID: PMC3819734  PMID: 24073615
Bibliographic databases; Database searching; Literature searching; Search strategies; Systematic reviews
10.  Benchmarking pain outcomes for children with sickle cell disease hospitalized in a tertiary referral pediatric hospital 
Painful vaso-occlusive crisis (VOC) is the most common reason for hospitalization in children with sickle cell disease.
To benchmark pain outcomes in sickle cell disease, including process outcomes (eg, pain assessment and documentation practices, pain management interventions) and clinical outcomes (eg, pain intensity over hospital stay), to identify areas for improvement.
A retrospective study was conducted on electronic charts of children hospitalized with a primary diagnosis of VOC between July 2007 and August 2008.
A convenience sample of 50 admissions was used. In terms of clinical outcomes, patients presented to the emergency department with an initial median pain intensity of 9/10 (interquartile range 8/10 to 10/10). Forty-three per cent had not used opioids for pain relief at home. The mean (± SD) length of stay was 4.0±2.3 days. For most patients, median scores for highest daily pain intensity remained moderate to high throughout hospitalization, although scores did decrease significantly per day of hospitalization. In terms of process outcomes, pain intensity was assessed according to hospital standards on 25% of days in both the emergency department and the ward. There was no discrepancy between prescribed and administered opioid doses and medication use. In 95% of cases, strong opioid use was in a subtherapeutic or low therapeutic dosage range.
The results showed three areas to target for improvement: improved pain assessment and documentation using valid pain tools; more aggressive multimodal management for peak VOC pain; and better education and support for pain management at home. Further studies are required to evaluate optimal pain treatment practices.
PMCID: PMC3411379  PMID: 22891195
Children; Pain assessment; Pain management; Sickle cell disease
11.  Improvements in pain outcomes in a Canadian pediatric teaching hospital following implementation of a multifaceted, knowledge translation initiative 
A previous audit performed at a tertiary/quaternary pediatric hospital in Toronto, Ontario, demonstrated suboptimal assessment and treatment of children’s pain. Knowledge translation (KT) initiatives (education, reminders, audit and feedback) were implemented to address identified care gaps; however, the impact is unknown.
To determine the impact of KT initiatives on pain outcomes including process outcomes (eg, pain assessment and management practices) and clinical outcomes (eg, pain prevalence and intensity); and to benchmark additional pain practices, particularly opioid administration and painful procedures.
Medical records at The Hospital for Sick Children (Toronto, Ontario) were reviewed on a single day in September 2007. Pain assessment and management practices, and pain prevalence and intensity in the preceding 24 h were recorded on a standardized data collection form. Where possible, pain outcomes were compared with previous audit results.
Records of 265 inpatients were audited. Sixty-three per cent of children underwent a documented pain assessment compared with 27% in an audit conducted previously (P<0.01). Eighty-three per cent of children with documented pain received at least one pain management intervention. Overall, 51% of children received pharmacological therapy, and 15% received either a psychological or physical pain-relieving intervention. Of those assessed, 44% experienced pain in the previous 24 h versus 66% in the previous audit (P<0.01). Fewer children experienced severe pain compared with the first audit (8.7% versus 26.1%; P<0.01). One-third of children received opioids; 19% of these had no recorded pain assessment. Among 131 children who underwent a painful procedure, 21% had a concurrent pain assessment. Painful procedures were accompanied by a pain-relieving intervention in 12.5% of cases.
Following KT initiatives, significant improvements in pain processes (pain assessment documentation and pain management interventions) and clinical outcomes (pain prevalence, pain intensity) were observed. Further improvements are recommended, specifically with respect to procedural pain practices and opioid utilization patterns.
PMCID: PMC3401088  PMID: 22606682
Knowledge translation; Pain assessment; Pain intensity; Pain management; Pain prevalence; Painful procedures
12.  Antioxidant Effectiveness of Vegetable Powders on the Lipid and Protein Oxidative Stability of Cooked Turkey Meat Patties: Implications for Health 
Nutrients  2013;5(4):1241-1252.
Lipid and protein oxidation decreases the shelf-life of foods and may result in formation of end-products potentially detrimental for health. Consumer pressure to decrease the use of synthetic phenolic antioxidants has encouraged identification of alternative compounds or extracts from natural sources. We have assessed whether inclusion of dried vegetable powders improves the oxidative stability of turkey meat patties. Such powders are not only potentially-rich sources of phenolic antioxidants, but also may impart additional health benefits, as inadequate vegetable consumption is a risk factor for heart disease and several cancers. In an accelerated oxidation system, six of eleven vegetable powders significantly (p < 0.05) improved oxidative stability of patties by 20%–30% (spinach < yellow pea < onion < red pepper < green pea < tomato). Improved lipid oxidative stability was strongly correlated with the decreased formation of protein carbonyls (r = 0.747, p < 0.01). However, improved lipid stability could not be ascribed to phenolic acids nor recognized antioxidants, such as α- and γ-tocopherol, despite their significant (p < 0.01) contribution to the total antioxidant capacity of the patties. Use of chemically complex vegetable powders offers an alternative to individual antioxidants for increasing shelf-life of animal-based food products and may also provide additional health benefits associated with increased vegetable intake.
PMCID: PMC3705345  PMID: 23595133
oxidative stability; turkey patties; vegetable powders; antioxidants
13.  Identification of pain-related psychological risk factors for the development and maintenance of pediatric chronic postsurgical pain 
Journal of Pain Research  2013;6:167-180.
The goals of this study were to examine the trajectory of pediatric chronic postsurgical pain (CPSP) over the first year after surgery and to identify acute postsurgical predictors of CPSP.
Eighty-three children aged 8–18 years (mean 13.8, standard deviation 2.4) who underwent major orthopedic or general surgery completed pain and pain-related psychological measures at 48–72 hours, 2 weeks (pain anxiety and pain measures only), and 6 and 12 months after surgery.
Results showed that 1 year after surgery, 22% of children developed moderate to severe CPSP with minimal functional disability. Children who reported a Numeric Rating Scale pain-intensity score ≥ 3 out of 10 two weeks after discharge were more than three times as likely to develop moderate/severe CPSP at 6 months and more than twice as likely to develop moderate/severe CPSP at 12 months than those who reported a Numeric Rating Scale pain score < 3 (6-month relative risk 3.3, 95% confidence interval 1.2–9.0 and 12-month relative risk 2.5, 95% confidence interval 0.9–7.5). Pain unpleasantness predicted the transition from acute to moderate/severe CPSP, whereas anxiety sensitivity predicted the maintenance of moderate/severe CPSP from 6 to 12 months after surgery.
This study highlights the prevalence of pediatric CPSP and the role played by psychological variables in its development/maintenance. Risk factors that are associated with the development of CPSP are different from those that maintain it.
PMCID: PMC3594915  PMID: 23503375
chronic postsurgical pain; children; adolescents; anxiety sensitivity
14.  Pain-related psychological correlates of pediatric acute post-surgical pain 
Journal of Pain Research  2012;5:547-558.
Post-surgical pain is prevalent in children, yet is significantly understudied. The goals of this study were to examine gender differences in pain outcomes and pain-related psychological constructs postoperatively and to identify pain-related psychological correlates of acute post-surgical pain (APSP) and predictors of functional disability 2 weeks after hospital discharge.
Eighty-three children aged 8–18 (mean 13.8 ± 2.4) years who underwent major orthopedic or general surgery completed pain and pain-related psychological measures 48–72 hours and 2 weeks after surgery.
Girls reported higher levels of acute postoperative anxiety and pain unpleasantness compared with boys. In addition, pain anxiety was significantly associated with APSP intensity and functional disability 2 weeks after discharge, whereas pain catastrophizing was associated with APSP unpleasantness.
These results highlight the important role played by pain-related psychological factors in the experience of pediatric APSP by children and adolescents.
PMCID: PMC3508661  PMID: 23204864
acute post-surgical pain; children; adolescents; pain anxiety; pain catastrophizing
15.  The Postoperative Pain Assessment Skills pilot trial 
A significant number of patients continue to experience unrelieved, moderate-to-severe postoperative pain, which can have cardiovascular, pulmonary, gastrointestinal and immunological consequences. Poor pain assessment skills and many common misconceptions about pain among health care professionals (HCPs) are among the factors contributing to inadequate postoperative pain assessment and relief. Although standardized patients (SP) have been successfully used as a simulation method to improve HCP’s assessment skills, not all centres have SP programs. Accordingly, this pilot study examined the efficacy of an alternative simulation method – deteriorating patient simulation – for improving HCP’s pain assessment skills.
Pain-related misbeliefs among health care professionals (HCPs) are common and contribute to ineffective postoperative pain assessment. While standardized patients (SPs) have been effectively used to improve HCPs’ assessment skills, not all centres have SP programs. The present equivalence randomized controlled pilot trial examined the efficacy of an alternative simulation method – deteriorating patient-based simulation (DPS) – versus SPs for improving HCPs’ pain knowledge and assessment skills.
Seventy-two HCPs were randomly assigned to a 3 h SP or DPS simulation intervention. Measures were recorded at baseline, immediate postintervention and two months postintervention. The primary outcome was HCPs’ pain assessment performance as measured by the postoperative Pain Assessment Skills Tool (PAST). Secondary outcomes included HCPs knowledge of pain-related misbeliefs, and perceived satisfaction and quality of the simulation. These outcomes were measured by the Pain Beliefs Scale (PBS), the Satisfaction with Simulated Learning Scale (SSLS) and the Simulation Design Scale (SDS), respectively. Student’s t tests were used to test for overall group differences in postintervention PAST, SSLS and SDS scores. One-way analysis of covariance tested for overall group differences in PBS scores.
DPS and SP groups did not differ on post-test PAST, SSLS or SDS scores. Knowledge of pain-related misbeliefs was also similar between groups.
These pilot data suggest that DPS is an effective simulation alternative for HCPs’ education on postoperative pain assessment, with improvements in performance and knowledge comparable with SP-based simulation. An equivalence trial to examine the effectiveness of deteriorating patient-based simulation versus standardized patients is warranted.
PMCID: PMC3298048  PMID: 22184553
Pain assessment; Randomized controlled trial; Simulation
17.  Primary squamous cell carcinoma of the pancreas: a case report and review of the literature 
Primary squamous cell carcinoma of the pancreas is a rare tumor with poor prognosis and is found in the literature only as case reports. The optimal management course remains poorly defined. We present a case of primary basaloid squamous cell carcinoma of the pancreas metastatic to the liver, which was treated with surgery and systemic chemotherapy. Our patient survived for 15 months: the longest survival reported in the literature to date.
Case presentation
A 70-year-old Caucasian man presented to hospital with a three-month history of weight loss, pruritus and icterus. Imaging studies confirmed the presence of an operable mass lesion in the head of the pancreas. Following a pancreaticoduodenectomy, histology results led us to make a diagnosis of squamous cell carcinoma. Postoperative restaging showed multiple metastases in the liver. He underwent palliative systemic chemotherapy with cisplatin and 5-fluorouracil achieving partial response and an excellent quality of life. He then went on to start second-line chemotherapy, but unfortunately died of sepsis soon thereafter.
This case report emphasizes that achievement of a worthwhile objective and symptomatic palliative response is possible using platinum-based chemotherapy in squamous cell carcinoma of the pancreas.
PMCID: PMC3460769  PMID: 22973995
18.  Pain management in children: Part 1 — Pain assessment tools and a brief review of nonpharmacological and pharmacological treatment options 
Canadian Pharmacists Journal : CPJ  2012;145(5):222-225.
If pain is not treated quickly and effectively in children, it can cause long-term physical and psychological sequelae. Therefore, it is important for all health care providers to understand the importance of effective pain control in children. This article is divided into 2 parts: Part 1 reviews the pharmacotherapy of pain management in children and Part 2 will review the problems relating to the use of codeine in children, and the rationale for recommending morphine as the opioid of choice in the treatment of moderate to severe pain. There has been growing concern about codeine's lack of efficacy and increased safety concerns in its use in children. Due to the variability of codeine metabolism and unpredictable effects on efficacy and safety, The Hospital for Sick Children in Toronto, Ontario, no longer includes codeine or codeine-containing products on the regular hospital formulary and now recommends oral morphine as the agent of choice for the treatment of moderate to severe pain in children. A knowledge translation (KT) strategy was developed and implemented by the hospital's Pain Task Force to support this practice change.
PMCID: PMC3567578  PMID: 23509570
19.  Relative Prognostic Value of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Operable Oesophagogastric Cancer 
ISRN Surgery  2012;2012:804891.
Aims. The aim of this study was to determine the prognostic significance of HER2 receptor expression in operable oesophagogastric adenocarcinoma. Methods. Eighty-five consecutive patients diagnosed with oesophagogastric adenocarcinoma [18 oesophageal (OC), 32 junctional (JC) and 35 gastric (GC)] undergoing potentially curative resection were studied retrospectively. Immunohistochemistry was used to determine HER2 status at endoscopic biopsy and resection specimen. The primary outcome measure was survival. Results. Twenty (24%) patients had HER2 positive tumours which was commoner in JC (14/32, 44% versus 2/18, 11% in OC and 4/35, 11% in GC, P = 0.003). The sensitivity, specificity, positive and negative predictive values of HER2 status at endoscopic biopsy were 56%, 93%, 63%, 91% respectively (weighted Kappa = 0.504, P < 0.0001). Five-year survival in OC HER2 positive negative was 100% and 36% (P = 0.167) compared with 14% and 44% (P = 0.0726) in JC and 50% and 46% (P = 0.942) in GC respectively. Conclusions. Endoscopic biopsy had a high specificity and negative predictive value in determining HER2 status. Patients with JC had a significantly higher rate of HER2 overexpression and this was associated with a nonsignificant poorer survival trend. A larger study is needed to confirm these findings because of the implications for neoadjuvant and adjuvant chemotherapy regimens.
PMCID: PMC3412097  PMID: 22900205
20.  Estrogen Receptor and Progesterone Receptor As Predictive Biomarkers of Response to Endocrine Therapy: A Prospectively Powered Pathology Study in the Tamoxifen and Exemestane Adjuvant Multinational Trial 
Journal of Clinical Oncology  2011;29(12):1531-1538.
The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included a prospectively planned pathology substudy testing the predictive value of progesterone receptor (PgR) expression for outcome of estrogen receptor–positive (ER-positive) early breast cancer treated with exemestane versus tamoxifen.
Patients and Methods
Pathology blocks from 4,781 TEAM patients randomly assigned to exemestane versus tamoxifen followed by exemestane for 5 years of total therapy were collected centrally, and tissue microarrays were constructed from samples from 4,598 patients. Quantitative analysis of hormone receptors (ER and PgR) was performed by using image analysis and immunohistochemistry, and the results were linked to outcome data from the main TEAM trial and analyzed relative to disease-free survival and treatment.
Of 4,325 eligible ER-positive patients, 23% were PgR-poor (Allred < 4) and 77% were PgR- rich (Allred ≥ 5). No treatment-by-marker effect for PgR was observed for exemestane versus tamoxifen (PgR-rich hazard ratio [HR], 0.83; 95% CI, 0.65 to 1.05; PgR-poor HR, 0.85; 95% CI, 0.61 to 1.19; P = .88 for interaction). Both PgR and ER expression were associated with patient prognosis in univariate (PgR HR, 0.53; 95% CI, 0.43 to 0.65; P < .001; ER HR, 0.66; 95% CI, 0.51 to 0.86; P = .002), and multivariate analyses (P < .001 and P = .001, respectively). A trend toward a treatment-by-marker effect for ER-rich patients was observed.
Preferential exemestane versus tamoxifen treatment benefit was not predicted by PgR expression; conversely, patients with ER-rich tumors may derive additional benefit from exemestane. Quantitative analysis of ER and PgR expression provides highly significant information on risk of early relapse (within 1 to 3 years) during treatment.
PMCID: PMC3082973  PMID: 21422407
21.  Rising Rates of All Types of Diabetes in South Asian and Non-South Asian Children and Young People Aged 0–29 Years in West Yorkshire, U.K., 1991–2006 
Diabetes Care  2011;34(3):652-654.
To investigate incidence trends of all diabetes types in all children and young people and in the south Asian subpopulation.
Annual incidence per 100,000 and time trends (1991–2006) were analyzed for 2,889 individuals aged 0–29 years diagnosed with diabetes while resident in West Yorkshire, U.K.
Diagnoses comprised type 1 (83%), type 2 (12%), maturity-onset diabetes of the young (0.7%), “J”-type/other (0.1%), and uncertain/unclassified (4%). There was a lower incidence of type 1 and a threefold excess of type 2 in south Asians compared with non-south Asians. Type 1 incidence leveled out and type 2 increased after the first south Asian case of type 2 was diagnosed in 1999. Type 2 and unclassified diabetes incidence rose in all population subgroups.
The burden of diabetes increased over time for both ethnic groups, with a significant excess of type 2 diabetes in south Asians. The rising incidence of type 1 diabetes in south Asians attenuated as type 2 diabetes increased after 1999.
PMCID: PMC3041200  PMID: 21278139
22.  Clinical Impact and Evidence Base for Physiotherapy in Treating Childhood Chronic Pain 
Physiotherapy Canada  2011;63(1):21-33.
Purpose: As part of the special series on pain, our objectives are to describe the key features of chronic pain in children, present the rationale for interdisciplinary treatment, report a case study based on our biopsychosocial approach, and highlight the integral role of physiotherapy in reducing children's pain and improving function. We also evaluate the evidence base supporting physiotherapy for treating chronic neuropathic pain in children.
Summary of Key Points: Chronic pain affects many children and adolescents. Certain challenging pain conditions begin primarily during adolescence and disproportionately affect girls and women. Children with these conditions require an interdisciplinary treatment programme that includes physiotherapy as well as medication and/or psychological intervention. Converging lines of evidence from cohort follow-up studies, retrospective chart reviews, and one randomized controlled trial support the effectiveness of physiotherapy within an interdisciplinary programme for treating children with chronic pain.
Conclusions: Evidence-based practice dictates that health care providers adopt clear guidelines for determining when treatments are effective and for identifying children for whom such treatments are most effective. Thus, additional well-designed trials are required to better identify the specific physiotherapy modalities that are most important in improving children's pain and function.
PMCID: PMC3024192  PMID: 22210976
biopsychosocial; evidence base for physiotherapy in treating chronic pain; interdisciplinary; inter-professional; paediatric chronic pain management; paediatric complex regional pain syndrome (CRPS); paediatric neuropathic pain; paediatric physiotherapy; biopsychosocial; gestion de la douleur chronique pédiatrique; interprofessionnel; multidisciplinaire; physiothérapie pédiatrique; preuves scientifiques de la physiothérapie pour le traitement de la douleur chronique; syndrome douloureux régional complexe (SDRC) pédiatrique
23.  Behavioural interventions for weight management in pregnancy: A systematic review of quantitative and qualitative data 
BMC Public Health  2011;11:491.
There is a rising prevalence of excessive weight gain in pregnancy and an increasing number of pregnant women who are overweight or obese at the start of the pregnancy. Excessive weight gain during pregnancy is associated with adverse maternal and neonatal consequences and increases the risk of long-term obesity. Pregnancy therefore may be a key time to prevent excessive weight gain and improve the health of women and their unborn child. This systematic review sought to assess the effectiveness of behavioural interventions to prevent excessive weight gain in pregnancy and explore the factors that influence intervention effectiveness.
We undertook a systematic review of quantitative and qualitative evidence. This included a meta-analysis of controlled trials of diet and physical activity interventions to prevent excessive weight gain during pregnancy and a thematic synthesis of qualitative studies that investigated the views of women on weight management during pregnancy. A thorough search of eleven electronic bibliographic databases, reference lists of included studies, relevant review articles and experts in the field were contacted to identify potentially relevant studies.
Two independent reviewers extracted data. RevMan software was used to perform the meta-analyses. Qualitative data was subject to thematic analysis. Both quantitative and qualitative data were aligned using a matrix framework.
Five controlled trials and eight qualitative studies were included. The overall pooled effect size found no significant difference in gestational weight gain amongst participants in the intervention group compared with the control group (mean difference -0.28 95% CI -0.64 to 0.09). The study designs, participants and interventions all varied markedly and there was significant heterogeneity within this comparison in the meta-analysis (I2 67%). Subgroup and sensitivity analysis did not identify contextual elements that influenced the effectiveness of the intervention.
In a thematic analysis of the qualitative studies, three major themes emerged relating to women's views of weight management in pregnancy: pregnancy as a time of transition and change, conflicting and contradictory messages and a perceived lack of control. When the results of both quantitative and qualitative data were aligned it was clear that some of the barriers that women described in achieving healthy weight gain in pregnancy were not addressed by the interventions evaluated. This may have contributed to the limited effectiveness of the interventions.
Despite intense and often tailored interventions there was no statistically significant effect on weight gain during pregnancy. Inadequate and often contradictory information regarding healthy weight management was reported by women in qualitative studies and this was addressed in the interventions but this in itself was insufficient to lead to reduced weight gain. Multiple types of interventions, including community based strategies are needed to address this complex health problem.
PMCID: PMC3154865  PMID: 21696589
24.  Epidemiology and management of painful procedures in children in Canadian hospitals 
Children being cared for in hospital undergo multiple painful procedures daily. However, little is known about the frequency of these procedures and associated interventions to manage the pain. We undertook this study to determine, for children in Canadian hospitals, the frequency of painful procedures, the types of pain management interventions associated with painful procedures and the influence of the type of hospital unit on procedural pain management.
We reviewed medical charts for infants and children up to 18 years of age who had been admitted to 32 inpatient units at eight Canadian pediatric hospitals between October 2007 and April 2008. We recorded all of the painful procedures performed and the pain management interventions that had been implemented in the 24-hour period preceding data collection. We performed descriptive and comparative (analysis of variance, χ2) analyses.
Of the 3822 children included in the study, 2987 (78.2%) had undergone at least one painful procedure in the 24-hour period preceding data collection, for a total of 18 929 painful procedures (mean 6.3 per child who had any painful procedure). For 2334 (78.1%) of the 2987 children who had a painful procedure, a pain management intervention in the previous 24 hours was documented in the chart: 1980 (84.8%) had a pharmacologic intervention, 609 (26.1%) a physical intervention, 584 (25.0%) a psychologic intervention and 753 (32.3%) a combination of interventions. However, for only 844 (28.3%) of the 2987 children was one or more pain management interventions administered and documented specifically for a painful procedure. Pediatric intensive care units reported the highest proportion of painful procedures and analgesics administered.
For less than one-third of painful procedures was there documentation of one or more specific pain management interventions. Strategies for implementing changes in pain management must be tailored to the type of hospital unit.
PMCID: PMC3080557  PMID: 21464171
25.  Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy 
Molecular Cancer  2011;10:37.
Nrf2 is a key transcriptional regulator of a battery of genes that facilitate phase II/III drug metabolism and defence against oxidative stress. Nrf2 is largely regulated by Keap1, which directs Nrf2 for proteasomal degradation. The Nrf2/Keap1 system is dysregulated in lung, head and neck, and breast cancers and this affects cellular proliferation and response to therapy. Here, we have investigated the integrity of the Nrf2/Keap1 system in pancreatic cancer.
Keap1, Nrf2 and the Nrf2 target genes AKR1c1 and GCLC were detected in a panel of five pancreatic cancer cell lines. Mutation analysis of NRF2 exon 2 and KEAP1 exons 2-6 in these cell lines identified no mutations in NRF2 and only synonomous mutations in KEAP1. RNAi depletion of Nrf2 caused a decrease in the proliferation of Suit-2, MiaPaca-2 and FAMPAC cells and enhanced sensitivity to gemcitabine (Suit-2), 5-flurouracil (FAMPAC), cisplatin (Suit-2 and FAMPAC) and gamma radiation (Suit-2). The expression of Nrf2 and Keap1 was also analysed in pancreatic ductal adenocarcinomas (n = 66 and 57, respectively) and matching normal benign epithelium (n = 21 cases). Whilst no significant correlation was seen between the expression levels of Keap1 and Nrf2 in the tumors, interestingly, Nrf2 staining was significantly greater in the cytoplasm of tumors compared to benign ducts (P < 0.001).
Expression of Nrf2 is up-regulated in pancreatic cancer cell lines and ductal adenocarcinomas. This may reflect a greater intrinsic capacity of these cells to respond to stress signals and resist chemotherapeutic interventions. Nrf2 also appears to support proliferation in certain pancreatic adenocarinomas. Therefore, strategies to pharmacologically manipulate the levels and/or activity of Nrf2 may have the potential to reduce pancreatic tumor growth, and increase sensitivity to therapeutics.
PMCID: PMC3098205  PMID: 21489257

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