Publications by authors named "Pamela Ng"

35 Publications

Significantly Minimizing Drug Wastage and the Cost of Cabazitaxel Used to Treat Metastatic Castration-Resistant Prostate Cancer.

Eur Urol 2021 Feb 21;79(2):177-179. Epub 2020 Oct 21.

Division of Medical Oncology, Department of Medicine, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Cabazitaxel is used to treat patients with metastatic castration-resistant prostate cancer progressing after docetaxel. It is prepackaged in 60 mg single-dose vials, a quantity much higher than the average prescribed dose, which leads to, substantial drug wastage (DW) and associated costs. To minimize DW we implemented a cost-saving, cohorting strategy where multiple patients scheduled to receive cabazitaxel (at a dose of 20mg/m every 3 wks) were cohorted and treated on a single weekday whenever possible. Excess drug from each vial was then saved and used for subsequent patients treated on the same day. The drug cost with cohorting was calculated from the actual number of vials used, and the drug cost without cohorting was estimated by assumingthat one vial was used per treatment. The cost of DW was determined based on the amount of drug that was discarded. All cost calculations also accounted for the discount incentives offered by Sanofi-Aventis. Over a 3-yr period, 74 patients received 402 treatments of cabazitaxel. Multiple patients were treated on 67.4% of the treatment days, and grouping of three patients on one day saved one vial. The estimated total drug cost saved was $394 536 CAD (21.1%). Pending further studies on safety and efficacy, this strategy could potentially be adopted to mitigate DW for cabazitaxel and similarly for other oncology drugs. This would significantly decrease the overall financial burden on patients, institutions, and stakeholders. PATIENT SUMMARY: Cabazitaxel chemotherapy is associated with substantial drug wastage and associated costs. By cohorting patients scheduled to receive cabazitaxel on a single weekday, the total drug cost was decreased by $394 536 CAD (21.1%) over a 3-yr period. Similar strategies could be considered to overcome the prohibitory costs associated with drug wastage for cabazitaxel and other cancer drugs.
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http://dx.doi.org/10.1016/j.eururo.2020.09.048DOI Listing
February 2021

Emergency Department Use in Children with Cerebral Palsy: A Data Linkage Study.

Can J Neurol Sci 2020 Oct 7:1-6. Epub 2020 Oct 7.

Departments of Pediatrics and Neurology & Neurosurgery, McGill University, Montréal, Quebec, Canada.

Objective: To describe the pattern of emergency department (ED) consultations in children with cerebral palsy (CP) compared to controls and factors predictive of ED consultations.

Methods: This retrospective cohort study linked data from the Registre de la paralysie cérébrale du Québec (REPACQ) and provincial administrative health databases. The CP cohort was comprised of children enrolled in REPACQ born between 1999 and 2002. REPACQ covers 6 of 17 Quebec health administrative regions. Region-, age-, and gender-matched controls were identified from administrative health databases in a 20:1 ratio. The primary outcome was high use of ED services (≥4 ED visits during the study period). Relative risk (RR) and 95% confidence interval (CI) were calculated.

Results: In total, 301 children with CP were linked to administrative data and 6040 peer controls were selected. Ninety-two percent (92%) of the CP cohort had at least one ED visit in the study period, compared to 74% among controls (RR 1.24, 95% CI 1.19-1.28). Children with CP were more likely than their peers to have high ED use (RR 1.40; 95% CI 1.30-1.52). Factors predictive of high ED use were comorbid epilepsy (RR 1.23; 95% CI 1.04-1.46) and severity of motor impairment (RR 1.14; 95% CI 0.95-1.37).

Conclusion: Children with CP are more likely to present to the ED than their peers, resulting in increased use of ED services. Coordinated care with improved access to same-day evaluations could decrease ED use. Health system factors and barriers should be investigated to ensure optimal and appropriate use of ED services.
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http://dx.doi.org/10.1017/cjn.2020.217DOI Listing
October 2020

Hospitalizations in School-Aged Children with Cerebral Palsy and Population-Based Controls.

Can J Neurol Sci 2020 Sep 11:1-8. Epub 2020 Sep 11.

Departments of Pediatrics and Neurology & Neurosurgery, McGill University, Montréal, QC, Canada.

Objective: To compare hospitalizations among children with cerebral palsy (CP) and healthy controls and to identify factors associated with hospitalizations in children with CP.

Methods: This retrospective cohort study linked data from a provincial CP Registry and administrative health databases. The CP cohort was comprised of children born from 1999 to 2002. Age, sex, and region-matched controls were identified from administrative health databases. Mean differences, relative risk (RR), and 95% confidence intervals (CIs) were calculated.

Results: A total of 301 children with CP were linked to administrative health data and matched to 6040 controls. Mean hospitalizations per child during the study period were higher in children with CP compared to controls (raw mean difference (RMD) 5.0 95% CI 4.7 to 5.2) with longer length of stay (RMD 2.8 95% CI 1.8 to 3.8) and number of diagnoses per hospitalization (RMD 1.6 95% CI 1.4 to 1.8). Increased risk of hospitalization was observed in non-ambulant children with CP (RR 1.12 95% CI 1.01 to 1.22) compared to ambulant children and among those with spastic tri/quadriplegic CP compared to other CP subtypes (RR 1.15, 95% CI 1.05 to 1.27). Feeding difficulties (RR 1.20 95% CI 1.13 to 1.27), cortical visual (RR 1.22 95% CI 1.13 to 1.32), cognitive (RR 1.16 95% CI 1.04 to 1.30), and communication impairment (RR 1.26 95% CI 1.10 to 1.44) were associated with increased hospitalizations.

Conclusions: Children with CP face more frequent, longer hospital stays than peers, especially those with a more severe CP profile. Coordinated interdisciplinary care is needed in school-aged children with CP and medical complexity.
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http://dx.doi.org/10.1017/cjn.2020.199DOI Listing
September 2020

Complementary and Alternative Therapy Use in Children with Cerebral Palsy.

Can J Neurol Sci 2020 Aug 28:1-7. Epub 2020 Aug 28.

Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Objective: To describe complementary and alternative medicine (CAM) use amongst children with cerebral palsy (CP) in Canada and to identify factors associated with CAM use.

Methods: We conducted a cross-sectional study, utilising data from the Canadian CP Registry. We explored the association between CAM use and regional, socioeconomic and CP phenotypic variables, and parental perception of the family-centredness of clinical care using the Measures of Process of Care-56 (MPOC-56). Chi-square analyses were performed, and odds ratios (OR) and 95% confidence intervals (CI) were obtained. Mann-Whitney U tests were used to compare MPOC-56 scores between CAM users and non-CAM users.

Results: The study sample consisted of 313 families of which 27% reported CAM use in the past year. Children with CP using CAM were more likely to reside in Western Canada (OR 3.3, 95% CI 1.6-6.7), live in a two-parent household (OR 3.5, 95% CI 1.5-8.4), have an ataxic/hypotonic or dyskinetic CP subtype (OR 3.0, 95% CI 1.5-6.1) and have a greater motor impairment (OR 2.8, 95% CI 1.7-4.9). MPOC-56 subscale scores were not significantly associated with CAM use.

Conclusion: Physicians need to be aware of existing CAM therapies, the level of evidence supporting their efficacy (beneficence), their associated risks of adverse events (non-maleficence) and enable fair access to care that may be of benefit to each child.
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http://dx.doi.org/10.1017/cjn.2020.188DOI Listing
August 2020

Reducing dexamethasone antiemetic prophylaxis during the COVID-19 pandemic: recommendations from Ontario, Canada.

Support Care Cancer 2020 Oct 30;28(10):5031-5036. Epub 2020 Jun 30.

Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.

Purpose: People with cancer face an elevated risk of infection and severe sequelae from COVID-19. Dexamethasone is commonly used for antiemetic prophylaxis with systemic therapy for cancer. However, dexamethasone is associated with increased risk of viral and respiratory infections, and causes lymphopenia, which is associated with worse outcomes during COVID-19 infections. Our purpose was to minimize dexamethasone exposure during antiemetic prophylaxis for systemic therapy for solid tumors during the COVID-19 pandemic, while maintaining control of nausea and emesis.

Methods: We convened an expert panel to systematically review the literature and formulate consensus recommendations.

Results: No studies considered the impact of dexamethasone-based antiemetic regimens on the risk and severity of COVID-19 infection. Expert consensus recommended modifications to the 2019 Cancer Care Ontario Antiemetic Recommendations.

Conclusion: Clinicians should prescribe the minimally effective dose of dexamethasone for antiemetic prophylaxis. Single-day dexamethasone dosing is recommended over multi-day dosing for regimens with high emetogenic risk excluding high-dose cisplatin, preferably in combination with palonosetron, netupitant, and olanzapine. For regimens with low emetogenic risk, 5-HT antagonists are recommended over dexamethasone.
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http://dx.doi.org/10.1007/s00520-020-05588-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324309PMC
October 2020

Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes.

J Immunother Cancer 2020 06;8(1)

Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada

Background: Immune checkpoint inhibitors (ICPi) are a novel and promising anti-cancer therapy. There are limited data on the incidence, risk factors and outcomes of acute kidney injury (AKI) in patients receiving ICPi.

Methods: We conducted a cohort study of patients receiving ICPi at our center between 2010 and 2017 via electronic health record. The primary outcome was AKI (increase of >50% from baseline serum creatinine (sCr)). Risk factors for AKI were assessed using logistic regression. Survival among those with and without AKI was compared using the Kaplan-Meier method.

Results: Among 309 patients on ICPi, 51 (16.5%) developed AKI (Kidney Disease Improving Global Outcomes (KDIGO) stages 1: 53%, 2: 22%, 3: 25%). AKI was associated with other immune-related adverse events (IRAE) (OR 3.2, 95% CI 1.6 to 6; p<0.001), hypertension (OR 4.3, 95% CI 1.8 to 6.1; p<0.001) and cerebrovascular disease (OR 9.2; 95% CI 2.1 to 40; p<0.001). Baseline sCr, cancer, and ICPi type was not associated with AKI. Use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (OR 2.9; 95% CI 1.5 to 5.7; p=0.002), diuretics (OR 4.3; 95% CI 1.9 to 9.8; p<0.001), and corticosteroid treatment (OR 1.9; 95% CI 1.1 to 3.6; p=0.03) were associated with AKI. In the multivariable analysis, AKI was associated only with other IRAE (OR 2.82; 95% CI 1.45 to 5.48; p=0.002) and hypertension (OR 2.96; 95% CI 1.33 to 6.59; p=0.008). AKI was not associated with increased risk of mortality (HR 1.1; 95% CI: 0.8 to 1.6; p=0.67). ICPi nephrotoxicity was attributed via biopsy or nephrologist assessment in 12 patients (six interstitial nephritis, two membranous nephropathy, two minimal change disease, and two thrombotic microangiopathy). Subsequent doses of ICPi were administered to 12 patients with prior AKI, with one (8.3%) having recurrent AKI.

Conclusion: AKI is a common complication in patients receiving ICPi treatment. The development of other IRAE and previous diagnosis of hypertension were associated with increased AKI risk. AKI was not associated with worse survival. Distinguishing kidney IRAE from other causes of AKI will present a frequent challenge to oncology and nephrology practitioners. Kidney biopsy should be considered to characterize kidney lesions and guide potential therapy.
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http://dx.doi.org/10.1136/jitc-2019-000467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326260PMC
June 2020

Congenital Malformations in Children With Cerebral Palsy: Is Prematurity Protective?

Pediatr Neurol 2020 07 12;108:70-76. Epub 2020 Feb 12.

Department of Pediatrics, McGill University, Montreal, Quebec City, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, Canada. Electronic address:

Background: Congenital malformations are more common in children who are born prematurely, and prematurity is the leading risk factor for cerebral palsy. The primary objective of this study was to describe the profile of congenital malformations in a Canadian cohort of children with cerebral palsy. The secondary objectives were to compare the profiles of children with cerebral palsy with and without a congenital malformation and explore the possible role of prematurity.

Methods: This retrospective cohort study utilized data from the Canadian Cerebral Palsy Registry, a population based registry of children with a confirmed diagnosis of cerebral palsy. Differences between groups were compared using Pearson's chi-square and Student t test as appropriate. Odds ratios and 95% confidence intervals were calculated RESULTS: Congenital malformations were present in 23% participants. In term-born children, brain malformations were the most common, whereas heart and gastrointestinal malformations were more common in children born prematurely. Children with a malformation had higher odds of being born at term (odds ratio 1.57, 95% confidence interval 1.20 to 2.04); having hypotonic, ataxic, or dyskinetic cerebral palsy (odds ratio 1.92, 95% confidence interval 1.35 to 2.72; being nonambulatory (odds ratio 1.70, 95% confidence interval 1.29 to 2.25); and having cerebral palsy-associated comorbidities.

Conclusions: One in four children with cerebral palsy have an associated congenital malformation. Their profile of term birth, higher Apgar scores, and lower frequency of perinatal seizures suggests a distinct causal pathway.
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http://dx.doi.org/10.1016/j.pediatrneurol.2020.02.002DOI Listing
July 2020

Ataxic-hypotonic cerebral palsy in a cerebral palsy registry: Insights into a distinct subtype.

Neurol Clin Pract 2020 Apr;10(2):131-139

Faculty of Medicine (JPL), McGill University, Montreal, QC; Department of Pediatrics and Neurology and Neurosurgery (MO, MS), McGill University, Montreal, QC; Centre for Outcomes Research and Evaluation (MO, PN, MS), Research Institute of the McGill University Health Centre, Montreal, QC; Department of Pediatrics (JA), University of Alberta, Edmonton, AB; Janeway Children's Hospital (DB), St. John's, NL; Department of Paediatrics (DF), University of Toronto, Bloorview Research Institute, Toronto, ON; Departments of Pediatrics and Clinical Neurosciences (AK), Cumming School of Medicine, University of Calgary, AB; Centre de réadaptation Marie Enfant du CHU Sainte-Justine (LK), Montreal, QC; Centre hospitalier universitaire de Sherbrooke (NP), Sherbrooke, QC; BC Children's Hospital (EvR), Vancouver, BC; and IWK Health Centre (EW), Halifax, NS, Canada.

Objective: To specifically report on ataxic-hypotonic cerebral palsy (CP) using registry data and to directly compare its features with other CP subtypes.

Methods: Data on prenatal, perinatal, and neonatal characteristics and gross motor function (Gross Motor Function Classification System [GMFCS]) and comorbidities in 35 children with ataxic-hypotonic CP were extracted from the Canadian Cerebral Palsy Registry and compared with 1,804 patients with other subtypes of CP.

Results: Perinatal adversity was detected significantly more frequently in other subtypes of CP (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.5-11.7). The gestational age at birth was higher in ataxic-hypotonic CP (median 39.0 weeks vs 37.0 weeks, = 0.027). Children with ataxic-hypotonic CP displayed more intrauterine growth restriction (OR 2.6, 95% CI 1.0-6.8) and congenital malformation (OR 2.4, 95% CI 1.2-4.8). MRI was more likely to be either normal (OR 3.8, 95% CI 1.4-10.5) or to show a cerebral malformation (OR 4.2, 95% CI 1.5-11.9) in ataxic-hypotonic CP. There was no significant difference in terms of GMFCS or the presence of comorbidities, except for more frequent communication impairment in ataxic-hypotonic CP (OR 4.2, 95% CI 1.5-11.6).

Conclusions: Our results suggest a predominantly genetic or prenatal etiology for ataxic-hypotonic CP and imply that a diagnosis of ataxic-hypotonic CP does not impart a worse prognosis with respect to comorbidities or functional impairment. This study contributes toward a better understanding of ataxic-hypotonic CP as a distinct nosologic entity within the spectrum of CP with its own pathogenesis, risk factors, clinical profile, and prognosis compared with other CP subtypes.
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http://dx.doi.org/10.1212/CPJ.0000000000000713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156190PMC
April 2020

Safety of two-hour intermittent intravenous infusions of tacrolimus in the allogeneic hematopoietic stem cell transplantation unit.

J Oncol Pharm Pract 2021 Jan 17;27(1):33-39. Epub 2020 Mar 17.

Messner Allogeneic Transplant Program, University Health Network, Toronto, Canada.

At our institution, tacrolimus is used as a second-line agent for the prevention and treatment of graft-versus-host-disease in the allogeneic hematopoietic stem cell transplantation (HSCT) unit after patients have experienced a serious or intolerable adverse event to cyclosporine. As per our standard practice, tacrolimus is administered via 2-h intermittent IV infusions (IIVs) every 12 h rather than continuous IV infusion. Shorter infusion times are cautioned due to concerns of higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions, although there is a paucity of data to support this claim. Our primary objective was to evaluate the safety of a 2-h IIV of tacrolimus in an adult HSCT population. We retrospectively reviewed the charts of 104 patients who received tacrolimus by IIV (3574 doses; median = 22, range 1-158, IQR = 28) from 2002 to 2016. Primary outcomes collected include rates of nephrotoxicity, neurotoxicity and infusion-related reactions. One (0.9%) grade 2 infusion-related reaction occurred and resolved without discontinuation of tacrolimus. Of 16 incidences (13.6%) of nephrotoxicity, all but 10 (8.5%) cases resolved. Precipitating factors for nephrotoxicity unrelated to tacrolimus were identified in all 10 cases. There were 41 incidences (35%) of neurotoxicity, of which, 8 (6.8%) were considered serious. All neurotoxicity reverted to baseline or resolved completely. We propose that a 2-h IIV of tacrolimus is a safe method of administration in the adult HSCT setting.
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http://dx.doi.org/10.1177/1078155220908948DOI Listing
January 2021

Optimizing the Care of Malignant Bowel Obstruction in Patients With Advanced Gynecologic Cancer.

J Oncol Pract 2019 12 24;15(12):e1066-e1075. Epub 2019 Sep 24.

Princess Margaret Cancer Centre, Toronto, ON, Canada.

Purpose: Malignant bowel obstruction (MBO) is a common and distressing complication in women with advanced gynecologic cancer. A pilot, interprofessional MBO program was launched in 2016 at a large Canadian tertiary cancer center to integrate these patients' complex care needs across multiple disciplines and support women with MBO.

Method: Retrospective analysis to evaluate the outcomes of women with advanced gynecologic cancer who were admitted to hospital because of MBO, before (2014 to 2016: baseline group) and after (2016 to 2018) implementation of the MBO program.

Results: Of the 169 women evaluated, 106 and 63 were in the baseline group and MBO program group, respectively. Most had ovarian cancer (n = 124; 73%) and had small-bowel obstruction (n = 131; 78%). There was a significantly shorter cumulative hospital length of stay (LOS) within the first 60 days of MBO diagnosis in the MBO program group compared with the baseline group (13 22 days, respectively; adjusted = .006). The median overall survival for women treated in the MBO program was also significantly longer compared with the baseline group (243 99 days, respectively; adjusted = .002). Using the interprofessional MBO care platform, a greater proportion of patients received palliative chemotherapy (83% 56%) and less surgery (11% 21%) in the MBO program group than in the baseline group, respectively. A subgroup of women (n = 11) received total parenteral nutrition for longer than 6 months.

Conclusion: Implementation of a comprehensive, interprofessional MBO program significantly affects patient care and may improve outcomes. Unique to this MBO program is an integrated outpatient model of care and education that empowers patients to recognize MBO symptoms for early intervention.
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http://dx.doi.org/10.1200/JOP.18.00793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911166PMC
December 2019

Is Cerebral Palsy Changing in High Resource Settings? Data From the Quebec Cerebral Palsy Registry.

J Child Neurol 2019 09 10;34(10):567-573. Epub 2019 May 10.

1 Department of Pediatrics, McGill University, Montreal, Québec, Canada.

Advances in maternal and perinatal care in developed countries have led to improved health outcomes for children. These changes may have impacted the profile of children with a cerebral palsy (CP) and groups at risk for CP over time. Using data from the Canadian CP Registry, the objectives of this retrospective cohort study were to describe the profile of children with CP in Quebec born between 1999 and 2010 and identify possible temporal variation in CP risk factors and phenotypic profile. Our sample consisted of 662 children with CP in Quebec. No change in profile or associated risk factors was observed across the birth cohorts 1999 to 2010. Prematurity remains the largest risk factor for CP in Quebec, and children with CP have multiple comorbidities that contribute to overall CP burden. CP registries offer a unique platform to study spectrum disorders and their longitudinal changes over time.
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http://dx.doi.org/10.1177/0883073819845272DOI Listing
September 2019

The Placenta in Neonatal Encephalopathy: A Case-Control Study.

J Pediatr 2018 11 29;202:77-85.e3. Epub 2018 Jun 29.

Department of Pediatrics and Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.

Objective: We assessed whether specific histologic placental lesions were associated with risk for neonatal encephalopathy, a strong predictor of death or cerebral palsy.

Study Design: Case-control study of singletons with gestational ages ≥35 weeks. Data were abstracted from a prospectively collected database of consecutive births at a hospital in which placental samples from specified sites are collected and stored for all inborn infants. Placentas of infants with neonatal encephalopathy were compared with randomly selected control infants (ratio of 1:3). Placental histologic slides were read by a single experienced perinatal pathologist unaware of case status, using internationally recommended definitions and terminology. Findings were grouped into inflammatory, maternal, or fetal vascular malperfusion (FVM) and other lesions.

Results: Placental samples were available for 73 of 87 (84%) cases and 253 of 261 (97%) controls. Delivery complications and gross placental abnormalities were more common in cases, of whom 4 died. Inflammation and maternal vascular malperfusion did not differ, and findings consistent with global FVM were more frequent in case (20%) than control (7%) placentas (P = .001). There was a trend toward more segmental FVM and high-grade FVM (fetal thrombotic vasculopathy) among cases. Some type of FVM was observed in 24% of placentas with neonatal encephalopathy. In infants with both neonatal encephalopathy and placental FVM, more often than in infants with neonatal encephalopathy without FVM, electronic fetal monitoring tracings were considered possibly or definitely abnormal (P = .028).

Conclusions: Vascular malperfusion of subacute or chronic origin on the fetal side of the placenta was associated with increased risk of neonatal encephalopathy.
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http://dx.doi.org/10.1016/j.jpeds.2018.06.005DOI Listing
November 2018

Family-centred health care for children with cerebral palsy.

Dev Med Child Neurol 2019 01 7;61(1):62-68. Epub 2018 Oct 7.

School of Physical and Occupational Therapy, McGill University, Montreal, QC, Canada.

Aim: To identify characteristics of young children with cerebral palsy (CP), and intrinsic and extrinsic factors, that may be associated with parental perceptions regarding family-centred health care services.

Method: We conducted a cross-sectional study, drawing our sample from the Canadian Cerebral Palsy Registry (CCPR). Parents rated the extent of family-centred care provided by their child's health care teams using the 56-item Measures of Process of Care (MPOC) questionnaire. Environmental and CP phenotypic variables were extracted from the CCPR for group comparisons. Low and high MPOC-56 raters were also compared.

Results: Valid responses were obtained from 282 families (90%). All MPOC-56 subscales were highly rated (median ≥6.0), indicating satisfaction with health care services, with the exception of the Providing General Information subscale (median 4.8, interquartile range 3.2-6.0). Parents from Nova Scotia rated all subscales significantly higher than parents from other regions. CP subtype and severity were not significantly associated with MPOC-56 subscale scores. Higher socio-economic status was associated with lower MPOC-56 subscale scores. Higher paternal educational attainment and household income were significantly associated with lower scores on the Providing General Information and Providing Specific Information about the Child subscales respectively.

Interpretation: Participants affirmed the provision of family-centred services from Canadian pediatric rehabilitation centres. Sociodemographic factors were associated with parental perceptions of family-centred services.

What This Paper Adds: Sociodemographic factors were associated with parental perceptions of family-centred care. Factors intrinsic to the child's cerebral palsy were not associated with parental perceptions.
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http://dx.doi.org/10.1111/dmcn.14053DOI Listing
January 2019

Malignant Bowel Obstruction in Advanced Gynecologic Cancers: An Updated Review from a Multidisciplinary Perspective.

Obstet Gynecol Int 2018 17;2018:1867238. Epub 2018 May 17.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre/University Health Network, Toronto, ON, Canada.

Malignant bowel obstruction (MBO) is a major complication in women with advanced gynecologic cancers which imposes a significant burden on patients, caregivers, and healthcare systems. Symptoms of MBO are challenging to palliate and result in progressive decompensation of already vulnerable patients with limited therapeutic options and a short prognosis. However, there is a paucity of guidelines or innovative approaches to improve the care of women who develop MBO. MBO is a complex clinical situation that requires a multidisciplinary approach to ensure the appropriate treatment modality and interprofessional care to optimally manage these patients. This review summarizes the current literature on the different approaches targeting MBO management including surgical intervention, chemotherapy, total parenteral nutrition, and pharmacological treatment. In addition, the impact of MBO management on patients' quality of life (QOL) is examined. This article focuses on the challenges in developing evidence-based treatment guidelines for MBO and barriers in clinical trial design for MBO and proposes strategies to advance the MBO management. Collaboration is essential to design studies that may improve the overall care and quality of life for these patients. Prospective data are needed to inform clinical practice, establish a new benchmark for evidence-based MBO management, and better understand the biology of MBO.
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http://dx.doi.org/10.1155/2018/1867238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985138PMC
May 2018

A case-control study analyzing mannitol dosing for prevention of cisplatin-induced acute nephrotoxicity.

J Oncol Pharm Pract 2019 Jun 3;25(4):875-883. Epub 2018 May 3.

1 Department of Pharmacy, Princess Margaret Cancer Centre, UHN, Toronto, Canada.

Background: Mannitol is an osmotic diuretic given routinely as part of cisplatin regimens to prevent nephrotoxicity, but there are limited data on the ideal dosage. At our center, three different doses of mannitol are used: 12, 20, and 40 g per cycle for cisplatin doses of ≥50 mg/m. The primary objective was to determine if variations in mannitol dosing significantly influence the incidence of cisplatin-induced acute nephrotoxicity.

Methods: A case-control study was performed. Electronic records of 1462 consecutive outpatients who received cisplatin at ≥ 50 mg/m per cycle between January 2010 and December 2014 were reviewed. Patients experiencing nephrotoxicity of any grade within 30 days of last cisplatin dose, as defined by NCI CTCAE 4.0, were matched to a minimum of two and maximum of five controls based on the following criteria: age ± 5 years, baseline estimated glomerular filtration rate ± 10 ml/min/1.73 m, cisplatin dose per cycle, and presence of diabetes. Conditional logistic regression was used to identify baseline predictors of cisplatin-induced acute nephrotoxicity.

Results: Of the 1245 included patients, 237 had nephrotoxicity and 1008 were matched controls. Median baseline estimated glomerular filtration rate for cases and controls were 83 and 80 ml/min/1.73 m, respectively. A total of 3.8% of cases experienced ≥ grade 3 nephrotoxicity. Univariable analysis showed that diabetes, lymphoma, low baseline estimated glomerular filtration rate, and low baseline magnesium level were significantly associated with nephrotoxicity, whereas mannitol dosing did not show any association (odds ratio 1.08; p = 0.29). In multivariable analysis, diabetes and lymphoma retained statistical significance, but baseline estimated glomerular filtration rate and baseline magnesium level showed nonsignificant associations with nephrotoxicity.

Conclusions: Cisplatin-induced acute nephrotoxicity remains common in patients with good baseline renal function despite preventive measures. Diabetes and lymphoma are predictors of nephrotoxicity, whereas mannitol dosing has no significant influence, suggesting that doses may be standardized across cisplatin regimens.
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http://dx.doi.org/10.1177/1078155218771461DOI Listing
June 2019

The Association Between Maternal Age and Cerebral Palsy Risk Factors.

Pediatr Neurol 2018 05 12;82:25-28. Epub 2018 Feb 12.

Department of Pediatrics, McGill University, Montreal, Quebec, Canada; Department of Neurology/Neurosurgery, McGill University, Montreal, Quebec, Canada.

Background: Advanced maternal age is associated with higher frequencies of antenatal and perinatal conditions, as well as a higher risk of cerebral palsy in offspring. We explore the association between maternal age and specific cerebral palsy risk factors.

Methods: Data were extracted from the Canadian Cerebral Palsy Registry. Maternal age was categorized as ≥35 years of age and less than 20 years of age at the time of birth. Chi-square and multivariate logistic regressions were performed to calculate odds ratios and their 95% confidence intervals.

Results: The final sample consisted of 1391 children with cerebral palsy, with 19% of children having mothers aged 35 or older and 4% of children having mothers below the age of 20. Univariate analyses showed that mothers aged 35 or older were more likely to have gestational diabetes (odds ratio 1.9, 95% confidence interval 1.3 to 2.8), to have a history of miscarriage (odds ratio 1.8, 95% confidence interval 1.3 to 2.4), to have undergone fertility treatments (odds ratio 2.4, 95% confidence interval 1.5 to 3.9), and to have delivered by Caesarean section (odds ratio 1.6, 95% confidence interval 1.2 to 2.2). These findings were supported by multivariate analyses. Children with mothers below the age of 20 were more likely to have a congenital malformation (odds ratio 2.4, 95% confidence interval 1.4 to 4.2), which is also supported by multivariate analysis.

Conclusions: The risk factor profiles of children with cerebral palsy vary by maternal age. Future studies are warranted to further our understanding of the compound causal pathways leading to cerebral palsy and the observed greater prevalence of cerebral palsy with increasing maternal age.
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http://dx.doi.org/10.1016/j.pediatrneurol.2018.01.005DOI Listing
May 2018

Neonatal Infection in Children With Cerebral Palsy: A Registry-Based Cohort Study.

Pediatr Neurol 2018 03 13;80:77-83. Epub 2017 Dec 13.

Department of Pediatrics, McGill University, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. Electronic address:

Background: The goal of this study was to explore the association between neonatal infection and outcomes in children with cerebral palsy.

Methods: We conducted a retrospective cohort study using the Canadian CP Registry. Neonatal infection was defined as meeting one of the following criteria: (1) septicemia, (2) septic shock, or (3) administration of antibiotics for ≥10 days. Phenotypic profiles of children with cerebral palsy with and without an antecedent neonatal infection were compared. Subgroup analysis was performed, stratified by gestational age (term versus preterm).

Results: Of the 1229 registry participants, 505 (41.1%) were preterm, and 192 (15.6%) met the criteria for neonatal infection with 29% of preterm children having a neonatal infection compared with 6.5% in term-born children. Children with prior neonatal infection were more likely to have a white matter injury (odds ratio 2.2, 95% confidence interval 1.5 to 3.2), spastic diplegic neurological subtype (odds ratio 1.6, 95% confidence interval 1.1 to 2.3), and sensorineural auditory impairment (odds ratio 2.1, 95% confidence interval 1.4 to 3.3). Among preterm children, neonatal infection was not associated with a difference in phenotypic profile. Term-born children with neonatal infection were more likely to have spastic triplegia or quadriplegia (odds ratio 2.4, 95% confidence interval 1.3 to 4.3), concomitant white matter and cortical injury (odds ratio 4.1, 95% confidence interval 1.6 to 10.3), and more severe gross motor ability (Gross Motor Function Classification System IV to V) (odds ratio 2.6, 95% confidence interval 1.4 to 4.8) compared with preterm children.

Conclusions: Findings suggest a role of systemic infection on the developing brain in term-born infants, and the possibility to develop targeted therapeutic and preventive strategies to reduce cerebral palsy morbidity.
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http://dx.doi.org/10.1016/j.pediatrneurol.2017.11.006DOI Listing
March 2018

Recurrent Body Rash Warranted Second Desensitization With Acyclovir in a Myeloma Patient: A Case Report.

J Clin Med Res 2017 Aug 1;9(8):725-728. Epub 2017 Jul 1.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada.

A 75-year-old woman developed a moderately severe rash about a week and a half after the start of bortezomib (Btb)-based chemotherapy for IgG lambda multiple myeloma; at the time, she was also receiving acyclovir as antiviral prophylaxis in addition to herpes zoster (HZ) vaccination. HZ reactivation rate is high in Btb recipients; therefore, the timing of antiviral prevention is critical in relation to Btb. Attempts were made to identify the offending agent based on the timing of drugs administered and the appearance of skin lesions in relation to other drugs. Both Btb and acyclovir were potential culprits. However, the timing of rash presented on days 9 - 10 revealed the offending agent when the corticosteroid was weaned off while acyclovir continued. A decision was made to administer acyclovir rapid desensitization program (RDP) for our patient.
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http://dx.doi.org/10.14740/jocmr2772wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505310PMC
August 2017

Accuracy of administrative claims data for cerebral palsy diagnosis: a retrospective cohort study.

CMAJ Open 2017 Jul;5(3):E570-E575

Affiliations: Departments of Pediatrics, Neurology and Neurosurgery (Oskoui, Shevell), McGill University; Research Institute of the McGill University Health Centre (Ng), Montréal, Que.; StatSciences Inc. (Dorais), Notre-Dame-de-l'Île-Perrot, Que.; Centre hospitalier universitaire de Sherbrooke (Pigeon), Sherbrooke, Que.; Centre de réadaptation Marie-Enfant (Koclas), Centre hospitalier universitaire Sainte-Justine; Institut de réadaptation Gingras-Lindsay de Montréal (Lamarre), Centre intégré universitaire de santé et de services sociaux du Centre-Est-de-l'Île-de-Montréal, Montréal, Que.; Département de réadaptation and Centre interdisciplinaire de recherche en réadaptation et intégration sociale (Malouin, Richards), Université Laval, Québec, Que.; Department of Epidemiology, Biostatistics and Occupational Health (Joseph), McGill University, Montréal, Que.

Background: Cerebral palsy is the most common cause of childhood physical disability, with multiple associated comorbidities. Administrative claims data provide population-level prevalence estimates for cerebral palsy surveillance; however, their diagnostic accuracy has never been validated in Quebec. This study aimed to assess the accuracy of administrative claims data for the diagnosis of cerebral palsy.

Methods: We conducted a retrospective cohort study of children with cerebral palsy born between 1999 and 2002 within 6 health administrative regions of Quebec. Provincial cerebral palsy registry data (reference standard) and administrative physician claims were linked. We explored differences between true-positive and false-negative cases using subgroup sensitivity analysis.

Results: A total of 301 children were identified with confirmed cerebral palsy from the provincial registry, for an estimated prevalence of 1.8 (95% confidence interval [CI] 1.6-2.1) per 1000 children 5 years of age. The sensitivity and specificity of administrative claims data for cerebral palsy were 65.5% (95% CI 59.8%-70.8%) and 99.9% (95% CI 99.9%-99.9%), respectively, yielding a prevalence of 2.0 (95% CI 1.9-2.3) per 1000 children 5 years of age. The positive and negative predictive values were 58.8% (95% CI 53.3%-64.1%) and 99.9% (95% CI 99.9%-99.9%), respectively. The κ value was 0.62 (95% CI 0.57-0.67). Administrative claims data were more sensitive for children from rural regions, born preterm, with spastic quadriparesis and with higher levels of motor impairment.

Interpretation: Administrative claims data do not capture the full spectrum of children with cerebral palsy. This suggests the need for a more sensitive case definition and caution when using such data without validation.
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http://dx.doi.org/10.9778/cmajo.20170013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5621965PMC
July 2017

Financial Impact of Cancer Drug Wastage and Potential Cost Savings From Mitigation Strategies.

J Oncol Pract 2017 07 12;13(7):e646-e652. Epub 2017 Jun 12.

Sunnybrook Health Sciences Centre; Princess Margaret Cancer Centre; and Canadian Centre for Applied Research in Cancer Control, Toronto, Ontario, Canada.

Purpose: Cancer drug wastage occurs when a parenteral drug within a fixed vial is not administered fully to a patient. This study investigated the extent of drug wastage, the financial impact on the hospital budget, and the cost savings associated with current mitigation strategies.

Methods: We conducted a cross-sectional study in three University of Toronto-affiliated hospitals of various sizes. We recorded the actual amount of drug wasted over a 2-week period while using current mitigation strategies. Single-dose vial cancer drugs with the highest wastage potentials were identified (14 drugs). To calculate the hypothetical drug wastage with no mitigation strategies, we determined how many vials of drugs would be needed to fill a single prescription.

Results: The total drug costs over the 2 weeks ranged from $50,257 to $716,983 in the three institutions. With existing mitigation strategies, the actual drug wastage over the 2 weeks ranged from $928 to $5,472, which was approximately 1% to 2% of the total drug costs. In the hypothetical model with no mitigation strategies implemented, the projected drug cost wastage would have been $11,232 to $149,131, which accounted for 16% to 18% of the total drug costs. As a result, the potential annual savings while using current mitigation strategies range from 15% to 17%.

Conclusion: The financial impact of drug wastage is substantial. Mitigation strategies lead to substantial cost savings, with the opportunity to reinvest those savings. More research is needed to determine the appropriate methods to minimize risk to patients while using the cost-saving mitigation strategies.
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http://dx.doi.org/10.1200/JOP.2017.022905DOI Listing
July 2017

Prevention of carboplatin-induced hypersensitivity reactions in women with ovarian cancer.

J Oncol Pharm Pract 2018 Mar 17;24(2):83-90. Epub 2016 Nov 17.

1 Division of Medical Oncology and Hematology, Faculty of Medicine, University of Toronto, Sunnybrook Odette Cancer Center, Toronto, Ontario, Canada.

Background Carboplatin-based chemotherapy offers high response rates and improved overall survival for women with epithelial ovarian cancer, but its use is limited by the occurrence of hypersensitivity reactions. To evaluate the efficacy of prophylactic diphenhydramine for hypersensitivity reaction prevention, we reviewed the incidence of hypersensitivity reactions and identified patients at high risk of hypersensitivity reactions. Methods Women receiving ≥6 cycles of carboplatin-based chemotherapy for epithelial ovarian cancer were identified from our institutional database at the Princess Margaret Cancer Centre. Institutional policy was changed in 2009 to introduce diphenhydramine prophylaxis for patients receiving ≥6 cycles of carboplatin. Additional clinical data were abstracted from the patient record. Results Between 2006 and 2012, 450 women received ≥6 cycles of carboplatin-based chemotherapy for epithelial ovarian cancer. Two hundred and ninety-one women received prophylaxis with diphenhydramine. Carboplatin-induced hypersensitivity reactions occurred in 41 of 449 patients (9%). Univariable predictors of carboplatin-induced hypersensitivity reactions included administration of 8 to 10 cycles of carboplatin, history of other drug allergies and a platinum-free interval >12 months. BRCA mutational status was not predictive. In a multivariable analysis, the number of cycles of carboplatin and a platinum-free interval >12 months were independent predictors of hypersensitivity reactions. There was a trend towards diphenhydramine prophylaxis reducing the incidence of hypersensitivity reactions in women with a platinum-free interval compared to continuous delivery; this was most marked when the platinum-free interval was >12 months (n = 64) (OR: 0.2 (95% CI: 0.046-0.83), p = 0.03). Conclusions The administration of diphenhydramine to women who have a platinum-free interval may reduce the risk of hypersensitivity reaction, but prospective evaluation is required.
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http://dx.doi.org/10.1177/1078155216679028DOI Listing
March 2018

Physician driven variation in the care of children with spinal muscular atrophy type 1.

Pediatr Pulmonol 2017 05 29;52(5):662-668. Epub 2016 Sep 29.

Department of Pediatrics, McGill University, Montréal, QC, Canada.

Background: Increasing numbers of families are requesting active supportive management for their child with spinal muscular atrophy type 1 (SMA1), leading to longer survival and greater prevalence of affected children. Strong opinions exist among physicians for and against the provision of care measures prolonging life.

Objective: To describe current practice in the care of SMA1 in Canada, and explore the factors underlying inter-physician variability.

Methods: A cross-sectional survey of Canadian hospital-based pediatric neurologists and pediatric respirologists was performed in 2015. Odds ratios and 95% confidence intervals were calculated to compare proportions between groups.

Results: There was a 54% completion rate (99 physicians). Over half of participants believed that a disease modifying therapy was likely within 10 years. Quebec respirologists were 50 times less likely to offer long-term non-invasive ventilation (NIV) than respirologists in other provinces (OR 50.6, 95% CI 2.4-1075.3), and 20 times less likely to discuss tracheostomy with families (OR 20.4, 95% CI 2.0-211.8). High raters of perceived happiness of affected children were more likely to find NIV an acceptable measure for acute (OR 6.7, 95% CI 1.7-26.0) and chronic (OR 13.7, 95% CI 4.0-46.4) respiratory failure and prophylactic use (OR 5.8, 95% CI 2.2-15.6).

Conclusion: Physician knowledge, opinions, subjective perception of child happiness, and regional factors, all influence physicians' practices and the shared decision-making process. Parents may not be informed or offered all the services available to their child. Knowledge translation initiatives are needed to enhance SMA1 care. Pediatr Pulmonol. 2017;52:662-668. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ppul.23616DOI Listing
May 2017

SCOPE of Pain: An Evaluation of an Opioid Risk Evaluation and Mitigation Strategy Continuing Education Program.

Pain Med 2016 Jan;17(1):52-63

Objective: Due to the high prevalence of prescription opioid misuse, the US Food and Drug Administration (FDA) mandated a Risk Evaluation and Mitigation Strategy (REMS) requiring manufacturers of extended-release/long-acting (ER/LA) opioid analgesics to fund continuing education based on a FDA Blueprint. This article describes the Safe and Competent Opioid Prescribing Education (SCOPE of Pain) program, an ER/LA opioid analgesic REMS program, and its impact on clinician knowledge, confidence, attitudes, and self-reported clinical practice.

Method: Participants of the 3-h SCOPE of Pain training completed pre-, immediate post- and 2-month post-assessments.

Subjects: The primary target group (n = 2,850), and a subset (n = 476) who completed a 2-month post-assessment, consisted of clinicians licensed to prescribe ER/LA opioid analgesics, who care for patients with chronic pain and who completed the 3-h training between February 28, 2013 and June 13, 2014.

Results: Immediately post-program, there was a significant increase in correct responses to knowledge questions (60% to 84%, P ≤ 0.02) and 87% of participants planned to make practice changes. At 2-months post-program, there continued to be a significant increase in correct responses to knowledge questions (60% to 69%, P ≤ 0.03) and 67% reported increased confidence in applying safe opioid prescribing care and 86% reported implementing practice changes. There was also an improvement in alignment of desired attitudes toward safe opioid prescribing.

Conclusions: The SCOPE of Pain program improved knowledge, attitudes, confidence, and self-reported clinical practice in safe opioid prescribing. This national REMS program holds potential to improve the safe use of opioids for the treatment of chronic pain.
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http://dx.doi.org/10.1111/pme.12878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718419PMC
January 2016

Tolerability of Vidaza (azacitidine) subcutaneous administration using a maximum volume of 3 ml per injection.

J Oncol Pharm Pract 2016 Aug 5;22(4):605-10. Epub 2015 Aug 5.

Department of Pharmacy, Princess Margaret Cancer Centre, UHN Toronto, ON

The azacitidine (Vidaza®) product monograph indicates that doses greater than 4 ml should be divided equally into two syringes and injected into different sites. Although 2 ml is a more commonly used maximum volume for subcutaneous injections, there is a lack of evidence to support the use of any given maximum volume with azacitidine. Applying the status quo of 2 ml to azacitidine results in patients receiving 3-4 injections per visit. This prospective study evaluated the frequency and type of injection site reactions when the maximum subcutaneous injection volume was increased from 2 to 3 ml per injection site. Among 30 patients, 309 doses were administered, and injection site reactions were noted in 92.9% of all doses, with the majority (82.2%) being grade 1; only 10.7% of doses resulted in grade 2 reactions, and there were no grade 3 or 4 reactions. There was no increase in frequency or severity of injection site reactions when the maximum volume was increased to 3 ml. The median number of injections that patients received per visit decreased from 3 to 2 after the volume was increased, and there was a statistically significant reduction in the incidence of pain. Decreasing the number of injections also facilitates ease of rotation of injection sites and decreases pharmacy preparation time. This is the first time that injection site reaction data relating to injection volume have been reported for azacitidine.
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http://dx.doi.org/10.1177/1078155215598854DOI Listing
August 2016

Clinical decision-making in multiple sclerosis: Challenges reported internationally with emerging treatment complexity.

Mult Scler Relat Disord 2015 Jul 22;4(4):320-8. Epub 2015 May 22.

AXDEV Group Inc., 210-8, Place du Commerce, Brossard, QC, Canada J4W 3H2.

Introduction: The introduction of several new disease-modifying therapies (DMTs) to the field of Multiple Sclerosis (MS) treatment requires that MS healthcare providers have a comprehensive understanding of the implications of each new treatment option in order to select the treatment that best suits their patient. An international study was conducted in 6 countries to obtain a better understanding of the issues and challenges experienced by Neurologists and Nurses in the treatment and management of their patients with MS. The goal of this research was to obtain evidence to inform future Continuing Medical Education (CME) initiatives and health policies that promote knowledge translation to clinical practice. This article focuses on challenges reported in relation to the use of newly approved therapies, in light of the risks of these new treatments, as well as screening and monitoring precautions that must be taken.

Materials And Methods: An exploratory study and literature review informed the design of an IRB-approved online survey deployed to MS Neurologists and Nurses practicing in 6 countries (Germany, France, Italy, Spain, UK, USA).

Results: The sample consisted of actively practicing Neurologists (n=156) and Nurses (n=153). Substantive challenges were reported in participant's knowledge of and confidence in three categories: i) safety profile of newly approved therapies, ii) screening patients for treatment with newly approved therapies, and iii) monitoring for serious adverse events.

Discussion And Conclusion: Findings indicate that, internationally, healthcare providers report substantive challenges integrating newly approved therapies into their clinical decision-making. This study highlights potential factors underlying the challenges, and identifies important targets for CME interventions and policymakers to enhance clinical decision-making amongst MS providers.
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http://dx.doi.org/10.1016/j.msard.2015.05.008DOI Listing
July 2015

Neuroimaging chronic pain: what have we learned and where are we going?

Future Neurol 2014 Nov;9(6):615-626

Department of Anesthesiology, Perioperative & Pain Medicine, Division of Pain Medicine, Stanford University School of Medicine, 1070 Arastradero Road, Suite 200, Palo Alto, CA 94304, USA.

Advances in neuroimaging have helped illuminate our understanding of how the brain works in the presence of chronic pain, which often persists with unknown etiology or after the painful stimulus has been removed and any wounds have healed. Neuroimaging has enabled us to make great progress in identifying many of the neural mechanisms that contribute to chronic pain, and to pinpoint the specific regions of the brain that are activated in the presence of chronic pain. It has provided us with a new perception of the nature of chronic pain in general, leading researchers to move toward a whole-brain approach to the study and treatment of chronic pain, and to develop novel technologies and analysis techniques, with real potential for developing new diagnostics and more effective therapies. We review the use of neuroimaging in the study of chronic pain, with particular emphasis on magnetic resonance imaging.
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http://dx.doi.org/10.2217/FNL.14.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289824PMC
November 2014

Tolerability of Velcade (Bortezomib) subcutaneous administration using a maximum volume of 3 mL per injection site.

J Oncol Pharm Pract 2015 Aug 29;21(4):285-92. Epub 2014 Apr 29.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, UHN, Toronto, ON.

Subcutaneous injection is now commonly used as a standard for bortezomib administration. The bortezomib (Velcade(®)) product monograph recommends that intravenous injections be prepared at a concentration of 1 mg/mL, while subcutaneous injections may be prepared at a concentration of 2.5 mg/mL. Many institutions and subcutaneous administration guidelines use 2 mL as the maximum volume for subcutaneous injection. Using 2 mL as the maximum volume for injection would mean that many patients receiving bortezomib will receive two injections during each visit with common dosing parameters. In this prospective study evaluating a change to subcutaneous administration, bortezomib 1 mg/mL was administered subcutaneously at a higher maximum of 3 mL per injection site. For 57 individual patients, 339 doses were administered. Skin reactions were noted in 42% with all reactions being Grade 1 or 2. Patients tolerated subcutaneous injections well and only four patients were switched back to intravenous route. This is the first time that subcutaneous bortezomib of a volume up to a maximum of 3 mL (bortezomib 3 mg) per injection site has been reported. This higher single dose is well tolerated with limited skin reactions, no significant hypotension and facilitates ease of administration with only 5 patients needing two injections per visit. If the maximum volume for injection was kept at 2 mL, a total of 46 patients would have received two injections per visit.
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http://dx.doi.org/10.1177/1078155214533367DOI Listing
August 2015

Assessing adherence to oral chemotherapy using different measurement methods: Lessons learned from capecitabine.

J Oncol Pharm Pract 2014 Aug 9;20(4):249-56. Epub 2013 Sep 9.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Ontario, Canada

Purpose: Adherence to oral medication is important in oncology. Few studies have evaluated adherence with cancer agents such as capecitabine, which is given on a complicated schedule. Furthermore, little guidance exists regarding the best methods for monitoring adherence with oral cancer drugs. The purpose of our study was to evaluate adherence to capecitabine using several accepted measures.

Patients And Methods: Patients treated with capecitabine for gastrointestinal cancers were included in this prospective cohort study. Adherence was evaluated during two consecutive cycles of capecitabine using three assessment methods: self-report, pill count, and use of a microelectronic monitoring system. The primary endpoint was proportion of patients adherent to capecitabine (>80% of adherence according to the three methods of measurement); the secondary objective was to compare the three methods of measurement.

Results: Nineteen patients were accrued to this study. Further accrual was stopped after the first planned analysis, because 18 and 19 patients were adherent by self-report and pill count, respectively. The overall adherence rates were 99, 100, and 61% with self-report, pill count, and microelectronic monitoring system cap, respectively. Ten (53%) patients were classified as nonadherent (<80% of adherence according to at least one method of measurement), but four of them transferred their pills into another medication container suggesting that measurement of adherence using microelectronic monitoring system technology may not be useful.

Conclusion: While we did not identify a major adherence issue with capecitabine in our study, it provides insight into problems associated with measurement of adherence in oncology and suggests that combining measures of adherence maximizes accuracy.
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http://dx.doi.org/10.1177/1078155213501100DOI Listing
August 2014

Disrupted reinforcement signaling in the orbitofrontal cortex and caudate in youths with conduct disorder or oppositional defiant disorder and a high level of psychopathic traits.

Am J Psychiatry 2011 Feb 15;168(2):152-62. Epub 2010 Nov 15.

Department of Clinical Neurological Sciences, Schulich School of Medicine, University of Western Ontario, Canada.

Objective: Dysfunction in the amygdala and orbitofrontal cortex has been reported in youths and adults with psychopathic traits. The specific nature of the functional irregularities within these structures remains poorly understood. The authors used a passive avoidance task to examine the responsiveness of these systems to early stimulus-reinforcement exposure, when prediction errors are greatest and learning maximized, and to reward in youths with psychopathic traits and comparison youths.

Method: While performing the passive avoidance learning task, 15 youths with conduct disorder or oppositional defiant disorder plus a high level of psychopathic traits and 15 healthy subjects completed a 3.0-T fMRI scan.

Results: Relative to the comparison youths, the youths with a disruptive behavior disorder plus psychopathic traits showed less orbitofrontal responsiveness both to early stimulus-reinforcement exposure and to rewards, as well as less caudate response to early stimulus-reinforcement exposure. There were no group differences in amygdala responsiveness to these two task measures, but amygdala responsiveness throughout the task was lower in the youths with psychopathic traits.

Conclusions: Compromised sensitivity to early reinforcement information in the orbitofrontal cortex and caudate and to reward outcome information in the orbitofrontal cortex of youths with conduct disorder or oppositional defiant disorder plus psychopathic traits suggests that the integrated functioning of the amygdala, caudate, and orbitofrontal cortex may be disrupted. This provides a functional neural basis for why such youths are more likely to repeat disadvantageous decisions. New treatment possibilities are raised, as pharmacologic modulations of serotonin and dopamine can affect this form of learning.
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http://dx.doi.org/10.1176/appi.ajp.2010.10010129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908480PMC
February 2011