A randomized double-blind controlled proof-of-concept study of alanyl-glutamine for reduction of post-myomectomy adhesions.

STUDY OBJECTIVE: To test the hypothesis that intraperitoneal instillation of a single bolus dose of l-alanyl-l-glutamine (AG) will reduce the incidence, extent and/or severity of adhesions following myomectomy and establish preliminary safety and tolerability of AG in humans. DESIGN: Phase 1,2 Randomized, double-blind, placebo-controlled study (DBRCT). SETTING: Tertiary care gynecology surgical centre. PATIENTS: Thirty-eight women who underwent myomectomies by laparoscopy (N = 38; AG-19 vs Placebo-19) or laparotomy (N = 10; AG-5 vs Placebo-5) with a scheduled second-look laparoscopy (SLL) 6-8 weeks later. Thirty-two patients in the laparoscopy arm completed SLL. INTERVENTIONS: Bolus dose of AG or normal saline solution control (0.9% NaCl) administered intraperitoneally immediately prior to suture closure of the laparoscopic ports. The average dose was 170 mL of AG or control based on a dosing scheme of 1 g/kg bodyweight. MEASUREMENTS: Digital recordings obtained for all procedures. The primary endpoint was reduction in the incidence, severity and extent of post-operative adhesions analyzed by intention-to-treat (ITT) approach. Three independent, blinded reviewers evaluated all operative video recordings to assess presence of adhesions. Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Secondary endpoints assessed safety and tolerability of AG. MAIN RESULTS: Administration of AG reduced the incidence, severity and/or extent of post-operative adhesions (p = 0.046). The presence of adhesions in the AG group was lower than in the Control group (p = 0.041). Adhesion improvement was achieved in 15 of 15 (100%) in the AG group versus 5 of 17 (29.6%) in the placebo group. No serious adverse events were reported. No differences in safety parameters were observed. CONCLUSIONS: Intraperitoneal l-alanyl-l-glutamine reduced adhesion formation in all patients following laparoscopic myomectomy. Complete absence of adhesions was achieved at all abdominal sites in 93% of patients. Results confirm AG's known effects on cellular mechanisms of adhesiogenesis and lay the foundation for new adhesion prophylaxis research and treatment.

Reinventing Nuclear Histo-score Utilizing Inherent Morphologic Cutoffs: Blue-brown Color H-score (BBC-HS).

Immunohistochemistry (IHC) is a testing methodology that is widely used for large number of diagnostic, prognostic, and predictive biomarkers. Although IHC is a qualitative methodology, in addition to threshold-based stratification (positive vs. negative), the increasing levels of expression of some of these biomarkers often lead to more intense staining, which published evidence linked to specific diagnosis, prognosis, and responses to therapy. It is essential that the descriptive thresholds between positive and negative staining, as well as between frequently used graded categories of staining intensity (eg, 1+, 2+, 3+) are standardized and reproducible. Histo-score (H-score) is a frequently used scoring system that utilizes these categories. Our study introduces categorization of the cutoff points between positive and negative results and graded categories of staining intensity for nuclear IHC biomarker assays based on color interaction between hematoxylin and diaminobenzidine (DAB); the Blue-brown Color H-score (BBC-HS). Six cases of diffuse large B-cell lymphoma were stained for a nuclear marker MUM1. The staining was assessed by H-score by 12 readers. Short tutorial and illustrated instructions were provided to readers. The novel scoring system in this study uses the interaction between DAB (DAB, brown stain) and hematoxylin (blue counterstain) to set thresholds between "0" (negative nuclei), "1+" (weakly positive nuclei), "2+" (moderately positive nuclei), and "3+" (strongly positive nuclei). The readers recorded scores for 300 cells. Krippendorff alpha (K-alpha) and intraclass correlation coefficient (ICC) were calculated. We have also assessed if reliability improved when counting the first 100 cells, first 200 cells, and for the total 300 cells using K-alpha and ICC. To assess the performance of each individual reader, the mean H-score and percent positive score (PPS) for each case was calculated, and the bias was calculated between each reader's score and the mean. K-alpha was 0.86 for H-score and 0.76 for PPS. ICC was 0.96 for H-score and 0.92 for PPS. The biases for H-score ranged from -58 to 41, whereas for PPS it ranged from -27% to 33%. Overall, most readers showed very low bias. Two readers were consistently underscoring and 2 were consistently overscoring compared with the mean. For nuclear IHC biomarker assays, our newly proposed cutoffs provide highly reliable/reproducible results between readers for positive and negative results and graded categories of staining intensity using existing morphologic parameters. BBC-HS is easy to teach and is applicable to both human eye and image analysis. BBC-HS application should facilitate the development of new reliable/reproducible scoring schemes for IHC biomarkers.

Early Single-Center Experience With Irreversible Electroporation for Stage 2, 3, and 4 Pancreatic Adenocarcinomas.

OBJECTIVES: Irreversible electroporation (IRE) is an ablation technology that uses electrical energy delivered between electrodes. If the electrodes are placed atraumatically, there is little to no risk of collateral injury, making IRE appealing for the treatment of pancreatic tumors. METHODS: We report on 20 patients with pancreatic adenocarcinoma (PAC) who underwent 21 IRE in our center. There were 6 IRE for stage 2 PAC, 11 for stage 3 PAC, 1 for stage 4 PAC, and 2 patients treated with IRE for recurrence after pancreaticoduodenectomy. One patient had local progression 18 months after IRE and received a second IRE treatment. Using propensity score matching (age, sex, stage, tumor size, and chemotherapy), cases were matched 2 to 1 with patients from the Surveillance, Epidemiology, and End Results database. RESULTS: A total of 7 cases experienced 8 complications; 4 complications were mild, and 4 were severe. Significant survival benefit was seen for patients with stage 3 PAC (27.5 vs 14.6 months for the matched group, P = 0.003); for stage 2, median survival was 15 months, and the single stage 4 patient survived 9 months after IRE treatment. CONCLUSIONS: Pancreatic cancers were safely and effectively treated with image-guided IRE in our medium-sized center.

Barriers to Care in ACHD: A Study of Young Adults in Saskatchewan.

BACKGROUND: Adults with congenital heart disease (CHD) are living longer with more complex disease. Maintaining lifelong care prevents morbidity and mortality, but many patients remain lost to follow-up or experience care gaps. We sought to assess barriers to care for patients with adult CHD (ACHD) in Saskatchewan, a Canadian province with no local congenital cardiac surgical support and no clear framework for ACHD care. METHODS: We performed a telephone survey of patients with CHD transferred from pediatric to adult cardiology from 2007 to 2014. Our primary outcome was loss to follow-up > 2 years from last recommended cardiology appointment and/or multiple missed cardiology appointments. Secondary outcomes were guideline-based care (specialist training, adherence to appropriate endocarditis prophylaxis, pre-pregnancy counselling for women), presence or absence of previously described barriers to care in ACHD, and health care autonomy using the Krantz Health Opinion Survey. RESULTS: We interviewed 32 patients (30% response rate). One-quarter met the primary outcome: lost to follow-up > 2 years from last recommended cardiology appointment and/or self-report of missed cardiology appointments. Only 69% of young adults in Saskatchewan were receiving guideline-based care for their CHD (appropriate level of specialist expertise and frequency of follow-up). Only 72% of patients were adhering to endocarditis prophylaxis recommendations and 61% of women surveyed received counselling regarding pregnancy. Patients indicated a low preference for participating in decision making regarding their care on the Krantz Health Opinion Survey. CONCLUSIONS: With our survey, we have created a novel snapshot of CHD care in Saskatchewan and have identified significant deficits.

CONTEXTE: Les adultes souffrant d'une cardiopathie congénitale vivent de plus en plus longtemps avec une maladie complexe. Les soins qui leur sont prodigués toute leur vie aident à prévenir la morbidité et la mortalité, mais nombreux sont les patients qui sont perdus de vue en cours de route ou qui vivent des périodes sans recevoir de soins. Nous avons tenté d'évaluer les obstacles aux soins des patients adultes atteints d'une cardiopathie congénitale en Saskatchewan, une province canadienne où il n'existe aucun programme local de soutien en matière de chirurgie cardiaque pour les troubles congénitaux ni de cadre définissant clairement les soins à prodiguer aux adultes atteints d'une cardiopathie congénitale. MÉTHODOLOGIE: Nous avons interviewé par téléphone des patients atteints d'une cardiopathie congénitale qui sont passés d'un suivi en cardiologie en soins pédiatriques aux soins aux adultes entre 2007 et 2014. Le critère d'évaluation principal était la perte de vue pendant plus de 2 ans après le dernier rendez-vous de suivi en cardiologie recommandé et/ou plusieurs rendez-vous en cardiologie manqués. Les critères d'évaluation secondaires étaient les soins recommandés dans les lignes directrices (formation spécialisée, observance d'une prophylaxie endocardite appropriée, counseling préalable à la grossesse chez les femmes), la présence ou l'absence d'obstacles aux soins relatifs à la cardiopathie congénitale chez l'adulte cités antérieurement et l'autonomie en matière de soins de santé selon le sondage d'opinion sur la santé de Krantz. RÉSULTATS: Nous avons interviewé 32 patients (taux de réponse de 30 %). Le quart des patients interrogés répondaient au critère d'évaluation principal, soit la perte de vue pendant plus de 2 ans après le dernier rendez-vous de suivi en cardiologie recommandé et/ou plusieurs rendez-vous en cardiologie manqués autodéclarés. Seulement 69 % des jeunes patients adultes de la Saskatchewan recevaient les soins recommandés dans les lignes directrices en matière de cardiopathie congénitale (degré approprié d'expertise spécialisée du médecin et fréquence des consultations de suivi). Seulement 72 % des patients observaient les recommandations en matière de prophylaxie endocardite, et 61 % des femmes interrogées avaient reçu des services de counseling concernant la grossesse. Selon les résultats au sondage d'opinion sur la santé de Krantz, les patients étaient généralement peu disposés à participer aux décisions concernant leur programme de soins. CONCLUSIONS: Grâce à notre enquête, nous disposons maintenant d'un portrait à jour des soins aux patients atteints de cardiopathie congénitale en Saskatchewan; l'exercice nous a par ailleurs permis de cerner d'importantes lacunes à cet égard.

Intravenous dextrose versus ondansetron for prevention of postoperative vomiting in children: a randomized non-inferiority trial.

BACKGROUND: Postoperative vomiting (POV) in children is frequent. Dextrose-containing intravenous fluids in the perioperative period have shown improvement of POV in adults. Similar studies have not been done in children. AIM: The primary purpose was to study the efficacy of intraoperative intravenous dextrose for antiemetic prophylaxis in children undergoing ambulatory surgery. METHODS: A non-inferiority randomized clinical trial of healthy children (three to nine years old) undergoing ambulatory dental surgery was conducted. The control group received dexamethasone (0.15 mg·kg-1 iv) and ondansetron (0.05 mg·kg-1 iv); the intervention group received dexamethasone (0.15 mg·kg-1 iv) and intravenous 5% dextrose in 0.9% normal saline according to a weight-based maintenance rate. The primary outcome was POV in the postanesthetic care unit (PACU) within two hr after surgery. Secondary outcomes included POV within 24 hr from discharge and unplanned hospital admission. A non-inferiority analysis was conducted on the primary outcome using an absolute risk difference of 7.5% as the non-inferiority margin. RESULTS: Data from 290 patients were analyzed. Demographics and intraoperative anesthetic management were similar between groups. Vomiting in the PACU occurred in 7.6% and 3.5% of the dextrose and ondansetron groups, respectively, with a risk difference of 4.2% (95% confidence interval [CI], -1.0 to 9.5). Given that the upper limit of the 95% CI exceeded our non-inferiority margin, non-inferiority of dextrose compared with ondansetron was not shown. CONCLUSION: These results do not support the use of intravenous dextrose as a satisfactory alternative to ondansetron to prevent POV in ambulatory pediatric dental surgery patients. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01912807); registered 18 July 2013.

RéSUMé: CONTEXTE: Les vomissements postopératoires (VPO) sont fréquents chez l'enfant. Il a été démontré qu'en période périopératoire, les solutés intraveineux contenant du dextrose entraînaient une diminution des VPO chez l'adulte, mais des études similaires n'ont pas été réalisées auprès de populations pédiatriques. OBJECTIF: L'objectif principal était d'évaluer l'efficacité du dextrose intraveineux peropératoire en tant que prophylaxie antiémétique chez les enfants subissant une chirurgie ambulatoire. MéTHODE: Une étude clinique randomisée de non-infériorité a été réalisée auprès d'enfants en bonne santé (de trois à neuf ans) devant subir une chirurgie dentaire en ambulatoire. Le groupe témoin a reçu de la dexaméthasone (0,15 mg·kg−1 iv) et de l'ondansétron (0,05 mg·kg−1 iv); le groupe intervention a reçu de la dexaméthasone (0,15 mg·kg−1 iv) et du dextrose intraveineux 5 % dans une solution de normal salin 0,9 % selon une échelle basée sur le poids. Le critère d'évaluation principal était la présence de VPO en salle de réveil au cours des deux heures suivant la chirurgie. Les critères d'évaluation secondaires comprenaient les VPO au cours des 24 h suivant le congé et une admission non planifiée à l'hôpital. L'analyse de non-infériorité a été réalisée pour le critère d'évaluation primaire en se fondant sur une différence de risque absolu de 7,5 % comme marge de non-infériorité. RéSULTATS: Les données de 290 patients ont été analysées. Les données démographiques et de prise en charge anesthésique peropératoire étaient semblables entre les deux groupes. Des vomissements sont survenus en salle de réveil chez 7,6 % et 3,5 % des groupes dextrose et ondansétron, respectivement, avec une différence de risque de 4,2 % (intervalle de confiance [IC] 95 %, -1,0 à 9,5). Étant donné que la limite supérieure de l'IC 95 % excédait notre marge de non-infériorité, la non-infériorité du dextrose comparativement à l'ondansétron n'a pas été démontrée. CONCLUSION: Ces résultats n'appuient pas l'utilisation de dextrose intraveineux en tant qu'alternative à l'ondansétron afin de prévenir les VPO chez les patients pédiatriques de chirurgie dentaire ambulatoire. ENREGISTREMENT DE L'éTUDE: www. CLINICALTRIALS: gov (NCT01912807); enregistrée le 18 juillet 2013.

Canadian Multicenter Project on Standardization of Programmed Death-Ligand 1 Immunohistochemistry 22C3 Laboratory-Developed Tests for Pembrolizumab Therapy in NSCLC.

INTRODUCTION: The programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assay is used to select patients for first or second-line pembrolizumab monotherapy in NSCLC. The PD-L1 IHC 22C3 pharmDx assay requires an Autostainer Link 48 instrument. Laboratories without this stainer have the option to develop a highly accurate 22C3 IHC laboratory-developed test (LDT) on other instruments. The Canadian 22C3 IHC LDT validation project was initiated to harmonize the quality of PD-L1 22C3 IHC LDT protocols across 20 Canadian pathology laboratories. METHODS: Centrally optimized 22C3 LDT protocols were distributed to participating laboratories. The LDT results were assessed against results using reference PD-L1 IHC 22C3 pharmDx. Analytical sensitivity and specificity were assessed using cell lines with varying PD-L1 expression levels (phase 1) and IHC critical assay performance controls (phase 2B). Diagnostic sensitivity and specificity were assessed using whole sections of 50 NSCLC cases (phase 2A) and tissue microarrays with an additional 50 NSCLC cases (phase 2C). RESULTS: In phase 1, 80% of participants reached acceptance criteria for analytical performance in the first attempt with disseminated protocols. However, in phase 2A, only 40% of participants reached the desired diagnostic accuracy for both 1% and 50% tumor proportion score cutoff. In phase 2B, further protocol modifications were conducted, which increased the number of successful laboratories to 75% in phase 2C. CONCLUSIONS: It is possible to harmonize highly accurate 22C3 LDTs for both 1% and 50% tumor proportion score in NSCLC across many laboratories with different platforms. However, despite a centralized approach, diagnostic validation of predictive IHC LDTs can be challenging and not always successful.

"Interchangeability" of PD-L1 immunohistochemistry assays: a meta-analysis of diagnostic accuracy.

Different clones, protocol conditions, instruments, and scoring/readout methods may pose challenges in introducing different PD-L1 assays for immunotherapy. The diagnostic accuracy of using different PD-L1 assays interchangeably for various purposes is unknown. The primary objective of this meta-analysis was to address PD-L1 assay interchangeability based on assay diagnostic accuracy for established clinical uses/purposes. A systematic search of the MEDLINE database using PubMed platform was conducted using "PD-L1" as a search term for 01/01/2015 to 31/08/2018, with limitations "English" and "human". 2,515 abstracts were reviewed to select for original contributions only. 57 studies on comparison of two or more PD-L1 assays were fully reviewed. 22 publications were selected for meta-analysis. Additional data were requested from authors of 20/22 studies in order to enable the meta-analysis. Modified GRADE and QUADAS-2 criteria were used for grading published evidence and designing data abstraction templates for extraction by reviewers. PRISMA was used to guide reporting of systematic review and meta-analysis and STARD 2015 for reporting diagnostic accuracy study. CLSI EP12-A2 was used to guide test comparisons. Data were pooled using random-effects model. The main outcome measure was diagnostic accuracy of various PD-L1 assays. The 22 included studies provided 376 2×2 contingency tables for analyses. Results of our study suggest that, when the testing laboratory is not able to use an Food and Drug Administration-approved companion diagnostic(s) for PD-L1 assessment for its specific clinical purpose(s), it is better to develop a properly validated laboratory developed test for the same purpose(s) as the original PD-L1 Food and Drug Administration-approved immunohistochemistry companion diagnostic, than to replace the original PD-L1 Food and Drug Administration-approved immunohistochemistry companion diagnostic with a another PD-L1 Food and Drug Administration-approved companion diagnostic that was developed for a different purpose.

Individualised behaviour change strategies for physical activity in multiple sclerosis (IPAC-MS): protocol for a randomised controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic, degenerative disease of the central nervous system. Because of the long-term and unpredictable nature of the disease, the burden of MS is significant from both a patient and societal perspective. Despite a recent influx of disease-modifying therapies to treat MS, many individuals continue to experience disability that negatively affects productivity and quality of life. Previous research indicates that physical activity has a positive impact on walking function in individuals with MS, in addition to the usual beneficial effects on overall health. However, most people with MS are not active enough to gain these benefits, and a lack of support to initiate and maintain physical activity has been identified as a major barrier. This study will evaluate the impact of a novel intervention involving individualised behaviour change strategies delivered by neurophysiotherapists on increasing physical activity levels in individuals with MS who are currently inactive. METHODS/DESIGN: This single-blind, parallel-group, randomised controlled trial will be conducted in Saskatchewan, Canada. Eligible participants include individuals with MS who are ambulatory but identified as currently inactive by the self-reported Godin Leisure-Time Exercise Questionnaire (GLTEQ). The intervention will be delivered by neurophysiotherapists and includes individualised behaviour change strategies aimed at increasing physical activity over a 12-month period. The control group will receive usual care during the 12-month study period. The primary outcome is the change in physical activity level, as measured by the change in the GLTEQ score from baseline to 12 months. Secondary outcomes include the change in patient-reported outcome measures assessing MS-specific symptoms, confidence and quality of life. DISCUSSION: Physical activity has been identified as a top research priority by the MS community. Findings from this novel study may result in new knowledge that could significantly impact the management and overall health of individuals with MS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04027114. Registered on 10 July 2019.

Fit-For-Purpose PD-L1 Biomarker Testing For Patient Selection in Immuno-Oncology: Guidelines For Clinical Laboratories From the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP).

Since 2014, programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have been approved by various regulatory agencies for the treatment of multiple cancers including melanoma, lung cancer, urothelial carcinoma, renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid tumors. Of these approved drug/disease combinations, a subset also has regulatory agency-approved, commercially available companion/complementary diagnostic assays that were clinically validated using data from their corresponding clinical trials. The objective of this document is to provide evidence-based guidance to assist clinical laboratories in establishing fit-for-purpose PD-L1 biomarker assays that can accurately identify patients with specific tumor types who may respond to specific approved immuno-oncology therapies targeting the PD-1/PD-L1 checkpoint. These recommendations are issued as 38 Guideline Statements that address (i) assay development for surgical pathology and cytopathology specimens, (ii) reporting elements, and (iii) quality assurance (including validation/verification, internal quality assurance, and external quality assurance). The intent of this work is to provide recommendations that are relevant to any tumor type, are universally applicable and can be implemented by any clinical immunohistochemistry laboratory performing predictive PD-L1 immunohistochemistry testing.

Direction of the Biopsy Needle in Ultrasound-Guided Renal Biopsy Impacts Specimen Adequacy and Risk of Bleeding.

INTRODUCTION: Although medical factors such as hypertension and coagulopathy have been identified that are associated with hemorrhage after renal biopsy, little is known about the role of technical factors. The purpose of our study was to examine the effects of biopsy needle direction on renal biopsy specimen adequacy and bleeding complications. METHODS: Two hundred and forty-two patients who had undergone ultrasound-guided renal biopsies were included. A printout of the ultrasound picture taken at the time of the biopsy was used to measure the biopsy angle ("angle of attack" [AOA]) and to determine if the biopsy needle was aimed at the upper or lower pole and if the medulla was targeted or avoided. RESULTS: Of the 3 groups of biopsy angle, an AOA of between 50°-70° yielded the most glomeruli per core (P = .001) and the fewest inadequate specimens (4% vs 15% for > 70°, and 9% for < 50°, P = .038). Biopsy directed at a pole vs an interpolar region resulted in fewer inadequate specimens (8% vs 23%, P = .005), while biopsies that were medulla-avoiding resulted in fewer inadequate specimens (5% vs 16%, P = .004) and markedly reduced bleeding complications (12% vs 46%, P < .001) compared to biopsies where the medulla was entered. DISCUSSION: An AOA of approximately 60°, aiming at the poles, and avoiding the medulla were each associated with fewer inadequate biopsies and bleeding complications. While biopsy of the medulla is necessary for some diagnoses, the increased bleeding risk emphasizes the need for communication between nephrologist, pathologist, and radiologist.

Diagnostic Accuracy in Fit-for-Purpose PD-L1 Testing.

PD-L1 testing by immunohistochemistry (IHC) has presented significant challenges not only for clinical laboratories, but also for external quality assurance (EQA) entities that provide proficiency testing (PT) for clinical laboratories. Canadian Immunohistochemistry Quality Control (CIQC) has used educational runs to explore approaches to sample design and analysis of results that would enhance patient safety. As PT for predictive biomarkers requires modeling at every level (design of the run, assessment of the run, and reporting of "pass" or "fail") based on "fit-for-purpose" principles, CIQC has applied those principles to PD-L1 PT runs. Each laboratory received unstained slides with TMA tissue cores from 104 randomly selected primary NSCLC and tonsil tissues to test with their current PD-L1 assay. Diagnostic sensitivity and specificity were calculated against designated gold standards based on the "3D" approach (drug-disease-diagnostic assay). Depending on the selection of fit-for-purpose gold standards and also on the selection of what was considered fit-for-purpose cut-off points, great variation in the performance (accuracy) of both companion/complementary diagnostic assays and laboratory developed tests was seen. "Fit-for-purpose" in PT for PD-L1 testing entails that the purpose(s) of each PT run is declared a priori, that the PT program has selected/designated purpose-specific gold standard results for the PT challenge, and that the PT materials for the PT run are designed and constructed to enable calculations of diagnostic accuracy.

Equality of care between First Nations and non-First Nations patients in Saskatoon emergency departments.

OBJECTIVE: Studies show that First Nations patients have worse health outcomes than non-First Nations patients, raising concerns that treatment within the healthcare system, including emergency care, is inequitable. METHODS: We performed a retrospective chart review of Status First Nations and non-First Nations patients presenting to two emergency departments in Saskatoon, Saskatchewan with abdominal pain and a Canadian Triage and Acuity Scale score of 3. From 190 charts (95 Status First Nations and 95 non-First Nations), data extracted included time to doctor, time to analgesia, length of stay, specialist consult, bloodwork, imaging, physical exam and history, and disposition. Univariate comparisons and multiple regression modelling were performed to compare care outcomes between patient groups. Equivalence testing comparing time intervals was also undertaken. RESULTS: No statistically significant differences in presentation characteristics were observed, although Status First Nations subjects showed a greater tendency towards weekend presentation and younger age. Care parameters were similar, although a marginally significant difference was observed in Status First Nations versus non-First Nations subjects for imaging (46% versus 60%, p=0.06), which resolved on adjustment for age and weekend presentation. Time to physician was found to be similar among First Nations patients on equivalence testing within a 15-minute margin. CONCLUSION: In this study, First Nations patients presenting with abdominal pain did not receive delayed care. There were no detectable differences in the time-related care parameters/variables that were provided relative to non-First Nations patients. Meaningful and important qualitative factors need to be examined in the future.

The Effect of MSM and CD4+ Count on the Development of Cancer AIDS (AIDS-defining Cancer) and Non-cancer AIDS in the HAART Era.

BACKGROUND: The HIV epidemic is increasing among Men who have Sex with Men (MSM) and the risk for AIDS defining cancer (ADC) is higher among them. OBJECTIVE: To examine the effect of MSM and CD4+ count on time to cancer AIDS (ADC) and noncancer AIDS in competing risks setting in the HAART era. METHOD: Using Ontario HIV Treatment Network Cohort Study data, HIV-positive adults diagnosed between January 1997 and October 2012 having baseline CD4+ counts ≤ 500 cells/mm3 were evaluated. Two survival outcomes, cancer AIDS and non-cancer AIDS, were treated as competing risks. Kaplan-Meier analysis, Cox cause-specific hazards (CSH) model and joint modeling of longitudinal and survival outcomes were used. RESULTS: Among the 822 participants, 657 (79.9%) were males; 686 (83.5%) received anti-retroviral (ARV) ever. Regarding risk category, the majority (58.5%) were men who have Sex with men (MSM). Mean age was 37.4 years (SD = 10.3). In the multivariate Cox CSH models, MSM were not associated with cancer AIDS but with non-cancer AIDS [HR = 2.92; P = 0.055, HR = 0.54; P = 0.0009, respectively]. However, in joint models of longitudinal and survival outcomes, MSM were associated with cancer AIDS but not with non-cancer AIDS [HR = 3.86; P = 0.013, HR = 0.73; P = 0.10]. CD4+ count, age, ARV ever were associated with both events in the joint models. CONCLUSION: This study demonstrates the importance of considering competing risks, and timedependent biomarker in the survival model. MSM have higher hazard for cancer AIDS. CD4+ count is associated with both survival outcomes.

The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: a phase 1 dosage escalation study.

BACKGROUND: Initial studies suggest pharmaceutical grade cannabidiol (CBD) can reduce the frequency of convulsive seizures and lead to improvements in quality of life in children affected by epileptic encephalopathies. With limited access to pharmaceutical CBD, Cannabis extracts in oil are becoming increasingly available. Physicians show reluctance to recommend Cannabis extracts given the lack of high quality safety data especially regarding the potential for harm caused by other cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC). The primary aims of the study presented in this protocol are (i) To determine whether CBD enriched Cannabis extract is safe and well-tolerated for pediatric patients with refractory epilepsy, (ii) To monitor the effects of CBD-enriched Cannabis extract on the frequency and duration of seizure types and on quality of life. METHODS: Twenty-eight children with treatment resistant epileptic encephalopathy ranging in age from 1 to 10 years will be recruited in four Canadian cities into an open-label, dose-escalation phase 1 trial. The primary objectives for the study are (i) To determine if the CBD-enriched Cannabis herbal extract is safe and well-tolerated for pediatric patients with treatment resistant epileptic encephalopathy and (ii) To determine the effect of CBD-enriched Cannabis herbal extract on the frequency and duration of seizures. Secondary objectives include (i) To determine if CBD-enriched Cannabis herbal extracts alter steady-state levels of co-administered anticonvulsant medications. (ii) To assess the relation between dose escalation and quality of life measures, (iii) To determine the relation between dose escalation and steady state trough levels of bioactive cannabinoids. (iv) To determine the relation between dose escalation and incidence of adverse effects. DISCUSSION: This paper describes the study design of a phase 1 trial of CBD-enriched Cannabis herbal extract in children with treatment-resistant epileptic encephalopathy. This study will provide the first high quality analysis of safety of CBD-enriched Cannabis herbal extract in pediatric patients in relation to dosage and pharmacokinetics of the active cannabinoids. TRIAL REGISTRATION: http://clinicaltrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016 Dec 16. Identifier NCT03024827, Cannabidiol in Children with Refractory Epileptic Encephalopathy: CARE-E; 2017 Jan 19 [cited 2017 Oct]; Available from: http://clinicaltrials.gov/ct2/show/NCT03024827.

The Effect of Extrinsic Material and Radiation Dose on Model-Based Iterative Reconstruction Chest Computed Tomography Reconstruction Time: A Phantom-Based Study.

OBJECTIVE: Compare effect of extrinsic materials and radiation dose levels on image processing times for model-based iterative reconstruction (MBIR) in computed tomography. METHODS: Chest computed tomography scans were performed on a phantom with three different levels of clothing and medical equipment at three tube current settings to reflect differing radiation doses. Reconstruction time for MBIR was recorded, and objective image quality was assessed via noise within the phantom mediastinum. Reconstruction time and noise were compared between scans, with noise also compared between MBIR and matching filtered back projection (FBP) images. RESULTS: Reconstruction times (minutes:seconds) ranged from 37:31 to 42:24. Times were generally faster with less extrinsic material and prolonged among high-dose scans when materials were present. On both the MBIR and FBP images, noise levels were improved with higher radiation doses, although for MBIR only minimally, and the relative effect of extrinsic materials at a given radiation dose was also minimal. In addition, noise was better with MBIR than FBP reconstruction for all conditions. CONCLUSIONS: Typical MBIR reconstruction times are faster with less extrinsic materials in the scan field of views, and removing extraneous blankets or medical devices could positively affect workflow over the course of the day. In addition, MBIR reconstruction times are also shorter when using lower dose protocols in situations requiring extensive materials.

Health-related quality of life of patients on antiretroviral treatment in Botswana: A cross-sectional study.

OBJECTIVE: Antiretroviral therapy (ART) affords longevity to patients infected with the human immune deficiency virus (HIV). Since little is known about the health-related quality of life (HRQoL) of persons who have been on ART for at least five years, the present study investigated the HRQoL of these patients in Botswana. METHOD: Medical records, structured interviews, and the World Health Organization Quality of Life-BREF (WHOQoL-HIV-BREF) instrument were employed to obtain information from 456 respondents. RESULTS: Univariate and multivariate regression analyses showed that respondents' highest scores were in the "physical" domain (mean = 15.8, SD = 3.5), while the lowest scores were in the "environment" domain (mean = 12.9, SD = 2.5). Thus, the physical domain had the greatest impact on patients' overall HRQoL. Self-education about HIV-related issues was significantly correlated with all domains of HRQoL scores: physical (ρ = -2.32, CI 95% = -3.02, -1.61); psychological (ρ = -2.26, CI 95% = -2.87, -1.65); independence (ρ = -1.81, CI 95% = -2.54, -1.06); social relationships (ρ = -1.40, CI 95% = -2.13, -0.67); environment (ρ = -1.58, CI 95% = -2.13, -1.04); and spirituality (ρ = -1.70, CI 95% = -82.27, -1.13). SIGNIFICANCE OF RESULTS: HRQoL assessments can identify and address patients' needs, and it is important that guidelines be developed that will yield improved care to ART patients in Botswana.

A Clinical Randomized Trial Comparing the Cycloplegic Effect of Cyclopentolate Drops Applied to Closed Eyelids Versus Open Eyelids.

BACKGROUND AND PURPOSE: Adequate cycloplegia and dilation are required for refraction and fundus exam in children. Standard practice is to instill cycloplegic drops in the inferior cul-de-sac, and this is often traumatic for children. Our study assesses the use of cyclopentolate on closed lids as a method of instillation for ensuring complete cycloplegia. PATIENTS AND METHOD: Ninety children presenting for annual refraction were enrolled. Three were excluded as they did not finish the testing. One drop of Alcaine® and one drop of cyclopentolate HCL 1% were used in each eye. Cyclopentolate drops were placed on the inner canthus near the lid margin on the closed eye and directly onto the conjunctiva of the fellow eye. RESULTS: Overall, 145/174 eyes (83%) were fully cyclopleged with one drop. The methods of instillation were equally successful (seventy-two indirect vs. seventy-three direct). Age, eye color, spherical refractive error, astigmatic refractive error, and presence of amblyopia on the study visit played no role in the success of either method. Dark irises where the pupil margin was clinically indistinguishable had the largest number of failures (n = 17/44) in comparison to light irises (12/130), but had an equal amount of failures for both direct and indirect methods. CONCLUSION: Placing one drop of cyclopentolate HCL 1% on a closed eyelid had a success rate for complete cycloplegia that was equivalent to placing one drop directly on the cornea.

Satisfaction and Quality of Life Related to Chemotherapy With an Arm Port: A Pilot Study.

PURPOSE: Placement of arm ports, or totally implanted venous access devices, is a common practice in our interventional radiology suite. We implant a miniaturized port in the upper arm for the provision of long-term chemotherapy. We hypothesized that there was general satisfaction with these arm ports and they have a minimal negative impact on quality of life. In this study we aimed to assess our hypotheses. METHODS: We surveyed subjects, who having previously received an arm port for chemotherapy to treat a malignancy, attended the interventional room for its removal. The survey assessed the port's effect on lifestyle, the degree of device-related pain, the acceptance of the port, and the willingness to have another port in the future. RESULTS: Survey responses from 77 subjects were reviewed. On a scale of 1 (most negative) to 10 (most positive), respondents indicated that the port system was a very positive enhancement to their treatment (satisfaction = 9.2 ± 2.0 and positivity = 8.8 ± 2.2). The port had little impact on daily activities. The mean score for the likelihood of choosing to have another port placed if additional treatment was required was 9.1 ± 2.1. DISCUSSION: The arm port in this study did not negatively impact subject satisfaction and quality of life for this cohort. Most subjects rated the device utility highly and felt that the port was a positive enhancement to their treatment, one that they would possibly utilise again in future, if need be.

Correlates of HIV infection among street-based and venue-based sex workers in Vietnam.

Commercial sex work is one of the driving forces of the HIV epidemic across the world. In Vietnam, although female sex workers (FSWs) carry a disproportionate burden of HIV, little is known about the risk profile and associated factors for HIV infection among this population. There is a need for large-scale research to obtain reliable and representative estimates of the measures of association. This study involved secondary data analysis of the 'HIV/STI Integrated Biological and Behavioral Surveillance' study in Vietnam in 2009-2010 to examine the correlates of HIV among FSWs. Data collected from 5298 FSWs, including 2530 street-based sex workers and 2768 venue-based sex workers from 10 provinces in Vietnam, were analyzed using descriptive statistics and bivariate and multivariate logistic regression analyses. HIV prevalence among the overall FSW population was 8.6% (n = 453). However, when stratified by FSW subpopulations, HIV prevalence was 10.6% (n = 267) for street-based sex workers and 6.7% (n = 186) for venue-based sex workers. Factors independently associated with HIV infection in the multivariate analysis, regardless of sex work types, were injecting drug use, high self-perceived HIV risk, and age ≥ 25 years. Additional factors independently associated with HIV risk within each FSW subpopulation included having ever been married among street-based sex workers and inconsistent condom use with clients and having sex partners who injected drugs among venue-based sex workers. Apart from strategies addressing modifiable risk behaviours among all FSWs, targeted strategies to address specific risk behaviours within each FSW subpopulation should be adopted.