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BackgroundHIV-related stigma negatively impacts HIV prevention, care, and treatment particularly children and adolescents in sub-Saharan Africa. Interventions that are culturally-grounded and relevant to address the root causes of stigma may reduce the stigma experienced by HIV positive and affected young people. This study in a post-conflict, rural setting in Omoro District, Uganda, will create and evaluate a transformative education and arts-based HIV-related stigma intervention rooted in local cultural knowledge to reduce stigma and improve HIV prevention and care for those living with HIV. The study will employ a mixed-methods, stepped-wedge cluster-randomized controlled trial, and community-based participatory research approach. The intervention will be delivered to children and youth in schools by Elders, with the support of teachers, through the transfer of local cultural knowledge and practices. The arts-based intervention aims to re-establish the important cultural and social role of Elders within a community that has suffered the loss of inter-generational transfer of cultural knowledge due to a 25-year civil war.MethodsA formative research phase consisting of interviews with students, teachers and Elders will inform the intervention and provide data for study objectives. Workshops will then be delivered to Elders and teachers in participating schools to build capacity for transformative, arts-based, educational workshops with students in the classroom. Government-funded schools located in Omoro District will be randomized into 3 blocks, each comprised of two primary and two secondary schools (n=1800 students). Schools will be randomly allocated to sequences of 8-week time periods in which they will crossover from control to the intervention condition. A process evaluation will be implemented throughout the study to evaluate intervention development, implementation, and effects.DiscussionThis study will generate comprehensive, in-depth research and evaluation data that will be integrated to inform an effective and sustainable protocol for implementing arts-based HIV-stigma interventions for young people in school settings. Findings will have widespread implications in post-conflict settings for HIV prevention, treatment and care.Trial registrationClinicalTrials.gov NCT04946071 (June 30, 2021; https://clinicaltrials.gov/ct2/show/NCT04946071)

Supplemental Material, sj-pdf-1-jhi-10.1177_14604582221106396 for Comparative analysis of machine learning approaches for predicting frequent emergency department visits by Razieh Safaripour and Hyun Ja “June” Lim in Health Informatics Journal

Objectives To determine if the depth of corticotomy done with the piezoelectric knife could play a role in the intensity of the regional acceleratory phenomenon (RAP). Materials and Methods Eighteen Sprague-Dawley rats were divided into two groups: untreated (3 rats) and treatment (15 rats). In the treatment group, a split-model design was used. The right tibia received transcortical (deep) penetrations with the piezoelectric knife, while intracortical (shallow) penetrations were performed on the left tibia of the same animal. The rats were euthanized at day 1, 3, 7, 14, and 28. Cone-beam computed tomography scans were taken for each sample and then assessed by histological analysis. Results Higher amounts of osteoclastic activity and new collagen formation were observed in the deep penetration group when compared with the shallow penetration group. The former peaked at day 14 for both groups (1.53% ± 0.01% vs 0.03% ± 0.0004%, respectively), and the latter peaked at day 28 (0.65 × 106 ± 0.01 vs 0.08 × 106 ± 0.0008, respectively). Conclusions Within the limitations of this study, it appears that the intensity of the RAP in the rat is corticotomy depth dependent. This is to be kept in mind when decorticating the bone during surgically facilitated orthodontic procedures.

Background Emergency Department (ED) overcrowding is an emerging risk to patient safety. This study aims to assess and compare the predictive ability of machine learning (ML) models for predicting frequent ED users. Method Korean Health Panel data from 2008 to 2015 were used for this study. Individuals with four or more visits per year were considered frequent ED users. Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM) as well as two ensemble models, namely Bagging and Voting, were trained and tested to examine their predictive performance. Results The ML classification algorithms identified frequent ED users with high precision (90%–98%) and sensitivity (87%–91%), whereas LR showed fair precision (65%) and sensitivity (67%). The ML algorithms showed a high area under the curve (AUC) values from 89% for SVM to 96% for Random Forest, while LR showed the lowest AUC (65%). The classification error varied among algorithms; LR had the highest classification error (24.07%) while RF had the least (3.8%). Conclusions Results show that ML classification algorithms are robust techniques to predict frequent ED users, and the variables in administrative health panels are reliable indicators for this purpose.

Background Conventional sunitinib dosing in metastatic renal cell carcinoma (mRCC) administers 50 mg daily on a 4 weeks on/2 weeks off (4/2) schedule. Not all patients tolerate this regimen and many undergo modifications to schedule, dose, or both. Material and Methods All patients with mRCC treated with sunitinib by the Saskatchewan Cancer Agency between January 1, 2006, and January 1, 2013, were included. Regimens were categorized as standard intermittent dosing (SID), modified intermittent schedule (MIS), modified intermittent dosing (MID), combination of modified schedule and dosing (MSD), or continuous dosing (CD). The primary objective was to compare overall survival (OS) between regimens. Secondary outcomes included progression-free survival (PFS), discontinuation due to adverse effects (AE), and medication cost. Results Among 161 patients, 18.0%, 51.6%, and 30.4% had favorable, intermediate, and poor Heng risk prognoses, respectively. A total of 140 (87.0%) received sunitinib as first-line therapy. MID was associated with longer OS compared with SID (estimated median 28.4 vs. 11.2 months). PFS was longer for MID, MSD, and CD compared with SID (estimated median 12.0, 9.0, and 8.0 months vs. 3.0 months, respectively). Adjustment for potential confounders did not negate these associations. SID also had higher average monthly drug costs than MIS, MID, and MSD. Overall discontinuation rate due to AE was high (24%). Conclusion An adjusted-dose sunitinib regimen is associated with improved OS and PFS over SID, with lower costs. The development of toxicities requiring dose reductions serves as a predictive biomarker for better outcomes.

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.The primary purpose was to study the efficacy of intraoperative intravenous dextrose for antiemetic prophylaxis in children undergoing ambulatory surgery.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·kgData 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.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.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.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·kgCes 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.gov (NCT01912807); enregistrée le 18 juillet 2013.

TPS445 Background: Pancreatic cancer is a major cause of cancer-related death. About 40% of patients with pancreatic cancer present with locally advanced disease and are not candidates for curative surgery. Most patients are treated with chemotherapy with a limited life expectancy. The role of local treatment such as radiation is not well defined. Other conventional ablative therapies, such as thermal or cryoablation have limited role due to the risk of collateral damage to the adjacent structures. Irreversible electroporation (IRE) is a novel non-thermal ablation technology that does not cause injury to nearby blood vessels, ducts, and bowel and has the potential to provide longer disease control and thereby better overall survival. We hypothesized that addition of IRE to combination chemotherapy in patients with locally advanced pancreatic cancer will improve their outcomes, and patients with undetectable 12-week post IRE circulating tumor cell DNA will have better prognoses. Methods: It is a prospective, multicenter, single-arm phase II study. The primary objective is to determine 12-month PFS rate of patients with locally advanced pancreatic cancer who are treated with combination chemotherapy and IRE. Secondary objectives include identification of prognostic and predictive biomarkers, 24-months survival rate, quality of life of subjects, as well as cost-effectiveness and complication rates of IRE. Based on the assumption that treatment with IRE and chemotherapy would result in doubling of PFS versus chemotherapy alone a sample of n = 27 of patients with locally advanced pancreatic adenocarcinoma is estimated. Eligible patients will be recruited at the two major cancer centers in Saskatchewan. All IRE-eligible patients will receive 12 weeks of induction combination chemotherapy and will undergo IRE if there is no disease progression. An additional 12 weeks of chemotherapy will be recommended. Patients who are not eligible for IRE will receive chemotherapy at the discretion of treating oncologist until disease progression or until they become eligible for IRE. Circulating tumor DNA and a panel of genes will be examined using next-generation sequencing for their correlation with prognosis. Quality of life will be assessed, and cost-effectiveness analysis of IRE will be performed.The results of this study will be used to develop a future multicenter, national phase III trial. Clinical trial information: NCT04276857.

TPS147 Background: Patients with mCRC generally have a limited life expectancy, however, a small number of patients with liver-only mCRC could be cured following metastasectomy. In highly selected patients with mCRC, FOLFOXIRI (5FU, oxaliplatin, and irinotecan) plus bev results in high response rates. However, very limited evidence is available about efficacy of this regimen in real-world patients with liver-only mCRC. Furthermore, there is paucity of biomarkers that predict liver metastasectomy in such patients. The current study aims a) to evaluate rate of conversion from unresectable to resectable liver metastases in real-world patients with liver-only mCRC following FOLFOXIRI-bev, b) to identify predictive markers including an early PET-FDG response that correlate with curative surgery, & c) to determine disease control rate, overall survival, quality of life, treatment toxicities, and cost-effectiveness of surgery. Methods: In this pragmatic phase 2 study, 37 patients with liver-only unresectable mCRC who are deemed eligible for FOLFOXIRI-bev by their oncologist will be recruited at the two major cancer centers in Saskatchewan. Patients will receive FOLFOXIRI-bev every two weeks for a total of 12 cycles and will undergo periodic imaging tests. The resectability of liver metastases will be determined by a multidisciplinary team. For those patients who are not able to undergo a curative surgery, a doublet chemotherapy regimen ±bev will be continued at the discretion of treating oncologist. . The prognostic and predictive value of mutations in specific genes involved in cell proliferation, cell death resistance, angiogenesis, and invasion in colorectal cancer along with the relationship between the abundance and characteristics of exRNA and conversion rate and survival will be assessed. Logistic regression and Cox proportional analyses will be performed to assess correlation between an eight-week FDG-PET/CT response to chemotherapy and other biomarkers and rate of removal of metastases and survival, respectively. This pragmatic study will help to determine conversion rate in real-world patients with FOLFOXIRI plus bev and role of early FDG-PET/CT scan response and other biomarkers in predicting metastasectomy along with cost-effectiveness of this approach. Clinical trial information: NCT03401294.

A pilot study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer has been started in Korea. Archival tumor samples were tested for HRD and PD-L1 status. Treatment arms will be allocated according to the test results. For HRD+ patients, we tested the synergistic effects of olaparib and other agents; treatment arms will randomly be allocated. (Arm 1: olaparib and cediranib; Arm 2: olaparib and durvalumab). For HRD- patients, we tested the role of biomarker-driven immunotherapy according to PD-L1 expression (Arm 3: durvalumab and chemotherapy in patients with high PD-L1 expression; Arm 4: durvalumab, tremelimumab, and chemotherapy in patients with low PD-L1 expression). Sixty-eight patients will be included from three Korean institutions within 1 year. The primary endpoint is the response rate according to RECIST 1.1 (6 months after treatment initiation). This trial has been registered with clinicaltrials.gov, and the registration number is NCT03699449.

Background Combination of an aromatase inhibitor and ovarian suppression is more effective than tamoxifen alone in premenopausal women with high risk ER or PR positive BC. However, combination therapy has been associated with more adverse effects, poor treatment adherence, and decline in QOL. Various behavioral interventions can be effective to reduce treatment-related side effects and thereby to improve treatment tolerance and QOL. Nevertheless, there is a paucity of evidence about effect of individualized behavioral and complementary interventions in younger women who are treated with combination endocrine therapy. The study aims to evaluate if younger women with early stage BC treated with combination endocrine therapy could benefit from individualized behavioral and complementary intervention (s) during their treatment. This benefit will be assessed primarily by change in QOL and cognitive function from the baseline measurement and secondarily by adherence to adjuvant endocrine treatment. Trial design In this phase 2 multicenter study 40 premenopausal women with stage I, II and III ER/PR positive BC treated with combination endocrine therapy are being recruited. All participants will be provided a list of behavioral interventions such as exercise, yoga, acupuncture, and massage therapy. A participant will be able to select one or more intervention based on her preferences. Assessments of patients reported outcomes will be performed at baseline, at 3, and every 6 months, thereafter for up to 3 years. The QOL and cognitive function will be assessed using Functional Assessment of Cancer Therapy – Breast Symptom Index (FACT-B), FACT – Endocrine System (FACT-ES), and FACT-Cognitive Function scales. Linear mixed models will be used to assess changes over time for overall QOL and for separate components of QOL. Treatment adherence will be monitored monthly basis. Individually-tailored behavioral and complementary interventions could promote self-management and empower the women with early stage BC to manage treatment related side effects. Clinical trial identification NCT03407768. Legal entity responsible for the study Shahid Ahmed. Funding College of Medicine, University of Saskatchewan. Disclosure All authors have declared no conflicts of interest.

This study has established a robust and straightforward method for the fabrication of uniform poly(vinylamine) hydrogel capsules without using templates that combines the dispersion polymerization and the sequential hydrolysis/cross-linking. The particle sizes are determined by the degree of cross-linking as well as by the cross-linking reaction time, while the shell thickness is independent of these variables. Diffusion-limited reactions occur at the periphery of the particles, leading to the formation of hydrogel shells with a constant thickness. The treatment of the surfaces of hollow hydrogel capsules with oppositely charged biopolymers limits the permeability through the shell of species even with low molecular weights less than 400 g/mol. Furthermore, we demonstrated that the hydrogel shell phase decorated with Au nanoparticles can be optically ruptured by exposure to laser pulse, a feature that has potential uses in optically responsive drug delivery.

Background: Despite the need for community services to support the intensive levels of care provided by dementia family caregivers, findings consistently indicate low rates of service utilization. This study aims to explore the extent of service use and examine the factors that may influence the use of services in a sample of family caregivers of Persons With Dementia (PWD).Methods: Two hundred and seventy-two family caregivers completed a questionnaire assessing caregiver burden, knowledge and use of services, dementia severity, frequency of problem behaviors and socio-demographic characteristics.Results: The rate of service use was modest with 39.9% using any of the available services. Reasons for non-use included lack of time (26.2%), perceived lack of need (18.5%), and presence of domestic help (21%). Separate regression models were evaluated to identify factors associated with caregiver service use and PWD service-use. Caregiver employment status (OR = 0.53, CI = 0.30–0.94) and knowledge of available services (OR = 4.22, CI = 2.23–7.98) contributed significantly to the model distinguishing caregiver service users from non-users. Knowledge of available services (OR = 2.14, CI = 1.23–3.71) was the only significant predictor of service use targeted at the PWD.Conclusions: Given that knowledge significantly increased the odds of service use, strategies should be designed to raise awareness about the availability of dementia support services in the community and provide a deeper understanding about the value of such services. Future research should employ larger sample sizes and explore factors not measured in this study that might potentially better explain use of services.

This cross-sectional study used the stress and coping paradigm to examine the factors associated with negative and positive adjustment outcomes among Asian family caregivers of persons with dementia (PWD) in Singapore. One hundred seven family caregivers completed measures assessing patient illness characteristics, general coping styles of caregivers, specific dementia management strategies, religion and spirituality, and caregiver adjustment outcomes of burden and gain. Multiple regressions revealed that behavioral problems in the PWD, dementia severity, and the use of behavioral disengagement and criticism as coping strategies were significant predictors of burden accounting for 48% of the explained variance [F(4,99)=23.12, P < 0.001]. The only significant predictor of gain was the use of encouragement as a specific dementia management strategy, explaining 18% of variance [F(3,102) = 7.39, P < 0.001]. Religion and spirituality predicted gain indirectly through the use of encouragement. Coping strategies had an independent effect on caregiver outcomes above and beyond PWD illness characteristics and caregiver characteristics. Hence, caregiver interventions should target coping strategies to improve outcomes of caregiving for dementia. Findings also support the need to examine religion and spirituality in future studies of caregiver adjustment outcomes and to explore the factors not measured in this study that might explain gain.

To describe and validate a new scale, Gain in Alzheimer care Instrument (GAIN), and to measure gains in dementia caregiving.Items in GAIN were derived through a qualitative study of family carers of persons with dementia (PWD). Content validity of GAIN was established by a team of dementia care experts (geriatrician, nurse, and social worker) and through focus group discussion with 15 family carers. Consecutive carers of PWD were administered a questionnaire containing GAIN and other measures.Ambulatory dementia clinic of a tertiary hospital and the local Alzheimer's Association.Family carers of PWD.The psychometric properties of GAIN were examined, in particular, exploratory factor analysis and construct validity through correlation with extant measures; Positive Aspects of Caregiving (PAC), Dementia Management Strategies Scale (DMSS), and Zarit Burden Interview (ZBI).Two hundred thirty-eight English-speaking carers completed the survey. Mean age of carers was 50.1 year (standard deviation [SD] 10.1) and females (68.1%) and child carers (81.3%) comprised the majority. Mean GAIN score was 30.5 (SD 6.5). Internal consistency of GAIN by Cronbach's alpha was 0.89 and test-retest reliability (2 weeks) by Intraclass Correlation Coefficient was 0.70. GAIN correlated strongly with PAC (r = 0.68, df = 236, p0.0001), moderately with DMSS (encouragement) (r = 0.35, df = 234, p0.0001) and DMSS (active management) (r = 0.42, df = 235, p0.0001), and modestly with DMSS (criticism) (r = -0.14, df = 236, p = 0.03) and ZBI (r = -0.15, df = 236, p = 0.02). Principal component analysis revealed a single component with an Eigen value1 at 5.28, accounting for 52.8% of the variance.GAIN is a psychometrically reliable and valid instrument for measuring gains in dementia caregiving. It adds an important dimension to carer assessment in dementia.

Background: Immunogenicity of the Human Leukocytes Antigens (HLA) is highly variable. It is hypothesized that responder’s HLA-DR phenotypes contribute preferentially to produce antibodies against certain HLA-DR antigens. This study aims to stratify the immunogenicity of donor/responder’s HLA-DR phenotype combinations. Methods: Subjects studied were HLA-DR-homozygous patients waiting for kidney transplant in UNOS (United Network for Organ Sharing) database (n=2294) with anti-HLA-DR antibodies. Immunogenicity of recipient/donor DR combinations was determined by presence of significant positive and negative associations between HLA-DR phenotypes and HLA-DR antibodies as determined by likelihood analysis including odds ratios. Peptide binding affinity was determined with computer algorithms to corroborate our findings. Results: Out of 146 associations analyzed between HLA-DR phenotypes and antibody specificities, 88 combinations were significantly positive, 24 combinations were significantly negative, while 34 combinations were statistically insignificant. The highest positive association was seen between HLA-DR4-homogenous responders and anti-HLA-DR17 antibody (odds ratio= 4.05, p

Objectives: This study compared the empathic behaviour of first year to final year dental and medical students in Malaysia and explored whether academic training of dental and medical students increases their subjective empathic tendencies. Methods: This cross-sectional study was carried out among 1020 first year to final year (fifth-year) undergraduate medical and dental students using a validated, self-administered Jefferson Scale of Empathy-Health Care Provider Student Version (JSE-HPS) questionnaire. The data were collected from first year to final year (fifth-year) students enrolled in Bachelor of Medicine/Bachelor of Surgery (MBBS) and Bachelor of Dental Surgery (BDS) degree programs at 2 government-funded universities and one private university. Results: Dental students had a significantly higher total mean empathy score than medical students (84.11 versus 81.96, p < 0.05). However, medical students had a narrow actual score range (59.35 - 133.35) than dental (22.05 - 133.35) students. Males (Medical: 82.57, Dental: 84.97) and students of Malay origin (Medical: 82.52, Dental: 85.11) were more empathic than females and students of other ethnic origins. The results also indicate that third-year medical students (mean: 82.95) and fourth-year dental students (mean: 86.36) were more empathic than students in other professional years. Conclusions: We recommend the use of some form of active training and assessment to assist in the development of empathy in medical and dental students. Medical and dental schools should place more emphasis on teaching empathic communication.

Objective To examine diagnostic agreement between Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) Neurocognitive Disorders (NCDs) criteria and DSM, Fourth Edition (DSM-IV) criteria for dementia and International Working Group (IWG) criteria for mild cognitive impairment (MCI) and DSM-V's impact on diagnostic classifications of NCDs. The authors further examined clinical factors for discrepancy in diagnostic classifications between the different operational definitions. Methods Using a cross-sectional study in tertiary memory clinic, the authors studied consecutive new patients aged 55 years or older who presented with cognitive symptoms. Dementia severity was scored based on the Clinical Dementia Rating scale (CDR). All patients completed neuropsychological evaluation. Agreement in diagnostic classifications between DSM-IV/IWG and DSM-V was examined using the kappa test and AC1 statistic, with multinomial logistic regression for factors contributing to MCI reclassification as major NCDs as opposed to diagnostically concordant MCI and dementia groups. Results Of 234 patients studied, 166 patients achieved concordant diagnostic classifications, with overall kappa of 0.41. Eighty-six patients (36.7%) were diagnosed with MCI and 131 (56.0%) with DSM-IV–defined dementia. With DSM-V, 40 patients (17.1%) were classified as mild NCDs and 183 (78.2%) as major NCDs, representing a 39.7% increase in frequency of dementia diagnoses. CDR sum-of-boxes score contributed independently to differentiation of MCI patients reclassified as mild versus major NCDs (OR: 0.01; 95% CI: 0–0.09). CDR sum-of-boxes score (OR: 5.18; 95% CI: 2.04–13.15), performance in amnestic (OR: 0.14; 95% CI: 0.06–0.34) and language (Boston naming: OR: 0.52; 95% CI: 0.29–0.94) tests, were independent determinants of diagnostically concordant dementia diagnosis. Conclusion The authors observed moderate agreement between the different operational definitions and a 40% increase in dementia diagnoses with operationalization of the DSM-V criteria.

To characterize and identify determinants of HIV disease progression among a predominantly injection drug use (IDU) HIV population in the highly active antiretroviral therapy era.The present retrospective study was based on 343 HIV patients diagnosed from 2005 to 2010 from two clinics in Saskatoon, Saskatchewan. Disease progression was defined as the time from diagnosis to immunological AIDS (CD4 count200 cells/μL) and death. Uni- and multivariable Cox proportional hazards models were used.Of the 343 patients, 79% had a history of IDU, 77% were hepatitis C virus (HCV) coinfected and 67% were of Aboriginal descent. The one-year and three-year immunological AIDS-free probabilities were 78% and 53%, respectively. The one-year and three-year survival probabilities were 97% and 88%, respectively. Multicollinearity among IDU, HCV and ethnicity was observed and, thus, separate models were built. HCV coinfection (HR 2.9 [95% CI 1.2 to 6.9]) was a significant predictor of progression to immunological AIDS when controlling for baseline CD4 counts, treatment, age at diagnosis and year of diagnosis. For survival, only treatment use was a significant predictor (HR 0.34 [95% CI 0.1 to 0.8]). HCV coinfection was marginally significant (P=0.067).Baseline CD4 count, HCV coinfection, year of diagnosis and treatment use were significant predictors of disease progression. This highlights the importance of early treatment and the need for targeted interventions for these particularly vulnerable populations to slow disease progression.Caractériser et établir les déterminants de la progression du VIH dans une population atteinte du VIH surtout composée d’utilisateurs de drogues injectables (UDI) à une époque d’antirétrovirothérapie très active.La présente étude rétrospective s’est fondée sur 343 patients atteints du VIH diagnostiqués entre 2005 et 2010 dans deux cliniques de Saskatoon, en Saskatchewan. La progression de la maladie était définie comme le moment du diagnostic jusqu’à l’apparition du sida immunologique (numération de CD4 inférieure à 200 cellules/μL), puis jusqu’au décès. Les chercheurs ont utilisé le modèle univariable et multivariable de risques proportionnels de Cox.Sur les 343 patients, 79 % avaient déjà été UDI, 77 % étaient co-infectés par le virus de l’hépatite C (VHC) et 67 % étaient d’origine autochtone. La probabilité de non-apparition de sida immunologique au bout d’un an et de trois ans correspondait à 78 % et à 53 %, respectivement. La probabilité de survie au bout d’un an et de trois ans s’élevait à 97 % et à 88 %, respectivement. Les chercheurs ont observé une multicolinéarité entre les UDI, le VHC et l’ethnie et ont donc préparé des modèles différents. La co-infection par le VHC (RC 2,9 [95 % IC 1,2 à 6,9]) était un prédicteur important de progression en sida immunologique lorsqu’on contrôlait l’effet de la numération de CD4 de référence, du traitement, de l’âge au diagnostic et de l’année de diagnostic. Seule l’utilisation du traitement était une prédicteur important de la survie (RC 0,34 [95 % IC 0,1 à 0,8]). La co-infection par le VHC avait peu d’importance (P=0,067).La numération de CD4 de référence, la co-infection par le VHC, l’année de diagnostic et l’utilisation d’un traitement étaient des prédicteurs importants de progression de la maladie. Ces constatations font ressortir l’importance d’un traitement rapide et la nécessité de procéder à des interventions ciblées pour ces populations particulièrement vulnérables afin de ralentir la progression de la maladie.

Objectives: Chemotherapy increases the risk of thromboembolism in patients with cancer. Although thrombocytopenia is a known side effect of chemotherapy, reactive thrombocytosis related to chemotherapy is uncommonly reported. The present study aimed to determine the incidence of gemcitabine-related thrombocytosis and the associated risk of thromboembolism. Methods: Medical records of 250 consecutive patients with a malignant disease who received gemcitabine-based therapy were reviewed. A multivariate analysis was done to determine factors associated with thromboembolism. Results: A total of 220 eligible patients with a median age of 63 years (range 26–83) were identified. Of these 220 patients, 95% had advanced malignancy and 59% had received prior chemotherapy. A total of 69% of patients received a platinum combination. In all, 46% patients experienced thrombocytosis following chemotherapy, with a median platelet count of 632 × 109/l (range 457–1,385). Twenty-three of the 220 patients experienced a vascular event within 6 weeks of treatment. Eleven patients with thrombocytosis experienced a vascular event compared with 10 patients without thrombocytosis (not significant). On multivariate analysis, leukocytosis (odds ratio 5.8, 95% confidence interval 2.1–15.8) and comorbid illnesses (odds ratio 4.1, 95% confidence interval 1.4–12.6) were correlated with thromboembolism. Conclusions: Although gemcitabine-based therapy has been associated with an increased incidence of thrombocytosis, it does not increase the risk of thromboembolism in cancer patients. Leukocytosis and comorbid illnesses do increase the risk of thromboembolism.

Introduction: This study aims to validate the Zarit Burden Interview as an instrument to measure the level of burden experienced by caregivers of patients with dementia (PWD) in Singapore. Materials and Methods: Adult family caregivers of PWD were recruited from the ambulatory dementia clinic of a tertiary hospital and the Alzheimer’s Disease Association. All subjects completed a battery of questionnaires which consisted of demographic questions and the following instruments: the Zarit Burden Interview (ZBI), Burden Assessment Scale (BAS), General Health Questionnaire (GHQ-28), Dementia Management Strategies Scale (DMSS), and the Revised Memory and Behaviour Problems Checklist (RMBPC). A subgroup of subjects also completed the ZBI for the second time 2 weeks after the fi rst survey. Results: A total of 238 subjects completed the survey. As hypothesised, the Zarit burden score was strongly correlated with BAS, GHQ-28, DMSS, and RMBPC scores (Pearson’s correlation coefficient: 0.53 to 0.73); caregivers who undertook the major role in caregiving, had spent >1 year in caregiving, or experienced financial problems had higher Zarit burden scores than those who were not main carers, with ≤1 year of caregiving, or reported no/minimal financial problems, respectively. The Cronbach’s alpha value for the ZBI items was 0.93; the intra-class correlation coefficient for the test-retest reliability of the Zarit burden score was 0.89 (n = 149). Conclusion: The results in this study demonstrated that the Zarit Burden Interview is a valid and reliable instrument for measuring the burden of caregivers of PWD in Singapore. Key words: Caregiver, Dementia, Scale, Validation

471 Background: Currently limited biomarkers are available to monitor disease status in cancer patients. Although host factors are critical in regulating cancer, the role of immune responses in aCRC is less clear. A predominant T helper 1 (Th1) response may be more effective to contain cancer than one with a substantial Th2 component. The Th1/Th2 phenotype can be inferred from relative prevalence of IgG isotypes among anti-cancer antibodies and may provide an innovative way to assess disease activity. The study aims to develop an ELISA assay to monitor IgG1:IgG2 and its utility in predicting disease status in aCRC. Methods: A validated ELISA assay (Bertech Pharma) utilizing CRC cell lines was developed to measure IgG1 (Th2) and IgG2 (Th1) levels. A sample size of 44 (24 CRC and 20 healthy control [HC]) was estimated to achieve 80% power and α error of 0.05 assuming that the assay correctly detect CRC specific antibody in > 80% cases. The IgG1:IgG2 was compared between/within groups with HC and aCRC. Results: Samples were collected from 62/66 individuals recruited at 2:1 over 1 yr. 43 CRC patients had median age of 65 yrs (39-86) and M:F 2.3:1. 25 had >1 metastatic site, 31 underwent primary tumor resection and 37 received chemotherapy. Using standard criteria, 14/43 (33%) CRC patients had elevated 1gG1 titer compared with 2/19 (10%) HCs (p = 0.06). Mean IgG1 of CRC group was 0.18±0.05 compared with 0.15±0.01 in HC (p = 0.01). Conversely, mean IgG2 level of CRC group was 0.26±0.11 compared with 0.38±0.15 in HC (p = 0.003). Mean IgG2:IgG1 of CRC group was 1.5±0.35 compared with 2.5±0.97 in HC (p < 0.001). Among 43 CRC patients, 7/12 (58%) with disease progression (DP) had elevated IgG1 compared 7/31 (23%) with stable disease (p = 0.03). Strikingly, 9/12 (75%) patients who died had elevated IgG1 compared with 5/31 (16%) who were alive during the follow up, p = 0.001. Logistic regression revealed positive association among elevated IgG1 and DP, HR:4.8 (95% CI:1.2-19.9) and mortality, HR:15 (95% CI:3.1-78.8). Conclusions: Our results revealed that patients with aCRC have abnormal IgG1:IgG2 compared with HC and elevated IgG1 (a predominant Th2 response) levels in aCRC correlate with DP and mortality.