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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.

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.

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

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.