Acute Hepatitis due to Primary Human Immunodeficiency Virus Infection.

The acute retroviral syndrome may present with diverse systemic manifestations and laboratory abnormalities. Here we present a rare case of primary human immunodeficiency virus (HIV) infection causing severe acute hepatitis. Liver histopathology demonstrated a pattern of lymphocytic inflammation consistent with acute hepatitis, high levels of HIV proviral DNA were detected within liver tissue, and immunofluorescence showed HIV p24 antigen within immune and parenchymal cells including hepatocytes. We review the literature pertaining to HIV infection of cell compartments within the liver and discuss the implications for HIV-associated acute liver disease.

Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel.

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies.

HIV Immunocapture Reveals Particles Expressed in Semen under INSTI-based Therapy are Largely Myeloid Cell-Derived and Disparate from Circulating Provirus.

As use of HIV integrase strand transfer inhibitors (INSTI) increases and formulations are being developed for maintenance therapies and chemoprophylaxis, assessing virus suppression under INSTI-based regimens in prevention-relevant biologic compartments, such as the male genital tract, is timely. We used cell-source marker virion immunocapture to examine amplification of particle RNA then assessed the phylogenetic relatedness of seminal and blood viral sequences from men with HIV who were prescribed INSTI-based regimens. Seminal plasma immunocaptures yielded amplifiable virion RNA from 13/24 (54%) men, and the sequences were primarily associated with markers indicative of macrophage and resident dendritic cell sources. Genetic distances were greatest (>2%) between seminal virions and circulating proviruses, pointing to ongoing low-level expression from tissue-resident cells. While the low levels in semen predict an improbable likelihood of transmission, viruses with large genetic distances are expressed under potent INSTI therapy and have implications for determining epidemiologic linkages if adherence is suboptimal.

Immunocapture of cell surface proteins embedded in HIV envelopes uncovers considerable virion genetic diversity associated with different source cell types.

HIV particles in the blood largely originate from activated lymphocytes and can overshadow variants which may be expressed from other cell types. Investigations of virus persistence must be able to distinguish cells refractory to viral clearance that serve as reservoirs. To investigate additional cell types that may be associated with in vivo HIV expression we developed a virus particle immunomagnetic capture method targeting several markers of cellular origin that become embedded within virion envelopes during budding. We evaluated the ability of markers to better distinguish cell lineage source subpopulations by assessing combinations of different antibodies with cell-sorted in vitro culture and clinical specimens. Various deductive algorithms were designed to discriminate source cell lineages and subsets. From the particle capture algorithms, we identified distinct variants expressed within individuals that were associated with disparate cellular markers. Among the variants uncovered were minority-level viruses with drug resistance mutations undetected by sequencing and often were associated with markers indicative of myeloid lineage (CD3-/CD10-/CD16+ or /CD14+, and CD3-/CD16-/CD14-/CD11c+ or /HLA-DR+) cell sources. The diverse HIV genetic sequences expressed from different cell types within individuals, further supported by the appearance of distinct drug-resistant variants, highlights the complexity of HIV reservoirs in vivo which must be considered for HIV cure strategies. This approach could also be helpful in examining in vivo host cell origins and genetic diversity in infections involving other families of budding viruses.

Exploring patient perspectives on EQ-5D-5L data visualization within an individualized decision aid for total knee arthroplasty (TKA) in Alberta, Canada.

BACKGROUND: Decision aids can help patients set realistic expectations. In this study, we explored alternative presentations to visualise patient-reported outcomes (EQ-5D-5L) data within an online, individualized patient decision aid for total knee arthroplasty (TKA) that, in part, generates individualized comparisons based on age, sex and body mass index, to enhance usability prior to implementation into routine clinical practice. METHODS: We used data visualization techniques to modify the presentation of EQ-5D-5L outcomes data within the decision aid. The EQ-5D-5L data was divided into two parts allowing patients to compare themselves to similar individuals (1) pre-surgery and (2) 1-year post-surgery. We created 2 versions for each part and sought patient feedback on comprehension, usefulness, and visual appeal. Patients from an urban orthopedic clinic were recruited and their ratings and comments were recorded using a researcher-administered checklist. Data were managed using Microsoft Excel, R version 3.6.1 and ATLAS.ti V8 and analyzed using descriptive statistics and directed content analysis. RESULTS: A total of 24 and 25 patients participated in Parts 1 and 2, respectively. Overall, there was a slight preference for Version 1 in Part 1 (58.3%) and Version 2 in Part 2 (64%). Most participants demonstrated adequate comprehension for all versions (range 50-72%) and commented that the instructions were clear. While 50-60% of participants rated the content as useful, including knowing the possible outcomes of surgery, some participants found the information interesting only, were unsure how to use the information, or did not find it useful because they had already decided on a treatment. Participants rated visual appeal for all versions favorably but suggested improvements for readability, mainly larger font and image sizes and enhanced contrast between elements. CONCLUSIONS: Based on the results, we will produce an enhanced presentation of EQ-5D-5L data within the decision aid. These improvements, along with further usability testing of the entire decision aid, will be made before implementation of the decision aid in routine clinical practice. Our results on patients' perspectives on the presentation of EQ-5D-5L data to support decision making for TKA treatments contributes to the knowledge on EQ-5D-5L applications within healthcare systems for clinical care.

Inhibiting the Keap1/Nrf2 Protein-Protein Interaction with Protein-Like Polymers.

Successful and selective inhibition of the cytosolic protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associating protein 1 (Keap1) can enhance the antioxidant response, with the potential for a therapeutic effect in a range of settings including in neurodegenerative disease (ND). Small molecule inhibitors have been developed, yet many have off-target effects, or are otherwise limited by poor cellular permeability. Peptide-based strategies have also been attempted to enhance specificity, yet face challenges due to susceptibility to degradation and lack of cellular penetration. Herein, these barriers are overcome utilizing a polymer-based proteomimetics. The protein-like polymer (PLP) consists of a synthetic, lipophilic polymer backbone displaying water soluble Keap1-binding peptides on each monomer unit forming a brush polymer architecture. The PLPs are capable of engaging Keap1 and displacing the cellular protective transcription factor Nrf2, which then translocates to the nucleus, activating the antioxidant response element (ARE). PLPs exhibit increased Keap1 binding affinity by several orders of magnitude compared to free peptides, maintain serum stability, are cell-penetrant, and selectively activate the ARE pathway in cells, including in primary cortical neuronal cultures. Keap1/Nrf2-inhibitory PLPs have the potential to impact the treatment of disease states associated with dysregulation of oxidative stress, such as NDs.

Canada population norms for the EQ-5D-5L.

OBJECTIVE: In Canada, population norms are only available for 2 provinces, Alberta and Quebec. The objective of this study was to derive the population norms for the EQ-5D-5L based on a representative sample of the Canadian general population. METHODS: Data from the Canadian EQ-5D-5L valuation study, a cross-sectional study, were used. A quota sampling method was used to recruit a representative sample of the Canadian general population in terms of age, sex, and education. EQ-5D-5L utilities and EQ VAS were summarized using descriptive statistics and the impact of demographic characteristics on the EQ-5D-5L utilities was evaluated using statistical hypothesis testing and Tobit regression. RESULTS: 1207 eligible participants were included in the analysis. Pain/discomfort (53.1%) was the most frequently reported domain with any problem, and self-care (7.6%) domain was the least. The mean (standard deviation [SD]) EQ-5D-5L utility was 0.864 (0.121) and the mean (SD) EQ VAS was 82.3 (14.23). The highest mean EQ-5D-5L utility was 0.881 in age group 25-34 while the lowest was 0.839 in age group 55-64. Participants who had full-time employment, were married, a higher annual household income and no chronic health conditions had significantly higher EQ-5D-5L utilities. CONCLUSION: This article reports the first Canadian population norms for the EQ-5D-5L and can be used as population references for economic evaluations and clinical research.

Preference-based measures of health-related quality of life in Indigenous people: a systematic review.

PURPOSE: In many countries, there are calls to address health inequalities experienced by Indigenous people. Preference-based measures (PBMs) provide a measurement of health-related quality of life and can support resource allocation decisions. This review aimed to identify, summarize, and appraise the literature reporting the use and performance of PBMs with Indigenous people. METHODS: Eleven major databases were searched from inception to August 31, 2022. Records in English that (1) assessed any measurement property of PBMs, (2) directly elicited health preferences, (3) reported the development or translation of PBMs for Indigenous people, or (4) measured health-related quality of life (HRQL) using PBMs were included. Ethically engaged research with Indigenous people was considered as an element of methodological quality. Data was synthesized descriptively (PROSPERO ID: CRD42020205239). RESULTS: Of 3139 records identified, 81 were eligible, describing psychometric evaluation (n = 4), preference elicitation (n = 4), development (n = 4), translation (n = 2), and HRQL measurement (n = 71). 31 reported ethically engaged research. Reports originated primarily from Australia (n = 38), New Zealand (n = 20), USA (n = 9) and Canada (n = 6). Nearly all (n = 73) reported indirect, multi-attribute PBMs, the most common of which was the EQ-5D (n = 50). CONCLUSION: A large number of recent publications from diverse disciplines report the use of PBMs with Indigenous people, despite little evidence on measurement properties in these populations. Understanding the measurement properties of PBMs with Indigenous people is important to better understand how these measures might, or might not, be used in policy and resource decisions affecting Indigenous people. (Funding: EuroQoL Research Foundation).

Association between pulse width and health-related quality of life after electroconvulsive therapy in patients with unipolar or bipolar depression: an observational register-based study.

AIMS: To examine the association between pulse width and HRQoL measured within one week after electroconvulsive therapy (ECT) and at six-month follow-up in patients with unipolar or bipolar depression. METHODS: This was an observational register study using data from the Swedish National Quality Registry for ECT (2011-2019). Inclusion criteria were: age ≥18 years; index treatment for unipolar/bipolar depression; unilateral electrode placement; information on pulse width; EQ-5D measurements before and after ECT. Multiple linear regressions were performed to investigate the association between pulse width (<0.5 ms; 0.5 ms; >0.5 ms) and HRQoL (EQ-5D-3L index; EQ VAS) one week after ECT (primary outcome) and six months after ECT (secondary outcome). RESULTS: The sample included 5,046 patients with unipolar (82%) or bipolar (18%) depression. At first ECT session, 741 patients (14.7%) had pulse width <0.5 ms, 3,639 (72.1%) had 0.5 ms, and 666 (13.2%) had >0.5 ms. There were no statistically significant associations between pulse width and HRQoL one week after ECT. In the subsample of patients with an EQ-5D index recorded six months after ECT (n = 730), patients receiving 0.5 ms had significantly lower HRQoL (-0.089) compared to <0.5 ms, after adjusting for demographic and clinical characteristics (p = .011). The corresponding analysis for EQ VAS did not show any statistically significant associations. CONCLUSION: No robust associations were observed between pulse width and HRQoL after ECT. On average, significant improvements in HRQoL were observed one week and six months after ECT for patients with unipolar or bipolar disease, independent of the pulse width received.

Effectiveness of RADAR on diabetes processes of care for First Nations communities in Alberta, Canada.

The epidemic of type-2 diabetes in First Nations communities is tragic. Culturally-appropriate approaches addressing multiple components, focusing beyond glycemic control, are urgently needed. Using an intention-to-treat framework, 13 processes of care indicators were assessed to compare proportions of patients who received care at baseline relative to 2-year follow-up. Clinical improvements were demonstrated across major process of care indicators (e.g. screening, education, and vaccination activities). We found RADAR improved reporting for most diabetes processes of care across seven FN communities and was effective in supporting diabetes care for FN communities, in Alberta Canada.

Reduced incidence of diabetes during the COVID-19 pandemic in Alberta: A time-segmented longitudinal study of Alberta's Tomorrow Project.

AIM: To characterize the impact of the COVID-19 pandemic on diabetes diagnosis using data from Alberta's Tomorrow Project (ATP), a population-based cohort study of chronic diseases in Alberta, Canada. MATERIALS AND METHODS: The ATP participants who were free of diabetes on 1 April 2018 were included in the study. A time-segmented regression model was used to compare incidence rates of diabetes before the COVID-19 pandemic, during the first two COVID-19 states of emergency, and in the period when the state of emergency was relaxed, after adjusting for seasonality, sociodemographic factors, socioeconomic status, and lifestyle behaviours. RESULTS: Among 43 705 ATP participants free of diabetes (65.5% females, age 60.4 ± 9.5 years in 2018), the rate of diabetes was 4.75 per 1000 person-year (PY) during the COVID-19 pandemic (up to 31 March 2021), which was 32% lower (95% confidence interval [CI] 21%, 42%; p < 0.001) than pre-pandemic (6.98 per 1000 PY for the period 1 April 2018 to 16 March 2020). In multivariable regression analysis, the first COVID-19 state of emergency (first wave) was associated with an 87.3% (95% CI -98.6%, 13.9%; p = 0.07) reduction in diabetes diagnosis; this decreasing trend was sustained to the second COVID-19 state of emergency and no substantial rebound (increase) was observed when the COVID-19 state of emergency was relaxed. CONCLUSIONS: The COVID-19 public health emergencies had a negative impact on diabetes diagnosis in Alberta. The reduction in diabetes diagnosis was likely due to province-wide health service disruptions during the COVID-19 pandemic. Systematic plans to close the post-COVID-19 diagnostic gap are required in diabetes to avoid substantial downstream sequelae of undiagnosed disease.

The use of EQ-5D-5L as a patient-reported outcome measure in evaluating community rehabilitation services in Alberta, Canada.

BACKGROUND: The purpose of this study was to describe the characteristics and health-related quality of life (HRQL) of patients accessing community rehabilitation services in Alberta, Canada, using routinely collected EQ-5D-5L data, and explore factors associated with the impact of these services. METHODS: A retrospective, longitudinal, observational design was used. Patients completed the EQ-5D-5L and demographic questions at intake and end of rehabilitation care. Change in EQ-5D-5L dimensions from intake until end of rehabilitation was examined using the Pareto Classification of Health Change. Change scores were calculated for the EQ-5D-5L index, VAS, and total sum scores. Change groups in the EQ-5D-5L index and VAS scores, were defined by minimally important differences of 0.04 and 7.0, respectively. One level change was considered important for the total sum score. Effect size of the change in index, VAS, and total sum scores was also examined. Chi-squared tests were conducted to examine whether change in EQ-5D-5L varied by age, gender, region, and having anxiety/depression at intake. RESULTS: Three service programs were examined; pulmonary rehabilitation (n = 542), group-based community exercise (n = 463), and physiotherapy for bone and joint care (n = 391). At intake, HRQL in all programs was lower than that of the general Alberta population norms and improved by end of rehabilitation. The mean (SD) change in index, VAS, and total sum scores were 0.02 (0.13), 6.0 (18.3), and - 0.5 (2.4) in pulmonary rehabilitation, 0.06 (0.13), 6.6 (18.7), - 1.2 (2.4) in community exercise, and 0.13 (0.16), 1.2 (0.9), and - 2.8 (2.8) in physiotherapy, respectively. Based on change of the index score, 24% deteriorated, 38% improved, and 38% had no change in pulmonary rehabilitation; 17% deteriorated, 51% improved, and 32% had no change in community exercise; 5% deteriorated, 72% improved, and 23% had no change in physiotherapy. Similar trends were seen in the VAS and total sum scores. Older age, urban region, and having anxiety/depression at intake were associated with positive change in EQ-5D-5L. CONCLUSIONS: The results of this study are intended to inform program/service level decisions by describing the characteristics and HRQL of patients accessing community rehabilitation, as well as the predictors of change in health status, which will help direct future program growth and service changes.

Effectiveness of RADAR: An Innovative Model to Organize Diabetes Care in First Nations Communities.

Challenges exist for the management of diabetes care in First Nations populations. RADAR (Reorganizing the Approach to Diabetes through the Application of Registries) is a culturally appropriate, innovative care model that incorporates a disease registry and electronic health record for local care provision with remote coordination, tailored for First Nations people. This study assessed the effectiveness of RADAR on patient outcomes and diabetes care organization in participating communities in Alberta, Canada. It revealed significant improvements in outcomes after 2 years, with 91% of patients achieving a primary combined end point of a 10% improvement in or persistence at target for A1C, systolic blood pressure, and/or LDL cholesterol. Qualitative assessment showed that diabetes care organization also improved. These multimethod findings support tailored diabetes care practices in First Nations populations.

Pharmacists' chronic disease management in chronic obstructive pulmonary disease: Effect on health services utilization.

BACKGROUND: There is limited real-world evidence on evaluation of chronic disease management initiatives provided by pharmacists to patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To evaluate changes in COPD-related health care resource utilization between patients with COPD who had pharmacist-provided chronic disease management (comprehensive annual care plan [CACP]) vs those who did not have CACP. METHODS: Patients with COPD who received a CACP in Alberta between 2012 and 2015 were identified within the Alberta Health administrative data. Each of these patients were matched with 2 control patients with COPD based on age, sex, provider, date of service, and qualifying comorbidities. Controlled interrupted time series analysis was used to evaluate changes in COPD-specific hospitalizations, emergency department (ED) visits, physician visits, and claims for pulmonary function test. Immediate and temporal changes were calculated for the difference in outcomes 1 year before and 1 year after receiving the CACP for the intervention group and matched controls. RESULTS: Eligible patients (N = 74,365), of whom 28,795 (38.7%) had received CACPs, were matched to a total of 45,570 controls. In 1 year after the CACPs implementation, the number of COPD-related hospitalization visits decreased by 174 (95% CI = -270.8 to -76.5) per 10,000 patients per month, COPD-related ED visits decreased by 123 (95% CI = -294.9 to 49.6) per 10,000 per month, general practitioner visits decreased by 153.9 per 10,000 per month (95% CI = -293.3 to -14.5), and pulmonary function test claims decreased by 19.5 per 10,000 per month (95% CI = -70.1 to 31.2) when compared with the matched controls. However, significant difference between the 2 groups was found for COPD-related hospitalizations only, which was not confirmed by the sensitivity analysis. CONCLUSIONS: In patients with COPD who were provided with care plans by their community pharmacists, there was no significant decrease in COPD-related hospitalizations or ED visits over 1 year compared with the matched controls who did not have a pharmacist-provided care plan. Physician visits and pulmonary function tests did not change significantly for those who had CACP compared with those who did not. There is a need to further understand how care plans can better impact other outcomes that are important in COPD management. DISCLOSURES: This study was supported by a grant from the M.S.I. Foundation (Grant#895) based in Alberta, Canada. Dr Bhutani has consulted for Astra Zeneca, GlaxoSmithKline, Boehringer Ingelheim, Valeo, Covis, and Sanofi. The authors declare no other relevant conflicts of interest or financial relationships. This study is based on data provided by Alberta Health. The interpretation and conclusions of the results are those of the researchers and do not necessarily represent the views of the government of Alberta nor the funder (M.S.I. Foundation). All authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors.

Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration.

Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells - astrocytes and mature myelin-forming oligodendrocytes - is a determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models, unbiased RNA sequencing, functional manipulation, and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation in focally-lesioned male mice yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.

Impact of Comorbidity on Hospitalization and Emergency Room Visits in Adults With Diabetes: A Longitudinal Study of Alberta's Tomorrow Project.

OBJECTIVE: Our aim in this study was to characterize the impact of comorbidities, including number and types, on hospitalization and emergency room (ER) visits in people with diabetes. METHODS: Incident cases of diabetes from Alberta's Tomorrow Project with >24 months of follow-up were included. Comorbidities, classified by Elixhauser conditions, were updated every 12 months after diagnosis. A generalized estimating equation model was used to examine the association (by incidence rate ratio [IRR]) between time-varying comorbidity profile and hospitalization and ER visits per year of follow-up after adjusting for sociodemographic factors, lifestyle behaviours, and historic health-care utilization in the previous 5 years. RESULTS: Among 2,110 incident cases of diabetes (51.0% females; median age at diagnosis: 59.5 years; median follow-up: 7.19 years), the average number of Elixhauser comorbidities was 1.9±1.6 in the first year of diagnosis and 3.3±2.0 in year 15 after diagnosis. The number of comorbidities in the previous year was positively associated with risk of hospitalization (IRR=1.33 [95% confidence interval {CI}: 1.04 to 1.70] and 2.14 [95% CI: 1.67 to 2.74] for 1 or 2 and ≥2 comorbidities, respectively) and ER visits (IRR=1.31 [95% CI: 1.15 to 1.50] and 1.62 [95% CI: 1.41 to 1.87] for 1 or 2 and ≥2 comorbidities, respectively) in the subsequent year. Cardiovascular diseases, peripheral vascular diseases, cancer, liver disease, fluid and electrolyte disorders, and depression were the conditions most typically associated with increased health-care utilization. CONCLUSIONS: The number of comorbidities was a major risk factor of health-care utilization for people with diabetes. Vascular diseases, cancer, and conditions closely related to diabetic frailty (e.g. fluid and electrolyte disorders and depression) were the main drivers of hospital care and ER visits.

Engaging Black or African American and Hispanic or Latino Men Who Have Sex With Men for HIV Testing and Prevention Services Through Technology: Protocol for the iSTAMP Comparative Effectiveness Trial.

BACKGROUND: Gay, bisexual, and other men who have sex with men (MSM), particularly Black or African American MSM (BMSM) and Hispanic or Latino MSM (HLMSM), continue to be disproportionately affected by the HIV epidemic in the United States. Previous HIV self-testing programs have yielded high testing rates, although these studies predominantly enrolled White, non-Hispanic MSM. Mobile health tools can support HIV prevention, testing, and treatment. This protocol details an implementation study of mailing free HIV self-tests (HIVSTs) nested within a randomized controlled trial designed to assess the benefit of a mobile phone app for increasing the uptake of HIV prevention and other social services. OBJECTIVE: This study was a comparative effectiveness trial of innovative recruitment and testing promotion strategies intended to effectively reach cisgender BMSM and HLMSM. We evaluated the use of a mobile app for increasing access to care. METHODS: Study development began with individual and group consultations that elicited feedback from 3 core groups: HIV care practitioners and researchers, HIV service organization leaders from study states, and BMSM and HLMSM living in the study states. Upon completion of the formative qualitative work, participants from 11 states, based on the observed areas of highest rate of new HIV diagnoses among Black and Hispanic MSM, were recruited through social networking websites and smartphone apps. After eligibility was verified, participants consented and were randomized to the intervention arm (access to the Know@Home mobile app) or the control arm (referral to web resources). We provided all participants with HIVSTs. The evaluation of the efficacy of a mobile phone app to support linkage to posttest prevention services that included sexually transmitted infection testing, pre-exposure prophylaxis initiation, antiretroviral treatment, and acquisition of condoms and compatible lubricants has been planned. Data on these outcomes were obtained from several sources, including HIVST-reporting surveys, the 4-month follow-up survey, laboratory analyses of dried blood spot cards returned by the participant, and data obtained from the state health department surveillance systems. Where possible, relevant subgroup analyses were performed. RESULTS: During the formative development phase, 9 consultations were conducted: 6 in-depth individual discussions and 3 group consultations. From February 2020 through February 2021, we enrolled 2093 MSM in the randomized controlled trial from 11 states, 1149 BMSM and 944 HLMSM. CONCLUSIONS: This study was designed and implemented to evaluate the effectiveness of recruitment strategies to reach BMSM and HMSM and of a mobile app with regard to linkage to HIV prevention or treatment services. Data were also obtained to allow for the analyses of cost and cost-effectiveness related to study enrollment, HIV testing uptake, identification of previously undiagnosed HIV, sexually transmitted infection testing and treatment, and linkage to HIV prevention or treatment services. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04219878); https://clinicaltrials.gov/ct2/show/NCT04219878. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43414.

"You need a team": perspectives on interdisciplinary symptom management using patient-reported outcome measures in hemodialysis care-a qualitative study.

BACKGROUND: Patient-reported outcome measures (PROMs) are standardized instruments used for assessing patients' perspectives on their health status at a point in time, including their health-related quality of life, symptoms, functionality, and physical, mental, and social wellbeing. For people with kidney failure receiving hemodialysis, addressing high symptom burden and complexity relies on care team members integrating their expertise to achieve common management goals. In the context of a program-wide initiative integrating PROMs into routine hemodialysis care, we aimed to explore patients' and clinicians' perspectives on the role of PROMs in supporting interdisciplinary symptom management. METHODS: We employed a qualitative descriptive approach using semi-structured interviews and observations. Eligible participants included adult patients receiving intermittent, outpatient hemodialysis for > 3 months, their informal caregivers, and hemodialysis clinicians (i.e., nurses, nephrologists, and allied health professionals) in Southern Alberta, Canada. Guided by thematic analysis, team members coded transcripts in duplicate and developed themes iteratively through review, refinement, and discussion. RESULTS: Thirty-three clinicians (22 nurses, 6 nephrologists, 5 allied health professionals), 20 patients, and one caregiver participated in this study. Clinicians described using PROMs to coordinate care across provider types using the resources available in their units, whereas patients tended to focus on the perceived impact of this concerted care on symptom trajectory and care experience. We identified 3 overarching themes with subthemes related to the role of PROMs in interdisciplinary symptom management in this setting: (1) Integrating care for interrelated symptoms ("You need a team", conducive setting, role clarity and collaboration); (2) Streamlining information sharing and access (symptom data repository, common language for coordinated care); (3) Reshaping expectations (expectations for follow-up, managing symptom persistence). CONCLUSIONS: We found that use of PROMs in routine hemodialysis care highlighted symptom interrelatedness and complexity and helped to streamline involvement of the interdisciplinary care team. Issues such as role flexibility and resource constraints may influence sustainability of routine PROM use in the outpatient hemodialysis setting.

People with kidney failure receiving hemodialysis are faced with complex symptoms that impact their day-to-day functioning and quality of life. Patient-reported outcome measures (PROMs) are tools used by patients to directly communicate symptoms to their care team and guide symptom-focused care. Little is known about how PROMs could be integrated into the team-based care models of outpatient hemodialysis centres. In this study, we conducted interviews with people receiving hemodialysis and their clinicians about their perspectives on how PROMs could support interdisciplinary symptom management (i.e., integration of expertise to achieve common management goals). Participants described how the interrelatedness of symptoms was well suited to an integrated care approach and how PROMs enhanced communication and access to information across team members. In cases where symptoms persisted despite appropriate treatment, patients and clinicians explained how PROMs served as a tool to set realistic goals and reshape illness perception. Findings from this study suggest that access to resources, role flexibility, and established relationships within hemodialysis centres are important for sustaining PROM use in this setting.

Impact of an online, individualised, patient reported outcome measures based patient decision aid on patient expectations, decisional regret, satisfaction, and health-related quality-of-life for patients considering total knee arthroplasty: Results from a randomised controlled trial.

RATIONALE: Total knee arthroplasty is a common surgical procedure but not appropriate for all patients with knee osteoarthritis. Patient decision aids (PtDAs) can promote shared decision making and enhance understanding and expectations of procedures among patients, resulting in better discussions between patients and healthcare providers about whether total knee arthroplasty is the most appropriate option. AIMS AND OBJECTIVES: Evaluate impact of an individualised PtDA for osteoarthritis patients considering total knee arthroplasty 1 year after baseline assessment. METHODS: Prospective, randomised controlled trial comparing an intervention arm (IA) and routine care arm (RCA). The IA included an online individualised patient reported outcome measures (PROMs) based PtDA and one-page summary report for the surgeon. We report secondary outcomes from the final assessment: patient expectations, decisional regret, patient satisfaction with outcomes of knee replacement, health-related quality-of-life (HRQOL) and depression. We report changes in HRQOL between baseline and final assessments, study arms, and surgical versus non-surgical patients. Descriptive statistics were used to describe participant characteristics and continuous variables. Dichotomous outcomes (expectations, decisional regret, satisfaction) were analyzed using logistic regression and continuous outcomes (HRQOL, depression) were modelled using linear regression. RESULTS: Overall, 140 participants completed all study assessments (IA: n = 69, RCA: n = 71); n = 108 underwent surgery (IA: n = 49, RCA: n = 59). Regardless of study arm, most participants reported expectations were met, minimal decisional regret, satisfaction with outcomes of knee replacement, and had improvements in HRQOL. While no significant differences in study outcomes were found between study arms, IA results were in the direction hypothesised in favour of the PtDA. CONCLUSIONS: Although we were not able to detect statistically significant benefits associated with implementing this PROMs-based PtDA, there was no apparent negative effect on these outcomes 1 year after baseline. We anticipate there may be benefit to implementing this PtDA earlier in the osteoarthritis care pathway where patients have more opportunities to manage their disease non-surgically.

An online individualised patient decision aid improves the quality of decisions in patients considering total knee arthroplasty in routine care: A randomized controlled trial.

Objective: The objective of this study was to evaluate the effectiveness of an online patient decision aid with individualised potential outcomes of surgery, on the quality of decisions for knee replacement surgery in routine clinical care. Design: A pragmatic Randomized Controlled Trial (RCT) in patients considering total knee replacement at a high-volume orthopedic clinic. Patients were randomized at their routine online pre-surgical assessment to either complete a decision aid or not. At their consultation, those in the intervention arm had a surgeon report summarizing the decision aid results. The primary outcome was decision quality, defined as being knowledgeable and choosing the option that matched informed treatment preferences. Multivariate logistic and linear regression analysis was conducted to consider surgeon level clustering and baseline differences between study arms. Results: Of 163 patients randomized, 155 completed post-surgical surveys and were included in the analysis. The average patient was aged 65 years, obese and had moderate to severe osteoarthritis symptoms at baseline. Patients in the intervention arm had a higher odds of making a quality decision (Odds Ratio â€‹= â€‹2.08, 95% CI: 1.08 to 4.02), predominantly through increased knowledge. Conclusions: This study supports the benefit of a decision aid in combination with a surgeon report to significantly improve decision quality in routine care. While the independent contribution of tailoring the decision aid to patient baseline characteristics and including a surgeon report remains unclear, we demonstrated the feasibility of integrating the decision aid into an online pre-surgical assessment in routine clinical care.