Evaluation of the implementation of single points of access for unattached patients in primary care and their effects: a study protocol.

INTRODUCTION: Attachment to a primary care provider is an important component of primary care as it facilitates access. In Québec, Canada, attachment to a family physician is a concern. To address unattached patients' barriers to accessing primary care, the Ministry of Health and Social Services mandated Québec's 18 administrative regions to implement single points of access for unattached patients (Guichets d'accès première ligne (GAPs)) that aim to better orient patients towards the most appropriate services to meet their needs. The objectives of this study are to (1) analyse the implementation of GAPs, (2) measure the effects of GAPs on performance indicators and (3) assess unattached patients' experiences of navigation, access and service utilisation. METHODS AND ANALYSIS: A longitudinal mixed-methods case study design will be conducted. Objective 1. Implementation will be analysed through semistructured interviews with key stakeholders, observations of key meetings and document analysis. Objective 2. GAP effects on indicators will be measured using performance dashboards produced using clinical and administrative data. Objective 3. Unattached patients' experiences will be assessed using a self-administered electronic questionnaire. Findings for each case will be interpreted and presented using a joint display, a visual tool for integrating qualitative and quantitative data. Intercase analyses will be conducted highlighting the similarities and differences across cases. ETHICS AND DISSEMINATION: This study is funded by the Canadian Institutes of Health Research (# 475314) and the Fonds de Soutien à l'innovation en santé et en services sociaux (# 5-2-01) and was approved by the CISSS de la Montérégie-Centre Ethics Committee (MP-04-2023-716).

Effects of Buprenorphine/Naloxone and Methadone on Depressive Symptoms in People with Prescription Opioid Use Disorder: A Pragmatic Randomised Controlled Trial.

OBJECTIVE: This study aimed to evaluate the effectiveness of flexible take-home dosing of buprenorphine/naloxone (BUP/NX) and methadone standard model of care in reducing depressive symptoms in people with prescription-type opioid use disorder (POUD). This trial also evaluated whether improvements in depressive symptoms were mediated by opioid use. METHODS: Analyzed data came from the OPTIMA study (clinicaltrials.gov identifier: NCT03033732), a pragmatic randomised controlled trial comparing flexible take-home dosing of BUP/NX and methadone standard model of care for reducing opioid use in people with POUD. A total of 272 participants were recruited in four Canadian provinces. Participants were randomised 1:1 to BUP/NX or methadone. After treatment induction, past two-week opioid use was measured using the Timeline Followback every two weeks for a total of 24 weeks. Depressive symptoms were measured with the Beck Depression Inventory at baseline, weeks 12 and 24. RESULTS: Both BUP/NX and methadone significantly reduced depressive symptoms at week 12 (aß ± SE = -3.167 ± 1.233; P < 0.001) and week 24 (aß ± SE = -7.280 ± 1.285; P < 0.001), with no interaction between type of treatment and time (P = 0.284). Improvements in depressive symptoms were only partially mediated by a reduction in opioid use (proportion mediated = 36.8%; 95% confidence interval = -1.158 to -0.070; P = 0.015). CONCLUSIONS: BUP/NX and methadone showed similar effectiveness in decreasing comorbid depressive symptoms in people with POUD. This effect was partially explained by a reduction in opioid use. As both treatments seem equally effective, clinicians are encouraged to tailor the selection of OAT to patients' needs and characteristics.

Buprenorphine/naloxone and methadone effectiveness for reducing craving in individuals with prescription opioid use disorder: Exploratory results from an open-label, pragmatic randomized controlled trial.

BACKGROUND: Craving reduction is an important target in the treatment of prescription-type opioid use disorder (POUD). In this exploratory analysis, we compared the effectiveness of BUP/NX flexible model of care relative to methadone for craving reduction in individuals with POUD. METHODS: We analyzed data from a multicentric, pragmatic, 24-week open-label randomized controlled trial conducted in participants with POUD (N = 272) who were randomly assigned to BUP/NX model of care with flexible take-home dosing (n = 138) or the standard model of care with closely supervised methadone (n = 134). Treatments were prescribed and administered according to local guidelines, in diverse clinical settings. Craving was measured using the Brief Substance Craving Scale at baseline, week 2, 6, 10, 14, 18 and 22. RESULTS: Cravings decreased in both treatment groups over 22 weeks (BUP/NX adjusted mean difference = -5.52, 95% CI = -6.91 to -4.13; methadone adjusted mean difference = -3.95, 95% CI = -5.28 to -2.63; p < 0.001), and were overall lower in the BUP/NX group (adjusted mean = 4.04, 95% CI = 3.43-4.64) than the methadone group (adjusted mean = 5.13, 95% CI = 4.51-5.74; p < 0.001). The time by treatment group interaction (favoring BUP/NX) was statistically significant at week 2 (adjusted mean difference = -1.58, 95% CI = -3.13 to -0.03; p = 0.041). CONCLUSIONS: Compared to the standard methadone model of care, flexible take-home dosing of BUP/NX was associated with lower craving in individuals with POUD. These findings can contribute to guiding shared decision-making regarding OAT treatment in this population.

Healthcare Professional Perspectives on the Use of Remote Patient-Monitoring Platforms during the COVID-19 Pandemic: A Cross-Sectional Study.

The COVID-19 pandemic created an urgent need to act to reduce the spread of the virus and alleviate congestion in healthcare services, protect health professionals, and help them maintain satisfactory quality and safety of care. Remote monitoring platforms (RPM) emerged as potential solutions. In this study, we evaluate, from health professionals' perspectives, the capacity and contribution of two different digital platforms to maintain quality, safety, and patient engagement in care. A cross-sectional study was conducted using a survey in which a total of 491 health professionals participated. The results show that, in general, user perceptions of the quality and safety of care provided through the platforms were positive. The ease of access to health professionals' services in general and shorter waiting times for patients were the two main features that were highly appreciated by most participants. However, some problems were encountered during the use of these two platforms, such as a lack of training and/or direct support for users. To improve the two platforms and maximize their use, the areas for improvement and the issues identified should be addressed as part of a collaborative process involving health professionals and patients as well as health system leaders, decision-makers, and digital platform providers.

Remote Patient Monitoring Program for COVID-19 Patients Following Hospital Discharge: A Cross-Sectional Study.

Background: The COVID-19 pandemic created an urgent need to act to reduce the spread of the virus and alleviate congestion from healthcare services, protect healthcare providers, and help them maintain satisfactory quality and safety of care. Remote COVID-19 monitoring platforms emerged as potential solutions. Objective: The purpose of this study was to evaluate the capacity and contribution of two different platforms used to remotely monitor patients with COVID-19 to maintain quality, safety, and patient engagement in care, as well as their acceptability, usefulness, and user-friendliness from the user's perspective. The first platform is focused on telecare phone calls (Telecare-Covid), and the second is a telemonitoring app (CareSimple-Covid). Methods: We performed a cross-sectional study. The data were collected through a phone survey from May to August 2020. Data were analyzed using descriptive statistics and t-test analysis. Participants' responses and comments on open-ended questions were analyzed using content analysis to identify certain issues and challenges and potential avenues for improving the platforms. Results: Fifty one patients participated in the study. Eighteen participants used the CareSimple-Covid platform and 33 participants used the Telecare-Covid platform. Overall, the satisfaction rate for quality and safety of care for the two platforms was 80%. Over 88% of the users on each platform considered the platforms' services to be engaging, useful, user-friendly, and appropriate to their needs. The survey identified a few significant differences in users' perceptions of each platform: empathy toward users and the quality and safety of the care received were rated significantly higher on the CareSimple-Covid platform than on the Telecare-Covid platform. Users appreciated four aspects of these telehealth approaches: (1) the ease of access to services and the availability of care team members; (2) the user-friendliness of the platforms; (3) the continuity of care provided, and (4) the wide range of services delivered. Users identified some technical limitations and raised certain issues, such as the importance of maintaining human contact, data security, and confidentiality. Improvement suggestions include promoting access to connected devices; enhancing communications between institutions, healthcare users, and the public on confidentiality and personal data protection standards; and integrating a participatory approach to telehealth platform development and deployment efforts. Conclusion: This study provides preliminary evidence that the two remote monitoring platforms are well-received by users, with very few significant differences between them concerning users' experiences and views. This type of program could be considered for use in a post-pandemic era and for other post-hospitalization clienteles. To maximize efficiency, the areas for improvement and the issues identified should be addressed with a patient-centered approach.

The Strong Cell-based Hydrogen Peroxide Generation Triggered by Cold Atmospheric Plasma.

Hydrogen peroxide (H2O2) is an important signaling molecule in cancer cells. However, the significant secretion of H2O2 by cancer cells have been rarely observed. Cold atmospheric plasma (CAP) is a near room temperature ionized gas composed of neutral particles, charged particles, reactive species, and electrons. Here, we first demonstrated that breast cancer cells and pancreatic adenocarcinoma cells generated micromolar level H2O2 during just 1 min of direct CAP treatment on these cells. The cell-based H2O2 generation is affected by the medium volume, the cell confluence, as well as the discharge voltage. The application of cold atmospheric plasma (CAP) in cancer treatment has been intensively investigated over the past decade. Several cellular responses to CAP treatment have been observed including the consumption of the CAP-originated reactive species, the rise of intracellular reactive oxygen species, the damage on DNA and mitochondria, as well as the activation of apoptotic events. This is a new previously unknown cellular response to CAP, which provides a new prospective to understand the interaction between CAP and cells in vitro and in vivo. The short-lived reactive species in CAP may activate cells in vivo to generate long-lived reactive species such as H2O2, which may trigger immune attack on tumorous tissues via the H2O2-mediated lymphocyte activation.

A Randomized Switch From Nevirapine-Based Antiretroviral Therapy to Single Tablet Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in Virologically Suppressed Human Immunodeficiency Virus-1-Infected Rwandans.

Background. Many human immunodeficiency virus (HIV)-infected patients remain on nevirapine-based antiretroviral therapy (ART) despite safety and efficacy concerns. Switching to a rilpivirine-based regimen is an alternative, but there is little experience with rilpivirine in sub-Saharan Africa where induction of rilpivirine metabolism by nevirapine, HIV subtype, and dietary differences could potentially impact efficacy. Methods. We conducted an open-label noninferiority study of virologically suppressed (HIV-1 ribonucleic acid [RNA] < 50 copies/mL) HIV-1-infected Rwandan adults taking nevirapine plus 2 nucleos(t)ide reverse-transcriptase inhibitors. One hundred fifty participants were randomized 2:1 to switch to coformulated rilpivirine-emtricitabine-tenofovir disoproxil fumarate (referenced as the Switch Arm) or continue current therapy. The primary efficacy endpoint was HIV-1 RNA < 200 copies/mL at week 24 assessed by the US Food and Drug Administration Snapshot algorithm with a noninferiority margin of 12%. Results. Between April and September 2014, 184 patients were screened, and 150 patients were enrolled; 99 patients switched to rilpivirine-emtricitabine-tenofovir, and 51 patients continued their nevirapine-based ART. The mean age was 42 years and 43% of participants were women. At week 24, virologic suppression (HIV-1 RNA level <200 copies/mL) was maintained in 93% and 92% in the Switch Arm versus the continuation arm, respectively. The Switch Arm was noninferior to continued nevirapine-based ART (efficacy difference 0.8%; 95% confidence interval, -7.5% to +12.0%). Both regimens were generally safe and well tolerated, although 2 deaths, neither attributed to study medications, occurred in participants in the Switch Arm. Conclusions. A switch from nevirapine-based ART to rilpivirine-emtricitabine-tenofovir disoproxil fumarate had similar virologic efficacy to continued nevirapine-based ART after 24 weeks with few adverse events.

Toward understanding the selective anticancer capacity of cold atmospheric plasma--a model based on aquaporins (Review).

Selectively treating tumor cells is the ongoing challenge of modern cancer therapy. Recently, cold atmospheric plasma (CAP), a near room-temperature ionized gas, has been demonstrated to exhibit selective anticancer behavior. However, the mechanism governing such selectivity is still largely unknown. In this review, the authors first summarize the progress that has been made applying CAP as a selective tool for cancer treatment. Then, the key role of aquaporins in the H2O2 transmembrane diffusion is discussed. Finally, a novel model, based on the expression of aquaporins, is proposed to explain why cancer cells respond to CAP treatment with a greater rise in reactive oxygen species than homologous normal cells. Cancer cells tend to express more aquaporins on their cytoplasmic membranes, which may cause the H2O2 uptake speed in cancer cells to be faster than in normal cells. As a result, CAP treatment kills cancer cells more easily than normal cells. Our preliminary observations indicated that glioblastoma cells consumed H2O2 much faster than did astrocytes in either the CAP-treated or H2O2-rich media, which supported the selective model based on aquaporins.

Principles of using Cold Atmospheric Plasma Stimulated Media for Cancer Treatment.

To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demonstrated several principles to optimize the anti-cancer capacity of the CAPs media on glioblastoma cells and breast cancer cells. Specifically, using larger wells on a multi-well plate, smaller gaps between the plasma source and the media, and smaller media volume enabled us to obtain a stronger anti-cancer CAPs media composition without increasing the treatment time. Furthermore, cysteine was the main target of effective reactive species in the CAPs media. Glioblastoma cells were more resistant to the CAPs media than breast cancer cells. Glioblastoma cells consumed the effective reactive species faster than breast cancer cells did. In contrast to nitric oxide, hydrogen peroxide was more likely to be the effective reactive species.

Treating psychological trauma among Rwandan orphans is associated with a reduction in HIV risk-taking behaviors: A pilot study.

The nongovernmental organization, Uyisenga N'Manzi (UNM), provides Rwandan orphans of genocide and HIV/AIDS with education, social, and mental health services. Many orphans in UNM report symptoms of psychological trauma. The primary study objective was to evaluate a multidisciplinary program integrating HIV prevention with an existing package of mental health services. We randomly selected 120 orphans between ages 15-25 years served by UNM and evaluated sexually-transmitted infections, HIV risk-taking behaviors and knowledge, and mental health at baseline, 5, 9, and 12 months. Increased trauma symptoms at baseline were associated with poorer coping skills and social functioning, and increased psychological distress and HIV risk-taking behavior. Following the 12-month intervention, trauma symptoms declined significantly, with those accessing counseling services showing greatest improvement. Orphans with the highest trauma scores benefited most from the intervention. In this at-risk population, addressing mental health issues in the context of HIV prevention is critical.

Management and treatment of hepatitis B virus in patients with HIV infection: A practical guide for health care professionals.

The management and treatment of HIV and hepatitis B virus (HBV)-coinfected patients present specific challenges for clinicians. The morbidity and mortality related to these concomitant infections are growing concerns, while the use of antiviral drugs effective against both viruses complicates therapeutic decision making. The present document provides guidelines for physicians regarding care and treatment of patients coinfected with HIV and HBV. Primary prevention of HBV in HIV-positive patients is achieved through appropriate vaccination schedules. Follow-up before treatment of HBV may include liver biopsy, screening for hepatocellular carcinoma and testing for esophageal varicies in cases of cirrhosis. In HBV-infected patients requiring treatment, recommendations regarding initiation, duration and choice of first-line drugs are made. Finally, in the case of resistance, appropriate alternative therapies are necessary.

Cost-effectiveness of antiretroviral regimens in the World Health Organization's treatment guidelines: a South African analysis.

OBJECTIVE: the World Health Organization (WHO) recently changed its first-line antiretroviral treatment guidelines in resource-limited settings. The cost-effectiveness of the new guidelines is unknown. DESIGN: comparative effectiveness and cost-effectiveness analysis using a model of HIV disease progression and treatment. METHODS: using a simulation of HIV disease and treatment in South Africa, we compared the life expectancy, quality-adjusted life expectancy, lifetime costs, and cost-effectiveness of five initial regimens. Four are currently recommended by the WHO: tenofovir/lamivudine/efavirenz; tenofovir/lamivudine/nevirapine; zidovudine/lamivudine/efavirenz; and zidovudine/lamivudine/nevirapine. The fifth is the most common regimen in current use: stavudine/lamivudine/nevirapine. Virologic suppression and toxicities determine regimen effectiveness and cost-effectiveness. RESULTS: choice of first-line regimen is associated with a difference of nearly 12 months of quality-adjusted life expectancy, from 135.2 months (tenofovir/lamivudine/efavirenz) to 123.7 months (stavudine/lamivudine/nevirapine). Stavudine/lamivudine/nevirapine is more costly and less effective than zidovudine/lamivudine/nevirapine. Initiating treatment with a regimen containing tenofovir/lamivudine/nevirapine is associated with an incremental cost-effectiveness ratio of $1045 per quality-adjusted life year compared with zidovudine/lamivudine/nevirapine. Using tenofovir/lamivudine/efavirenz was associated with the highest survival, fewest opportunistic diseases, lowest rate of regimen substitution, and an incremental cost-effectiveness ratio of $5949 per quality-adjusted life year gained compared with tenofovir/lamivudine/nevirapine. Zidovudine/lamivudine/efavirenz was more costly and less effective than tenofovir/lamivudine/nevirapine. Results were sensitive to the rates of toxicities and the disutility associated with each toxicity. CONCLUSION: among the options recommended by WHO, we estimate only three should be considered under normal circumstances. Choice among those depends on available resources and willingness to pay. Stavudine/lamivudine/nevirapine is associated with the poorest quality-adjusted survival and higher costs than zidovudine/lamivudine/nevirapine.

Predicting tipranavir and darunavir resistance using genotypic, phenotypic, and virtual phenotypic resistance patterns: an independent cohort analysis of clinical isolates highly resistant to all other protease inhibitors.

Genotypic interpretation systems (GISs) for darunavir and tipranavir susceptibility are rarely tested by the use of independent data sets. The virtual phenotype (the phenotype determined by Virco [the "Vircotype"]) was used to interpret all genotypes in Québec, Canada, and phenotypes were determined for isolates predicted to be resistant to all protease inhibitors other than darunavir and tipranavir. We used multivariate analyses to predict relative phenotypic susceptibility to darunavir and tipranavir. We compared the performance characteristics of the Agence Nationale de Recherche sur le Sida scoring algorithm, the Stanford HIV database scoring algorithm (with separate analyses of the discrete and numerical scores), the Vircotype, and the darunavir and tipranavir manufacturers' scores for prediction of the phenotype. Of the 100 isolates whose phenotypes were determined, 89 and 72 were susceptible to darunavir and tipranavir, respectively. In multivariate analyses, the presence of I84V and V82T and the lack of L10F predicted that the isolates would be more susceptible to darunavir than tipranavir. The presence of I54L, V32I, and I47V predicted that the isolates would be more susceptible to tipranavir. All GISs except the system that provided the Stanford HIV database discrete score performed well in predicting the darunavir resistance phenotype (R(2) = 0.61 to 0.69); the R(2) value for the Stanford HIV database discrete scoring system was 0.38. Other than the system that provided the Vircotype (R(2) = 0.80), all GISs performed poorly in predicting the tipranavir resistance phenotype (R(2) = 0.00 to 0.31). In this independent cohort harboring highly protease inhibitor-resistant HIV isolates, reduced phenotypic susceptibility to darunavir and tipranavir was rare. Generally, GISs predict susceptibility to darunavir substantially better than they predict susceptibility to tipranavir.

Switch from enfuvirtide to raltegravir in virologically suppressed HIV-1 infected patients: effects on level of residual viremia and quality of life.

BACKGROUND: Raltegravir is a potential treatment option for virologically suppressed HIV-1 infected patients on enfuvirtide with injection site reactions. OBJECTIVES: To characterize safety and efficacy of an enfuvirtide to raltegravir switch including changes in T-cells, quality of life, and residual viremia. STUDY DESIGN: In patients with viral load <50 copies/mL and injection site reactions, enfuvirtide was switched to raltegravir without additional changes to the antiretroviral regimen. Virologic failure was defined as a viral load >1000 copies/mL or two consecutive viral load measurements between 50 and 1000 copies/mL (low-level viremia). Over the 24 week study, we compared changes in T-cells, injection site reactions, quality of life, and residual viremia, as measured through the single-copy assay which can detect plasma virus down to a single copy, using paired t-tests. RESULTS: Fourteen patients with a median CD4+ T-cell count of 420 cells/microL were enrolled. After the switch, two patients experienced virologic failure due to confirmed low-level viremia. However, both patients subsequently were re-suppressed, one without any changes to his regimen. There was no change in CD4+ T-cell count. Injection site reactions resolved. However, there was little reported change in quality of life. The baseline median level of residual viremia was 6 copies/mL and did not change after the switch to raltegravir. CONCLUSIONS: A switch to raltegravir in virologically suppressed patients on enfuvirtide is effective in maintaining immunologic and virologic control at 24 weeks but did not result in a change in residual viremia.

Contribution of cannabis and MDMA ("ecstasy") to cognitive changes in long-term polydrug users.

RATIONALE: Establishing whether cognitive changes follow long-term use of MDMA ("ecstasy") in humans has been difficult because of possible confounds with other drug use, particularly cannabis. Convincing evidence may be only obtained using experimental designs that account for such confounds. OBJECTIVE: In the present study, cognitive/behavioural measures were used to investigate whether long-term MDMA use or long-term cannabis use is responsible for the changes sometimes observed in recreational MDMA users. METHOD: Tests of attention and memory were administered to subjects who used both MDMA and cannabis, cannabis only, or neither drug. RESULTS: The main finding was that cannabis users, whether or not they also used MDMA, showed significantly impaired memory function on word free-recall and on immediate and delayed story recall compared to non-users. CONCLUSIONS: The findings highlight the importance of controlling for other drug use (particularly cannabis) when investigating persistent effects of MDMA in humans.