Medication utilization patterns in patients with post-COVID syndrome (PCS): Implications for polypharmacy and drug-drug interactions.

BACKGROUND: Post-COVID syndrome (PCS) causes lasting symptoms like fatigue and cognitive issues. PCS treatment is nonspecific, focusing on symptom management, potentially increasing the risk of polypharmacy. OBJECTIVES: To describe medication use patterns among patients with Post-COVID Syndrome (PCS) and estimate the prevalence of polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden. METHODS: A cross-sectional analysis of baseline data from the Quebec Action for Post-COVID cohort, consisting of individuals self-identifying with persistent COVID-19 symptoms beyond 12 weeks. Medications were categorized using Anatomical Therapeutic Classification (ATC) codes. Polypharmacy was defined as using 5 or more concurrent medications. The Anticholinergic and Sedative Burden Catalog assessed anticholinergic and sedative loads. The Lexi-Interact checker identified potential drug-drug interactions, which were categorized into 3 severity tiers. RESULTS: Out of 414 respondents, 154 (average age 47.7 years) were prescribed medications related to persistent COVID-19 symptoms. Drugs targeting the nervous system were predominant at 54.5%. The median number of medications was 2, while 11.7% reported polypharmacy. Over half of the participants prescribed medications used at least 1 anticholinergic or sedative medication, and 25% had the potential risk for clinically significant drug-drug interactions, primarily needing therapy monitoring. CONCLUSIONS: Our study reveals prescription patterns for PCS, underscoring the targeted management of nervous system symptoms. The risks associated with polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden stress the importance of judicious prescribing. While limitations like recall bias and a regional cohort are present, the findings underscore the imperative need for vigilant PCS symptom management.

The Patient Generated Index (PGI) as an early-warning system for predicting brain health challenges: a prospective cohort study for people living with Human Immunodeficiency Virus (HIV).

PURPOSE: In research people are often asked to fill out questionnaires about their health and functioning and some of the questions refer to serious health concerns. Typically, these concerns are not identified until the statistician analyses the data. An alternative is to use an individualized measure, the Patient Generated Index (PGI) where people are asked to self-nominate areas of concern which can then be dealt with in real-time. This study estimates the extent to which self-nominated areas of concern related to mood, anxiety and cognition predict the presence or occurrence of brain health outcomes such as depression, anxiety, psychological distress, or cognitive impairment among people aging with HIV at study entry and for successive assessments over 27 months. METHODS: The data comes from participants enrolled in the Positive Brain Health Now (+ BHN) cohort (n = 856). We analyzed the self-nominated areas that participants wrote on the PGI and classified them into seven sentiment groups according to the type of sentiment expressed: emotional, interpersonal, anxiety, depressogenic, somatic, cognitive and positive sentiments. Tokenization was used to convert qualitative data into quantifiable tokens. A longitudinal design was used to link these sentiment groups to the presence or emergence of brain health outcomes as assessed using standardized measures of these constructs: the Hospital Anxiety and Depression Scale (HADS), the Mental Health Index (MHI) of the RAND-36, the Communicating Cognitive Concerns Questionnaire (C3Q) and the Brief Cognitive Ability Measure (B-CAM). Logistic regressions were used to estimate the goodness of fit of each model using the c-statistic. RESULTS: Emotional sentiments predicted all of the brain health outcomes at all visits with adjusted odds ratios (OR) ranging from 1.61 to 2.00 and c-statistics > 0.73 (good to excellent prediction). Nominating an anxiety sentiment was specific to predicting anxiety and psychological distress (OR 1.65 & 1.52); nominating a cognitive concern was specific to predicting self-reported cognitive ability (OR 4.78). Positive sentiments were predictive of good cognitive function (OR 0.36) and protective of depressive symptoms (OR 0.55). CONCLUSIONS: This study indicates the value of using this semi-qualitative approach as an early-warning system in predicting brain health outcomes.

"Alone, there is nobody": A qualitative study of the lived experience of loneliness in older men living with HIV.

Loneliness has been shown to be a predictor of poor health and early mortality in the general population. Older men living with human immunodeficiency virus (HIV) are at heightened risk of experiencing loneliness. Here, we aim to describe the lived experience of loneliness in older men living with HIV and identify targets for intervention. We used grounded theory with a theoretical framework of narrative phenomenology to focus data collection and analysis on significant experiences related to loneliness. Based on individual narrative interviews with 10 older men living with HIV, experiences of loneliness related to "multiple losses," "being invisible" and "hiding out" as emergent themes. Participants also described living with loneliness by "finding meaning," "creating social experiences," "pursuing interests and things to 'live for'" and attending events in which "everyone is welcome." The discussion situates experiences of loneliness within the accumulation of losses and stigmas over time and how the participants strategies for living with loneliness could inform interventions to reduce loneliness in older men living with HIV at individual and societal levels.

Impact of Hepatitis C Virus Cure on Depressive Symptoms in the Human Immunodeficiency Virus-Hepatitis C Virus Coinfected Population in Canada.

BACKGROUND: Depression is common in people with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), with biological and psychosocial mechanisms at play. Direct acting antivirals (DAA) result in high rates of sustained virologic response (SVR), with minimal side-effects. We assessed the impact of SVR on presence of depressive symptoms in the HIV-HCV coinfected population in Canada during the second-generation DAA era (2013-2020). METHODS: We used data from the Canadian CoInfection Cohort (CCC), a multicenter prospective cohort of people with a HIV and HCV coinfection, and its associated sub-study on food security. Because depression screening was performed only in the sub-study, we predicted Center for Epidemiologic Studies Depression Scale-10 classes in the CCC using a random forest classifier and corrected for misclassification. We included participants who achieved SVR and fit a segmented modified Poisson model using an interrupted time series design, adjusting for time-varying confounders. RESULTS: We included 470 participants; 58% had predicted depressive symptoms at baseline. The median follow-up was 2.4 years (interquartile range [IQR]: 1.0-4.5.) pre-SVR and 1.4 years (IQR: 0.6-2.5) post-SVR. The pre-SVR trend suggested depressive symptoms changed little over time, with no immediate level change at SVR. However, post-SVR trends showed a reduction of 5% per year (risk ratio: 0.95 (95% confidence interval [CI]: .94-.96)) in the prevalence of depressive symptoms. CONCLUSIONS: In the DAA era, predicted depressive symptoms declined over time following SVR. These improvements reflect possible changes in biological pathways and/or better general health. If such improvements in depression symptoms are durable, this provides an additional reason for treatment and early cure of HCV.

Safety and Tolerability of Oral Cannabinoids in People Living with HIV on Long-Term ART: A Randomized, Open-Label, Interventional Pilot Clinical Trial (CTNPT 028).

BACKGROUND: With anti-inflammatory properties, cannabinoids may be a potential strategy to reduce immune activation in people living with HIV (PLWH) but more information on their safety and tolerability is needed. METHODS: We conducted an open-label interventional pilot study at the McGill University Health Centre in Montreal, Canada. PLWH were randomized to oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (THC 2.5 mg/CBD 2.5 mg) or CBD-only capsules (CBD 200 mg). Individuals titrated doses as tolerated to a maximum daily dose THC 15 mg/CBD 15 mg or 800 mg CBD, respectively, for 12 weeks. The primary outcome was the percentage of participants without any significant toxicity based on the WHO toxicity scale (Grades 0-2 scores). RESULTS: Out of ten individuals, eight completed the study. Two from the CBD-only arm were withdrawn for safety concerns: phlebotomy aggravating pre-existing anemia and severe hepatitis on 800 mg CBD with newly discovered pancreatic adenocarcinoma, respectively. Seven did not have any significant toxicity. Cannabinoids did not alter hematology/biochemistry profiles. CD4 count, CD4/CD8 ratio, and HIV suppression remained stable. Most adverse effects were mild-moderate. CONCLUSIONS: In PLWH, cannabinoids seem generally safe and well-tolerated, though larger studies are needed. Screening for occult liver pathology should be performed and hepatic enzymes monitored, especially with high CBD doses.

Trajectories of systemic agent use and associated depression- and anxiety-related health care costs among patients with psoriasis.

Background: Systemic treatment patterns and related mental health disorders and economic burden among patients with psoriasis are largely unknown. Objective: To assess systemic treatment patterns and associated depression and anxiety-related health care costs among patients with psoriasis initiating a conventional systemic treatment (CST). Methods: Using a retrospective cohort design with sequence and cluster analyses, we assessed systemic treatment trajectories (CST and tumor necrosis factor inhibitors or ustekinumab, [TNFi/UST]) over a 2-year period following CST initiation. We compared health care costs between trajectories using 2-part models. Results: We included 781 patients and identified 8 trajectories: persistent methotrexate users, persistent acitretin users, early CST discontinuation, late methotrexate discontinuation, switch to TNFi/UST, adding TNFi/UST, discontinuation then restart on methotrexate, and discontinuation then restart on acitretin or multiple CST switches. Overall, 165 (21%) patients incurred depression- and anxiety-related health care costs (median annual cost, CAN$56; quartiles, $14-$127). Compared with persistent methotrexate users, adding a TNFi/UST (cost ratio, 3.63; 95% CI, 1.47-5.97) and discontinuation then restart on acitretin or multiple switches between systemic agents (cost ratio, 13.3; 95% CI 5.76-22.47) had higher costs. Limitations: Trajectory misclassification may have occured. These date represent an association, and causality cannot be inferred, particularly given the risk of confounding. Conclusion: Depression- and anxiety-related health care costs were high among patients adding TNFi/UST and those discontinuing then restarting on acitretin or experiencing multiple switches between systemic agents.

Sex Differences in the Patterns of Systemic Agent use Among Patients With Psoriasis: A Retrospective Cohort Study in Quebec, Canada.

Background: Sex differences exist in psoriasis manifestation and expectations from treatment with systemic agents, including, conventional systemic agents (CSA) and tumor necrosis factor inhibitors or ustekinumab (TNFi/UST). However, sex differences in patterns of systemic agent use, such as CSA discontinuation and switch from CSA to TNFi/UST have not been examined. Objectives: To assess sex differences in patterns of CSA use and identify factors associated with switch to (or add) a TNFi/UST and those associated with CSA discontinuation. Methods: We conducted a retrospective cohort study using the Quebec health administrative databases. We included patients with psoriasis initiating a CSA in 2002-2015. We excluded patients with a psoriasis diagnosis in the 3 years prior to the first diagnosis date between 2002 and 2015, and those with a systemic agent dispensation in the year prior to that date. We used Cox regression models with the Least Absolute Shrinkage and Selection Operator method to identify factors associated with Switch/add TNFi/UST, and those associated with CSA discontinuation. Separate analyses were performed for male and female patients. Results: We included 1,644 patients (55.7% females, mean age 60.3 years), among whom 60.4% discontinued their CSA and 7.4%, switched/added TNFi/UST (3.4% switched and 4.0% added) within a median of 0.78 years of follow-up. Among male and female patients, rates of Switch/add TNFi/UST per 1,000 person-year were 49.1 and 41.0 and rates of CSA discontinuation were 381.2 and 352.8. Clinical obesity in male patients (HR 3.53, 95% CI 1.20-10.35), and adjustment/somatoform/dissociative disorders (HR 3.17, 95% CI 1.28-7.85) and use of nonsteroidal anti-inflammatory drugs (HR 2.70, 95% CI 1.56-4.70) in female patients were associated with Switch/add TNFi/UST. Male patients followed by a rheumatologist (HR 0.66, 95% CI 0.46-0.94) and those with a prior hospitalization (HR 0.70, 95% CI 0.57-0.87) were at lower risk of CSA discontinuation, while those initiated on acitretin (vs methotrexate) were at higher risk to discontinue their CSA (HR 1.61, 95% CI 1.30-2.01). Female patients with rheumatoid arthritis comorbidity (HR 0.69, 95% CI 0.51-0.93), those with a dispensed lipid-lowering agent (HR 0.72, 95% CI 0.59-0.88) and hypoglycemic agent (HR 0.75, 95% CI 0.57-0.98) and those initiated on methotrexate (vs all other CSAs) were less likely to discontinue their CSA. Male and female patients entering the cohort between 2011 and 2015 were at reduced risk of CSA discontinuation compared to those entering the cohort before 2011. Conclusion: Most male and female patients discontinued their CSA within 1 year of follow-up. Our study highlighted sex differences in patients' characteristics associated with switch/add a TNFi/UST and CSA discontinuation; treatment switch and discontinuation may be indications of treatment failure in most patients.

A mixed-method randomized feasibility trial evaluating progressive muscle relaxation or autogenic training on depressive symptoms and quality of life in people living with human immunodeficiency virus (HIV) who have depressive symptoms.

BACKGROUND: Progressive muscle relaxation (PMR) and autogenic training (AT) are effective relaxation techniques to reduce depressive symptoms. However, no studies on their effectiveness have been conducted among people living with HIV and depressive symptoms. The primary aim of this pilot study was to assess the feasibility and acceptability of PMR and AT interventions among people living with HIV who have depressive symptoms. A secondary aim was to assess the potential effectiveness of these interventions on depressive symptoms and quality of life. METHODS: This study was a three-arm pilot randomized control trial with mixed methods. Participants were randomized to PMR, AT, or a control group (CG), with four assessments (baseline, and at one, three, and six months). The PMR and AT interventions consisted of six 1 h sessions of individual training over 12 weeks, plus home practice. Recruitment, attrition, and completion rates were calculated. Depressive symptoms and quality of life were assessed at all times. Participants' perceptions of the interventions were collected in semi-structured interviews. RESULTS: Following the screening, 54/63 people met the inclusion criteria, and 42/54 were randomly allocated to the PMR group (n=14), AT group (n=14), and CG (n=14). Six participants (43%; 95% CI 18-71%) in the PMR group and 10 (71%; 95% CI 42-92%) in the AT group completed the intervention. Participants reported better emotion management and improvements in depressive symptoms and quality of life. CONCLUSIONS: The pilot study suggests that a randomized trial to test the effectiveness of these interventions is feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT01901016.

In support of an individualized approach to assessing quality of life: comparison between Patient Generated Index and standardized measures across four health conditions.

BACKGROUND: Individualized measures of health-related quality life (HRQL) have been used for decades and shown to provide unique information, but little work has been done to explain this uniqueness particularly across health conditions. AIMS: To estimate, across four health conditions, the magnitude of the association between scores derived from the Patient Generated Index (PGI) and those from fully standardized generic and disease-specific measures of the HRQL; to identify the extent to which the areas generated from the PGI are covered by the content of the fully standardized measures. METHODS: The PGI and other generic and disease-specific measures had been used in four different samples of people: stroke (n = 222), multiple sclerosis (MS; n = 185); advanced cancer (n = 173), and HIV+ (n = 690). Areas nominated on the PGI were harmonized to a standard nomenclature. Pearson correlations were estimated between PGI and other measures. RESULTS: Data from 1263 people indicated that PGI provided the lowest rating for HRQL across all health conditions. The areas nominated differed across conditions with walking/mobility: the most common for stroke (42%), work/school for MS (62%), health for HIV+ (97%), and fatigue for cancer (39%). Many of the aspects of health included in generic measures were not nominated using the PGI and vice versa. The highest correlations between the PGI and other measures were observed for people with MS, with correlations between 0.53 and 0.59; lowest correlations were observed for people with HIV and cancer, ≤0.33. DISCUSSION: The PGI scores reflect those aspects of quality of life that are important to patients in which they would most value an improvement. Heterogeneity in HRQL across health conditions is poorly discriminated using standardized measures. A "one-size-fits-all" approach to HRQL assessment may not provide the most useful representation of this important construct.

The role of extended-release niacin on immune activation and neurocognition in HIV-infected patients treated with antiretroviral therapy - CTN PT006: study protocol for a randomized controlled trial.

BACKGROUND: Approximately 30% of HIV-1-infected patients receiving antiretroviral therapy who achieve virologic control have unsatisfactory immune reconstitution, with CD4+ T-cell counts persistently below 350 cells/µL. These patients are at elevated risk for clinical progression to AIDS and non-AIDS events. CD4+ T-cell depletion following infection and persistent immune activation can partially explain this low CD4+ T-cell recovery. Recent data suggest a link between the tryptophan oxidation pathway, immune activation and HIV disease progression based on overstimulation of the tryptophan oxidation pathway by HIV antigens and by interferon-gamma. This overstimulation reduces levels of circulating tryptophan, resulting in inflammation which has been implicated in the development of neurocognitive dysfunction. Niacin (vitamin B3) is able to control the excess tryptophan oxidation, correcting tryptophan depletion, and therefore represents an interesting strategy to improve CD4 recovery.We aim to design a crossover proof-of-concept study to assess supplementation with an extended-release form of niacin (Niaspan FCT™) in combination with antiretroviral therapy, compared to antiretroviral therapy alone, on T-cell immune activation as defined by changes in the percentage of CD8+ CD38+ HLA-DR+ T-cells. METHODS/DESIGN: This randomized, open-label, interventional crossover study with an immediate versus deferred use of Niaspan FCT for 24 weeks will assess its ability to reduce immune activation and thus increase CD4 recovery in 20 HIV-infected individuals with suboptimal immune responses despite sustained virologic suppression. A substudy evaluating neurocognitive function will also be conducted. DISCUSSION: This randomized trial will provide an opportunity to evaluate the potential benefit of oral extended-release niacin, a drug that can indirectly increase tryptophan, to reduce immune activation and in turn increase CD4+ T-cell recovery. The study will also allow for the evaluation of the impact of Niaspan FCT on neurocognitive function in HIV-infected individuals with suboptimal immune responses despite sustained virologic suppression. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov on 17 December 2013 (registration number: NCT02018965).