Feasibility of a Hospital Peer Review Continuous Quality Improvement Program for Pharmacists' Documentation: A Mixed-Methods Study.

Background: Peer review to assess the quality of documentation is essential, as it provides a framework for constructive feedback, using evaluators with similar qualifications to increase acceptability. Objective: To determine the feasibility of implementing a peer review continuous quality improvement program for pharmacists' documentation at the Montreal Children's Hospital. Methods: A prospective, single-centre mixed-methods feasibility study was conducted (from January to June 2021) to evaluate the practicality and acceptability of a peer review program (PRP) for assessing the quality of pharmacists' documentation. A peer review committee of 5 pharmacists evaluated their peers' clinical notes using a standardized assessment tool. Practicality was determined through the time required for administrative and evaluative tasks and the resources needed for each evaluation cycle. Acceptability was determined through pooled quantitative data related to pharmacists' perceived relevance of the PRP, confidence in their peers, and satisfaction with the evaluation process. Qualitative data collected through surveys, a focus group, and semistructured individual interviews helped to further explain the results. Results: A total of 37.4 hours was required to complete both administrative and evaluative tasks in one peer review cycle, which respected the budgeted cut-off for practicality. Acceptability was also achieved, given that more than 80% of survey respondents found the PRP relevant to their practice, were confident in their peers, and were satisfied with the PRP. Qualitative results showed that participants found the PRP to be instructive and that qualitative feedback was preferred over a grade issued as a percentage. Conclusion: This study showed that it is feasible to implement a PRP to assess the quality of pharmacists' documentation. To ensure success, it is key that documentation objectives and department resources be predefined.

Contexte: L'évaluation par les pairs afin d'évaluer la qualité de la documentation est essentielle, car elle fournit un cadre pour une rétroaction constructive émise par des évaluateurs ayant des qualifications similaires afin d'augmenter l'acceptabilité. Objectif: Déterminer la faisabilité d'implanter un programme d'évaluation par les pairs en continu de la qualité de la documentation des pharmaciens à l'Hôpital de Montréal pour Enfants. Méthodes: Une étude de faisabilité prospective, monocentrique et de méthodes mixtes a été menée (de janvier à juin 2021) pour évaluer la praticité et l'acceptabilité d'un programme d'évaluation par les pairs (PEP) ayant pour but d'évaluer la qualité de la documentation des pharmaciens. Un comité d'évaluation par les pairs composé de 5 pharmaciens a évalué les notes cliniques de leurs pairs à l'aide d'un outil d'évaluation standardisé. La praticité a été déterminée par le temps requis pour les tâches administratives et d'évaluation et les ressources nécessaires pour chaque cycle d'évaluation. L'acceptabilité a été déterminée grâce à des données quantitatives regroupées liées à la pertinence perçue du PEP par les pharmaciens, à la confiance envers leurs pairs et à la satisfaction à l'égard du processus d'évaluation. Les données qualitatives recueillies par le biais de sondages, d'un groupe de discussion et d'entretiens individuels semi-structurés ont permis d'expliquer davantage les résultats. Résultats: Un total de 37,4 heures a été nécessaire pour accomplir les tâches administratives et d'évaluation dans un cycle d'évaluation par les pairs, ce qui respectait le seuil budgété pour des raisons pratiques. L'acceptabilité a également été atteinte puisque plus de 80 % des répondants au sondage trouvaient le PEP pertinent pour leur pratique, avaient confiance en leurs pairs et étaient satisfaits du programme. Les résultats qualitatifs ont montré que les participants trouvaient le PEP instructif et que la rétroaction sous forme de commentaires état préférée à une note émise en pourcentage. Conclusion: Cette étude a démontré qu'il est possible de mettre en place un PEP pour évaluer la qualité de la documentation des pharmaciens. Pour garantir sa réussite, il est essentiel de prédéfinir les objectifs de documentation et les ressources départementales à disposition.

Pharmacotherapeutic Interventions in People Living With HIV Undergoing Solid Organ Transplantation: A Scoping Review.

The pharmacotherapeutic management of people living with HIV (PLWHIV) undergoing solid organ transplantation (SOT) is clinically challenging, mainly due to the frequent occurrence of complex drug-drug interactions. Although various strategies have been proposed to improve treatment outcomes in these patients, several uncertainties remain, and consensus practice guidelines are just beginning to emerge. The main objective of this scoping review was to map the extent of the literature on the pharmacotherapeutic interventions performed by healthcare professionals for PLWHIV undergoing SOT. Methods: We searched Medline, Embase, and the Cochrane databases as well as gray literature for articles published between January 2010 and February 2020. Study selection was performed by at least 2 independent reviewers. Articles describing pharmacotherapeutic interventions in PLWHIV considered for or undergoing SOT were included in the study. Results: Of the 12 599 references identified through our search strategy, 209 articles met the inclusion criteria. Results showed that the vast majority of reported pharmacotherapeutic interventions concerned the management of immunosuppressive and antimicrobial therapy, including antiretrovirals. Analysis of the data demonstrated that for several aspects of the pharmacotherapeutic management of PLWHIV undergoing SOT, there were differing practices, such as the choice of immunosuppressive induction and maintenance therapy. Other important aspects of patient management, such as patient counseling, were rarely reported. Conclusions: Our results constitute an extensive overview of current practices in the pharmacotherapeutic management of SOT in PLWHIV and identify knowledge gaps that should be addressed to help improve patient care in this specific population.

Relationship between raltegravir trough plasma concentration and virologic response and the impact of therapeutic drug monitoring during pregnancy.

BACKGROUND: Limited data is available on raltegravir (RAL) pharmacokinetics during pregnancy and the value of therapeutic drug monitoring (TDM) in pregnancy is unknown. This study aims to describe RAL trough plasma concentrations (Ctrough) during pregnancy and review the impact of RAL TDM on outcomes. METHODS: Women from the prospective mother-infant HIV cohort of Mother and Children's Infectious Diseases Center who received RAL during their pregnancy between 2011-2020 were included. TDM reports were reviewed and Ctrough values estimated when possible, using historical RAL half-lives. RESULTS: We included 76 pregnant women of which 47 underwent TDM. We observed a significant association between virological response and Ctrough (p-value .034) with an increase of 0.1 mg/L corresponding to a 2.96 reduction in the risk of having a detectable viral load. The results indicated that in pregnant women a RAL Ctrough threshold of 0.04 mg/L has a higher specificity (75%) as compared to our current Ctrough target value of 0.02 mg/L (25%) and an acceptable sensitivity (77%). No significant differences were observed between Ctrough at each trimester. When comparing pregnancies with and without TDM, no statistically significant differences were observed in the virologic response during pregnancy and at delivery, or with the need for triple antiretroviral prophylaxis in newborns. CONCLUSIONS: An association between RAL Ctrough and viral load was observed and achieving a RAL Ctrough of 0.04 mg/L or greater is a predictor of virologic response in pregnant women. The impact of TDM in pregnancy, however, could not be demonstrated.

Use and safety of appearance and performance enhancing supplements in gay, bisexual, and other men who have sex with men receiving daily tenofovir disoproxil fumarate/emtricitabine as HIV pre-exposure prophylaxis.

Appearance- and performance-enhancing supplements (APES) may be associated with liver and renal toxicity, but use is often under-reported. This study describes the use and safety of APES among gay, bisexual, and other men-who-have-sex with men (gbMSM) attending an urban HIV pre-exposure prophylaxis (PrEP) clinic. A cross-sectional study was conducted between February 2018 to September 2018 to assess APES usage in gbMSM taking daily tenofovir disoproxil fumarate/emtricitabine for PrEP. Renal and liver function were assessed from electronic medical records. Among 50 participants (98% male, median 32 years, 52% White, on PrEP for a median 4.4 years), 72% reported lifetime APES use, with 52% currently using APES (median 1.5 products/person) and 28% never used APES. The most common products included whey protein, creatine supplements and anabolic steroids. The primary reason for APES use was to increase muscle mass. Three (12%) current APES users had elevated serum creatinine (stage 1) versus zero (0%) in the non-APES group. Two (8%) current APES users experienced grade 3-4 ALT/AST elevations versus zero (0%) in the non-APES group. APES usage among gbMSM taking PrEP was high and may be associated with liver/renal lab abnormalities. Increased awareness of APES use and potential toxicity is encouraged to enhance safety.

Understanding the Risks and Benefits of a Patient Portal Configured for HIV Care: Patient and Healthcare Professional Perspectives.

BACKGROUND: Like other chronic viral illnesses, HIV infection necessitates consistent self-management and adherence to care and treatment, which in turn relies on optimal collaboration between patients and healthcare professionals (HCPs), including physicians, nurses, pharmacists, and clinical care coordinators. By providing people living with HIV (PLHIV) with access to their personal health information, educational material, and a communication channel with HCPs, a tailored patient portal could support their engagement in care. Our team intends to implement a patient portal in HIV-specialized clinics in Canada and France. We sought to understand the perceived risks and benefits among PLHIV and HCPs of patient portal use in HIV clinical care. METHODS: This qualitative study recruited PLHIV and HIV-specialized HCPs, through maximum variation sampling and purposeful sampling, respectively. Semi-structured focus group discussions (FGDs) were held separately with PLHIV and HCPs between August 2019 and January 2020. FGDs were recorded, transcribed, coded using NVivo 12 software, and analyzed using content analysis. RESULTS: A total of twenty-eight PLHIV participated in four FGDs, and thirty-one HCPs participated in six FGDs. PLHIV included eighteen men, nine women, and one person identifying as other; while, HCPs included ten men, twenty women, and one person identifying as other. A multi-disciplinary team of HCPs were included, involving physicians, nurses, pharmacists, social workers, and clinical coordinators. Participants identified five potential risks: (1) breach of confidentiality, (2) stress or uncertainty, (3) contribution to the digital divide, (4) dehumanization of care, and (5) increase in HCPs' workload. They also highlighted four main benefits of using a patient portal: (1) improvement in HIV self-management, (2) facilitation of patient visits, (3) responsiveness to patient preferences, and (4) fulfillment of current or evolving patient needs. CONCLUSION: PLHIV and HCPs identified both risks and benefits of using a patient portal in HIV care. By engaging stakeholders and understanding their perspectives, the configuration of a patient portal can be optimized for end-users and concerns may be mitigated during its implementation.

Camu Camu effects on microbial translocation and systemic immune activation in ART-treated people living with HIV: protocol of the single-arm non-randomised Camu Camu prebiotic pilot study (CIHR/CTN PT032).

INTRODUCTION: Despite the success of antiretroviral therapy (ART) in transforming HIV disease into a chronic infection, people living with HIV (PLWH) remain at risk for various non-AIDS inflammatory comorbidities. Risk of non-AIDS comorbidities is associated with gut dysbiosis, epithelial gut damage and subsequent microbial translocation, and increased activation of both circulating CD4+ and CD8+ T-cells. Therefore, in addition to ART, novel gut microbiota-modulating therapies could aid in reducing inflammation and immune activation, gut damage, and microbial translocation. Among various gut-modulation strategies under investigation, the Amazonian fruit Camu Camu (CC) presents itself as a prebiotic candidate based on its anti-inflammatory and antioxidant properties in animal models and tobacco smokers. METHOD AND ANALYSIS: A total of 22 PLWH on ART for more than 2 years, with a viral load <50 copies/mL, a CD4 +count >200 and a CD4+/CD8 +ratio <1 (suggesting increased inflammation and risk for non-AIDS comorbidities), will be recruited in a single arm, non-randomised, interventional pilot trial. We will assess tolerance and effect of supplementation with CC in ART-treated PLWH on reducing gut damage, microbial translocation, inflammation and HIV latent reservoir by various assays. ETHICS AND DISSEMINATION: The Canadian Institutes of Health Research (CIHR)/Canadian HIV Trials Network (CTN) pilot trial protocol CTNPT032 was approved by the Natural and Non-prescription Health Products Directorate of Health Canada and the research ethics board of the McGill university Health Centre committee (number 2020-5903). Results will be made available as free access through publications in peer-reviewed journals and through the CIHR/CTN website. TRIAL REGISTRATION NUMBER: NCT04058392.

Predictive Factors of Detectable Viral Load in HIV-Infected Patients.

Despite availability of effective antiretroviral therapy (ART), many HIV patients still have a detectable viral load (VL). Predictive factors of detectable VL are not well documented. This study was done at two large multidisciplinary HIV outpatient clinics at the Centre hospitalier de l'Université de Montréal (CHUM) and the McGill University Health Centre (MUHC). This is a retrospective case-control study of patients treated between 2016 and 2018. Cases had a VL ≥50 copies/mL in 2018. Controls had an undetectable VL from 2016 to 2018. Matching was based on gender and year of HIV diagnosis. Primary objective was to identify predictive factors of detectable VL. Secondary objectives included to identify predictive factors of virologic failure, low persistent viremia, and viral blip. A forward stepwise model selection by the Akaike Information Criterion of the conditional logistic regression was used to identify predictive factors. Two hundred cases were identified and matched with 200 controls. The cohort was mostly male (68.0%) with a median age of 54 years (21-83 years). Among cases, viral blip was the most common type of detectable VL (43.0%). The strong predictive factors for a detectable VL were adherence to ART and seeking health care services. Asylum seekers were less at risk of detectable VL. Adherence to ART was the only strong predictive factor for virologic failure. Three main predictive factors of detectable VL were identified in two ambulatory clinic hospitals in Montreal. Ascertaining these factors will allow for identification of patients more at risk of detectable VL.

Evaluation of cabergoline for lactation inhibition in women living with HIV.

We wished to evaluate the efficacy, safety, and acceptability of cabergoline for lactation inhibition in women who live with HIV. In this multicenter prospective observational study, cabergoline was offered as a single oral dose of 1 mg within the first 48 h postpartum. Women were recruited if they delivered a live infant after 35 weeks of gestational age. Participants filled out a questionnaire regarding symptoms of lactation and cabergoline adverse effects on day 2 and day 14 postpartum. On day 14, they also completed a questionnaire about their satisfaction with cabergoline treatment. Prolactin serum level was measured on both visits. Among 68 participants, all but one received cabergoline. The overall effectiveness defined by partial or complete success at day 14 was 98.3% (confidence intervals: 89.5-99.9). At day 14, 67.4% of women who received cabergoline had prolactin serum levels <25 mcg/L (threshold necessary for galactopoiesis). Mild nonspecific adverse effects were experienced by 24 (29.9%) women on day 2 and 24 (41.4%) on day 14, and lasted 48 h or less. Overall, 96% of women were satisfied with cabergoline's ability to prevent postpartum lactation symptoms. In conclusion, cabergoline is an effective, well-accepted, and well-tolerated medication for lactation inhibition in WLWH.

Delayed linkage to HIV care among asylum seekers in Quebec, Canada.

BACKGROUND: Migrants represent an increasing proportion of people living with HIV in many developed countries. We aimed to describe the HIV care cascade and baseline genotypic resistance for newly diagnosed asylum seekers referred to the McGill University Health Centre (MUHC) in Montreal, Quebec, Canada. METHODS: We conducted a retrospective cohort study of patients linked to the MUHC from June 1, 2017 to October 31, 2018. We calculated the median time (days; interquartile range (IQR)) from: 1) entry into Canada to immigration medical examination (IME) (i.e. HIV screening); 2) IME to patient notification of diagnosis; 3) notification to linkage to HIV care (defined as a CD4 or viral load (VL) measure); 4) linkage to HIV care to combination antiretroviral therapy (cART) prescription; and 5) cART prescription to viral suppression (defined as a VL < 20 copies/mL). We reviewed baseline genotypes and interpreted mutations using the Stanford University HIV Drug Resistance Database. We calculated the proportion with full resistance to > 1 antiretroviral. RESULTS: Overall, 43% (60/139) of asylum seekers were newly diagnosed in Canada. Among these, 62% were late presenters (CD4 < 350 cells/µl), 22% presented with advanced HIV (CD4 < 200 cells/µl), and 25% with high-level viremia (VL > 100,000 copies/ml). Median time from entry to IME: 27 days [IQR:13;55]; IME to notification: 28 days [IQR:21;49]; notification to linkage: 6 days [IQR:2;19]; linkage to cART prescription: 11 days [IQR:6;17]; and cART to viral suppression: 42 days [IQR:31;88]; 45% were linked to HIV care within 30 days. One-fifth (21%) had baseline resistance to at least one antiretroviral agent; the K103 N/S mutation was the most common mutation. CONCLUSIONS: While the majority of newly diagnosed asylum seekers were late presenters, only 45% were linked to care within 30 days. Once linked, care and viral suppression were rapid. Delays in screening and linkage to care present increased risk for onward transmission, and in the context of 21% baseline resistance, consideration of point-of-care testing and immediate referral at IME screening should be made.

Optimizing concentrations of concomitant antiretrovirals by reducing etravirine doses: two case reports of complex drug-drug interactions.

We report the cases of two treatment-experienced HIV-infected patients with complex antiretroviral regimens that showed significant drug-drug interactions with etravirine. Unexpectedly high etravirine concentrations likely caused subtherapeutic levels of darunavir, elvitegravir and dolutegravir through concentration-dependent metabolic induction. Therapeutic drug monitoring allowed safe etravirine dose decreases to manage these interactions.

Exploring an alternative explanation for the second phase of viral decay: Infection of short-lived cells in a drug-limited compartment during HAART.

Most HIV-infected patients who initiate combination antiretroviral therapy experience a viral load decline in several phases. These phases are characterized by different rates of viral load decay that decrease when transitioning from one phase to the next. There is no consensus as to the origin of these phases. One hypothesis put forward is that short- and long-lived infected cells are responsible for the first and second phases of decay, respectively. However, significant differences in drug concentrations are observed in monocytes from various tissues, suggesting the first two phases of decay in viral loads could instead be attributed to short-lived cells being differently exposed to drugs. Compared to a well-exposed compartment, new cell infection can be expected in a compartment with limited drug exposure, thus leading to a slower viral load decay with potential virologic failure and drug resistance. In the current study, the latter hypothesis was investigated using a model of viral kinetics. Empirical datasets were involved in model elaboration and parameter estimation. In particular, susceptibility assay data was used for an in vitro to in vivo extrapolation based on the expected drug concentrations inside physiological compartments. Results from numerical experiments of the short-term evolution of viral loads can reproduce the first two phases of viral decay when allowing new short-lived cell infections in an unidentified drug-limited compartment. Model long-term predictions are however less consistent with clinical observations. For the hypothesis to hold, efavirenz, tenofovir and emtricitabine drug exposure in the drug-limited compartment would have to be very low compared to exposure in peripheral blood. This would lead to significant long-term viral growth and the frequent development of resistant strains, a prediction not supported by clinical observations. This suggests that the existence of a drug-limited anatomical compartment is unlikely, by itself, to explain the second phase of viral load decay.

Therapeutic drug monitoring in treatment-experienced HIV-infected patients receiving darunavir-based salvage regimens: A case series.

Therapeutic drug monitoring (TDM) constitutes a compelling approach for the optimization of antiretroviral therapy in treatment-experienced HIV-1 patients. While various inhibitory indices have been proposed to predict virologic outcome, there is a lack of consensus on the clinical value of TDM. Here, we report the comparative results of TDM in 14 HIV-1-infected patients who had previously received at least two different PI-based regimens and who initiated darunavir (DRV)-based salvage therapy. Pharmacokinetic/pharmacodynamics (PK/PD) parameters were calculated for each subject. Seventy-nine percent of subjects had a viral load <50 copies/mL at 48 weeks. The only subject with two consecutive viral loads >50 copies/mL at the end of the study period was the patient with the lowest instantaneous inhibitory potential (IIP). The sample size was insufficient to show an association between any of the PK/PD parameters and virologic response. Based on our observations, we suggest that the utility of IIP for antiretroviral combinations for the prediction of virologic outcome in HIV-1 drug-experienced patients should be studied further.

PHIRST Trial - pharmacist consults: prioritization of HIV-patients with a referral screening tool.

The role of pharmacists in HIV outpatient clinics has greatly increased in the past decades. Given the limited resources of the health system, the prioritization of pharmacist consults is now a main concern. This study aimed to create a scoring system allowing for standardized prioritization of pharmacist consults for patients living with HIV. Data was retrospectively collected from 200 HIV patients attending the Chronic Viral Illness Service at the McGill University Health Center. An expert panel consisting of four pharmacists working in the field of HIV prioritized each patient individually, after which a consensus was established and was considered as the gold standard. In order to create a scoring system, two different methods (Delphi, statistical) were used to assign a weight to each characteristic considered to be important in patient prioritization. A third method (equal weight to each characteristic) was also evaluated. The total score per patient for each method was then compared to the expert consensus in order to establish the score cut-offs to indicate the appropriate categories of delay in which to see the patient. All three systems failed to accurately prioritize patients into urgency categories ("less than 48 h", "less than 1 month", "less than 3 months", "no consult required") according to expert pharmacist consensus. The presence of high level interactions between patient characteristics, the limited number of patients and the low prevalence of some characteristics were hypothesized as the main causes for the results. Creating a prioritization tool for pharmacy consults in HIV outpatient clinics is a complex task and developing a decision tree algorithm may be a more appropriate approach in the future to take into account the importance of combinations of patient characteristic.

Therapeutic drug monitoring guided raltegravir dosing for prevention of vertical transmission in a premature neonate born to a woman living with perinatally acquired HIV.

We report a case of therapeutic drug monitoring guided raltegravir use for the prevention of vertical HIV transmission in a premature neonate born to a woman living with perinatally acquired HIV and documented resistance to multiple HIV drugs. Maternal viral load was above 1,000 copies/ml at delivery. This case demonstrates delayed raltegravir elimination in a neonate born at 33 weeks gestational age and a need for less frequent raltegravir dosing than is used in older infants and children.

Antiretroviral drug transporters and metabolic enzymes in human testicular tissue: potential contribution to HIV-1 sanctuary site.

OBJECTIVES: The testes are a potential viral sanctuary site for HIV-1 infection. Our study aims to provide insight into the expression and localization of key drug transporters and metabolic enzymes relevant to ART in this tissue compartment. METHODS: We characterized gene and protein expression of 12 representative drug transporters and two metabolic enzymes in testicular tissue samples obtained from uninfected (n = 8) and virally suppressed HIV-1-infected subjects on ART (n = 5) and quantified antiretroviral drug concentrations in plasma and testicular tissues using LC/MS/MS from HIV-1-infected subjects. RESULTS: Our data demonstrate that key ABC drug transporters (permeability glycoprotein, multidrug-resistance protein 1, 2 and 4, and breast cancer resistance protein), solute carrier transporters (organic anion transporting polypeptides 1B1 and 2B1, organic anion transporter 1, concentrative nucleoside transporter 1, equilibrative nucleoside transporter 2) and cytochrome P450 metabolic enzymes (CYP3A4 and CYP2D6) previously shown to interact with many commonly used antiretroviral drugs are expressed at the mRNA and protein level in the testes of both subject groups and localize primarily at the blood-testis barrier, with no significant differences between the two groups. Furthermore, we observed that PIs known to be substrates for ATP-binding cassette membrane transporters, displayed variable testicular tissue penetration, with darunavir concentrations falling below therapeutic values. In contrast, the NRTIs emtricitabine, lamivudine and tenofovir displayed favourable tissue penetration, reaching concentrations comparable to plasma levels. We also demonstrated that nuclear receptors, peroxisome proliferator-activated receptors α and γ exhibited higher gene expression in the testicular tissue compared with pregnane X receptor and constitutive androstane receptor, suggesting a potential regulatory pathway governing drug transporter and metabolic enzyme expression in this tissue compartment. CONCLUSIONS: Our data suggest the testes are a complex pharmacological compartment that can restrict the distribution of certain antiretroviral drugs and potentially contribute to HIV-1 persistence.

Citalopram for the prevention of depression and its consequences in HIV-hepatitis C coinfected individuals initiating pegylated interferon/ribavirin therapy: a multicenter randomized double-blind placebo-controlled trial.

BACKGROUND: Depression related to interferon-alpha (IFN-α) is common, may reduce adherence, and can be treatment limiting. HIV-HCV coinfected persons experience lower sustained virologic response rates and commonly have psychiatric comorbidities, thus they may benefit from prevention of depression. OBJECTIVE: The aim of the study was to determine whether prophylactic citalopram can increase HCV treatment adherence and reduce the incidence of moderate depression in HIV-HCV coinfected patients initiating PEG-IFN-α/ribavirin therapy. METHODS: This was an investigator-initiated Canadian multicenter randomized, double-blind placebo-controlled trial. HIV-HCV coinfected patients were randomized in a 1:1 ratio to receive citalopram or placebo 3 weeks prior to starting PEG-IFN-α2b/ribavirin, stratified by study center and HCV genotype. The protocol design permitted the comparison of prophylaxis with the treatment of emergent depression. The primary outcomes were adherence (assessed through questionnaire and returned medication) and time to moderate depression measured by Beck Depression Inventory-II (BDI- II) score greater than 15, confirmed 2 weeks apart. RESULTS: Seventy-six patients (36 citalopram/40 placebo) were randomized. Overall adherence was high, ranging from 95% (week 12) to 91% (week 48). There was no difference between arms with respect to mean or median adherence at any study time point. Cumulative incidence of moderate depression did not differ significantly by group (log rank P = .32). The hazard ratio for moderate depression was 0.81 (95% CI, 0.26 to 2.54) for citalopram compared with placebo when adjusted for baseline BDI-II score. CONCLUSIONS: A strategy of prophylactic citalopram compared to treatment of emergent depression was not associated with higher adherence or a reduction in treatment-limiting depression nor did it significantly reduce depressive symptoms among HIV-HCV coinfected persons during treatment for HCV.

Understanding and preventing drug-drug and drug-gene interactions.

Concomitant administration of multiple drugs can lead to unanticipated drug interactions and resultant adverse drug events with their associated costs. A more thorough understanding of the different cytochrome P450 isoenzymes and drug transporters has led to new methods to try to predict and prevent clinically relevant drug interactions. There is also an increased recognition of the need to identify the impact of pharmacogenetic polymorphisms on drug interactions. More stringent regulatory requirements have evolved for industry to classify cytochrome inhibitors and inducers, test the effect of drug interactions in the presence of polymorphic enzymes, and evaluate multiple potentially interacting drugs simultaneously. In clinical practice, drug alert software programs have been developed. This review discusses drug interaction mechanisms and strategies for screening and minimizing exposure to drug interactions. We also provide future perspectives for reducing the risk of clinically significant drug interactions.

Students' perceptions of a community-based service-learning project related to aging in place.

This article describes a service-learning project that was designed to help undergraduate health professions students understand the complexities related to aging in place. The service-learning project also incorporated a research component to expose the students to the research process. Students' reflections regarding the benefits that they derived from the experience suggest that they value learning about older adults through one-on-one interactions more than they value the opportunity to participate in the research project. Implications for undergraduate health professional education are discussed.