Needs Assessment for Pharmacy Program Creation Designed to Serve Minority Francophone Populations in Canada.

OBJECTIVES: Current literature provides little insight into the need for French-language pharmaceutical services in Francophone minority settings in Canada. This study aims to understand the pharmaceutical care and services offered in French in Canada. It also aims to conduct a needs assessment in the context of curriculum development, by validating whether pharmaceutical needs are being met in Francophone minority settings in Canada. METHODS: An online survey was sent to community members and health care professionals. Respondents were asked to identify the perceived importance of pharmaceutical needs and the degree to which they perceive these to be fulfilled in French and English in their communities. RESULTS: A total of 113 community members and 109 health care professionals completed the survey. Most respondents were from Ontario (64.84%), Quebec (10.50%), or Atlantic Provinces (10.05%). In total, > 95% of survey respondents identified that pharmaceutical needs assessed were of very high importance. The rate of pharmaceutical need fulfillment was lower in French than English across all pharmaceutical needs assessed. The greatest difference in rate of pharmaceutical need fulfillment was seen with "Having safe access to required medication". The perception of pharmaceutical needs being met was congruent between community members and health care professionals. CONCLUSION: These results confirm a lack of pharmaceutical needs being met in French in Canadian Francophone minority communities. There is a lack of French-language services that limit the ability to receive care in one's own language. Pharmacy education in French may be an effective approach to improve pharmaceutical care services received in French in Francophone minority communities.

Management and Outcome of COVID-19 Infection Using Nirmatrelvir/Ritonavir in Kidney Transplant Patients.

BACKGROUND: Nirmatrelvir/ritonavir has been shown to reduce the risk of COVID-19 related complications in patients at high risk for severe COVID-19. However, clinical experience of nirmatrelvir/ritonavir in the transplant recipient population is scattered due to the complex management of drug-drug interactions with calcineurin inhibitors. We describe the clinical experience with nirmatrelvir/ritonavir at The Ottawa Hospital kidney transplant program. METHODS: Patients who received nirmatrelvir/ritonavir between April and June 2022 were included and followed up 30 days after completion of treatment. Tacrolimus was withheld for 24 hours and resumed 72 hours after the last dose of nirmatrelvir/ritonavir (on Day 8) based on drug level the day before. The first 30 patients had their dose adjusted according to drug levels performed twice in the first week and as needed thereafter. Subsequently, a simplified algorithm with less frequent calcineurin inhibitor level monitoring was implemented. Outcomes including tacrolimus level changes, serum creatinine and acute kidney injury (AKI, defined as serum creatinine increase by 30%) and clinical outcomes were described globally and compared between algorithms. RESULTS: Fifty-one patients received nirmatrelvir/ritonavir. Tacrolimus levels drawn at the first timepoint, 7 days after withholding of calcineurin inhibitor and 2 days after discontinuing nirmatrelvir/ritonavir were within the therapeutic target in 17/44 (39%), subtherapeutic in 21/44(48%) and supratherapeutic in 6/44 (14%). Two weeks after, 55% were within the therapeutic range, 23% were below, and 23% were above it. The standard and simplified algorithms provided similar tacrolimus level (median 5.2 ug/L [4.0, 6.2] versus 4.8 ug/L [4.3, 5.7] p=0.70). There were no acute rejections or other complications. CONCLUSIONS: Withholding tacrolimus starting the day before initiation of nirmatrelvir/ritonavir with resumption 3 days after completion of therapy resulted in a low incidence of supratherapeutic levels but a short period of subtherapeutic levels for many patients. AKI was infrequent. The data are limited by the small sample size and short follow-up.

Enhancing COVID Rehabilitation with Technology (ECORT): protocol for an open-label, single-site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms.

BACKGROUND: As of May 2022, Ontario has seen more than 1.3 million cases of COVID-19. While the majority of individuals will recover from infection within 4 weeks, a significant subset experience persistent and often debilitating symptoms, known as "post-COVID syndrome" or "Long COVID." Those with Long COVID experience a wide array of symptoms, with variable severity, including fatigue, cognitive impairment, and shortness of breath. Further, the prevalence and duration of Long COVID is not clear, nor is there evidence on the best course of rehabilitation for individuals to return to their desired level of function. Previous work with chronic conditions has suggested that the addition of electronic case management (ECM) may help to improve outcomes. These platforms provide enhanced connection with care providers, detailed symptom tracking and goal setting, and access to relevant resources. In this study, our primary aim is to determine if the addition of ECM with health coaching improves Long COVID outcomes at 3 months compared to health coaching alone. METHODS: The trial is an open-label, single-site, randomized controlled trial of ECM with health coaching (ECM+) compared to health coaching alone (HC). Both groups will continue to receive usual care. Participants will be randomized equally to receive health coaching (± ECM) for a period of 8 weeks and a 12-week follow-up. Our primary outcome is the WHO Disability Assessment Scale (WHODAS), 36-item self-report total score. Participants will also complete measures of cognition, fatigue, breathlessness, and mental health. Participants and care providers will be asked to complete a brief qualitative interview at the end of the study to evaluate acceptability and implementation of the intervention. DISCUSSION: There is currently little evidence about the optimal treatment of Long COVID patients or the use of digital health platforms in this population. The results of this trial could result in rapid, scalable, and personalized care for people with Long COVID which will decrease morbidity after an acute infection. Results from this study will also inform decision making in Long COVID and treatment guidelines at provincial and national levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT05019963. Registered on 25 August 2021.

Efficacy, Safety, and Practicality of Tacrolimus Monitoring after Bone Marrow Transplant: Assessment of a Change in Practice.

BACKGROUND: Currently, there is no standardized approach to the frequency of monitoring tacrolimus levels in patients who have undergone hematopoietic stem cell transplant (HSCT). Previously, the practice at the study hospital was to monitor tacrolimus levels daily throughout a patient's admission. A recent institutional study suggested that measurement of tacrolimus level is more frequent than needed to achieve consistent time in the therapeutic range (TTR), particularly after the first 7 days. As a result, tacrolimus monitoring was changed to daily measurement for the initial week of therapy, followed by measurements on Monday, Wednesday, and Friday in subsequent weeks. OBJECTIVE: To confirm the safety and efficacy of the recent practice change. METHODS: This retrospective chart review of HSCT patients admitted to The Ottawa Hospital involved 68 patients in the pre-practice change group and 43 patients in the post-practice change group. Data on tacrolimus measurement were collected for up to 21 days after initiation of this medication. The proportion of TTR was compared between the 2 groups. Differences in the incidence and severity of renal dysfunction and the incidence of acute graft versus host disease (GVHD) were determined and described. RESULTS: In the pre-practice change cohort, the median proportion of TTR for tacrolimus was 40.5% for days 1-7, 65.1% for days 8-14, and 78.9% for days 15-21, similar to the values for the post-practice change group (46.6% [p = 0.09], 62.9% [p = 0.93], and 70.0% [p = 0.22], respectively, for the same periods). The incidence of acute GVHD within 100 days after HSCT was 24% and 33% for the pre- and post-practice change cohorts, respectively. The incidence and severity of renal dysfunction were similar between the 2 groups. CONCLUSION: The proportion of TTR for tacrolimus was not significantly affected by the recent practice change. Similarly, the incidence and severity of renal dysfunction and the incidence of acute GVHD did not appear to differ between the pre- and post-practice change groups.

CONTEXTE: Il n'existe actuellement aucune approche standardisée portant sur la fréquence des contrôles des valeurs du tacrolimus pour les patients ayant subi une greffe de cellules souches hématopoïétiques (GCSH). Dans le passé, la pratique à l'hôpital où s'est déroulée l'étude consistait à les contrôler quotidiennement durant tout le séjour du patient. Une récente étude institutionnelle a laissé entendre que cette mesure était plus fréquente que nécessaire pour obtenir une marge thérapeutique régulière (TTR), particulièrement après les sept premiers jours. Par conséquent, une modification du contrôle des valeurs du tacrolimus préconise désormais des mesures quotidiennes pendant la première semaine de la thérapie, suivies de mesures le lundi, le mercredi et le vendredi au cours des semaines suivantes. OBJECTIF: Confirmer la sécurité et l'efficacité du récent changement apporté à la pratique. MÉTHODE: Cet examen rétrospectif des dossiers des patients GCSH admis à l'Hôpital d'Ottawa concernait 68 patients du groupe « avant le changement de pratique ¼ et 43 du groupe « après le changement de pratique ¼. Les données relatives aux mesures des valeurs du tacrolimus ont été recueillies pendant les 21 premiers jours après le début de l'administration de ce médicament. La comparaison entre les deux groupes portait sur la proportion de TTR. Les différences d'incidence et de gravité du dysfonctionnement rénal et l'apparition de réaction aiguë du greffon contre l'hôte (GVHD) ont été définies et décrites. RÉSULTATS: Dans la cohorte « avant le changement de pratique ¼, la proportion moyenne de TTR du tacrolimus était de 40,5 % du 1er au 7e jour; de 65,1 % du 8e au 14e jour et de 78,9 % du 15e au 21e jour. Ces valeurs sont similaires à celles du groupe « après le changement de pratique ¼ (respectivement 46,6 % [p = 0,09], 62,9 % [p = 0,93] et 70,0 % [p = 0,22] pendant les mêmes périodes). L'incidence de réaction aiguë du greffon contre l'hôte dans les 100 jours après la GCSH se montait respectivement à 24 % et à 33 % dans les cohortes « avant et après le changement de pratique ¼. L'incidence et la gravité du dysfonctionnement rénal étaient similaires dans les deux groupes. CONCLUSION: La proportion de TTR relative au tacrolimus n'a pas été modifiée de manière significative par le changement récent de pratique. De même, l'incidence et la gravité du dysfonctionnement rénal et l'incidence de réaction aiguë du greffon contre l'hôte ne semblaient pas différer entre les groupes avant et après le changement de pratique.

Getting to the Heart of the Matter: A Review of Drug Interactions Between HIV Antiretrovirals and Cardiology Medications.

The past 20 years have seen remarkable advances in the treatment of HIV such that most people diagnosed with HIV today can live long, healthy lives by taking antiretrovirals which are usually life-long. Advancements in antiretroviral therapy include the availability of well tolerated, single tablet regimens that are associated with a lower risk of drug-drug interactions. Despite this, many people living with HIV infection might be taking antiretroviral agents that are associated with significant drug-drug interactions. Because HIV infection itself is associated with cardiovascular complications and this population is living longer, concomitant use of antiretrovirals and medications to treat cardiovascular-related diseases is often required. For this reason, it is imperative that clinicians are aware of the potential for clinically significant drug-drug interactions between antiretroviral agents and cardiac medications as well as the useful HIV drug interaction resources that might provide guidance. Available data on significant interactions are summarized and suggested guidance regarding management is discussed.

Outcomes Associated with Reducing the Urine Alkalinization Threshold in Patients Receiving High-Dose Methotrexate.

STUDY OBJECTIVES: Urine alkalinization increases methotrexate (MTX) solubility and reduces the risk of nephrotoxicity. The objectives of this study were to determine whether a reduction in the urine pH threshold from 8 to 7 in patients receiving high-dose methotrexate (HDMTX) results in a shorter length of hospital stay, delayed MTX clearance, or higher rates of nephrotoxicity; and to determine whether specific factors were associated with prolonged MTX clearance. DESIGN: Retrospective cohort study. SETTING: Hematology service of a large university-affiliated teaching hospital in Ottawa, Canada. PATIENTS: Sixty-five adults with 150 HDMTX exposures who had elective admissions for HDMTX between September 1, 2014, and December 18, 2015, were included. Thirty-four patients (with 79 HDMTX exposures) had their urine alkalinized to a pH of 8 or higher, and 31 patients (with 71 HDMTX exposures) had their urine alkalinized to a pH of 7 or higher, after an institutional change in the urine pH threshold from 8 to 7 was implemented on May 1, 2015. MEASUREMENTS AND MAIN RESULTS: Data related to patient demographics, urine alkalinization, MTX serum concentration monitoring, hospital length of stay, and renal function were collected retrospectively from patients' electronic health records. Lowering the urine pH threshold from 8 to 7 did not significantly affect hospital length of stay (absolute difference 3.5 hrs, 95% confidence interval -4.0 to 10.9) or clearance of MTX (elimination rate constant 0.058 in the pH of 7 or higher group vs 0.064 in the pH of 8 or higher group, p=0.233). Nephrotoxicity rates were similar between groups (15.5% in the pH of 7 or higher group vs 10.1% in the pH of 8 or higher group, p=0.34). Higher MTX dose and interacting medications (e.g., proton pump inhibitors and sulfonamide antibiotics) were significantly associated with delayed MTX elimination. CONCLUSION: No significant differences in HDMTX-associated hospital length of stay, MTX clearance, or rates of nephrotoxicity were noted between patients in the urine pH of 7 or higher and 8 or higher groups. Interacting medications and higher MTX dose were associated with delayed MTX elimination, suggesting that a closer review of interacting medications before HDMTX administration may be warranted.

CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core Research Group: 2016 Updated Canadian HIV/Hepatitis C Adult Guidelines for Management and Treatment.

Background. Hepatitis C virus (HCV) coinfection occurs in 20-30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Purpose. To update national standards for management of HCV-HIV coinfected adults in the Canadian context with evolving evidence for and accessibility of effective and tolerable DAA therapies. The document addresses patient workup and treatment preparation, antiviral recommendations overall and in specific populations, and drug-drug interactions. Methods. A standing working group with HIV-HCV expertise was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published HCV antiviral data and update Canadian HIV-HCV Coinfection Guidelines. Results. The gap in sustained virologic response between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All coinfected individuals should be assessed for interferon-free, Direct Acting Antiviral HCV therapy. Regimens vary in content, duration, and success based largely on genotype. Reimbursement restrictions forcing the use of pegylated interferon is not acceptable if optimal patient care is to be provided. Discussion. Recommendations may not supersede individual clinical judgement. Treatment advances published since December 2015 are not considered in this document.

Appropriateness of Dabigatran and Rivaroxaban Prescribing for Hospital Inpatients.

BACKGROUND: Recent approval of the new oral anticoagulants dabigatran and rivaroxaban has led to rapid changes in anticoagulant prescribing practices. Postmarketing reports have highlighted safety concerns with these agents, and their use outside of evidence-based recommendations was noted at the authors' centre. OBJECTIVES: To determine the incidence of and risk factors associated with inappropriate prescribing of dabigatran and rivaroxaban. METHODS: This retrospective cohort study investigated randomly selected dabigatran or rivaroxaban prescriptions for patients admitted to a tertiary teaching hospital between January 2010 and December 2012. Appropriateness of prescribing was determined from the documented indication, drug dosage, patient's renal function, and presence of drug interactions, if applicable. RESULTS: Among a total of 321 medication orders reviewed, the incidence of inappropriate use was 31.2% (34/109) for dabigatran and 26.9% (57/212) for rivaroxaban. Of the 97 reasons for inappropriate use that were identified, the most common were prescribing for an unapproved indication (49/97 [50.5%]), concomitant prescribing of another anticoagulant (22/97 [22.7%]), and high prescribed dose (9/97 [9.3%]). The prescribing service was found to be an independent risk factor for inappropriate prescribing (p = 0.041). Corrections were made to 23.1% (21/91) of the incorrect regimens before hospital discharge. In a sensitivity analysis using calculated ideal body weight to estimate renal function, the overall incidence of inappropriate prescribing increased to 31.5% (101/321). CONCLUSIONS: The proportion of patients with inappropriate prescribing of dabigatran or rivaroxaban in clinical practice was higher than expected. Educational interventions and pharmacy-led initiatives with a focus on appropriate indications, concomitant anticoagulant prescribing, and review of dosage regimens are recommended to improve patient safety.

CONTEXTE: La récente approbation de deux nouveaux anticoagulants oraux, le dabigatran et le rivaroxaban, a mené à de rapides changements dans les habitudes de prescription pour l'anticoagulothérapie. Des rapports de pharmacovigilance ont relevé des risques pour la santé relativement à ces agents. De plus, on a noté au centre où travaillent les auteurs que ces médicaments n'étaient pas toujours utilisés selon les recommandations fondées sur des données probantes. OBJECTIFS: Déterminer quelle est l'incidence des prescriptions inadéquates de dabigatran et de rivaroxaban et quels sont les facteurs de risque qui y sont associés. MÉTHODES: La présente étude de cohorte rétrospective a examiné des ordonnances choisies au hasard de dabigatran ou de rivaroxaban, lesquelles étaient destinées à des patients admis dans un hôpital universitaire de soins tertiaires entre janvier 2010 et décembre 2012. La pertinence des prescriptions était établie à l'aide des informations consignées sur l'indication, la posologie, la fonction rénale du patient et la présence d'interactions médicamenteuses, le cas échéant. RÉSULTATS: Parmi l'ensemble des 321 ordonnances analysées, l'incidence d'utilisation inadéquate était de 31,2 % (34/109) pour le dabigatran et de 26,9 % (57/212) pour le rivaroxaban. Des 97 raisons d'utilisation inadéquate qui ont été recensées, les plus fréquentes étaient : la prescription pour une indication non approuvée (49/97 [50,5 %]), la prescription concomitante d'un autre anticoagulant (22/97 [22,7 %]) et la prescription d'une dose élevée (9/97 [9,3 %]). Le service auquel appartenait le prescripteur s'est révélé être un facteur de risque indépendant de prescription inadéquate (p = 0.041). Des corrections ont été apportées à 23,1 % (21/91) des schémas erronés avant que le congé ne soit donné. Dans une analyse de sensibilité qui s'appuyait sur le calcul du poids idéal pour estimer la fonction rénale, le taux global d'incidence de prescription inadéquate augmentait à 31,5 % (101/321). CONCLUSIONS: La proportion de patients pour qui la prescription de dabigatran ou de rivaroxaban était inadéquate dans la pratique clinique était plus élevée que prévu. Afin d'améliorer la sécurité des patients, on recommande l'adoption d'interventions éducatives et d'initiatives dirigées par les services de pharmacie qui porteront sur les indications adéquates, la prescription concomitante d'anticoagulants et la révision des schémas posologiques.

Evaluation of Sodium Polystyrene Sulfonate Dosing Strategies in the Inpatient Management of Hyperkalemia.

BACKGROUND: Hyperkalemia occurs frequently in an inpatient setting, for which sodium polystyrene sulfonate (SPS) is a common treatment modality. Few studies have investigated the dose-response of SPS. OBJECTIVE: To quantify the change in serum potassium after 15-, 30-, and 60-g oral and 30-g rectal doses of SPS. Secondary objectives were to compare the proportion of patients attaining post-SPS dose normokalemia between dosing groups and to investigate the effect of certain characteristics on SPS dose-response. METHODS: The reduction in serum potassium after 15-, 30-, and 60-g oral and 30-g rectal doses of SPS administered to adult inpatients was evaluated through a retrospective chart review. Ottawa Hospital Research Ethics Board approval was obtained prior to data collection. RESULTS: A total of 118 patients were included in the analysis. Serum potassium levels were reduced by 0.39, 0.69, 0.91, and 0.22 mEq/L following 15-, 30-, and 60-g oral doses and a 30-g rectal dose of SPS, respectively. A greater proportion of patients (50% vs 23%) remained hyperkalemic in the 15-g versus the 60-g group (P = 0.018), and all patients in the rectal group remained hyperkalemic. No patient in any group experienced postdose hypokalemia. The influence of all studied interindividual characteristics on SPS dose-response was clinically nonsignificant. CONCLUSION: Mild hyperkalemia can be effectively treated with a single 60-g oral dose of SPS as monotherapy, with minimal risk of hypokalemia. Moderate to severe hyperkalemic episodes warrant alternative therapy. The potassium-lowering effect is correlated to SPS dose and is independent of interindividual characteristics.

Impact of an electronic tool in prescribing primary prophylaxis with ciprofloxacin or granulocyte colony-stimulating factor for breast cancer patients receiving TC chemotherapy.

BACKGROUND: The US Oncology Trial 9735 (doxorubicin and cyclophosphamide (AC) versus docetaxel and cyclophosphamide (TC)) reported febrile neutropenia (FN) in 5 % of patients receiving TC chemotherapy, in the absence of routine primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) or antibiotics. In contrast, higher rates of FN have been reported in the 'real world' setting. This retrospective study compares the incidence and severity of FN and other TC-related toxicities before and after implementation of a primary prophylaxis computerized prescribing tool. METHODS: Medical records of 207 patients receiving adjuvant TC between May 1, 2006, and November 1, 2011, were reviewed for toxicity. The incidence for each TC adverse event was measured by an incident rate ratio (IRR), and chi-square analysis was used to compare the differences in severity of TC toxicities before and after use of a primary prophylaxis computerized prescribing tool, and to compare G-CSF and ciprofloxacin groups. RESULTS: The implementation of a computerized prescribing tool significantly increased the proportion of patients prescribed primary prophylaxis (18.2 vs. 97.4 %; p < 0.001). Prior to the change in practice, the incidence of FN (incidence rate ratio 3.87; 95 % CI [1.3, 11.5]) and neutropenia (OR 4.8; 95 % CI [2.0, 11.7]) was significantly higher. Primary prophylaxis significantly reduced the rate of febrile neutropenia (20 vs. 5.3 %, p = 0.003). No significant differences were found in incidence and severity of other TC-related toxicities. Patients who did not receive G-CSF were at a greater risk for neutropenia (OR 5.1, 95 % CI [1.06, 24.3]). There were insufficient patients treated with antibiotics alone to compare to those treated with G-CSF. CONCLUSIONS: Implementation of a computerized prescribing tool significantly increased the use of primary prophylaxis by treating physicians in patients receiving TC chemotherapy, which was associated with reduced incidence of febrile neutropenia. Further research efforts should focus on the incorporation and routine use of evidence-based practices using tools such as alerts and prompts, in order to optimize patient care and improve outcomes.

CIHR Canadian HIV Trials Network Co-Infection and Concurrent Diseases Core: Updated Canadian guidelines for the treatment of hepatitis C infection in HIV-hepatitis C coinfected adults.

BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Management of HIV-HCV coinfection is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens. OBJECTIVE: To update national standards for the management of HCV-HIV coinfected adults in the Canadian context. METHODS: A standing working group with specific clinical expertise in HIV-HCV coinfection was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published data regarding HCV antiviral treatments and to update the Canadian HIV-HCV coinfection guidelines. RESULTS: Recent data suggest that the gap in sustained virological response rates between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All HIV-HCV coinfected individuals should be assessed for HCV therapy. First-line treatment for genotypes 1 through 6 includes pegylated interferon and weight-based ribavirin dosing plus the nucleotide sofosbuvir for 12 weeks. Sofosbuvir in combination with the protease inhibitor simeprevir is another first-line consideration for genotype 1 infection. Sofosbuvir with ribavirin for 12 weeks (genotype 2) and 24 weeks (genotype 3) is also recommended as first-line treatment. DISCUSSION: Recommendations may not supersede individual clinical judgement.

HISTORIQUE: De 20 % à 30 % des Canadiens qui vivent avec le VIH sont co-infectés par le virus de l'hépatite C (VHC), lequel est responsable d'une morbidité et d'une mortalité importantes. La prise en charge du VIH et du VHC est plus complexe en raison de l'évolution accélérée de la maladie hépatique, du choix et des critères d'initiation de la thérapie antirétrovirale et du traitement anti-VHC, de la prise en charge de la santé mentale et des toxicomanies, des obstacles socioéconomiques et des interactions entre les nouvelles thérapies antivirales à action directe du VHC et les antirétroviraux. OBJECTIF: Mettre à jour les normes nationales pour la prise en charge des adultes co-infectés par le VHC et le VIH dans le contexte canadien. MÉTHODOLOGIE: Le Réseau canadien pour les essais VIH des Instituts de recherche en santé du Canada a réuni un groupe d'experts possédant des compétences cliniques en coinfection par le VIH et le VHC pour réviser les publications récentes sur les traitements antiviraux contre le VHC et mettre à jour les lignes directrices canadiennes sur la coinfection du VIH et du VHC. RÉSULTATS: Selon de récentes données, les nouvelles posologies antivirales ont éliminé la disparité entre le taux de réponse virologique soutenue de la monoinfection par le VIH et celui de la coinfection par le VIH et le VHC. Toutes les personnes co-infectées par le VIH et le VHC devraient subir une évaluation en vue de recevoir un traitement du VHC. Le traitement de première ligne du VHC des génotypes 1 à 6 inclut un régime composé d'interféron pégylé et de ribavirine dosée en fonction du poids, associé au sofosbuvir, un analogue des nucléotides, pendant 12 semaines. Le sofosbuvir combiné au siméprévir, un inhibiteur de la protéase, peut également constituer un traitement de première ligne pour l'infection par le génotype 1. Le sofosbuvir associé à de la ribavirine pendant 12 semaines (génotype 2) et 24 semaines (génotype 3) est également recommandé en première ligne. EXPOSÉ: Les recommandations ne se substituent pas nécessairement au jugement clinique personnel.

Effectiveness of Unfractionated Heparin in Normal Saline versus Dextrose for Achieving and Maintaining Therapeutic Anti-Factor Xa Levels in Patients with Non-ST-Elevation Acute Coronary Syndrome.

BACKGROUND: Unfractionated heparin (UFH) administered by IV infusion is effective in preventing myocardial infarction and death after non-ST-elevation acute coronary syndrome. At the authors' centre, preparations of UFH in 0.9% sodium chloride (normal saline; UFH-NS) were used during a shortage of commercially available UFH in dextrose 5% in water (UFH-D5W), the usual preparation. Anecdotal observations raised concerns about the effectiveness of the saline-based preparation in achieving minimally therapeutic anticoagulation. OBJECTIVE: To compare the effectiveness of UFH-NS and UFH-D5W for achieving and maintaining therapeutic anti-factor Xa levels in patients with non-ST-elevation acute coronary syndrome. METHODS: A retrospective cohort study was conducted with 2 groups of 100 consecutive patients who received either UFH-NS or UFH-D5W for a minimum of 24 h after non-ST-elevation acute coronary syndrome in accordance with a weight-based dosing nomogram. RESULTS: A minimally therapeutic level of anti-Xa (≥ 0.31 IU/mL) was achieved within 24 h for 92% of the patients receiving UFH-D5W and 67% of those receiving UFH-NS (absolute risk difference 25%, 95% confidence interval [CI] 13.4%-36.6%; p < 0.001). Infusion of UFH-NS was associated with lower probability of achieving minimally therapeutic anticoagulation (hazard ratio [HR] 2.30, 95% CI 1.68-3.15; p < 0.001) and maintaining therapeutic anticoagulation (HR 2.31, 95% CI 1.69-3.17; p < 0.001) relative to UFH-D5W. Significant differences in the numbers of patients with subtherapeutic and therapeutic anticoagulation, favouring UFH-D5W, were observed at each of the first, second, and third anti-Xa measurements (p < 0.05). Patients receiving UFH-NS required a greater median number of adjustments to the infusion rate during the first 48 h (1.0 v. 0.5 adjustment per day, p < 0.001). There was no difference between groups in terms of major reductions in hemoglobin. CONCLUSIONS: Infusion of UFH-NS was inferior to UFH-D5W for achieving and maintaining therapeutic anticoagulation in patients with non-ST-elevation acute coronary syndrome. Until further study, saline-based heparin infusions should be used with caution, and patients should be monitored closely to ensure timely achievement and maintenance of therapeutic anticoagulation.

CONTEXTE: La perfusion intraveineuse d'héparine non fractionnée (HNF) est efficace pour prévenir l'infarctus du myocarde et la mortalité après la survenue d'un syndrome coronarien aigu sans élévation du segment ST. Au centre hospitalier des auteurs, des préparations de ce médicament dans du chlorure de sodium à 0,9 % (solution physiologique salée [SP]; HNF-SP) ont été utilisées lors d'une pénurie de solutions commercialisées d'HNF dans du dextrose à 5 % dans l'eau (HNF-D5E) d'usage habituel. Quelques observations ont soulevé des inquiétudes quant à l'efficacité des préparations à base de SP pour obtenir une anticoagulation thérapeutique minimale. OBJECTIF: Comparer l'efficacité de l'HNF dans la SP et le D5E pour obtenir et maintenir des concentrations thérapeutiques d'anti-facteur Xa chez des patients ayant subi un syndrome coronarien aigu sans élévation du segment ST. MÉTHODES: Une étude de cohorte rétrospective a été menée à partir de deux séries consécutives de 100 patients qui ont reçu de l'HNF dans une SP ou du D5E pendant un minimum de 24 heures après la survenue du syndrome coronarien aigu sans élévation du segment ST, selon un nomogramme posologique en fonction du poids. RÉSULTATS: Des concentrations thérapeutiques minimales d'anti-Xa (≥ 0,31 UI/mL) ont été obtenues en 24 heures chez 92 % des patients ayant reçu l'HNF-D5E et chez 67 % de ceux ayant reçu l'HNF-SP (différence de risque absolu de 25 %, intervalle de confiance [IC] à 95 % de 13,4 % à 36,6 %; p < 0,001). La perfusion de la préparation à base de SP a été associée à une probabilité plus faible d'obtenir une anticoagulation thérapeutique minimale (rapport de risque [RR] de 2,30, IC à 95 % de 1,68 à 3,15; p < 0,001) et de maintenir une anticoagulation thérapeutique (RR de 2,31, IC à 95 % de 1,69 à 3,17; p < 0,001) par rapport à la préparation dans du D5E. Des différences significatives dans le nombre de patients ayant obtenu une anticoagulation thérapeutique et subthérapeutique, en faveur de l'HNF-D5E, ont été observées à chacune des premières, deuxièmes et troisièmes mesures des concentrations d'anti-Xa (p < 0,05). Les patients ayant reçu l'HNF-SP ont requis un nombre médian supérieur d'ajustements de la vitesse de perfusion pendant les 48 premières heures (1,0 contre 0,5 ajustement par jour, p < 0,001). Il n'y avait aucune différence entre les groupes en termes de réductions importantes de l'hémoglobine. CONCLUSIONS: La perfusion d'HNF-SP s'est révélée inférieure à celle de l'HNF-D5E pour obtenir et maintenir une anticoagulation thérapeutique chez les patients ayant subi un syndrome coronarien aigu sans élévation du segment ST. Jusqu'à ce que d'autres études soient menées, la perfusion d'héparine dans une solution physiologique salée doit être utilisée avec circonspection et les patients doivent être surveillés étroitement afin d'assurer l'obtention en temps opportun et le maintien d'une anticoagulation thérapeutique. [Traduction par l'éditeur].

Psychiatric treatment considerations with direct acting antivirals in hepatitis C.

BACKGROUND: Despite recent advances in hepatitis C (HCV) treatment, specifically the addition of direct acting antivirals (DAAs), pegylated interferon-alpha remains the backbone of HCV therapy. Therefore, the impact of DAAs on the management of co-morbid psychiatric illness and neuropsychiatric sequalae remains an ongoing concern during HCV therapy. This paper provides a review of the neuropsychiatric adverse effects of DAAs and drug-drug interactions (DDIs) between DAAs and psychiatric medications. METHODS: We conducted a Pubmed search using relevant search terms and hand searched reference lists of related review articles. In addition, we searched abstracts for major hepatology conferences and contacted respective pharmaceutical companies for additional studies. RESULTS: Limited data is available on the neuropsychiatric adverse effects of DAAs; however, data from major clinical trials suggest that DAAs have minimal neuropsychiatric risk. DAAs can potentially interact with a variety of psychotropic agents via cytochrome P450 and p-glycoprotein interactions. Triazolam, oral midazolam, St. John's Wort, carbamazepine and pimozide, are contraindicated with DAAs. DDIs between DAAs and antidepressants, anxiolytics, hypnotics, mood stabilizers, antipsychotics and treatments for opioid dependence are summarized. CONCLUSIONS: Although DAAs do not add significant neuropsychiatric risk, the potential for DDIs is high. Consideration of DDIs is paramount to improving medication adherence and mitigating adverse effects during HCV therapy.

CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core: Canadian guidelines for management and treatment of HIV/hepatitis C coinfection in adults.

BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV, and is responsible for a heavy burden of morbidity and mortality. HIV-HCV management is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens. OBJECTIVE: To develop national standards for the management of HCV-HIV coinfected adults in the Canadian context. METHODS: A panel with specific clinical expertise in HIV-HCV co-infection was convened by The CIHR HIV Trials Network to review current literature, existing guidelines and protocols. Following broad solicitation for input, consensus recommendations were approved by the working group, and were characterized using a Class (benefit verses harm) and Level (strength of certainty) quality-of-evidence scale. RESULTS: All HIV-HCV coinfected individuals should be assessed for HCV therapy. Individuals unable to initiate HCV therapy should initiate antiretroviral therapy to slow liver disease progression. Standard of care for genotype 1 is pegylated interferon and weight-based ribavirin dosing plus an HCV protease inhibitor; traditional dual therapy for 24 weeks (for genotype 2/3 with virological clearance at week 4); or 48 weeks (for genotypes 2-6). Therapy deferral for individuals with mild liver disease may be considered. HIV should not be considered a barrier to liver transplantation in coinfected patients. DISCUSSION: Recommendations may not supersede individual clinical judgement.

Atazanavir-associated choledocholithiasis leading to acute hepatitis in an HIV-infected adult.

OBJECTIVE: To report a case of atazanavir-associated choledocholithiasis in an HIV-infected individual. CASE SUMMARY: A 47-year-old treatment-naïve HIV-positive African female presented to the emergency department with a 3-day history of right epigastric pain. Six weeks prior to this episode, she began antiretroviral therapy with a regimen consisting of atazanavir 400 mg and abacavir/lamivudine 600/300 mg once daily. Alanine aminotransferase (766 U/L), aspartate aminotransferase (876 U/L), gamma-glutamyltransferase (588 U/L), alkaline phosphatase (348 U/L), and total bilirubin (3.9 mg/dL) levels were elevated. Abdominal ultrasound revealed obstructive choledocholithiasis as well as intra- and extrahepatic biliary dilatation. She underwent a laparoscopic cholecystectomy, which revealed approximately 50 small calculi present in the gallbladder. Since previous ultrasounds had also shown gallstones, an analysis of the extracted calculi was performed to determine the possible association with atazanavir use; low amounts of atazanavir were detected. DISCUSSION: Atazanavir is an inhibitor of the bilirubin-conjugating enzyme UGT1A1 and has been frequently linked to the occurrence of hyperbilirubinemia without complications. This individual experienced hyperbilirubinemia that peaked at hospital presentation after she developed choledocholithiasis and secondary acute hepatitis. Analysis of the extracted gallstones revealed that smaller stones contained a higher content of atazanavir than larger stones, which suggests that atazanavir precipitation may play a role in cholelithiasis, although the mechanism remains unknown. The low yield of atazanavir may be explained by the short, 6-week duration of drug exposure as well as the lack of assay for metabolites. The Naranjo probability scale implicated choledocholithiasis as a possible atazanavir-associated adverse event. This report provides the first published evidence that even short-term use of atazanavir may lead to hyperbilirubinemia with choledocholithiasis and secondary acute hepatitis in HIV-infected adults. CONCLUSIONS: Atazanavir should be considered a possible contributor in the development of cholelithiasis or choledocholithiasis, and people with HIV should receive adequate counseling in the recognition of symptoms associated with gallstones. The exact incidence and mechanism still need to be elucidated.