Electronic Decision Support for Deprescribing in Patients on Hemodialysis: Clinical Research Protocol for a Prospective, Controlled, Quality Improvement Study.

Background: Patients on dialysis are commonly prescribed multiple medications (polypharmacy), many of which are potentially inappropriate medications (PIMs). Potentially inappropriate medications are associated with an increased risk of falls, fractures, and hospitalization. MedSafer is an electronic tool that generates individualized, prioritized reports with deprescribing opportunities by cross-referencing patient health data and medications with guidelines for deprescribing. Objectives: Our primary aim was to increase deprescribing, as compared with usual care (medication reconciliation or MedRec), for outpatients receiving maintenance hemodialysis, through the provision of MedSafer deprescribing opportunity reports to the treating team and patient empowerment deprescribing brochures provided directly to the patients themselves. Design: This controlled, prospective, quality improvement study with a contemporary control builds on existing policy at the outpatient hemodialysis centers where biannual MedRecs are performed by the treating nephrologist and nursing team. Setting: The study takes place on 2 of the 3 outpatient hemodialysis units of the McGill University Health Centre in Montreal, Quebec, Canada. The intervention unit is the Lachine Hospital, and the control unit is the Montreal General Hospital. Patients: A closed cohort of outpatient hemodialysis patients visit one of the hemodialysis centers multiple times per week for their hemodialysis treatment. The initial cohort of the intervention unit includes 85 patients, whereas the control unit has 153 patients. Patients who are transplanted, hospitalized during their scheduled MedRec, or die before or during the MedRec will be excluded from the study. Measurements: We will compare rates of deprescribing between the control and intervention units following a single MedRec. On the intervention unit, MedRecs will be paired with MedSafer reports (the intervention), and on the control unit, MedRecs will take place without MedSafer reports (usual care). On the intervention unit, patients will also receive deprescribing patient empowerment brochures for select medication classes (gabapentinoids, proton-pump inhibitors, sedative hypnotics and opioids for chronic non-cancer pain). Physicians on the intervention unit will be interviewed post-MedRec to determine implementation barriers and facilitators. Methods: The primary outcome will be the proportion of patients with 1 or more PIMs deprescribed on the intervention unit, as compared with the control unit, following a biannual MedRec. This study will build on existing policies aimed at optimizing medication therapy in patients undergoing maintenance hemodialysis. The electronic deprescribing decision support tool, MedSafer, will be tested in a dialysis setting, where nephrologists are regularly in contact with patients. MedRecs are an interdisciplinary clinical activity performed biannually on the hemodialysis units (in the Spring and Fall), and within 1 week following discharge from any hospitalization. This study will take place in the Fall of 2022. Semi-structured interviews will be conducted among physicians on the intervention unit to determine barriers and facilitators to implementation of the MedSafer-supplemented MedRec process and analyzed according to grounded theory in qualitative research. Limitations: Deprescribing can be limited due to nephrologists' time constraints, cognitive impairment of the hemodialyzed patient stemming from their illness and complex medication regimens, and lack of sufficient patient resources to learn about the medications they are taking and their potential harms. Conclusions: Electronic decision support can facilitate deprescribing for the clinical team by providing a nudge reminder, decreasing the time it takes to review and effectuate guideline recommendations, and by lowering the barrier of when and how to taper. Guidelines for deprescribing in the dialysis population have recently been published and incorporated into the MedSafer software. To our knowledge, this will be the first study to examine the efficacy of pairing these guidelines with MedRecs by leveraging electronic decision support in the outpatient dialysis population. Trial registration: This study was registered on Clinicaltrials.gov (NCT05585268) on October 2, 2022, prior to the enrolment of the first participant on October 3, 2022. The registration number is pending at the time of protocol submission.

Contexte: Les patients sous dialyse se voient souvent prescrire de nombreux médicaments (polypharmacie), dont plusieurs médicaments potentiellement inappropriés (MPI). Les MPI sont associés à un risque accru de chutes, de fractures et d'hospitalisations. MedSécure est un outil électronique qui génère des rapports individualisés et classés par ordre de priorité indiquant les possibilités de déprescription. L'outil fonctionne en croisant les données sur la santé des patients et les médicaments sous ordonnance avec des lignes directrices pour la déprescription. Objectifs de l'étude: L'objectif principal est de favoriser la déprescription par rapport aux soins habituels (Medication Reconciliation [MedRecs] ou bilan comparatif des médicaments) chez les patients ambulatoires recevant une hémodialyse d'entretien, en fournissant des rapports MedSécure de déprescription à l'équipe soignante et des brochures encourageant la déprescription aux patients. Conception: Cette étude prospective et contrôlée (témoin contemporain) d'amélioration de la qualité s'appuie sur la politique existante dans les centers d'hémodialyse ambulatoires où un bilan des médicaments (MedRecs) est effectué deux fois par année par le néphrologue traitant et l'équipe de soins infirmiers. Cadre: L'étude a lieu dans deux des trois unités d'hémodialyse ambulatoire du Center universitaire de santé McGill à Montréal (Québec, Canada). L'unité d'intervention est l'Hôpital de Lachine et l'unité témoin est l'Hôpital général de Montréal. Sujets: Une cohorte fermée de patients ambulatoires sous hémodialyse qui visitent plusieurs fois par semaine un center d'hémodialyse pour leurs traitements. La cohorte initiale de l'unité d'intervention compte 85 patients, tandis que l'unité témoin compte 132 patients. Seront exclus les patients qui recevront une greffe, qui seront hospitalisés pendant leur MedRecs ou qui décèderont avant ou pendant le MedRecs. Mesures: Nous comparerons les taux de déprescription entre les unités témoin et d'intervention après un seul MedRecs. Dans l'unité d'intervention, le MedRecs sera associé aux rapports MedSécure (l'intervention); dans l'unité témoin, le MedRecs aura lieu sans rapports MedSécure (soins habituels). Au sein de l'unité d'intervention, les patients recevront également des brochures encourageant la déprescription pour certaines classes de médicaments (gabapentinoïdes, inhibiteurs de la pompe à protons, hypnotiques sédatifs et opioïdes pour les douleurs chroniques non cancéreuses). Les médecins de l'unité d'intervention seront interviewés après le MedRec pour déterminer les obstacles et les facilitateurs à la mise en œuvre. Méthodologie: Le principal critère d'évaluation sera la proportion de patients dans l'unité d'intervention chez qui au moins un MPI sera déprescrit après un MedRec semestriel, par rapport à l'unité témoin. L'étude s'appuiera sur les politiques existantes visant à optimiser la médication chez les patients suivant des traitements d'hémodialyse d'entretien. L'outil électronique d'aide à la décision de déprescription MedSécure sera testé en contexte de dialyse, où les néphrologues sont régulièrement en contact avec les patients. Les MedRecs sont une activité clinique interdisciplinaire effectuée semestriellement sur les unités d'hémodialyse (au printemps et à l'automne) et dans la semaine suivant un congé de l'hôpital. Cette étude aura lieu à l'automne 2022. Des entretiens semi-structurés seront menés avec les médecins de l'unité d'intervention afin d'établir les obstacles et les facilitateurs à la mise en œuvre du processus MedRec complété par MedSécure, puis analysés selon une théorie fondée sur la recherche qualitative. Limites: La déprescription peut être limitée par des contraintes de temps des néphrologues, des troubles cognitifs résultant des maladies et des régimes médicamenteux complexes des patients sous hémodialyse ou par un manque de ressources pour éduquer les patients sur les médicaments qu'ils prennent et leurs méfaits potentiels. Conclusion: Un outil électronique d'aide à la décision peut faciliter le processus de déprescription pour l'équipe clinique en fournissant un rappel, en réduisant le temps nécessaire à l'examen et à l'application des recommandations, et en limitant les obstacles liés au moment et à la façon de réduire le nombre de médicaments. Des lignes directrices sur la déprescription dans la population des patients sous dialyse ont récemment été publiées et incorporées au logiciel MedSécure. À notre connaissance, il s'agit de la première étude à examiner l'efficacité du couplage des lignes directrices avec le MedRecs en tirant parti de l'outil électronique d'aide à la décision en contexte d'hémodialyse ambulatoire.

Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 : A Randomized Platform Trial.

BACKGROUND: Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19. OBJECTIVE: To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population. DESIGN: Randomized, placebo-controlled, adaptive platform trial. (ClinicalTrials.gov: NCT04727424). SETTING: 12 clinical sites in Brazil. PARTICIPANTS: Symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease. INTERVENTION: Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) plus inhaled budesonide (800 mcg twice daily for 10 days) or matching placebos. MEASUREMENTS: The primary outcome was a composite of emergency setting retention for COVID-19 for more than 6 hours, hospitalization, and/or suspected complications due to clinical progression of COVID-19 within 28 days of randomization. Secondary outcomes included health care attendance (defined as hospitalization for any cause or emergency department visit lasting >6 hours), time to hospitalization, mortality, patient-reported outcomes, and adverse drug reactions. RESULTS: Randomization occurred from 15 January to 6 July 2022. A total of 738 participants were allocated to oral fluvoxamine plus inhaled budesonide, and 738 received placebo. The proportion of patients observed in an emergency setting for COVID-19 for more than 6 hours or hospitalized due to COVID-19 was lower in the treatment group than the placebo group (1.8% [95% credible interval {CrI}, 1.1% to 3.0%] vs. 3.7% [95% CrI, 2.5% to 5.3%]; relative risk, 0.50 [95% CrI, 0.25 to 0.92]), with a probability of superiority of 98.7%. No relative effects were found between groups for any of the secondary outcomes. More adverse events occurred in the intervention group than the placebo group, but no important differences between the groups were detected. LIMITATION: Low event rate overall, consistent with contemporary trials in vaccinated populations. CONCLUSION: Treatment with oral fluvoxamine plus inhaled budesonide among high-risk outpatients with early COVID-19 reduced the incidence of severe disease requiring advanced care. PRIMARY FUNDING SOURCE: Latona Foundation, FastGrants, and Rainwater Charitable Foundation.

Proton pump inhibitors and the risk of inflammatory bowel disease: population-based cohort study.

OBJECTIVE: To determine whether the use of proton pump inhibitors (PPIs) compared with the use of histamine-2 receptor antagonists (H2RAs) is associated with an increased risk of inflammatory bowel disease (IBD). DESIGN: Population-based cohort study designed to address the impact of protopathic bias. SETTING: General practices contributing data to the UK Clinical Practice Research Datalink GOLD. PARTICIPANTS: 1 498 416 initiators of PPIs and 322 474 initiators of H2RAs from 1 January 1990 to 31 December 2018, with follow-up until 31 December 2019. Patients were analysed according to the timing of the IBD diagnosis after treatment initiation (early vs late). MAIN OUTCOME MEASURES: Standardised morbidity ratio weighted Cox proportional hazards models were used to estimate marginal HRs and 95% CIs. In the early-event analysis, IBD diagnoses were assessed within the first 2 years of treatment initiation, an analysis subject to potential protopathic bias. In the late-event analysis, all exposures were lagged by 2 years to account for latency and minimise protopathic bias. RESULTS: In the early-event analysis, the use of PPIs was associated with an increased risk of IBD within the first 2 years of treatment initiation, compared with H2RAs (HR 1.39, 95% CI 1.14 to 1.69). In contrast, the use of PPIs was not associated with an increased risk of IBD in the late-event analysis (HR 1.05, 95% CI 0.90 to 1.22). The results remained consistent in several sensitivity analyses. CONCLUSIONS: Compared with H2RAs, PPIs were not associated with an increased risk of IBD, after accounting for protopathic bias.

Proton pump inhibitors and risk of gastric cancer: population-based cohort study.

OBJECTIVE: To determine whether new users of proton pump inhibitors (PPIs) are at an increased risk of gastric cancer compared with new users of histamine-2 receptor antagonists (H2RAs). DESIGN: Using the UK Clinical Practice Research Datalink, we conducted a population-based cohort study using a new-user active comparator design. From 1 January 1990 to 30 April 2018, we identified 973 281 new users of PPIs and 193 306 new users of H2RAs. Cox proportional hazards models were fit to estimate HRs and 95% CIs of gastric cancer, and the number needed to harm was estimated using the Kaplan-Meier method. The models were weighted using standardised mortality ratio weights using calendar time-specific propensity scores. Secondary analyses assessed duration and dose-response associations. RESULTS: After a median follow-up of 5.0 years, the use of PPIs was associated with a 45% increased risk of gastric cancer compared with the use of H2RAs (HR 1.45, 95% CI 1.06 to 1.98). The number needed to harm was 2121 and 1191 for five and 10 years after treatment initiation, respectively. The HRs increased with cumulative duration, cumulative omeprazole equivalents and time since treatment initiation. The results were consistent across several sensitivity analyses. CONCLUSION: The findings of this large population-based cohort study indicate that the use of PPIs is associated with an increased risk of gastric cancer compared with the use of H2RAs, although the absolute risk remains low.

Proton pump inhibitors and risk of colorectal cancer.

OBJECTIVE: To determine whether proton pump inhibitors (PPIs) are associated with an increased risk of colorectal cancer, compared with histamine-2 receptor antagonists (H2RAs). DESIGN: The United Kingdom Clinical Practice Research Datalink was used to identify initiators of PPIs and H2RA from 1990 to 2018, with follow-up until 2019. Cox proportional hazards models were fit to estimate marginal HRs and 95% CIs of colorectal cancer. The models were weighted using standardised mortality ratio weights using calendar time-specific propensity scores. Prespecified secondary analyses assessed associations with cumulative duration, cumulative dose and time since treatment initiation. The number needed to harm was calculated at five and 10 years of follow-up. RESULTS: The cohort included 1 293 749 and 292 387 initiators of PPIs and H2RAs, respectively, followed for a median duration of 4.9 years. While the use of PPIs was not associated with an overall increased risk of colorectal cancer (HR: 1.02, 95% CI 0.92 to 1.14), HRs increased with cumulative duration of PPI use (<2 years, HR: 0.93, 95% CI 0.83 to 1.04; 2-4 years, HR: 1.45, 95% CI 1.28 to 1.60; ≥4 years, HR: 1.60, 95% CI 1.42 to 1.80). Similar patterns were observed with cumulative dose and time since treatment initiation. The number needed to harm was 5343 and 792 for five and 10 years of follow-up, respectively. CONCLUSION: While any use of PPIs was not associated with an increased risk of colorectal cancer compared with H2RAs, prolonged use may be associated with a modest increased risk of this malignancy.

Trends in acid suppressant drug prescriptions in primary care in the UK: a population-based cross-sectional study.

OBJECTIVE: To examine proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) prescribing patterns over a 29-year period by quantifying annual prevalence and prescribing intensity over time. DESIGN: Population-based cross-sectional study. SETTING: More than 700 general practices contributing data to the UK Clinical Practice Research Datalink (CPRD). PARTICIPANTS: Within a cohort of 14 242 329 patients registered in the CPRD, 3 027 383 patients were prescribed at least one PPI or H2RA from 1 January 1990 to 31 December 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: Annual prescription rates were estimated by dividing the number of patients prescribed a PPI or H2RA by the total CPRD population. Change in prescribing intensity (number of prescriptions per year divided by person-years of follow-up) was calculated using negative binomial regression. RESULTS: From 1990 to 2018, 21.3% of the CPRD population was exposed to at least one acid suppressant drug. During that period, PPI prevalence increased from 0.2% to 14.2%, while H2RA prevalence remained low (range: 1.2%-3.4%). Yearly prescribing intensity to PPIs increased during the first 15 years of the study period but remained relatively constant for the remainder of the study period. In contrast, yearly prescribing intensity of H2RAs decreased from 1990 to 2009 but has begun to slightly increase over the past 5 years. CONCLUSIONS: While PPI prevalence has been increasing over time, its prescribing intensity has recently plateaued. Notwithstanding their efficacy, PPIs are associated with a number of adverse effects not attributed to H2RAs, whose prescribing intensity has begun to increase. Thus, H2RAs remain a valuable treatment option for individuals with gastric conditions.

Potentially Inappropriate Medication Use in Older Adults in the Preoperative Period: A Retrospective Study of a Noncardiac Surgery Cohort.

BACKGROUND: Few studies have evaluated the prevalence of potentially inappropriate medications (PIMs) and its association with postoperative outcomes in a geriatric population in the preoperative setting. OBJECTIVES: The purpose of this study was to evaluate the prevalence of PIMs in an older elective surgery population and to explore associations between PIMs and postoperative length of stay (LOS) and emergency department (ED) visits in the 90 days post hospital discharge, depending on frailty status. METHODOLOGY: We performed a retrospective cohort study of older adults awaiting major elective noncardiac surgery and undergoing an evaluation in the preoperative clinic at a tertiary academic center between 2017 and 2018. We identified PIMs using MedSafer, a software tool built to improve the safety of prescribing. Frailty status was assessed using the 7-point Clinical Frailty Scale. We estimated the association between PIMs and postoperative LOS and ED visits in the 90 days post hospital discharge. RESULTS: The MedSafer software generated 394 recommendations on PIMs in 1619 medications for 252 patients. In total, 197 (78%) patients had at least one PIM. The cohort included 138 (51%) robust, 87 (32.2%) vulnerable and 45 (16.7%) frail patients. The association between PIMs and LOS was not significant for the robust and frail subgroups. For the vulnerable patients, every additional PIM increased LOS by 20% (incidence rate ratio 1.20; 95% confidence interval 0.90-1.44; p = 0.089) without reaching statistical significance. No association was found between PIMs and ED visits. CONCLUSION: PIMs identified by the MedSafer software were prevalent. Preoperative evaluation represents an opportunity to plan deprescribing of PIMs.

The Opportunities and Challenges of Pragmatic Randomized Trials Using a Specialized Software: CloudTrials Project.

Pragmatic randomized trials are essential to improve knowledge of real world clinical practice. Pragmatic trials design reflect routine clinical care, which have advantages to initiate and conduct, compared to classical clinical trials. Trials help to: engage bedside clinicians, increase efficiency of patient recruitment and follow up, minimize loss to follow up and include technological patient reported outcomes. The objective is to describe the opportunities and challenges designing a specialized software to administrate pragmatic randomized trials.