Medication Deprescribing in Patients Receiving Hemodialysis: A Prospective Controlled Quality Improvement Study.

Rationale & Objective: Patients treated with dialysis are commonly prescribed multiple medications (polypharmacy), including some potentially inappropriate medications (PIMs). PIMs are associated with an increased risk of medication harm (eg, falls, fractures, hospitalization). Deprescribing is a solution that proposes to stop, reduce, or switch medications to a safer alternative. Although deprescribing pairs well with routine medication reviews, it can be complex and time-consuming. Whether clinical decision support improves the process and increases deprescribing for patients treated with dialysis is unknown. This study aimed to test the efficacy of the clinical decision support software MedSafer at increasing deprescribing for patients treated with dialysis. Study Design: Prospective controlled quality improvement study with a contemporaneous control. Setting & Participants: Patients prescribed ≥5 medications in 2 outpatient dialysis units in Montréal, Canada. Exposures: Patient health data from the electronic medical record were input into the MedSafer web-based portal to generate reports listing candidate PIMs for deprescribing. At the time of a planned biannual medication review (usual care), treating nephrologists in the intervention unit additionally received deprescribing reports, and patients received EMPOWER brochures containing safety information on PIMs they were prescribed. In the control unit, patients received usual care alone. Analytical Approach: The proportion of patients with ≥1 PIMs deprescribed was compared between the intervention and control units following a planned medication review to determine the effect of using MedSafer. The absolute risk difference with 95% CI and number needed to treat were calculated. Outcomes: The primary outcome was the proportion of patients with one or more PIMs deprescribed. Secondary outcomes include the reduction in the mean number of prescribed drugs and PIMs from baseline. Results: In total, 195 patients were included (127, control unit; 68, intervention unit); the mean age was 64.8 ± 15.9 (SD), and 36.9% were women. The proportion of patients with ≥1 PIMs deprescribed in the control unit was 3.1% (4/127) vs 39.7% (27/68) in the intervention unit (absolute risk difference, 36.6%; 95% CI, 24.5%-48.6%; P < 0.0001; number needed to treat = 3). Limitations: This was a single-center nonrandomized study with a type 1 error risk. Deprescribing durability was not assessed, and the study was not powered to reduce adverse drug events. Conclusions: Deprescribing clinical decision support and patient EMPOWER brochures provided during medication reviews could be an effective and scalable intervention to address PIMs in the dialysis population. A confirmatory randomized controlled trial is needed.

Patients treated with dialysis are commonly prescribed multiple medications, some of which are potentially inappropriate medications (PIMs). PIMs can increase a patient's pill burden and are associated with an increased risk of harm (some examples include falls, fractures, and hospitalization). Deprescribing is a proposed solution that aims to highlight medications that can be stopped, reduced, or switched to a safer option, under supervision of a health care provider. We aimed to determine if a quality improvement intervention in the dialysis unit could increase deprescribing compared to usual care. The study took place in 2 outpatient hemodialysis units where usual care involves nurses and nephrologists performing medication reviews twice a year. The intervention was a deprescribing report that was generated with the help of a software tool called MedSafer, along with brochures for patients with information on PIMs they were taking. In the intervention unit, we increased the number of patients who had a medication safely deprescribed by 36.6% more than on the control unit. Although the study was small, a future larger study in dialysis patients might show that a computer software such as MedSafer can prevent harmful complications from taking too many medications.

Evaluation of Oseltamivir Used to Prevent Hospitalization in Outpatients With Influenza: A Systematic Review and Meta-Analysis.

Importance: Despite widespread use, summary evidence from prior meta-analyses has contradictory conclusions regarding whether oseltamivir decreases the risk of hospitalization when given to outpatients. Several large investigator-initiated randomized clinical trials have not yet been meta-analyzed. Objective: To assess the efficacy and safety of oseltamivir in preventing hospitalization among influenza-infected adult and adolescent outpatients. Data Sources: PubMed, Ovid MEDLINE, Embase, Europe PubMed Central, Web of Science, Cochrane Central, ClinicalTrials.gov, and WHO International Clinical Trials Registry were searched from inception to January 4, 2022. Study Selection: Included studies were randomized clinical trials comparing oseltamivir vs placebo or nonactive controls in outpatients with confirmed influenza infection. Data Extraction and Synthesis: In this systematic review and meta-analysis, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Two independent reviewers (R.H. and É.B.C.) extracted data and assessed risk of bias using the Cochrane Risk of Bias Tool 2.0. Each effect size was pooled using a restricted maximum likelihood random effects model. The quality of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Main Outcomes and Measures: Hospitalization was pooled as risk ratio (RR) and risk difference (RD) estimates with 95% CIs. Results: Of 2352 studies identified, 15 were included. The intention-to-treat infected (ITTi) population was comprised of 6166 individuals with 54.7% prescribed oseltamivir. Across study populations, 53.9% (5610 of 10 471) were female and the mean age was 45.3 (14.5) years. Overall, oseltamivir was not associated with reduced risk of hospitalization within the ITTi population (RR, 0.79; 95% CI, 0.48 to 1.29; RD, -0.17%; 95% CI, -0.23% to 0.48%). Oseltamivir was also not associated with reduced hospitalization in older populations (mean age ≥65 years: RR, 1.01; 95% CI, 0.21 to 4.90) or in patients considered at greater risk of hospitalization (RR, 0.65; 0.33 to 1.28). Within the safety population, oseltamivir was associated with increased nausea (RR, 1.43; 95% CI, 1.13 to 1.82) and vomiting (RR, 1.83; 95% CI, 1.28 to 2.63) but not serious adverse events (RR, 0.71; 95% CI, 0.46 to1.08). Conclusions and Relevance: In this systematic review and meta-analysis among influenza-infected outpatients, oseltamivir was not associated with a reduced risk of hospitalization but was associated with increased gastrointestinal adverse events. To justify continued use for this purpose, an adequately powered trial in a suitably high-risk population is justified.

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.

Diagnostic yield of CT head in delirium and altered mental status-A systematic review and meta-analysis.

BACKGROUND: CT head is commonly performed in the setting of delirium and altered mental status (AMS), with variable yield. We aimed to evaluate the yield of CT head in hospitalized patients with delirium and/or AMS across a variety of clinical settings and identify factors associated with abnormal imaging. METHODS: We included studies in adult hospitalized patients, admitted to the emergency department (ED) and inpatient medical unit (grouped together) or the intensive care unit (ICU). Patients had a diagnosis of delirium/AMS and underwent a CT head that was classified as abnormal or not. We searched Medline, Embase and other databases (informed by PRISMA guidelines) from inception until November 11, 2021. Studies that were exclusively performed in patients with trauma or a fall were excluded. A meta-analysis of proportions was performed; the pooled proportion of abnormal CTs was estimated using a random effects model. Heterogeneity was determined via the I2 statistic. Factors associated with an abnormal CT head were summarized qualitatively. RESULTS: Forty-six studies were included for analysis. The overall yield of CT head in the inpatient/ED was 13% (95% CI: 10.2%-15.9%) and in ICU was 17.4% (95% CI: 10%-26.3%), with considerable heterogeneity (I2 96% and 98% respectively). Heterogeneity was partly explained after accounting for study region, publication year, and representativeness of the target population. Yield of CT head diminished after year 2000 (19.8% vs. 11.1%) and varied widely depending on geographical region (8.4%-25.9%). The presence of focal neurological deficits was a consistent factor that increased yield. CONCLUSION: Use of CT head to diagnose the etiology of delirium and AMS varied widely and yield has declined. Guidelines and clinical decision support tools could increase the appropriate use of CT head in the diagnostic etiology of delirium/AMS.

Observational versus randomized controlled trials to inform antibiotic treatment durations: a narrative review.

BACKGROUND: Studies comparing shorter and longer antibiotic treatment durations are increasingly common. Randomized controlled trials (RCTs) are an ideal methodological approach to study antibiotic treatment durations; however, these trials can be logistically and financially challenging to conduct. OBJECTIVES: In this narrative review, we sought to compare the strengths and limitations of observational study data with those of RCT data in evaluating antibiotic treatment durations. We used uncomplicated Gram-negative bacteraemia as an illustrative case example because several published RCTs and observational studies have been conducted in similar patient populations. SOURCES: We searched MEDLINE for articles comparing treatment durations for gram-negative bacteremia from inception to June 9th, 2022. We included studies reporting on all-cause mortality and/or relapse at day 28-30. Data comparing short- versus long-course therapy were pooled by Bayesian random effects meta-analyses to assess the odds ratios (OR) of all-cause mortality and relapse at 30 days, stratified by study design. Parameters were summarized with median and 95% highest-density credible intervals (CrI). Posterior probabilities of OR > 1.0 were estimated. Observational studies were further examined to determine if and how they addressed potential sources of bias. CONTENT: We identified 1671 unique records and included 10 studies (seven observational and three RCTs). With respect to 30-day mortality, the Bayesian posterior probability that a longer course of therapy was better (i.e. OR >1.0) was 42% in RCTs (OR, 0.94; 95% CrI, 0.51-1.68) and 91% in observational studies (OR, 1.25; 95% CrI, 0.88-1.73). No observational study fully addressed all potential sources of bias. IMPLICATIONS: On the basis of our findings, we discuss future directions for antibiotic treatment duration trials, including approaches to limit sources of bias in observation data and novel trial designs.

MedSafer to Support Deprescribing for Residents of Long-Term Care: a Mixed-Methods Study.

Background: Polypharmacy is prevalent in long-term care homes (LTCH) and increases the risk of adverse drug events. Feasible and effective deprescribing interventions applicable in the LTCH environment are needed. Methods: We performed a mixed methods study to evaluate the feasibility, applicability, and effectiveness of an electronic deprescribing tool, MedSafer, to facilitate quarterly medication reviews (QMRs) on two pilot units in an academic long-term care home (LTCH). Chart reviews collected resident health data. The prevalence of deprescribing at a standard QMR was compared with a QMR conducted three months later with MedSafer. Feedback from physicians on their experience with MedSafer was obtained through semi-structured interviews. Results: Physicians found MedSafer helpful in guiding deprescribing decisions and suggested software improvements to increase the feasibility in LTCH. The average number of medications deprescribed per resident was significantly higher at the MedSafer QMR (mean reduction = 1.1 medications, SD = 1.3) compared to the standard QMR (mean reduction = 0.5, SD = 0.9) (absolute difference of 0.5; SD 1.1; p = .02). Conclusion: MedSafer has the potential to increase deprescribing in LTCHs by flagging potentially inappropriate medications. Integration in the electronic medical record might increase uptake in LTCHs. Further research should investigate the generalizability of MedSafer in a larger population and in non-academic LTCHs.

Deprescribing Opportunities for Hospitalized Patients With End-Stage Kidney Disease on Hemodialysis: A Secondary Analysis of the MedSafer Cluster Randomized Controlled Trial.

Background: End-stage kidney disease patients on dialysis have a substantial risk of polypharmacy due their propensity for comorbidity and contact with the health care system. MedSafer is an electronic decision support tool that integrates patient comorbidity and medication lists to generate personalized deprescribing reports focused on identifying potentially inappropriate medications (PIMs). Objective: To conduct a secondary analysis of patients on regular hemodialysis included in the MedSafer randomized controlled trial to investigate the patterns of polypharmacy and evaluate the efficacy of the MedSafer deprescribing algorithms. Design: Secondary analysis of a cluster randomized clinical trial. Setting: Medical units in 11 acute care hospitals in Canada. Patients: The MedSafer trial enrolled 5698 participants with an expected prognosis of >3 months, age 65 years and older, and on 5 or more daily home medications; 140 participants were receiving chronic hemodialysis. Measurements: The primary outcome of the trial was 30-day adverse drug events (ADEs) post-hospital discharge, and a key secondary outcome was deprescribing. Methods: Control patients received usual care (medication reconciliation), whereas clinicians caring for intervention patients received a MedSafer report that highlighted individualized opportunities for deprescribing. Results: There were 70 patients in each of the control and intervention arms. The median number of home medications was 14 (compared with a median of 10 medications in the general trial population). The most frequent medications observed that were potentially inappropriate were proton pump inhibitors (potentially inappropriate in 55/76 users; 72.4%), diabetes medications in patients with a HBA1C <7.5% (36/65 users; 55.4%), docusate (27/27 users; 100%), gabapentinoids (27/36 users; 75%), and combination antiplatelet/anticoagulants (22/97 users; 22.7%). The proportion of PIMs deprescribed was higher during the intervention phase (28.8% vs 19.3%; absolute increase 9.4% [95% confidence interval 1.3%-17.6%]) compared with the control phase. There was no observed difference in ADEs at 30-day post-discharge between the control and the intervention groups. The most common ADE (n = 3) was gastrointestinal bleeding attributed to antiplatelet agents. Limitations: This was a post hoc exploratory analysis, the original trial did not stratify by hemodialysis status, and the small sample size precludes drawing any definitive conclusions. Conclusion: MedSafer facilitates deprescribing in hospitalized patients on hemodialysis. Larger-scale implementation of decision support software for deprescribing in dialysis and long-term follow-up are likely required to demonstrate an impact on ADEs.

Contexte: Le risque de polypharmacie est important chez les patients atteints d'insuffisance rénale terminale (IRT) sous dialyse en raison de leurs nombreuses comorbidités et de leurs contacts fréquents avec le système de santé. MedSafer est un outil électronique d'aide à la décision qui intègre les comorbidités et la liste de médicaments des patients pour générer des rapports de déprescription personnalisés, axés sur l'identification de médicaments potentiellement inappropriés (MPI). Objectifs: Procéder à une analyse secondaire des patients sous hémodialyse inclus dans l'essai contrôlé randomisé MedSafer dans le but d'examiner les profils de polypharmacie et d'évaluer l'efficacité des algorithmes de déprescription de MedSafer. Type d'étude: Analyse secondaire d'un essai clinique randomisé en grappes. Cadre: Les unités médicales de onze hôpitaux de soins aigus au Canada. Sujets: L'essai MedSafer a inclus 5698 patients de 65 ans et plus avec un pronostic attendu de plus de trois mois et prenant au moins cinq médicaments quotidiennement à domicile; 140 patients étaient traités par hémodialyse chronique. Mesures: Le principal critère d'évaluation de l'essai était la survenue d'événements indésirables attribuables aux médicaments (ÉIM) dans les 30 jours suivant le congé de l'hôpital. Un des principaux critères d'évaluation secondaires était la déprescription. Méthodologie: Les patients du groupe témoin recevaient les soins habituels (bilan comparatif des médicaments) alors qu'un rapport MedSafer soulignant les possibilités de déprescription individuelles était envoyé aux cliniciens qui prenaient en charge les patients du groupe d'intervention. Résultats: Chaque bras de l'essai (témoin et intervention) comptait 70 sujets. Le nombre médian de médicaments pris à domicile était de 14 (comparativement à 10 dans la population générale de l'essai). Les médicaments les plus souvent cités comme potentiellement inappropriés étaient les inhibiteurs de la pompe à protons (55/76 patients; 72,4%), les médicaments contre le diabète chez les patients avec un taux d'HbA1c inférieur à 7,5% (36/65 patients; 55,4%), le docusate (27/27 patients; 100%), les gabapentinoïdes (27/36 patients; 75%) et les antiplaquettaires/anticoagulants combinés (22/97 patients; 22,7%). La proportion de MPI déprescrits était plus élevée dans la phase d'intervention que dans la phase témoin (28,8% c. 19,3%; augmentation absolue de 9,4% [IC 95%: 1,3 à 17,6%]). Aucune différence n'a été observée entre les deux groupes en ce qui concerne les ÉIM dans les 30 jours suivant le congé de l'hôpital. Une hémorragie gastro-intestinale attribuable aux agents antiplaquettaires était l'événement indésirable le plus fréquent (n = 3). Limites: Il s'agit d'une analyse exploratoire a posteriori. L'essai initial n'a pas été stratifié selon le status en hémodialyse. La faible taille de l'échantillon ne permet pas de tirer des conclusions définitives. Conclusion: MedSafer facilite la déprescription chez les patients hospitalisés qui reçoivent des traitements d'hémodialyse. Pour démontrer un éventuel impact sur les événements indésirables attribuables aux médicaments, il apparaît nécessaire de faire un suivi à plus long terme et à plus grande échelle du logiciel d'aide à la décision de déprescription en contexte de dialyse.

Fluvoxamine for Outpatient Management of COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-analysis.

Importance: Widely available and affordable options for the outpatient management of COVID-19 are needed, particularly for therapies that prevent hospitalization. Objective: To perform a meta-analysis of the available randomized clinical trial evidence for fluvoxamine in the outpatient management of COVID-19. Data Sources: World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. Study Selection: Studies with completed outpatient trials with available results that compared fluvoxamine with placebo were included. Data Extraction and Synthesis: The PRISMA 2020 guidelines were followed and study details in terms of inclusion criteria, trial demographics, and the prespecified outcome of all-cause hospitalization were extracted. Risk of bias was assessed by the Cochrane Risk of Bias 2 tool and a bayesian random effects meta-analysis with different estimates of prior probability was conducted: a weakly neutral prior (50% chance of efficacy with 95% CI for risk ratio [RR] between 0.5 and 2.0) and a moderately optimistic prior (85% chance of efficacy). A frequentist random-effects meta-analysis was conducted as a senstivity analysis, and the results were contextualized by estimating the probability of any association (RR ≤ 1) and moderate association (RR ≤ 0.9) with reduced hospitalization. Main Outcomes and Measures: All-cause hospitalization. Results: This systematic review and meta-analysis of 3 randomized clinical trials and included 2196 participants. The RRs for hospitalization were 0.78 (95% CI, 0.58-1.08) for the bayesian weakly neutral prior, 0.73 (95% CI, 0.53-1.01) for the bayesian moderately optimistic prior, and 0.75 (95% CI, 0.58-0.97) for the frequentist analysis. Depending on the scenario, the probability of any association with reduced hospitalization ranged from 94.1% to 98.6%, and the probability of moderate association ranged from 81.6% to 91.8%. Conclusions and Relevance: In this systematic review and meta-analysis of data from 3 trials, under a variety of assumptions, fluvoxamine showed a high probability of being associated with reduced hospitalization in outpatients with COVID-19. Ongoing randomized trials are important to evaluate alternative doses, explore the effectiveness in vaccinated patients, and provide further refinement to these estimates. Meanwhile, fluvoxamine could be recommended as a management option, particularly in resource-limited settings or for individuals without access to SARS-CoV-2 monoclonal antibody therapy or direct antivirals.

The MedSafer Study-Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial.

IMPORTANCE: Scalable deprescribing interventions may reduce polypharmacy and the use of potentially inappropriate medications (PIMs); however, few studies have been large enough to evaluate the impact that deprescribing may have on adverse drug events (ADEs). OBJECTIVE: To evaluate the effect of an electronic deprescribing decision support tool on ADEs after hospital discharge among older adults with polypharmacy. DESIGN, SETTING, AND PARTICIPANTS: This was a cluster randomized clinical trial of older (≥65 years) hospitalized patients with an expected survival of more than 3 months who were admitted to 1 of 11 acute care hospitals in Canada from August 22, 2017, to January 13, 2020. At admission, participants were taking 5 or more medications per day. Data analyses were performed from January 3, 2021, to September 23, 2021. INTERVENTIONS: Personalized reports of deprescribing opportunities generated by MedSafer software to address usual home medications and measures of prognosis and frailty. Deprescribing reports provided to the treating team were compared with usual care (medication reconciliation). MAIN OUTCOMES AND MEASURES: The primary outcome was a reduction of ADEs within the first 30 days postdischarge (including adverse drug withdrawal events) captured through structured telephone surveys and adjudicated blinded to intervention status. Secondary outcomes were the proportion of patients with 1 or more PIMs deprescribed at discharge and the proportion of patients with an adverse drug withdrawal event (ADWE). RESULTS: A total of 5698 participants (median [range] age, 78 [72-85] years; 2858 [50.2%] women; race and ethnicity data were not collected) were enrolled in 3 clusters and were adjudicated for the primary outcome (control, 3204; intervention, 2494). Despite cluster randomization, there were group imbalances, eg, the participants in the intervention arm were older and had more PIMS prescribed at baseline. After hospital discharge, 4989 (87.6%) participants completed an ADE interview. There was no significant difference in ADEs within 30 days of discharge (138 [5.0%] of 2742 control vs 111 [4.9%] of 2247 intervention participants; adjusted risk difference [aRD] -0.8%; 95% CI, -2.9% to 1.3%). Deprescribing increased from 795 (29.8%) of 2667 control to 1249 (55.4%) of 2256 intervention participants [aRD, 22.2%; 95% CI, 16.9% to 27.4%]. There was no difference in ADWEs between groups. Several post hoc sensitivity analyses, including the use of a nonparametric test to address the low cluster number, group imbalances, and potential biases, did not alter study conclusions. CONCLUSIONS AND RELEVANCE: This cluster randomized clinical trial showed that providing deprescribing clinical decision support during acute hospitalization had no demonstrable impact on ADEs, although the intervention was safe and led to improvements in deprescribing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03272607.

Spread and scale of an electronic deprescribing software to improve health outcomes of older adults living in nursing homes: study protocol for a stepped wedge cluster randomized trial.

BACKGROUND: Medication overload or problematic polypharmacy is a major problem causing widespread harm, particularly to older adults. Taking multiple medications increases the risk of potentially inappropriate medications (PIMs), and residents in long-term care (LTC) are frequently prescribed 10 or more medications at once. One strategy to address this problem is for the physician and/or pharmacist to perform regular medication reviews; however, this process can be complicated and time-consuming. With a prescription review, medications may be decreased, changed, or stopped altogether. MedReviewRx is a software that runs an analysis using deprescribing rules to produce a report to guide medication reviews addressing medication overload for residents in LTC. METHODS: This study will employ a mixed methods effectiveness-implementation hybrid type 2 study design. To measure effectiveness, a stepped wedge cluster randomized trial design is planned, which allows us to approximate a randomized clinical trial. Approximately 1000 residents living in LTC will be recruited from five facilities in New Brunswick. The study will begin with 3 months of baseline data on rates of deprescribing. Thereafter, every 3 months a new cluster will enter the intervention mode. The intervention consists of medication reviews augmented with the MedReviewRx software, which will be used by staff and clinicians in the facilities. The estimated study duration is 18 months and the main outcome will be the proportion of patients with one or more PIMs deprescribed (reduced/stopped or changed to a safer alternative) in the 90 days following a prescription review. The goal is to study the impact of MedReviewRx on medication overload among older adults living in LTC. In typical fashion of a stepped wedge cluster randomized trial, each cluster acts as an internal control (before and after) as well as a control for the other clusters (external control). Qualitative data collected will include resident/caregiver attitudes towards deprescribing and semi-structured interviews with staff working in the long-term care homes. DISCUSSION: This study design addresses issues with seasonality and allows all clusters to participate in the intervention, which is an advantage when the intervention is related to quality improvement. This study will provide valuable information on PIM use, cost savings, and facilitators and challenges associated with medication reviews and deprescribing. This study represents an important step towards understanding and promoting tools to guide safe and rational reduction of PIM use among older adults. TRIAL REGISTRATION: NCT04762303 , Registered February 21, 2021.