Coordination of oral anticoagulant care at hospital discharge (COACHeD): pilot randomised controlled trial.

OBJECTIVES: To evaluate whether a focused, expert medication management intervention is feasible and potentially effective in preventing anticoagulation-related adverse events for patients transitioning from hospital to home. DESIGN: Randomised, parallel design. SETTING: Medical wards at six hospital sites in southern Ontario, Canada. PARTICIPANTS: Adults 18 years of age or older being discharged to home on an oral anticoagulant (OAC) to be taken for at least 4 weeks. INTERVENTIONS: Clinical pharmacologist-led intervention, including a detailed discharge medication management plan, a circle of care handover and early postdischarge virtual check-up visits to 1 month with 3-month follow-up. The control group received the usual care. OUTCOMES MEASURES: Primary outcomes were study feasibility outcomes (recruitment, retention and cost per patient). Secondary outcomes included adverse anticoagulant safety events composite, quality of transitional care, quality of life, anticoagulant knowledge, satisfaction with care, problems with medications and health resource utilisation. RESULTS: Extensive periods of restriction of recruitment plus difficulties accessing patients at the time of discharge negatively impacted feasibility, especially cost per patient recruited. Of 845 patients screened, 167 were eligible and 56 were randomised. The mean age (±SD) was 71.2±12.5 years, 42.9% females, with two lost to follow-up. Intervention patients were more likely to rate their ability to manage their OAC as improved (17/27 (63.0%) vs 7/22 (31.8%), OR 3.6 (95% CI 1.1 to 12.0)) and their continuity of care as improved (21/27 (77.8%) vs 2/22 (9.1%), OR 35.0 (95% CI 6.3 to 194.2)). Fewer intervention patients were taking one or more inappropriate medications (7 (22.5%) vs 15 (60%), OR 0.19 (95% CI 0.06 to 0.62)). CONCLUSION: This pilot randomised controlled trial suggests that a transitional care intervention at hospital discharge for older adults taking OACs was well received and potentially effective for some surrogate outcomes, but overly costly to proceed to a definitive large trial. TRIAL REGISTRATION NUMBER: NCT02777047.

Proarrhythmic major adverse cardiac events with donepezil: A systematic review with meta-analysis.

BACKGROUND: Cholinesterase inhibitors (ChEIs) are regularly used in Alzheimer's disease. Of the three ChEIs approved for dementia, donepezil is among the most prescribed drugs in the United States with nearly 6 million prescriptions in 2020; however, it is classified as a "known risk" QT interval-prolonging medication (QTPmed). Given this claim is derived from observational data including single case reports, we aimed to evaluate high-quality literature on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) associated with donepezil. METHODS: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onwards for randomized controlled trials (RCTs) involving patients age ≥18 years comparing donepezil to placebo. The MACE composite included mortality, sudden cardiac death, non-fatal cardiac arrest, Torsades de pointes, ventricular tachyarrhythmia, seizure or syncope. Random-effects meta-analyses were performed with a treatment-arm continuity correction for single and double zero event studies. RESULTS: Sixty RCTs (n = 12,463) were included. Twenty-five of 60 trials (n = 5886) investigated participants with Alzheimer's disease and 33 trials monitored electrocardiogram data. The mean follow-up duration was 31 weeks (SD = 36). Mortality was the most commonly reported MACE (252/331, 75.8% events), the remainder were syncope or seizures, with no arrhythmia events. There was no increased risk of MACE with exposure to donepezil compared to placebo (risk ratio [RR] 1.08, 95% CI 0.88-1.33, I2 = 0%) and this was consistent in the subgroup analysis of trials including participants with cardiovascular morbidities (RR 1.14, 95% CI 0.88-1.47). Subgroup analysis suggested a trend toward more events with donepezil with follow-up ≥52 weeks (RR: 1.32, 0.98-1.79). CONCLUSIONS: This systematic review with meta-analysis found donepezil may not be arrhythmogenic. Donepezil was not associated with mortality, ventricular arrhythmias, seizure or syncope, although longer durations of therapy need more study. Further research to clarify actual clinical outcomes related to QTPmed is important to inform prescribing practices.

Outcomes of Vasopressin-Receptor Agonists Versus Norepinephrine in Adults With Perioperative Hypotension: A Systematic Review.

Consensus statements recommend the use of norepinephrine and/or vasopressin for hypotension in cardiac surgery. However, there is a paucity of data among other surgical subgroups and vasopressin analogs. Therefore, the authors conducted a systematic review of randomized controlled trials (RCTs) to compare vasopressin-receptor agonists with norepinephrine for hypotension among those undergoing surgery with general anesthesia. This review was registered prospectively (CRD42022316328). Literature searches were conducted by a medical librarian to November 28, 2023, across MEDLINE, EMBASE, CENTRAL, and Web of Science. The authors included RCTs enrolling adults (≥18 years of age) undergoing any surgery under general anesthesia who developed perioperative hypotension and comparing vasopressin receptor agonists with norepinephrine. The risk of bias was assessed by the Cochrane risk of bias tool for randomized trials (RoB-2). Thirteen (N = 719) RCTs were included, of which 8 (n = 585) enrolled patients undergoing cardiac surgery. Five trials compared norepinephrine with vasopressin, 4 trials with terlipressin, 1 trial with ornipressin, and the other 3 trials used vasopressin as adjuvant therapy. There was no significant difference in all-cause mortality. Among patients with vasoplegic shock after cardiac surgery, vasopressin was associated with significantly lower intensive care unit (N = 385; 2 trials; mean 100.8 v 175.2 hours, p < 0.005; median 120 [IQR 96-168] v 144 [96-216] hours, p = 0.007) and hospital lengths of stay, as well as fewer cases of acute kidney injury and atrial fibrillation compared with norepinephrine. One trial also found that terlipressin was associated with a significantly lower incidence of acute kidney injury versus norepinephrine overall. Vasopressin and norepinephrine restored mean arterial blood pressure with no significant differences; however, the use of vasopressin with norepinephrine was associated with significantly higher mean arterial blood pressure versus norepinephrine alone. Further high-quality trials are needed to determine pooled treatment effects, especially among noncardiac surgical patients and those treated with vasopressin analogs.

Pharmacological prevention of bone loss and fractures following solid organ transplantations: Protocol for a systematic review and network meta-analysis.

INTRODUCTION: Solid organ transplant (SOT) recipients can experience bone loss caused by underlying conditions and the use of immunosuppressants. As a result, SOT recipients are at risk for decreased bone mineral density (BMD) and increased fracture incidences. We propose a network meta-analysis (NMA) that incorporates all available randomized control trial (RCT) data to provide the most comprehensive ranking of anti-osteoporotic interventions according to their ability to decrease fracture incidences and increase BMD in SOT recipients. METHODS: We will search MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL and CNKI for relevant RCTs that enrolled adult SOT recipients, assessed anti-osteoporotic therapies, and reported relevant outcomes. Title and full-text screening as well as data extraction will be performed in-duplicate. We will report changes in BMD as weighted or standardized mean differences, and fracture incidences as risk ratios. SUCRA scores will be used to provide rankings of interventions, and quality of evidence will be examined using RoB2 and CINeMA. DISCUSSIONS: To our knowledge, this systematic review and NMA will be the most comprehensive quantitative analysis regarding the management of bone loss and fractures in SOT recipients. Our analysis should be able to provide physicians and patients with an up-to-date recommendation for pharmacotherapies in reducing incidences of bone loss and fractures associated with SOT. The findings of the NMA will be disseminated in a peer-reviewed journal.

Outcomes of Acute Respiratory Failure in Patients With Cancer in the United States.

OBJECTIVE: To determine the epidemiological effect-magnitude and outcomes of patients with cancer vs those without cancer who are hospitalized with acute respiratory failure (ARF). PATIENTS AND METHODS: We reviewed hospitalizations within the National Inpatient Sample (NIS) database between January 1, 2016, and December 31, 2018. Patients were classified based on a diagnosis of solid-organ cancer, hematologic cancer, or no cancer. Noninvasive positive pressure ventilation (NIPPV) failure was defined as patients who initially received NIPPV and had progression to invasive mechanical ventilation. Weighted samples were used to derive population estimates. RESULTS: During the study period, there were an estimated 8,837,209 admissions with ARF in the United States, 8.9% (783,625) of which had solid-organ cancer and 2.0% (176,095) had hematologic cancers. Annually, 319,907 patients with cancer are admitted with ARF, with 27.3% (87,302) requiring invasive mechanical ventilation and 10.0% (31,998) requiring NIPPV. In-hospital mortality was higher in patients with cancer vs those without cancer (24.0% [76,813] vs 12.3% [322,465]; P<.001), and this proprotion persisted when stratified by the highest method of oxygen delivery. Patients with cancer had longer hospital length of stay (7.0 days [3.0 to 12.0 days] vs 5.0 days [3.0 to 10.0 days]; P<.001) and were more likely to have NIPPV failure (14.9% [3,992] vs 12.8% [41,875]). Compared with those with solid-organ cancer, patients with hematologic cancers experienced worse outcomes. The association between underlying cancer diagnosis and outcomes remained consistent when adjusted for age, sex, and comorbidities. CONCLUSION: In the United States, patients with cancer account for over 10% of ARF hospital admissions (959,720 of 8,837,209). They experience an approximately 2-fold higher mortality versus those without cancer. Those with hematologic cancers appear to experience worse outcomes than patients with solid-organ cancers.

Assessing the research landscape and clinical utility of large language models: a scoping review.

IMPORTANCE: Large language models (LLMs) like OpenAI's ChatGPT are powerful generative systems that rapidly synthesize natural language responses. Research on LLMs has revealed their potential and pitfalls, especially in clinical settings. However, the evolving landscape of LLM research in medicine has left several gaps regarding their evaluation, application, and evidence base. OBJECTIVE: This scoping review aims to (1) summarize current research evidence on the accuracy and efficacy of LLMs in medical applications, (2) discuss the ethical, legal, logistical, and socioeconomic implications of LLM use in clinical settings, (3) explore barriers and facilitators to LLM implementation in healthcare, (4) propose a standardized evaluation framework for assessing LLMs' clinical utility, and (5) identify evidence gaps and propose future research directions for LLMs in clinical applications. EVIDENCE REVIEW: We screened 4,036 records from MEDLINE, EMBASE, CINAHL, medRxiv, bioRxiv, and arXiv from January 2023 (inception of the search) to June 26, 2023 for English-language papers and analyzed findings from 55 worldwide studies. Quality of evidence was reported based on the Oxford Centre for Evidence-based Medicine recommendations. FINDINGS: Our results demonstrate that LLMs show promise in compiling patient notes, assisting patients in navigating the healthcare system, and to some extent, supporting clinical decision-making when combined with human oversight. However, their utilization is limited by biases in training data that may harm patients, the generation of inaccurate but convincing information, and ethical, legal, socioeconomic, and privacy concerns. We also identified a lack of standardized methods for evaluating LLMs' effectiveness and feasibility. CONCLUSIONS AND RELEVANCE: This review thus highlights potential future directions and questions to address these limitations and to further explore LLMs' potential in enhancing healthcare delivery.

The effects of pks+ Escherichia coli and bile acid in colorectal tumorigenesis among people with cholelithiasis or cholecystectomy.

BACKGROUND AND AIM: Patients with cholelithiasis (CL) or cholecystectomy (CE) would have more chances of getting colorectal adenoma (CRA) or cancer (CRC). We aimed to figure out the effects of gut microbiota and bile acid on colorectal neoplasm in CL and CE patients. METHODS: This was a retrospective observational study that recruited 514 volunteers, including 199 people with normal gallbladders (normal), 152 CL, and 163 CE patients. Discovery cohort was established to explore the difference in gut microbiota through 16S rRNA and metagenomics sequencing. Validation cohort aimed to verify the results through quantitative polymerase chain reaction (qPCR). RESULTS: Significant enrichment of Escherichia coli was found in patients with cholelithiasis or cholecystectomy both in the discovery cohort (16S rRNA sequencing, PNormal-CL = 0.013, PNormal-CE = 0.042; metagenomics sequencing, PNormal-CE = 0.026) and validation cohort (PNormal-CL < 0.0001, PNormal-CE < 0.0001). Pks+ E. coli was found enriched in CL and CE patients through qPCR (in discovery cohort: PNormal-CE = 0.018; in validation cohort: PNormal-CL < 0.0001, PNormal-CE < 0.0001). The differences in bile acid metabolism were found both through Tax4Fun analysis of 16S rRNA sequencing (Ko00120, primary bile acid biosynthesis, PNormal-CE = 0.014; Ko00121, secondary bile acid biosynthesis, PNormal-CE = 0.010) and through metagenomics sequencing (map 00121, PNormal-CE = 0.026). The elevation of serum total bile acid of CE patients was also found in validation cohort (PNormal-CE < 0.0001). The level of serum total bile acid was associated with the relative abundance of pks+ E. coli (r = 0.1895, P = 0.0012). CONCLUSIONS: E. coli, especially pks+ species, was enriched in CL and CE patients. Pks+ E. coli and bile acid metabolism were found associated with CRA and CRC in people after cholecystectomy.

Automated Paper Screening for Clinical Reviews Using Large Language Models: Data Analysis Study.

BACKGROUND: The systematic review of clinical research papers is a labor-intensive and time-consuming process that often involves the screening of thousands of titles and abstracts. The accuracy and efficiency of this process are critical for the quality of the review and subsequent health care decisions. Traditional methods rely heavily on human reviewers, often requiring a significant investment of time and resources. OBJECTIVE: This study aims to assess the performance of the OpenAI generative pretrained transformer (GPT) and GPT-4 application programming interfaces (APIs) in accurately and efficiently identifying relevant titles and abstracts from real-world clinical review data sets and comparing their performance against ground truth labeling by 2 independent human reviewers. METHODS: We introduce a novel workflow using the Chat GPT and GPT-4 APIs for screening titles and abstracts in clinical reviews. A Python script was created to make calls to the API with the screening criteria in natural language and a corpus of title and abstract data sets filtered by a minimum of 2 human reviewers. We compared the performance of our model against human-reviewed papers across 6 review papers, screening over 24,000 titles and abstracts. RESULTS: Our results show an accuracy of 0.91, a macro F1-score of 0.60, a sensitivity of excluded papers of 0.91, and a sensitivity of included papers of 0.76. The interrater variability between 2 independent human screeners was κ=0.46, and the prevalence and bias-adjusted κ between our proposed methods and the consensus-based human decisions was κ=0.96. On a randomly selected subset of papers, the GPT models demonstrated the ability to provide reasoning for their decisions and corrected their initial decisions upon being asked to explain their reasoning for incorrect classifications. CONCLUSIONS: Large language models have the potential to streamline the clinical review process, save valuable time and effort for researchers, and contribute to the overall quality of clinical reviews. By prioritizing the workflow and acting as an aid rather than a replacement for researchers and reviewers, models such as GPT-4 can enhance efficiency and lead to more accurate and reliable conclusions in medical research.

The use of large language models in medicine: proceeding with caution.

Large language models, like ChatGPT and Bard, have potential clinical applications due to their ability to generate conversational responses and encode medical knowledge. However, their clinical adoption faces challenges including hallucinations, lack of transparency, and lack of consistency. Ethicolegal concerns surrounding patient consent, legal liability, and data privacy further complicate matters. Despite their promise, an optimistic but cautious approach is essential for the safe integration of large language models into clinical settings.

Evaluating fluvoxamine for the outpatient treatment of COVID-19: A systematic review and meta-analysis.

This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of fluvoxamine for the outpatient management of COVID-19. We conducted this review in accordance with the PRISMA 2020 guidelines. Literature searches were conducted in MEDLINE, EMBASE, International Pharmaceutical Abstracts, CINAHL, Web of Science, and CENTRAL up to 14 September 2023. Outcomes included incidence of hospitalisation, healthcare utilization (emergency room visits and/or hospitalisation), mortality, supplemental oxygen and mechanical ventilation requirements, serious adverse events (SAEs) and non-adherence. Fluvoxamine 100 mg twice a day was associated with reductions in the risk of hospitalisation (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.58-0.97; I 2  = 0%) and reductions in the risk of healthcare utilization (RR 0.68, 95% CI 0.53-0.86; I 2  = 0%). While no increased SAEs were observed, fluvoxamine 100 mg twice a day was associated with higher treatment non-adherence compared to placebo (RR 1.61, 95% CI 1.22-2.14; I 2  = 53%). In subgroup analyses, fluvoxamine reduced healthcare utilization in outpatients with BMI ≥30 kg/m2 , but not in those with lower BMIs. While fluvoxamine offers potential benefits in reducing healthcare utilization, its efficacy may be most pronounced in high-risk patient populations. The observed non-adherence rates highlight the need for better patient education and counselling. Future investigations should reassess trial endpoints to include outcomes relating to post-COVID sequelaes. Registration: This review was prospectively registered on PROSPERO (CRD42023463829).

Hydroxychloroquine-Chloroquine, QT-Prolongation, and Major Adverse Cardiac Events: A Meta-analysis and Scoping Review.

OBJECTIVES: We aimed to evaluate the high-quality literature on the frequency and nature of major adverse cardiac events (MACE) associated with either hydroxychloroquine (HCQ) or chloroquine (CQ). DATA SOURCES: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onward using search strategies created in collaboration with medical science librarians. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials (RCTs) published in English language from January 1996 to September 2022, involving adult patients at least 18 years of age, were selected. Outcomes of interest were death, arrhythmias, syncope, and seizures. Random-effects meta-analyses were performed with a Treatment Arm Continuity Correction for single and double zero event studies. DATA SYNTHESIS: By study drug, there were 31 HCQ RCTs (n = 6677), 9 CQ RCTs (n = 622), and 1 combined HCQ-CQ trial (n = 105). Mortality was the most commonly reported MACE at 220 of 255 events (86.3%), with no reports of torsades de pointes or sudden cardiac death. There was no increased risk of MACE with exposure to HCQ-CQ compared with control (risk ratio [RR] = 0.90, 95% CI = 0.69-1.17, I2 = 0%). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: These findings have important implications with respect to patient reassurance and updated guidance for prescribing practices of these medications. CONCLUSIONS: Despite listing as QT-prolonging meds, HCQ-CQ did not increase the risk of MACE.

Enhancing Offensive Language Detection with Data Augmentation and Knowledge Distillation.

Offensive language detection has received important attention and plays a crucial role in promoting healthy communication on social platforms, as well as promoting the safe deployment of large language models. Training data is the basis for developing detectors; however, the available offense-related dataset in Chinese is severely limited in terms of data scale and coverage when compared to English resources. This significantly affects the accuracy of Chinese offensive language detectors in practical applications, especially when dealing with hard cases or out-of-domain samples. To alleviate the limitations posed by available datasets, we introduce AugCOLD (Augmented Chinese Offensive Language Dataset), a large-scale unsupervised dataset containing 1 million samples gathered by data crawling and model generation. Furthermore, we employ a multiteacher distillation framework to enhance detection performance with unsupervised data. That is, we build multiple teachers with publicly accessible datasets and use them to assign soft labels to AugCOLD. The soft labels serve as a bridge for knowledge to be distilled from both AugCOLD and multiteacher to the student network, i.e., the final offensive detector. We conduct experiments on multiple public test sets and our well-designed hard tests, demonstrating that our proposal can effectively improve the generalization and robustness of the offensive language detector.

Appraisal of Postoperative Outcomes of Volatile and Intravenous Anesthetics: A Network Meta-Analysis of Patients Undergoing Cardiac Surgery.

OBJECTIVES: To determine the relative efficacy of specific regimens used as primary anesthetics, as well as the potential combination of volatile and intravenous anesthetics among patients undergoing cardiac, thoracic, and vascular surgery. DESIGN: This frequentist, random-effects network meta-analysis was registered prospectively (CRD42022316328) and conducted according to the PRISMA-NMA framework. Literature searches were conducted up to April 1, 2022 across relevant databases. Risk of bias (RoB) and confidence of evidence were assessed by RoB-2 and CINeMA, respectively. Pooled treatment effects were compared with propofol monotherapy. SETTING: Fifty-three randomized controlled trials (N = 8,085) were included, of which 46 trials (N = 6,604) enrolled patients undergoing cardiac surgery. PARTICIPANTS: Trials enrolling adults (≥18) undergoing cardiac, thoracic, and vascular surgery, using the same induction regimens, and comparing volatile and/or total intravenous anesthesia for the maintenance of anesthesia. Given that the majority of trials focused on those undergoing cardiac surgery and the heterogeneity, analyses were restricted to this population. MEASUREMENT AND MAIN RESULTS: Outcomes of interest included intensive care unit (ICU) length of stay (LOS), myocardial infarction, in-hospital and 30-day mortality, stroke, and delirium. Across 19 trials (N = 1,821; 9 arms; I2 = 64.5%), sevoflurane combined with propofol decreased ICU LOS (mean difference [MD] -18.26 hours; 95% CI -34.78 to -1.73 hours), whereas midazolam with propofol (MD 17.51 hours; 95% CI 2.78-32.25 hours) was associated with a significant increase in ICU LOS, when compared with propofol monotherapy. Among 27 trials (N = 4,080; 10 arms; I2 = 0%), midazolam was associated with significantly greater risk of myocardial infarction versus propofol (risk ratio 1.94; 95% CI 1.01-3.71). There were no significant differences across other outcomes. CONCLUSION: In patients undergoing cardiac surgery, sevoflurane with propofol was associated with decreased ICU LOS compared with propofol monotherapy. Midazolam with propofol increased ICU LOS compared with propofol alone. The combined use of intravenous and volatile anesthetics should be explored further. Future trials in thoracic and vascular surgery are warranted.

Noninvasive predictive models based on lifestyle analysis and risk factors for early-onset colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) incidence has increased among patients aged <50 years. Exploring high-risk factors and screening high-risk populations may help lower early-onset CRC (EO-CRC) incidence. We developed noninvasive predictive models for EO-CRC and investigated its risk factors. METHODS: This retrospective multicenter study collected information on 1756 patients (811 patients with EO-CRC and 945 healthy controls) from two medical centers in China. Sociodemographic features, clinical symptoms, medical and family history, lifestyle, and dietary factors were measured. Patients from one cohort were randomly assigned (8:2) to two groups for model establishment and internal validation, and another independent cohort was used for external validation. Multivariable logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost) were performed to establish noninvasive predictive models for EO-CRC. Some variables in the model influenced EO-CRC occurrence and were further analyzed. Multivariable logistic regression analysis yielded adjusted odd ratios (ORs) and 95% confidence intervals (CIs). RESULTS: All three models showed good performance, with areas under the receiver operator characteristic curves (AUCs) of 0.82, 0.84, and 0.82 in the internal and 0.78, 0.79, and 0.78 in the external validation cohorts, respectively. Consumption of sweet (OR 2.70, 95% CI 1.89-3.86, P < 0.001) and fried (OR 2.16, 95% CI 1.29-3.62, P < 0.001) foods ≥3 times per week was significantly associated with EO-CRC occurrence. CONCLUSION: We established noninvasive predictive models for EO-CRC and identified multiple nongenetic risk factors, especially sweet and fried foods. The model has good performance and can help predict the occurrence of EO-CRC in the Chinese population.

Comparative Efficacy of Adjuvant Nonopioid Analgesia in Adult Cardiac Surgical Patients: A Network Meta-Analysis.

OBJECTIVES: To compare the relative efficacy of adjuvant nonopioid analgesic regimens in adult cardiac surgical patients. DESIGN: This frequentist, random-effects network meta-analysis (NMA) was prospectively registered on PROSPERO (CRD42021282913) and conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses for Network Meta-Analyses (PRISMA-NMA). The risk of bias (RoB) and confidence of evidence were assessed by RoB 2 and Confidence in Network Meta-Analysis, respectively. Relevant databases were searched from inception to October 9, 2021. SETTING: A total of 124 (N = 26,257) randomized controlled trials were included, of which 110 were analyzed. PARTICIPANTS: Trials enrolling adults (≥18 years of age) undergoing cardiac surgery that compared nonopioid analgesics against other nonopioid analgesics, placebo, or no additional treatment, as adjuvants to standard analgesic management, and reported at least 1 of the outcomes of interest. MEASUREMENT AND MAIN RESULTS: Outcomes of interest included resting postoperative pain scores at 24 hours. Compared with standard care and/or placebo, pain scores were reduced significantly by 10 different regimens, including acetaminophen (N = 176; mean difference [MD] -0.66 points, 95% CI -1.16 to -0.15 points; high confidence), magnesium (N = 323; -0.05 points, 95% CI -0.07 to -0.02 points; high confidence), gabapentin (N = 96; MD -0.40 points, 95% CI -0.71 to -0.09; moderate confidence), and clonidine (N = 64; MD v0.38 points, 95% CI -0.73 to v0.04 points; moderate confidence). Indomethacin, diclofenac, magnesium, and gabapentin significantly reduced 24-hour opioid consumption. Four regimens significantly decreased the intensive care unit length of stay. Hydrocortisone, dexmedetomidine, and clonidine significantly decreased the duration of mechanical ventilation. Magnesium decreased, while methylprednisolone significantly increased, the risk of myocardial infarction. CONCLUSIONS: Given the increasing emphasis on enhanced recovery after surgery(ERAS) protocols and the eventual goal of limiting opiate prescriptions postoperatively, the authors' data suggested far greater use of nonopioid adjuncts to minimize pain and enhance recovery following cardiac surgery.