The Safety of Inpatient Health Care.

BACKGROUND: Adverse events during hospitalization are a major cause of patient harm, as documented in the 1991 Harvard Medical Practice Study. Patient safety has changed substantially in the decades since that study was conducted, and a more current assessment of harm during hospitalization is warranted. METHODS: We conducted a retrospective cohort study to assess the frequency, preventability, and severity of patient harm in a random sample of admissions from 11 Massachusetts hospitals during the 2018 calendar year. The occurrence of adverse events was assessed with the use of a trigger method (identification of information in a medical record that was previously shown to be associated with adverse events) and from review of medical records. Trained nurses reviewed records and identified admissions with possible adverse events that were then adjudicated by physicians, who confirmed the presence and characteristics of the adverse events. RESULTS: In a random sample of 2809 admissions, we identified at least one adverse event in 23.6%. Among 978 adverse events, 222 (22.7%) were judged to be preventable and 316 (32.3%) had a severity level of serious (i.e., caused harm that resulted in substantial intervention or prolonged recovery) or higher. A preventable adverse event occurred in 191 (6.8%) of all admissions, and a preventable adverse event with a severity level of serious or higher occurred in 29 (1.0%). There were seven deaths, one of which was deemed to be preventable. Adverse drug events were the most common adverse events (accounting for 39.0% of all events), followed by surgical or other procedural events (30.4%), patient-care events (which were defined as events associated with nursing care, including falls and pressure ulcers) (15.0%), and health care-associated infections (11.9%). CONCLUSIONS: Adverse events were identified in nearly one in four admissions, and approximately one fourth of the events were preventable. These findings underscore the importance of patient safety and the need for continuing improvement. (Funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.).

The Safety of Outpatient Health Care : Review of Electronic Health Records.

BACKGROUND: Despite considerable emphasis on delivering safe care, substantial patient harm occurs. Although most care occurs in the outpatient setting, knowledge of outpatient adverse events (AEs) remains limited. OBJECTIVE: To measure AEs in the outpatient setting. DESIGN: Retrospective review of the electronic health record (EHR). SETTING: 11 outpatient sites in Massachusetts in 2018. PATIENTS: 3103 patients who received outpatient care. MEASUREMENTS: Using a trigger method, nurse reviewers identified possible AEs and physicians adjudicated them, ranked severity, and assessed preventability. Generalized estimating equations were used to assess the association of having at least 1 AE with age, sex, race, and primary insurance. Variation in AE rates was analyzed across sites. RESULTS: The 3103 patients (mean age, 52 years) were more often female (59.8%), White (75.1%), English speakers (90.8%), and privately insured (70.4%) and had a mean of 4 outpatient encounters in 2018. Overall, 7.0% (95% CI, 4.6% to 9.3%) of patients had at least 1 AE (8.6 events per 100 patients annually). Adverse drug events were the most common AE (63.8%), followed by health care-associated infections (14.8%) and surgical or procedural events (14.2%). Severity was serious in 17.4% of AEs, life-threatening in 2.1%, and never fatal. Overall, 23.2% of AEs were preventable. Having at least 1 AE was less often associated with ages 18 to 44 years than with ages 65 to 84 years (standardized risk difference, -0.05 [CI, -0.09 to -0.02]) and more often associated with Black race than with Asian race (standardized risk difference, 0.09 [CI, 0.01 to 0.17]). Across study sites, 1.8% to 23.6% of patients had at least 1 AE and clinical category of AEs varied substantially. LIMITATION: Retrospective EHR review may miss AEs. CONCLUSION: Outpatient harm was relatively common and often serious. Adverse drug events were most frequent. Rates were higher among older adults. Interventions to curtail outpatient harm are urgently needed. PRIMARY FUNDING SOURCE: Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.

The use and safety risk of repurposed drugs for COVID-19 patients: lessons learned utilizing the Food and Drug Administration's Adverse Event Reporting System.

Objectives: This study was designed to assess the disproportionality analyses of adverse drug reactions (ADRs) related to hydroxychloroquine and remdesivir and how ADR reporting fluctuated during the COVID-19 pandemic. Methods: A retrospective observational study was conducted utilizing the Food and Drug Administration's Adverse Event Reporting System (FAERS) data between 2019 and 2021. The study was conducted in two phases. In the first phase, all reports associated with the drugs of interest were evaluated to assess all related adverse drug reactions. In the second phase, specific outcomes of interest (i.e., QT prolongation and renal and hepatic events) were determined to study their association with the drugs of interest. A descriptive analysis was conducted for all adverse reactions related to the drugs being studied. In addition, disproportionality analyses were conducted to compute the reporting odds ratio, the proportional reporting ratio, the information component, and the empirical Bayes geometric mean. All analyses were conducted using RStudio. Results: A total of 9,443 ADR reports related to hydroxychloroquine; 6,160 (71.49) patients were female, and higher percentage of patients of both sexes were over the age of 65 years. QT prolongation (1.48%), pain (1.38%), and arthralgia (1.25%) were most frequently reported ADRs during the COVID-19 pandemic. The association of QT prolongation with use of hydroxychloroquine was statistically significant (ROR 47.28 [95% CI 35.95-62.18]; PRR 42.41 [95% CI 32.25-55.78]; EBGM 16.08; IC 4.95) compared with fluoroquinolone. The outcome was serious medical events in 48.01% of ADR reports; 27.42% required hospitalization and 8.61% resulted in death. Of 6,673 ADR reports related to remdesivir, 3,928 (61.13%) patients were male. During 2020, the top three ADR reports were elevated liver function tests (17.26%), acute kidney injury (5.95%) and death (2.84%). Additionally, 42.71% of ADR reports indicated serious medical events; 19.69% resulted in death and 11.71% indicated hospitalization. The ROR and PRR of hepatic and renal events associated with remdesivir were statistically significant, (4.81 [95% CI 4.46-5.19] and 2.96 [95% CI 2.66-3.29], respectively. Conclusion: Our study showed that several serious ADRs were reported with the use of hydroxychloroquine, which resulted in hospitalization and death. Trends with the use of remdesivir were similar, but to a lesser extent. Therefore, this study showed us that off-label use should be based on thorough evidence-based evaluation.

Tramadol use in U.S. adults with commercial health insurance, 2005-2021.

INTRODUCTION: Tramadol has been associated with chronic opioid use and emergency room (ER) visits. However, little is known about trends in prescription tramadol use in the US. METHODS: Optum's de-identified Clinformatics® Data Mart Database was used to assess trends in monthly incident and prevalent tramadol use from 2005 to 2021, stratified by sex and age (18-64 vs. ≥65 years). State-specific trends following scheduling of tramadol as Class IV controlled substance in August 2014 were analyzed with random effects regression models. Demographics, comorbidities, initiation setting, dose, and co-dispensing with other opioids and central nervous system (CNS) agents were assessed in people initiating tramadol, stratified by age and initiation year (2005-2010, 2011-2015, 2016-2021). Analyses were performed in 2023 and 2024. RESULTS: During 2005-2021, the mean percentage using tramadol in a given month was 0.88% of younger females, 0.55% of younger males, 1.97% of older females, and 1.14% of older males; 5,729,652 initiations were identified. Since 2014, estimated relative yearly decrease was 4% (95% CI 3%; 5%) in use and 5% (95% CI 4%; 5%) in initiation, with variation across states. Primary care percentage of tramadol initiations declined from 49.2% in 2005-2010 to 37.2% in 2016-2021. During 2016-2021, co-dispensing with other CNS agents occurred in 37.8% of younger and 32.1% of older adults initiating tramadol. CONCLUSIONS: Tramadol use was higher in females and older adults, exhibited heterogeneous trends across states, and shifted from primary care to ER and specialist settings over time. Co-dispensing with other CNS agents was common and warrants further monitoring.

A Case Series on Serotonin Syndrome from Concomitant use of linezolid With Methadone, Buprenorphine, and/or Dextroamphetamine.

BACKGROUND AND OBJECTIVES: The risk of serotonin syndrome (SS), especially when linezolid is used concomitantly with methadone, buprenorphine, and/or dextroamphetamine, remains widely unstudied and may limit the options for antimicrobial therapy in these patient populations. METHODS: We reviewed all adult encounters on linezolid with concomitant methadone, buprenorphine, and/or dextroamphetamine from April 2016 to June 2022. The primary outcomes included characterizing prescribing preferences and prevalence of confirmed and possible serotonin syndrome using ICD-10 diagnosis codes, cyproheptadine administration, and electronic medical record chart review using the Hunter Serotonin Toxicity Criteria. RESULTS: Overall, 194 encounters were evaluated. 16.5%, 17.8%, and 7.1% were on high dose methadone, buprenorphine, and dextroamphetamine, respectively. Mean duration of overlap with linezolid was 4.6, 3.3, and 7 days respectively. One confirmed and two possible cases of serotonin syndrome were identified. CONCLUSION: Linezolid may be considered in patients who are concomitantly on methadone, buprenorphine, and/or dextroamphetamine. In our analysis of 194 encounters, one definitive case and two possible cases of SS were identified. Additional real-world studies are necessary to identify if exposure and/or duration may be correlated with an increased risk of serotonin syndrome.

Performance of a Web-Based Reference Database With Natural Language Searching Capabilities: Usability Evaluation of DynaMed and Micromedex With Watson.

BACKGROUND: Evidence-based point-of-care information (POCI) tools can facilitate patient safety and care by helping clinicians to answer disease state and drug information questions in less time and with less effort. However, these tools may also be visually challenging to navigate or lack the comprehensiveness needed to sufficiently address a medical issue. OBJECTIVE: This study aimed to collect clinicians' feedback and directly observe their use of the combined POCI tool DynaMed and Micromedex with Watson, now known as DynaMedex. EBSCO partnered with IBM Watson Health, now known as Merative, to develop the combined tool as a resource for clinicians. We aimed to identify areas for refinement based on participant feedback and examine participant perceptions to inform further development. METHODS: Participants (N=43) within varying clinical roles and specialties were recruited from Brigham and Women's Hospital and Massachusetts General Hospital in Boston, Massachusetts, United States, between August 10, 2021, and December 16, 2021, to take part in usability sessions aimed at evaluating the efficiency and effectiveness of, as well as satisfaction with, the DynaMed and Micromedex with Watson tool. Usability testing methods, including think aloud and observations of user behavior, were used to identify challenges regarding the combined tool. Data collection included measurements of time on task; task ease; satisfaction with the answer; posttest feedback on likes, dislikes, and perceived reliability of the tool; and interest in recommending the tool to a colleague. RESULTS: On a 7-point Likert scale, pharmacists rated ease (mean 5.98, SD 1.38) and satisfaction (mean 6.31, SD 1.34) with the combined POCI tool higher than the physicians, nurse practitioner, and physician's assistants (ease: mean 5.57, SD 1.64, and satisfaction: mean 5.82, SD 1.60). Pharmacists spent longer (mean 2 minutes, 26 seconds, SD 1 minute, 41 seconds) on average finding an answer to their question than the physicians, nurse practitioner, and physician's assistants (mean 1 minute, 40 seconds, SD 1 minute, 23 seconds). CONCLUSIONS: Overall, the tool performed well, but this usability evaluation identified multiple opportunities for improvement that would help inexperienced users.

Correction: Performance of a Web-Based Reference Database With Natural Language Searching Capabilities: Usability Evaluation of DynaMed and Micromedex With Watson.

[This corrects the article DOI: 10.2196/43960.].

Intelligent Telehealth in Pharmacovigilance: A Future Perspective.

Pharmacovigilance improves patient safety by detecting and preventing adverse drug events. However, challenges exist that limit adverse drug event detection, resulting in many adverse drug events being underreported or inaccurately reported. One challenge includes having access to large data sets from various sources including electronic health records and wearable medical devices. Artificial intelligence, including machine learning methods, such as natural language processing and deep learning, can detect and extract information about adverse drug events, thus automating the pharmacovigilance process and improving the surveillance of known and documented adverse drug events. In addition, with the increased demand for telehealth services, for managing both acute and chronic diseases, artificial intelligence methods can play a role in detecting and preventing adverse drug events. In this review, we discuss two use cases of how artificial intelligence methods may be useful to improve the quality of pharmacovigilance and the role of artificial intelligence in telehealth practices.

Surgery vs. Biopsy in the Treatment of Butterfly Glioblastoma: A Systematic Review and Meta-Analysis.

Butterfly glioblastomas (bGBM) are grade IV gliomas that spread to bilateral hemispheres by infiltrating the corpus callosum. Data on the effect of surgery are limited to small case series. The aim of this meta-analysis was to compare resection vs. biopsy in terms of survival outcomes and postoperative complications. A systematic review of the literature was conducted using PubMed, EMBASE, and Cochrane databases through March 2021 in accordance with the PRISMA checklist. Pooled hazard ratios were calculated and meta-analyzed in a random-effects model including assessment of heterogeneity. Out of 3367 articles, seven studies were included with 293 patients. Surgical resection was significantly associated with longer overall survival (HR 0.39, 95%CI 0.2-0.55) than biopsy. Low heterogeneity was observed (I2: 0%). In further analysis, the effect persisted in extent of resection subgroups of both ≥80% and <80%. No statistically significant difference between surgery and biopsy was detected in terms of postoperative complications, although these were numerically larger for surgery. In patients with bGBM, surgical resection was associated with longer survival prospects compared with biopsy.

Key use cases for artificial intelligence to reduce the frequency of adverse drug events: a scoping review.

Adverse drug events (ADEs) represent one of the most prevalent types of health-care-related harm, and there is substantial room for improvement in the way that they are currently predicted and detected. We conducted a scoping review to identify key use cases in which artificial intelligence (AI) could be leveraged to reduce the frequency of ADEs. We focused on modern machine learning techniques and natural language processing. 78 articles were included in the scoping review. Studies were heterogeneous and applied various AI techniques covering a wide range of medications and ADEs. We identified several key use cases in which AI could contribute to reducing the frequency and consequences of ADEs, through prediction to prevent ADEs and early detection to mitigate the effects. Most studies (73 [94%] of 78) assessed technical algorithm performance, and few studies evaluated the use of AI in clinical settings. Most articles (58 [74%] of 78) were published within the past 5 years, highlighting an emerging area of study. Availability of new types of data, such as genetic information, and access to unstructured clinical notes might further advance the field.

High-priority drug-drug interaction clinical decision support overrides in a newly implemented commercial computerized provider order-entry system: Override appropriateness and adverse drug events.

OBJECTIVE: The study sought to determine frequency and appropriateness of overrides of high-priority drug-drug interaction (DDI) alerts and whether adverse drug events (ADEs) were associated with overrides in a newly implemented electronic health record. MATERIALS AND METHODS: We conducted a retrospective study of overridden high-priority DDI alerts occurring from April 1, 2016, to March 31, 2017, from inpatient and outpatient settings at an academic health center. We studied highest-severity DDIs that were previously designated as "hard stops" and additional high-priority DDIs identified from clinical experience and literature review. All highest-severity alert overrides (n = 193) plus a stratified random sample of additional overrides (n = 371) were evaluated for override appropriateness, using predetermined criteria. Charts were reviewed to identify ADEs for overrides that resulted in medication administration. A chi-square test was used to compare ADE rate by override appropriateness. RESULTS: Of 16 011 alerts presented to providers, 15 318 (95.7%) were overridden, including 193 (87.3%) of the highest-severity DDIs and 15 125 (95.8%) of additional DDIs. Override appropriateness was 45.4% overall, 0.5% for highest-severity DDIs and 68.7% for additional DDIs. For alerts that resulted in medication administration (n = 423, 75.0%), 29 ADEs were identified (6.9%, 5.1 per 100 overrides). The rate of ADEs was higher with inappropriate vs appropriate overrides (9.4% vs 4.3%; P = .038). CONCLUSIONS: The override rate was nearly 90% for even the highest-severity DDI alerts, indicating that stronger suggestions should be made for these alerts, while other alerts should be evaluated for potential suppression.

Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection: a systematic review and meta-analysis.

BACKGROUND: In patients with one to three brain metastases who undergo resection, options for post-operative treatments include whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) of the resection cavity. In this meta-analysis, we sought to compare the efficacy of each post-operative radiation modality with respect to tumor recurrence and survival. METHODS: Pubmed, Embase and Cochrane databases were searched through June 2016 for cohort studies reporting outcomes of SRS or WBRT after metastasis resection. Pooled effect estimates were calculated using fixed-effect and random-effect models for local recurrence, distant recurrence, and overall survival. RESULTS: Eight retrospective cohort studies with 646 patients (238 with SRS versus 408 with WBRT) were included in the analysis. Comparing SRS to WBRT, the overall crude risk ratio using the fixed-effect model was 0.59 for local recurrence (95%-CI: 0.32-1.09, I2: 3.35%, P-heterogeneity = 0.36, 3 studies), 1.09 for distant recurrence (95%-CI: 0.74-1.60, I2: 50.5%, P-heterogeneity = 0.13; 3 studies), and 2.99 for leptomeningeal disease (95% CI 1.55-5.76; I2: 14.4% p-heterogeneity: 0.28; 2 studies). For the same comparison, the risk ratio for median overall survival was 0.47 (95% CI: 0.41-0.54; I2: 79.1%, P-heterogeneity < 0.01; 4 studies) in a fixed-effect model, but was no longer significant (0.63; 95%-CI: 0.40-1.00) in a random-effect model. SRS was associated with a lower risk of leukoencephalopathy (RR: 0.15, 95% CI: 0.07-0.33, 1 study), yet with a higher risk of radiation-necrosis (RR: 19.4, 95% CI: 1.21-310, 1 study). CONCLUSION: Based on retrospective cohort studies, the results of this study suggest that SRS of the resection cavity may offer comparable survival and similar local and distant control as adjuvant WBRT, yet may be associated with a higher risk for developing leptomeningeal disease. Future research on SRS should focus on achieving a better understanding of the various factors that may favor SRS over WBRT.