Deletion of exons 2 and 3 from Actb and cell immortalization lead to widespread, ß-actin independent alterations in gene expression associated with cell cycle control.

The cytoplasmic actin proteins, ß- and γ-actin, are 99% identical but thought to perform non-redundant functions. The nucleotide coding regions of cytoplasmic actin genes, Actb and Actg1, are 89% identical. Knockout (KO) of Actb by Cre-mediated deletion of first coding exons 2 and 3 in mice is embryonic lethal and fibroblasts derived from KO embryos (MEFs) fail to proliferate. In contrast, Actg1 KO MEFs display with a much milder defect in cell proliferation and Actg1 KO mice are viable, but present with increased perinatal lethality. Recent studies have identified important protein-independent functions for both Actb and Actg1 and demonstrate that deletions within the Actb nucleotide sequence, and not loss of the ß-actin protein, cause the most severe phenotypes in KO mice and cells. Here, we use a multi-omics approach to better understand what drives the phenotypes of Actb KO MEFs. RNA-sequencing and mass spectrometry reveal largescale changes to the transcriptome, proteome, and phosphoproteome in cells lacking Actb but not those only lacking ß-actin protein. Pathway analysis of genes and proteins differentially expressed upon Actb KO suggest widespread dysregulation of genes involved in the cell cycle that may explain the severe defect in proliferation.

National Survey of Patient Safety Experiences in Hospital Medicine During the COVID-19 Pandemic.

BACKGROUND: During the COVID-19 pandemic, hospitals were caring for increasing numbers of patients with a novel and highly contagious respiratory illness, forcing adaptations in care delivery. The objective of this study was to understand the impact of these adaptations on patient safety in hospital medicine. METHODS: The authors conducted a nationwide survey to understand patient safety challenges experienced by hospital medicine clinicians during the COVID-19 pandemic. The survey was distributed to members of the Society of Hospital Medicine via an e-mail listserv. It consisted of closed- and open-ended questions to elicit respondents' experience in five domains: error reporting and communication, staffing, equipment, personal protective equipment (PPE) and isolation practices, and infrastructure. Quantitative questions were reported as counts and percentages; qualitative responses were coded and analyzed for relevant themes. RESULTS: Of 196 total responses, 167 respondents (85.2%) were attending physicians and 85 (43.8%) practiced at teaching hospitals. Safety concerns commonly identified included nursing shortages (71.0%), limiting patient interactions to conserve PPE (61.9%), and feeling that one was practicing in a more hazardous environment (61.4%). In free-text responses, clinicians described poor outcomes and patient decompensation due to provider and equipment shortages, as well as communication lapses and diagnostic errors resulting from decreased patient contact and the need to follow isolation protocols. CONCLUSION: Efforts made to accommodate shortages in staff and equipment, adapt to limited PPE, and enforce isolation policies had unintended consequences that affected patient safety and created a more hazardous environment characterized by less efficient care, respiratory decompensations, diagnostic errors, and poor communication with patients.

Self-Reported Injuries in Indoor Gym-Based Rock Climbers: A Retrospective Study of Predictors of Prolonged Injury and Seeking Medical Care.

INTRODUCTION: Indoor climbing injuries are often related to overuse, and climbers choose between self-management and seeing a medical practitioner. This study evaluated predictors of prolonged injury and seeking medical care for indoor climbing injuries. METHODS: A convenience sample of adult climbers from 5 gyms in New York City was interviewed about injuries over the past 3 y, because of which they stopped climbing for at least a week or saw a medical practitioner. RESULTS: In total, 122 of 284 (43%) participants had at least 1 injury, for a total of 158 injuries. Fifty (32%) were prolonged, lasting at least 12 wk. Predictors of prolonged injury included older age (odds ratio [OR], 2.28, per 10-y increase; 95% CI, 1.31-3.96), hours per week spent climbing (OR, 1.14, per 1-h increase; 95% CI, 1.06-1.24), climbing difficulty (OR, 2.19, per difficulty group increase; 95% CI, 1.31-3.66), and years of climbing experience (OR, 3.99, per 5-y increase; 95% CI, 1.61-9.84). Only 38% of injuries were seen by a medical practitioner. Predictors of seeking care included prolonged injury (OR, 3.04; 95% CI, 1.39-6.64) and rope climbing preference (OR, 1.98; 95% CI, 1.02-3.82). The most common theme for seeking care was serious pain or interference with climbing or daily activities. CONCLUSIONS: Despite prolonged injuries being common, especially in older, more experienced, and higher-level climbers, only a third of climbers with injuries seek medical care. Outside of injuries causing minimal pain or limitation, those who self-managed reported receiving advice from other climbers or online research as a prominent reason for that choice.

RSV causes more severe respiratory illness than influenza in admitted children under 2-years-old.

INTRODUCTION: Both respiratory syncytial virus (RSV) and influenza-associated lower respiratory tract infections (LRTI) cause serious respiratory infections in infants and toddlers. We aimed to assess the frequency of complex hospital courses among patients admitted with influenza versus RSV LRTI. METHODS: A retrospective cohort study was performed on admissions of children <2 years who were admitted for LRTI and tested positive for influenza or RSV from 2016 to 2019. The primary outcome, complex hospital course, was a composite including: intensive care unit admission, respiratory support, nasogastric tube feeds, prolonged length of stay, and death. Secondary outcomes included 7-day readmission and time to respiratory support. Differences between RSV and influenza groups were assessed and unadjusted and adjusted regression models and competing risks time to event models were developed. RESULTS: There were 1094 (89%) RSV admissions and 134 (11%) influenza admissions. Children admitted for influenza were significantly older (336 vs. 165 days, p < 0.001), more likely to present with an abnormal heart rate for age (84.3% vs. 73.5%, p < 0.01) and a fever (27.6% vs. 18.9%, p = 0.02). Admissions with RSV were significantly more likely to experience a complex hospital course (ORadj = 3.5, 95% CI: 2.2-5.6). In time to event analysis, RSV admissions had a significantly higher rate of respiratory support (HRadj = 3.2, 95% CI: 2.0, 5.2). Readmission rates were similar. CONCLUSIONS: RSV admissions were associated with a higher risk for a complex hospital course and required higher rates of respiratory support than influenza admissions. This information may help in evaluating hospital resources and admissions.

Effect of restricting electronic health records on clinician efficiency: substudy of a randomized clinical trial.

A prior randomized controlled trial (RCT) showed no significant difference in wrong-patient errors between clinicians assigned to a restricted electronic health record (EHR) configuration (limiting to 1 record open at a time) versus an unrestricted EHR configuration (allowing up to 4 records open concurrently). However, it is unknown whether an unrestricted EHR configuration is more efficient. This substudy of the RCT compared clinician efficiency between EHR configurations using objective measures. All clinicians who logged onto the EHR during the substudy period were included. The primary outcome measure of efficiency was total active minutes per day. Counts were extracted from audit log data, and mixed-effects negative binomial regression was performed to determine differences between randomized groups. Incidence rate ratios (IRRs) were calculated with 95% confidence intervals (CIs). Among a total of 2556 clinicians, there was no significant difference between unrestricted and restricted groups in total active minutes per day (115.1 vs 113.3 min, respectively; IRR, 0.99; 95% CI, 0.93-1.06), overall or by clinician type and practice area.

Addiction Consult Service and Inpatient Outcomes Among Patients with Alcohol Use Disorder.

BACKGROUND: Alcohol use disorder (AUD) is the most prevalent substance use disorder, but evidence-based medications to treat AUD (MAUD), including naltrexone and acamprosate, are substantially underutilized. Hospitalization provides an opportunity to start MAUD for patients who may not otherwise seek treatment. Addiction consultation services (ACSs) have been increasingly utilized to ensure appropriate treatment. There is little research examining the effect of an ACS on health outcomes among patients with AUD. OBJECTIVE: To determine the association between an ACS consultation and provision of MAUD during admission and MAUD at discharge among admissions with AUD. DESIGN: Retrospective study comparing admissions which received an ACS consult and propensity score-matched historical control admissions. Subjects A total of 215 admissions with a primary or secondary diagnosis of AUD who received an ACS consult and 215 matched historical control admissions. Intervention ACS consultation from a multidisciplinary team offering withdrawal management, substance use disorder treatment, patient-centered counseling, discharge planning, and linkage to outpatient care for patients with substance use disorders, including AUD. Main Measures Primary outcomes were initiation of new MAUD during admission and new MAUD at discharge. Secondary outcomes were patient-directed discharge, time to 7- and 30-day readmission, and time to 7- and 30-day post-discharge ER visit. Key Results Among 430 admissions with AUD, those that received an ACS consultation were significantly more likely to receive new inpatient MAUD (33.0% vs 0.9%; OR 52.5 [CI 12.6-218.6]) and significantly more likely to receive new MAUD at discharge (41.4% vs 1.9%; OR 37.3 [13.3-104.6]), compared with historical controls. ACS was not significantly associated with patient-directed discharge, time to readmission, or time to post-discharge ER visit. CONCLUSIONS: ACS was associated with a large increase in provision of new inpatient MAUD and new MAUD at discharge when compared to propensity-matched historical controls.

Reducing Opioid Analgesic Prescribing in Dentistry Through Prescribing Defaults: A Cluster-Randomized Controlled Trial.

OBJECTIVE: To determine the effect of a uniform, reduced, default dispense quantity for new opioid analgesic prescriptions on the quantity of opioids prescribed in dentistry practices. METHODS: We conducted a cluster-randomized controlled trial within a health system in the Bronx, NY, USA. We randomly assigned three dentistry sites to a 10-tablet default, a 5-tablet default, or no change (control). The primary outcome was the quantity of opioid analgesics prescribed in the new prescription. Secondary outcomes were opioid analgesic reorders and health service utilization within 30 days after the new prescription. We analyzed outcomes from 6 months before implementation through 18 months after implementation. RESULTS: Overall, 6,309 patients received a new prescription. Compared with the control site, patients at the 10-tablet-default site had a significantly larger change in prescriptions for 10 tablets or fewer (38.7 percentage points; confidence interval [CI]: 11.5 to 66.0), lower number of tablets prescribed (-3.3 tablets; CI: -5.9 to -0.7), and lower morphine milligram equivalents (MME) prescribed (-14.1 MME; CI: -27.8 to -0.4), which persisted in the 30 days after the new prescription despite a higher percentage of reorders (3.3 percentage points; CI: 0.2 to 6.4). Compared with the control site, patients at the 5-tablet-default site did not have a significant difference in any outcomes except for a significantly higher percentage of reorders (2.6 percentage points; CI: 0.2 to 4.9). CONCLUSIONS: Our findings further support the efficacy of strategies that lower default dispense quantities, although they indicate that caution is warranted in the selection of the default. TRIAL REGISTRATION: ClinicalTrials.org ID: NCT03030469.

Factors Associated with Mortality in Coronavirus-Associated Mucormycosis: Results from Mycotic Infections in COVID-19 (MUNCO) Online Registry.

BACKGROUND: COVID-19-associated mucormycosis (CAM) is associated with high morbidity and mortality. MUNCO is an international database used to collect clinical data on cases of CAM in real time. Preliminary data from the Mycotic Infections in COVID-19 (MUNCO) online registry yielded 728 cases from May to September 2021 in four South Asian countries and the United States. A majority of the cases (694; 97.6%) consisted of a mucormycosis infection. The dataset allowed for the analysis of the risk factors for adverse outcomes from CAM and this analysis is presented in this paper. METHODS: The submission of cases was aided by a direct solicitation and social media online. The primary endpoints were full recovery or death measured on day 42 of the diagnosis. All patients had histopathologically confirmed CAM. The groups were compared to determine the contribution of each patient characteristic to the outcome. Multivariable logistic regression models were used to model the probability of death after a CAM diagnosis. RESULTS: The registry captured 694 cases of CAM. Within this, 341 could be analyzed as the study excluded patients with an unknown CAM recovery status due to either an interruption or a lack of follow up. The 341 viable cases consisted of 258 patients who survived after the completion of treatment and 83 patients who died during the period of observation. In a multivariable logistic regression model, the factors associated with an increased risk of mortality include old age (OR = 1.04, 95% CI 1.02-1.07, p = 0.001), history of diabetes mellitus (OR 3.5, 95% CI 1.01-11.9, p = 0.02) and a lower BMI (OR 0.9, 95% CI 0.82-0.98, p = 0.03). Mucor localized to sinus disease was associated with 77% reduced odds of death (OR = 0.23, 95% CI 0.09-0.57, p = 0.001), while cerebral mucor was associated with an increased odds of death (OR = 10.96, 95% CI 4.93-24.36, p = ≤0.0001). CONCLUSION: In patients with CAM, older age, a history of diabetes and a lower body mass index is associated with increased mortality. Disease limited to the sinuses without a cerebral extension is associated with a lower risk of mortality. Interestingly, the use of zinc and azithromycin were not associated with increased mortality in our study.

Critical Care Clinicians' Experiences of Patient Safety During the COVID-19 Pandemic.

OBJECTIVE: It is unknown how hospital- and systems-level factors have impacted patient safety in the intensive care unit (ICU) during the COVID-19 pandemic. We sought to understand how the pandemic has exacerbated preexisting patient safety issues and created novel patient safety challenges in ICUs in the United States. METHODS: We performed a national, multi-institutional, mixed-methods survey of critical care clinicians to elicit experiences related to patient safety during the pandemic. The survey was disseminated via email through the Society of Critical Care Medicine listserv. Data were reported as valid percentages, compared by COVID caseload and peak of the pandemic; free-text responses were analyzed and coded for themes. RESULTS: We received 335 survey responses. On general patient safety, 61% felt that conditions were more hazardous when compared with the prepandemic period. Those who took care of mostly COVID-19 patients were more likely to perceive that care was more hazardous (odds ratio, 4.89; 95% CI, 2.49-9.59) compared with those who took care of mostly non-COVID-19 or no COVID-19 patients. In free-text responses, providers identified patient safety risks related to pandemic adaptations, such as ventilator-related lung injury, medication and diagnostic errors, oversedation, oxygen device removal, and falls. CONCLUSIONS: Increased COVID-19 case burden was significantly associated with perceptions of a less safe patient care environment by frontline ICU clinicians. Results of the qualitative analysis identified specific patient safety hazards in ICUs across the United States as downstream consequences of hospital and provider strain during periods of the COVID-19 pandemic.

Early treatment with thiamine and mortality among patients with alcohol use disorder who are hospitalized for pneumonia.

BACKGROUND: The paucity of research linking thiamine treatment with improved outcomes may be driving its underutilization among patients at risk for Wernicke encephalopathy. OBJECTIVE: To assess relationships of thiamine usage to outcomes of patients hospitalized with alcohol use disorder and pneumonia. DESIGN, SETTING AND PARTICIPANTS: This is a retrospective cohort study of adult patients hospitalized with pneumonia who also have alcohol use disorder and were treated with benzodiazepines during the initial two hospital days, between 2010 and 2015 at hospitals participating in the Premier Healthcare Database. EXPOSURE: Any thiamine treatment, and, among those treated, high-dose thiamine treatment, during the initial two hospital days. MAIN OUTCOME AND MEASURES: Death on days 3-14 of hospitalization (primary); discharge home; transfer to intensive care unit; length of stay (LOS). We used propensity-weighted models to estimate treatment effects. RESULTS: Among 36,732 patients from 625 hospitals, 26,520 (72.2%) patients received thiamine, with mortality of 6.5% and 8.1% among recipients and nonrecipients, respectively. With propensity score adjustment, thiamine was associated with reduced mortality (odds ratio [OR]: 0.80, 95% confidence interval [CI]: 0.75-0.85) and more frequent discharges to home (OR: 1.10, 95% CI: 1.06-1.14). Other outcomes were similar. Relative to low-dose thiamine, high-dose thiamine was not associated with mortality (adjusted OR: 0.99, 95% CI: 0.89-1.10), but LOS was longer (ratio of means: 1.06, 95% CI: 1.04-1.08), and discharges to home were less frequent (OR: 0.92, 95% CI: 0.87-0.97). CONCLUSION: Thiamine is not reliably given to patients with pneumonia and alcohol use disorder receiving benzodiazepines. Improving thiamine administration may represent an opportunity to save lives in this high-risk group of inpatients.

Nucleotide- and Protein-Dependent Functions of Actg1.

Cytoplasmic ß- and γ-actin proteins are 99% identical but support unique organismal functions. The cytoplasmic actin nucleotide sequences Actb and Actg1, respectively, are more divergent but still 89% similar. Actb-/- mice are embryonic lethal and Actb-/- cells fail to proliferate, but editing the Actb gene to express γ-actin (Actbc-g) resulted in none of the overt phenotypes of the knockout revealing protein-independent functions for Actb. To determine if Actg1 has a protein-independent function, we crossed Actbc-g and Actg1-/- mice to generate the bG/0 line, where the only cytoplasmic actin expressed is γ-actin from Actbc-g. The bG/0 mice were viable but showed a survival defect despite expressing γ-actin protein at levels no different from bG/gG with normal survival. A unique myopathy phenotype was also observed in bG/0 mice. We conclude that impaired survival and myopathy in bG/0 mice are due to loss of Actg1 nucleotide-dependent function(s). On the other hand, the bG/0 genotype rescued functions impaired by Actg1-/-, including cell proliferation and auditory function, suggesting a role for γ-actin protein in both fibroblasts and hearing. Together, these results identify nucleotide-dependent functions for Actg1 while implicating γ-actin protein in more cell-/tissue-specific functions.

Association Between English Proficiency and Timing of Analgesia Administration After Surgery.

BACKGROUND: Pediatric patients from families with limited English proficiency (LEP) are at risk for health care disparities. We examined timeliness of analgesic administration in pediatric postoperative patients with a limb fracture from LEP versus non-LEP families. METHODS: This was a retrospective cohort study of children aged 1 year to <18 years of age, hospitalized to the general inpatient floor after surgical correction of single limb fractures between July 2016 and July 2019 were eligible. Patients whose consent was in a non-English language or for whom an interpreter was used were classified as from LEP families. The primary outcome was time to first analgesia. Secondary outcomes included time to first opioid, proportion with any analgesia and opioid analgesia, and number of pain assessments. Associations between LEP and outcomes were tested by using χ2 tests, Kaplan-Meier plots, and Cox proportional hazards models. RESULTS: We examined 306 patients, of whom 59 (19%) were from LEP families. Children in LEP families were significantly less likely to receive any analgesia (86.4% vs 96.8%, P ≤ .01) and experienced longer time to first analgesia in unadjusted (hazard ratio = 0.68, 95% confidence interval: 0.50-0.92) and adjusted analyses (hazard ratio = 0.68, 95% confidence interval: 0.50-0.94). There was no significant association between LEP and time to first opioid, proportion given opioid analgesia, or number of pain assessments. CONCLUSION: Hospitalized children from LEP families experience a longer time to analgesia administration after surgery. The mechanisms that lead to these differences in care must be identified so that interventions can be designed to address them.

SARS-CoV-2 coinfection with additional respiratory virus does not predict severe disease: a retrospective cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) claimed over 4 million lives by July 2021 and continues to pose a serious public health threat. OBJECTIVES: Our retrospective study utilized respiratory pathogen panel (RPP) results in patients with SARS-CoV-2 to determine if coinfection (i.e. SARS-CoV-2 positivity with an additional respiratory virus) was associated with more severe presentation and outcomes. METHODS: All patients with negative influenza/respiratory syncytial virus testing who underwent RPP testing within 7 days of a positive SARS-CoV-2 test at a large, academic medical centre in New York were examined. Patients positive for SARS-CoV-2 with a negative RPP were compared with patients positive for SARS-CoV-2 and positive for a virus by RPP in terms of biomarkers, oxygen requirements and severe COVID-19 outcome, as defined by mechanical ventilation or death within 30 days. RESULTS: Of the 306 SARS-CoV-2-positive patients with RPP testing, 14 (4.6%) were positive for a non-influenza virus (coinfected). Compared with the coinfected group, patients positive for SARS-CoV-2 with a negative RPP had higher inflammatory markers and were significantly more likely to be admitted (P = 0.01). Severe COVID-19 outcome occurred in 111 (36.3%) patients in the SARS-CoV-2-only group and 3 (21.4%) patients in the coinfected group (P = 0.24). CONCLUSIONS: Patients infected with SARS-CoV-2 along with a non-influenza respiratory virus had less severe disease on presentation and were more likely to be admitted-but did not have more severe outcomes-than those infected with SARS-CoV-2 alone.

Medical Student Personality Traits and Clinical Grades in the Internal Medicine Clerkship.

BACKGROUND: Third year clerkship grades include subjective evaluations. The purpose of this study is to identify if personality traits and self-esteem predispose students to better clerkship performance. METHODS: Third-year medical students completed the OCEAN Five Factor Model Personality Test and Rosenberg Self-Esteem Scale. Clerkship grades were matched to survey results. Chi-squared and linear regression analyses assessed the correlation between students' clerkship grades, personality traits, and self-esteem. RESULTS: There was no association between OCEAN personality domains and any component of clerkship grade. In secondary post hoc analysis, students who are "deep thinking" (OR 2.97, 95% CI 1.26-7.01, p = 0.01), "sophisticated" (OR 2.70, 95% CI 1.12-6.50, p = 0.03), and "outgoing" (OR 2.45, 95% CI 1.02-5.89, p = 0.04) were significantly more likely to get an overall clerkship grade of Honors. "Deep thinking" (OR 3.44, 95% CI 1.47-8.04, p = 0.004) and "efficient" (OR 2.87, 95% CI 1.12-7.36, p = 0.03) students scored better on shelf exams, while "shy" students scored worse (OR 0.30, 95% CI 0.13-0.69, p = 0.004); "aloof" students received worse clinical scores (OR 0.57, 95% CI 0.37-0.89, p = 0.03), and "rude" (OR 5.08, 95% CI 1.03-24.94, p = 0.03) and "sophisticated" (OR 2.47, 95% CI 1.02-6.00, p = 0.04) students received higher preceptor scores. There was no correlation between self-esteem and clerkship grades. CONCLUSION: Students with certain personality traits may be predisposed to success during clerkships. Medical educators should be cognizant of biases favoring certain personalities and help students maximize success by recognizing their strengths and identifying gaps.

Effect of Real-Time Feedback Devices on Primary Care Patient Experience Scores: A Cluster-Randomized Trial.

Patient experience is a critical measure for ambulatory primary care, although it is unclear how to best improve patient experience scores. This study aimed to determine whether use of a real-time feedback (RTF) device improved patient experience scores in a cluster-randomized trial. The primary outcomes were change from baseline in 9 Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) question and domain scores most closely related to the RTF questions asked in a linear mixed effects model. There were no observed statistically significant intervention-related differences in CG-CAHPS scores in any of the 9 CG-CAHPS questions or domains (P = .12-.99). In intervention clinics, there were no statistically significant correlation between CG-CAHPS top box scores and RTF device scores (P = .23-.98). Clinics in an urban primary care network randomized to receive RTF devices did not significantly improve related CG-CAHPS question or domain scores nor were those scores correlated with RTF device scores. More research is needed to identify effective interventions to improve ambulatory primary care patient experience.

Teamwork and Leadership Under Fire at the Epicenter of the COVID-19 Epidemic in the Bronx.

The first Covid-19 patient was admitted to Montefiore Medical Center (MMC) on March 10, 2020. Soon thereafter there was a rapid and exponential surge of Covid-19 admissions to MMC that could have resulted in catastrophic consequences if MMC had been overwhelmed, as happened in Europe. To adjust to this crisis our institution, under the inspiring leadership of Dr. Philip Ozuah, President and CEO of Montefiore Medicine, adopted an "all hands on deck" approach, mobilizing our entire workforce to expand our units to accommodate the growing number of patients being admitted. Given that the internal medicine (IM) and ICU units are part of the department of medicine (DOM), the DOM was at the center of this mobilization. The DOM is the largest department at MMC and mobilizing it required careful planning, seamless teamwork, and strong leadership. To achieve that goal, we applied a framework that we designate the "3C framework," denoting Coordination, Communication, and Collaboration. In this report we describe the many initiatives the Montefiore Einstein DOM implemented during the Covid-19 pandemic using the 3C framework. These included establishing the Medicine Covid-19 Taskforce to lead our efforts, starting a daily newsletter for up-to-date communications, rapidly expanding the ICU and IM units, converting most specialty inpatient consults to eConsults, coordinating research studies, and more. The goal of this report is to serve as a guide on how the 3C framework helped us organize, mobilize, and energize the department of medicine effectively and efficiently during this unprecedented crisis.

Effect of Changing Electronic Health Record Opioid Analgesic Dispense Quantity Defaults on the Quantity Prescribed: A Cluster Randomized Clinical Trial.

Importance: Interventions to improve judicious prescribing of opioid analgesics for acute pain are needed owing to the risks of diversion, misuse, and overdose. Objective: To assess the effect of modifying opioid analgesic prescribing defaults in the electronic health record (EHR) on prescribing and health service use. Design, Setting, and Participants: A cluster randomized clinical trial with 2 parallel arms was conducted between June 13, 2016, and June 13, 2018, in a large urban health care system comprising 32 primary care and 4 emergency department (ED) sites in the Bronx, New York. Data were analyzed using a difference-in-differences method from 6 months before implementation through 18 months after implementation. Data were analyzed from January 2019 to February 2020. Interventions: A default dispense quantity for new opioid analgesic prescriptions of 10 tablets (intervention) vs no change (control) in the EHR. Main Outcomes and Measures: The primary outcome was the quantity of opioid analgesics prescribed with the new default prescription. Secondary outcomes were opioid analgesic reorders and health service use within 30 days after the new prescription. Intention-to-treat analysis was conducted. Results: Overall, 21 331 patients received a new opioid analgesic prescription from 490 prescribers. Comparing the intervention and control arms, site, prescriber, and patient characteristics were similar. For the new prescription, compared with the control arm, patients in the intervention arm had significantly more prescriptions for 10 tablets or fewer (7.6 percentage points; 95% CI, 6.1-9.2 percentage points), a lower number of tablets prescribed (-2.1 tablets; 95% CI, -3.3 to -0.9 tablets), and lower morphine milligram equivalents (MME) prescribed (-14.6 MME; 95% CI, -22.6 to -6.6 MME). Within 30 days after the new prescription, significant differences remained in the number of tablets prescribed (-2.7 tablets; 95% CI, -4.8 to -0.6 tablets), but not MME (-15.8 MME; 95% CI, -33.8 to 2.2 MME). Within this 30-day period, there were no significant differences between the arms in health service use. Conclusions and Relevance: In this study, implementation of a uniform reduced default dispense quantity of 10 tablets for opioid analgesic prescriptions led to a modest reduction in the quantity prescribed initially, without significantly increasing health service use. However, during 30 days after implementation, the influence on prescribing was mixed. Reducing EHR default dispense quantities for opioid analgesics is a feasible strategy that can be widely disseminated and may modestly reduce prescribing. Trial Registration: ClinicalTrials.gov Identifier: NCT03003832.

Early and Significant Reduction in C-Reactive Protein Levels After Corticosteroid Therapy Is Associated With Reduced Mortality in Patients With COVID-19.

BACKGROUND: Corticosteroids may be beneficial in a subset of patients with coronavirus disease 2019 (COVID-19), but predictors of therapeutic response remain unknown. C-reactive protein (CRP) is a routinely measured biomarker, and reduction in its levels after initiation of therapy may predict inpatient mortality. METHODS: In this retrospective cohort study, the charts of patients who were admitted to Montefiore Medical Center between March 10, 2020, and May 2, 2020 for the management of COVID-19 were examined. Of all patients who met inclusion criteria, patients who received corticosteroid treatment were categorized as CRP responders (≥50% CRP level reduction) and CRP nonresponders (<50% CRP level reduction) based on change in CRP within 72 hours of corticosteroid treatment initiation. The outcomes of interest were two-fold: (1) CRP response after treatment with corticosteroid, and (2) differences in mortality among patients with CRP response compared those without. RESULTS: Of 2,707 patients admitted during the study period, 324 received corticosteroid treatment. Of patients who received corticosteroid treatment, CRP responders had reduced risk of death compared with risk among CRP nonresponders (25.2% vs 47.8%; unadjusted odds ratio [OR], 0.37; 95% CI, 0.21-0.65; P <.001). This effect remained strong and significant after adjustment for potential confounders (adjusted OR, 0.27; 95% CI, 0.14-0.54; P <.001). CONCLUSION: Reduction in CRP by 50% or more within 72 hours of initiating corticosteroid therapy potentially predicts inpatient mortality. This may serve as an early biomarker of response to corticosteroid therapy in patients with COVID-19.