Comparison of registered and published outcomes in randomized controlled trials: a systematic review.

BACKGROUND: Clinical trial registries can improve the validity of trial results by facilitating comparisons between prospectively planned and reported outcomes. Previous reports on the frequency of planned and reported outcome inconsistencies have reported widely discrepant results. It is unknown whether these discrepancies are due to differences between the included trials, or to methodological differences between studies. We aimed to systematically review the prevalence and nature of discrepancies between registered and published outcomes among clinical trials. METHODS: We searched MEDLINE via PubMed, EMBASE, and CINAHL, and checked references of included publications to identify studies that compared trial outcomes as documented in a publicly accessible clinical trials registry with published trial outcomes. Two authors independently selected eligible studies and performed data extraction. We present summary data rather than pooled analyses owing to methodological heterogeneity among the included studies. RESULTS: Twenty-seven studies were eligible for inclusion. The overall risk of bias among included studies was moderate to high. These studies assessed outcome agreement for a median of 65 individual trials (interquartile range [IQR] 25-110). The median proportion of trials with an identified discrepancy between the registered and published primary outcome was 31%; substantial variability in the prevalence of these primary outcome discrepancies was observed among the included studies (range 0% (0/66) to 100% (1/1), IQR 17-45%). We found less variability within the subset of studies that assessed the agreement between prospectively registered outcomes and published outcomes, among which the median observed discrepancy rate was 41% (range 30% (13/43) to 100% (1/1), IQR 33-48%). The nature of observed primary outcome discrepancies also varied substantially between included studies. Among the studies providing detailed descriptions of these outcome discrepancies, a median of 13 % of trials introduced a new, unregistered outcome in the published manuscript (IQR 5-16%). CONCLUSIONS: Discrepancies between registered and published outcomes of clinical trials are common regardless of funding mechanism or the journals in which they are published. Consistent reporting of prospectively defined outcomes and consistent utilization of registry data during the peer review process may improve the validity of clinical trial publications.

Malnutrition among cognitively intact, noncritically ill older adults in the emergency department.

STUDY OBJECTIVE: We estimate the prevalence of malnutrition among older patients presenting to an emergency department (ED) in the southeastern United States and identify subgroups at increased risk. METHODS: We conducted a cross-sectional study with random time block sampling of cognitively intact patients aged 65 years and older. Nutrition was assessed with the Mini Nutritional Assessment Short-Form (0 to 14 scale), with malnutrition defined as a score of 7 or less and at risk for malnutrition defined as a score of 8 to 11. The presence of depressive symptoms was defined as a Center for Epidemiological Studies Depression-10 score of 4 or more (0 to 10 scale). RESULTS: Among 138 older adults, 16% (95% confidence interval [CI] 11% to 23%) were malnourished and 60% (95% CI 52% to 68%) were either malnourished or at risk for malnutrition. Seventeen of the 22 malnourished patients (77%) denied previously receiving a diagnosis of malnutrition. The prevalence of malnutrition was not appreciably different between men and women, across levels of patient education, or between those living in urban and rural areas. However, the prevalence of malnutrition was higher among patients with depressive symptoms (52%), those residing in assisted living (44%), those with difficulty eating (38%), and those reporting difficulty buying groceries (33%). CONCLUSION: Among a random sample of cognitively intact older ED patients, more than half were malnourished or at risk for malnutrition, and the majority of malnourished patients had not previously received a diagnosis. Higher rates of malnutrition among individuals with depression, difficulty eating, and difficulty buying groceries suggest the need to explore multifaceted interventions.

Implementation strategies to address the determinants of adoption, implementation, and maintenance of a clinical decision support tool for emergency department buprenorphine initiation: a qualitative study.

BACKGROUND: Untreated opioid use disorder (OUD) is a significant public health problem. Buprenorphine is an evidence-based treatment for OUD that can be initiated in and prescribed from emergency departments (EDs) and office settings. Adoption of buprenorphine initiation among ED clinicians is low. The EMBED pragmatic clinical trial investigated the effectiveness of a clinical decision support (CDS) tool to promote ED clinicians' behavior related to buprenorphine initiation in the ED. While the CDS intervention was not associated with increased rates of buprenorphine treatment for patients with OUD at intervention ED sites, attending physicians at intervention EDs were more likely to initiate buprenorphine at least once over the duration of the study compared to those in the usual care arms (44.4% vs 34.0%, P = 0.01). This suggests the CDS intervention may be associated with increased adoption of buprenorphine initiation. As a secondary aim, we sought to identify the determinants of CDS adoption, implementation, and maintenance in a variety of ED settings and geographic locations. METHODS: We purposively sampled and conducted semi-structured, in-depth interviews with clinicians across EMBED trial sites randomized to the intervention arm from five healthcare systems. Interviews elicited clinician experiences regarding buprenorphine initiation and CDS use. Interviews were analyzed using directed content analysis informed by the Practical, Robust Implementation and Sustainability Model (PRISM). We used a hybrid approach (a priori codes informed by PRISM and emergent codes) for codebook development. ATLAS.ti (version 9.0) was used for data management. Coded data were analyzed within individual interview transcripts and across all interviews to identify major themes. This process involved (1) combining, comparing, and making connections between codes; (2) writing analytic memos about observed patterns; and (3) frequent team meetings to discuss emerging patterns. RESULTS: Twenty-eight interviews were conducted. Major themes that influenced the successful adoption, implementation, and maintenance of the EMBED intervention and ED-initiated BUP were organizational culture and commitment, clinician training and support, the ability to connect patients to ongoing treatment, and the ability to tailor implementation to each ED. These findings informed the identification of implementation strategies (framed using PRISM domains) to enhance the ED initiation of buprenorphine. CONCLUSION: The findings from this qualitative analysis can provide guidance to build better systems to promote the adoption of ED-initiated buprenorphine.

Racial and ethnic disparities in emergency department-initiated buprenorphine across five health care systems.

BACKGROUND: Opioid overdose deaths have disproportionately impacted Black and Hispanic populations, in part due to disparities in treatment access. Emergency departments (EDs) serve as a resource for patients with opioid use disorder (OUD), many of whom have difficulty accessing outpatient addiction programs. However, inequities in ED treatment for OUD remain poorly understood. METHODS: This secondary analysis examined racial and ethnic differences in buprenorphine access using data from EMBED, a study of 21 EDs across five health care systems evaluating a clinical decision support system for initiating ED buprenorphine. The primary outcome was receipt of buprenorphine, ED administered or prescribed. Hospital type (academic vs. community) was evaluated as an effect modifier. Hierarchical models with cluster effects for site and clinician were used to assess buprenorphine receipt by race and ethnicity. RESULTS: Black patients were less likely to receive buprenorphine (6.4% [51/801] vs. White patients 8.5% [268/3154], odds ratio [OR] 0.59, 95% confidence interval [CI] 0.45-0.78). This association persisted after adjusting for age, insurance, gender, clinician X-waiver, hospital type, and urbanicity (adjusted OR [aOR] 0.64, 95% CI 0.48-0.84) but not when discharge diagnosis was included (aOR 0.75, 95% CI 0.56-1.02). Hispanic patients were more likely to receive buprenorphine (14.8% [122/822] vs. non-Hispanic patients, 11.6% [475/4098]) in unadjusted (OR 1.57, 95% CI 1.09-1.83) and adjusted models (aOR 1.41, 95% CI 1.08-1.83) but not including discharge diagnosis (aOR 1.32, 95% CI 0.99-1.77). Odds of buprenorphine were similar in academic and community EDs by race (interaction p = 0.97) and ethnicity (interaction p = 0.64). CONCLUSIONS: Black patients with OUD were less likely to receive buprenorphine whereas Hispanic patients were more likely to receive buprenorphine in academic and community EDs. Differences were attenuated with discharge diagnosis, as fewer Black and non-Hispanic patients were diagnosed with opioid withdrawal. Barriers to medication treatment are heterogenous among patients with OUD; research must continue to address the multiple drivers of health inequities at the patient, clinician, and community level.

Interrupted Time Series of User-centered Clinical Decision Support Implementation for Emergency Department-initiated Buprenorphine for Opioid Use Disorder.

OBJECTIVES: Adoption of emergency department (ED) initiation of buprenorphine (BUP) for opioid use disorder (OUD) into routine emergency care has been slow, partly due to clinicians' unfamiliarity with this practice and perceptions that it is complicated and time-consuming. To address these barriers and guide emergency clinicians through the process of BUP initiation, we implemented a user-centered computerized clinical decision support system (CDS). This study was conducted to assess the feasibility of implementation and to evaluate the preliminary efficacy of the intervention to increase the rate of ED-initiated BUP. METHODS: An interrupted time series study was conducted in an urban, academic ED from April 2018 to February 2019 (preimplementation phase), March 2019 to August 2019 (implementation phase), and September 2019 to December 2019 (maintenance phase) to study the effect of the intervention on adult ED patients identified by a validated electronic health record (EHR)-based computable phenotype consisting of structured data consistent with potential cases of OUD who would benefit from BUP treatment. The intervention offers flexible CDS for identification of OUD, assessment of opioid withdrawal, and motivation of readiness to start treatment and automates EHR activities related to ED initiation of BUP (including documentation, orders, prescribing, and referral). The primary outcome was the rate of ED-initiated BUP. Secondary outcomes were launch of the intervention, prescription for naloxone at ED discharge, and referral for ongoing addiction treatment. RESULTS: Of the 141,041 unique patients presenting to the ED over the preimplementation and implementation phases (i.e., the phases used in primary analysis), 906 (574 preimplementation and 332 implementation) met OUD phenotype and inclusion criteria. The rate of BUP initiation increased from 3.5% (20/574) in the preimplementation phase to 6.6% (22/332) in the implementation phase (p = 0.03). After the temporal trend of the number of physician's with X-waiver training and other covariates were adjusted for, the relative risk of BUP initiation rate was 2.73 (95% confidence interval [CI] = 0.62 to 12.0, p = 0.18). Similarly, the number of unique attendings who initiated BUP increased modestly 7/53 (13.0%) to 13/57 (22.8%, p = 0.10) after offering just-in-time training during the implementation period. The rate of naloxone prescribed at discharge also increased (6.5% preimplementation and 11.5% implementation; p < 0.01). The intervention received a system usability scale score of 82.0 (95% CI = 76.7 to 87.2). CONCLUSION: Implementation of user-centered CDS at a single ED was feasible, acceptable, and associated with increased rates of ED-initiated BUP and naloxone prescribing in patients with OUD and a doubling of the number of unique physicians adopting the practice. We have implemented this intervention across several health systems in an ongoing trial to assess its effectiveness, scalability, and generalizability.

Progress Report on EMBED: A Pragmatic Trial of User-Centered Clinical Decision Support to Implement EMergency Department-Initiated BuprenorphinE for Opioid Use Disorder.

Buprenorphine (BUP) can safely and effectively reduce craving, overdose, and mortality rates in people with opioid use disorder (OUD). However, adoption of ED-initiation of BUP has been slow partly due to physician perception this practice is too complex and disruptive. We report progress of the ongoing EMBED (EMergency department-initiated BuprenorphinE for opioid use Disorder) project. This project is a five-year collaboration across five healthcare systems with the goal to develop, integrate, study, and disseminate user-centered Clinical Decision Support (CDS) to promote the adoption of Emergency Department (ED)-initiation of buprenorphine/naloxone (BUP) into routine emergency care. Soon to enter its third year, the project has already completed multiple milestones to achieve its goals including (1) user-centered design of the CDS prototype, (2) integration of the CDS into an automated electronic health record (EHR) workflow, (3) data coordination including derivation and validation of an EHR-based computable phenotype, (4) meeting all ethical and regulatory requirements to achieve a waiver of informed consent, (5) pilot testing of the intervention at a single site, and (6) launching a parallel group-randomized 18-month pragmatic trial in 20 EDs across 5 healthcare systems. Pilot testing of the intervention in a single ED was associated with increased rates of ED-initiated BUP and naloxone prescribing and a doubling of the number of unique physicians adopting the practice. The ongoing multi-center pragmatic trial will assess the intervention's effectiveness, scalability, and generalizability with a goal to shift the emergency care paradigm for OUD towards early identification and treatment. TRIAL REGISTRATION: Clinicaltrials.gov # NCT03658642.

An integrated web application for decision support and automation of EHR workflow: a case study of current challenges to standards-based messaging and scalability from the EMBED trial.

Computerized clinical decision support (CDS) faces challenges to interoperability and scalability. Centralized, web-based solutions offer a mechanism to share the cost of CDS development, maintenance, and implementation across practices. Data standards have emerged to facilitate interoperability and rapid integration of such third-party CDS. This case report describes the challenges to implementation and scalability of an integrated, web-based CDS intervention for EMergency department-initiated BuprenorphinE for opioid use Disorder which will soon be evaluated in a trial across 20 sites in five healthcare systems. Due to limitations of current standards, security concerns, and the need for resource-intensive local customization, barriers persist related to centralized CDS at this scale. These challenges demonstrate the need and importance for future standards to support two-way messaging (read and write) between electronic health records and web applications, thus allowing for more robust sharing across health systems and decreasing redundant, resource-intensive CDS development at individual sites.

A Prospective Evaluation of Shared Decision-making Regarding Analgesics Selection for Older Emergency Department Patients With Acute Musculoskeletal Pain.

OBJECTIVES: Musculoskeletal pain is a common reason for emergency department (ED) visit by older adults. Outpatient pain management following ED visits in this population is challenging as a result of contraindications to, and side effects from, available therapies. Shared decision-making (SDM) between patients and emergency physicians may improve patient experiences and health outcomes. Among older ED patients with acute musculoskeletal pain, we sought to characterize their desire for involvement in the selection of outpatient analgesics. We also sought to assess the impact of SDM on change in pain at 1 week, patient satisfaction, and side effects. METHODS: This was a prospective study of adults aged 60 years and older presenting to the ED with acute musculoskeletal pain. Participants' desire to contribute to outpatient analgesic selection was assessed by phone within 24 hours of ED discharge using the Control Preferences Scale and categorized as active, collaborative, or passive. The extent to which SDM occurred in the ED was also assessed within 24 hours of discharge using the 9-item Shared Decision Making Questionnaire, and scores were subsequently grouped into tertiles of low, middle, and high SDM. The primary outcome was change in pain severity between the ED visit and 1 week. Secondary outcomes included satisfaction regarding the decision about how to treat pain at home, satisfaction with the pain medication itself, and side effects. RESULTS: Desire of participants (N = 94) to contribute to the decision regarding selection of outpatient analgesics varied: 16% active (i.e., make the final decision themselves), 37% collaborative (i.e., share decision with provider), and 47% passive (i.e., let the doctor make the final decision). The percentage of patients who desired an active role in the decision was higher for patients who were college educated versus those who were not college educated (28% vs. 11%; difference 17%, 95% confidence interval [CI] = 0% to 35%), received care from a nurse practitioner versus a resident or an attending physician (32% vs. 9%; difference 23%, 95% CI = 4% to 42%), or received care from a female versus a male provider (24% vs. 5%; difference 19%, 95% = CI 5% to 32%). After potential confounders were adjusted for, the mean decrease in pain severity from the ED visit to 1-week follow-up was not significantly different across tertiles of SDM (p = 0.06). Higher SDM scores were associated with greater satisfaction with the discharge pain medications (p = 0.006). SDM was not associated with the class of analgesic received. CONCLUSIONS: In this sample of older adults with acute musculoskeletal pain, the reported desire of patients to contribute to decisions regarding analgesics varied based on both patient and provider characteristics. SDM was not significantly related to pain reduction in the first week or type of pain medication received, but was associated with greater patient satisfaction.

Willingness and Ability of Older Adults in the Emergency Department to Provide Clinical Information Using a Tablet Computer.

OBJECTIVES: To estimate the proportion of older adults in the emergency department (ED) who are willing and able to use a tablet computer to answer questions. DESIGN: Prospective, ED-based cross-sectional study. SETTING: Two U.S. academic EDs. PARTICIPANTS: Individuals aged 65 and older. MEASUREMENTS: As part of screening for another study, potential study participants were asked whether they would be willing to use a tablet computer to answer eight questions instead of answering questions orally. A custom user interface optimized for older adults was used. Trained research assistants observed study participants as they used the tablets. Ability to use the tablet was assessed based on need for assistance and number of questions answered correctly. RESULTS: Of 365 individuals approached, 248 (68%) were willing to answer screening questions, 121 of these (49%) were willing to use a tablet computer; of these, 91 (75%) were able to answer at least six questions correctly, and 35 (29%) did not require assistance. Only 14 (12%) were able to answer all eight questions correctly without assistance. Individuals aged 65 to 74 and those reporting use of a touchscreen device at least weekly were more likely to be willing and able to use the tablet computer. Of individuals with no or mild cognitive impairment, the percentage willing to use the tablet was 45%, and the percentage answering all questions correctly was 32%. CONCLUSION: Approximately half of this sample of older adults in the ED was willing to provide information using a tablet computer, but only a small minority of these were able to enter all information correctly without assistance. Tablet computers may provide an efficient means of collecting clinical information from some older adults in the ED, but at present, it will be ineffective for a significant portion of this population.