Do goals of care documentation reflect the conversation?: Evaluating conversation-documentation accuracy.

BACKGROUND: Documenting goals of care in the electronic health record is meant to relay patient preferences to other clinicians. Evaluating the content and documentation of nurse and social worker led goals of care conversations can inform future goals of care initiative efforts. METHODS: As part of the ADvancing symptom Alleviation with Palliative Treatment trial, this study analyzed goals of care conversations led by nurses and social workers and documented in the electronic health record. Informed by a goals of care communication guide, we identified five goals of care components: illness understanding, goals and values, end of life planning, surrogate, and advance directives. Forty conversation transcripts underwent content analysis. Through an iterative team process, we defined documentation accuracy as four categories: (1) Complete-comprehensive accurate documentation of the conversation, (2) Incomplete-partial documentation of the conversation, (3) Missing-discussed and not documented, and (4) Incorrect-misrepresented in documentation. We also defined-Not Discussed-for communication guide questions that were not discussed nor documented. A constant comparative approach was used to determine the presence or absence of conversation content in the documentation. RESULTS: All five goals of care components were discussed in 67% (27/40) of conversation transcripts. Compared to the transcripts, surrogate (37/40, 93%) and advance directives (36/40, 90%) were often documented completely. Almost 40% of goals and values (15/40, 38%) and half of end of life planning (19/40, 48%) were incomplete. Illness understanding was missing (13/40, 33%), not discussed (13/40, 33%), or incorrect (2/40, 5%). CONCLUSION: Nurse and social worker led goals of care conversations discussed and documented most components of the goals of care communication guide. Further research may guide how best to determine the relative importance of accuracy, especially in the broad setting of incomplete, missing, and incorrect EHR documentation.

Drivers of Decision-Making for Adult Tracheostomy for Prolonged Mechanical Ventilation: A Qualitative Study.

Background: Decision-making about tracheostomy and prolonged mechanical ventilation (PMV) is emotionally complex. Expectations of surrogate decision-makers and physicians rarely align. Little is known about what surrogates need to make goal-concordant decisions. We sought to identify drivers of tracheostomy and PMV decision-making. Methods: Using Grounded Theory, we performed a qualitative study with semi-structured interviews with surrogates of patients receiving mechanical ventilation (MV) being considered for tracheostomy and physicians routinely caring for patients receiving MV. Recruitment was stopped when thematic saturation was reached. Separate codebooks were created for surrogate and physician interviews. Themes and factors affecting decision-making were identified and a theoretical model tracheostomy decision-making was developed. Results: 43 participants (23 surrogates and 20 physicians) completed interviews. A theoretical model of themes and factors driving decision-making emerged for the data. Hope, Lack of Knowledge & Data, and Uncertainty emerged as the three main themes all which were interconnected with one another and, at times, opposed each other. Patient Wishes, Past Activity/Medical History, Short and Long-Term Outcomes, and Meaningful Recovery were key factors upon which surrogates and physicians based decision-making. The themes were the lens through which the factors were viewed and decision-making existed as a balance between surrogate emotions and understanding and physician recommendations. Conclusions: Tracheostomy and prolonged MV decision-making is complex. Hope and Uncertainty were conceptual themes that often battled with one another. Lack of Knowledge & Data plagued both surrogates and physicians. Multiple tangible factors were identified that affected surrogate decision-making and physician recommendations. Implications: Understanding this complex decision-making process has the potential to improve the information provided to surrogates and, potentially, increase the goal concordant care and alignment of surrogate and physician expectations. Highlights: Decision-making for tracheostomy and prolonged mechanical ventilation is a complex interactive process between surrogate decision-makers and providers.Using a Grounded Theory framework, a theoretical model emerged from the data with core themes of Hope, Uncertainty, and Lack of Knowledge & Data that was shared by both providers and surrogates.The core themes were the lenses through which the key decision-making factors of Patient Wishes, Past Activity/Medical History, Short and Long-Term Outcomes, and Meaningful Recovery were viewed.The theoretical model provides a roadmap to design a shared decision-making intervention to improve tracheostomy and prolonged mechanical ventilation decision-making.

Nurse and Social Worker Palliative Telecare Team and Quality of Life in Patients With COPD, Heart Failure, or Interstitial Lung Disease: The ADAPT Randomized Clinical Trial.

Importance: Many patients with chronic obstructive pulmonary disease (COPD), heart failure (HF), and interstitial lung disease (ILD) endure poor quality of life despite conventional therapy. Palliative care approaches may benefit this population prior to end of life. Objective: Determine the effect of a nurse and social worker palliative telecare team on quality of life in outpatients with COPD, HF, or ILD compared with usual care. Design, Setting, and Participants: Single-blind, 2-group, multisite randomized clinical trial with accrual between October 27, 2016, and April 2, 2020, in 2 Veterans Administration health care systems (Colorado and Washington), and including community-based outpatient clinics. Outpatients with COPD, HF, or ILD at high risk of hospitalization or death who reported poor quality of life participated. Intervention: The intervention involved 6 phone calls with a nurse to help with symptom management and 6 phone calls with a social worker to provide psychosocial care. The nurse and social worker met weekly with a study primary care and palliative care physician and as needed, a pulmonologist, and cardiologist. Usual care included an educational handout developed for the study that outlined self-care for COPD, ILD, or HF. Patients in both groups received care at the discretion of their clinicians, which could include care from nurses and social workers, and specialists in cardiology, pulmonology, palliative care, and mental health. Main Outcomes and Measures: The primary outcome was difference in change in quality of life from baseline to 6 months between the intervention and usual care groups (FACT-G score range, 0-100, with higher scores indicating better quality of life, clinically meaningful change ≥4 points). Secondary quality-of-life outcomes at 6 months included disease-specific health status (Clinical COPD Questionnaire; Kansas City Cardiomyopathy Questionnaire-12), depression (Patient Health Questionnaire-8) and anxiety (Generalized Anxiety Disorder-7) symptoms. Results: Among 306 randomized patients (mean [SD] age, 68.9 [7.7] years; 276 male [90.2%], 30 female [9.8%]; 245 White [80.1%]), 177 (57.8%) had COPD, 67 (21.9%) HF, 49 (16%) both COPD and HF, and 13 (4.2%) ILD. Baseline FACT-G scores were similar (intervention, 52.9; usual care, 52.7). FACT-G completion was 76% (intervention, 117 of 154; usual care, 116 of 152) at 6 months for both groups. Mean (SD) length of intervention was 115.1 (33.4) days and included a mean of 10.4 (3.3) intervention calls per patient. In the intervention group, 112 of 154 (73%) patients received the intervention as randomized. At 6 months, mean FACT-G score improved 6.0 points in the intervention group and 1.4 points in the usual care group (difference, 4.6 points [95% CI, 1.8-7.4]; P = .001; standardized mean difference, 0.41). The intervention also improved COPD health status (standardized mean difference, 0.44; P = .04), HF health status (standardized mean difference, 0.41; P = .01), depression (standardized mean difference, -0.50; P < .001), and anxiety (standardized mean difference, -0.51; P < .001) at 6 months. Conclusions and Relevance: For adults with COPD, HF, or ILD who were at high risk of death and had poor quality of life, a nurse and social worker palliative telecare team produced clinically meaningful improvements in quality of life at 6 months compared with usual care. Trial Registration: ClinicalTrials.gov Identifier: NCT02713347.

Criteria for Enrollment of Patients With COPD in Palliative Care Trials: A Systematic Review.

CONTEXT: Use of palliative care interventions in chronic obstructive pulmonary disease (COPD) has increased in recent years and inclusion criteria used to identify patients with COPD appropriate for palliative care vary widely. We evaluated the inclusion criteria to identify ways to improve enrollment opportunities for patients with COPD. OBJECTIVES: To determine inclusion criteria used to select patients with COPD for palliative care trials. METHODS: A systematic review was conducted to determine criteria used to select patients with COPD for palliative care randomized controlled trials. A narrative synthesis was conducted for all trials. RESULTS: Inclusion criteria were highly heterogeneous. Most studies (n = 11, 79%) used a combination of criteria to identify patients with COPD. Commonly used criteria included hospitalization for an acute exacerbation of COPD (n = 8, 57%), home supplemental oxygen use (n = 8, 57%), and spirometry values confirming COPD (n = 6, 43%). Three studies (21.4%) used Modified Medical Research Council score and two studies (21%) used physician prognosis or a performance scale. CONCLUSION: The most common criteria, a hospitalization for acute exacerbation of COPD or supplemental oxygen use at home, both have the benefit of selecting patients who have a higher symptom burden or higher healthcare utilization who might therefore benefit more from palliative care. By describing the landscape and variability of previously used inclusion criteria, this article serves as a resource for clinicians and researchers. Developing a consistent set of inclusion criteria in the future would help generate generalizable results that can be translated into clinical practice to improve the lives of patients with COPD. PROSPERO REGISTRATION NUMBER: CRD42022306752.

How Important is Spirometry for Identifying Patients with COPD Appropriate for Palliative Care?

BACKGROUND: Providing palliative care to patients with chronic obstructive pulmonary disease (COPD) is a priority. Spirometry demonstrating airflow limitation is a diagnostic test for COPD and a common inclusion criterion for palliative care research. However, requiring spirometry with airflow limitation may exclude appropriate patients unable to complete spirometry, or patients with preserved-ratio impaired spirometry and symptoms or imaging consistent with COPD. MEASURES: To determine differences in quality of life (QOL) and symptoms between patients with COPD identified based on International Classification of Diseases (ICD) codes and spirometry with airflow limitation compared to ICD codes only. INTERVENTION: Patients with COPD enrolled in a palliative care trial were included. Patients were at high risk of hospitalization and death and reported poor QOL. Baseline measures of QOL (Functional Assessment of Cancer Therapy-General (FACT-G), the Clinical COPD Questionnaire, and Quality of Life at the End of Life), and symptoms (Patient Health Questionnaire-8, Generalized Anxiety Disorder-7, fatigue, Insomnia Severity Index) were compared. OUTCOMES: Two hundred eight patients with COPD were predominantly male, White, and average age was 68.4. Between patients with ICD codes and spirometry with airflow limitation compared to patients with ICD codes only, there were no significant differences in FACT-G (59.0 vs. 55.0, P = 0.33), other measures of QOL, or symptoms between groups. CONCLUSION: These results imply that spirometry may not need to be a requirement for inclusion into palliative care research or clinical care for patients with poor quality of life and at high risk for adverse outcomes.

Reliability, Validity, and Responsiveness of the DEG, a Three-Item Dyspnea Measure.

BACKGROUND: Dyspnea is a common and debilitating symptom that affects many different patient populations. Dyspnea measures should assess multiple domains. OBJECTIVE: To evaluate the reliability, validity, and responsiveness of an ultra-brief, multi-dimensional dyspnea measure. DESIGN: We adapted the DEG from the PEG, a valid 3-item pain measure, to assess average dyspnea intensity (D), interference with enjoyment of life (E), and dyspnea burden with general activity (G). PARTICIPANTS: We used data from a multi-site randomized clinical trial among outpatients with heart failure. MAIN MEASURES: We evaluated reliability (Cronbach's alpha), concurrent validity with the Memorial-Symptom-Assessment-Scale (MSAS) shortness-of-breath distress-orbothersome item and 7-item Generalized-Anxiety-Disorder (GAD-7) scale, knowngroups validity with New-York-Heart-Association-Functional-Classification (NYHA) 1-2 or 3-4 and presence or absence of comorbid chronic obstructive pulmonary disease (COPD), responsiveness with the MSAS item as an anchor, and calculated a minimal clinically important difference (MCID) using distribution methods. KEY RESULTS: Among 312 participants, the DEG was reliable (Cronbach's alpha 0.92). The mean (standard deviation) DEG score was 5.26 (2.36) (range 0-10) points. DEG scores correlated strongly with the MSAS shortness of breath distress-or-bothersome item (r=0.66) and moderately with GAD-7 categories (ρ=0.36). DEG scores were statistically significantly lower among patients with NYHA 1-2 compared to 3-4 [mean difference (standard error): 1.22 (0.27) points, p<0.01], and those without compared to with comorbid COPD [0.87 (0.27) points, p<0.01]. The DEG was highly sensitive to change, with MCID of 0.59-1.34 points, or 11-25% change. CONCLUSIONS: The novel, ultra-brief DEG measure is reliable, valid, and highly responsive. Future studies should evaluate the DEG's sensitivity to interventions, use anchor-based methods to triangulate MCID estimates, and determine its prognostic usefulness among patients with chronic cardiopulmonary and other diseases.

Assessing efficacy of intravenous acetaminophen for perioperative pain control for oocyte retrieval: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the effect of preoperative intravenous (IV) acetaminophen versus oral (PO) acetaminophen or placebo on postoperative pain scores and the time to discharge in women undergoing oocyte retrieval. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Single academic fertility center. PATIENT(S): Women aged 18-43 years undergoing oocyte retrieval. INTERVENTION(S): Randomization to preoperative 1,000 mg IV acetaminophen and PO placebo (group A), IV placebo and 1,000 mg PO acetaminophen (group B), or IV and PO placebo (group C) MAIN OUTCOME MEASURE(S): Difference in patient-reported postoperative visual analog scale pain scores from baseline and the time to discharge. RESULT(S): Of the 159 women who completed the study, there were no differences in the mean postoperative pain score differences or the time to discharge. Although not statistically significant, the mean postoperative opioid dose requirement in group A was lower than that in groups B and C (0.24 vs. 0.59 vs. 0.58 mg IV morphine equivalents, respectively) due to fewer women in group A requiring rescue pain medication (8% vs. 19% vs. 15%, respectively). Group A also reported less constipation when compared with groups B and C (19% vs. 33% vs. 40%, respectively). The rates of postoperative nausea were similar, and there were no differences in embryology or early pregnancy outcomes between the study groups. CONCLUSION(S): Preoperative IV acetaminophen for women undergoing oocyte retrieval did not reduce postoperative pain scores or shorten the time to discharge when compared with PO acetaminophen or placebo and, thus, cannot currently be recommended routinely in this patient population. CLINICAL TRIAL REGISTRATION NUMBER: NCT03073980.

Dissecting the roles of Cse1 and Nup2 in classical NLS-cargo release in vivo.

The importin α/ß transport machinery mediates the nuclear import of cargo proteins that bear a classical nuclear localization sequence (cNLS). These cargo proteins are linked to the major nuclear protein import factor, importin-ß, by the importin-α adapter, after which cargo/carrier complexes enter the nucleus through nuclear pores. In the nucleus, cargo is released by the action of RanGTP and the nuclear pore protein Nup2, after which the importins are recycled to the cytoplasm for further transport cycles. The nuclear export of importin-α is mediated by Cse1/CAS. Here, we exploit structures of functionally important complexes to identify residues that are critical for these interactions and provide insight into how cycles of protein import and recycling of importin-α occur in vivo using a Saccharomyces cerevisiae model. We examine how these molecular interactions impact protein localization, cargo import, function and complex formation. We show that reversing the charge of key residues in importin-α (Arg44) or Cse1 (Asp220) results in loss of function of the respective proteins and impairs complex formation both in vitro and in vivo. To extend these results, we show that basic residues in the Nup2 N-terminus are required for both Nup2 interaction with importin-α and Nup2 function. These results provide a more comprehensive mechanistic model of how Cse1, RanGTP and Nup2 function in concert to mediate cNLS-cargo release in the nucleus.

End-of-Life Care in Cystic Fibrosis: Comparing Provider Practices Based on Lung Transplant Candidacy.

Background: The optimal timing to introduce palliative care (PC) and end-of-life (EOL) conversations into the lives of people with cystic fibrosis (CF) has not been established. Objective: Compare EOL care practices for people with CF who died without a lung transplant (LT), are living without an LT, and those who received an LT. Design: Retrospective chart review. Setting/Subjects: People with CF who received care from 2012 to 2017 at the University of Texas Southwestern Medical Center. Measurements: Primary outcomes were (1) EOL discussion with a pulmonologist, (2) time of EOL discussion before death or LT, (3) evaluation by PC, and (4) documentation of advanced directive or medical power of attorney. Results: Twenty-three patients died without LT, 40 patients received an LT, and 222 were living without an LT. Among LT recipients, 10% had EOL conversations compared with 74% of deceased patients and 5% of living patients without LT (p = 0.001). Among deceased patients, 39% had EOL conversations more than six months before death, while 5% of transplanted patients had EOL conversation more than six months before LT (p < 0.001). Deceased patients were more likely to have seen PC (57%) than either patients who received LT (2%) or those living without LT (3%, p = 0.0001). Conclusions: Patients who died without LT were more likely to have seen PC and had an EOL conversation than patients who received LT or who are living without LT. Further research should explore the optimal timing to discuss EOL care and the best timing to involve PC.

Fatal case of macrophage activation syndrome (MAS) in a patient with dermatomyositis and cytomegalovirus (CMV) viraemia.

We describe a case of an adult with dermatomyositis (DM) who presents with a rash, high fevers, tachycardia and hypotension, initially concerning for an infectious aetiology or a DM flare. She was found to have cytomegalovirus viraemia which improved after starting valganciclovir. After extensive workup and lack of improvement with broad-spectrum antimicrobial therapy, intravenous immunoglobulin and steroids, the patient was diagnosed with macrophage activation syndrome after bone marrow biopsy and levels of soluble CD25 (soluble interleukin (IL)-2 receptor) and IL2 were obtained. Unfortunately, despite therapy with dexamethasone, anakinra and etoposide, the patient decompensated and the patient's family opted for comfort care. The patient subsequently expired in the intensive care unit.

Communication between nurse care managers and patients who take opioids for chronic pain: Strategies for exploring aberrant behavior.

OBJECTIVE: One approach to potential misuse of prescription opioids by patients with chronic pain is team-based collaborative primary care, with primary care visits complemented by frequent visits with nurse care managers (NCMs) specializing in addiction care. However, little is known about the communication strategies NCMs employ in these visits. This study aimed to describe strategies NCMs used with patients when discussing aberrancies encountered during opioid monitoring. DESIGN: Observational study of NCM-patient interactions. Patients' primary care providers had been randomized to the treatment arm of a study evaluating an intervention, of which NCM visits were part, to change opioid prescribing patterns. The overall intervention was found to be successful. SETTING: Four primary care settings. PARTICIPANTS: Two NCMs and 41 patients. MAIN OUTCOME MEASURE: Forty one interactions between two NCMs and 41 unique patients were directly observed, and the detailed field notes coded for strategies using conventional content analysis. RESULTS: Five themes describing strategies that NCMs use to navigate aberrant patient behavior emerged: (1) NCM develops therapeutic relationship with patient; (2) NCM encourages adherence to monitoring strategies by contextualizing intensive opioid management for patient; (3) NCM inquires into discrepancies between patient's narrative and objective data to further understand aberrancy; (4) NCM assesses patient's medication use and pain to obtain more information about aberrancy and determine risk for opioid misuse; and (5) NCM educates patient and makes recommendations to guide appropriate medication use. CONCLUSIONS: These findings provide a potential model for the replication of intensive care management strategies utilizing NCMs in primary care.

Inhibiting TRK Proteins in Clinical Cancer Therapy.

Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers. The tropomyosin receptor kinase (TRK) family of tyrosine receptor kinases is emerging as an important target for cancer therapeutics. The TRK family contains three members, TRKA, TRKB, and TRKC, and these proteins are encoded by the genes NTRK1, NTRK2, and NTRK3, respectively. To activate TRK receptors, neurotrophins bind to the extracellular region stimulating dimerization, phosphorylation, and activation of downstream signaling pathways. Major known downstream pathways include RAS/MAPK/ERK, PLCγ, and PI3K/Akt. While being rare in most cancers, TRK fusions with other proteins have been well-established as oncogenic events in specific malignancies, including glioblastoma, papillary thyroid carcinoma, and secretory breast carcinomas. TRK protein amplification as well as alternative splicing events have also been described as contributors to cancer pathogenesis. For patients harboring alterations in TRK expression or activity, TRK inhibition emerges as an important therapeutic target. To date, multiple trials testing TRK-inhibiting compounds in various cancers are underway. In this review, we will summarize the current therapeutic trials for neoplasms involving NTKR gene alterations, as well as the promises and setbacks that are associated with targeting gene fusions.

Interaction between STAT3 and GLI1/tGLI1 oncogenic transcription factors promotes the aggressiveness of triple-negative breast cancers and HER2-enriched breast cancer.

Signal transducer and activator of transcription 3 (STAT3), glioma oncogene homolog 1 (GLI1), and truncated GLI1 (tGLI1) are oncogenic transcription factors playing important roles in breast cancer. tGLI1 is a gain-of-function GLI1 isoform. Whether STAT3 physically and/or functionally interacts with GLI1/tGLI1 has not been explored. To address this knowledge gap, we analyzed 47 node-positive breast cancer specimens using immunohistochemical staining and found that phosphorylated-STAT3 (Y705), GLI1, and tGLI1 are co-overexpressed in the majority of triple-negative breast carcinomas (64%) and HER2-enriched (68%) breast carcinomas, and in lymph node metastases (65%). Using gene set enrichment analysis, we analyzed 710 breast tumors and found that STAT3 activation and GLI1/tGLI1 activation signatures are co-enriched in triple-negative subtypes of breast cancers and HER2-enriched subtypes of breast cancers, but not in luminal subtypes of breast cancers. Patients with high levels of STAT3 and GLI1/tGLI1 co-activation in their breast tumors had worse metastasis-free survival compared to those with low levels. Since these proteins co-overexpress in breast tumors, we examined whether they form complexes and observed that STAT3 interacted with both GLI1 and tGLI1. We further found that the STAT3-GLI1 and STAT3-tGLI1 complexes bind to both consensus GLI1-binding and STAT3-binding sites using chromatin immunoprecipitation (ChIP) assay, and that the co-overexpression markedly activated a promoter controlled by GLI1-binding sites. To identify genes that can be directly co-activated by STAT3 and GLI1/tGLI1, we analyzed three ChIP-seq datasets and identified 34 potential target genes. Following validations using reverse transcription polymerase chain reaction and survival analysis, we identified three genes as novel transcriptional targets of STAT3 and GLI1/tGLI1, R-Ras2, Cep70, and UPF3A. Finally, we observed that co-overexpression of STAT3 with GLI1/tGLI1 promoted the ability of breast cancer cells to form mammospheres and that STAT3 only cooperates with tGLI1 in immortalized mammary epithelial cells. In summary, our study identified novel physical and functional cooperation between two families of oncogenic transcription factors, and the interaction contributes to aggressiveness of breast cancer cells and poor prognosis of triple-negative breast cancers and HER2-enriched breast cancers.

Dual Modulation of Human P-Glycoprotein and ABCG2 with Prodrug Dimers of the Atypical Antipsychotic Agent Paliperidone in a Model of the Blood-Brain Barrier.

Many atypical antipsychotic drugs currently prescribed for the treatment of schizophrenia have limited brain penetration due to the efflux activity of ATP-binding cassette (ABC) transporters at the blood-brain barrier (BBB), including P-glycoprotein (P-gp) and ABCG2. Herein, we describe the design and synthesis of the first class of homodimeric prodrug dual inhibitors of P-gp and ABCG2. These inhibitors are based on the structure of the atypical antipsychotic drug paliperidone (Pal), a transport substrate for both transporters. We synthesized and characterized a small library of homodimeric bivalent Pal inhibitors that contain a variety of tethers joining the two monomers via ester linkages. The majority of our compounds were low micromolar to sub-micromolar inhibitors of both P-gp and ABCG2 in cells overexpressing these transporters and in immortalized human hCMEC/D3 cells that are derived from the BBB. Our most potent dual inhibitor also contained an internal disulfide bond in the tether (Pal-8SS) that allowed for rapid reversion to monomer in the presence of reducing agents or plasma esterases. To increase stability against these esterases, we further engineered Pal-8SS to contain two hindering methyl groups alpha to the carbonyl of the ester moiety within the tether. The resulting dimer, Pal-8SSMe, was also a potent dual inhibitor that remained susceptible to reducing conditions but was more resistant to breakdown in human plasma. Importantly, Pal-8SSMe both accumulated and subsequently reverted to the therapeutic Pal monomer in the reducing environment of BBB cells. Thus, these molecules serve two purposes, acting as both inhibitors of P-gp and ABCG2 at the BBB and as prodrugs, effectively delivering therapies to the brain that would otherwise be precluded.

A Multicomponent Intervention to Improve Primary Care Provider Adherence to Chronic Opioid Therapy Guidelines and Reduce Opioid Misuse: A Cluster Randomized Controlled Trial Protocol.

BACKGROUND: Prescription opioid misuse is a significant public health problem as well as a patient safety concern. Primary care providers (PCPs) are the leading prescribers of opioids for chronic pain, yet few PCPs follow standard practice guidelines regarding assessment and monitoring. This cluster randomized controlled trial will determine whether four implementation strategies; nurse care management, use of a patient registry, academic detailing, and electronic tools, will increase PCP adherence to chronic opioid therapy guidelines and reduce opioid misuse among patients, relative to electronic tools alone. The implementation strategies and intervention content are based on the chronic care model. METHODS: We include 53 PCPs from three Boston-area community health centers and one urban safety-net hospital-based primary care practice who have at least four patients meeting the following inclusion criteria: 1) age≥18; 2) one or more completed visits to the primary care practice in the past year; 3) long-term opioid treatment defined as three or more opioid prescriptions written at least 21days apart within 6months and 4) an inpatient or outpatient ICD-9-CM diagnosis for musculoskeletal or neuropathic pain. We consider PCPs to be study subjects, and obtained a waiver of informed consent for patients because the study is promoting an established standard of care. We enrolled participants (PCPs) from December 2012 through March 2015. PCPs were randomized to receive the intervention, which includes four components: 1) nurse care management, 2) use of a patient registry, 3) academic detailing, and 4) electronic tools, or a control condition, which includes only the use of the electronic tools. The intervention PCPs receive the services of a nurse-managed registry for planning individual patient care and conducting population-based care for patients receiving opioids for chronic pain. In academic detailing visits, trained co-investigators provide intervention PCPs with individualized education to change prescribing practice. Electronic tools, located on a web site external to the EMR, www.mytopcare.org, include validated instruments to assess patient status, and management resources to facilitate PCP adherence to suggested monitoring. Electronic tools are available to PCPs in both study arms. The primary outcomes are PCP adherence to chronic opioid therapy guidelines and patient opioid misuse. Secondary outcomes include measures of substance abuse, possible opioid diversion, and level of opioid risk among patients. We will follow PCPs and their estimated 1200 chronic pain patients for 1year after study enrollment. To determine whether the intervention condition achieves greater adherence to guidelines and reduced opioid misuse after 1year compared to the control condition, we will compare the baseline and follow-up measures of the individual patients, stratifying by intervention status and noting differences that are statistically significant at the p=0.05 level. Analyses will be based on intent-to-treat. RESULTS: Randomization resulted in groups with similar baseline characteristics. The ages of PCPs are evenly distributed, with inclusion of both PCPs who have recently completed training and those who have been in practice for more than 20years. Two-thirds of enrolled PCPs are women, and one-third are non-white. DISCUSSION: The study will determine the impact of this multicomponent intervention on improving PCP adherence to guidelines and reducing opioid misuse among patients.

Prenatal substance exposure: What predicts behavioral resilience by early adolescence?

Understanding behavioral resilience among at-risk adolescents may guide public policy decisions and future programs. We examined factors predicting behavioral resilience following intrauterine substance exposure in a prospective longitudinal birth-cohort study of 136 early adolescents (ages 12.4-15.9 years) at risk for poor behavioral outcomes. We defined behavioral resilience as a composite measure of lack of early substance use initiation (before age 14), lack of risky sexual behavior, or lack of delinquency. Intrauterine substance exposures included in this analysis were cocaine, tobacco, alcohol, and marijuana. We recruited participants from Boston Medical Center as mother-infant dyads between 1990 and 1993. The majority of the sample was African American/Caribbean (88%) and 49% female. In bivariate analyses, none and lower intrauterine cocaine exposure level predicted resilience compared with higher cocaine exposure, but this effect was not found in an adjusted model. Instead, strict caregiver supervision (adjusted odds ratio [AOR] = 6.02, 95% confidence interval (CI) [1.90, 19.00], p = .002), lower violence exposure (AOR = 4.07, 95% CI [1.77, 9.38], p < .001), and absence of intrauterine tobacco exposure (AOR = 3.71, 95% CI [1.28, 10.74], p = .02) predicted behavioral resilience. In conclusion, caregiver supervision in early adolescence, lower violence exposure in childhood, and lack of intrauterine tobacco exposure predicted behavioral resilience among a cohort of early adolescents with significant social and environmental risk. Future interventions should work to enhance parental supervision as a way to mitigate the effects of adversity on high-risk groups of adolescents. (PsycINFO Database Record

Variability in opioid prescription monitoring and evidence of aberrant medication taking behaviors in urban safety-net clinics.

Little is known about variability in primary care providers' (PCPs) adherence to opioid-monitoring guidelines for patients. We examined variability of adherence to monitoring guidelines among PCPs and ascertained the relationship between PCP adherence and opioid misuse by their patients. We included primary care patients receiving long-term opioids (≥3 prescriptions within 6 months) for chronic noncancer pain and PCPs with ≥4 eligible patients. We examined guideline adherence using: (1) electronic health record documentation of opioid treatment agreement, (2) past-year urine drug screen (UDS), and (3) evidence of misuse through early refills (≥2 opioid prescriptions written 7-25 days after the previous prescription). Covariates included morphine equivalent daily opioid medication dose (MED, >50 mg/d vs ≤50mg/d). Multilevel regression models assessed variability among PCPs, and odds ratios examined associations among patient-level binary outcomes. Sixty-seven PCPs prescribed opioids to 1546 patients. Significant variability was found between PCPs in use of agreement (variance = 1.27, P < 0.001), UDS (variance = 1.75, P < 0.001), and early refills (variance = 0.29, P = 0.002). Primary care providers had a mean of 48% of patients with agreement (range, 9%-84%), 56% with ≥1 UDS (range, 7%-91%) and 36% with early refills (range, 19%-60%). High MED among patients was associated with increased odds of agreement (1.93, confidence interval [CI], 1.53-2.44), UDS (2.65, CI: 2.06-3.41), and early refill (2.92, CI: 2.30-3.70). Primary care providers varied significantly in adherence to opioid prescription guidelines. Increased patient risk was associated with increased monitoring and with greater misuse. Future work should study system-level interventions to enable clinical monitoring and support opioid guideline adherence.

Adherence to prescription opioid monitoring guidelines among residents and attending physicians in the primary care setting.

OBJECTIVE: The aim of this study was to compare adherence to opioid prescribing guidelines and potential opioid misuse in patients of resident vs attending physicians. DESIGN: Retrospective cross-sectional study. SETTING: Large primary care practice at a safety net hospital in New England. SUBJECTS: Patients 18-89 years old, with at least one visit to the primary care clinic within the past year and were prescribed long-term opioid treatment for chronic noncancer pain. METHODS: Data were abstracted from the electronic medical record by a trained data analyst through a clinical data warehouse. The primary outcomes were adherence to any one of two American Pain Society Guidelines: (1) documentation of at least one opioid agreement (contract) ever and (2) any urine drug testing in the past year, and evidence of potential prescription misuse defined as ≥2 early refills. We employed logistic regression analysis to assess whether patients' physician status predicts guideline adherence and/or potential opioid misuse. RESULTS: Similar proportions of resident and attending patients had a controlled substance agreement (45.1% of resident patients vs. 42.4% of attending patient, P = 0.47) or urine drug testing (58.6% of resident patients vs. 63.6% of attending patients, P = 0.16). Resident patients were more likely to have two or more early refills in the past year relative to attending patients (42.8% vs. 32.5%; P = 0.004). In the adjusted regression analysis, resident patients were more likely to receive early refills (odds ratio 1.82, 95% confidence interval 1.26-2.62) than attending patients. CONCLUSIONS: With some variability, residents and attending physicians were only partly compliant with national guidelines. Residents were more likely to manage patients with a higher likelihood of opioid misuse.