Overcoming challenges in acute care hospitalizations for patients with opioid use disorder.

BACKGROUND: Hospitalized patients with opioid use disorder (OUD) present unique challenges and opportunities for inpatient medical teams. Having the ability to initiate medications for opioid use disorder (MOUD) and linkage to outpatient treatment are key to improve inpatient care of patients with OUD. OBJECTIVE: This study aimed to describe the process taken by a multidisciplinary work group to improve the acute care management of patients with OUD. PRACTICE DESCRIPTION: In 2018, we identified that inpatient care teams at the University of Chicago Medicine (UCM) lacked a standardized approach to the management of hospitalized patients with OUD and that the care typically did not include evidence-based therapies. Herein, we describe the process taken to develop the OUD workgroup and the work completed by the workgroup. PRACTICE INNOVATION: The OUD workgroup spearheaded the development of an OUD consult service, formulary revisions, education for health care workers (inpatient nurse training and X-waiver training for prescribers), and outpatient partnerships. Pharmacy-led initiatives included formulary management, electronic medication orders, naloxone co-prescribing decision support, and MOUD education. EVALUATION METHODS: The OUD consult service was granted an Institutional Review Board exemption for quality improvement analysis through UCM. A data analytics dashboard was built to track consult service volumes and outcomes. RESULTS: From July 2020 to April 2021, 296 OUD consults occurred. In total, 103 consult patients (35%) received and were discharged with buprenorphine. An additional 118 patients (40%) were managed with methadone and linked to outpatient care. Naloxone dispensing at discharge increased to over 65%, which did not include patients who opted out or were discharged to a facility. CONCLUSION: The ongoing OUD epidemic presents a need for the development of services to improve management of patients with OUD in the acute care setting. The OUD workgroup has improved the management of patients admitted with OUD. Pharmacy-based initiatives are key to the development of safe and effective management of OUD in hospitalized patients.

Low dose IV buprenorphine inductions for patients with opioid use disorder and concurrent pain: a retrospective case series.

BACKGROUND: Hospitalizations are a vital opportunity for the initiation of life-saving opioid agonist therapy (OAT) for patients with opioid use disorder. A novel approach to OAT initiation is the use of IV buprenorphine for low dose induction, which allows patients to immediately start buprenorphine at any point in a hospitalization without stopping full agonist opioids or experiencing significant withdrawal. METHODS: This is a retrospective case series of 33 patients with opioid use disorder concurrently treated with full agonist opioids for pain who voluntarily underwent low dose induction at a tertiary academic medical center. Low dose induction is the process of initiating very low doses of buprenorphine at fixed intervals with gradual dose increases in patients who recently received or are simultaneously treated with full opioid agonists. Our study reports one primary outcome: successful completion of the low dose induction (i.e. transitioned from low dose IV buprenorphine to sublingual buprenorphine-naloxone) and three secondary outcomes: discharge from the hospital with buprenorphine-naloxone prescription, self-reported pain scores, and nursing-assessed clinical opiate withdrawal scale (COWS) scores over a 6-day period, using descriptive statistics. COWS and pain scores were obtained from day 0 (prior to starting the low dose induction) to day 5 to assess the effect on withdrawal symptoms and pain control. RESULTS: Thirty patients completed the low dose induction (30/33, 90.9%). Thirty patients (30/33, 90.9%) were discharged with a buprenorphine prescription. Pain and COWS scores remained stable over the course of the study period. Mean COWS scores for all patients were 2.6 (SD 2.8) on day 0 and 1.6 (SD 2.6) on day 5. Mean pain scores for all patients were 4.4 (SD 2.1) on day 0 and 3.5 on day 5 (SD 2.1). CONCLUSIONS: This study found that an IV buprenorphine low dose induction protocol was well-tolerated by a group of 33 hospitalized patients with opioid use disorder with co-occurring pain requiring full agonist opioid therapy. COWS and pain scores improved for the majority of patients. This is the first case series to report mean daily COWS and pain scores over an extended period throughout a low dose induction process.

Elevated Patellofemoral and Tibiofemoral T1ρ Relaxation Times Following a First Time Patellar Dislocation.

OBJECTIVE: The study was performed to evaluate cartilage within the knee following a first-time patellar dislocation, using elevated MRI-based T1ρ relaxation times as an indicator of low proteoglycan concentration. The hypothesis is that MRI-based T1ρ relaxation times for patellofemoral and tibiofemoral cartilage are significantly longer for knees being treated for patellar dislocation than for healthy control knees. DESIGN: Twenty-one subjects being treated for a first-time, unilateral dislocation of the patella and 16 healthy controls participated in MRI-based T1ρ relaxation time mapping. Mean relaxation times were quantified for patellofemoral and tibiofemoral regions for injured knees, the contralateral knees, and healthy controls. T1ρ values for each region were compared between the 3 groups with generalized estimating equations. Linear regressions were also performed to correlate T1ρ relaxation times with time from injury. RESULTS: The knees with a disloction had longer T1ρ relaxation times than the contralateral knees and control group at the medial patella and longer relaxation times than the control group at the lateral tibia (P < 0.05). T1ρ relaxation times at the medial patella also decreased with time from injury (r2 = 0.21, P = 0.037). CONCLUSIONS: Compositional changes to cartilage on the medial patella are related to traumatic impact during a dislocation. Potential exists for cartilage properties at the medial patella to improve with time. Cartilage degradation at the lateral tibia is not directly related to traumatic impact. The current baseline data are a starting point to characterize the pathway from a first-time dislocation to progressive cartilage degradation and osteoarthritis.

Amantadine withdrawal syndrome masquerading as COVID-19 encephalopathy: a case report and review of the literature.

Amantadine withdrawal syndrome (AWS) is a rare but recognized cause of severe and persistent altered mental status sometimes with co-occurring extrapyramidal symptoms. First described in a case series from 1987, its clinical manifestations have been characterized along a spectrum ranging from profound hypoactive delirium to hyperactive delirium with hallucinations. Risk factors for withdrawal include abrupt medication discontinuation, prolonged use, older age and underlying dementia. Herein we describe a case of a 52-year-old woman who presented with confusion, hallucinations, and coronavirus disease-2019 infection. She subsequently developed a prolonged hypoactive delirium after her amantadine was tapered and held. Her hypoactive delirium entirely resolved with resumption of amantadine confirming the diagnosis of AWS. This case illustrates the importance of slowly tapering dopaminergic medications and being aware of rare pharmacologic side effects.

Implementation and Assessment of a Proning Protocol for Nonintubated Patients With COVID-19.

INTRODUCTION: The COVID-19 pandemic has caused over 1,250,000 deaths worldwide. With limited therapeutic options, proning nonintubated patients emerged as a safe and affordable intervention to manage hypoxemia. METHODS: A proning protocol to identify and prone eligible patients was implemented. Patients were encouraged to self-prone for 2-3 hours, 3 times daily. Investigators created educational materials for nurses and patients and developed a COVID-19-specific proning order within the electronic health record (EHR). Investigators completed an 800-person retrospective chart review to study the implementation of this protocol. RESULTS: From March 22, 2020, to June 5, 2020, 586 patients were admitted to the COVID-19 floor. Of these patients, 42.8% were eligible for proning. Common contraindications were lack of hypoxia, altered mental status, and fall risk. The proning protocol led to a significant improvement in provider awareness of patients appropriate for proning, increasing from 12% to 83%, as measured by placement of a proning order into the EHR. There was a significant improvement in all appropriate patients documented as proned, increasing from 18% to 45% of eligible patients. CONCLUSIONS: The creation of an effective hospital-wide proning protocol to address the exigencies of the COVID-19 pandemic is possible and may be accomplished in a short period of time.

MRI of sonographically indeterminate adnexal masses.

OBJECTIVE: The purpose of this study was to assess the ability of MRI to characterize sonographically indeterminate adnexal masses and to define the sonographic features contributing to indeterminate diagnoses. MATERIALS AND METHODS: Two blinded radiologists retrospectively reviewed the MRI examinations of 87 patients with 95 sonographically indeterminate adnexal masses. Reviewers determined the origin of a mass, its tissue content (cystic, solid, complex cystic, or cystic and solid), tissue characteristics (fat, blood, fibrous, or leiomyomatous), and benignity versus malignancy. Sonograms were reviewed by three reviewers to determine the origin of a mass, its tissue content, and reasons for an indeterminate diagnosis. Sensitivity and specificity of MRI were calculated, and agreement of sonography and MRI with the final diagnosis was determined using kappa statistics. The final diagnosis was determined by histopathology, surgical findings, or imaging or clinical follow-up. RESULTS: The sensitivity of MRI for identifying malignancy (n = 5) was 100% and its specificity for benignity (n = 90) was 94%. Excellent agreement was seen between MRI and the final diagnosis for determining the origin (kappa = 0.93), tissue content (kappa = 0.98), and tissue characteristics (kappa = 0.91) of a mass. Sonography had poor agreement with the final diagnosis for the origin (kappa = 0.19) and tissue content (kappa = 0.33) of a mass. The main reasons for indeterminate sonographic diagnoses were the inability to determine origin because of location and large mass size and the appearances of purely solid or complex cystic masses. CONCLUSION: Sonographically indeterminate adnexal masses of uncertain origin and solid or complex cystic content benefit from further evaluation with MRI, which is highly accurate for identifying the origin of a mass and characterizing its tissue content, obviating surgery.

Phosphorylation of the platelet-derived growth factor receptor-beta and epidermal growth factor receptor by G protein-coupled receptor kinase-2. Mechanisms for selectivity of desensitization.

Accumulating evidence suggests that receptor protein-tyrosine kinases, like the platelet-derived growth factor receptor-beta (PDGFRbeta) and epidermal growth factor receptor (EGFR), may be desensitized by serine/threonine kinases. One such kinase, G protein-coupled receptor kinase-2 (GRK2), is known to mediate agonist-dependent phosphorylation and desensitization of multiple heptahelical receptors. In testing whether GRK2 could phosphorylate and desensitize the PDGFRbeta, we first found by phosphoamino acid analysis that cells expressing GRK2 could serine-phosphorylate the PDGFRbeta in an agonist-dependent manner. Augmentation or inhibition of GRK2 activity in cells, respectively, reduced or enhanced tyrosine phosphorylation of the PDGFRbeta but not the EGFR. Either overexpressed in cells or as a purified protein, GRK2 demonstrated agonist-promoted serine phosphorylation of the PDGFRbeta and, unexpectedly, the EGFR as well. Because GRK2 did not phosphorylate a kinase-dead (K634R) PDGFRbeta mutant, GRK2-mediated PDGFRbeta phosphorylation required receptor tyrosine kinase activity, as does PDGFRbeta ubiquitination. Agonist-induced ubiquitination of the PDGFRbeta, but not the EGFR, was enhanced in cells overexpressing GRK2. Nevertheless, GRK2 overexpression did not augment PDGFRbeta down-regulation. Like the vast majority of GRK2 substrates, the PDGFRbeta, but not the EGFR, activated heterotrimeric G proteins allosterically in membranes from cells expressing physiologic protein levels. We conclude that GRK2 can phosphorylate and desensitize the PDGFRbeta, perhaps through mechanisms related to receptor ubiquitination. Specificity of GRK2 for receptor protein-tyrosine kinases, expressed at physiologic levels, may be determined by the ability of these receptors to activate heterotrimeric G proteins, among other factors.