A Guide to Expanding the Use of Buprenorphine Beyond Standard Initiations for Opioid Use Disorder.

Buprenorphine has become an important medication in the context of the ongoing opioid epidemic. However, complex pharmacologic properties and varying government regulations create barriers to its use. This narrative review is intended to facilitate buprenorphine use-including non-traditional initiation methods-by providers ranging from primary care providers to addiction specialists. This article briefly discusses the opioid epidemic and the diagnosis and treatment of opioid use disorder (OUD). We then describe the basic and complex pharmacologic properties of buprenorphine, linking these properties to their clinical implications. We guide readers through the process of initiating buprenorphine in patients using full agonist opioids. As there is no single recommended approach for buprenorphine initiation, we discuss the details, advantages, and disadvantages of the standard, low-dose, bridging-strategy, and naloxone-facilitated initiation techniques. We consider the pharmacology of, and evidence base for, buprenorphine in the treatment of pain, in both OUD and non-OUD patients. Throughout, we address the use of buprenorphine in children and adolescent patients, and we finish with considerations related to the settings of pregnancy and breastfeeding.

Clinical Factors and Outcomes When Real-World Heart Teams Overruled STS Risk Scores in TAVR Cases.

Objectives: This study was conducted to determine why heart teams recommended transcatheter aortic valve replacement (TAVR) versus surgical AVR (SAVR) for patients at low predicted risk of mortality (PROM) and describe outcomes of these cases. Background: Historically, referral to TAVR was based predominately on the Society of Thoracic Surgeons (STS) risk model's PROM >3%. In selected cases, heart teams had latitude to overrule these scores. The clinical reasons and outcomes for these cases are unclear. Methods: Retrospective data were gathered for all TAVR and SAVR cases conducted by 9 hospitals between 2013 and 2017. Results: Cases included TAVR patients with STS PROM >3% (n = 2,711) and ≤3% (n = 415) and SAVR with STS PROM ≤3% (n = 1,438). Leading reasons for recommending TAVR in the PROM ≤3% group were frailty (57%), hostile chest (22%), severe lung disease (16%), and morbid obesity (13%), and 44% of cases had multiple reasons. Most postoperative and 30-day outcomes were similar between TAVR groups, but the STS PROM ≤3% group had a one-day shorter length of stay (2.5 ± 3.4 vs. 3.5 ± 4.7 days; p ≤ 0.001) and higher one-year survival (91.6% vs. 86.0%, p=0.002). In patients with STS PROM ≤3%, 30-day mortality was higher for TAVR versus SAVR (2.0% vs. 0.6%; p < 0.001). Conclusions: Heart teams recommended TAVR in patients with STS PROM ≤3% primarily due to frailty, hostile chest, severe lung disease, and/or morbid obesity. Similar postoperative outcomes between these patients and those with STS PROM >3% suggest that decisions to overrule STS PROM ≤3% were merited and may have reduced SAVR 30-day mortality rate.

Patient experience and healthcare utilization for a COVID-19 telemedicine home monitoring program offered in English and Spanish.

BACKGROUND: Telemedicine is a vital component of the healthcare system's response to COVID-19. In March of 2020, Providence health system rapidly implemented a telemedicine home monitoring program (HMP) for COVID-19 patients that included use of at-home pulse oximeters and thermometers and text-based surveys to monitor symptoms. By June 2020, Providence updated the HMP to be offered in Spanish. This program was implemented before COVID-19 testing was readily available and therefore was offered to all patients suspected of having COVID-19. This study examines engagement, experience, and utilization patterns for English and Spanish-speaking patients engaged in the COVID-19 HMP. METHODS: A retrospective review of program data was used to understand HMP patient engagement (responsiveness to three daily text to monitor symptoms), satisfaction with the program (likelihood to recommend the program) as well as comfort using home monitoring devices and comfort recovering from home. To understand impact on care for COVID-19 confirmed cases, we used electronic health records to measure patterns in healthcare use for COVID-19 positive HMP participants and non-HMP propensity weighted controls. All patients enrolled in the COVID-19 HMP from March-October 2020 were included in the study. Patients tested for COVID-19 during the time window and not enrolled in HMP were included in the propensity-weighted comparison group. Descriptive and regression analyses were performed overall and stratified by English and Spanish speakers. RESULTS: Of the 4,358 HMP participants, 75.5% identified as English speakers and 18.2% identified as Spanish speakers. There was high level of responsiveness to three daily text-based surveys monitoring symptoms engagement (>80%) and a high level of comfort using the home monitoring devices (thermometers and pulse oximeters) for English- and Spanish-speaking participants (97.3% and 99.6%, respectively). The majority of English (95.7%) and Spanish-speaking (100%) patients felt safe monitoring their condition from home and had high satisfaction with the HMP (76.5% and 83.6%, respectively). English and Spanish-speaking COVID-19 positive HMP participants had more outpatient and emergency departments (ED) encounters than non-participants 7 and 30 days after their positive test. CONCLUSION: This widely implemented HMP provided participants with a sense of safety and satisfaction and its use was associated with more outpatient care and ED encounters. These outcomes were comparable across English and Spanish-speakers, highlighting the importance and potential impact of language-concordant telemedicine.

Who was at risk for COVID-19 late in the US pandemic? Insights from a population health machine learning model.

Notable discrepancies in vulnerability to COVID-19 infection have been identified between specific population groups and regions in the USA. The purpose of this study was to estimate the likelihood of COVID-19 infection using a machine-learning algorithm that can be updated continuously based on health care data. Patient records were extracted for all COVID-19 nasal swab PCR tests performed within the Providence St. Joseph Health system from February to October of 2020. A total of 316,599 participants were included in this study, and approximately 7.7% (n = 24,358) tested positive for COVID-19. A gradient boosting model, LightGBM (LGBM), predicted risk of initial infection with an area under the receiver operating characteristic curve of 0.819. Factors that predicted infection were cough, fever, being a member of the Hispanic or Latino community, being Spanish speaking, having a history of diabetes or dementia, and living in a neighborhood with housing insecurity. A model trained on sociodemographic, environmental, and medical history data performed well in predicting risk of a positive COVID-19 test. This model could be used to tailor education, public health policy, and resources for communities that are at the greatest risk of infection.

Comparison of 26-mm Evolut and 23-mm Sapien 3 Valves in TAVR for Small Aortic Annulus.

BACKGROUND: Patients with small aortic annuli (SAA) are prone to higher post-transcatheter aortic valve replacement (TAVR) transvalvular gradients and development of prosthesis-patient mismatch (PPM). In many patients with SAA, the choice of TAVR valve commonly involves choosing between the 26-mm Medtronic Evolut 2 (ME26) or the 23-mm Edwards Sapien 3 valve (ES23). We compared echocardiographic and clinical outcomes in patients with SAA undergoing TAVR with either valve. METHODS: We queried the Providence St. Joseph Health Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry database for patients undergoing TAVR with either the ES23 or ME26 between July 2015 and December 2018 at 11 hospitals. Post-TAVR echocardiographic and clinical results in-hospital, at 1 month, and at 1 year were examined. High gradient (HG) was defined as mean gradient (MG) ≥20 mm Hg. RESULTS: We identified 1162 patients with SAA undergoing TAVR with either the ME26 (n = 233) or ES23 valve (n = 929). Baseline characteristics between groups were similar. At 1 month, the ME26 was associated with a lower MG than the ES23 (7.7 ± 4.7 mm Hg vs 13.1 ± 4.9 mm Hg; P<.001) and moderate or severe PPM (11% and 3% vs 27% and 13%; P<.001). Occurrence of HG at 1 year was lower with the ME26 valve vs the ES23 valve (0% vs 15%; P<.001). In-hospital and follow-up clinical outcomes to 1 year were similar for both groups. CONCLUSION: TAVR in SAA with the ME26 is associated with lower incidence of HG or PPM compared with the ES23. While clinical outcomes at 1 year were similar, the long-term implications of these findings remain unknown.

A Case of Potential Pharmacokinetic Kratom-drug Interactions Resulting in Toxicity and Subsequent Treatment of Kratom Use Disorder With Buprenorphine/Naloxone.

The botanical product kratom produces opioid-like effects at high doses and is sometimes used for opioid replacement by individuals with opioid use disorder. Mitragynine, a major alkaloid contained in kratom leaves, has been shown to inhibit multiple cytochromes P450 (CYPs) in vitro, including CYP2D6 and CYP3A. As such, kratom may precipitate pharmacokinetic drug interactions when co-consumed with certain medications. We present a case of a patient taking 150 mg venlafaxine (CYP2D6/3A substrate), 300 mg quetiapine (CYP3A substrate), and a high amount of kratom (~90 g) daily. The patient presented to the emergency department with serotonin syndrome and corrected electrocardiogram abnormalities that may have been secondary to supratherapeutic exposure to venlafaxine and/or quetiapine. The patient's symptoms resolved after discontinuation of venlafaxine and quetiapine. He was amenable to medication therapy for kratom discontinuation and successfully completed an at-home induction with buprenorphine/naloxone. This case report adds to the literature about potential pharmacokinetic kratom-drug interactions and suggests that buprenorphine/naloxone can facilitate recovery from kratom use disorder.

Integration of Point-of-Care Ultrasound Education Into the Internal Medicine Core Clerkship Experience.

Point-of-care ultrasound (POCUS) is becoming an essential skill for internists. To date, there are no professional guidelines for how POCUS skills should be taught to medical students. A panel of POCUS experts from seven academic medical centers in the United States was convened to describe the components of independently developed IM clerkship POCUS training programs, identify areas of similarity and difference, and propose recommendations for alignment.

Adapting regulatory drug-drug interaction guidance to design clinical pharmacokinetic natural product-drug interaction studies: A NaPDI Center recommended approach.

Pharmacokinetic drug interactions precipitated by botanical and other natural products (NPs) remain critically understudied. Investigating these complex interactions is fraught with difficulties due to the methodologic and technical challenges associated with the inherently complex chemistries and product variability of NPs. This knowledge gap is perpetuated by a continuing absence of a harmonized framework regarding the design of clinical pharmacokinetic studies of NPs and NP-drug interactions. Accordingly, this Recommended Approach, the fourth in a series of Recommended Approaches released by the Center of Excellence for Natural Product Drug Interaction Research (NaPDI Center), provides recommendations for the design of clinical pharmacokinetic studies involving NPs. Building on prior Recommended Approaches and data generated from the NaPDI Center, such a framework is presented for the design of (1) phase 0 studies to assess the pharmacokinetics of an NP and (2) clinical pharmacokinetic NP-drug interaction studies. Suggestions for NP sourcing, dosing, study design, participant selection, sampling periods, and data analysis are presented. With the intent to begin addressing the gap between regulatory agencies' guidance documents about drug-drug interactions and contemporary NPDI research, the objective of this Recommended Approach is to propose methods for the design of clinical pharmacokinetic studies of NPs and NP-drug interactions.

Rapid Transition to Buprenorphine in a Patient With Methadone-Related QTc Interval Prolongation.

BACKGROUND: Patients with opioid use disorder (OUD) who are managed on methadone often require transition to buprenorphine therapy. Current recommendations require months to gradually taper off of methadone; however, in some cases, the need to transition is urgent. Only a few rapid methadone-to-buprenorphine transitions have been reported and there are no established protocols to guide clinicians in these cases. CASE PRESENTATION: A 43-year-old man on 95 mg methadone for opioid use disorder experienced cardiac arrest attributable to ventricular fibrillation caused by QTc interval prolongation from methadone. In the hospital, a gradual taper of methadone was initiated but proved intolerable; the patient requested to restart his home dose of methadone and leave against medical advice. A rapid transition was initiated instead. Naltrexone (25 mg) was used to precipitate acute withdrawal followed 1 hour later by a "rescue" with buprenorphine/naloxone (16 mg/4 mg). The Clinical Opiate Withdrawal Score (COWS) peaked at 21 post-naltrexone and fell quickly to 15 within a half-hour of buprenorphine/naloxone administration. The patient was maintained on a total daily dose of 16 mg/4 mg buprenorphine/naloxone through the time of discharge. CONCLUSIONS: A patient requiring an urgent taper off of methadone due to adverse cardiac effects successfully transitioned to buprenorphine/naloxone within 2 hours by using naltrexone to precipitate withdrawal followed by a "rescue" with buprenorphine/naloxone. A relatively high dose of 16 mg/4 mg buprenorphine/naloxone successfully arrested withdrawal symptoms. With further refinement, this protocol may be an important technique for urgent methadone-to-buprenorphine transitions in the inpatient setting.

Evaluation of Shared Experiences Among Patients and Providers Following Behavioral Health Integration in Primary Care.

Behavioral health integration (BHI) changes the paradigm of primary care delivery by integrating behavioral healthcare into primary care. Thus, BHI likely alters the shared experiences of both patients and providers in an interrelated manner; however, their experiences are usually evaluated separately. The purpose of this study was to analyze these shared experiences together within patient-provider pairs in integrated clinics. First, patient interviews were conducted using semi-structured interview guides and transcripts were analyzed for major themes of patient experience. Next, providers named in patient interviews were interviewed around these same themes. Thematic analysis was performed on 18 transcripts (11 patients, 7 providers). Common themes included BHI experience, pain management, feeling heard by providers, and health care experiences. Areas of alignment included positive perception of BHI, an absence of long-term care, and a desire to share decision-making. Pain management was a persistent area of conflict, and the differing experiences were consistent with a change in the psychodynamic patient-provider model. This conflict highlights a gap in BHI and a need for provider education about psychodynamic relationship models.

Comparing accuracy of bedside ultrasound examination with physical examination for detection of pleural effusion.

BACKGROUND: In detecting pleural effusion, bedside ultrasound (US) has been shown to be more accurate than auscultation. However, US has not been previously compared to the comprehensive physical examination. This study seeks to compare the accuracy of physical examination with bedside US in detecting pleural effusion. METHODS: This study included a convenience sample of 34 medical inpatients from Calgary, Canada and Spokane, USA, with chest imaging performed within 24 h of recruitment. Imaging results served as the reference standard for pleural effusion. All patients underwent a comprehensive lung physical examination and a bedside US examination by two researchers blinded to the imaging results. RESULTS: Physical examination was less accurate than US (sensitivity of 44.0% [95% confidence interval (CI) 30.0-58.8%], specificity 88.9% (95% CI 65.3-98.6%), positive likelihood (LR) 3.96 (95% CI 1.03-15.18), negative LR 0.63 (95% CI 0.47-0.85) for physical examination; sensitivity 98% (95% CI 89.4-100%), specificity 94.4% (95% CI 72.7-99.9%), positive LR 17.6 (95% CI 2.6-118.6), negative LR 0.02 (95% CI 0.00-0.15) for US). The percentage of examinations rated with a confidence level of 4 or higher (out of 5) was higher for US (85% of the seated US examination and 94% of the supine US examination, compared to 35% of the PE, P < 0.001), and took less time to perform (P < 0.0001). CONCLUSIONS: US examination for pleural effusion was more accurate than the physical examination, conferred higher confidence, and required less time to complete.

Modeling Pharmacokinetic Natural Product-Drug Interactions for Decision-Making: A NaPDI Center Recommended Approach.

The popularity of botanical and other purported medicinal natural products (NPs) continues to grow, especially among patients with chronic illnesses and patients managed on complex prescription drug regimens. With few exceptions, the risk of a given NP to precipitate a clinically significant pharmacokinetic NP-drug interaction (NPDI) remains understudied or unknown. Application of static or dynamic mathematical models to predict and/or simulate NPDIs can provide critical information about the potential clinical significance of these complex interactions. However, methods used to conduct such predictions or simulations are highly variable. Additionally, published reports using mathematical models to interrogate NPDIs are not always sufficiently detailed to ensure reproducibility. Consequently, guidelines are needed to inform the conduct and reporting of these modeling efforts. This recommended approach from the Center of Excellence for Natural Product Drug Interaction Research describes a systematic method for using mathematical models to interpret the interaction risk of NPs as precipitants of potential clinically significant pharmacokinetic NPDIs. A framework for developing and applying pharmacokinetic NPDI models is presented with the aim of promoting accuracy, reproducibility, and generalizability in the literature. SIGNIFICANCE STATEMENT: Many natural products (NPs) contain phytoconstituents that can increase or decrease systemic or tissue exposure to, and potentially the efficacy of, a pharmaceutical drug; however, no regulatory agency guidelines exist to assist in predicting the risk of these complex interactions. This recommended approach from a multi-institutional consortium designated by National Institutes of Health as the Center of Excellence for Natural Product Drug Interaction Research provides a framework for modeling pharmacokinetic NP-drug interactions.

COVID-19 as the cause of thrombosis: recognising COVID-19 infection in apparently asymptomatic patients.

COVID-19 has serious thrombotic complications in critically ill patients; however, thrombus is not a typical presenting symptom. This case report describes a patient with no respiratory symptoms who presented to the emergency department with abdominal pain. The pain was attributed to renal thrombosis, but the patient was found to have no risk factors for thrombotic disease and subsequent hypercoagulable work-up was unremarkable. Pulmonary manifestations of COVID-19 infection were detected incidentally on the abdominal CT scan and confirmed via PCR test. The patient was isolated and went on to develop mild respiratory failure secondary to COVID-19 infection. This case suggests that unexplained thrombus in otherwise asymptomatic patients can be a direct result of COVID-19 infection, and serves as a call to action for emergency department clinicians to treat unexplained thrombotic events as evidence of COVID-19.

Incretin drugs in diabetic kidney disease: biological mechanisms and clinical evidence.

As the prevalence of diabetes continues to climb, the number of individuals living with diabetic complications will reach an unprecedented magnitude. The emergence of new glucose-lowering agents - sodium-glucose cotransporter 2 inhibitors and incretin therapies - has markedly changed the treatment landscape of type 2 diabetes mellitus. In addition to effectively lowering glucose, incretin drugs, which include glucagon-like peptide 1 receptor (GLP1R) agonists and dipeptidyl peptidase 4 (DPP4) inhibitors, can also reduce blood pressure, body weight, the risk of developing or worsening chronic kidney disease and/or atherosclerotic cardiovascular events, and the risk of death. Although kidney disease events have thus far been secondary outcomes in clinical trials, an ongoing phase III trial in patients with diabetic kidney disease will test the effect of a GLP1R agonist on a primary kidney disease outcome. Experimental data have identified the modulation of innate immunity and inflammation as plausible biological mechanisms underpinning the kidney-protective effects of incretin-based agents. These drugs block the mechanisms involved in the pathogenesis of kidney damage, including the activation of resident mononuclear phagocytes, tissue infiltration by non-resident inflammatory cells, and the production of pro-inflammatory cytokines and adhesion molecules. GLP1R agonists and DPP4 inhibitors might also attenuate oxidative stress, fibrosis and cellular apoptosis in the kidney.

POCUS Evaluation in Acute Kidney Injury.

Acute kidney injury is a common clinical problem encountered in general internal medicine. The evaluation of acute kidney injury is mainly driven by the patient's clinical history, physical exam, and laboratory investigation including urinalysis and urine sediment examination. Point of care ultrasound (POCUS) may be a useful tool to help clinicians to narrow and/or prioritize differential diagnosis in patients presenting with acute kidney injury. Here we present a case of a 67-year-old male presenting with dysuria, fevers, and flank pain along with elevation in serum creatinine who was admitted with concern for acute kidney injury secondary to complicated urinary tract infection. Subsequent kidney POCUS of the kidneys and bladder showed bilateral anechoic fluid collection within the kidney sinus with dilated calyces suggestive of bilateral hydronephrosis, most likely due to a new diagnosis of benign prostatic hyperplasia. This case demonstrates the use of POCUS-obtained valuable diagnostic information and subsequent therapeutic management for this patient presenting with suspected acute kidney injury.

Prevalence of intra-atrial reentrant tachycardia following mitral valve surgery: Relationship to surgical approach.

BACKGROUND AND AIM: Mitral valve (MV) surgeries create electrophysiological substrates that give rise to postoperative arrhythmias. MV surgical procedures have been associated with macro- and microreentrant arrhythmogenic circuits, as well as circuits involving the atrial roof. It is not well understood why such arrhythmias develop; therefore, the aim of this study was to describe clinical and procedure characteristics associated with atrial arrhythmias in patients with prior MV surgery. METHODS: This retrospective chart review evaluated patients who had prior MV surgery and ablation procedures for atrial tachycardia between 2014 and 2018 (n = 20). Patients were classified into those exhibiting typical atrial flutter or another atrial tachyarrhythmia. RESULTS: Within the 20 patient cases reviewed, 30 arrhythmias were documented. Two-thirds of arrhythmias were typical atrial flutter; the percent incidence of arrhythmias originating in the right atrial (RA) roof, around the right atriotomy scar, in the left atrium, and at the crista terminalis was 20%, 3%, 7%, and 7%, respectively. Nearly every case of RA roof flutter (n = 5/6) and most arrhythmias (n = 20/30) occurred in patients who had a transseptal approach during MV surgery. Voltage maps did not show clear differences in scarring between groups. CONCLUSION: Results from this study suggest that an arrhythmogenic substrate for RA roof tachycardias is generated by transseptal approaches for MV surgery. This substrate is not clearly related to a surgical scar. These data suggest that other approaches should be considered for MV surgeries. Additionally, more research is needed to determine the mechanism for this nonscar-related arrhythmia substrate.

Eye-controlled, power wheelchair performs well for ALS patients.

BACKGROUND: Our pilot study tested the feasibility and performance of an eye-controlled power wheelchair for amyotrophic lateral sclerosis (ALS) patients. METHODS: In this prospective pilot study, participants drove the wheelchair three times around an indoor course. We assessed the time to complete the course; starting and stopping on command; turning 90, 135, and 180 degrees; time to backup; and obstacle negotiation. Following their use of the wheelchair, subjects were given a questionnaire to assess user experience. RESULTS: Twelve patients participated, and all were able to complete three trials without difficulty. Eight participants completed all of the individual tasks (eg, turning, stopping, etc.) without any errors. Overall performance ratings were high across all participants (4.6/5-excellent). CONCLUSIONS: Our eye-controlled power wheelchair prototype is feasible and has a very favorable user experience. This system has the potential to improve the mobility and independence of ALS patients, and other groups with motor impairments.