Reported adverse events related to use of hepatitis C virus direct-acting antivirals with opioids: 2017-2021.

INTRODUCTION: Due to concerns over potential interactions between some hepatitis C direct-acting antivirals (DAAs) and opioids, we describe adverse event (AE) reports of concomitant use of opioids and DAAs. METHODS: AEs reported (July 28, 2017-December 31, 2021) with the administration of the DAAs glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir/voxilaprevir, and elbasvir/grazoprevir as suspect products were downloaded from the US Food and Drug Administration AE Reporting System Public Dashboard. The number of AE reports containing opioids (fentanyl, hydrocodone, oxycodone) as co-suspect products/concomitant products were counted and summarized by severity, reporting country and whether an outcome of death was reported. Overdose AEs were counted irrespective of opioid use, and changes over time were assessed. RESULTS: In total, 40 AEs were reported for DAAs and concomitant fentanyl use, 25 (62.5%) were in the USA, 35 (87.5%) were considered serious, and 14 (35.0%) resulted in death; and 626 were reported with concomitant oxycodone/hydrocodone use, 596 (95.2%) were in the USA, 296 (47.3%) were considered serious, and 28 (4.5%) resulted in death. There were 196 overdose AEs (32 [16%] deaths) declining from 2018 (N = 56) to 2021 (N = 29). CONCLUSIONS: Treating people with hepatitis C virus (HCV) infection who use drugs is key to achieving HCV elimination. Low numbers of DAA AE reports with opioids may provide reassurance to prioritize HCV treatment in this population. These data contribute to evidence supporting the continued scale-up of DAA treatment among people who use drugs to achieve HCV elimination goals.

Assessment of Drug-Drug Interaction Risk Between Intravenous Fentanyl and the Glecaprevir/Pibrentasvir Combination Regimen in Hepatitis C Patients Using Physiologically Based Pharmacokinetic Modeling and Simulations.

INTRODUCTION: An unsafe injection practice is one of the major contributors to new hepatitis C virus (HCV) infections; thus, people who inject drugs are a key population to prioritize to achieve HCV elimination. The introduction of highly effective and well-tolerated pangenotypic direct-acting antivirals, including glecaprevir/pibrentasvir (GLE/PIB), has revolutionized the HCV treatment landscape. Glecaprevir is a weak cytochrome P450 3A4 (CYP3A4) inhibitor, so there is the potential for drug-drug interactions (DDIs) with some opioids metabolized by CYP3A4, such as fentanyl. This study estimated the impact of GLE/PIB on the pharmacokinetics of intravenous fentanyl by building a physiologically based pharmacokinetic (PBPK) model. METHODS: A PBPK model was developed for intravenous fentanyl by incorporating published information on fentanyl metabolism, distribution, and elimination in healthy individuals. Three clinical DDI studies were used to verify DDIs within the fentanyl PBPK model. This model was integrated with a previously developed GLE/PIB PBPK model. After model validation, DDI simulations were conducted by coadministering GLE 300 mg + PIB 120 mg with a single dose of intravenous fentanyl (0.5 µg/kg). RESULTS: The predicted maximum plasma concentration ratio between GLE/PIB + fentanyl and fentanyl alone was 1.00, and the predicted area under the curve ratio was 1.04, suggesting an increase of only 4% in fentanyl exposure. CONCLUSION: The administration of a therapeutic dose of GLE/PIB has very little effect on the pharmacokinetics of intravenous fentanyl. This negligible increase would not be expected to increase the risk of fentanyl overdose beyond the inherent risks related to the amount and purity of the fentanyl received during recreational use.

Evaluation of feasibility and user acceptance of lateral-flow self-testing for viral illness in a residential treatment rehabilitation facility.

BACKGROUND: The role of rapid testing has proven vital in reducing infection incidence in communities through swift identification and isolation of infected individuals. The COVID-19 pandemic has been particularly catastrophic for residential carceral and rehabilitation facilities that are high-risk settings for transmission of contagious diseases. Centralized provider-based viral testing employing conventional diagnostic techniques is labor-intensive and time-consuming. There is a marked unmet need for quick, inexpensive, and simple viral testing strategies. We hypothesized that rehabilitation residents could successfully test themselves employing inexpensive, disposable, antigen-based influenza lateral-flow tests and would be willing to self-isolate and self-report to health authorities if positive. METHODS: We evaluated self-testing among 50 rehabilitation residents ages 18 and older in Pomona, California, where participants self-administered influenza lateral-flow diagnostic test (without specimen collection) with the goal of appropriately observing a control line and completed two brief written surveys on self-testing and COVID-19, one before self-administering the lateral-flow test and one after, to determine the overall feasibility of viral self-testing and to characterize attitudes comparing self-testing and provider-based testing. FINDINGS: A total of 50 rehabilitation residents were enrolled in this study and all 50 conducted a lateral-flow test and answered the provided surveys. Among the participants, 96% (48 of 50) achieved a positive-control line from their lateral-flow test. Most participants, 83% (34 of 41) indicated that they would prefer to perform their own rapid test instead of having a health care provider administer the test. Notably, 98% (49 of 50) indicated that they would self-isolate if the lateral-flow test returned a positive indicator suggesting the presence of a viral infection and 96% (48 of 50) would report positive results to their corresponding public health department. INTERPRETATION: Residents in a residential rehabilitation center were widely able to successfully self-administer standard lateral-flow antigen-based rapid diagnostic kits. Self-testing was strongly preferred over tests administered by a healthcare provider. Reassuringly, almost every resident indicated that they would report any positive test result to the health department and self-isolate accordingly. Self-testing offers a promising adjunct to centralized testing, potentially better enabling swift and effective management of life-threatening infectious outbreaks among those living in high-risk congregate living settings.

White coat hypertension: relevance to clinical and emergency medical services personnel.

CONTEXT: White-coat hypertension (WCHT) is a relatively unexplored cause of elevated blood pressure readings in the clinic and in prehospital emergency medical services (EMS) settings. OBJECTIVE: The purpose is to summarize WCHT in the clinical office setting and speculate on its relevance in the prehospital setting. This review emphasizes the etiology, diagnosis, prognosis, and application of WCHT in both the clinical and prehospital settings. DATA SOURCES: A systematic literature review was undertaken with the Medline PubMed database, UpToDate, and Web of Science. The following search queries were used: "prehospital WCHT, " " prehospital white coat hypertension, " "EMS WCHT, " " emergency medical services white coat hypertension, " " ambulatory WCHT, " " ambulatory white coat hypertension, " " labile HTN, " " labile hypertension, " " variable HTN, " and " variable hypertension " limited to 1980-July 2006. Only human studies published in English were included. STUDY SELECTION: The reviews yielded 233 articles initially, which were narrowed down to those mentioned herein by direct relevance to either the observed WCHT effect in the clinic or the prehospital setting. DATA SYNTHESIS: WCHT has not been applied or explored in the prehospital setting as of yet, and thus all data were shown to be related to clinical WCHT. It was found that WCHT may not be simply a benign entity but rather part of a continuum in the development of true essential hypertension. It was found that WCHT patients, when followed, had higher morbidity than non-WCHT patients but less morbidity than established essential hypertensive patients. CONCLUSIONS: WCHT may be a significant step toward the evolution into full-blown hypertension. For many populations, routine access to a healthcare provider is not possible, and thus their only interaction with healthcare providers may be in the prehospital EMS setting. On the basis of findings of true organic morbidity in WCHT, it comes to reason that contact with patients in the setting should be thorough--including urging follow-up for those whose blood pressure is found to be elevated in the presence of healthcare professionals.

Cytomegalovirus Colitis and Subsequent New Diagnosis of Inflammatory Bowel Disease in an Immunocompetent Host: A Case Study and Literature Review.

BACKGROUND Infection with gastrointestinal cytomegalovirus in an immunocompetent host is a rather rare occurrence in the literature. There are a few reports of gastrointestinal infection in the immunocompetent who are then subsequently given a new diagnosis of inflammatory bowel disease. It is speculated that the initial cytomegalovirus colitis infection triggers the onset of inflammatory bowel disease. CASE REPORT Herein we report a case of cytomegalovirus colitis and new diagnosis of inflammatory bowel disease identified in a 40-year-old immunocompetent adult man who presented with gastrointestinal symptoms and disseminated cytomegalovirus infection requiring anti-viral therapy, which successfully treated the episode of cytomegalovirus infection. He then went on to have persistent symptomatic inflammatory bowel disease confirmed by pathology. CONCLUSIONS In this paper we will review the literature and explore the rare case of cytomegalovirus colitis in the immunocompetent host and discuss the pathology, physiology, diagnosis, and treatment of cytomegalovirus colitis.

Surgery for Tetralogy of Fallot in Adults: Early Outcomes.

Objective: To study the in-hospital outcome of adult patients who had undergone surgical repair for Tetralogy of Fallot. Methods: A retrospective descriptive study was conducted at the Punjab Institute of Cardiology searching the hospital records. All those adult patients who had undergone repair for Tetralogy of Fallot from January 2012 to December 2014 were included in the study. All the patients were operated by the same surgical team. Patients who underwent primary repair as well as those with previous palliative procedures were included in the study. Thirty days outcome was studied by recording variables from the database. Data was analysed using Statistical Package for Social Sciences version 16. Results: A total of 80 patients was included in the study, in which there were 48 (60%) male patients and 32 (40%) female patients. Mean age was 21±0.21 years. Those with previous palliation were 15 (18.75%). The associated problems observed were: atrial septal defect 27 (33.75%), right aortic arch 30 (37.5%), patent ductus arteriosus 6 (7.5%) and double outlet right ventricle 3 (3.75%). In-hospital mortality recorded was 7 (8%). Postoperative complications encountered were low cardiac output syndrome 9 (11.25%), pleural effusion requiring tapping 3 (3.75%), reoperation for bleeding 3 (3.8%), pulmonary regurgitation (moderate to severe) 20 (25%) which occurred in the transannular patch group only and atrial arrhythmia 4 (5%). Conclusion: A large number of adult patients are still operated for tetralogy of Fallot in Pakistan. With increasing experience in the technique the mortality and morbidity is comparable to international literature.

Surgery for tetralogy of fallot in adults: early outcomes

Abstract Objective: To study the in-hospital outcome of adult patients who had undergone surgical repair for Tetralogy of Fallot. Methods: A retrospective descriptive study was conducted at the Punjab Institute of Cardiology searching the hospital records. All those adult patients who had undergone repair for Tetralogy of Fallot from January 2012 to December 2014 were included in the study. All the patients were operated by the same surgical team. Patients who underwent primary repair as well as those with previous palliative procedures were included in the study. Thirty days outcome was studied by recording variables from the database. Data was analysed using Statistical Package for Social Sciences version 16. Results: A total of 80 patients was included in the study, in which there were 48 (60%) male patients and 32 (40%) female patients. Mean age was 21±0.21 years. Those with previous palliation were 15 (18.75%). The associated problems observed were: atrial septal defect 27 (33.75%), right aortic arch 30 (37.5%), patent ductus arteriosus 6 (7.5%) and double outlet right ventricle 3 (3.75%). In-hospital mortality recorded was 7 (8%). Postoperative complications encountered were low cardiac output syndrome 9 (11.25%), pleural effusion requiring tapping 3 (3.75%), reoperation for bleeding 3 (3.8%), pulmonary regurgitation (moderate to severe) 20 (25%) which occurred in the transannular patch group only and atrial arrhythmia 4 (5%). Conclusion: A large number of adult patients are still operated for tetralogy of Fallot in Pakistan. With increasing experience in the technique the mortality and morbidity is comparable to international literature.