Methadone Blockade of Cardiac Inward Rectifier K+ Current Augments Membrane Instability and Amplifies U Waves on Surface ECGs: A Translational Study.

Background Methadone is associated with a disproportionate risk of sudden death and ventricular tachyarrhythmia despite only modest inhibition of delayed rectifier K+ current (IKr), the principal mechanism of drug-associated arrhythmia. Congenital defects of inward rectifier K+ current (IK1) have been linked to increased U-wave amplitude on ECG and fatal arrhythmia. We hypothesized that methadone may also be a potent inhibitor of IK1, contributing to delayed repolarization and manifesting on surface ECGs as augmented U-wave integrals. Methods and Results Using a whole-cell voltage clamp, methadone inhibited both recombinant and native IK1 with a half-maximal inhibitory concentration IC50) of 1.5 µmol/L, similar to that observed for IKr block (half-maximal inhibitory concentration of 2.9 µmol/L). Methadone modestly increased the action potential duration at 90% repolarization and slowed terminal repolarization at low concentrations. At higher concentrations, action potential duration at 90% repolarization lengthening was abolished, but its effect on terminal repolarization rose steadily and correlated with increased fluctuations of diastolic membrane potential. In parallel, patient ECGs were analyzed before and after methadone initiation, with 68% of patients having a markedly increased U-wave integral compared with premethadone (lead V3; mean +38%±15%, P=0.016), along with increased QT and TPeak to TEnd intervals, likely reflective of IKr block. Conclusions Methadone is a potent IK1 inhibitor that causes augmentation of U waves on surface ECG. We propose that increased membrane instability resulting from IK1 block may better explain methadone's arrhythmia risk beyond IKr inhibition alone. Drug-induced augmentation of U waves may represent evidence of blockade of multiple repolarizing ion channels, and evaluation of the effect of that agent on IK1 may be warranted.

Viral Hepatitis and Human Immunodeficiency Virus Testing and Linkage to Care for Individuals Enrolled in an Opioid Treatment Program.

BACKGROUND: In the United States, many opioid treatment programs (OTPs) do not offer viral hepatitis (VH) or human immunodeficiency virus (HIV) testing despite high prevalence among OTP clients. We initiated an opt-out VH and HIV testing and linkage-to-care program within our OTP. METHODS: All OTP intakes are screened for VH and HIV and evaluated for rescreening annually. A patient navigator reviews laboratory results and provides counseling in the OTP clinic. The medical record is queried to identify individuals with previously diagnosed, untreated VH or HIV. Navigation support is provided for linkage or relinkage to VH or HIV care. RESULTS: Between March 2018 and Februrary 2019, 532 individuals were screened for hepatitis C virus (HCV), 180 tested HCV antibody positive (34%), and 108 were HCV-ribonucleic acid (RNA) positive (20%). Sixty individuals were identified with previously diagnosed, untreated HCV. Of all HCV RNA+, 49% reported current injection drug use (82 of 168). Ninety-five individuals were seen by an HCV specialist (57% of HCV RNA+), 72 started treatment (43%), and 69 (41%) completed treatment. Individuals with primary care providers were most likely to start treatment. Four individuals were diagnosed with hepatitis B; 0 were diagnosed with HIV. CONCLUSIONS: The implementation of an OTP-based screening and navigation protocol has enabled significant gains in the identification and treatment of VH in this high prevalence setting.

Risk Factors for Readmission on an Adult Inpatient Psychiatric Unit.

OBJECTIVE: Readmission rates have been proposed as a possible quality metric for inpatient psychiatry. Little is known about predicting readmissions and identifying modifiable factors that may reduce early readmissions in these settings. METHODS: We reviewed 693 medical records from our adult inpatient psychiatric unit to identify factors associated with patients' readmission within 90 days of discharge. RESULTS: After adjusting for all variables, and including interactions between identified factors, we found several demographic features predicting readmission, including male gender with suicidal ideation on admission (odds ratio [OR] = 13.2; 95% confidence interval [CI], 3.4-51.9), a diagnosis of a psychotic disorder with a prior medical admission (OR = 5.7; 95% CI, 1.7-20.6), and suicidal ideation with comorbid personality disorder (OR = 5.3; 95% CI, 1.4-20.6). Demographic features decreasing the odds of readmission included being non-white with homeless living situation (OR = 0.18; 95% CI, 0.04-0.82), medication changes made within 48 hours of discharge (OR = 0.44; 95% CI, 0.23-0.84), and the number of medications dispensed without documented follow-up plan or appointment (OR = 0.88; 95% CI, 0.81-0.96). CONCLUSION: Future prospective studies utilizing qualitative and quantitative methods are required to more precisely define a wider array of metrics. Improved identification of demographic features associated with early readmissions may suggest areas to target as we seek to the quality of inpatient psychiatric care.