Repeated or Continuous Medically Supervised Ketamine Administration Associated with Hepatobiliary Adverse Events: A Retrospective Case Series.

INTRODUCTION: Emerging off-label medical uses of ketamine for the treatment of persistent conditions such as depression and chronic pain often require repeated administration. Cases reported by other countries suggest that long-term and repeated exposure to ketamine may be associated with several risks, including but not limited to hepatobiliary damage. OBJECTIVE: We aimed (1) to characterize the association between repeated administration of ketamine for off-label medical use and hepatobiliary events and (2) to describe recent trends in the use of ketamine across different clinical settings. METHODS: We conducted a retrospective case series analysis, utilizing reports identified from the US Food and Drug Administration Adverse Event Reporting System database as well as the medical literature. We included all cases reported through July 2018 describing both repeated exposure to ketamine in a hospital or ambulatory setting and a hepatobiliary adverse event. We excluded cases describing ketamine abuse. We identified adverse hepatobiliary events using the Medical Dictionary for Regulatory Activities (MedDRA®) and summarized various case characteristics including: patient demographics, route of ketamine administration, dose, time to onset of event, type of event, and pre-existing risk factors for hepatobiliary disease. To assess trends in the demand for ketamine, we used IQVIA, National Sales Perspectives™ to provide the nationally estimated number of vials sold for ketamine from the manufacturer to all US channels of distribution from 2013 through 2017. RESULTS: We identified 14 unique cases that met selection criteria with 21 hepatobiliary adverse events including liver enzyme elevation in all cases, biliary dilation with liver cirrhosis (n = 1), biliary dilation with cholangitis (n = 1), and pericholeductal fibrosis (n = 1). Most cases received ketamine for the treatment of complex regional pain syndrome or chronic pain. In cases with a reported time to onset, the majority of events occurred within 4 days. The nationally estimated number of ketamine vials sold in the USA from manufacturers to various channels of distribution increased from 1.2 million in 2013 to 2.1 million in 2017. CONCLUSIONS: We report an association between repeated or continuous administration of ketamine and hepatobiliary adverse events. Increased awareness among clinicians may mitigate these adverse outcomes, especially in the context of growing ketamine sales.

Days' Supply of Initial Opioid Analgesic Prescriptions and Additional Fills for Acute Pain Conditions Treated in the Primary Care Setting - United States, 2014.

During 2017, opioids were associated with 47,600 deaths in the United States, approximately one third of which involved a prescription opioid (1). Amid concerns that overprescribing to patients with acute pain remains an essential factor underlying misuse, abuse, diversion, and unintentional overdose, several states have restricted opioid analgesic prescribing (2,3). To characterize patterns of opioid analgesic use for acute pain in primary care settings before the widespread implementation of limits on opioid prescribing (2,3), patients filling an opioid analgesic prescription for acute pain were identified from a 2014 database of commercial claims. Using a logistic generalized additive model, the probability of obtaining a refill was estimated as a function of the initial number of days supplied. Among 176,607 patients with a primary care visit associated with an acute pain complaint, 7.6% filled an opioid analgesic prescription. Among patients who received an initial 7-day supply, the probability of obtaining an opioid analgesic prescription refill for nine of 10 conditions was <25%. These results suggest that a ≤7-day opioid analgesic prescription might be sufficient for most, but not all, patients seen in primary care settings with acute pain who appear to need opioid analgesics. However, treatment strategies should account for patient and condition characteristics, which might alternatively reduce or extend the anticipated duration of benefit from opioid analgesic therapy.

Changes in Outpatient Use of Antibiotics by Adults in the United States, 2006-2015.

INTRODUCTION: Numerous initiatives over the past decade have targeted the problem of antibiotic overuse in the US; however, the cumulative impact of such initiatives upon recent patterns of use is not known. OBJECTIVES: The aims of this study were to (1) describe general trends in outpatient antibiotic use among adults over the period 2006-2015; and (2) identify rapid shifts in use during this time period as potential indicators for key events. METHODS: This was an observational study set in the ambulatory setting. Patients ≥ 18 years of age were selected from the Optum Clinformatics Datamart™, a commercial insurance claims database. The outcome measures of interest were prescriptions filled/1000 enrolled individuals, by year or quarter. We used linear regression to identify trends in use over multiple years, and change-point regression to identify rapid shifts in use within individual years. RESULTS: From 2006 to 2015, antibiotic use declined significantly, decreasing by 12% for adults younger than 65 years of age (913-807 prescriptions/1000 individuals, p = 0.0001) and by 5% for adults ≥ 65 years of age (991-943 prescriptions/1000 individuals, p = 0.018). With change-point regression, we identified a number of rapid shifts in the use of specific antibiotic classes, such as downward shifts in the use of quinolones and macrolides during the second quarter of 2008 and 2013, respectively. CONCLUSIONS: Over the period 2006-2015 outpatient use of antibiotics decreased substantially among adults. Rapid shifts in use occurring in 2008 and 2013 may reflect the presence of key drivers of change, such as abrupt changes in access to care or perceived antibiotic safety.

Patterns of opioid initiation at first visits for pain in United States primary care settings.

PURPOSE: The primary objective of this study was to characterize variation in patterns of opioid prescribing within primary care settings at first visits for pain, and to describe variation by condition, geography, and patient characteristics. METHODS: 2014 healthcare utilization data from Optum's Clinformatics™ DataMart were used to evaluate individuals 18 years or older with an initial presentation to primary care for 1 of 10 common pain conditions. The main outcomes assessed were (1) the proportion of first visits for pain associated with an opioid prescription fill and (2) the proportion of opioid prescriptions with >7 days' supply. RESULTS: We identified 205 560 individuals who met inclusion criteria; 9.1% of all visits were associated with an opioid fill, ranging from 4.1% (headache) to 28.2% (dental pain). Approximately half (46%) of all opioid prescriptions supplied more than 7 days, and 10% of prescriptions supplied ≥30 days. We observed a 4-fold variation in rates of opioid initiation by state, with highest rates of prescribing in Alabama (16.6%) and lowest rates in New York (3.7%). CONCLUSIONS: In 2014, nearly half of all patients filling opioid prescriptions received more than 7 days' of opioids in an initial prescription. Policies limiting initial supplies have the potential to substantially impact opioid prescribing in the primary care setting.

Use of Electronic Health Record Data to Evaluate the Impact of Race on 30-Day Mortality in Patients Admitted to the Intensive Care Unit.

INTRODUCTION: The current body of literature examining the impact of race upon outcomes for patients admitted to the intensive care unit (ICU) is limited. The primary objective of our study was to explore this question using a large cohort drawn from an electronic health record (EHR)-based data source. METHODS: We conducted a retrospective cohort study using Multiparameter Intelligent Monitoring in Intensive Care (MIMIC-II), an EHR-derived database encompassing ICU admissions to an academic medical center in Boston, Massachusetts, between 2001 and 2008. Adults admitted to a medical or surgical ICU were assessed for the primary outcome of 30-day mortality and secondary outcomes of in-hospital mortality and hospital length-of-stay. Multivariate logistic regression was used to determine the association between race and the primary outcome. RESULTS: The study cohort consisted of 14,684 adult ICU patients-10,562 White, 1311 Black, 363 Asian, 868 "Other," and 1580 without known race. Thirty-day mortality rates experienced by Black and Asian individuals were significantly lower than mortality among those identified as White, with odds ratios of 0.62 (95 % CI 0.50-0.77) and 0.64 (95 % CI 0.44-0.93), respectively. Patients without known race experienced the highest crude mortality overall (27.4 %) and twice the adjusted odds of mortality compared with the White group. CONCLUSIONS: In a large, racially diverse cohort of general ICU patients, White patients experienced significantly higher mortality than non-White patients. Our results are consistent with findings from other studies that indicate that the non-White race does not appear to negatively impact short-term survival following ICU admission.

The Risk of Achilles or Biceps Tendon Rupture in New Statin Users: A Propensity Score-Matched Sequential Cohort Study.

INTRODUCTION: Case reports and pharmacovigilance data reported cases of tendon ruptures in statin users, but evidence from observational studies is scarce and inconclusive. We aimed to assess the association between new statin use and tendon rupture. METHODS: We performed a propensity score (PS)-matched sequential cohort study, using data from the Clinical Practice Research Datalink. Patients aged ≥45 years with at least one new statin prescription between 1995 and 2014 were PS-matched within 2-year entry blocks to patients without a statin prescription during the block. We followed patients until they had a recorded Achilles or biceps tendon rupture, completed 5 years of follow-up, or were censored for change in exposure status or another censoring criterion. We calculated hazard ratios (HRs) with 95 % confidence intervals (CIs), applying Cox proportional hazard analyses in the overall cohort (crude and multivariable) and in the PS-matched cohort. We performed subgroup analyses by sex, age, treatment duration, and statin dose. RESULTS: We observed a crude HR of 1.32 (95 % CI 1.21-1.44) in the overall cohort, which attenuated after multivariable adjustment (HR 1.02, 95 % CI 0.92-1.12) and after PS-matching (HR 0.95, 95 % CI 0.84-1.08). Crude HRs were higher in women than in men, but remained around null in both sexes after multivariable adjustment and PS-matching. Subgroup analyses by age, treatment duration, and statin dose revealed null results across all subgroups. CONCLUSION: The results of this cohort study suggest that statin use does not increase the risk of tendon rupture, irrespective of gender, age, statin dose, or treatment duration.

The role of echocardiography in the evaluation and management of aortic stenosis in the older adult.

Aortic stenosis is currently the most predominant valvular pathology in older adults. Signs and symptoms of aortic stenosis in this age-group may be difficult to recognize due to the decreased activity associated with aging and attribution of symptoms to other conditions. Echocardiography can be very helpful in the assessment of valvular structure and real time hemodynamic evaluation as well as in the progression of the disease over time. Unprecedented advances in echocardiography, including real time three-dimensional echocardiography, facilitate a comprehensive assessment of this condition and help in the decision-making process. Recent innovations in the percutaneous treatment of valvular diseases promise a revolution in the treatment of aortic stenosis especially in older adults.

Echocardiographic evaluation of calcific aortic stenosis in the older adult.

Aortic stenosis is the most predominant valvular pathology occurring in older adults with an expected increase over time. Multiple comorbidities and highly variable clinical presentations which characterize the aging population necessitate the use of echocardiography in the assessment of valvular structure and real time hemodynamic evaluation. This article reviews the pathophysiology and clinical presentation of aortic stenosis in this unique population and the critical role of various echocardiographic modalities. The value of real time three-dimensional real time echocardiography in the assessment and management of aortic stenosis in older adults is emphasized.