High prevalence of urine tampering in an office-based opioid treatment practice detected by evaluating the norbuprenorphine to buprenorphine ratio.

The prevalence of urine tampering within office-based opioid treatment (OBOT) is not currently known. This study was a cross-sectional analysis of an OBOT practice in New York City that experienced both a change in provider and a change in electronic medical record software. At that time, every patient in the practice received a urine drug test for "quantitative buprenorphine metabolites." METHODS: Outcomes of the first three urine drug tests were tabulated and analyzed with specific attention to the frequency of buprenorphine-positive (bup+), norbuprenorphine-negative (norbup-) samples, a pattern consistent with urine tampering. RESULTS: On the first sample 6/33 (18%) of patients submitted bup+/norbup- samples, and an additional 3 patients submitted bup+/norbup- samples on subsequent urine tests. Retention to the end of the study period among patients with bup+/norbup- samples was 33%, while in those with bup+/norbup+samples it was 96%. A scatter plot of norbuprenorphine vs. buprenorphine levels estimated that a ratio of <0.2 indicated tampering. CONCLUSION: Testing for buprenorphine metabolites yields valuable clinical information. The prevalence of a result pattern consistent with tampering by "urine spiking," the addition of unconsumed buprenorphine into the urine sample, may be higher than previous estimates. Previous lower cutoffs of the norbuprenorphine:buprenorphine metabolic ratio may miss a substantial proportion of these likely tampered samples.

Telemetry Monitor Watchers Reduce Bedside Nurses' Exposure to Alarms by Intercepting a High Number of Nonactionable Alarms.

Cardiac telemetry, designed to monitor hospitalized patients with active cardiac conditions, is highly utilized outside the intensive care unit but is also resource-intensive and produces many nonactionable alarms. In a hospital setting in which dedicated monitor watchers are set up to be the first responders to system-generated alerts, we conducted a retrospective study of the alerts produced over a continuous 2-month period to evaluate how many were intercepted before nurse notification for being nonactionable, and how many resulted in code team activations. Over the 2-month period, the system generated 20,775 alerts (5.1/patient-day, on average), of which 87% were intercepted by monitor watchers. None of the alerts for asystole, ventricular fibrillation, or ventricular tachycardia resulted in a code team activation. Our results highlight the high burden of alerts, the large majority of which are nonactionable, as well as the role of monitor watchers in decreasing the alarm burden on nurses. Measures are needed to decrease telemetry-related alerts in order to reduce alarm-related harms, such as alarm fatigue. Journal of Hospital Medicine 2017;12:447-449.

Ral signaling pathway in health and cancer.

The Ral (Ras-Like) signaling pathway plays an important role in the biology of cells. A plethora of effects is regulated by this signaling pathway and its prooncogenic effectors. Our team has demonstrated the overactivation of the RalA signaling pathway in a number of human malignancies including cancers of the liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors. Additionally, we have shown that the activation of RalA in cancer stem cells is higher in comparison with differentiated cancer cells. In this article, we review the role of Ral signaling in health and disease with a focus on the role of this multifunctional protein in the generation of therapies for cancer. An improved understanding of this pathway can lead to development of a novel class of anticancer therapies that functions on the basis of intervention with RalA or its downstream effectors.

The Effect of a Payer-Mandated Decrease in Buprenorphine Dose on Aberrant Drug Tests and Treatment Retention Among Patients with Opioid Dependence.

BACKGROUND: The optimal dose for office-based buprenorphine therapy is not known. This study reports on the effect of a change in payer policy, in which the insurer of a subset of patients in an office-based practice imposed a maximum sublingual buprenorphine dose of 16 mg/day, thereby forcing those patients on higher daily doses to decrease their dose. This situation created conditions for a natural experiment, in which treatment outcomes for patients experiencing this dose decrease could be compared to patients with other insurance who were not challenged with a dose decrease. METHODS: Subjects were 297 patients with opioid use disorder in a primary care practice who were prescribed buprenorphine continuously for at least 3 months. Medical records were retrospectively reviewed for urine drug test results and treatment retention. Rates of aberrant urine drug tests were calculated in the period before the dose decrease and compared to rate after it with patients serving as their own controls. Comparison groups were formed from patients with the same insurance on buprenorphine doses of 16 mg/day or lower, patients with different insurance on 16 mg/day or lower, and patients with different insurance on greater than 16 mg/day. Rates of aberrant drug tests and treatment retention of patients on 16 mg/day or less of buprenorphine were compared to that of patients on higher daily doses. RESULTS: The rate of aberrant urine drug tests among patients who experienced a dose decrease rose from 27.5% to 34.2% (p=0.043). No comparison group showed any significant change in aberrant drug test rates. Moreover, all groups who were prescribed buprenorphine doses greater than 16 mg/day displayed lower rates of aberrant urine drug tests than groups prescribed lower doses. Retention in treatment was also highest among those prescribed greater than 16 mg/day (100% vs. 86.8%, 90.1%, and 84.4% p=0.010). DISCUSSION: An imposed buprenorphine dose decrease was associated with an increase in aberrant drug tests. Patients in a control group with higher buprenorphine doses had greater retention in treatment. These findings suggest that buprenorphine doses greater than 16 mg/day are more effective for some patients and that dose limits at this level or lower are harmful.

Impact of hepatitis C status on 20-year mortality of patients with substance use disorders.

BACKGROUND: The magnitude of the effect of hepatitis C viral infection on survival is still not fully understood. The objective of this study was to determine whether the presence of hepatitis C viral antibodies in 1991 was associated with increased mortality 20 years later within a cohort of patients with substance use disorders. Secondary objectives were to determine other factors that were associated with increased mortality in the cohort. METHODS: A subset of a 1991 study cohort of patients who had presented for detoxification was reexamined 20 years later. The Social Security Death Index was queried to identify which of the original patients had died. Attributes of survivors and non-survivors were compared, with special attention to their hepatitis C status in 1991. The original study and this analysis were conducted in the chemical detoxification unit at Johns Hopkins Bayview (previously Francis Scott Key Hospital), an academic urban hospital. All participants met the criteria for alcohol or opioid dependence at the time of admission in 1991. The primary study outcome was 20-year mortality after initial admission in 1991, with a planned analysis of hepatitis C status. RESULTS: Twenty years after admission, 362 patients survived and 82 had died. Of the 284 patients who were hepatitis C positive, 228 survived (80 %). Of the 160 patients who were hepatitis C negative, 134 survived (84 %). This absolute risk increase of 4 % was not statistically significant (p = 0.37). Factors associated with increased mortality included male sex, white race, older age, and reported use of alcohol, cocaine, and illicit methadone. Binary logistic regression including hepatitis C status and these other variables yielded an adjusted odds ratio of 0.87 (95 % CI 0.49-1.55); (p = 0.64) for hepatitis C positive 20-year survival. CONCLUSIONS: Hepatitis C positivity was not associated with a statistically significant difference in 20-year survival. The effect of the virus on mortality, if present, is small, relative to the effect of substance use disorders alone.

Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base.

The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed.

Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal.

Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.