Abuse Potential with Oral Route of Administration of a Hydrocodone Extended-Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent, Recreational Opioid Users.

Objective: To compare the oral abuse potential of hydrocodone extended-release (ER) tablet developed with CIMA ® Abuse-Deterrence Technology with that of hydrocodone immediate release (IR).

Design: Randomized, double-blind, placebo-controlled, crossover study.

Setting And Patients: One study site in the United States; adult nondependent, recreational opioid users.

Efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet for the treatment of adults with opioid dependence: A randomized trial.

This prospective, randomized, active-controlled, non-inferiority study evaluated the efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet (Zubsolv; buprenorphine/naloxone rapidly dissolving tablet) versus generic buprenorphine for induction of opioid maintenance among dependent adults. The study, conducted at 13 sites from June 2013 to January 2014, included a 2-day blinded induction phase and a 27-day open-label stabilization/maintenance phase. During the blinded induction, patients received fixed doses of buprenorphine/naloxone rapidly dissolving tablets or generic buprenorphine.

Intravenous abuse potential study of oxycodone alone or in combination with naltrexone in nondependent recreational opioid users.

Background: ALO-02, comprising pellets of extended-release oxycodone surrounding sequestered naltrexone, is intended to deter abuse.

Objective: Determine the abuse potential of intravenous oxycodone combined with naltrexone, which represents simulated crushed ALO-02 in solution, compared with intravenous oxycodone in nondependent, recreational opioid users.

Methods: A randomized, double-blind, placebo-controlled, three-way crossover study with naloxone challenge, drug discrimination, and treatment phases.

Chronic Pain and the Opioid Conundrum.

Opioids prescribed for chronic cancer and noncancer pain have been embroiled in public policy debates as to effectiveness and potential for contributing to society's problem with misuse, addiction, and overdose mortality. The conundrum of opioid prescribing is to determine who will most likely benefit from opioids and how medical practitioners may safely provide chronic opioid therapy, while also identifying patients who are unlikely to benefit or could divert illicit pharmaceuticals into society. Risk assessment and monitoring are essential to meet the standard of care, as is compliance with federal controlled substances law as well as state regulations.

Assessment of contaminant concentrations in sediments, fish and mussels sampled from the North Atlantic and European regional seas within the ICON project.

Understanding the status of contaminants in the marine environment is a requirement of European Union Directives and the Regional Seas Conventions, so that measures to reduce pollution can be identified and their efficacy assessed. The international ICON workshop (Hylland et al., in this issue) was developed in order to test an integrated approach to assessing both contaminant concentrations and their effects.

Does delay in referral of proliferative diabetic retinopathy from the diabetic eye screening programme lead to visual loss?

AimsTo ascertain the effect on visual acuity (VA) of a delay in Hospital Eye Service (HES) consultation for patients referred with proliferative diabetic retinopathy (PDR; R3) from the Diabetic Eye Screening Programme (DESP).MethodsAll patients referred to Moorfields Eye Hospital from DESP between April and December 2013 with a referral diagnosis of PDR in at least one eye were eligible. Screening programme VA was compared with VA at first HES appointment and final follow-up appointment.

Glucose and lipid effects of the ileal apical sodium-dependent bile acid transporter inhibitor GSK2330672: double-blind randomized trials with type 2 diabetes subjects taking metformin.

Aims: To investigate the pharmacodynamics, pharmacokinetics and safety/tolerability of blocking reuptake of bile acids using the inhibitor GSK2330672 (GSK672) in patients with type 2 diabetes (T2D).

Methods: Subjects with T2D taking metformin were enrolled in two studies in which they took metformin 850 mg twice daily for 2 weeks prior to and during the randomized treatment periods. In the first crossover study (n = 15), subjects received GSK672 45 mg, escalating to 90 mg, twice daily, or placebo for 7 days.

Evaluation of the Tolerability of Switching Patients on Chronic Full μ-Opioid Agonist Therapy to Buccal Buprenorphine.

Objective: Assess whether patients with chronic pain receiving 80 to 220 mg oral morphine sulfate equivalent of a full Μ: -opioid agonist could be transitioned to buccal buprenorphine at approximately 50% of their full dose without inducing opioid withdrawal or sacrificing analgesic efficacy.

Methods: A randomized, double-blind, double-dummy, active-controlled, two-period crossover study in adult patients receiving around-the-clock full opioid agonist therapy and confirmed to be opioid dependent by naloxone challenge. Study doses were substituted at the time of the regular dose schedule for each patient.

Spectral variation of fluorescence lifetime near single metal nanoparticles.

We explore the spectral dependence of fluorescence enhancement and the associated lifetime modification of fluorescent molecules coupled to single metal nanoparticles. Fluorescence lifetime imaging microscopy and single-particle dark-field spectroscopy are combined to correlate the dependence of fluorescence lifetime reduction on the spectral overlap between the fluorescence emission and the localised surface plasmon (LSP) spectra of individual gold nanoparticles. A maximum lifetime reduction is observed when the fluorescence and LSP resonances coincide, with good agreement provided by numerical simulations.

An Online Survey of Patients' Experiences Since the Rescheduling of Hydrocodone: The First 100 Days.

Objective: To conduct an Internet patient survey through the National Fibromyalgia & Chronic Pain Association on reactions to the first 100 days following the rescheduling of hydrocodone.

Methods: Face-valid survey questions were created with expert consensus along with repurposed questions used on previous NFMCPA surveys covering domains such as demographics and symptoms. The questionnaire was designed to be administered over the Internet.

A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone.

Objective: Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein "DETERx").

Design: Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study.

Setting: Clinical research site.

EPR detection and characterisation of a paramagnetic Mo(iii) dihydride intermediate involved in electrocatalytic hydrogen evolution.

EPR spectroscopy and theoretical data show that the slow heterogeneous electron-transfer kinetics associated with the reduction of an 18-electron Mo(IV) acetato dihydride are a consequence of an η(2)-η(1) rearrangement of the carboxylate ligand which gives a unique paramagnetic 17-electron Mo(III) dihydride.

Hypothermia Associated With Thioridazine Use in an Intellectually Disabled Patient.

Purpose: To report a case of hypothermia in a patient with intellectual disability treated with thioridazine.

Summary: A 59-year-old female presented to the emergency department with altered mental status, generalized weakness, chills, and fatigue and was diagnosed with a urinary tract infection. Upon completion of a history and physical examination, the patient was found to be hypothermic with a temperature of 91 F.

Power Mobility Training for Young Children with Multiple, Severe Impairments: A Case Series.

Aims: Young children with neurodevelopmental conditions are often limited in their ability to explore and learn from their environment. The purposes of this case series were to (1) describe the outcomes of using an alternative power mobility device with young children who had multiple, severe impairments; (2) develop power mobility training methods for use with these children; and (3) determine the feasibility of using various outcome measures.

Methods: Three children with cerebral palsy (Gross Motor Function Classification System Levels IV, V, and V) ages 17 months to 3.

Self-reports of prescription opioid abuse and diversion among recreational opioid users in a Canadian and a United States city.

Objective: To explore behaviors related to prescription opioid abuse and diversion in individuals who self-reported past recreational (nonmedical) opioid use.

Design: A questionnaire was developed and included in two abuse potential clinical studies conducted in Canada (Toronto, ON, August 2010 to January, 2011) and the United States (Salt Lake City, UT, February-May 2011).

Participants: Recreational opioid users.

Safety profile of extended-release morphine sulfate with sequestered naltrexone hydrochloride in older patients: pooled analysis of three clinical trials.

Objective: Clinical trial safety data following chronic administration of extended-release opioids within an older population is limited. Embeda * is an extended-release formulation of morphine sulfate surrounding sequestered naltrexone hydrochloride (MSN) and is designed to deter opioid misuse and abuse. The present analysis compared pooled safety outcomes among patients aged ≥65 years and those aged <65 years from three phase 2/3 studies (ranging from 2 weeks to 12 months) in patients treated with MSN.

A randomized, phase 2 study investigating TRV130, a biased ligand of the μ-opioid receptor, for the intravenous treatment of acute pain.

Efficacy of conventional opioids can be limited by adverse events (AEs). TRV130 is a structurally novel biased ligand of the μ-opioid receptor that activates G protein signaling with little β-arrestin recruitment. In this phase 2, randomized, placebo- and active-controlled study, we investigated the efficacy and tolerability of TRV130 in acute pain after bunionectomy.

No Need to Object: Ethical Obligations for Interprofessional Collaboration in Emergency Department Discharge Planning.

Emergency departments (EDs) serve a wide range of patient needs. A crucial aspect of safe and effective care in the ED is to appropriately transition patients to the next level of care. In most EDs, this disposition planning is done exclusively by physicians, which has the potential to result in unacceptable harm.

Opioid abuse-deterrent strategies: role of clinicians in acute pain management.

Opioid abuse is a healthcare and societal problem that burdens individuals, their families and the healthcare professionals who care for them. Restricting access to opioid analgesics is one option to deter abuse, but this may prevent pain patients in need from obtaining effective analgesics. Therefore, strategies that mitigate the risk of opioid abuse while maintaining access are being pursued by several stakeholders including federal agencies, state governments, payors, researchers, the pharmaceutical industry and clinicians.

Low-dose naloxone provides an abuse-deterrent effect to buprenorphine.

In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine-naloxone (BN) sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose.

Analysis of opioid-mediated analgesia in Phase III studies of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain.

Background: Subcutaneous methylnaltrexone is efficacious and well tolerated for opioid-induced constipation (OIC) but may theoretically disrupt opioid-mediated analgesia.

Methods: Opioid use, pain intensity, and opioid withdrawal (Objective Opioid Withdrawal Scale [OOWS] and Subjective Opiate Withdrawal Scale [SOWS] scores) were reported in a randomized, double-blind trial with an open-label extension (RCT) and an open-label trial (OLT) evaluating safety in adults with chronic noncancer pain. In the RCT, patients taking ≥50 mg of oral morphine equivalents daily with <3 rescue-free bowel movements weekly received methyl naltrexone 12 mg once daily (n=150), every other day (n=148), or placebo (n=162) for 4 weeks, followed by open-label methylnaltrexone 12 mg (as needed [prn]; n=364) for 8 weeks.

Consensus Recommendations on Initiating Prescription Therapies for Opioid-Induced Constipation.

Objective: Aims of this consensus panel were to determine (1) an optimal symptom-based method for assessing opioid-induced constipation in clinical practice and (2) a threshold of symptom severity to prompt consideration of prescription therapy.

Methods: A multidisciplinary panel of 10 experts with extensive knowledge/experience with opioid-associated adverse events convened to discuss the literature on assessment methods used for opioid-induced constipation and reach consensus on each objective using the nominal group technique.

Results: Five validated assessment tools were evaluated: the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), Stool Symptom Screener (SSS), Bowel Function Index (BFI), and Bowel Function Diary (BF-Diary).

Current Regulations Related to Opioid Prescribing.

It is the responsibility of medical professionals to do all that is possible to safely alleviate pain. Opioids are frequently prescribed for pain but are associated with the potential for misuse, addiction, diversion, and overdose mortality, and thus they are strictly regulated. To adhere to legitimate practice standards, physicians and other health care providers who prescribe opioids for pain, particularly on a long-term basis, need current information on federal and state laws, treatment guidelines, and regulatory actions aimed at reducing opioid-related harm.