Three Newly Recognized Likely Pathogenic Gene Variants Associated with Hereditary Transthyretin Amyloidosis.

Introduction: Hereditary transthyretin amyloidosis (ATTRv [variant]) is a clinically heterogeneous, progressively debilitating, fatal disease resulting from the deposition of insoluble amyloid fibrils in various organs and tissues. Early diagnosis of ATTRv can be facilitated with genetic testing; however, such testing of the TTR gene identifies variants of uncertain significance (VUS) in a minority of cases, a small percentage of which have the potential to be pathogenic. The Akcea/Ambry VUS Initiative is dedicated to gathering molecular, clinical, and inheritance data for each TTR VUS identified by genetic testing programs to reclassify TTR variants to a clinically actionable status (e.

Newborn screening for Duchenne muscular dystrophy in China: follow-up diagnosis and subsequent treatment.

Background: Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province, China and is under consideration in other countries, including the United States. As China begins to implement DMD newborn screening (DMD-NBS), there is ongoing discussion regarding the steps forward for follow up care of positively identified patients as well as false positive and false negative results.

Data Sources: Relevant papers related to DMD-NBS, and NBS in China were reviewed in PubMed.

Efficacy and tolerability of a hydrocodone extended-release tablet formulated with abuse-deterrence technology for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis or low back pain.

This double-blind, placebo-controlled study evaluated the efficacy and safety of hydrocodone extended release (ER) developed with abuse-deterrence technology to provide sustained pain relief and limit effects of alcohol and tablet manipulation on drug release. Eligible patients with chronic moderate-to-severe low back or osteoarthritis pain were titrated to an analgesic dose of hydrocodone ER (15-90 mg) and randomized to placebo or hydrocodone ER every 12 hours. The primary efficacy measure was change from baseline to week 12 in weekly average pain intensity (API; 0=no pain, 10=worst pain imaginable).

National Breakthrough Pain Study: prevalence, characteristics, and associations with health outcomes.

The National Breakthrough Pain Study is a large observational study that assessed breakthrough pain (BTP) in a population of commercially insured community-dwelling patients with opioid-treated chronic pain. Eligible patients were identified from an administrative claims database, and consenting patients were asked to complete a structured telephone interview and several validated questionnaires. Questionnaires assessed pain interference with function (Brief Pain Inventory-Short Form), health status (Short Form 12 [SF-12] Health Survey), disability (Sheehan Disability Scale), work performance (World Health Organization Health and Work Performance Questionnaire), and mood (Generalized Anxiety Disorder-7 Screener [GAD-7] and Patient Health Questionnaire-2 [PHQ-2]).

Aberrant drug-related behavior observed during a 12-week open-label extension period of a study involving patients taking chronic opioid therapy for persistent pain and fentanyl buccal tablet or traditional short-acting opioid for breakthrough pain.

Objective: Evaluate aberrant drug-related behaviors in patients administering fentanyl buccal tablet or traditional short-acting opioids for breakthrough pain.

Design: Twelve-week open-label extension.

Setting: Forty-two US sites.

Fentanyl buccal tablet compared with immediate-release oxycodone for the management of breakthrough pain in opioid-tolerant patients with chronic cancer and noncancer pain: a randomized, double-blind, crossover study followed by a 12-week open-label phase to evaluate patient outcomes.

Objective: Evaluate analgesic efficacy, functional benefit, and patient satisfaction with fentanyl buccal tablet vs immediate-release oxycodone for breakthrough pain (BTP).

Design: Randomized, double-blind, active-controlled crossover trial and 12-week open-label extension.

Setting: Forty-two U.

Treatment of breakthrough pain with fentanyl buccal tablet in opioid-tolerant patients with chronic pain: appropriate patient selection and management.

Background: Opioids can be a safe and effective option for carefully selected patients with a structured treatment program that includes consistent monitoring. However, the benefits and risks of opioid therapy for patients with chronic pain, and society as a whole, have been sharply debated. A key component of this debate has involved the administration of rapid-onset opioids for the management of breakthrough pain.

Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations.

There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions.

Ambulatory blood pressure and coronary artery calcification in middle-aged and younger adults.

Background: The objective of this study was to investigate relationships between blood pressure (BP) determined by ambulatory monitoring and coronary artery calcification (CAC) determined by electron beam computed tomography (EBCT) in middle-aged and younger adults without symptoms of coronary artery disease.

Methods: Measures of office and ambulatory BP were analyzed in 298 asymptomatic adults (134 women and 164 men) from the white population of Rochester, MN, who were 20 to 60 years old (mean +/- SD, 40 +/- 9 years). For the ambulatory BP measurements, the active period of the day was defined as the daytime, out-of-bed hours and the inactive period as the nighttime, in-bed hours.