Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation.

BACKGROUND: Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. AIM: To evaluate the long-term safety and tolerability of naloxegol, an oral, peripherally acting µ-opioid receptor antagonist (PAMORA), in patients with noncancer pain and OIC. METHODS: A 52-week, multicenter, open-label, randomised, parallel-group phase 3 study was conducted in out-patients taking 30-1000 morphine-equivalent units per day for ≥4 weeks. Patients were randomised 2:1 to receive naloxegol 25 mg/day or usual-care (UC; investigator-chosen laxative regimen) treatment for OIC. RESULTS: The safety set comprised 804 patients (naloxegol, n = 534; UC, n = 270). Mean exposure duration was 268 days with naloxegol and 297 days with UC. Frequency of adverse events (AEs) was 81.8% with naloxegol and 72.2% with UC. Treatment-emergent AEs occurring more frequently for naloxegol vs. UC were abdominal pain (17.8% vs. 3.3%), diarrhoea (12.9% vs. 5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 4.8%), flatulence (6.9% vs. 1.1%) and upper abdominal pain (5.1% vs. 1.1%). Most naloxegol-emergent gastrointestinal AEs occurred early, resolving during or after naloxegol discontinuation and were mild or moderate in severity; 11 patients discontinued due to diarrhoea and nine patients owing to abdominal pain. Pain scores and mean daily opioid doses remained stable throughout the study; no attributable opioid withdrawal AEs were observed. Two patients in each group had an adjudicated major adverse cardiovascular event unrelated to study drug; no AEs were reported nor adjudicated as bowel perforations. CONCLUSION: In patients with noncancer pain and opioid-induced constipation, naloxegol 25 mg/day up to 52 weeks was generally safe and well tolerated.

Application of metrics constructed from vibrotactile thresholds to the assessment of tactile sensory changes in the hands.

Two tools for assessing tactile sensory disturbances in the hands have been constructed from mechanoreceptor-specific vibrotactile threshold shifts, and thresholds changes with time, and employed in a prospective study of forest workers (N=18). Statistically significant positive threshold shifts (i.e., reductions in sensitivity compared to the hands of healthy persons) were found in five hands at study inception (13.9%), and 15 hands at follow-up (41.7%). Four patterns of threshold shift could be identified, involving selectively the median and/or ulnar nerve pathways and/or end organs. Statistically significant positive threshold changes (i.e., reductions in sensitivity with time) were recorded in 69.4% of the hands over a five-year period, even though a majority of the workers remained symptom free. If the thresholds recorded from subjects not working with power tools are used to control for aging, lifestyle, and environmental factors during the five year period, then 40% of the remaining subjects are found to be experiencing work-related threshold changes in their hands. The ability of the threshold shift metric to predict the numbness reported by these subjects shows that it is closely associated with the tactile sensory changes occurring in their hands.

Trends in work-related musculoskeletal disorder reports by year, type, and industrial sector: a capture-recapture analysis.

BACKGROUND: Musculoskeletal disorders (MSD) are thought to be declining based on Bureau of Labor Statistics survey data, but there is also evidence of MSD under-reporting, raising the possibility of contrary trends. The magnitude of MSD under-reporting over time, and its industry distribution have not been adequately described. METHODS: Capture-recapture analysis of 7 years of Connecticut MSD (1995-2001), utilizing Workers' Compensation and physician reporting data was performed. RESULTS: Only 5.5%-7.9% of MSD cases appear to be reported to Workers Compensation annually. The capture-recapture estimated average annual rate for upper-extremity MSD was 133.1 per 10,000 employed persons, far above BLS rates. By industry, Manufacturing, State Government, and the Finance/Insurance/Real Estate sectors all had significantly higher MSD rates than Wholesale/Retail Trade. CONCLUSIONS: Upper-extremity MSD appears to be significantly under-reported, and rates are not decreasing over time. Capture-recapture methods provide an improved surveillance method for monitoring temporal trends in injury rates.