Bioabsorbable, subcutaneous naltrexone implants mitigate fentanyl-induced respiratory depression at 3 months-A pilot study in male canines.

The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly-d,l-Lactic Acid (PDLLA) and/or Polycaprolactone (PCL-1 or PCL-2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97-100 days after implantation. Following the administration of a 30 µg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre-dose respiratory rate (RR). The BIOPIN NTX-implanted dogs were exposed to escalating doses of intravenous fentanyl (30 µg/kg, 60 µg/kg, 90 µg/kg, and 120 µg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 µg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 µg/kg and especially at 120 µg/kg. Bioabsorbable, extended-release BIOPIN naltrexone implants are effective in mitigating fentanyl-induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl-induced respiratory depression in humans.

A Retrospective Chart Review Evaluating the Relationship between Cancer Diagnosis and Residential Water Source on the Lower Eastern Shore of Maryland, USA.

Well water contamination in heavily agricultural regions has previously been linked with increased cancer incidence and mortality. The lower Eastern shore of Maryland is a rural, agricultural region with some of the highest rates of cancer in Maryland and the United States. Our study sought to characterize residential private well water use among cancer patients on the lower Eastern shore of Maryland, and to compare private well water utilization between cancer patients and the general regional population. Retrospective chart review was conducted to identify patients diagnosed with colon, lung, melanoma or breast cancer at a regional hospital from 1 January 2017 through 31 December 2018. Residential water source was determined using residential address and municipal water records. Fisher's exact test was used to compare residential private well water utilization between our study population and the baseline regional population. The majority of cancer patients (57%) lived in homes supplied by private well water (428/746). Cancer patients were more likely to live in homes supplied by private well water compared to individuals in the general regional population (57% vs. 32%, p < 0.001). In conclusion, cancer patients on the lower Eastern shore of Maryland were more likely to live in homes supplied by residential private well water than the regional population. Additional studies are needed to evaluate well water use and cancer risk in this vulnerable region.