Blood-brain barrier: mechanisms governing permeability and interaction with peripherally acting μ-opioid receptor antagonists.

The blood-brain barrier (BBB) describes the unique properties of endothelial cells (ECs) that line the central nervous system (CNS) microvasculature. The BBB supports CNS homeostasis via EC-associated transport of ions, nutrients, proteins and waste products between the brain and blood. These transport mechanisms also serve as physiological barriers to pathogens, toxins and xenobiotics to prevent them from contacting neural tissue. The mechanisms that govern BBB permeability pose a challenge to drug design for CNS disorders, including pain, but can be exploited to limit the effects of a drug to the periphery, as in the design of the peripherally acting μ-opioid receptor antagonists (PAMORAs) used to treat opioid-induced constipation. Here, we describe BBB physiology, drug properties that affect BBB penetrance and how data from randomized clinical trials of PAMORAs improve our understanding of BBB permeability

Determinants of a GP visit and cervical cancer screening examination in Great Britain.

Objective: In the UK, women are requested to attend a cervical cancer test every 3 years as part of the NHS Cervical Screening Programme. This analysis compares the determinants of a cervical cancer screening examination with the determinants of a GP visit in the same year and investigates if cervical cancer screening participation is more likely for women who visit their GP. Methods: A recursive probit model was used to analyse the determinants of GP visits and cervical cancer screening examinations. GP visits were considered to be endogenous in the cervical cancer screening examination. The analysed sample consisted of 52,551 observations from 8,386 women of the British Household Panel Survey. Results: The analysis showed that a higher education level and a worsening self-perceived health status increased the probability of a GP visit, whereas smoking decreased the probability of a GP visit. GP visits enhanced the uptake of a cervical cancer screening examination in the same period. The only variables which had the same positive effect on both dependent variables were higher education and living with a partner. The probability of a cervical cancer screening examination increased also with previous cervical cancer screening examinations and being in the recommended age groups. All other variables had different results for the uptake of a GP visit or a cervical cancer screening examination. Conclusions: Most of the determinants of visiting a GP and cervical cancer screening examination differ from each other and a GP visit enhances the uptake of a smear test

Recommendations for effective documentation in regional anesthesia: an expert panel Delphi consensus project

Background and objectives: Documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of this study was to establish recommendations for documentation in regional anesthesia. Methods: Following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live polling on items not yet excluded or accepted from previous rounds. Progression or exclusion of potential components through the rounds was based on the achievement of strong consensus. Strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement. Results: Seventy-seven collaborators participated in both rounds 1 and 2, while 50 collaborators took part in round 3. In total, experts voted on 83 items and achieved a strong consensus on 51 items, weak consensus on 3 and rejected 29. Conclusion: By means of a modified Delphi process, we have established expert consensus on documentation in regional anesthesia

Peripherally Acting μ-Opioid Receptor Antagonists in the Management of Postoperative Ileus: a Clinical Review.

Postoperative ileus (POI) and constipation are common secondary effects of opioids and carry significant clinical and economic impacts. μ-Opioid receptors mediate opioid analgesia in the central nervous system (CNS) and gastrointestinal-related effects in the periphery. Peripherally acting μ-opioid receptor antagonists (PAMORAs) block the peripheral effects of opioids in the gastrointestinal tract, while maintaining opioid analgesia in the CNS. While most are not approved for POI or postoperative opioid-induced constipation (OIC), PAMORAs have a potential role in these settings via their selective effects on the μ-opioid receptor. This review will discuss recent clinical trials evaluating the safety and efficacy of PAMORAs, with a focus on alvimopan (Entereg®) and methylnaltrexone (Relistor®) in patients with POI or postoperative OIC. We will characterize potential factors that may have impacted the efficacy observed in phase 3 trials and discuss future directions for the management and treatment of POI

Peripherally Acting μ-Opioid Receptor Antagonists in the Management of Postoperative Ileus: a Clinical Review.

Postoperative ileus (POI) and constipation are common secondary effects of opioids and carry significant clinical and economic impacts. μ-Opioid receptors mediate opioid analgesia in the central nervous system (CNS) and gastrointestinal-related effects in the periphery. Peripherally acting μ-opioid receptor antagonists (PAMORAs) block the peripheral effects of opioids in the gastrointestinal tract, while maintaining opioid analgesia in the CNS. While most are not approved for POI or postoperative opioid-induced constipation (OIC), PAMORAs have a potential role in these settings via their selective effects on the μ-opioid receptor. This review will discuss recent clinical trials evaluating the safety and efficacy of PAMORAs, with a focus on alvimopan (Entereg®) and methylnaltrexone (Relistor®) in patients with POI or postoperative OIC. We will characterize potential factors that may have impacted the efficacy observed in phase 3 trials and discuss future directions for the management and treatment of POI