Ethanol reversal of tolerance to the respiratory depressant effects of morphine

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO(2) in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths

Exploring how mindfulness can support young children’s well-being in the nursery school

This paper explores how a mindfulness approach can support young children’s well-being in nursery schools. The research draws on a small scale qualitative research project with four maintained nursery schools in the South of England. In total there were 33 participants including 5 early years professionals and 27 children aged between 3 and 4 years. An action research approach was adopted involving the nursery schools in each stage of the project. Mixed methods were used including semi-structured interviews, narrative observations, and reflective journals. In line with previous research, the findings from this study suggest that mindfulness supports children’s well-being and self-regulation. Key factors integral to the success of the project included: the role of the mindfulness champion; high-quality training, and an adaptable and flexible approach. In conclusion it is argued that mindfulness practices are an appropriate way of supporting children’s well-being in the early years; and that a Train The Trainer [TTT] approach is cost effective and sustainable

Sinus Irrigation Penetration After Proposed Modified Draf IIa Technique in a Side-to-Side Cadaveric Model

Background Endoscopic sinus surgery (ESS) is an effective intervention for patients with medically refractory chronic rhinosinusitis. Frontal sinusotomy is the most challenging part of ESS, with one of the key outcomes being access for topical irrigations. Objective The purpose of this study is to compare irrigation penetration into the frontal sinus following Draf IIa versus modified Draf IIa frontal sinusotomy. Methods Four fresh cadaver heads were used in this experiment. Draf IIa was performed on one side of each head and a modified Draf IIa on the contralateral side. This proposed modification consists of a Draf IIa combined with an agger nasi punch-out procedure and partial trimming of the vertical lamella of the middle turbinate back to the posterior table of the frontal sinus without drilling the beak. Each head was irrigated with methylene blue-dyed water and recorded by rigid endoscopy through an endonasal view (EV) of the frontal sinus and frontal trephination view (TV). Two blinded rhinologists scored the extent of staining (using an ordinal scale of 0 to 3) for each side. A case report where the modified Draf IIa was performed is also described. Results After modified Draf IIa sinuosotomy, the mean score for the EV was 2.125 and for the TV was 2, versus 0.875 and 0.625 for traditional Draf IIa, respectively. There was a statistically significant increase for both EV (p = 0.019) and TV (p = 0.018) after modified Draf IIa. Conclusion In our cadaveric model, this procedural modification improved penetration of postoperative irrigations into the frontal sinus. This simple technique may be easily adapted into frontal ESS when indicated. </jats:sec

3030 Symptom profile of chronic rhinosinusitis versus obstructive sleep apnea in a tertiary rhinology clinic

OBJECTIVES/SPECIFIC AIMS: Patients with undiagnosed obstructive sleep apnea (OSA) will often present to an otolaryngologist with symptoms of chronic rhinosinusitis (CRS). Differentiating CRS from OSA may help obviate unnecessary and costly work-up for CRS. This study analyzes symptom profiles of such patients to help identify which require polysomnography. METHODS/STUDY POPULATION: This is a three-year retrospective analysis of adult patients seen in an academic practice with a rhinologic chief complaint. The 22-Item Sinonasal Outcomes Test (SNOT-22) survey, which is a validated patient-reported outcome measure widely adopted for CRS featuring a symptom scale of 1 (least severe) to 5 (most severe), was completed by patients with untreated OSA confirmed on polysomnography without CRS (OSA group) and a control group of CRS patients (CRS group). Results were compared using Chi-square test (categorical) and Wilcoxon rank-sum test (continuous) with Bonferroni correction, and multiple logistic regression. RESULTS/ANTICIPATED RESULTS: 43 patients were included in the OSA group [mean apnea-hypopnea index: 27.9 (SD: 21.2)] and 124 patients were included in the CRS group. The CRS group demonstrated significantly higher scores in nasal (p &lt; 0.001), extra-nasal (p &lt; 0.001) and ear/facial symptom domains (p = 0.001) while the OSA group reported higher psychological (p = 0.028) and sleep symptom domain scores (p = 0.052). As for the cardinal symptoms of CRS, nasal discharge and loss of smell were significantly higher in the CRS group (both p &lt; 0.001), whereas facial pain (p = 0.117) and nasal obstruction (p = 0.198) were not significantly different between the two groups. After adjustment, for every 1-point increase in a patient’s score for ear pain, thick nasal discharge and loss of smell or taste, their odds of having CRS increased by a factor of 3.18 [(95% CI 1.61-6.29), p = 0.001], 1.60 [(95% CI 1.22-2.10], p = 0.001] and 1.36 [(95% CI 1.04-1.78), p = 0.025], respectively, compared to having OSA. OSA patients were more likely to choose a sleep-related symptom as a “most important complaint” (MIC) (p &lt; 0.001). Facial pain and nasal obstruction were the most common MIC in the rhinologic domain for OSA patients, whereas thick nasal discharge and post-nasal discharge were the most common MIC for CRS patients. DISCUSSION/SIGNIFICANCE OF IMPACT: For patients presenting with rhinologic symptoms, the SNOT-22 can help identify those with undiagnosed OSA. OSA should be suspected in patients with sleep and psychological dysfunction as their primary complaints without the significant nasal drainage and anosmia that characterizes CRS.</jats:p

Sinus Irrigation Penetration After Proposed Modified Draf IIa Technique in a Side-to-Side Cadaveric Model

Background Endoscopic sinus surgery (ESS) is an effective intervention for patients with medically refractory chronic rhinosinusitis. Frontal sinusotomy is the most challenging part of ESS, with one of the key outcomes being access for topical irrigations. Objective The purpose of this study is to compare irrigation penetration into the frontal sinus following Draf IIa versus modified Draf IIa frontal sinusotomy. Methods Four fresh cadaver heads were used in this experiment. Draf IIa was performed on one side of each head and a modified Draf IIa on the contralateral side. This proposed modification consists of a Draf IIa combined with an agger nasi punch-out procedure and partial trimming of the vertical lamella of the middle turbinate back to the posterior table of the frontal sinus without drilling the beak. Each head was irrigated with methylene blue-dyed water and recorded by rigid endoscopy through an endonasal view (EV) of the frontal sinus and frontal trephination view (TV). Two blinded rhinologists scored the extent of staining (using an ordinal scale of 0 to 3) for each side. A case report where the modified Draf IIa was performed is also described. Results After modified Draf IIa sinuosotomy, the mean score for the EV was 2.125 and for the TV was 2, versus 0.875 and 0.625 for traditional Draf IIa, respectively. There was a statistically significant increase for both EV (p = 0.019) and TV (p = 0.018) after modified Draf IIa. Conclusion In our cadaveric model, this procedural modification improved penetration of postoperative irrigations into the frontal sinus. This simple technique may be easily adapted into frontal ESS when indicated

Olfactory-Specific Quality of Life Outcomes after Endoscopic Endonasal Surgery of the Sella

Objective To assess olfactory outcomes as measured by an olfactory-specific quality of life (QOL) questionnaire in patients undergoing EESBS for sellar lesions. Design Retrospective case series. Setting Tertiary academic medical center. Participants In total, 36 patients undergoing EESBS for lesions limited to the sella were evaluated. Main Outcome Measures The following were performed before and three months after surgery: 22-Item Sinonasal Outcomes Test (SNOT-22), University of Pennsylvania Smell Identification Test (UPSIT), and the Assessment of Self-reported Olfactory Functioning (ASOF), which has three domains: subjective olfactory capability scale (SOC), smell-related problems (SRP), and olfactory-related quality of life (ORQ). Results Median age at surgery was 52.5 years, with a median tumor size of 1.8 cm (range: 0.2 to 3.9 cm). Pre- and postoperative median scores were 35 [34, 36.2] and 34.5 [32, 36] for UPSIT, 21 [7.5, 33.5] and 21.5 [6.8, 35.7] for SNOT-22, 10 [9, 10] and 9 [8, 10] for ASOF-SOC, 5 [4.8, 5] and 4.5 [4, 5] for ASOF-SRP, and 5 [5, 5] and 5 [4.5, 5] for ASOF-ORQ. There was no significant change in the two of the three domains of the ASOF. Correlation between ASOF and UPSIT scores were weak. Older age and larger tumor size were associated with worsened olfaction after surgery. Conclusions Patients did not experience significant changes in olfactory-specific QOL three months after EESBS, as measured by two domains of the ASOF. The ASOF may serve as a useful adjunctive tool for assessing olfaction after surgery. The lack of correlation between UPSIT and ASOF suggests the need for more research in subjective olfactory-related quality of life after surgery. </jats:sec