The case for a medication first approach to the treatment of opioid use disorder

Background: The opioid addiction and overdose crisis continues to ravage communities across the U.S. Maintenance pharmacotherapy using buprenorphine or methadone is the most effective intervention for Opioid Use Disorder (OUD), yet few have immediate and sustained access to these medications. Objectives: To address lack of medication access for people with OUD, the Missouri Department of Mental Health began implementing a Medication First (Med First) treatment approach in its publicly-funded system of comprehensive substance use disorder treatment programs. Methods: This Perspective describes the four principles of Med First, which are based on evidence-based guidelines. It draws conceptual comparisons between the Housing First approach to chronic homelessness and the Med First approach to pharmacotherapy for OUD, and compares state certification standards for substance use disorder (SUD) treatment (the traditional approach) to Med First guidelines for OUD treatment. Finally, the Perspective details how Med First principles have been practically implemented. Results: Med First principles emphasize timely access to maintenance pharmacotherapy without requiring psychosocial services or discontinuation for any reason other than harm to the client. Early results regarding medication utilization and treatment retention are promising. Feedback from providers has been largely favorable, though clinical- and system-level obstacles to effective OUD treatment remain. Conclusion: Like the Housing First model, Medication First is designed to decrease human suffering and activate the strengths and capacities of people in need. It draws on decades of research and facilitates partnerships between psychosocial and medical treatment providers to offer effective and life-saving care to persons with OUD.     

Evaluating the responsiveness of the endometriosis health profile questionnaire: The EHP-30

OBJECTIVES: To evaluate the sensitivity to change of the Endometriosis Health Profile-30 (EHP-30) questionnaire. SETTING: The Women's Center, John Radcliffe Hospital, Oxford. DESIGN: Postal survey to 66 women undergoing conservative surgery for the treatment of endometriosis-associated pain. The EHP-30 and the Short Form-36 (SF-36) were administered 2 weeks before the operation, and 4 months post-operatively. At T2 a transition question was included to evaluate changes in patients health status. To evaluate responsiveness effect sizes, standardised response means, the index of responsiveness and the minimally and clinically important differences were calculated. RESULTS: Forty (66.6%) patients returned the questionnaires at time 1 and 2. Overall less responsive effect size scores were found for the SF-36 (0.1-0.5) compared to the EHP-30 (-0.1-1.1) for all patients who had undergone treatment. Minimally important differences and the index of responsiveness were overall higher for the EHP-30 (0.4-2.0) compared to the SF-36 (0.1-1.0). Change scores for four of the five scales were significantly correlated with women's responses to the transition question. CONCLUSIONS: Results suggest that the EHP-30 is sensitive to change. Its application in clinical trials should prove beneficial in assessing the impact of medical and surgical interventions upon quality of life for women with endometriosis.     

Teaching with a Video System Improves the Training Period but Not Subsequent Success of Tracheal Intubation with the Bullard Laryngoscope

Background: The Bullard laryngoscope is useful for the management of a variety of airway management scenarios. Without the aid of a video system, teaching laryngoscopy skills occurs with indirect feedback to the instructor. The purpose of this study was to determine if use of a video system would quicken the process of learning the Bullard laryngoscope or improve the performance (speed or success) of its use.

Methods: Thirty-six anesthesia providers with no previous Bullard laryngoscope experience were randomly divided into two groups: initial training (first 15 intubations) with looking directly through the eyepiece (n = 20), or with the display of the scope on a video monitor (n = 16). The subjects each then performed 15 Bullard intubations by looking directly through the eyepiece.

Results: There was not an overall significant difference in laryngoscopy or intubation times between the groups. When only the first 15 intubations were considered, the laryngoscopy time was shorter in the video group (26 +/- 24) than in the nonvideo group (32 +/- 34;P < 0.04). In the first 15 patients, there were fewer single attempts at intubation (67.9%vs. 80.3%;P < 0.002) and more failed intubations (17.2%vs. 6.0%;P < 0.0001) in the nonvideo group.     

Decreased amygdala CRF-binding protein mRNA in post-mortem tissue from male but not female bipolar and schizophrenic subjects.

Stressful life events are commonly associated with the onset and maintenance of psychopathology and much research has focused on the role of the corticotropin-releasing factor (CRF) system in mediating psychopathology. Since CRF serves to integrate the stress response, it is possible that the CRF system plays a role as a neurochemical linkage between stress and psychopathology. CRF-binding protein (CRF-BP) is thought to modulate CRF activity by decreasing its actions. Therefore, in some psychopathological states, alterations in CRF-BP function may contribute to dysregulation of the CRF system. Since the amygdala CRF system mediates stress- and anxiety-related behaviors and alterations in amygdala function are associated with psychopathology, we examined amygdala CRF-BP gene expression in post-mortem brains from subjects with major depression, bipolar disorder, and schizophrenia as well as in controls. In addition to characterizing the anatomic distribution of CRF-BP mRNA in the human amygdala and medial temporal lobe region, we found a significant decrease in CRF-BP mRNA levels in the basolateral amygdala of male bipolar and male schizophrenic subjects and the lateral amygdala of male bipolar subjects. These results raise the possibility that men with decreased amygdala CRF-BP may be more vulnerable to the effects of stress exposure on the etiology or maintenance of bipolar disorder or schizophrenia.     

Quality of life in patients undergoing inguinal hernia repair.

Inguinal hernia repair is one of the most common surgical procedures undertaken in the NHS. Despite this, no previous work has examined quality of life in this patient group. This study examines quality of life preoperatively and at 3 and 6 months postoperatively in 140 patients undergoing inguinal hernia repair in the context of a randomised controlled trial of laparoscopic versus open hernia repair. Surgery was undertaken on a day case basis, and quality of life was assessed using the Short Form 36 (SF36). In the initial phase of the study, 57% of those screened for suitability met the study inclusion criteria and were randomised. No significant differences were found between laparoscopic and open hernia repair in terms of quality of life at 3 and 6 months postoperatively. No difference was found between 3 and 6 month scores, suggesting that patients had already made a good recovery by 3 months. A significant improvement was found between preoperative and postoperative scores, with the greatest change arising on dimensions assessing pain, physical function, and role limitation owing to physical restriction. After standardising for age, sex, and social class, a comparison of the hernia patients to population norms for the SF36 was consistent with improvement from preoperative to postoperative assessment. This study has demonstrated the improvement in quality of life in patients undergoing elective inguinal hernia repair by experienced surgeons on a day case basis. It has also demonstrated the feasibility of assessing quality of life using generic measures in this patient group. Further work in this area is required. Ultimately, the priority given to elective inguinal hernia repair will depend on how the demonstrated benefits compare with those derived from other elective surgical procedures.     

The effect of noradrenaline on the end-plate potential in twitch fibres of the frog

1. The action of noradrenaline in increasing the amplitude of the end-plate potential (e.p.p.) has been studied in magnesium-blocked frog skeletal muscle.2. Noradrenaline (10(-5)M) increased the e.p.p. by about 20% without causing any comparable change in the amplitude of the miniature end-plate potentials (m.e.p.p.s). It was concluded that noradrenaline acts by potentiating the release of acetylcholine by the nerve impulse, rather than by increasing the sensitivity of the end-plate.3. In support of this, it was found that the increase in e.p.p. amplitude was associated with a reduction in the variability of successive e.p.p.s, as is to be expected if the quantal content of the e.p.p. became larger. Further, noradrenaline was without effect on the response to iontophoretically-applied acetylcholine, although it potentiated depolarizations elicited by acetylcholine applied for much longer periods in the bathing fluid.4. Noradrenaline increased the frequency of occurrence of m.e.p.p.s, and unusually large m.e.p.p.s. were occasionally observed.     

Structure-function studies of the C3a-receptor: C-terminal serine and threonine residues which influence receptor internalization and signaling

The anaphylatoxic peptide C3a is a pro-inflammatory mediator generated during complement activation, whose specific G protein coupled receptor is expressed on granulocytes, monocytes, mast cells, activated lymphocytes, and in the nervous tissue. We have generated RBL-2H3 cell clones stably expressing mutants of the human C3a-receptor (C3aR) with combined alanine (Ala) substitutions of ten C-terminal serine (Ser) or threonine (Thr) residues, which may represent putative phosphorylation sites to characterize their role in ligand-induced C3aR internalization and signaling. Ser475/479 and Thr480/481 as well as Ser449 seemed not to be involved in ligand-induced receptor internalization. Either directly or by a conformational change they even "inhibit" C3aR internalization. In contrast, mutants with Ala substitutions at Ser465/470 and Thr463/466 were poorly internalized, and Thr463 seemed to be the most important C-terminal Thr or Ser residue directly effecting receptor internalization. However, it is likely that other C3aR regions additionally participate in this negative feed-back mechanism since even mutants with multiple Ala substitutions still internalized to a limited degree. Interestingly, in a mutant with a single exchange of Ser449 to Ala, the signal transduction assessed by a Ca(2+) assay and [(35)S]GTP gamma S-binding on HEK cells transiently co-transfected with G-alpha 16 or G-alpha O, respectively, was severely impaired, indicating that this residue of C3aR is involved in G protein coupling.