Perioperative Management of Buprenorphine/Naloxone in a Large, National Health Care System: a Retrospective Cohort Study.

BACKGROUND: Medication for opioid use disorder, including buprenorphine and methadone, is considered the gold standard treatment for opioid use disorder (OUD). As the number of patients receiving buprenorphine has grown, clinicians increasingly care for patients prescribed buprenorphine who present for surgery and require management of perioperative pain. OBJECTIVE: To describe practice patterns of perioperative and post-surgical use of buprenorphine among patients prescribed buprenorphine for OUD who experience major surgery. DESIGN: Retrospective cohort study utilizing data from the VA Corporate Data Warehouse (CDW), a national repository of patient-level data. Data not accessible in CDW, including clinical instructions to patients to modify buprenorphine dose, were accessed via chart review. PARTICIPANTS: National sample of patients receiving care through the Veterans Health Administration. MAIN MEASURES: We report descriptive statistics on the incidence of buprenorphine dose hold prior to, during, and immediately following surgery, as well as post-surgical outcomes. Multivariable logistic regression identified socio-demographic and clinical characteristics associated with perioperative hold. KEY RESULTS: Our final sample comprised 183 patients, the majority of whom were white and male. Most patients (66%) experienced a perioperative buprenorphine dose hold: during the pre-operative, day of surgery, and post-operative periods, 40%, 62%, and 55% of patients had buprenorphine held. Buprenorphine dose hold was less likely for patients who had experienced homelessness/housing insecurity in the year prior to surgery (aOR = 0.25; 95% CI 0.10-0.61) as well as patients residing in rural areas (aOR=0.29; 0.12-0.68). Within the 12-month period following surgery, 122 patients (67%) were retained on buprenorphine, 10 patients (5.5%) had experienced an overdose, and 15 (8.2%) had died. CONCLUSIONS: We identified high rates of perioperative buprenorphine dose holds. As holding buprenorphine perioperatively does not align with emerging clinical recommendations and carries significant risks, educational campaigns or other provider-targeted interventions may be needed to ensure patients with OUD receive recommended care.

Values in First-Episode Schizophrenia.

OBJECTIVE: Functional impairment continues to represent a major challenge in schizophrenia. Surprisingly, patients with schizophrenia report a level of happiness comparable with control subjects, even in the face of the prominent functional deficits, a finding at odds with evidence indicating a positive relation between happiness and level of functioning. In attempting to reconcile these findings, we chose to examine the issue of values, defined as affectively infused criteria or motivational goals used to select and justify actions, people, and the self, as values are related to both happiness and functioning. METHODS: Fifty-six first-episode patients in remission and 56 healthy control subjects completed happiness and values measures. Statistical analyses included correlations, analysis of variance, structural equation modelling, and smallest space analysis. RESULTS: Results indicated that patients with schizophrenia placed significantly greater priority on the value dimensions of Tradition (P = 0.02) and Power (P = 0.03), and significantly less priority on Self-direction (P = 0.007) and Stimulation, (P = 0.008). CONCLUSIONS: Essentially, people with schizophrenia place more emphasis on the customs and ideas that traditional culture or religion provide in conjunction with a decreased interest in change, which is at odds with the expectations of early adulthood. This value difference could be related to functional deficits. To this point, we have assumed that people hold to the same values that guided them before the illness' onset, but this may not be the case. Our study indicates that values differ in people with schizophrenia, compared with control subjects, even early in the illness and in the face of symptomatic remission.

Exploring the effect of inducing long-term potentiation in the human motor cortex on motor learning.

BACKGROUND: Paired-associative stimulation (PAS) represents a neurophysiologic paradigm that involves peripheral nerve stimulation (PNS) of the median nerve, followed by the transcranial magnetic stimulation (TMS) of the contralateral motor cortex. PAS has been shown to result in long-term potentiation-like activity (PAS-LTP) if PNS precedes TMS by 25 milliseconds (PAS-25). PAS-LTP has also been shown to relate to simple motor performance. However, to date, no studies have directly investigated whether the induction of PAS-LTP is associated with enhanced motor learning. OBJECTIVE: The objective of this study was to assess the short- and long-term effect of PAS-25 on motor learning. METHODS: This was a randomized controlled pilot study in which the control condition was PAS-10, whereby PNS precedes TMS by 10 milliseconds. Motor learning was assessed using the rotary pursuit task at baseline prior to PAS-25 or PAS-10 and 45 minutes and 1 week post-PAS. RESULTS: As expected PAS-25 but not PAS-10 was associated with PAS-LTP as indexed by a significant potentiation of the motor evoked potential. Also, PAS-25 resulted in enhanced motor learning at 1 week post-PAS (F (2, 44) = 3.441, P = .041). CONCLUSIONS: This is the first PAS study showing long-term behavioral effect and suggests, albeit indirectly, that PAS-25 can trigger slowly manifesting cellular and structural changes that result in long-term improvement in motor performance. Larger studies with neurophysiologic or neuroimaging outcomes are needed to confirm such preliminary findings.

Safety of influenza vaccination in patients with myasthenia gravis: a population-based study.

Influenza vaccination has been associated with adverse events including Guillain-Barré syndrome. Because the safety of influenza vaccination in patients with myasthenia gravis (MG) has not been established, some clinicians discourage vaccination for these patients. We explored whether the administration of influenza vaccine to patients with MG might increase the risk of myasthenic crisis. Using population-based healthcare data from Ontario, Canada, from 1992 to 2007, we utilized the self-matched, case-series method of detecting adverse events following vaccination. We studied patients with established myasthenia who were hospitalized for MG within 42 weeks of influenza vaccination. We defined the primary risk interval as the 6 weeks following vaccination. Between January 1, 1992 and March 31, 2006, we identified 3667 hospital admissions for MG. No seasonal trend in MG admissions was evident. In 513 instances, hospitalization occurred within 42 weeks following vaccination in patients previously diagnosed with MG. Among these patients, 266 (52%) were men, the median age was 74 years, and 86 (17%) had previously undergone thymectomy. The estimated relative incidence of admission for MG in the primary risk interval compared with the control interval was 0.84 (95% confidence interval 0.65-1.09). We found similar results in stratified analyses according to gender, age, and thymectomy status. Vaccination of patients with MG against influenza was not found to be associated with exacerbations of the disease. Our findings do not support the practice of withholding influenza vaccination in patients with MG.

Peritoneal morphological and functional changes associated with platelet-derived growth factor B.

BACKGROUND: Morphological changes associated with long-term peritoneal dialysis (PD) include increased vascular surface area due to angiogenesis, submesothelial fibrosis and epithelial mesenchymal transition. Platelet-derived growth factor (PDGF) has been associated with all of these phenomena, and is a prototypical 'response to injury' growth factor. METHODS: Rats received an intraperitoneal injection of adenoviral vector expressing PDGF-B. At sacrifice, we analysed the structure and function of the peritoneal membrane. Gene expression in the peritoneal tissue was assessed for changes suggestive of epithelial mesenchymal transition. RESULTS: Over-expression of PDGF in the rat peritoneum led to significant angiogenesis, cellular proliferation and submesothelial thickening. Although PDGF induced expression of transforming growth factor beta, there was a lack of activation of this growth factor, and we believe that this explains the lack of significant collagen accumulation observed by a hydroxyproline assay. Despite evidence of angiogenesis and subsequent increased solute transport, we observed only a transient, non-significant impact on ultrafiltration function. This suggests that increased vascular surface area is necessary, but not sufficient, to produce ultrafiltration dysfunction. There was no evidence of epithelial mesenchymal transition observed either in regulation of associated genes such as Snail or E-Cadherin or in the lack of dual-labelled epithelial and mesenchymal cells on immunofluorescence. Mesothelial cells exposed to PDGF-B demonstrated increased collagen gene expression. CONCLUSIONS: PDGF-B induced angiogenesis without fibrosis in the peritoneum. The lack of significant ultrafiltration dysfunction and epithelial mesenchymal transition, as observed in patients on PD, suggests that PDGF-B may play a role, but is not the integral component, in response to peritoneal injury.