Rett Syndrome is a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2), a transcriptional regulator. In addition to cognitive, communication, and motor problems, affected individuals have abnormalities in autonomic function and respiratory control that may contribute to premature lethality. Mice lacking Mecp2 die early and recapitulate the autonomic and respiratory phenotypes seen in humans. The association of autonomic and respiratory deficits with premature death suggests Mecp2 is critical within autonomic and respiratory control centers for survival. To test this, we compared the autonomic and respiratory phenotypes of mice with a null allele of Mecp2 to mice with Mecp2 removed from their brainstem and spinal cord. We found that MeCP2 is necessary within the brainstem and spinal cord for normal lifespan, normal control of heart rate, and respiratory response to hypoxia. Restoration of MeCP2 in a subset of the cells in this same region is sufficient to rescue abnormal heart rate and abnormal respiratory response to hypoxia. Furthermore, restoring MeCP2 function in neural centers critical for autonomic and respiratory function alleviates the lethality associated with loss of MeCP2 function, supporting the notion of targeted therapy towards treating Rett syndrome.

Introduction: Patients undergoing oncologic surgery are at risk for persistent postoperative opioid use. As a quality improvement initiative, we sought to characterize provider perceptions regarding opioid prescribing after oncologic procedures.Methods: Surgical oncology attending physicians, clinical fellows, and advanced practice providers (APPs) at a high-volume cancer center were surveyed before and after educational sessions focusing on the opioid epidemic with review of departmental data.Results: Pre-education response rates were 72/103 (70%): 22/34 (65%) attendings, 19/21 (90%) fellows, 31/48 (65%) APPs. For 5 index operations (open abdominal resection, laparoscopic colectomy, wide local excision, thyroidectomy, port), fellows answered that patients should be off opioids sooner than attendings/APPs. For 4/5 procedures, APPs recommended higher discharge opioid prescriptions than attendings/fellows. Forty-six providers (45%) responded to both pre-and post-education surveys. After the intervention, providers recommended lower numbers of opioid pills and indicated that patients should be off opioids sooner for all procedures. Compared to preeducation, more providers agreed that discharge opioid prescriptions should be based on a patient's last 24 hours of inpatient opioid use (83% vs. 91%, p=0.006). Providers who did not attend a session showed no difference in perceptions or recommendations on repeat assessment.Conclusions: Variation exists in perioperative opioid prescribing among provider types, with those most involved in daily care and discharge processes generally recommending more opioids. After education, providers lowered discharge opioid recommendations and felt patients should be off opioids sooner. Next steps include assessing for quantitative changes in opioid prescribing and implementing standardized opioid prescription algorithms.

Rett syndrome (RTT), an X-linked postnatal disorder, results from mutations in Methyl CpG-binding protein 2 (MECP2). Survival and breathing in Mecp2(NULL/Y) animals are improved by an N-terminal tripeptide of insulin-like growth factor I (IGF-I) treatment. We determined that Mecp2(NULL/Y) animals also have a metabolic syndrome and investigated whether IGF-I treatment might improve this phenotype. Mecp2(NULL/Y) mice were treated with a full-length IGF-I modified with the addition of polyethylene glycol (PEG-IGF-I), which improves pharmacological properties. Low-dose PEG-IGF-I treatment slightly improved lifespan and heart rate in Mecp2(NULL/Y) mice; however, high-dose PEG-IGF-I decreased lifespan. To determine whether insulinotropic off-target effects of PEG-IGF-I caused the detrimental effect, we treated Mecp2(NULL/Y) mice with insulin, which also decreased lifespan. Thus, the clinical benefit of IGF-I treatment in RTT may critically depend on the dose used, and caution should be taken when initiating clinical trials with these compounds because the beneficial therapeutic window is narrow.

Background and Objectives A department‐wide opioid reduction education program resulted in a 1‐month change in perceptions of opioid needs and prescribing recommendations for surgical oncology patients. This study's aim was to re‐evaluate if early trends were retained 1 year later. Methods Surgical Oncology attendings, fellows, and advanced practice providers at a Comprehensive Cancer Center were surveyed 1‐year after an August 2018 opioid reduction education program, to compare departmental and individual opioid prescribing habits. Results The September 2019 response rate was 54/93 (58%), with 41 completing both the post‐education and 1‐year follow‐up surveys. The departmental and matched cohort continued to recommend a lower quantity of discharge opioids for all five index operations (by >50%) and expected less postoperative days to zero opioid needs, when compared to pre‐education perceptions. Providers continued to agree that discharge opioid prescriptions should be based on a patient's last 24 hours of inpatient opioid use. There was universal agreement that each respondent's opioid administration had decreased in the past year. Conclusions The initial 1‐month improvements in perioperative opioid prescribing perceptions were retained 1 year later by Surgical Oncology providers who recommended fewer discharge opioids, faster weaning to zero opioids, and standardized patient‐specific discharge opioid volume calculations.

State-specific limits on total days and procedure-specific recommendations of discharge opioid volumes have had mixed success in mitigating postoperative opioid dissemination. 1,2 Most prescribers still expose their clinician-specific bias in writing round numbers of opioid doses (eg, 30-50 pills). In the theme of patient-centered care, this study analyzed oncologic surgery discharge opioid prescriptions and 30-day refills when a novel, patient-centered prescription calculation was implemented.

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