RESUMO
BCG vaccine has been used for 100 years to prevent tuberculosis. Not all countries, including the United States, adopted the initial World Health Organization recommendation to use BCG. Moreover, many Western countries that had routinely used BCG have discontinued its use. Recent population studies demonstrate lower prevalence of Alzheimer's disease (AD) in countries with high BCG coverage. Intravesicular instillation of BCG is also used to treat bladder cancer that has not invaded the bladder muscle wall and has been shown to reduce recurrence. Several retrospective studies of bladder cancer patients demonstrated that BCG treatment was associated with a significantly reduced risk of developing AD. Plasma amyloid ß assessment has become a fertile area of study for an AD biomarker that is predictive of a positive amyloid PET scan. Mass spectrometry-based plasma amyloid 42/40 ratio has proven to be accurate and robust, and when combined with age and ApoE, is shown to accurately predict current and future brain amyloid status. These parameters, amyloid 42/40 ratio, age and ApoE genotype are incorporated into an Amyloid Probability Score (APS)-a score that identifies low, intermediate or high risk of having a PET scan positive for cerebral amyloid. Community recruitment was used for this open-label pilot study. Forty-nine BCG-naïve, immunocompetent individuals completed our study: prior to BCG prime and boost, as determined by the APS, 34 had low risk (APS 0-35), 5 had intermediate risk (APS 36-57) and 10 had high risk (APS 58-100). The APS range for the participant group was 0 to 94. Follow-up plasma amyloid testing 9 months after vaccination revealed a reduction in the APS in all the risk groups: low risk group (p = 0. 37), intermediate risk group (p = 0.13) and the high-risk group (statistically significant, p = 0.016). Greater benefit was seen in younger participants and those with the highest risk. The small number of participants and the nascent status of plasma amyloid testing will rightfully temper embracement of these results. However, both the favorable direction of change after BCG as well as the utility of the APS-a valuable surrogate AD biomarker-may prompt a definitive large-scale multicenter investigation of BCG and AD risk as determined by plasma amyloid peptide ratios and APS.
RESUMO
BACKGROUND: The US government affirmed the opioid epidemic as a public health emergency in late 2017. Prior to that, as part of the Heroin, Opiate, Prevention, and Education (HOPE) Agenda, the state of Wisconsin enacted 2015 Wisconsin Act 266. This law, which went into effect April 1, 2017, requires prescribers to review data from the state's enhanced Prescription Drug Monitoring Program (ePDMP) before issuing an opioid prescription, in order to reduce inappropriate prescriptions and, ultimately, decrease opioid overuse. OBJECTIVE: To evaluate the effect of 2015 Wisconsin Act 266 on opioid prescriptions for acute pain in Mayo Clinic Health System sites in northwest Wisconsin. PATIENTS AND METHODS: This retrospective review included all eligible patients who were discharged from emergency or urgent care departments in the Mayo Clinic Health System at northwest Wisconsin sites during the study period. The quantity of opioids prescribed (measured in morphine milligram equivalents per patient encounter) and the total number of opioid prescriptions were compared for the periods May and June 2016 (prior to implementation of Act 266) versus May and June 2017 (post-implementation of Act 266). RESULTS: A 33% reduction occurred in the median opioid quantity prescribed per patient encounter in the post-implementation period vs the pre-implementation period (P <0.001). In addition, a 13% relative reduction occurred in the percentage of patient encounters that involved an opioid prescription (P <0.001). No difference was observed in opioid prescription agents between time periods, except for an increase in morphine prescriptions (P <0.001. CONCLUSION: The HOPE Agenda, specifically 2015 Wisconsin Act 266, appears to have had a positive effect on decreased opioid prescriptions for acute pain at Mayo Clinic Health System sites in northwest Wisconsin.
