Cross-sectional study of rapid tapering of opioid prescriptions following medical regulatory intervention in Alberta from 2013 to 2020.

OBJECTIVE: To determine if inappropriate tapering/discontinuation of opioids to Alberta patients occurred from mid-2013-2020, as unintended consequences of prescribing guidelines, regulations and policies in response to the North American opioid crisis. DESIGN: A population-based, repeated cross-sectional time-series study. SETTING: Alberta, Canada. PARTICIPANTS: Residents of Alberta, Canada aged 18 and older who received an opioid dispense from a community pharmacy from 2013 to 2020. MAIN OUTCOME MEASURES: The prevalence of potential rapid tapering was measured at a given date (reference day), enveloped by a data window. Dose changes were measured as oral morphine equivalents (OME) per patient, at multiple time points ('data window' around a reference day). Chronic recipients were identified, and their prescriptions were contrasted 90 days before and after the reference day to measure OME/day changes. RESULTS: Approximately 9000 dispenses (totalling ~6 million OME) per day were analysed from 2013 to 2020. The total number of opioid recipients was highly cyclic in nature (peaking in winter). The number of chronic opioid recipients remained somewhat stable from ~70K in 2013 to ~86K at the end of 2020. The number of chronic high and very high dose recipients presented a significant decrease after 2017. Approximately 11%-12% of chronic high-dose recipients experienced potential rapid dose tapering at a rate of 50% or more prereference to postreference day at any given point of time. For chronic very high dose recipients, approximately 11.5% experience potential rapid dose tapering at a rate of 50% or more prereference to postreference day at any given point of time. Potential discontinuation remained constant and the interventions did not have a significant impact on the trend. CONCLUSION: The evidence suggests that changes in prescribing guidelines were not associated with an increase of rapid opioid tapering/discontinuation in Alberta.

Reducing prescribing of benzodiazepines in older adults: a comparison of four physician-focused interventions by a medical regulatory authority.

BACKGROUND: The inappropriate and/or high prescribing of benzodiazepine and 'Z' drugs (BDZ +) is a major health concern. The purpose of this study was to determine whether physician or pharmacist led interventions or a simple letter or a personalized prescribing report from a medical regulatory authority (MRA) was the most effective intervention for reducing BDZ + prescribing by physicians to patients 65 years of age or older. METHODS: This was a four-armed, one year, blinded, randomized, parallel-group, investigational trial in Alberta, Canada. Participants were fully licensed physicians (n = 272) who had prescribed 4 times the defined daily dose (4 + DDD) or more of any BDZ + to an older patient at least once in the 3rd quarter of 2016. All physician-participants were sent a personalized prescribing profile by the MRA. They were then randomized into four groups that received either nothing more, an additional personal warning letter from the MRA, a personal phone call from an MRA pharmacist or a personal phone call from an MRA physician. The main outcomes were prescribing behavior change of physicians at one year in terms of: change in mean number of older patients receiving 4 + DDD BDZ + and mean dose BDZ + prescribed per physician. To adjust for multiple statistical testing, we used MANCOVA to test both main outcome measures simultaneously by group whilst controlling for any baseline differences. RESULTS: All groups experienced a significant fall in the total number of older patients receiving 4 + DDD of BDZ + by about 50% (range 43-54%) per physician at one year, and a fall in the mean dose of BDZ + prescribed of about 13% (range 10-16%). However, there was no significant difference between each group. CONCLUSIONS: A personalized prescribing report alone sent from the MRA appears to be an effective intervention for reducing very high levels of BDZ + prescribing in older patients. Additional interventions by a pharmacist or physician did not result in additional benefit. The intervention needs to be tested further on a more general population of physicians, prescribing less extreme doses of BDZ + and that looks at more clinical and healthcare utilization outcomes.

Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens.

BACKGROUND: Fomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities. The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs. Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues. METHODS: We developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces. We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites). We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types. To parameterize the model for each pathogen we conducted a thorough literature search. RESULTS: Based on parameter estimates from the literature the reproductive number ([Formula: see text]) for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission. For influenza, on the other hand, [Formula: see text] for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission. Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus. The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands. Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding. CONCLUSIONS: Fomite-mediated transmission is an important pathway for the three pathogens examined. The effectiveness of environmental interventions differs significantly both by pathogen and venue. While fomite-based interventions may be able to lower [Formula: see text] for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious ([Formula: see text]) that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens.

Mathematical models of Ebola-Consequences of underlying assumptions.

Mathematical models have been used to study Ebola disease transmission dynamics and control for the recent epidemics in West Africa. Many of the models used in these studies are based on the model of Legrand et al. (2007), and most failed to accurately project the outbreak's course (Butler, 2014). Although there could be many reasons for this, including incomplete and unreliable data on Ebola epidemiology and lack of empirical data on how disease-control measures quantitatively affect Ebola transmission, we examine the underlying assumptions of the Legrand model, and provide alternate formulations that are simpler and provide additional information regarding the epidemiology of Ebola during an outbreak. We developed three models with different assumptions about disease stage durations, one of which simplifies to the Legrand model while the others have more realistic distributions. Control and basic reproduction numbers for all three models are derived and shown to provide threshold conditions for outbreak control and prevention.

Discrete stochastic metapopulation model with arbitrarily distributed infectious period.

In this study, a stochastic discrete-time model is developed to study the spread of an infectious disease in an n-patch environment. The model includes an arbitrary distribution of the (random) infectious period T, and the results are used to investigate how the distribution of T may influence the model outcomes. General results are applied to specific distributions including Geometric, Negative Binomial, Poisson and Uniform. The model outcomes are contrasted both numerically and analytically by comparing the corresponding basic reproduction numbers R0 and probability of a minor epidemic (or probability of disease extinction) P0. It is shown analytically that for n = 2 the reproduction numbers corresponding to different distributions of T can be ordered based on the probability generating function ϕT of T. In addition, numerical simulations are carried out to examine the final epidemic size F and duration of the epidemic D of a two-patch model.

Discrete epidemic models with arbitrary stage distributions and applications to disease control.

W.O. Kermack and A.G. McKendrick introduced in their fundamental paper, A Contribution to the Mathematical Theory of Epidemics, published in 1927, a deterministic model that captured the qualitative dynamic behavior of single infectious disease outbreaks. A Kermack­McKendrick discrete-time general framework, motivated by the emergence of a multitude of models used to forecast the dynamics of epidemics, is introduced in this manuscript. Results that allow us to measure quantitatively the role of classical and general distributions on disease dynamics are presented. The case of the geometric distribution is used to evaluate the impact of waiting-time distributions on epidemiological processes or public health interventions. In short, the geometric distribution is used to set up the baseline or null epidemiological model used to test the relevance of realistic stage-period distribution on the dynamics of single epidemic outbreaks. A final size relationship involving the control reproduction number, a function of transmission parameters and the means of distributions used to model disease or intervention control measures, is computed. Model results and simulations highlight the inconsistencies in forecasting that emerge from the use of specific parametric distributions. Examples, using the geometric, Poisson and binomial distributions, are used to highlight the impact of the choices made in quantifying the risk posed by single outbreaks and the relative importance of various control measures.