Maternal opioid treatment after delivery and risk of adverse infant outcomes: population based cohort study.

OBJECTIVE: To examine whether maternal opioid treatment after delivery is associated with an increased risk of adverse infant outcomes. DESIGN: Population based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: 865 691 mother-infant pairs discharged from hospital alive within seven days of delivery from 1 September 2012 to 31 March 2020. Each mother who filled an opioid prescription within seven days of discharge was propensity score matched to a mother who did not. MAIN OUTCOME MEASURES: The primary outcome was hospital readmission of infants for any reason within 30 days of their mother filling an opioid prescription (index date). Infant related secondary outcomes were any emergency department visit, hospital admission for all cause injury, admission to a neonatal intensive care unit, admission with resuscitation or assisted ventilation, and all cause death. RESULTS: 85 675 mothers (99.8% of the 85 852 mothers prescribed an opioid) who filled an opioid prescription within seven days of discharge after delivery were propensity score matched to 85 675 mothers who did not. Of the infants admitted to hospital within 30 days, 2962 (3.5%) were born to mothers who filled an opioid prescription compared with 3038 (3.5%) born to mothers who did not. Infants of mothers who were prescribed an opioid were no more likely to be admitted to hospital for any reason than infants of mothers who were not prescribed an opioid (hazard ratio 0.98, 95% confidence interval 0.93 to 1.03) and marginally more likely to be taken to an emergency department in the subsequent 30 days (1.04, 1.01 to 1.08), but no differences were found for any other adverse infant outcomes and there were no infant deaths. CONCLUSIONS: Findings from this study suggest no association between maternal opioid prescription after delivery and adverse infant outcomes, including death.

Body Weight at Age Four Years and Readiness to Start School: A Prospective Cohort Study.

Background: Adolescents with obesity have lower academic performance, but little is known about the association between body weight in early childhood and school readiness. The objective was to examine the association between age- and sex-standardized body mass index (zBMI) and body weight status and school readiness in young children. Methods: A prospective cohort study in Toronto, Canada, was conducted in young children enrolled in TARGet Kids!. Children's weight and height were measured before the start of kindergarten. Children's school readiness was measured by the Early Development Instrument (EDI), a validated teacher-completed instrument that assesses children's skills and behaviors in five developmental domains in kindergarten. Generalized estimating equations, adjusted for relevant confounders, were used in the analysis. Results: The study included 1015 children (1217 observations): 52% were male and mean age at zBMI was 4.2 years [50 months (SD 12.1)] and school readiness was 5.2 years [62.7 months (SD 6.9)]. There was no evidence found that zBMI was associated with school readiness. However, in a post hoc analysis, being classified as overweight or with obesity in kindergarten was associated with twofold higher odds of vulnerability in school readiness and a lower social competence score compared with their normal weight peers. Conclusions: Being classified as overweight or with obesity was associated with poor school readiness in year 2 of kindergarten. Early interventions to promote healthy growth before school entry may help promote development and school readiness in young children. www.clinicaltrials.gov (NCT01869530).

Changing patterns of opioid initiation for pain management in Ontario, Canada: A population-based cross-sectional study.

INTRODUCTION: The recent publication of a national guideline and quality standards in Canada have provided clinicians with new, evidence-based recommendations on safe, appropriate opioid use. We sought to characterize how well opioid initiation practices aligned with these recommendations before and following their release. METHODS: We conducted a population-based study among people initiating opioids prior to the release of national guidelines (April 2015-March 2016; fiscal year [FY] 2015) and in the most recent year available (January-December 2019) in Ontario, Canada. We used linked administrative claims data to ascertain the apparent indication for opioid therapy, and characterized the initial daily dose (milligrams morphine or equivalent; MME) and prescription duration for each indication. RESULTS: In FY2015, 653,885 individuals commenced opioids, compared to 571,652 in 2019. Over time, there were small overall reductions in the prevalence of initial daily doses exceeding 50MME (23.9% vs. 20.1%) and durations exceeding 7 days (17.4% vs. 14.8%); but the magnitude of the reductions varied widely by indication. The prevalence of high dose (>50MME) initial prescriptions reduced significantly across all indications, with the exception of dentist-prescribed opioids (13.6% vs. 12.1% above 50MME). In contrast, there was little change in initial durations exceeding 7 days across most indications, with the exception of some surgical indications (e.g. common excision; 9.3% vs. 6.2%) and among those in palliative care (35.2% vs. 29.2%). CONCLUSION: Despite some modest reductions in initiation of high dose and long duration prescription opioids between 2015 and 2019, clinical practice is highly variable, with opioid prescribing practices influenced by clinical indication. These findings may help identify medical specialties well-suited to targeted interventions to promote safer opioid prescribing.

Impact of changes in opioid funding and clinical policies on rapid tapering of opioids in Ontario, Canada.

ABSTRACT: Reports have emerged of abrupt tapering among recipients of long-term prescription opioids to conform new prescribing guidelines. We conducted a population-based, repeated cross-sectional time-series study among very high-dose (≥200 MME) opioid recipients in Ontario, Canada, to examine changes in the monthly prevalence of rapid tapering from 2014 to 2018, defined as recipients experiencing either a ≥50% reduction in daily doses or abrupt discontinuation sustained for 30 days. Interventional autoregressive integrated moving average models were used to test for significant changes following key guidelines and drug policies and programs. A sensitivity analysis examined rapid tapering sustained for 90 days. The monthly prevalence of rapid tapering events was stable from January 2014 to September 2016 (average monthly prevalence: 1.4%) but increased from 1.4% in October 2016 to 1.8% in April 2017 (P = 0.001), coincident with Ontario's Fentanyl Patch-for-Patch Return Program implementation. Transient spikes in the prevalence of rapid tapering also occurred 2 months after Ontario's delisting of publicly funded high-strength opioids and the release of updated Canadian Opioid Prescribing Guideline for Chronic Pain, reaching 2.3% in March 2017 and July 2017, respectively. However, this prevalence decreased to 1.2% in December 2018 (P < 0.0001). Although the prevalence of abrupt opioid discontinuation was lower, similar trends were observed. Our sensitivity analysis examining long-lasting rapid tapering found similar trends but lower prevalence, with no changes in complete discontinuation. These temporary increases in rapid tapering events highlight the need for improved communication and evidence-based resources for prescribers to minimize negative consequences of evolving policies and guidelines.

Projected impact of biosimilar substitution policies on drug use and costs in Ontario, Canada: a cross-sectional time series analysis.

BACKGROUND: Several Canadian provinces have introduced reimbursement policies mandating substitution of innovator biologics with lower-cost biosimilars. We estimated the number of patients affected and cost implications if such policy changes were to be implemented in Ontario, Canada. METHODS: We conducted a cross-sectional time series analysis of Ontarians dispensed publicly funded biologics indicated for inflammatory diseases (rheumatic conditions, inflammatory bowel disease: infliximab, etanercept, adalimumab) between January 2018 and December 2019, and forecasted trends to Dec. 31, 2020. The primary source of data was pharmacy claims data for all biologics reimbursed by the public drug program. We modelled the number of patients affected and government expenditures (in nominal Canadian dollars) of several biosimilar policy options, including mandatory nonmedical biosimilar substitution, substitution in new users, introduction of a biosimilar for adalimumab, and price negotiations. In a secondary analysis, we included insulin glargine. RESULTS: In 2018, 14 089 individuals were prescribed a publicly funded biologic for inflammatory diseases. A mandatory nonmedical biosimilar substitution would potentially have affected 7209 patients and saved $238.6 million from 2018 to 2020. A new-user substitution would have affected 757 patients and saved $34.2 million. If an adalimumab biosimilar were to become available, 12 928 patients would be affected by a mandatory nonmedical substitution and the 3-year savings would increase to $645.9 million (all biosimilars priced at 25% of innovator biologics). Finally, an expanded nonmedical substitution policy including insulin glargine would affect 115 895 patients and save $288.7 million (not including adalimumab). INTERPRETATION: Policies designed to curb rising costs of biologics can have substantially different effects on patients and government expenditures. Such analyses warrant careful consideration of the balance between cost savings and effects on patients.

Assessment of Stimulant Use and Cardiovascular Event Risks Among Older Adults.

Importance: Use of stimulants continues to increase among older adults for a variety of indications. An association between stimulant use and increased risk of cardiovascular (CV) events has been established among children and young adults, but few studies have explored the risk of CV events among older patients, a group with increased baseline risk. Objective: To evaluate the association between stimulant use and risk of CV events among older adults. Design, Setting, and Participants: This propensity score-matched cohort study, with 4 nonusers per 1 user, was conducted from July 1, 2017, to June 27, 2019, using data from population-based health care databases from Ontario, Canada, from January 1, 2002, to December 31, 2016. Included individuals were outpatients aged 66 years or older. Exposures: Initiation of a prescription stimulant. Main Outcomes and Measures: The primary outcome was a CV event, defined as a composite of emergency department visit or hospitalization for myocardial infarction, stroke or transient ischemic attack (TIA), or ventricular arrhythmia. Risk of CV event was assessed at 30 days, 180 days, and 365 days after initiation of stimulants from Cox proportional hazard models. A secondary analysis assessed each component of the primary outcome separately. Results: Among 6457 older adults who initiated a prescription stimulant (ie, the exposed group) and 24 853 older adults who did not initiate such treatment (ie, the unexposed group), the distribution of baseline patient characteristics was well balanced after matching (sex: 3173 [49.1%] men vs 12 112 [48.7%] men; standardized difference, 0.01; median [IQR] age: 74 [69-80] years vs 74 [69-80] years; standardized difference, 0.01). Within this cohort, there were 932 CV events during the 365-day follow-up (5.11 events per 100 person-years among individuals who initiated stimulants). In the primary analysis, stimulant initiation was associated with increased risk of CV events at 30 days (hazard ratio [HR], 1.4; 95% CI, 1.1-1.8) but not at 180 days (HR, 1.2; 95% CI, 0.9-1.6) or 365 days (HR, 1.0; 95% CI, 0.6 to 1.8). In the secondary analysis, stimulant initiation was associated with increased risk of ventricular arrhythmias (HR, 3.0; 95% CI, 1.1-8.7) and stroke or TIA (HR, 1.6; 95% CI, 1.1-2.1) at 30 days. Conclusions and Relevance: This cohort study found that stimulant use was associated with an early increase in CV events among older adults with no association for long-term use.

Dental Opioid Prescription Characteristics and the Risk of New, Persistent Use.

INTRODUCTION: Dentists are a common source of opioid exposure. This study investigates the association between initial dental opioid prescription characteristics and subsequent persistent use and examines the rate of opioid overdose after initiation. METHODS: A retrospective cohort study was conducted among Ontario residents who were dispensed an initial opioid prescription originating from a dentist between October 2014 and September 2018 (data were analyzed in October 2019-May 2020). Exposures were characterized on the basis of the average daily dose in milligram morphine equivalents and the duration and formulation (long versus short acting) of the initial prescription. New, persistent use was defined as ≥1 opioid prescription within 90 days and another within 91-365 days after the initial prescription. The rate of an opioid overdose within 90 days after initiation was examined. RESULTS: Among 786,125 Ontarians who initiated a dentist-prescribed opioid, 34,880 (4.4%) developed persistent use, whereas 140 (0.72 per 1,000 person-years) had evidence of an overdose within 90 days. People dispensed an initial daily dose >90 milligram morphine equivalents (n=5,644, 0.7%) had significantly greater odds of persistence (AOR=1.20, 95% CI=1.07, 1.34) than those dispensed ≤20 milligram morphine equivalents (n=179,884, 22.9%). Persistence was also significantly associated with receiving longer prescription durations and a long-acting opioid on initiation. CONCLUSIONS: Among people who initiated a dentist-prescribed opioid, 1 in 23 experienced persistent use, and persistence was associated with the characteristics of the prescription. Prescribing lower doses, prescribing for shorter durations, and avoiding long-acting formulations may be an opportunity to lessen the risk of persistent opioid use.

Impact of a Publicly Funded Herpes Zoster Immunization Program on the Burden of Disease in Ontario, Canada: A Population-based Study.

BACKGROUND: In September 2009, a live attenuated herpes zoster vaccine (ZVL) became available in Canada. Beginning in September 2016, ZVL was made available to all Ontario residents aged 65-70 through a publicly funded immunization program. We assessed the impact of ZVL availability and its subsequent public funding on herpes zoster burden in this population. METHODS: A population-based study of Ontario residents aged 65-70 between January 2005 and September 2018. We used interventional autoregressive integrated moving average models to examine the impact of ZVL market availability and the publicly funded ZVL program on monthly incidence rate of medically attended herpes zoster, defined as an outpatient visit for herpes zoster with a prescription for a herpes zoster antiviral dispensed ≤5 days before or after the visit, or a herpes zoster-related emergency department (ED) visit or hospitalization. In secondary analyses, we examined impacts on any herpes zoster-related ED visits and hospitalizations. RESULTS: We found no association between ZVL market availability and monthly incidence of herpes zoster (P = .32) or monthly rates of ED visits and hospitalizations (P = .88). Conversely, the introduction of publicly funded ZVL reduced the monthly rate of medically attended herpes zoster by 19.1% (from 4.8 to 3.8 per 10 000 population; P < .01) and herpes zoster-related ED visits and hospitalizations by 38.2% (from 1.7 to 1.0 per 10 000 population; P < .05). CONCLUSIONS: The introduction of a publicly funded immunization program for herpes zoster was associated with reduced disease burden and related acute healthcare service use.

Metronidazole-associated Neurologic Events: A Nested Case-control Study.

BACKGROUND: Case reports have described instances of peripheral and central nervous system toxicity during treatment with metronidazole; however, no large-scale studies have examined this association. METHODS: We conducted a population-based nested case-control study of adults aged 66 years or older living in Ontario, Canada, between 1 April 2003 and 31 March 2017. Cases were individuals who attended hospital for any of cerebellar dysfunction, encephalopathy, or peripheral neuropathy within 100 days of a prescription for either metronidazole or clindamycin. We matched each case patient with up to 10 event-free control subjects who also received metronidazole or clindamycin. We used conditional logistic regression to test the association between metronidazole exposure and neurologic events, with clindamycin as the reference exposure. RESULTS: We identified 1212 cases with recent use of either metronidazole or clindamycin and 12 098 controls. Neurologic adverse events were associated with an increased odds of metronidazole exposure compared to clindamycin (odds ratio [OR], 1.72 [95% confidence interval {CI}, 1.53-1.94]), which persisted after accounting for patient demographics, comorbidities, and other medication exposures (adjusted odds ratio [aOR], 1.43 [95% CI, 1.26-1.63]). We found a consistent association limited to either central (aOR, 1.46 [95% CI, 1.27-1.68]) or peripheral (aOR, 1.34 [95% CI, 1.02-1.76]) nervous system events. Among metronidazole recipients, the overall incidence of neurologic events at 100 days was approximately 0.25%. CONCLUSIONS: Metronidazole is associated with an increased risk of adverse peripheral and central nervous system events relative to clindamycin. Clinicians and patients should be aware of these rare but potentially serious adverse events.

Initial opioid prescription patterns and the risk of ongoing use and adverse outcomes.

PURPOSE: As clinical practice moves towards more judicious opioid prescribing, physicians require information on how to safely initiate opioids. The objective of this study was to examine the association between initial opioid prescription characteristics and risks of harm and long-term use. METHODS: We conducted a population-based retrospective cohort study among Ontario residents newly dispensed an opioid for pain between July 2013 and March 2016. The primary exposure was the average daily opioid dose dispensed at initiation (in milligram morphine equivalents; MME), with secondary exposures including the initial prescription's duration and formulation. The primary outcome was fatal or non-fatal opioid overdose. A secondary analysis studied continued opioid use for at least 1 year. RESULTS: Among the 2 021 371 individuals meeting our inclusion criteria, 1121 (0.56 per 1000 person-years) experienced an opioid overdose within 1 year and 64 013 (3.17%) continued treatment for at least 1 year. Higher initial daily dose, longer prescription duration, and receipt of a long-acting formulation at initiation were significantly associated with higher hazard of overdose. Compared to daily doses of 20 MME or lower, initial doses exceeding 200 MME daily were associated with a particularly high hazard of overdose (aHR 2.97, 95% confidence interval [CI] 1.62 to 5.44). In the secondary analysis, there were similar associations between initial dose, duration, and formulation and long-term use. CONCLUSIONS: Although the absolute risk of an opioid overdose within the first year of prescription opioid use is low, better alignment of opioid initiation practices with guidelines may reduce opioid-related harm.

Characteristics of high-drug-cost beneficiaries of public drug plans in 9 Canadian provinces: a cross-sectional analysis.

BACKGROUND: Drugs are the fastest growing cost in the Canadian health care system, owing to the increasing number of high-cost drugs. The objective of this study was to examine the characteristics of high-drug-cost beneficiaries of public drug plans across Canada relative to other beneficiaries. METHODS: We conducted a cross-sectional study among public drug plan beneficiaries residing in all provinces except Quebec. We used the Canadian Institute for Health Information's National Prescription Drug Utilization Information System to identify all drugs dispensed to beneficiaries of public drug programs in 2016/17. We stratified the cohort into 2 groups: high-drug-cost beneficiaries (top 5% of beneficiaries based on annual costs) and other beneficiaries (remaining 95%). For each group, we reported total drug costs, prevalence of high-cost claims (> $1000), median number of drugs, proportion of beneficiaries aged 65 or more, the 10 most costly reimbursed medications and the 10 medications most commonly reimbursed. We reported estimates overall and by province. RESULTS: High-drug-cost beneficiaries accounted for nearly half (46.5%) of annual spending, with an average annual spend of $14 610 per beneficiary, compared to $1570 among other beneficiaries. The median number of drugs dispensed was higher among high-drug-cost beneficiaries than among other beneficiaries (13 [interquartile range (IQR) 7-19] v. 8 [IQR 4-13]), and a much larger proportion of high-drug-cost beneficiaries than other beneficiaries received at least 1 high-cost claim (40.9% v. 0.6%). Long-term medications were the most commonly used medications for both groups, whereas biologics and antivirals were the most costly medications for high-drug-cost beneficiaries. INTERPRETATION: High-drug-cost beneficiaries were characterized by the use of expensive medications and polypharmacy relative to other beneficiaries. Interventions and policies to help reduce spending need to consider both of these factors.

Oxycodone, Hydromorphone, and the Risk of Suicide: A Retrospective Population-Based Case-Control Study.

INTRODUCTION: Opioids have been increasingly associated with suicide, but whether they are independent contributors is unclear. Oxycodone and hydromorphone are commonly prescribed high-potency opioids that can differentially affect mood. OBJECTIVE: The objective of this study was to explore whether oxycodone and hydromorphone are differentially associated with suicide. METHODS: We conducted a retrospective population-based case-control study in Ontario, Canada, from 1992 to 2014. Using coronial data, we defined case subjects as individuals who died by suicide involving an opioid overdose. Each of these was matched with up to four controls who died of accidental opioid overdose. We ascertained exposure to oxycodone, hydromorphone, and other opioids from postmortem toxicology testing. We used odds ratios and 95% confidence intervals to examine whether opioid-related suicide was disproportionately associated with oxycodone relative to hydromorphone. RESULTS: We identified 438 suicides and 1212 accidental deaths, each of which involved either oxycodone or hydromorphone but not both. The median age at death was 49 years and 51% were men. After adjusting for a history of self-harm, psychiatric illness, and exposure to other opioids, we found that oxycodone was more strongly associated with suicide than hydromorphone (adjusted odds ratio 1.59; 95% confidence interval 1.20-2.11). In a secondary analysis, we observed a trend of similar magnitude in which combined exposure to oxycodone and hydromorphone was more strongly associated with suicide than hydromorphone alone (adjusted odds ratio 1.68; 95% confidence interval 0.92-3.09). CONCLUSIONS: While preliminary, these findings support the possibility that some high-potency opioids might independently influence the risk of suicide in susceptible individuals.

Effect on Treatment Adherence of Distributing Essential Medicines at No Charge: The CLEAN Meds Randomized Clinical Trial.

Importance: Nonadherence to treatment with medicines is common globally, even for life-saving treatments. Cost is one important barrier to access, and only some jurisdictions provide medicines at no charge to patients. Objective: To determine whether providing essential medicines at no charge to outpatients who reported not being able to afford medicines improves adherence. Design, Setting, and Participants: A multicenter, unblinded, parallel, 2-group, superiority, outcomes assessor-blinded, individually randomized clinical trial conducted at 9 primary care sites in Ontario, Canada, enrolled 786 patients between June 1, 2016, and April 28, 2017, who reported cost-related nonadherence. Follow-up occurred at 12 months. The primary analysis was performed using an intention-to-treat principle. Interventions: Patients were randomly allocated to receive free medicines on a list of essential medicines in addition to otherwise usual care (n = 395) or usual medicine access and usual care (n = 391). Main Outcomes and Measures: The primary outcome was adherence to treatment with all medicines that were appropriately prescribed for 1 year. Secondary outcomes were hemoglobin A1c level, blood pressure, and low-density lipoprotein cholesterol levels 1 year after randomization in participants taking corresponding medicines. Results: Among the 786 participants analyzed (439 women and 347 men; mean [SD] age, 51.7 [14.3] years), 764 completed the trial. Adherence to treatment with all medicines was higher in those randomized to receive free distribution (151 of 395 [38.2%]) compared with usual access (104 of 391 [26.6%]; difference, 11.6%; 95% CI, 4.9%-18.4%). Control of type 1 and 2 diabetes was not significantly improved by free distribution (hemoglobin A1c, -0.38%; 95% CI, -0.76% to 0.00%), systolic blood pressure was reduced (-7.2 mm Hg; 95% CI, -11.7 to -2.8 mm Hg), and low-density lipoprotein cholesterol levels were not affected (-2.3 mg/dL; 95% CI, -14.7 to 10.0 mg/dL). Conclusions and Relevance: The distribution of essential medicines at no charge for 1 year increased adherence to treatment with medicines and improved some, but not other, disease-specific surrogate health outcomes. These findings could help inform changes to medicine access policies such as publicly funding essential medicines. Trial Registration: ClinicalTrials.gov identifier: NCT02744963.

Nursing resource team capacity planning using forecasting and optimization methods: A case study.

AIM: To estimate the cost-minimizing size and skill mix of a nursing resource team (NRT). BACKGROUND: Nurse absences can be filled by an NRT at lower hourly cost than staffing agencies or nurses working overtime, but an NRT must be appropriately sized to minimize total cost. METHODS: Using all registered nurse (RN) absences at an academic teaching hospital from 1 October 2014 to 31 March 2018, we developed a generalized additive model (GAM) to forecast the weekly frequency of each of ten types of absence over 52 weeks. We used the forecasts in an optimization model to determine the cost-minimizing NRT composition. RESULTS: The median weekly frequencies for the ten absence types ranged between 12 and 65.5. The root mean squared errors of the GAMs ranged between 4.55 and 9.07 on test data. The NRT dimensioned by the optimization model yields an estimated annual cost reduction of $277,683 (Canadian dollars) (7%). CONCLUSIONS: The frequency of RN absences in a hospital can be forecasted with high accuracy, and the use of forecasting and optimization to dimension an NRT can substantially reduce the cost of filling RN absences. IMPLICATIONS FOR NURSING MANAGEMENT: This methodology can be adapted by any hospital to optimize nurse staffing.

Comprehensive Drug-Class Review Framework for improved evidence-based drug policy and formulary modernization.

Formularies are used by payers to optimize access and ensure the appropriate use of medications. Lack of follow-up and re-evaluation can lead to outdated formularies that are not reflective of current evidence. Formulary modernization, an approach to re-align formularies with current evidence has proven successful. The Ontario Drug Policy Research Network (ODPRN) launched a framework for conducting comprehensive drug-class reviews. This commentary describes the individual components of this framework and lessons learned through completion of 12 reviews between 2013 and 2016. We present the ODPRN drug-class review of treatments for chronic hepatitis B as a case example to illustrate the components and impact. The incorporation of foundational health technology assessment components such as economic evaluations and knowledge synthesis with contextualizing evidence such as patient and clinician perspectives (through qualitative studies), real-world evidence (through data analytics), and cross-jurisdictional comparisons (through environmental scans and data analytics), successfully developed jurisdictionally specific policy recommendations grounded in up-to-date evidence. The ODPRN framework for conducting comprehensive drug-class reviews is a robust and feasible approach to conduct formulary modernization. This framework allows for actionable and specific policies which are likely to be considered by decision makers. Adoption of similar frameworks in other jurisdictions may improve uptake of evidence-informed policy recommendations.

Linking Quality Improvement and Health Information Technology through the QI-HIT Figure 8.

The implementation of health information technology (HIT) is complex. A method for mitigating complexity is incrementalism. Incrementalism forms the foundation of both incremental software development models, like agile, and the Plan-Do-Study-Act cycles (PDSAs) of quality improvement (QI), yet we often fail to be incremental at the union of the disciplines. We propose a new model for HIT implementation that explicitly links incremental software development cycles with PDSAs, the QI-HIT Figure 8 (QIHIT-F8). We then detail a subsequent local HIT implementation where we demonstrated its use. The QIHIT-F8 requires a reprioritization of project management activities around tests of change, strong QI principles to detect these changes, and the presence of both baseline and prospective data about the chosen indicators. These conditions are most likely to be present when applied to indicators of high strategic importance to an organization.

Impact of delisting high-strength opioid formulations from a public drug benefit formulary on opioid utilization in Ontario, Canada.

PURPOSE: High-strength opioid formulations were delisted (removed) from Ontario's public drug formulary in January 2017, except for palliative patients. We evaluated the impact of this policy on opioid utilization and dosing. METHODS: We conducted a longitudinal study among patients receiving publicly funded, high-strength opioids from August 2016 to July 2017. The primary outcome measure was weekly median daily opioid dose (in milligrams of morphine or equivalent; MME) of (1) publicly funded and (2) all opioid prescriptions irrespective of funding source, evaluated using interrupted time series analyses and stratified by palliative care status. RESULTS: Following policy implementation, the weekly median daily dose of publicly funded opioids decreased immediately among non-palliative patients by 10 MME (95% confidence limit [CL], -16.8 to -3.1) from a pre-intervention dose of 424.5 MME (95% CL, 417.8-431.2) and fell gradually among palliative patients by 3.9 MME per week (95% CL, -5.5 to -2.3) from a pre-intervention dose of 450.1 MME (95% CL, 432.5-467.7). In contrast, among all opioid prescriptions, gradual reductions in weekly median daily doses were observed only for non-palliative patients, which decreased by 0.7 MME per week (95% CL, -1.3 to -0.2) from a pre-intervention dose of 426.2 MME (95% CL, 420.9-431.5). CONCLUSION: The delisting of publicly-funded, high-strength opioids was accompanied by changes in funding source and small reductions in the weekly median daily doses dispensed. Although observed dose reductions of less than 1 MME weekly are likely not clinically relevant, safety implications of these changes require further monitoring.

Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits.

OBJECTIVES: Tramadol is a widely prescribed analgesic that influences both opioid and monoamine neurotransmission. While seizures have been reported with its use, the risk in clinical practice has not been well characterised. We examined risk of seizure with tramadol relative to codeine, a comparable opioid analgesic. DESIGN: Retrospective nested case-control study. For each case, we identified up to 10 controls matched on age, sex, US state of residence and date of cohort entry (±365 days). We calculated ORs to determine the association between seizure and exposure to tramadol, codeine (≥15 mg), both or neither, in the preceding 30 days. SETTING: Cohort of patients, who had continuous health coverage and resided in the same state for≥3 years, identified from linked administrative health data in US MarketScan databases from 2009 to 2012. PARTICIPANTS: We identified 96 753 patients with seizure and 888 540 matched controls. PRIMARY AND SECONDARY OUTCOME MEASURES: In the primary analysis, we defined cases using a broad definition of seizure (based on either an outpatient physician claim for seizure disorder or a seizure-related emergency department visit or hospitalisation). In a secondary analysis, we used a more specific definition of seizure restricted to a hospital visit with a principal diagnosis of seizure. RESULTS: In the primary analysis, we found no association between risk of seizure and exposure to tramadol compared with codeine (OR 1.03, 95% CI 0.93 to 1.15). However, in the secondary analysis (using a more specific definition of seizure), this association was statistically significant (OR 1.41, 95% CI 1.11 to 1.79). CONCLUSIONS: Tramadol was not associated with an increased risk of seizure defined by inpatient and outpatient diagnoses. However, this finding was sensitive to the outcome definition used and requires further study.

Evaluation of the fentanyl patch-for-patch program in Ontario, Canada.

BACKGROUND: Rising use of prescription opioids is a major public health concern associated with increased risk of mortality worldwide. Fentanyl, a synthetic opioid available in patch form, is particularly concerning given its high potency. To curb the misuse and diversion of fentanyl patches, a Patch-for-Patch (P4P) program was implemented in some counties in Ontario between 2012 and 2015. The program requires that patients prescribed fentanyl must return used patches to the pharmacy before receiving more patches. OBJECTIVE: To evaluate the impact of the P4P program on fentanyl and non-fentanyl dispensing and opioid-related hospitalizations and deaths. METHODS: We conducted a repeated cross-sectional time-series analysis among counties that implemented the P4P program using Ontario administrative claims data. Because intervention dates varied by county due to staggered program initiation, we aligned all intervention months and examined outcome rates in the 5 years preceding and 12 and 24 months following implementation. We explored the monthly rate of prescriptions dispensed for fentanyl and non-fentanyl opioids, opioid toxicity-related hospital and emergency department visits, and opioid-related deaths. We modeled each outcome using an interventional autoregressive integrated moving average (ARIMA) model and tested the impact of the P4P program using a ramp function. RESULTS: We analyzed 16 counties that implemented the P4P program and had at least 12 months of follow-up. The introduction of the P4P program was associated with a 30.5% decline in the volume of fentanyl patches dispensed at 24 months (from 1,277-888 patches per 10,000 population; p = 0.04). In contrast, there was no significant change in the rate of non-fentanyl opioid dispensing (p = 0.32), opioid toxicity related hospitalizations and emergency department visits (p = 0.4) or opioid-related deaths (p = 0.96) in the 12 months following implementation of the program. CONCLUSIONS: We found that the implementation of a P4P program in select counties in Ontario was associated with a lower volume of fentanyl patches dispensed by pharmacies, without an increase in use of other opioids. The program had no measurable impact on rates of opioid toxicity-related hospital visits or deaths. Policymakers should consider the use of P4P programs as part of larger opioid strategy.