Patterns of antiemetic medication use during pregnancy: A multi-country retrospective cohort study.

OBJECTIVE: To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014. METHODS: We constructed population-based cohorts of pregnant women using administrative healthcare data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Saskatchewan), the Clinical Practice Research Datalink from the United Kingdom, and the IBM MarketScan Research Databases from the United States. We included pregnancies ending in live births, stillbirth, spontaneous abortion, or induced abortion. We determined maternal use of antiemetics from pharmacy claims in Canada and the United States and from prescriptions in the United Kingdom. RESULTS: The most common outcome of 3 848 734 included pregnancies (started 2002-2014) was live birth (66.7% of all pregnancies) followed by spontaneous abortion (20.2%). Use of antiemetics during pregnancy increased over time in all three countries. Canada had the highest prevalence of use of prescription antiemetics during pregnancy (17.7% of pregnancies overall, 13.2% of pregnancies in 2002, and 18.9% in 2014), followed by the United States (14.0% overall, 8.9% in 2007, and 18.1% in 2014), and the United Kingdom (5.0% overall, 4.2% in 2002, and 6.5% in 2014). Besides use of antiemetic drugs being considerably lower in the United Kingdom, the increase in its use over time was more modest. The most commonly used antiemetic was combination doxylamine/pyridoxine in Canada (95.2% of pregnancies treated with antiemetics), ondansetron in the United States (72.2%), and prochlorperazine in the United Kingdom (63.5%). CONCLUSIONS: In this large cohort study, we observed an overall increase in antiemetic use during pregnancy, and patterns of use varied across jurisdictions. Continued monitoring of antiemetic use and further research are warranted to better understand the reasons for differences in use of these medications and to assess their benefit-risk profile in this population.

Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort.

Importance: Ondansetron is frequently used to treat nausea and vomiting during pregnancy. Although some studies reported important safety signals, few studies have been sufficiently large to assess rare pregnancy outcomes. Objective: To study the association between ondansetron exposure during pregnancy and the risks of spontaneous abortion, stillbirth, and major congenital malformations. Design, Setting, and Participants: This is a cohort study conducted in 3 countries, with a meta-analysis. Participants included women and girls aged 12 to 55 years who experienced spontaneous abortion, induced abortion, stillbirth, or live birth between April 2002 and March 2016, as recorded in administrative data from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, and Ontario), the US IBM MarketScan Research Databases, and the UK Clinical Practice Research Datalink. The statistical analysis was completed in October 2020. Exposures: Exposure to ondansetron during pregnancy was compared with exposure to other commonly used antiemetics to minimize confounding by indication. Main Outcomes and Measures: The primary outcome was fetal death, defined as either spontaneous abortion or stillbirth. Secondary outcomes were the 2 components of the primary outcome and major congenital malformations identified during the year after a live birth. Adjusted hazard ratios were estimated using Cox proportional hazards models with time-dependent drug exposures and were adjusted using high-dimensional propensity scores. For major congenital malformations, adjusted odds ratios were estimated from logistic models. Site-level results were pooled using random-effects meta-analysis. Sensitivity analyses considered second-line antiemetic exposure and exposure specifically during 4 to 10 weeks of gestation. Results: Data from 456 963 pregnancies were included in this study of fetal death (249 787 [54.7%] in Canada, 197 913 [43.3%] in the US, and 9263 [2.0%] in the UK; maternal age, ≤24 years, 93 201 patients [20.4%]; 25-29 years, 149 117 patients [32.6%]; 30-34 years, 142 442 patients [31.2%]; and ≥35 years, 72 203 patients [15.8%]). Fetal death occurred in 12 907 (7.9%) of 163 810 pregnancies exposed to ondansetron, and 17 476 (5.7%) of 306 766 pregnancies exposed to other antiemetics. The adjusted hazard ratios were 0.91 (95% CI, 0.67-1.23) for fetal death with time-dependent ondansetron exposure during pregnancy, 0.82 (95% CI, 0.64-1.04) for spontaneous abortion, and 0.97 (95% CI, 0.79-1.20) for stillbirth. For major congenital malformations, the estimated odds ratio was 1.06 (95% CI, 0.91-1.22). Results of sensitivity analyses were generally consistent with those of the primary analyses. Conclusions and Relevance: In this large, multicenter cohort study, there was no association between ondansetron exposure during pregnancy and increased risk of fetal death, spontaneous abortion, stillbirth, or major congenital malformations compared with exposure to other antiemetic drugs.

The impact of a physician detailing and sampling program for generic atorvastatin: an interrupted time series analysis.

BACKGROUND: In 2011, Manitoba implemented a province-wide program of physician detailing and free sampling for generic atorvastatin to increase use of this generic statin. We examined the impact of this unique combined program of detailing and sampling for generic atorvastatin on the use and cost of statin medicines, market share of generic atorvastatin, the choice of starting statin for new users, and switching from a branded statin to generic atorvastatin. METHODS: We conducted a retrospective study of Manitoba insurance claims data for all continuously enrolled patients who filled one or more prescriptions for a statin between 2008 and 2013. Data were linked to physician-level data on the number of detailing visits and sample provision. We used interrupted time series analyses to assess policy-related changes in the use and cost of statin medicines, market share of generic atorvastatin, the choice of starting statin for new users, and switching from a branded statin to generic atorvastatin. RESULTS: The detailing program reached 31% (651/2103) of physicians who prescribed a statin during the study period. Collectively, these physicians prescribed 61% of statins dispensed in the province. Free sample cards were provided to 61% (394/651) of the detailed physicians. The program did not change the level or trend in the overall statin use rate and the total cost of statins or increase the number of patients switching from another branded statin to generic atorvastatin. We found the program had a small impact on atorvastatin's market share of new prescriptions, with a level increase of 2.6%. CONCLUSIONS: Though physician detailers were skilled at targeting high-prescribing physicians, a combined program of detailing visits and sample provision for generic atorvastatin did not lower overall statin costs or lead to switching from branded statins to the generic. The preceding introduction of generic atorvastatin appeared sufficient to modify prescribing patterns and decrease costs.

Opioid use during pregnancy: a population-based cohort study.

BACKGROUND: Opioid use has increased dramatically in North America. The safety of opioids in pregnancy is uncertain, but they are associated with several fetal abnormalities and contribute to rising rates of neonatal abstinence syndrome. We examined opioid use before and during pregnancy in a complete population-based cohort. METHODS: We examined opioid use in a cohort of all pregnant women in Manitoba, Canada, from 2001 to 2013. Opioid use was defined by prescriptions for opioids, converted to oral morphine equivalents (MEQ), during the 3 months before pregnancy and for each trimester. Given that the exposure per person may vary (because not all women complete all time periods), we determined a weighted number of pregnancies in each period. RESULTS: During the study period, 174 848 completed pregnancies were eligible for analysis (173 680 live births and 1168 stillbirths and intrauterine deaths), which represented a weighted value of 175 174 pregnancies. Among these pregnancies, 6.7% of the women filled opioid prescriptions in the 3 months before pregnancy. Use declined to 4.2% during the first trimester and further declined to 3.0% and 2.9% in the second and third trimesters, respectively. Over the study period, there was a modest increase in opioid use overall (from 7.3% to 7.7%). MEQ did not decline during pregnancy, and the mean MEQ increased significantly over the study period (from 284 mg to 1218 mg). Prescriptions for codeine were filled by 96.9% of the users, accounting for 66.2% of MEQ. INTERPRETATION: Although many of the women using opioids before pregnancy discontinued or reduced use of these drugs during pregnancy, the volume of opioids consumed by those who continued opioid use did not decline during pregnancy. The increasing dosage and increased use of higher-potency opioids by pregnant women highlights the need for continued evaluation of and education about the benefits and risks of this practice.

A comparison of opioid use between WCB recipients and other Manitobans for knee, shoulder, back and carpal tunnel release procedures.

BACKGROUND: This study's objectives were to evaluate whether WCB claimants with conditions requiring certain surgical procedures are more likely to be prescribed outpatient opioids than other Manitobans and whether those prescribed opioids are more likely to still be on opioid medications 6 months post procedure. METHODS: We compared 7,246 WCB claims for a number of surgical procedures to 65,032 similar procedures performed in other Manitobans. Logistic regression was used to explore the association between being a WCB claimant and being prescribed opioids, while controlling for type of surgical procedure and other potential confounders. RESULTS: WCB claimants were more likely than other Manitobans to be prescribed opioids (adjusted OR 1.38; 95%CI 1.30-1.47). Amongst those prescribed opioids, the odds of being still on opioids 6 months post-procedure were not significantly elevated for WCB claimants (adjusted OR 1.09 95%CI 0.97-1.23). CONCLUSIONS: WCB claimants are prescribed opioids more often than non-claimants for similar procedures.

Proportion of opioid use due to compensated workers' compensation claims in Manitoba, Canada.

BACKGROUND: This study identifies the percentage of opioids prescribed for compensated workplace conditions in Manitoba, Canada and whether Workers Compensation Board (WCB) status is associated with higher prescription opioid doses. METHODS: Opioid prescriptions for WCB recipients were linked with databases housed at the Manitoba Center for Health Policy. Duration of continuous opioid prescription and morphine equivalents (ME) per day (ME/D) were calculated for individuals age 18-65. RESULTS: Over the period from 1998 to 2010, 3.8% of the total opioid dosage of medication prescribed in the study population were prescribed to WCB recipients. WCB recipients accounted for 2.1% of the individuals prescribed opioids. In adjusted analyses WCB recipients were more likely to be prescribed over 120 ME/D (OR 2.06 95% CI, 1.58-2.69). CONCLUSIONS: WCB recipients account for a small, but significant amount of the total opioid prescribed in Manitoba. Manitoba's WCB population is a group at increased risk of being prescribed over 120 ME/day.

Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases.

OBJECTIVE: To evaluate the incremental increase in new onset diabetes from higher potency statins compared with lower potency statins when used for secondary prevention. DESIGN: Eight population based cohort studies and a meta-analysis. SETTING: Six Canadian provinces and two international databases from the UK and US. PARTICIPANTS: 136,966 patients aged ≥ 40 years newly treated with statins between 1 January 1997 and 31 March 2011. METHODS: Within each cohort of patients newly prescribed a statin after hospitalisation for a major cardiovascular event or procedure, we performed as-treated, nested case-control analyses to compare diabetes incidence in users of higher potency statins with incidence in users of lower potency statins. Rate ratios of new diabetes events were estimated using conditional logistic regression on different lengths of exposure to higher potency versus lower potency statins; adjustment for confounding was achieved using high dimensional propensity scores. Meta-analytic methods were used to estimate overall effects across sites. MAIN OUTCOME MEASURES: Hospitalisation for new onset diabetes, or a prescription for insulin or an oral antidiabetic drug. RESULTS: In the first two years of regular statin use, we observed a significant increase in the risk of new onset diabetes with higher potency statins compared with lower potency agents (rate ratio 1.15, 95% confidence interval 1.05 to 1.26). The risk increase seemed to be highest in the first four months of use (rate ratio 1.26, 1.07 to 1.47). CONCLUSIONS: Higher potency statin use is associated with a moderate increase in the risk of new onset diabetes compared with lower potency statins in patients treated for secondary prevention of cardiovascular disease. Clinicians should consider this risk when prescribing higher potency statins in secondary prevention patients.

Cost analysis of an intravenous to subcutaneous epoetin α conversion.

BACKGROUND/AIMS: A cost analysis of a conversion from intravenous (IV) to subcutaneous (SC) epoetin α in patients receiving chronic in-center hemodialysis (HD). METHODS: This retrospective analysis compared epoetin α drug costs during a 6-month period of IV usage (July to December 2010, period 1) to a 6-month period of SC usage (July to December 2011, period 2) in four large in-center HD units. Data were collected from quarterly counts of HD patients receiving epoetin α and monthly inventory billing records. RESULTS: 622 HD patients who received IV epoetin α (period 1) were compared to 609 HD patients who received SC epoetin α (period 2). A 12.6% decrease in dose was observed. The average weekly cost of epoetin α was USD 173.02 per patient during the IV period versus USD 151.20 per patient during the SC period. This equated to a yearly cost savings of USD 1,135 per patient with SC epoetin α. CONCLUSION: The switch from IV to SC epoetin α was successfully implemented in all four centers and realized significant cost savings.

Evaluation of a medication order writing standards policy in a regional health authority.

BACKGROUND: The Winnipeg Regional Health Authority (WRHA) implemented a medication order writing standards (MOWS) policy (including banned abbreviations) to improve patient safety. Widespread educational campaigns and direct prescriber feedback were implemented. METHODS: We audited orders within the WRHA from 2005 to 2009 and surveyed all WRHA staff in 2011 about the policy and suggestions for improving education and compliance. RESULTS: Overall, orders containing banned abbreviations, acronyms or symbols numbered 2261/8565 (26.4%) preimplementation. After WRHA-wide didactic education, the proportion declined to 1358/5461 (24.9%) (p = 0.043) and then, with targeted prescriber feedback, to 1186/6198 (19.1%) (p < 0.0001). A survey of 723 employees showed frequent violations of the MOWS, despite widespread knowledge of the policy. Respondents supported ongoing efforts to enforce the policy within the WRHA. Nonprescribers were significantly more likely than prescribers to agree with statements regarding enhancing compliance by defining prescriber/transcriber responsibilities and placing sanctions on noncompliant prescribers. DISCUSSION: Education, raising general awareness and targeted feedback to prescribers alone are insufficient to ensure compliance with MOWS policies. WRHA staff supported ongoing communication, improved tools such as compliant preprinted orders and reporting and feedback about medication incidents. A surprising number of respondents supported placing sanctions on noncompliant prescribers. CONCLUSION: Serial audits and targeted interventions such as direct prescriber feedback improve prescription quality in inpatient hospital settings. Education plus direct prescriber feedback had a greater impact than education alone on improving compliance with a MOWS policy. Future efforts at the WRHA to improve compliance will require an expanded focus on incentives, resources and development of action plans that involve all affected staff, not just prescribers. Plans include continued advertising, MOWS summaries in all charts, all-staff education, reminders and exploration of sustainable interventions for targeted feedback for prescribers.

Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases.

OBJECTIVE: To quantify an association between acute kidney injury and use of high potency statins versus low potency statins. DESIGN: Retrospective observational analysis of administrative databases, using nine population based cohort studies and meta-analysis. We performed as treated analyses in each database with a nested case-control design. Rate ratios for different durations of current and past statin exposure to high potency or low potency statins were estimated using conditional logistic regression. Ratios were adjusted for confounding by high dimensional propensity scores. Meta-analytic methods estimated overall effects across participating sites. SETTING: Seven Canadian provinces and two databases in the United Kingdom and the United States. PARTICIPANTS: 2,067,639 patients aged 40 years or older and newly treated with statins between 1 January 1997 and 30 April 2008. Each person hospitalized for acute kidney injury was matched with ten controls. INTERVENTION: A dispensing event was new if no cholesterol lowering drug or niacin prescription was dispensed in the previous year. High potency statin treatment was defined as ≥ 10 mg rosuvastatin, ≥ 20 mg atorvastatin, and ≥ 40 mg simvastatin; all other statin treatments were defined as low potency. Statin potency groups were further divided into cohorts with or without chronic kidney disease. MAIN OUTCOME MEASURE: Relative hospitalization rates for acute kidney injury. RESULTS: Of more than two million statin users (2,008,003 with non-chronic kidney disease; 59,636 with chronic kidney disease), patients with similar propensity scores were comparable on measured characteristics. Within 120 days of current treatment, there were 4691 hospitalizations for acute kidney injury in patients with non-chronic kidney injury, and 1896 hospitalizations in those with chronic kidney injury. In patients with non-chronic kidney disease, current users of high potency statins were 34% more likely to be hospitalized with acute kidney injury within 120 days after starting treatment (fixed effect rate ratio 1.34, 95% confidence interval 1.25 to 1.43). Users of high potency statins with chronic kidney disease did not have as large an increase in admission rate (1.10, 0.99 to 1.23). χ(2) tests for heterogeneity confirmed that the observed association was robust across participating sites. CONCLUSIONS: Use of high potency statins is associated with an increased rate of diagnosis for acute kidney injury in hospital admissions compared with low potency statins. The effect seems to be strongest in the first 120 days after initiation of statin treatment.

Audit of renal drug dosing: comparison of 2 methods and evaluation of pharmacists' knowledge, attitudes, and behaviour.

BACKGROUND: The renal dosing directive of the Winnipeg Regional Health Authority Pharmacy Program outlines an auditable pharmacy service whereby pharmacists are required to perform documentation (i.e., document their rationale) only if they do not adjust the dose of any medications listed in the directive. OBJECTIVE: To compare the suitability of manual orders (hard copy) and reports from the pharmacy information system (computer-generated) for determining pharmacists' compliance with the renal dosing directive; to measure compliance with the renal dosing directive; and to determine pharmacists' opinions about audit programs. METHODS: A retrospective audit was used to compare 400 manual orders with the corresponding orders in reports from the pharmacy information system, to determine compliance with the renal dosing directive. An e-mail survey was performed to gather pharmacists' opinions about audit programs. RESULTS: Of the 400 orders evaluated, 86 (22%) required consideration of a dose adjustment. Of these, 78 (91%) showed that dosing followed the guidelines for renal dysfunction in standard pharmacy references. Six (7%) of 86 manual orders and 8 (9%) of 86 pharmacy information system orders were not compliant with the renal dosing directive (i.e., no dosage adjustment and no documentation of rationale). Of 77 pharmacists approached, 34 (44%) completed the survey. Most respondents (31/34 [91%]) agreed that auditing is beneficial to patients, and the same number (31/34 [91%]) agreed that auditing provides important information to the pharmacy program. Only 17 (50%) were aware of medications listed in the renal dosing directive, and 14 (41%) felt that they had received sufficient education about pharmacy directives. Most respondents (29/34 [85%]) agreed that audits would reveal areas for improvement, and all (34/34 [100%]) would comply with any changes required to facilitate performance of an audit if such changes did not increase workload. CONCLUSIONS: Similar results were obtained with the 2 auditing methods used for this study (manual orders and reports from the pharmacy information system). However, pharmacists' current use of electronic documentation limits the feasibility of pharmacy information system audits. Survey respondents claimed that they were not familiar with the renal dosing directive, but they did agree that auditing clinical services is beneficial.

Development and evaluation of a workplace-based preceptor training course for pharmacy practitioners.

BACKGROUND: There has been limited research about preceptor training programs that include coaching, experiential practice or development of preceptor coaching capacity. We describe the development and evaluation of a workplace preceptor training course for pharmacists and pharmacy technicians within a large regional health authority. METHODS: The instructional format was self-study readings and interactive seminars followed by structured practical experience plus feedback from a preceptor coach. During the structured practical experience, each participant served as a preceptor for a student or new staff member. Course evaluations and qualitative interviews were used to evaluate utility and perceived value among participants. Interview transcripts were analyzed using qualitative description and themes were aggregated; illustrative quotes are presented. RESULTS: Since 2006, a total of 40 pharmacists and technicians have participated in the course and interviews were conducted with 14 of these participants. Aspects of the course that interview participants found to be particularly useful included receiving feedback from a coach, implementing a lesson plan and identifying and using different learning and teaching styles. Some participants described changes in attitudes or behaviours toward new employees or students, the use of new learning styles and changes in focus and approach to being a preceptor. DISCUSSION: This unique course could be applied in other workplaces where pharmacy staff members help to deliver experiential education programs. The delivery format was appropriate for a mixed group of pharmacist and technician participants. CONCLUSION: A preceptor training course of readings, seminars and structured practical experience with feedback from a coach resulted in satisfaction with learning experiences and evidence of attitudinal and behavioural change up to 3 years after the course.

Attitudes and behaviours of hospital pharmacy staff toward near misses.

Near misses may be early warning signals for errors. The purpose of this study was to examine the attitudes and behaviours of Manitoba hospital pharmacists and technicians toward near misses and reporting. A web-based survey of pharmacy staff at hospitals (all have non-punitive paper-based incident reporting systems) was conducted in 2009. Survey respondents were asked via a validated survey about experience with and attitudes and behaviours toward near misses. Factor analysis and Cronbach's α were used to determine internal consistency reliability. Differences between pharmacists and technicians were compared using Fisher's exact test for categorical data and t tests for survey scales. Of 37 hospitals, one large tertiary care hospital declined to participate. Of approximately 500 pharmacy staff, 122 (24%) responded. The majority (54.1%) were pharmacists, and most worked in Winnipeg (73.8%). The majority of respondents (62% overall--48% of technicians and 73% of pharmacists (p=.008)--had experienced at least one near miss within the previous three months. However, only 27% had reported a near miss with occurrence-reporting forms. There was no difference in the reporting behaviours scale (eight items, Cronbach's α=.824) between pharmacists and technicians (pharmacist score 30.9 ± 4.8, technician score 29.6 ± 6.0; p=.215). There was no difference in the attitudes scale (23 items, Cronbach's α=.873) between pharmacists and technicians (pharmacist score 81.9 ± 9.4, technician score 80.2 ± 10.6; p=.388). We observed similar behaviours and attitudes between hospital pharmacists and technicians, although reporting of near misses was low. Education of pharmacy staff and managers about near misses may help to encourage reporting.