Month: July 2020

What is the current situation?

Streptococcus pyogenes (group A streptococci, GAS) causes syndromes ranging from localized illness to invasive and severe disease. Invasive GAS (iGAS) infection causes significant morbidity and mortality, and the risk of contracting GAS infection is higher among close contacts of iGAS index cases. The Public Health Agency of Canada (PHAC) recommends the use of antibiotic prophylaxis among close contacts of iGAS, but a recent study did not find sufficient evidence to support this practice.

What was the aim of the study?

To determine if antibiotic prophylaxis is effective at preventing subsequent GAS infection in persons exposed to iGAS cases. To determine if the benefit outweighs the risk of unintended harm (adverse drug events).

How was the study conducted?

In MarketScan Commercial and Medicare databases (2010-2019) and the Quebec Pregnancy Cohort (QPC, 1998-2021), we studied the effectiveness of antibiotic prophylaxis in close contacts of confirmed or probable iGAS cases. MarketScan databases provide longitudinal data on inpatient/outpatient medical services, with identifiers that link family members on the same insurance plan. The QPC is a prospective cohort of all pregnancies of women covered by the Public Prescription Drug Insurance in Quebec. The QPC provides longitudinal information for mothers and their children on inpatient and outpatient medical services. In both databases, antibiotic treatment was considered prophylactic if initiated in close contacts within 7 days after the iGAS diagnosis in the index case, while subsequent cases were defined as the occurrence of GAS infection among close contacts within 30 days of the iGAS diagnosis of the index case. Unintended harms in those receiving prophylaxis included the occurrence of any adverse reaction to antibiotics within 30 days of the index case date.

What did the study find?

In QPC, we found 67 index cases of probable iGAS infection and 117 close contacts In close contacts, 29.9% (35/117) were exposed to antibiotic prophylaxis. No subsequent cases of GAS infection were identified among close contacts In the MarketScan database there were 17,078 index cases and 21,032 close contacts. 4.4% of close contacts were exposed to antibiotic prophylaxis o 25 subsequent cases of GAS infection were identified among close contacts o Secondary attack rates were 13.2 (95% CI 1.9-93.7) and 14.8 (95% CI 9.9-22.1) per 1,000 person-year in subjects exposed and unexposed to antibiotic prophylaxis In multivariate analyses, we observed a slight trend towards lower risk of GAS infection with antibiotic prophylaxis versus the unexposed group, though not statistically significant (OR 0.88; 95% CI 0.12-6.51; model adjusted for sex, age, comorbidity, steroid use, and recent past infection). The incidence of potential adverse drug events was 39.6/100 person-years (95% CI 27.7-56.6) among those receiving antibiotic prophylaxis and 10.6/100 person- years (95% CI 9.1-12.3) among those not receiving antibiotic prophylaxis.

In summary, our study was unable to demonstrate real-world effectiveness for antibiotic prophylaxis to prevent GAS infection in close contacts of iGAS cases. We did note a clear 3-fold increase in potential adverse drug events in the antibiotic prophylaxis.

For more information, contact: Autumn Neville, Research Coordinator. [email protected]

This research was funded by CIHR-DSEN 
Lead investigators: Dr. Sasha Bernatsky and Dr. Anick Berard
Query 20-07 raised by the Public Health Agency of Canada, Centre for Immunization and Respiratory Infectious Diseases

Low rates of influenza vaccination during pregnancy continue despite efficacy in preventing influenza infection in infants. Health care providers may be hesitant to suggest the vaccine to pregnant women due to safety concerns. Though it is generally believed that the benefits of protecting pregnant women and their newborns from influenza complications outweigh the small risks of vaccination, updated evidence is needed to support these recommendations.

This project aimed to determine if influenza vaccination during pregnancy is safe and effective for women and their newborn babies.  We studied women from the 3D Cohort Study (Design, Develop, Discover), comprising 2,366 women recruited during the first trimester of pregnancy (8–14 weeks) in Quebec.

Influenza vaccine during pregnancy was not clearly associated with all-cause hospitalizations in newborns, small birth weight, or being small for gestational age. Our estimates for spontaneous abortions were not conclusive due to relatively low precision. In sensitivity analyses related to the timing of vaccine exposure, we were unable to determine if risk differed according to trimester.

Our study confirms low influenza vaccine uptake in pregnancy, suggesting the need to promote influenza vaccine uptake in this group.

For more information, contact: Autumn Neville, Research Coordinator. [email protected]

This research was funded by CIHR-DSEN 
Lead investigators: Dr. Anick Berard and Dr. Sasha Bernatsky
Query 19-08 raised by the Public Health Agency of Canada, Infectious Disease Prevention and Control, Centre for Immunization and Respiratory Infectious Diseases

This project aimed to provide real-world evidence on the comparative effectiveness of influenza vaccines in seniors using MarketScan® databases. This retrospective cohort study compared the effectiveness of standard-dose (SD) trivalent, high-dose (HD) trivalent, SD quadrivalent, and adjuvanted trivalent influenza vaccines in cohorts of Medicare beneficiaries 65 years of age and older over six influenza seasons (2012/2013-2017/2018 seasons).

We analyzed the data pooled from all six seasons as well as each season separately. In the pooled analysis across all seasons, HD trivalent was associated with a lower risk of influenza-related hospitalization versus SD trivalent or SD quadrivalent. HD trivalent was also associated with a lower risk for pneumonia-related hospitalization than SD trivalent. Adjuvanted trivalent was associated with a higher risk for influenza-related outpatient visits than HD trivalent, SD trivalent, or SD quadrivalent. Risk estimates varied across seasons. Compared to SD trivalent, subjects who received HD trivalent had a lower risk of influenza- or pneumonia-related hospitalization in 2015/2016, 2013/2014, and 2012/2013 seasons, and a lower risk of influenza-related outpatient visits in 2017/2018 and 2012/2013 seasons. Compared to SD quadrivalent, HD trivalent was associated with a decreased risk of hospitalized influenza or pneumonia in 2013/2014 and a lower risk of influenza-related outpatient visits in 2014/2015. Compared to adjuvanted trivalent, HD trivalent was associated with a lower risk of influenza-related outpatient visits in 2017/2018. 

Results were presented in July 2020 for the CORE Summer Student Seminar Series at the Research Institute of the McGill University Health Centre and to the PHAC/NACI working group in November 2020. Final results were presented to the PHAC/NACI working group in February 2021.

For more information, contact: Autumn Neville, Research Coordinator. [email protected]

This research is funded by CIHR-DSEN 
Lead investigator: Dr. Sasha Bernatsky
Query 19-07 raised by  Public Health Agency of Canada, Infectious Disease Prevention and Control, Centre for Immunization and Respiratory Infectious Diseases

What is the current situation?

High levels of prescription opioid use in Canada are cause for concern. Many cough and cold prescription products (CCOMs) contain codeine, hydrocodone or normethadone. Although these products, like opioids, may be misused and abused, no current data are available to quantify the prevalence and incidence of abuse, misuse, addiction, overdose, and dependence in children. Following a signal assessment (SA) regarding the risks in children using CCOMs, Health Canada advised that children and adolescents (under 18 years old) should not use CCOMs as a precautionary measure. Studies aiming to address the potential role of CCOMs in the opioid-related risks among the pediatric population can help to provide Canadian prescribers and patients with meaningful information for decision making. They can also validate the recommendation provided in the SA and help to understand the individual contribution of CCOMs to the National opioid crisis.

What was the aim of the study?

To compare the prescribed and utilization patterns of CCOMs among the pediatric population in 5 Canadian provinces How was the study conducted? We used prospective data collection of medical services, prescription drugs, and hospitalization archives data from the Canadian Mother-Child Cohort (CAMCCO) Active Surveillance Initiative (provinces Alberta (AB), Manitoba (MB), Ontario (ON), Quebec (QC), and Saskatchewan (SK)). The study period covered the following years: 2005-2018 for Alberta, 1995-2019 for Manitoba, 2012-2020 for Ontario, 1999-2015 for Quebec, and 1998- 2020 for Saskatchewan. The CAMCCO platform employs a common data model to enable data linkages, construction of variables and patient follow-up in a similar way across provinces with standardized protocols. We included all liveborn children included within the province-specific calendar years. Each child was followed from the entry date (DOB) up to the date of death, or the child’s 18th birthday, the end of the public prescription drug coverage, or the end of the study period (last province-specific calendar year), whichever came first.

What did the study find?

Medication prescription drug lists vary; for example, QC only included codeine and hydrocodone, partly explaining lower exposure rates A decrease in exposed subjects ≤ 12 years old was observed in all provinces. An increase of exposed subjects > 12 years old was observed in QC and AB. Commonly prescribed CCOMs include codeine (AB, MB, SK, QC), dextromethorphan (MB), and hydrocodone (ON, QC) The cumulative dosage of codeine and hydrocodone in morphine milligram equivalent (MME) was higher in MB vs AB, ON and QC in each age category. General practitioners were frequent prescribers in all provinces, followed by pediatricians (AB and MB) and surgeons (ON and SK) Notably, 40.4% of SK CCOM prescription fillings did not include the prescriber’s specialty Respiratory illness was the most prevalent indication for CCOM prescriptions and injury and poisoning (SK, ON) diseases of the central nervous system and sense organs (AB, MB, QC) Our findings suggest a decrease in the number of exposed subjects in the pediatric population. Identifying prescription patterns allows for targeted approaches to provide prescribers with meaningful evidence to support decision-making with CCOMs.

For more information, contact: Autumn Neville, Research Coordinator. [email protected]

This research is funded by CIHR-DSEN 
Lead investigator: Dr. Anick Berard and Dr. Sasha Bernatsky
Query 19-06 raised by Health Canada, Opioids Scientific Section – Marketed Pharmaceuticals & Medical Devices Bureau (MPB) Marketed Health Products Directorate (MHPD)

Non-melanoma skin cancer (NMSC) is thought to be the most commonly diagnosed cancer in Canadians. There are two main types of NMSC, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) and common risk factors include race/ethnicity, altitude, occupation and ultraviolet exposure. Hydrochlorothiazide, a widely prescribed antihypertensive agent, can increase skin sensitivity to sunlight and ultraviolet radiation. Our objective is to to determine if hydrochlorothiazide is associated with NMSC in adults and, if so, to determine if there is a cumulative dose-response relationship. We will also look for associations between the risk of melanoma and hydrochlorothiazide. We will use clinical cohort data from the Canadian Partnership for Tomorrow’s Health (CanPath), linked with administrative data collected by provincial Ministries of Health, and MarketScan.

For more information, contact: Autumn Neville, Research Coordinator. [email protected]

This research is funded by CIHR-DSEN 
Lead investigator: Dr. Sasha Bernatsky
Query 19-05 raised by Health Canada, Marketed Pharmaceuticals and Medical Devices Bureau (MPMDB)Marketed Health Products Directorate (MHPD)

Query 19-03: Active Surveillance & Canadian multi-province Cohorts of Pregnant Women and Children.

This research is funded by the Drug Safety and Effectiveness Network (DSEN) and conducted by the following investigators: Anick Berard, Sasha Bernatsky, Cristiano Soares de Moura, Dan Chateau, Brandy Winquist, Bruce Carleton, Simon Vigod, Cindy-Lee Dennis, Padma Kaul, Sherif Eltonsy, Judith Maro.

Issue:

• To date, the majority of studies on the risks and benefits of medication use during pregnancy include small sample sizes, lack of statistical power, or have sub-optimal study designs to investigate rare outcomes such as congenital malformations, low birth weight or prematurity.
• To circumvent these limitations, in recent years, large national administrative databases or registries have been increasingly used in the field of perinatal pharmacoepidemiology, recognizing the importance of large size longitudinal pregnancy cohorts.

Study aim:

• To develop a provincial mother-child longitudinal, population-based cohorts in Canada (QC, ON, MB, SK, AB, BC);
• To develop standardized and harmonized tools (Common Data Models (CDM)/Definitions/Codes/Algorithms) to adequately and similarly identify pregnancy/child cohorts with longitudinal follow-up within 6 participating provinces using linkages between administrative and hospital databases based on the Quebec Pregnancy/Child Cohort (QPC), and the US Sentinel Program;
• To put in place a common repository using the CIHR funded Maelstrom Database Research platform in order to share codes, algorithms, CDM, etc, and start downloading aggregate data (means, prevalences, risks) relevant to decision-makers such as the prevalence of medication use during pregnancy and childhood, the prevalence of major malformations, prematurity, low-birth-weight, etc., that will come directly from the 6 participating province databases;
• To conduct a systematic review of active surveillance methodologies and perform pilot studies on active surveillance using the Canadian Healthcare system data and other types of data that may inform pharmacovigilance in Canada.

Study description:

• We propose to bring together data from six provinces – Quebec (QC), Ontario (ON), Manitoba (MB), Saskatchewan (SK), Alberta (AB), and British Columbia (BC) – to address a critical public health issue facing Canada and the rest of the world: the impact of prescription drug use during pregnancy on long-term health outcomes in the mother and child.
• The six provincial pregnancy-birth cohorts that we intend to align will be developed by linking several healthcare administrative databases available through the individual provinces’ ministries of health. Healthcare administrative databases have become a cornerstone in the process of assessing performance and providing feedback to improve the quality of healthcare delivery and outcomes at a population-level.
• The single-payer integrated system of health care delivery in Canada has facilitated the linking of inpatient, outpatient (including emergency department (ED) visits), hospital, ambulatory care, pharmaceutical, immunization, and laboratory data in the six provinces. The volume of data generated by linking the health care databases to environment and census data has brought us into the wider realm of “big-data”.
• During the current 12-month project, we intend to further develop standardized and harmonized algorithms and coding systems for the analysis of the pregnancy-birth cohort data across the six provinces. The resulting data infrastructure, the ‘Canadian Multi-Province Cohorts of Pregnant Women and Children’, can serve multiple functions and will result in specific tangible benefits for Canada, including:
  1. Finding cost-effective health strategies and policies improving the health of mothers, children, and the overall Canadian population;
  2. Providing a pharmacovigilance resource that can be used to rapidly answer queries from policymakers;
  3. Building capacity and training the next generation of Canadian researchers so that they can maintain their competitive advantage at the international level in the field of Medications and Pregnancy; and
  4. Developing a Canadian consortium of researchers, technicians, and knowledge users that can continue to take an active leadership role in building an international collaborative network. The expertise and access to big data necessary to build this proposed infrastructure are already present and in place in Canada.

Current status:

We have developed a website for the current study (motherchildcohort.ca). The methodology sharing platform has been developed and used by participating provinces/team members. The repository is underway but has slowed due to COVID-19.

For more information, contact: Autumn Neville, Research Coordinator. [email protected]