Causality assessment of adverse drug reaction: A narrative review to find the most exhaustive and easy-to-use tool in post-authorization settings.

BACKGROUND: The core motive of pharmacovigilance is the detection and prevention of adverse drug reactions (ADRs), to improve the risk-benefit balance of the drug. However, the causality assessment of ADRs remains a major challenge among clinicians, and none of the available tools of causality assessment used for assessing ADRs have been universally accepted. OBJECTIVE: To provide an up-to-date overview of the different causality assessment tools. METHODS: We conducted electronic searches in MEDLINE, EMBASE, and the Cochrane database. The eligibility of each tool was screened by three reviewers. Each eligible tool was then scrutinized for its domains (the reported specific set of questions/areas used for calculating the likelihood of cause-and-effect relation of an ADR) to discover the most comprehensive tool. Finally, we subjectively assessed the tool's ease-of-use in a Canadian, Indian, Hungarian, and Brazilian clinical context. RESULTS: Twenty-one eligible causality assessment tools were retrieved. Naranjo's tool and De Boer's tool appeared the most comprehensive among all the tools, covering 10 domains each. Regarding "ease-of-use" in a clinical setting, we judged that many tools were hard to implement in a clinical context because of their complexity and/or lengthiness. Naranjo's tool, Jones's tool, Danan and Benichou's tool, and Hsu and Stoll's tool appeared to be the easiest to implement into various clinical contexts. CONCLUSION: Among the many tools identified, 1981 Naranjo's scale remains the most comprehensive and easy to use for performing causality assessment of ADRs. Upcoming analysis should compare the performance of each ADR tool in clinical settings.

Reporting Rates of Opioid-Related Adverse Events Since 1965 in Canada: A Descriptive Retrospective Study.

BACKGROUND: Patients with chronic or acute/postoperative pain frequently use opioids. However, opioids may cause considerable adverse reactions (ARs), such as respiratory depression, which could be lethal. Unfortunately, only 5% of drug-related ARs (including those to opioids) are reported to health authorities. Therefore, little is known regarding the occurrence of opioid-related ARs at the population level. OBJECTIVE: The aim of this study was to investigate how the rates of reported opioid-related ARs have changed in Canada since 1965. METHODS: Our retrospective study examined trends of reported opioid-related ARs occurring in hospitalized and outpatients. Data on opioid-related ARs and mortality between 1965 and 2019 were obtained from the Canada Vigilance and Statistics Canada databases. Descriptive and Joinpoint regression analyses were performed. RESULTS: Oxycodone and normethadone were the most and least involved opioid agents, respectively, among the 18,407 reported ARs. The highest rate of reported opioid ARs (3.8 per 100,000 person-years) was recorded in 2012, whereas the lowest was recorded in 1965 (0.1 per 100,000 person-years). Between 1965 and 2019, annual rates climbed by 4.2% (95% confidence interval [CI] 3.1-5.2), and many fluctuations were observed: 1965-1974: +22.3% (95% CI 12.0-33.6); 1974-2000: - 4.1% (95% CI - 5.3 to - 2.9); 2000-2008: +30.3% (95% CI 22.6-38.4); 2008-2014: +4.1% (95% CI - 1.5 to 10.1); 2014-2017: -26.0% (95% CI - 44.7 to - 0.9); and, finally, 2017-2019: +35.4% (95% CI 3.8-76.7). CONCLUSION: Reported opioid-related ARs have increased since 1965, although fluctuations were observed in recent decades. The absolute number of opioid-related ARs might be seriously underestimated. Future studies should look into how to close this gap.

Using Data from the Canadian Post-marketing Spontaneous Pharmacovigilance System for Drug Safety Research: A Feasibility Study.

INTRODUCTION: Post-marketing studies involve the detection and interpretation of potential problems associated with the use of a given drug. Post-marketing spontaneous pharmacovigilance systems, such as the Canada Vigilance program, may constitute a gold mine of free data for drug safety research. However, the quantity and the quality of data remain to be demonstrated. OBJECTIVE: To assess the feasibility to use the Canada Vigilance database for academic drug safety research, and to document the characteristics of data that are extractable. METHODS: This is a descriptive retrospective analysis study design. The beta-blocker and anticoagulant adverse reactions (AR) in Canada were analyzed. Tests for data extraction from the Canada Vigilance database were performed in October 2019; data were then available from January 1, 1966 to June 30, 2019. RESULTS: There were 41 variables with extractable data. For anticoagulants, data were extracted in Excel and.pdf file format, while it was only plain text.pdf files for beta-blockers. Overall, there were 4707 reported ARs with the use of anticoagulants and 6332 cases reported for beta-blockers. The trend of ARs related to anticoagulants steadily increased in the study period, with a notable increase in 2009 while direct oral anticoagulants were marketed. The proportion of missing data varied from 0 to 98%, but most important variables were all available. It was not possible to distinguish brand names and generic drugs in the database. CONCLUSION: It seems feasible to use data from the Canadian Post-marketing Spontaneous Pharmacovigilance System for academic drug safety research. Upcoming studies should validate the quality of reports compared to actual medical charts.

Attitudes of Nigerian women toward the presence of their husband or partner as a support person during labor.

OBJECTIVE: To assess the attitudes of Nigerian women regarding the presence of a husband/partner during labor. METHODS: Women who were invited to participate in a randomized trial regarding companionship in labor at the Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Nigeria, were interviewed in a qualitative cross-sectional survey. Demographic characteristics and opinions regarding the presence of a partner/husband as a support person during labor were assessed. RESULTS: Of the 197 women interviewed, 69 declined all forms of social companionship during labor; of the remaining 128 participants--who did not object to having a social companion--71 declined to have their husband/partner present during labor because of: personal embarrassment (28 [39.4%]); fear of loss of sexual attractiveness (19 [26.8%]); concern for their husband/partner (17 [23.9%]); and lack of privacy (15 [21.1%]). Of the 57 women whose husband/partner accompanied them during labor, 38 (66.7%) said that they would repeat the experience in subsequent labor, and 34 (59.6%) would recommend it. However, 15 (26.3%) expressed dissatisfaction. CONCLUSION: The issue of husband/partner companionship during labor is viewed with concern by Nigerian women, who should be allowed to make an informed decision.

Assisted breech delivery, is the art fading?

OBJECTIVE: To review the modes of breech delivery over a 5 year period in Khamis Civil Hospital, Khamis Mushayt, Kingdom of Saudi Arabia, and to evaluate the trend and associated complications. METHODS: Relevant data was extracted from the delivery room records of all women delivered in Khamis Civil Hospital, Khamis Mushayt, Kingdom of Saudi Arabia, from 1st January 1996 through 31st December 2000. Available data was analyzed. RESULTS: There were 375 breech deliveries, constituting 2.8% of the entire deliveries in the hospital. Eighty-two percent of the breeches were delivered by cesarean section while 18% had assisted vaginal delivery (p=0.0193). Amongst 72 primigravidae breeches, 68 (94.4%) were delivered by cesarean section while 238 (78.5%) out of 303 multigravidae were delivered by cesarean section. There were 2 unexplained neonatal deaths among the vaginal delivery group in multigravidae. Cesarean delivery was associated with less morbidity compared to vaginal delivery. CONCLUSION: This study has demonstrated a significant increase in delivery of breeches by cesarean section and the resultant drop, in the number available for assisted breech delivery. Less obstetricians will therefore be exposed practically to the art of assisted breech delivery. Most practicing obstetricians seem to be more inclined towards delivering breeches by cesarean section. If this trend continues, the art of assisted breech delivery may fade.