Pharmacoepidemiology, Volume 2, Issue 1 (March 2023) – 10 articles

People with HIV (PWH) experience higher rates of cardiovascular events (CVEs) compared with the general population. A substantial body of evidence supports that select biomarkers of inflammation (soluble CD14 [sCD14], soluble CD163 [sCD163], highly sensitive C-reactive protein [hs-CRP], interleukin-6 [IL-6]) and coagulation (D-dimer) are elevated in PWH and related to increased rates of CVEs. Our previous work showed that smoking compared with nonsmoking was associated with significantly elevated sCD14, a biomarker of monocyte activation. We aimed to explore the effect of electronic cigarette (EC) provision on inflammatory biomarkers in PWH who smoked daily and then switched to an EC. Nineteen PWH were enrolled in a pilot study in which an EC and e-liquid were provided weekly for 8 weeks. Blood specimens for inflammatory biomarker analysis were obtained at baseline (BL) and at week 8. Biomarker levels were high at BL and did not differ significantly at week 8. There were small nonsignificant reductions in sCD163 and CRP levels. Non-significant increases in IL-6, D-dimer, and sCD14 levels were also noted. Use of ECs for 8 weeks does not appear to significantly increase or decrease inflammatory biomarker levels in SWH. Further research with larger samples and a control group is needed. Full article

COVID-19 antiviral medications approved or authorized for emergency use by the U.S. Food and Drug Administration are reported to have high efficacy in preventing severe illness, hospitalizations, and deaths. However, reports for some of these antivirals use relative risk reductions from clinical trials without absolute risk reductions. The present paper reappraises recently published clinical trial data for the COVID-19 antivirals paxlovid, remdesivir, and molnupiravir, and reports absolute risk reductions, relative risk reductions, as well as number needed to treat to reduce severe illness, hospitalizations, and deaths. Relative risk reductions are 88.88% for paxlovid (95% CI: 72.13–95.56%), 86.48% for remdesivir (95% CI: 41.41–96.88%), and 30.41% for molnupiravir (95% CI: 0.81–51.18%), while absolute risk reductions are much lower at 5.73% for paxlovid (95% CI: 3.79–7.68%), 4.58% for remdesivir (95% CI: 1.79–7.38%), and 2.96% for molnupiravir (95% CI: 0.09–5.83%). Low absolute risk reductions and the high number of patients needed to treat to reduce severe COVID-19 infections, hospitalizations, and deaths challenge the clinical efficacy of antivirals approved or authorized by the U.S Food and Drug Administration. These findings apply to other populations with similar control event rates. Accurate information should be disseminated to the public when selecting treatments for COVID-19. Full article

Atrial fibrillation has been described as a global epidemic with a three-fold increase in prevalence in the last 50 years. As the prevalence of atrial fibrillation continues to grow, multiple landmark trials have been designed to determine the best method to treat atrial fibrillation. Initial trials have stated that rate control was not inferior to rhythm control, however, as the efficacy of rhythm control of atrial fibrillation has improved, a benefit in rhythm control has been shown. Because of this trend towards increased rhythm control, more patients have been placed on anti-arrhythmic medications. This paper will review the epidemiology and clinical impact of the utilization of anti-arrhythmic medications. As we enter the era of rhythm control, increased awareness is needed regarding the monitoring and potential adverse events that can occur with these medications. Providers must balance the increased emphasis on rhythm control with the overall clinical impact on their patients due to drug-to-drug interactions and adverse effects that can occur with different co-morbidities. If the clinical momentum towards rhythm control continues, real-world data analysis will be needed to evaluate the clinical impact of the use, risk, and benefits of anti-arrhythmic medications. Full article

This study aimed to investigate the knowledge and practices among dental practitioners in Saudi Arabia regarding the use of antimicrobials for periodontal diseases. An online questionnaire was sent to senior dental students and dental practitioners including interns, general dental practitioners (GDP), and periodontists in Saudi Arabia. Two hundred and twenty-three dental practitioners responded and participated in the study. The potential associations between the use of antimicrobials and different variables were assessed by a chi-square test. The majority of the participants (84.3%) reported prescribing systemic antimicrobials for a periodontal abscess or acute necrotizing periodontal disease. Surprisingly, 31% of participants reported prescribing systemic antimicrobials for deep localized periodontal pockets or for acute gingivitis associated with herpes simplex in children. Noteworthy is that 66% of the participants thought that mechanical periodontal treatment alone, without adjunctive antimicrobial therapy, is adequate to resolve the clinical condition in most cases of periodontal diseases. Almost half of the participants recommended the use of local antimicrobials for a periodontal pocket (45.3%), a recurrent periodontal pocket (45.4%), and refractory periodontitis (43.7%). The barriers against the use of local antimicrobials were a lack of knowledge and a lack of continuous education after graduation, as reported by 64% of the participants. In conclusion, knowledge and practices regarding antimicrobial use for periodontal diseases were inadequate, especially among practitioners other than periodontists. Full article

The objective of this study was to describe pregnancy- and birth-related experiences of postpartum women during the third wave of the COVID-19 pandemic and their association with mental health outcomes. An online questionnaire was distributed in five European countries (Belgium, The Netherlands, Norway, Switzerland, UK) between June and August 2021. Participants were recruited though social media platforms including pregnancy- and motherhood-related websites, pregnancy fora, and apps. Postpartum women were asked eleven specific questions about pregnancy- and birth-related changes and the presence of support during delivery. The Edinburgh Depression Scale was used to assess depressive and anxiety symptoms. Covariates included sociodemographics, health and reproductive characteristics, and COVID-19 status. Associations were estimated with logistic regression. The study included 1730 postpartum women. Frequent changes included the exclusion of the partner from pregnancy care appointments (83.2%), changed prenatal care settings (64.4%), and cancellation of hospital information visits (42.7%). Few women, however, were without support apart from medical staff during delivery (1.4%). The number of pregnancy- and birth-related changes was associated with each woman’s mental health status, as well as the type of change. Experiencing changes related to delivery and cancellation or reduction of prenatal examination was associated with a doubling in the odds of symptoms of major depression and anxiety postpartum. These findings highlight the importance of ensuring adequate maternity care for women’s mental health postpartum, as well as during a pandemic. Full article

Irrational and inappropriate prescribing of antibiotics is a major problem that can lead to the development of antimicrobial resistance (AMR). In Zambia, there is insufficient information on the prescribing patterns of antibiotics according to the World Health Organization (WHO) AWaRe classification. Therefore, this study assessed the prescribing patterns of antibiotics using the AWaRe classification during the COVID-19 pandemic at the University Teaching Hospital in Lusaka, Zambia. A cross-sectional study was conducted using 384 patient medical files at the University Teaching Hospital in Lusaka, Zambia, from August 2022 to September 2022. All antibiotics were classified according to the WHO “AWaRe” tool and assessed for appropriateness using the 2020 Zambian Standard Treatment Guidelines. Of the 384 patient medical files reviewed, antibiotics were prescribed 443 times. The most prescribed antibiotics were ceftriaxone (26.6%), metronidazole (22.6%), amoxicillin (10.4%), amoxicillin/clavulanic acid (5.6%), and azithromycin (5%). The prescribing of 42.1% of “Watch” group antibiotics was greater than the recommended threshold by the WHO. Most antibiotics were prescribed for respiratory infections (26.3%) and gastrointestinal tract infections (16.4%). The most prescribed antibiotic was ceftriaxone, a Watch antibiotic. This is a worrisome observation and calls for strengthened antimicrobial stewardship and implementation of the AWaRe framework in prescribing antibiotics. Full article

Heart disease and cancer are the main causes of morbidity and mortality worldwide. As the number of cancer survivors increases, cardiotoxicity associated with cancer treatment has become a major concern as it presents a substantial challenge in the follow-up of these patients. Here, we aimed to map the clinical indicators for cardiovascular risk in adult patients undergoing chemotherapy. A scoping review protocol adhering to the PRISMA-P statement and in accordance with the JBI guidelines will be conducted. Cochrane Library, MEDLINE/PubMed, Cochrane Library, EMBASE, Scopus, Web of Science, and PsycINFO as well as register sites such as ClinicalTrials.gov and WHO-ICTRP will be searched. Additional sources, including Google Scholar, The British Library, and medRXiv, will also be searched, with no date or idiom restrictions. A combination of subject headings, MeSH terms, Emtree terms, CINAHL Headings, and APA Thesaurus, using the Boolean terms AND/OR, will be performed. In addition, two independent researchers will conduct the overall steps of this review. The results will be presented via narrative summaries, considering the types of clinical indicators. To the best of our knowledge, this will be the first scoping review in the cardio-oncology field to map, via a rigorous review method, the clinical indicators for cardiovascular risk in adult cancer patients receiving chemotherapy. Full article

Although 5-Aminosalicylate (5-ASA) has been shown to act on the local mucosa, when 5-ASA is orally administered, most of it is absorbed in the upper gastrointestinal tract and does not reach the large intestine, where lesions are present. Therefore, different drug delivery systems have been developed for each oral 5-ASA formulation. Currently, the oral 5-ASA formulation approved in Japan is salazosulfapyridine (SALAZOPYRIN^®; Pfizer Japan Inc.: Tokyo, Japan), in which 5-ASA and sulfapyridine are azo-bonded. In addition, there are several 5-ASA release formulations, including ASACOL^®; ZERIA Pharmaceutical Co., Ltd.: Tokyo, Japan (delayed release formulation dependent on pH), PENTASA^®; KYORIN Pharmaceutical Co., Ltd.: Tokyo, Japan (delayed release formulation dependent on time), and LIALDA^®; MOCHIDA Pharmaceutical Co., Ltd.: Tokyo, Japan (delayed release formulation dependent on pH and time). Adverse events may occur because of differences in the drug delivery systems of these products. In this study, we focused on the adverse events of different 5-ASA formulations and investigated differences in the detection of safety signals for each 5-ASA formulation using disproportionality analysis. There were 15 adverse events detected only with SALAZOPYRIN^®. On the other hand, ASACOL^®, PENTASA^®, and LIALDA^® have different drug delivery systems. Although the detected signal intensities varied, the detected adverse events were not significantly different. These findings provide important insights, which should be considered by physicians during treatment selection and drug manufacturers during drug development. Full article

We aimed to evaluate the adverse birth outcomes of anticancer drug prescription during pregnancy using a Japanese claims database from 2005 to 2019. We applied validated claims-based algorithms to identify pregnant women with birth outcomes, and evaluated drug prescription during pregnancy. The causal relationship between anticancer drugs and adverse birth outcomes was evaluated using the Council for International Organizations of Medical Sciences Working Group VI criteria. Thirteen women with anticancer drugs prescription during pregnancy were identified (mean age: 34.6 years). Atrial/ventricular septal defect was observed in one infant after exposure to cyclophosphamide and doxorubicin for breast cancer in the second and third trimesters. One woman on several anticancer drugs (cyclophosphamide, cytarabine, daunorubicin, l-asparaginase, methotrexate, nelarabine, and vincristine) for acute lymphoblastic leukemia, one on imatinib for chronic myeloid leukemia, and one on cisplatin and fluorouracil for cervical cancer had miscarriages after exposure in the first trimester. A relationship between those anticancer drugs and miscarriage could not be ruled out, while no relationship was identified regarding the atrial/ventricular septal defect considering the period of exposure and organogenesis. Our results suggest increased risk of miscarriage with the use of several anticancer drugs such as methotrexate, imatinib, cisplatin, and fluorouracil in the first trimester. Full article

Unique aspects of New Zealand’s (NZ) health system allow for a novel pharmacoepidemiologic approach to conducting population-based clinical research. A defined cohort of surgical and trauma patients would facilitate future studies into opioid utilisation, outcomes, and other questions related to surgery and trauma. We aimed to describe all patients admitted to a NZ hospital with trauma or to undergo surgery between 1 January 2007 to 31 December 2019. This was a retrospective population-based study involving all hospital centres in NZ. We excluded patients with hospitalisation episodes for surgery or trauma one year before the event. We identified 1.78 million surgical only patients, 633,386 trauma only, and 250,800 trauma with surgery patients. Trauma only patients had the highest prevalence of death within one year of event (17.8%), history of opioid dispensing (18.3%), mental health disorders (17.0%) and chronic pain (2.3%). Moreover, trauma patients also had the highest prevalence of those with higher comorbidity burden. We plan to use this dataset for future research into the prevalence and outcomes of persistent opioid use, and to make our dataset available to other researchers upon request. Our findings of significant differences between cohorts suggest studies should treat surgical and trauma patients separately. Full article