BMJ Open. 2022 Nov 2;12(11):e062853. doi: 10.1136/bmjopen-2022-062853.

ABSTRACT

INTRODUCTION: Adverse drug events (ADEs) among hospitalised older adults are common yet often preventable. Efforts to recognise ADEs using pharmacist review and electronic health record adaptations have had mixed results. Our health system developed and implemented a geriatric prescribing context designed to offer age-friendly dose and frequency defaults for hospitalised patients 75 years and older. The impact of this context on ADEs remains unknown. To measure its impact, our team created a list of ADE-related International Classification of Diseases (ICD) codes specific to 10 commonly used medications at our institution. This protocol paper presents the process of designing a screening tool for ADEs, validating the tool with manual chart reviews and measuring the impact of the context on ADEs.

METHODS AND ANALYSIS: This retrospective cross-sectional study will assess our list of ICD-10 codes against manual chart review to determine its accuracy. An electronic health record report for patients aged 75 years and older admitted to the hospital for a minimum of two nights was generated to identify 100 test positives and 100 test negatives. Test positives need at least one code from each level of our ICD-10 code list. The first level of codes identifies any possible ADEs while the second level is more symptom based. Test negatives must not have any code from the list. Two physicians blinded to test status will complete a structured chart review to determine if a patient had an ADE during their hospitalisation. Acceptable inter-rater reliability will need to be met before proceeding with independent chart review. Positive predictive value and negative predictive value will be calculated once all the chart reviews are completed.

ETHICS AND DISSEMINATION: The Oregon Health & Science University Institutional Review Board approved this study (#21385). The results of the study will be disseminated in peer-reviewed journals and conference presentations.

PMID:36323472 | DOI:10.1136/bmjopen-2022-062853

Expert Rev Gastroenterol Hepatol. 2022 Nov 2. doi: 10.1080/17474124.2022.2143346. Online ahead of print.

ABSTRACT

OBJECTIVE: Different classes of medication have been reported in the literature to be associated with an increased risk of gastrointestinal perforation. However, little is known about the risk of drug-induced perforated appendicitis.

METHODS: We analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS), a large national database of reported adverse events associated with post-market FDA-approved medications from Jan 2011 through Oct 2021. Patients of any age group with appendiceal perforation were included. Duplicated reports and other anatomical areas of gastrointestinal tract perforation outside the appendix were excluded.

RESULTS: During the study period, 474 event cases met inclusion criteria, of which 284 were females. Most reports of perforation occurred in patients 40-49 years (n=110) and 50-59 years (n=144). Cases of perforated appendicitis occurred in patients being treated for multiple sclerosis (31.5%) and rheumatoid arthritis (17.1%). Perforation occurred in patients receiving interferon beta 1a (23.6%), adalimumab (17.9%), etanercept (14.1%), natalizumab (12.2%), clozapine (10.1%), infliximab (9.9%), bevacizumab (7.2%), and calcium chloride (4.9%). Sixteen fatal outcomes were reported.

CONCLUSION: Findings from the FAERS database highlight the risk of appendiceal perforation in the context of different classes of drugs. Larger pharmacovigilance studies are needed to confirm these observations as well as overcome inherent reporting biases.

PMID:36322707 | DOI:10.1080/17474124.2022.2143346

Rev Panam Salud Publica. 2022 Oct 25;46:e166. doi: 10.26633/RPSP.2022.166. eCollection 2022.

ABSTRACT

OBJECTIVE: To identify central nervous system (CNS) adverse events potentially associated with prophylaxis or drug treatment for COVID-19, and to describe the characteristic of the individuals affected.

METHODS: A scoping review was performed using a search strategy to retrieve articles from PubMed, EMBASE, SciELO, Scopus, CINAHL and BVS databases. Studies reporting on individuals receiving prophylactic or curative drugs for COVID-19 with at least one CNS adverse event were included. Articles reporting on CNS adverse events associated with medication for other health conditions were excluded.

RESULTS: The search retrieved 1 547 articles, eight of which met the inclusion criteria. Seven studies had an observational design. A total of 3 035 individuals were assessed, of whom 1 701 were health care professionals and 1 978 were women. Curative treatment with hydroxychloroquine, chloroquine, lopinavir/ritonavir, and azithromycin was the most frequent (n = 5). The most common adverse events were headache, dizziness, mood disturbances, and drowsiness. Suicide was the most frequent severe event. Six adverse events were unexpected for hydroxychloroquine, chloroquine, and doxycycline.

CONCLUSION: Potential CNS adverse events were unspecific and in general potentially associated with the use of hydroxychloroquine (monotherapy or associated with antibiotics). The data confirm the unfavorable risk/benefit profile of these drugs for the prevention and management of signs and symptoms of SARS-CoV-2 infection.

PMID:36320207 | PMC:PMC9595226 | DOI:10.26633/RPSP.2022.166

PLoS One. 2022 Nov 1;17(11):e0272022. doi: 10.1371/journal.pone.0272022. eCollection 2022.

ABSTRACT

BACKGROUND: Treatment options for many cancers include immune checkpoint inhibitor (ICI) monotherapy and combination therapy with impressive clinical benefit across cancers. We sought to define the comparative cardiac risks of ICI combination and monotherapy.

METHODS: We used VigiBase, the World Health Organization pharmacovigilance database, to identify cardiac ADRs (cADRs), such as carditis, heart failure, arrhythmia, myocardial infarction, and valvular dysfunction, related to ICI therapy. To explore possible relationships, we used the reporting odds ratio (ROR) as a proxy of relative risk. A lower bound of a 95% confidence interval of ROR > 1 reflects a disproportionality signal that more ADRs are observed than expected due to chance.

RESULTS: We found 2278 cADR for ICI monotherapy and 353 for ICI combination therapy. Combination therapy was associated with significantly higher odds of carditis (ROR 6.9, 95% CI: 5.6-8.3) versus ICI monotherapy (ROR 5.0, 95% CI: 4.6-5.4). Carditis in ICI combination therapy was fatal in 23.4% of reported ADRs, compared to 15.8% for ICI monotherapy (P = 0.058).

CONCLUSIONS: Using validated pharmacovigilance methodology, we found increased odds of carditis for all ICI therapies, with the highest odds for combination therapy. Given the substantial risk of severe ADR and death, clinicians should consider these findings when prescribing checkpoint inhibitors.

PMID:36318537 | PMC:PMC9624428 | DOI:10.1371/journal.pone.0272022

Medicine (Baltimore). 2022 Oct 28;101(43):e31296. doi: 10.1097/MD.0000000000031296.

ABSTRACT

BACKGROUND: Nefopam is a non-opioid, non-nonsteroidal anti-imflammatory drug, analgesic drug that inhibits the reuptake of serotonin, norepinephrine, and dopamine. It is widely used as an adjuvant for pain. This study investigated whether the intraoperative, intravenous infusion of nefopam (20 mg) reduces postoperative morphine consumption, pain scores, and alleviates neuropathic pain in patients undergoing cervical spine surgery.

METHODS: A prospective, paralleled design, randomized study was conducted on 50 patients (aged 18-75 years) in a university-based hospital. The patients were assigned to an intervention or a control group (25 patients in each). The intervention group received a 1-hour infusion of nefopam (20 mg) before the end of surgery. The control group received normal saline (NSS). The outcome measures were morphine consumption during the first 24 postoperative hours, numerical rating scale (NRS) pain scores, and scores for the Thai version of the Neuropathic Pain Symptom Inventory (NPSI-T) in patients with neuropathic pain and adverse drug reactions. The NPSI-T scores were assessed on the preoperative day, postoperative day 1, 3, 15, and 30. The outcome assessors were blinded to group allocation.

RESULTS: Fifty patients were analyzed. During the first 24 postoperative hours, morphine consumption was 8 mg (nefopam) and 12 mg (NSS; P = .130). The intervention and control groups demonstrated no significant differences in the median NRS scores or total NPSI-T scores or adverse drug reactions.

CONCLUSIONS: A single, intraoperative infusion of 20 mg of nefopam did not significantly reduce postoperative (24 hours) morphine consumption in patients undergoing anterior cervical spine surgery.

PMID:36316913 | DOI:10.1097/MD.0000000000031296

Respir Res. 2022 Oct 31;23(1):299. doi: 10.1186/s12931-022-02218-z.

ABSTRACT

BACKGROUND: The effect of ambient temperature on respiratory mortality has been consistently observed throughout the world under different climate change scenarios. Countries experiencing greater inter-annual variability in winter temperatures (and may not be lowest winter temperatures) have greater excess winter mortality compared to countries with colder winters. This study investigates the association between temperature and respiratory deaths in Malta which has one of the highest population densities in the world with a climate that is very hot in summer and mild in winter.

METHODS: Daily number of respiratory deaths (7679 deaths) and meteorological data (daily average temperature, daily average humidity) were obtained from January 1992 to December 2017. The hot and cold effects were estimated at different temperatures using distributed lag non-linear models (DLNM) with a Poisson distribution, controlling for time trend, relative humidity and holidays. The reference temperature (MMT) for the minimum response-exposure relationship was estimated and the harvesting effects of daily temperature (0-27 lag days) were investigated for daily respiratory mortality. Effects were also explored for different age groups, gender and time periods.

RESULTS: Cooler temperatures (8-15 °C) were significantly related to higher respiratory mortality. At 8.9 °C (1st percentile), the overall effect of daily mean temperature was related to respiratory deaths (RR 2.24, 95%CI 1.10-4.54). These effects were also found for males (95%CI 1.06-7.77) and males across different age groups (Males Over 65 years: RR 4.85, 95%CI 2.02-11.63 vs Males between 16 and 64 years: RR 5.00, 95%CI 2.08-12.03) but not for females. Interestingly, colder temperatures were related to respiratory deaths in the earliest time period (1992-2000), however, no strong cold effect was observed for later periods (2000-2017). In contrast, no heat effect was observed during the study period and across other groups.

CONCLUSIONS: The higher risk for cold-related respiratory mortality observed in this study could be due to greater inter-annual variability in winter temperatures which needs further exploration after adjusting for potential physical and socio-demographic attributes. The study provides useful evidence for policymakers to improve local warning systems, adaptation, and intervention strategies to reduce the impact of cold temperatures.

PMID:36316676 | DOI:10.1186/s12931-022-02218-z

BMC Gastroenterol. 2022 Oct 31;22(1):441. doi: 10.1186/s12876-022-02542-0.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide every year, and most HCC patients are diagnosed with advanced disease and can only receive systemic treatment. TKIs are the most important components of the systemic treatment of HCC and have both good efficacy and adverse events (AEs). METHODS: This analysis included 207 patients with locally advanced unresectable or metastatic HCC who received oral treatment with apatinib. We analyzed the overall survival (OS) and progression-free survival (PFS) of patients with or without corresponding AEs to evaluate which AEs can predict the efficacy of apatinib.

RESULTS: Patients with hand-foot syndrome (HFS; p = 0.005), proteinuria (p = 0.006) and diarrhea (p < 0.001) had significantly better OS than those without corresponding AEs, and the appearance of HFS (p = 0.006) and proteinuria (p = 0.004) was associated with longer PFS.

CONCLUSION: Among all the AEs induced by apatinib in the treatment of advanced HCC, proteinuria could potentially predict PFS, and diarrhea was a potential predictor of OS.

PMID:36316630 | DOI:10.1186/s12876-022-02542-0

Int J Med Sci. 2022 Oct 9;19(12):1816-1823. doi: 10.7150/ijms.76139. eCollection 2022.

ABSTRACT

Adverse drug events due to drug-drug interactions can be prevented by avoiding concomitant use of causative drugs; therefore, it is important to understand drug combinations that cause drug-drug interactions. Although many attempts to identify drug-drug interactions from real-world databases such as spontaneous reporting systems have been performed, little is known about drug-drug interactions caused by three or more drugs in polypharmacy, i.e., multiple drug-drug interactions. Therefore, we attempted to detect multiple drug-drug interactions using decision tree analysis using the Japanese Adverse Drug Event Report (JADER) database, a Japanese spontaneous reporting system. First, we used decision tree analysis to detect drug combinations that increase the risk of rhabdomyolysis in cases registered in the JADER database that used six statins. Next, the risk of three or more drug combinations that significantly increased the risk of rhabdomyolysis was validated with in vivo experiments in rats. The analysis identified a multiple drug-drug interaction signal only for pitavastatin. The reporting rate of rhabdomyolysis for pitavastatin in the JADER database was 0.09, and it increased to 0.16 in combination with allopurinol. Furthermore, the rate was even higher (0.40) in combination with valsartan. Additionally, necrosis of leg muscles was observed in some rats simultaneously treated with these three drugs, and their creatine kinase and myoglobin levels were elevated. The combination of pitavastatin, allopurinol, and valsartan should be treated with caution as a multiple drug-drug interaction. Since multiple drug-drug interactions were detected with decision tree analysis and the increased risk was verified in animal experiments, decision tree analysis is considered to be an effective method for detecting multiple drug-drug interactions.

PMID:36313225 | PMC:PMC9608045 | DOI:10.7150/ijms.76139

Asian Pac J Cancer Prev. 2022 Oct 1;23(10):3323-3330. doi: 10.31557/APJCP.2022.23.10.3323.

ABSTRACT

OBJECTIVE: Supporting data exists concerning short hydration to prevent cisplatin-induced nephrotoxicity. However, only a few studies exist. Further, data remains limited, comprising mostly retrospective data. Therefore, the study would like to evaluate the efficacy of short hydration using a prospective cohort study.

MATERIALS AND METHODS: This is a prospective cohort non-randomized controlled study in patients receiving intermediate to high doses of cisplatin. Short hydration was set as the intervention arm, while conventional hydration was set as the controlled arm. The consecutive estimates glomerular filtration rates (eGFR) were compared at baseline, Week 3, Week 6, Week 9, Week 12, and Week 15 for both groups by using multilevel regression analysis with the random-effects model with double adjustment (propensity score and confounding adjustment) was used. The trial was registered with the Thai Registry of Clinical Trials, SHORTCIS ThaiClinicalTrials.org, number TCTR20210128002.

RESULTS: 30 patients were registered. 14 were assigned to a short hydration group, while 16 were assigned to a conventional hydration group. The levels of consecutive eGFR of the group receiving short hydration were stable (regression coefficients 0.05), while the levels of consecutive eGFR of the group receiving conventional hydration were declined (regression coefficients -1.94). The multilevel regression analysis of consecutive eGFR between conventional group and short hydration group when adjusted for random-effects parameters and double adjustment were significantly different (p-value = 0.001). When analyzing the relationship of received short hydration, it could significantly reduce the risk of nephrotoxicity as well, i.e. acute kidney injury (odds ratio 0.06, 95%CI 0.003, 0.990, p-value 0.049).

CONCLUSION: Short hydration was more efficient for preventing nephrotoxicity than conventional hydration protocols in patients receiving intermediate to high doses of cisplatin.

PMID:36308355 | DOI:10.31557/APJCP.2022.23.10.3323

Nat Commun. 2022 Oct 28;13(1):6453. doi: 10.1038/s41467-022-33834-4.

ABSTRACT

Cancer vaccines as immunotherapy for solid tumours are currently in development with promising results. We report a phase 1 study of Ad-sig-hMUC1/ecdCD40L (NCT02140996), an adenoviral-vector vaccine encoding the tumour-associated antigen MUC1 linked to CD40 ligand, in patients with advanced adenocarcinoma. The primary objective of this study is safety and tolerability. We also study the immunome in vaccinated patients as a secondary outcome. This trial, while not designed to determine clinical efficacy, reports an exploratory endpoint of overall response rate. The study meets its pre-specified primary endpoint demonstrating safety and tolerability in a cohort of 21 patients with advanced adenocarcinomas (breast, lung and ovary). The maximal dose of the vaccine is 1 ×1011 viral particles, with no dose limiting toxicities. All drug related adverse events are of low grades, most commonly injection site reactions in 15 (71%) patients. Using exploratory high-dimensional analyses, we find both quantitative and relational changes in the cancer immunome after vaccination. Our data highlights the utility of high-dimensional analyses in understanding and predicting effective immunotherapy, underscoring the importance of immune competency in cancer prognosis.

PMID:36307410 | DOI:10.1038/s41467-022-33834-4

Ophthalmology. 2022 Oct 25:S0161-6420(22)00832-6. doi: 10.1016/j.ophtha.2022.10.017. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the risk of ocular adverse events after COVID-19 mRNA vaccination.

DESIGN: Matched cohort and self-controlled case series (SCCS) studies.

SUBJECTS/CONTROLS: We used a population-based database of medical claims and vaccination records in a large city of Japan. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from non-vaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events from February 2021 to the end of follow-up.

METHODS: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared to the remaining periods.

MAIN OUTCOME MEASURES: Composite outcome of uveitis, scleritis, retinal vein occlusion, and optic neuritis.

RESULTS: There were 99,718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100,000 persons and 51.3 (16.2 to 84.3) events/100,000 persons, respectively, for the first and second dose. The SCCS study showed the incidence rate ratios of 0.89 (0.62 to 1.28) and 0.89 (0.71 to 1.11) for the first and second doses, respectively.

CONCLUSIONS: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events.

PMID:36306975 | DOI:10.1016/j.ophtha.2022.10.017

Ocul Immunol Inflamm. 2022 Oct 28:1-6. doi: 10.1080/09273948.2022.2137045. Online ahead of print.

ABSTRACT

We reviewed the medical charts of five patients diagnosed with brimonidine tartrate (BT)-related corneal disorders. A fan-shaped corneal opacity was present in four patients and limbal corneal infiltrations were present in one patient. In vivo confocal microscopy revealed dendritic cells and lipid deposits in the fan-shaped opacity as well as neutrophils in limbal infiltrations. BT instillation was discontinued and topical administration of a corticosteroid was initiated for all patients. The limbal infiltrations improved after BT discontinuation. Conversely, the fan-shaped opacity remained in all affected patients. After a fan-shaped opacity has developed in a patient with a BT-related corneal disorder, the lesion is difficult to resolve. However, limbal infiltrations respond well to treatment. Therefore, BT should be discontinued and anti-inflammatory treatment initiated before a fan-shaped opacity forms.

PMID:36306423 | DOI:10.1080/09273948.2022.2137045

Front Pediatr. 2022 Jul 19;10:903677. doi: 10.3389/fped.2022.903677. eCollection 2022.

ABSTRACT

BACKGROUND AND AIMS: In recent years, biological agents, such as anti-TNF-α blockers, have been introduced and have shown efficacy in pediatric patients with inflammatory bowel disease (IBD). Here, the prescription mode differentiated into a first/second line application, and efficacy and side effects are evaluated beginning from 2004 until today.

METHODS: Statistical analyses of the prospective and ongoing CEDATA multicenter registry data from the Society of Pediatric Gastroenterology and Nutrition (GPGE) were performed for patients receiving a biological agent at least once during the period from June 2004 until November 2020 (n = 487). The analyzed parameters were patient demographics, disease extent and behavior, prior or concurrent therapies, duration and outcome of biological therapy, disease-associated complications, drug-related complications, laboratory parameters and treatment response as determined by the Physician's Global Assessment.

RESULTS: Crohn's disease (CD) was present in 71.5% of patients, and 52% were boys. Patients showed high disease activity when receiving a first-line TNF-α blocker. After 2016, patients who failed to respond to anti-TNF-α induction therapy were treated with off-label biologics (vedolizumab 4.3% and ustekinumab 2.1%). Propensity score matching indicated that patients with CD and higher disease activity benefitted significantly more from early anti-TNF-α therapy. This assessment was based on a clinical evaluation and lab parameters related to inflammation compared to delayed second-line treatment. Additionally, first-line treatment resulted in less treatment failure and fewer extraintestinal manifestations during TNF-α blockade.

CONCLUSION: First-line treatment with anti-TNF-α drugs is effective and safe. An earlier start significantly reduces the risk of treatment failure and is associated with fewer extraintestinal manifestations during longitudinal follow-up.

PMID:36304532 | PMC:PMC9595023 | DOI:10.3389/fped.2022.903677

Br J Gen Pract. 2022 Oct 27;72(724):539. doi: 10.3399/bjgp22X721133. Print 2022 Nov.

NO ABSTRACT

PMID:36302682 | DOI:10.3399/bjgp22X721133

J Clin Psychiatry. 2022 Oct 24;83(6):21m14267. doi: 10.4088/JCP.21m14267.

ABSTRACT

Objective: Ketamine is increasingly prescribed for treatment-resistant depression (TRD), often as add-on to regular antidepressants. Augmentation of ketamine to monoamine oxidase inhibitors (MAOIs) is advised against, as this practice might increase blood pressure or cause serotonin syndrome. Despite the potential relevance for patients, little is known about actual side effects of combined use. We summarize literature on the safety and add results of our case series.

Evidence Review: PubMed and Embase were searched from inception to July 2021 for English-language articles describing concomitant use of ketamine and MAOIs. The search strategy included terms for "ketamine" AND "monoamine oxidase inhibitor" including generic and brand names. Additionally, we describe the safety of twice weekly oral esketamine administration over the course of 5 weeks to 9 months in 8 TRD patients using MAOIs.

Findings: After deduplication, we screened 138 articles and assessed 43 full texts. Twelve studies were included with a total of 39 patients receiving ketamine and MAOIs. Blood pressure and heart rate increased in multiple cases, though this was deemed clinically insignificant in all but 1 patient. No signs of hypertensive crisis or serotonin syndrome were observed. In our case series, we observed minor elevations in blood pressure and heart rate and no serious adverse events.

Conclusions and Relevance: The results suggest that combined use of MAOIs and esketamine is less prone to severe side effects than presumed. The investigated sample size was small, and prescribed doses of MAOIs were relatively low. Further research is required before definite conclusions about the safety of this combination can be drawn.

PMID:36300995 | DOI:10.4088/JCP.21m14267

G Ital Cardiol (Rome). 2022 Nov;23(11):e. doi: 10.1714/3900.38832.

NO ABSTRACT

PMID:36300396 | DOI:10.1714/3900.38832

Int J Environ Res Public Health. 2022 Oct 13;19(20):13167. doi: 10.3390/ijerph192013167.

ABSTRACT

The most common effects reported by the Italian Medicine Agency following administration of SARS-CoV-2 vaccine are myalgia, soreness to the arm of inoculation, fever, and asthenia. To date, there are no specific and official reports registered by the Italian Medicine Agency on possible alterations of the menstrual cycle, or of the female reproductive system, following the vaccine. Actually, clinical experience showed a spread of transient adverse drug reactions of the menstrual cycle, following the administration of all COVID-19 vaccine types, both mRNA and Adenovirus vectored ones. In this work, we conducted the first retrospective study on Italian patients vaccinated for SARS-CoV-2 in the period between April 2021 and April 2022, to report the onset of menstrual changes after the vaccine in order to understand: etiology, duration of possible adverse effects, and the extent of the phenomenon. We recruited 100 women aged 18-45, vaccinated for SARS-CoV-2, who were asked to complete a questionnaire consisting of 12 multiple choice questions about the effects of the vaccine on the reproductive system. Thirty-seven of them received three doses of the vaccine, while the remaining 63 received two doses. Symptoms such as delayed menstruation and abnormal uterine bleeding (metrorrhagia, menometrorrhagia, and menorrhagia) were generally reported within the first three weeks of vaccination, especially after the second dose, with a percentage of 23% and 77%, respectively. These preliminary data suggest that this problem may be broader and deserving of further investigation in the future.

PMID:36293746 | DOI:10.3390/ijerph192013167

BMC Health Serv Res. 2022 Oct 26;22(1):1292. doi: 10.1186/s12913-022-08685-w.

ABSTRACT

BACKGROUND: Risk management in the post-marketing phase is crucial to minimize health problems caused by drugs. Because ethnic factors may affect drug safety, the objective of this study was to explore concrete approaches to reflecting ethnic factors in risk management under multi-regional drug development.

METHODS: We assessed Pharmaceuticals and Medical Devices Agency (PMDA) review reports on antineoplastic drugs approved as new molecular entities in the last 10 years to identify any differences in the incidence of adverse drug reactions (ADRs) related to myelosuppression, hepatic impairment, renal impairment, and interstitial lung disease between Japanese and non-Japanese populations. In addition, we investigated how those ADRs were handled in the labeling of each drug.

RESULTS: In total, 44 drugs were available for comparing the incidence of ADRs between Japanese and non-Japanese populations. Of these, 32 drugs had a higher incidence of ADRs in the Japanese population. However, the incidence of ADRs in the Japanese population was described in the labeling for 7 drugs, and only the incidence in the overall population in multi-regional phase III trials was described in the labeling for the remaining 25 drugs. Of these 25 drugs, two drugs were immediately placed under emergency safety control measures after approval because of the high incidence of ADRs in Japanese patients.

CONCLUSIONS: For drugs that might cause serious ADRs and with a higher incidence in the Japanese population, information should be provided on the incidence in the Japanese population as well as in the overall population.

PMID:36289504 | DOI:10.1186/s12913-022-08685-w

Front Med (Lausanne). 2022 Oct 10;9:933914. doi: 10.3389/fmed.2022.933914. eCollection 2022.

ABSTRACT

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused many complications, the invention of coronavirus disease 2019 (COVID-19) vaccines has also brought about several adverse events, from common side effects to unexpected and rare ones. Common vaccine-related adverse reactions manifest locally or systematically following any vaccine, including COVID-19 vaccines. Specific side effects, known as adverse events of particular interest (AESI), are unusual and need more evaluation. Here, we discuss some of the most critical rare adverse events of COVID-19 vaccines.

PMID:36300183 | PMC:PMC9589063 | DOI:10.3389/fmed.2022.933914

ERJ Open Res. 2022 Oct 24;8(4):00240-2022. doi: 10.1183/23120541.00240-2022. eCollection 2022 Oct.

ABSTRACT

INTRODUCTION: BI 1015550 is a phosphodiesterase 4 (PDE4) inhibitor that has antifibrotic properties. Phase I and Ic studies were conducted to investigate the safety, tolerability and pharmacokinetics of BI 1015550 in healthy male subjects and patients with idiopathic pulmonary fibrosis (IPF).

METHODS: In the phase I study, 42 subjects were partially randomised to receive placebo or BI 1015550 in single rising doses of 36 mg and 48 mg, or multiple rising doses of 6 mg and 12 mg twice daily over 14 days. In the phase Ic study, 15 patients with IPF were randomised to receive 18 mg BI 1015550 or placebo twice daily for up to 12 weeks. For both studies, the primary endpoint was the number of subjects with drug-related adverse events (AEs).

RESULTS: In the Phase I study, drug-related AEs were reported for 50.0% of healthy male subjects treated with a single dose of BI 1015550, compared with 16.7% receiving placebo. For those receiving multiple doses, drug-related AEs were reported for 37.5% of those treated with BI 1015550 and 12.5% receiving placebo. The most frequently reported AEs by organ class were nervous system disorders, which were largely driven by headache. In the Phase Ic study, drug-related AEs were reported in 90.0% of patients treated with BI 1015550, compared with 60.0% of those receiving placebo. The most frequent AEs by organ class were gastrointestinal AEs.

CONCLUSIONS: BI 1015550 had an acceptable safety profile in healthy male subjects and male and female patients with IPF, supporting further development in larger trials.

PMID:36299369 | PMC:PMC9589333 | DOI:10.1183/23120541.00240-2022