Drug Ther Bull. 2022 Dec 13:dtb-2022-000071. doi: 10.1136/dtb.2022.000071. Online ahead of print.

NO ABSTRACT

PMID:36600442 | DOI:10.1136/dtb.2022.000071

J Exp Clin Cancer Res. 2023 Jan 5;42(1):4. doi: 10.1186/s13046-022-02568-y.

ABSTRACT

BACKGROUND: Immune-related adverse events (irAEs) are a common phenomenon in cancer patients treated with immune checkpoint inhibitors (ICIs). Surprisingly, the toxicity burdens of these irAEs have not been illustrated clearly. In this study, we analyzed irAEs for seven FDA-approved ICIs in cancer treatment to show the pattern of toxicity burden among cancer patients.

METHODS: irAEs associated with seven FDA-approved ICIs, including three PD-1 inhibitors (cemiplimab, nivolumab and pembrolizumab), three PD-L1 inhibitors (atezolizumab, avelumab and durvalumab), and one CTLA-4 inhibitor (ipilimumab), were analyzed based on data from 149,303 reported cases (from January 1, 2015 to June 30, 2022) collected from the FDA Adverse Events Reporting System (FAERS) public dashboard. Proportions of serious irAEs and correlations with tumor type, age and sex were assessed via R package and GraphPad software.

RESULTS: irAEs related to anti-PD-1 ICIs required less hospital care resources compared with anti-PD-L1 and anti-CTLA-4 ICIs. Patients treated with pembrolizumab had relatively fewer serious cases. Treatment with ICIs led to the highest probability of serious irAEs in patients with lung cancer. 'Respiratory, thoracic and mediastinal disorders' and 'gastrointestinal disorders' were the two most common groups of disorders caused by the seven ICIs studied. 'Cardiac disorders' was the main type of disorders caused by these ICIs in cancer patients aged 65-85, while 'reproductive system and breast disease' was the main type of disorder in cancer patients aged 18-64. 'Respiratory, thoracic, mediastinal diseases' and 'reproductive system and breast diseases' were the main types of disorders associated with treatment with these ICIs in male and female patients, respectively.

CONCLUSION: Tissue and organ toxicities of ICIs are age and sex specific. There are risks of respiratory and urinary system toxicity in male patients and reproductive system toxicity in female patients treated with the ICIs studied. Future studies on the toxicity burden of ICIs should incorporate age and sex differences to better understand the relevance of ICI toxicity burden to human immune function to develop appropriate tumor immune and therapeutic intervention strategies.

PMID:36600271 | DOI:10.1186/s13046-022-02568-y

BMJ Case Rep. 2023 Jan 4;16(1):e251974. doi: 10.1136/bcr-2022-251974.

ABSTRACT

Risperidone and aripiprazole are increasingly used for behavioural indications in children and adolescents with intellectual disabilities, including autism. Although there are some reports in literature, the side effect profile in this population remains poorly defined and there is a need to raise awareness among clinicians across specialties. We present two patients with significant intellectual disabilities who developed extrapyramidal side effects (EPSE) including oculogyric crisis following risperidone and aripiprazole use. The onset of these side effects can be insidious and the non-specific nature of the presentation, for example, poor mobility and increased drooling on a background of severe intellectual disability, can lend itself to delay in recognition and reporting by families. There is also reduced awareness among paediatricians, which can further delay the treatment of this reversible condition. There needs to be ongoing vigilance for EPSE as they can develop years after treatment has been initiated.

PMID:36599495 | DOI:10.1136/bcr-2022-251974

J Toxicol Sci. 2023;48(1):1-14. doi: 10.2131/jts.48.1.

ABSTRACT

Although microsampling of blood is recommended to promote the 3Rs in toxicokinetic (TK) evaluation, there are few reports applying microsampling in actual toxicity evaluation. Here, we assessed the effects of microsampling on toxicological evaluation of methapyrilene hydrochloride, a hepatotoxic substance. Female SD rats received methapyrilene hydrochloride orally at dose levels of 0 (vehicle), 10, and 30 mg/kg BW, once daily for 4 weeks. Each dose level included a microsampling group and a non-microsampling group (n = 5). In the microsampling groups, blood sampling (50 µL/time point) was performed at 6 time points on day 1 of administration and 7 time points on day 27-28; all the animals underwent necropsy on day 29. Toxicity studies and TK analysis were performed, and through these studies in 2 organizations, cross-organization validation of the effect on toxicity evaluation was conducted. In one organization, microsampling obscured changes in some parameters in hematology due to the administration of methapyrilene hydrochloride. In the other organization, although the relationship between the developing pattern of histopathological findings in the liver and the blood sampling was suspected, it was associated with poor reproducibility; this was considered as a change within a variation range of biological reactions. Each of these phenomena was observed in only one organization without consistency. In both organizations, no effect of blood microsampling was observed in other endpoints. In conclusion, microsampling is considered to be a technique applicable to safety studies of drugs showing hepatotoxicity, as it did not show a marked influence on the toxicological evaluation of methapyrilene hydrochloride.

PMID:36599423 | DOI:10.2131/jts.48.1

Praxis (Bern 1994). 2023 Jan;112(1):5-10. doi: 10.1024/1661-8157/a003960.

ABSTRACT

Choosing Wisely in Patients with Polypharmacy Abstract. Polypharmacy and potentially inappropriate medication have a negative impact on health. For reducing or stopping medication (deprescribing) patient benefits are crucial. The following stepwise approach has turned out to be successful: a. ask patients to bring along all their medication and compare them with the current medication list; b. offer shared decision making; c. evaluate every drug for indication, balance between benefit and harm, side effects and dose; d. prioritize benefit and harm according to values, preferences and goals of the patient; e. decide together about deprescribing; f. track changes in the medication plan und arrange a follow-up consultation. We illustrate this approach by the example of an older, frail female patient with polypharmacy. Deprescribing is just as important for patients' well-being as is prescribing!

PMID:36597681 | DOI:10.1024/1661-8157/a003960

J Coll Physicians Surg Pak. 2023 Jan;33(1):107-108. doi: 10.29271/jcpsp.2023.01.107.

ABSTRACT

Medication errors cause harm to patients at any point along the medication administration process and can be prevented. Barcoding medication administration (BCMA) is effective as a clinical decision support system (CDSS) to avoid errors. This viewpoint proposes the implementation of BCMA to avoid potential adverse events. The opinion piece gives an overview of BCMA, reviews the current literature on its effectiveness, and sheds light on the associated challenges and how to overcome them. The objective of this article is to increase awareness regarding BCMA and how it can decrease patient morbidity and mortality, enhance safety, and lower overall hospital-associated costs by preventing medication errors. Key Words: Bar-code medication administration, Medication errors, Adverse drug events, Patient safety.

PMID:36597245 | DOI:10.29271/jcpsp.2023.01.107

BMC Med. 2023 Jan 4;21(1):2. doi: 10.1186/s12916-022-02669-7.

ABSTRACT

BACKGROUND: HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations.

METHODS: This was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5-18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D.

RESULTS: Between September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 mg twice daily. The RP2D was 12 mg twice daily. The most common all-grade drug-related adverse events (AEs) across all dose levels were rash (61.9%), increased creatine phosphokinase (CK, 59.5%), face edema (50.0%), increased aspartate aminotransferase (47.6%), peripheral edema (40.5%), diarrhea (33.3%), alanine aminotransferase (33.3%), and paronychia (19.0%), most of which were grade 1 and 2. Most frequency of grade ≥ 3 AEs were CK (14.2%), asthenia (7.1%), peripheral edema (4.8%), and acneiform dermatitis (4.8%). In the cohort of 12 mg twice daily dose (15 patients), confirmed objective response rate was 26.7%; disease control rate was 86.7%; median duration of response was 2.9 months; median progression-free survival was 3.6 months.

CONCLUSIONS: The HL-085 showed acceptable tolerability and substantial clinical activity in patients with advanced melanoma harboring NRAS mutations.

TRIAL REGISTRATION: Trial registration ClinicalTrials.gov number: NCT03973151.

PMID:36600247 | DOI:10.1186/s12916-022-02669-7

Drug Ther Bull. 2023 Jan 4:dtb-2022-000077. doi: 10.1136/dtb.2022.000077. Online ahead of print.

ABSTRACT

Overview of: Joy M, Williams J, Emanuel S, et al Trends in direct oral anticoagulant (DOAC) prescribing in English primary care (2014-2019). Heart 2022. doi: 10.1136/heartjnl-2022-321377. [Epub ahead of print 9 Sept 2022].

PMID:36599656 | DOI:10.1136/dtb.2022.000077

J Clin Anesth. 2023 Jan 2;85:111047. doi: 10.1016/j.jclinane.2022.111047. Online ahead of print.

ABSTRACT

STUDY OBJECTIVE: Ciprofol, a novel intravenous anesthetic, provides rapid recovery in patients undergoing colonoscopy. We aimed to examine the efficacy and safety of ciprofol in comparison with propofol for sedation or anesthesia in non-operating room settings including endoscopic submucosal dissection, endoscopic retrograde cholangiopancreatography, and flexible bronchoscopy (FB).

DESIGN: Prospective, randomized, double-blind, parallel-group clinical trial.

SETTING: University-affiliated teaching hospital.

PATIENTS: We recruited 207 patients scheduled for an endoscopic procedure from October 2021 to December 2021.

INTERVENTIONS: Patients were randomized into three groups according to the dose during induction (n = 69 each): 1) ciprofol 6 mg/kg/h, 2) ciprofol 8 mg/kg/h, or 3) propofol 40 mg/kg/h. Ciprofol or propofol was administered throughout the procedure.

MEASUREMENTS: The primary outcome was the success rate of sedation or anesthesia for the procedures. Secondary outcomes included induction time, endoscope insertion time, recovery time, discharge time, incidence of drug-related adverse events (AEs), neurological and inflammatory outcomes.

MAIN RESULTS: The procedure success rates in the three groups were 100%. The induction time in the 6 (3.3 ± 1.0 min) and 8 mg/kg/h (2.9 ± 0.6 min) ciprofol groups was longer than that in the propofol group (2.5 ± 0.6 min) only in patients undergoing FB (p = 0.004). The time for patients to be fully alert and discharged from the post-anesthesia care unit was comparable across the three groups (p > 0.05). The incidence of drug-related AEs in the propofol and 6 and 8 mg/kg/h ciprofol groups was 84.1%, 76.8%, and 79.7%. No pain on injection was reported by ciprofol groups. Neurological outcomes and inflammatory responses were comparable among the three groups.

CONCLUSIONS: Ciprofol induced a level of sedation or anesthesia equivalent to that induced by propofol in non-operating room settings except for a prolonged induction time in patients undergoing FB. Ciprofol had a safety profile similar to that of propofol. No pain on injection was reported by ciprofol.

PMID:36599219 | DOI:10.1016/j.jclinane.2022.111047

JCO Oncol Pract. 2023 Jan 4:OP2200447. doi: 10.1200/OP.22.00447. Online ahead of print.

ABSTRACT

PURPOSE: Several new treatment combinations have been approved in metastatic renal cell carcinoma (mRCC). To determine the optimal therapy on the basis of cost and health outcomes, we performed a cost-effectiveness analysis of approved immunotherapy-tyrosine kinase inhibitor/immunotherapy drug combinations and sunitinib using public payer acquisition costs in the United States.

METHODS: We constructed a decision model with a 10-year time horizon. The seven treatment drug strategies included atezolizumab + bevacizumab, avelumab + axitinib, pembrolizumab + axitinib, nivolumab + ipilimumab (NI), nivolumab + cabozantinib, lenvatinib + pembrolizumab, and sunitinib. The effectiveness outcome in our model was quality-adjusted life-years (QALYs) with utility values on the basis of the published literature. Costs included drug acquisition costs and costs for management of grade 3-4 drug-related adverse events. We used a partitioned survival model in which patients with mRCC transitioned between three health states (progression-free, progressive disease, and death) at monthly intervals on the basis of parametric survival function estimated from published survival curves. To determine cost-effectiveness, we constructed incremental cost-effectiveness ratios (ICERs) by dividing the difference in cost by the difference in effectiveness between nondominated treatments.

RESULTS: The least expensive treatment was sunitinib ($357,948 US dollars [USD]-$656,100 USD), whereas the most expensive was either lenvatinib + pembrolizumab or pembrolizumab + axitinib ($959,302 USD-$1,403,671 USD). NI yielded the most QALYs (3.6), whereas avelumab + axitinib yielded the least (2.5). NI had an incremental ICER of $297,465 USD-$348,516 USD compared with sunitinib. In sensitivity analyses, this ICER fell below $150,000 USD/QALY if the initial 4-month cost of NI decreased by 22%-38%.

CONCLUSION: NI was the most effective combination for mRCC, but at a willingness-to-pay threshold of $150,000 USD/QALY, sunitinib was the most cost-effective approach.

PMID:36599117 | DOI:10.1200/OP.22.00447

Expert Opin Drug Saf. 2022 Dec;21(12):1483-1494. doi: 10.1080/14740338.2022.2160446.

ABSTRACT

INTRODUCTION: Liver involvement in COVID-19 is multifactorial, and the three potential mechanisms are direct hepatocyte viral damage, vascular or cellular damage during the cytokine storm of severe COVID-19 and drug-induced liver injury. To date, three antivirals are licensed for the treatment of COVID-19 by most guidelines: remdesivir, molnupiravir, and ritonavir-boosted nirmatrelvir.

AREAS COVERED: We performed a narrative review about the hepatic safety profile of the three antivirals licensed for COVID-19 treatment. We used data about hepatobiliary adverse events from English-language randomized clinical trials (RCTs).

EXPERT OPINION: Remdesivir was found to be potentially hepatotoxic, and liver biochemistry abnormalities were common (2-34%) but mild and reversible. Molnupiravir exhibits a favorable safety profile and the increase in aminotransferases was usually mild and reversible (up to 11% of patients in one study). Ritonavir-boosted nirmatrelvir is potentially hepatotoxic, but in the only phase 3 RCT there were no safety issues and aspartate aminotransferase/alanine aminotransferase levels increase did not exceed 2.4% of patients. All antivirals have a favorable safety profile, but they are not sufficiently studied in patients with underlying chronic kidney or liver disease. In this special populations, antivirals should be used with caution and careful monitoring during treatment should be pursued on a case-by-case basis.

PMID:36597859 | DOI:10.1080/14740338.2022.2160446

Cleve Clin J Med. 2023 Jan 3;90(1):53-62. doi: 10.3949/ccjm.90a.22069.

ABSTRACT

Data have been accumulating on the risk of developing type 2 diabetes in patients receiving statins and on the potential adverse effects of these drugs on glycemic control in patients who already have type 2 diabetes. This article reviews data linking statin use and new-onset diabetes mellitus, the effects of statins on glycemic control in type 2 diabetes, the benefit-risk considerations of statin use and type 2 diabetes, and how these factors affect patient management.

PMID:36596598 | DOI:10.3949/ccjm.90a.22069

PLoS One. 2023 Jan 3;18(1):e0279842. doi: 10.1371/journal.pone.0279842. eCollection 2023.

ABSTRACT

To reduce adverse drug events (ADEs), hospitals need a system to support them in monitoring ADE occurrence routinely, rapidly, and at scale. Natural language processing (NLP), a computerized approach to analyze text data, has shown promising results for the purpose of ADE detection in the context of pharmacovigilance. However, a detailed qualitative assessment and critical appraisal of NLP methods for ADE detection in the context of ADE monitoring in hospitals is lacking. Therefore, we have conducted a scoping review to close this knowledge gap, and to provide directions for future research and practice. We included articles where NLP was applied to detect ADEs in clinical narratives within electronic health records of inpatients. Quantitative and qualitative data items relating to NLP methods were extracted and critically appraised. Out of 1,065 articles screened for eligibility, 29 articles met the inclusion criteria. Most frequent tasks included named entity recognition (n = 17; 58.6%) and relation extraction/classification (n = 15; 51.7%). Clinical involvement was reported in nine studies (31%). Multiple NLP modelling approaches seem suitable, with Long Short Term Memory and Conditional Random Field methods most commonly used. Although reported overall performance of the systems was high, it provides an inflated impression given a steep drop in performance when predicting the ADE entity or ADE relation class. When annotating corpora, treating an ADE as a relation between a drug and non-drug entity seems the best practice. Future research should focus on semi-automated methods to reduce the manual annotation effort, and examine implementation of the NLP methods in practice.

PMID:36595517 | PMC:PMC9810201 | DOI:10.1371/journal.pone.0279842

BMJ Case Rep. 2022 Dec 8;15(12):e251966. doi: 10.1136/bcr-2022-251966.

ABSTRACT

Pembrolizumab, a humanised monoclonal antibody and immune checkpoint inhibitor (ICI) that blocks programmed death receptor 1 and its ligands, is an effective immunotherapy for malignancies such as melanoma, lung, head and neck, cancers, and Hodgkin's lymphoma. It has an overall response rate between 73% and 83%, with complete response rate of 27%-30%. It is well tolerated with minor side effects in 70% of cases characterised by fatigue, rash, pruritus and diarrhoea. In rare cases, more serious and life-threatening complications can occur at a rate of 0.3%-1.3%. We report a case of a woman in her 70s with non-small-cell lung cancer treated with ICI. She presented to the emergency department with left-sided ptosis and muscle weakness 3 weeks of her first dose of pembrolizumab infusion as a treatment plan of her cancer. She was diagnosed with myasthenia gravis, myocarditis and myositis as ICI-induced immune-related adverse effects resistant to medical intervention. We wish to raise awareness of the triad of life-threatening complication of ICI therapy that accounts for 30%-50% of fatal complications.

PMID:36593626 | DOI:10.1136/bcr-2022-251966

Trials. 2023 Jan 3;24(1):4. doi: 10.1186/s13063-022-06982-7.

ABSTRACT

BACKGROUND: The prognosis for patients with relapsed and/or refractory (R/R) non-Hodgkin's lymphoma (NHL) or acute lymphoblastic leukaemia (ALL) remains poor, with existing treatments having significant side effects. Developed for the treatment of these cancers, AFM11 is a tetravalent, bispecific humanised recombinant antibody construct (TandAb®) designed to bind to human CD19 and CD3 and lead to the activation of T cells inducing apoptosis and killing of malignant B cells.

METHODS: Two open-label, multicentre, dose-escalation phase 1 studies evaluated the safety, pharmacokinetics and activity of AFM11 in patients with R/R CD19-positive B cell NHL (AFM11-101) and in patients with CD19 + B-precursor Philadelphia-chromosome negative ALL (AFM11-102). Adverse events (AEs) were assessed and recorded; imaging (NHL) or bone marrow assessment (ALL) were used to evaluate response. Additional pharmacodynamic assays undertaken included cytokine release analysis and B-cell and T-cell depletion.

RESULTS: In AFM11-101, 16 patients with R/R NHL received AFM11 in five different dose cohorts. Of which, 14 experienced drug-related treatment-emergent AEs (TEAEs) [including five serious AEs (SAEs)], five patients experienced dose-limiting toxicity (DLT) and ten patients discontinued the study. The high number of neurological events led to a decrease in infusion frequency during the study. No objective response to treatment was observed. In AFM11-102, 17 patients with R/R ALL received AFM11 in six different dose cohorts. Thirteen patients experienced drug-related TEAEs (including four SAEs), DLTs occurred in two patients and five patients discontinued the study. An objective response was recorded in three patients. The maximum tolerated dose could not be determined in either study due to early termination.

CONCLUSIONS: AFM11 treatment was associated with frequent neurological adverse reactions that were severe in some patients. In ALL, some signs of activity, albeit short-lived, were observed whereas no activity was observed in patients with NHL; therefore, further clinical development was terminated.

TRIAL REGISTRATION: NCT02106091 . Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL. Registered April 2014. NCT02848911 . Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL. Registered July 2016.

PMID:36597128 | DOI:10.1186/s13063-022-06982-7

BMC Psychiatry. 2023 Jan 3;23(1):4. doi: 10.1186/s12888-022-04348-6.

ABSTRACT

BACKGROUND: Creating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be the most effective medication for smoking cessation and abstinence when compared to results from placebo medications, nicotine patches and bupropion, caution is needed when starting patients on this medication. With the high prevalence of concurrent mental health and substance use disorders in vulnerably-housed populations in Canada, it becomes increasingly important to advocate for increased guidance and research into treating concurrent disorders.

CASE PRESENTATION: In this case, a young female patient provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance use and medication noncompliance. She also endorsed a long history of tobacco, alcohol, cocaine, cannabis and ketamine use. Perceptual abnormalities, including auditory hallucinations, were not recorded at admission. In addition to being stabilized for bipolar diagnosis, the patient was started on nicotine replacement therapy on Day 7 of admission followed by initiation of varenicline for smoking cessation on Day 14 of admission. Soon after the varenicline treatment was started, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought form disorganization. In this case, these symptoms were thought to be secondary to varenicline after the consideration of potential alternative contributors.

CONCLUSION: The occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder. Patients may also benefit from increased collaboration between psychiatric and addiction services as that may allow for earlier recognition and intervention of symptoms to minimize distress.

PMID:36597062 | DOI:10.1186/s12888-022-04348-6

Reg Anesth Pain Med. 2023 Jan 3:rapm-2022-104193. doi: 10.1136/rapm-2022-104193. Online ahead of print.

NO ABSTRACT

PMID:36596581 | DOI:10.1136/rapm-2022-104193

BMJ Open Qual. 2023 Jan;12(1):e002002. doi: 10.1136/bmjoq-2022-002002.

ABSTRACT

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic and anti-inflammatory action, but the gastrointestinal (GI) adverse effects are a known cause of preventable harm. A medication safety audit was incentivised for community pharmacies in England in 2 successive years as part of the Pharmacy Quality Scheme (PQS) to address GI safety of NSAIDs.

AIMS: To evaluate community pharmacy's contributions to NSAID safety and determine any change between audit 1 (2018-2019) and audit 2 (2019-2020).

METHOD: Patients aged 65 years or over prescribed an NSAID were included in both audits. The audit tool assessed compliance with national standards relating to co-prescribed gastroprotection, referrals to the prescriber and patient advice on long-term NSAID use and effects, with responses submitted via an online portal. Descriptive analyses were performed to explore differences between the years and tested for significance using Χ2 tests. Qualitative data were analysed using an inductive thematic approach.

KEY FINDINGS: Data from 91 252 patients in audit 1 and 73 992 in audit 2 were analysed. More patients were prescribed gastroprotection in audit 2 (85.0%) than audit 1 (80.7%, p<0.001). More patients without gastroprotection in audit 2 had a current or recent referral (67.5%) than in audit 1 (58.8%, p<0.001). Verbal or other communications between pharmacists and patients about their NSAID medication were reported more frequently in audit 2 (76.0% vs 63.5%, p<0.001).

CONCLUSION: During two audits, community pharmacists in England reported referring more than 15 000 patients at risk of preventable harm from NSAIDs to prescribers for review. The audits demonstrated significant potential for year-on-year improvement in GI safety for a large cohort of older patients prescribed NSAIDs. This evaluation provides evidence of how the PQS can effectively address a specific aspect of medicines safety and the place of community pharmacy more broadly in improving medicines safety.

PMID:36593072 | PMC:PMC9809222 | DOI:10.1136/bmjoq-2022-002002

In Vivo. 2023 Jan-Feb;37(1):345-356. doi: 10.21873/invivo.13085.

ABSTRACT

BACKGROUND/AIM: The COVID-19 prophylactic vaccine for the prevention of coronavirus infection was approved in Japan on February 14, 2021. Adverse event reports for the vaccine were collected from the Japan Adverse Drug Event Relief (JADER) database, similar to those for drugs. Reported odds ratios (RORs) and proportional reporting ratios (PRRs) are commonly used in disproportionality analysis to detect safety signals. Therefore, adverse event reports from the vaccinated population may affect the detection of safety signals for the registered drugs. This study determined the impact of adverse event reports on the detection of safety signals for a COVID-19 prophylactic vaccine by analyzing the JADER database using disproportionality analysis.

PATIENTS AND METHODS: We extracted data from the JADER dataset, in which the COVID-19 vaccine was reported as a suspected drug, and selected the top 10 adverse events in terms of the number of reports. We then extracted the top 30 drugs by the amount of information in the selected 10 adverse events and compared the changes in the number of signal detections with and without the COVID-19 vaccine report data.

RESULTS: The total number of adverse events reported in the JADER database during the study period was 2,002,564. Of the total number of reports, 85,489 (4.3%) reported adverse events related to the COVID-19 vaccine. Of the top 30 drugs reported in the 10 selected adverse events, the ROR and PRR were found to be lower with the inclusion of COVID-19 vaccine data than without. Detection by ROR excluded 23 out of 245 drugs, and detection by PRR excluded 34 out of 204 drugs.

CONCLUSION: The rapid increase in the number of adverse event reports for the COVID-19 vaccine in JADER may affect the detection of safety signals by disproportionality analysis.

PMID:36593055 | DOI:10.21873/invivo.13085

Pathol Oncol Res. 2022 Dec 16;28:1610752. doi: 10.3389/pore.2022.1610752. eCollection 2022.

ABSTRACT

Introduction: Olanzapine (OLZ) is one of the second-generation antipsychotics drugs (APDs) used to treat several psychiatric illnesses. Olanzapine treatment is often associated with many metabolic side effects in a dose dependent manner such as obesity, dyslipidemia and insulin resistance, induction of type II diabetes and acute pancreatitis in some patients. Methods: Hyperbaric Oxygen therapy (HBOT) was investigated as a tool to mitigate olanzapine metabolic side effects in rats. Thirty-six female Sprague Dawley (SD) rats were divided into 4 groups; rats on olanzapine treatment either exposed to hyperbaric oxygen therapy (HBOOLZ) or left without exposure (OLZ) then non-treated rats that either exposed to hyperbaric oxygen therapy or left without exposure (control). Rats received Hyperbaric Oxygen therapy for 35 days at 2.4 atmospheres absolute (ATA) for 2.5 h daily followed by intraperitoneal injection of olanzapine at 10 mg/kg or placebo. Results: Rats on either hyperbaric oxygen therapy or olanzapine had a significant loss in body weight. Olanzapine treatment showed a decrease in serum insulin level, triglyceride, highdensity lipoprotein (HDL) cholesterol, and lipase level but an increase in fasting blood sugar (FBS), insulin resistance index (HOMA-IR) and amylase, while rats' exposure to hyperbaric oxygen therapy reversed these effects. The Pancreatic Langerhans islets were up-regulated in both hyperbaric oxygen therapy and olanzapine treatments but the combination (HBOOLZ) doubled these islets number. Discussion: This study advocated that hyperbaric oxygen therapy can be an alternative approach to control or reverse many metabolic disorders (MDs) associatedwith olanzapine treatment. In addition, it seems that hyperbaric oxygen therapy positively affect the pancreatic Langerhans cells activity and architecture.

PMID:36590387 | PMC:PMC9801520 | DOI:10.3389/pore.2022.1610752