BMC Public Health. 2022 Nov 18;22(1):2121. doi: 10.1186/s12889-022-14586-8.

ABSTRACT

BACKGROUND: Illicit drug poisoning (overdose) continues to be an important public health problem with overdose-related deaths currently recorded at an unprecedented level. Understanding the geographic variations in fatal overdose mortality is necessary to avoid disproportionate risk resulting from service access inequity.

METHODS: We estimated the odds of fatal overdose per event from all cases captured by the overdose surveillance system in British Columbia (2015 - 2018), using both conventional logistic regression and Generalized Additive Models (GAM). The results of GAM were mapped to identify spatial-temporal trends in the risk of fatal overdose.

RESULTS: We found that the odds of fatal overdose were about 30% higher in rural areas than in large urban centers, with some regions reporting odds 50% higher than others. Temporal variations in fatal overdose revealed an increasing trend over the entire province. However, the increase occurred earlier and faster in the Interior and Northern regions.

CONCLUSION: Rural areas were disproportionately affected by fatal overdose; lack of access to harm reduction services may partly explain the elevated risk in these areas.

PMID:36401244 | PMC:PMC9675064 | DOI:10.1186/s12889-022-14586-8

BMC Health Serv Res. 2022 Nov 17;22(1):1363. doi: 10.1186/s12913-022-08696-7.

ABSTRACT

BACKGROUND: Drug overuse or drug underuse are the most common causes of adverse drug events and can lead to hospital admissions. Using clinical pharmacists in the emergency department may improve patient safety as they are specialised in recognising of adverse drug events and tackling drug overuse and drug underuse. This study tested the effect of an emergency department pharmacist on the number of medication changes for drug overuse and drug underuse taking place in patients with an adverse drug event-related hospitalisation following an emergency department visit.

METHODS: A multicenter prospective non-randomized controlled intervention study was conducted in a university hospital and a general teaching hospital. Trained emergency department pharmacists included patients in the intervention group with a hospital admission related to an adverse drug event. The interdisciplinary intervention consisted of a pharmacist-led medication review, patient counselling regarding medication, and information transmission to general practitioners and community pharmacies after discharge. The control patients were also admitted after an emergency department visit and received the usual care. The primary outcome was the number of medication changes for drug overuse and drug underuse that took place during hospital admission and persisted 6 months thereafter. Poisson regression analysis was used to estimate the difference in these medication changes between the intervention group and the control group.

RESULTS: A total of 216 patients were included (intervention group 104, control group 112). In the intervention group, 156 medication changes for drug overuse and drug underuse persisted 6 months after admission compared to 59 in the control group (adjusted rate ratio 1.22 [95%CI 1.01-1.49] p = 0.039).

CONCLUSION: Emergency department pharmacists do contribute to reduction of drug overuse and drug underuse of medication in patients with a hospitalisation related to adverse drug events after an emergency department visit.

PMID:36397102 | PMC:PMC9670389 | DOI:10.1186/s12913-022-08696-7

Indian J Tuberc. 2022;69 Suppl 2:S202-S204. doi: 10.1016/j.ijtb.2022.10.022. Epub 2022 Oct 26.

ABSTRACT

The article deals with challenges faced by the geriatric populations while on MDR treatment. Risk factors like tobacco use, low socio-economic status, previous disease, longer delays in seeking treatment and reduced mobility are some of the challenges while initiating MDR treatment. Other issues like drug-related adverse events and increased co-morbidity pose a major challenge while treating patients. Susceptibility among the geriatric age group includes various anatomical and physiological changes including nutritional deficiencies and co morbidities.

PMID:36400509 | DOI:10.1016/j.ijtb.2022.10.022

Lancet Glob Health. 2022 Dec;10(12):e1845-e1854. doi: 10.1016/S2214-109X(22)00450-8.

ABSTRACT

BACKGROUND: HIV-associated cryptococcal meningitis is a leading cause of AIDS-related mortality. The AMBITION-cm trial showed that a regimen based on a single high dose of liposomal amphotericin B deoxycholate (AmBisome group) was non-inferior to the WHO-recommended treatment of seven daily doses of amphotericin B deoxycholate (control group) and was associated with fewer adverse events. We present a five-country cost-effectiveness analysis.

METHODS: The AMBITION-cm trial enrolled patients with HIV-associated cryptococcal meningitis from eight hospitals in Botswana, Malawi, South Africa, Uganda, and Zimbabwe. Taking a health service perspective, we collected country-specific unit costs and individual resource-use data per participant over the 10-week trial period, calculating mean cost per participant by group, mean cost-difference between groups, and incremental cost-effectiveness ratio per life-year saved. Non-parametric bootstrapping and scenarios analyses were performed including hypothetical real-world resource use. The trial registration number is ISRCTN72509687, and the trial has been completed.

FINDINGS: The AMBITION-cm trial enrolled 844 participants, and 814 were included in the intention-to-treat analysis (327 from Uganda, 225 from Malawi, 107 from South Africa, 84 from Botswana, and 71 from Zimbabwe) with 407 in each group, between Jan 31, 2018, and Feb 17, 2021. Using Malawi as a representative example, mean total costs per participant were US$1369 (95% CI 1314-1424) in the AmBisome group and $1237 (1181-1293) in the control group. The incremental cost-effectiveness ratio was $128 (59-257) per life-year saved. Excluding study protocol-driven cost, using a real-world toxicity monitoring schedule, the cost per life-year saved reduced to $80 (15-275). Changes in the duration of the hospital stay and antifungal medication cost showed the greatest effect in sensitivity analyses. Results were similar across countries, with the cost per life-year saved in the real-world scenario ranging from $71 in Botswana to $121 in Uganda.

INTERPRETATION: The AmBisome regimen was cost-effective at a low incremental cost-effectiveness ratio. The regimen might be even less costly and potentially cost-saving in real-world implementation given the lower drug-related toxicity and the potential for shorter hospital stays.

FUNDING: European Developing Countries Clinical Trials Partnership, Swedish International Development Cooperation Agency, Wellcome Trust and Medical Research Council, UKAID Joint Global Health Trials, and the National Institute for Health Research.

TRANSLATIONS: For the Chichewa, Isixhosa, Luganda, Setswana and Shona translations of the abstract see Supplementary Materials section.

PMID:36400090 | DOI:10.1016/S2214-109X(22)00450-8

Stem Cell Res. 2022 Nov 14;65:102970. doi: 10.1016/j.scr.2022.102970. Online ahead of print.

ABSTRACT

Cytochrome P450 (CYP) reaction phenotyping has become crucial for predicting drug reactions and side effects. Single nucleotide polymorphisms (SNPs) in CYP genes alter drug metabolism capacity and cause unexpected drug-related reactions. Here, we established two human induced pluripotent stem cell (hiPSC) lines with pharmacologically important SNPs in CYP2D6 in conjunction with CYP2C19 or CYP3A5 genes. These hiPSC lines can serve as valuable resources for expanding our understanding of the relationships between genotypes and drug reactions.

PMID:36399926 | DOI:10.1016/j.scr.2022.102970

J Popul Ther Clin Pharmacol. 2022 Nov 12;29(4):e46-e54. doi: 10.15586/jptcp.2022.967. eCollection 2022.

ABSTRACT

Teratogenicity and hyperuricemia are considered as the major adverse effects of favipiravir, but less is known about other possible side effects which includes drug-induced liver damage and renal injury. In the current research, assessment of favipiravir-induced liver injury was performed by evaluating liver enzymes among patients with mild to moderate COVID-19 infection. A prospective cohort study was conducted on 66 patients diagnosed with mild to moderate COVID-19 infection who were treated with favipiravir for 5 days. During this period, a baseline assessment of liver enzymes (aspartate aminotransferase - AST, alanine transaminase - ALT and alkaline phosphatase - ALP) in addition to bilirubin before initiation of therapy and after 1 day of completion of therapy were carried out. The comparison of all measured parameters among all patients before and after receiving the treatment showed that non-significant differences were obtained in their levels. It was noticed that COVID-19 patients demonstrated high AST levels in which only 16 patients out of the all-subjected cases (66 patients) had AST levels of less than 45 U/L whereas the majority of patients showed normal ALT, ALP, and bilirubin levels. It was concluded that 5 days administration of favipiravir in mild to moderate COVID-19 patients who had no previous liver diseases did not affect the liver enzymes significantly and only transient elevations were occurred.

PMID:36398597 | DOI:10.15586/jptcp.2022.967

Drug Des Devel Ther. 2022 Nov 10;16:3915-3927. doi: 10.2147/DDDT.S236926. eCollection 2022.

ABSTRACT

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder of the central nervous system. Disease-modifying drugs (DMDs) and subsequent adherence are crucial for preventing reversible episodes of neurological dysfunction and delayed onset of progressive accumulation of irreversible deficits. Yet, side effects may limit their usage in clinical practice. Gastrointestinal (GI) side effects are a significant limitation of the use of dimethyl fumarate (DMF), the most frequently prescribed oral DMD in MS worldwide. Diroximel fumarate (DRF) is a second-generation oral fumaric acid ester (FAE) that was developed as a formulation with better GI tolerability. The improved tolerability is assumed to be related to a lower synthesis of gut-irritating methanol. Other explanations for DRF's lower extent of GI irritation include a more modest off-target activity due to its chemical structure. The superior GI tolerability of DRF compared to DMF could be proven in clinical trials and lead to approval of DRF for the treatment of relapsing forms of MS/relapsing-remitting MS (United States Food and Drug Administration and European Medicines Agency, respectively). Here, we summarize the mode of action of oral FAE and compare the chemical and physiological characteristics of DMF and DRF. Moreover, we discuss the adverse effects of FAE and introduce the emerging preclinical and trial data leading to the approval of DRF in MS. This article additionally reviews our current understanding of coronavirus disease 2019 (COVID-19) and the efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in people treated with FAE.

PMID:36388086 | PMC:PMC9663167 | DOI:10.2147/DDDT.S236926

Intern Med. 2022;61(22):3435-3438. doi: 10.2169/internalmedicine.9430-22. Epub 2022 Nov 15.

ABSTRACT

Miller Fisher syndrome (MFS) is a variant of Guillain-Barré syndrome. Delayed facial palsy (DFP) is a symptom that occurs after other neurological symptoms begin to recover within four weeks from the onset of MFS. As there have been few detailed reports about DFP in MFS cases treated with additional immunotherapy, we investigated three cases of DFP in MFS treated with additional steroid therapies. The duration of facial palsy in our cases was 12-24 days. No severe adverse effects were observed. Although adverse side effects should be carefully monitored, additional steroid therapy might be a treatment option for MFS-DFP.

PMID:36385049 | DOI:10.2169/internalmedicine.9430-22

Dtsch Arztebl Int. 2022 Aug 8;119(31-32):550. doi: 10.3238/arztebl.m2022.0098.

NO ABSTRACT

PMID:36384929 | DOI:10.3238/arztebl.m2022.0098

Am J Nurs. 2022 Dec 1;122(12):23. doi: 10.1097/01.NAJ.0000904084.55613.b6.

ABSTRACT

Ibrutinib (Imbruvica) has received a new indication for the treatment of graft-versus-host disease in pediatric patients at least one year of age when one or more systemic therapies have failed.The product's labeling warns of the risk of hemorrhage, infections, cardiac arrythmias, cardiac failure and sudden death, hypertension, cytopenia, secondary primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity.The most common adverse effects include laboratory abnormalities, musculoskeletal pain, pyrexia, pneumonia, abdominal pain, stomatitis, diarrhea, and headache. Nurses should carefully assess for these adverse effects and provide appropriate education regarding their prevention.

PMID:36384792 | DOI:10.1097/01.NAJ.0000904084.55613.b6

Am J Nurs. 2022 Dec 1;122(12):22-23. doi: 10.1097/01.NAJ.0000904080.71037.14.

ABSTRACT

The Food and Drug Administration (FDA) has approved capmatinib (Tabrecta) for the treatment of metastatic non-small cell lung cancer in adults whose tumors have a mutation leading to mesenchymal-epithelial transition exon 14 skipping.Nurses should monitor patients for serious adverse effects such as interstitial lung disease/pneumonitis, hepatotoxicity, pancreatic toxicity, photosensitivity, and embryo-fetal toxicity.The FDA has granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of unresectable or metastatic non-small cell lung cancer in adults whose tumors have activating human epidermal growth factor receptor 2 mutations and who have received a prior systemic therapy.Enhertu carries a boxed warning regarding the risk of interstitial lung disease and embryo-fetal toxicity.

PMID:36384791 | DOI:10.1097/01.NAJ.0000904080.71037.14

Front Pharmacol. 2022 Oct 28;13:1053356. doi: 10.3389/fphar.2022.1053356. eCollection 2022.

ABSTRACT

Background and objective: Idiopathic pulmonary fibrosis (IPF) is a critical disease, with limited treatments available. Clinical practices show that traditional Chinese medicine (TCM) has certain efficacy. This study was preliminarily to evaluate the efficacy and safety of TCM treatment based on syndrome differentiation in IPF. Methods: A study design of exploratory, multi-centers, randomized, double-blinded, placebo controlled trial has been adopted. A total of 80 IPF patients from four sub-centers were enrolled. All the patients were randomly assigned into TCM group (TCMG) or control group (CG) in 1:1. Patients in TCMG were given CM granules, as patients in CG given with the placebo of CM granule. All the patients received a 26-week treatment. The efficacy was assessed by acute exacerbations (AEs) of IPF, pulmonary function, clinical symptoms, dyspnea scores (mMRC), health-related quality of life (HRQoL), 6-min walk test (6MWT) and all-cause mortality. Safety has also been assessed. Results: A total of 67 patients completed the trial with 35 in TCM group and 32 in control group. Meaningful differences have been observed in mean changes in AEs (-1.56 times; 95% CI, -2.69 to -0.43, p = 0.01), DLco% (5.29; 95% CI, 0.76 to 9.81, p = 0.02), cough scores (-0.38 points; 95% CI, -0.73 to -0.04, p = 0.03), and 6MWT (30.43 m; 95% CI, 2.85 to 58.00, p = 0.03), with no statistical differences in FEV1, FVC, expectoration, chest tightness, Shortness of breath, Fatigue, Cyanosis, mMRC, CAT, SF-36, and SGRQ total scores in 26 weeks after treatment than before treatment. At of the end of follow-up, a total of 10 patients died, including three and seven in the TCM and control group respectively. And the HR (Hazard ratio) for CM granules in all-cause mortality was 0.39 (95% CI, 0.10-1.52). The drug-related adverse events were not observed. Conclusion: CM granules, as compared with placebo, could reduce frequencies of AEs, improve pulmonary function, HRQoL, exercise capacity and symptoms and signs for IPF to some extent with acceptable side-effect.

PMID:36386223 | PMC:PMC9649819 | DOI:10.3389/fphar.2022.1053356

Front Pharmacol. 2022 Oct 25;13:1043828. doi: 10.3389/fphar.2022.1043828. eCollection 2022.

ABSTRACT

GPR40 is a class A G-protein coupled receptor (GPCR) mainly expressed in pancreas, intestine, and brain. Its endogenous ligand is long-chain fatty acids, which activate GPR40 after meal ingestion to induce secretion of incretins in the gut, including GLP-1, GIP, and PYY, the latter control appetite and glucose metabolism. For its involvement in satiety regulation and metabolic homeostasis, partial and AgoPAM (Positive Allosteric Modulation agonist) GPR40 agonists had been developed for type 2 diabetes (T2D) by many pharmaceutical companies. The proof-of-concept of GPR40 for control of hyperglycemia was achieved by clinical trials of partial GPR40 agonist, TAK-875, demonstrating a robust decrease in HbA1c (-1.12%) after chronic treatment in T2D. The development of TAK-875, however, was terminated due to liver toxicity in 2.7% patients with more than 3-fold increase of ALT in phase II and III clinical trials. Different mechanisms had since been proposed to explain the drug-induced liver injury, including acyl glucuronidation, inhibition of mitochondrial respiration and hepatobiliary transporters, ROS generation, etc. In addition, activation of GPR40 by AgoPAM agonists in pancreas was also linked to β-cell damage in rats. Notwithstanding the multiple safety concerns on the development of small-molecule GPR40 agonists for T2D, some partial and AgoPAM GPR40 agonists are still under clinical development. Here we review the most recent progress of GPR40 agonists development and the possible mechanisms of the side effects in different organs, and discuss the possibility of developing novel strategies that retain the robust efficacy of GPR40 agonists for metabolic disorders while avoid toxicities caused by off-target and on-target mechanisms.

PMID:36386134 | PMC:PMC9640913 | DOI:10.3389/fphar.2022.1043828

CNS Drugs. 2022 Nov 16. doi: 10.1007/s40263-022-00970-w. Online ahead of print.

ABSTRACT

BACKGROUND: Emulsified isoflurane was designed to circumvent the deficiencies of inhalation anesthetics, which have a longer time to onset, result in a higher drug consumption, and for which a specific anesthesia machine is required for clinical use. The aim of this study was to compare the efficacy and safety of emulsified isoflurane with propofol for anesthesia induction in adults patients.

METHODS: This multicenter, randomized, double-blind, positive-controlled, non-inferiority, phase III clinical trial compared the efficacy and safety of emulsified isoflurane with propofol for anesthesia induction. Each patient in the emulsified isoflurane group received a single bolus injection of 12% emulsified isoflurane at a dose of 30 mg/kg, and each patient in the propofol group received a single bolus injection of 0.8% propofol at a dose of 2 mg/kg. The primary outcome of the efficacy evaluation was the proportion of participants with successful anesthesia induction, which was regarded as a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of < 1 and lack of use of other sedative drugs. A number of secondary efficacy outcomes were also assessed. Safety was monitored based on (1) adverse events, (2) repeated measurement of vital signs; (3) physical examination, (4) routine laboratory examinations of hematology, biochemistry, urine, coagulation function, and (5) 12-lead electrocardiogram.

RESULTS: A total of 416 patients were enrolled (n = 208 in each group) and 398 patients were administered study drug. The proportion of participants with successful anesthesia induction was 100% with a 95% confidence interval of - 1.9% to + 1.9% for the emulsified isoflurane and propofol groups, which met the predesigned non-inferiority criteria of 5%. The study demonstrated the non-inferiority of sedation produced by emulsified isoflurane compared to propofol. Among the secondary efficacy outcomes, emulsified isoflurane showed a better cardiovascular stability than propofol. The number of patients from the emulsified isoflurane group who experienced drug-related adverse events was significantly higher than that of patients from the propofol group. However, there was no significant difference between the two groups in terms of adverse events or drug-related adverse events of grades 3-5.

CONCLUSIONS: Emulsified isoflurane exhibited non-inferiority of anesthesia/sedation compared to propofol in patients undergoing anesthesia induction.

CLINICAL TRIAL REGISTRATION: ChiCTR2000038185, registered on 12 December, 2020 ( www.chictr.org.cn ).

PMID:36385453 | DOI:10.1007/s40263-022-00970-w

Dtsch Med Wochenschr. 2022 Nov;147(23):1513-1522. doi: 10.1055/a-1810-9275. Epub 2022 Nov 16.

ABSTRACT

Drug-induced cardiovascular side effects have a significant impact on morbidity and mortality. The demographic change and improved long-term survival particularly in cancer patients have caused an increasing number of affected patients, hence emphasizing the importance of the best possible treatment of such complications. This article gives an overview of classic and modern groups of substances with cardiotoxic effects and summarizes the principles of diagnostics and therapy. After characterizing the common cardiovascular side effects caused by anthracycline chemotherapy, we focus on complications caused by modern forms of immunotherapy, considering its significant impact on oncological therapy in the future due to its growing clinical application. In addition to specific cancer therapies, accompanying measures such as blood transfusions in patients with hematologic diseases can also lead to severe cardiovascular complications. In the last section, we classify important features and therapeutic approaches in cardiac involvement of transfusion-related hemochromatosis. A good knowledge of the characteristics of specific cardiovascular side effects can help to improve the management of affected patients.

PMID:36384152 | DOI:10.1055/a-1810-9275

Cureus. 2022 Oct 13;14(10):e30273. doi: 10.7759/cureus.30273. eCollection 2022 Oct.

ABSTRACT

Marijuana is among the most widely used recreational drugs in the United States. The most common side effects of marijuana include mood changes, impaired memory, impaired body movements, and hallucination. Chronic use of marijuana is associated with transaminitis and hepatomegaly. Reported cases of acute hepatitis secondary to heavy marijuana smoking are very rare.

PMID:36381892 | PMC:PMC9653216 | DOI:10.7759/cureus.30273

Cureus. 2022 Oct 4;14(10):e29921. doi: 10.7759/cureus.29921. eCollection 2022 Oct.

ABSTRACT

Background KLS-1 is zinc (Zn) aspartate enriched with isotope 64Zn to 99.2% mass fraction of total zinc. KLS-1 is intended as a novel therapeutic approach for patients with a variety of diseases including but not limited to different forms of cancer and neurodegenerative diseases. The purpose of this first-in-human study was to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics (PK) in patients with medical disorders. Methods The study was designed as consisting of two consecutive parts: the dose escalation part and the dose expansion part. Adult patients with refractory glioblastoma, primary progressive aphasia/dementia, amyotrophic lateral sclerosis, Parkinson's disease (PD), and type 1 diabetes were included. KLS-1 formulated as a 10 mL water solution containing 26.42 mg/mL of 64zinc aspartate (that is equivalent to 5.184 mg/mL of 64Zn) was administered twice weekly in two-week cycles via two-hour intravenous (IV) infusion at various dose levels during the dose escalation part and twice weekly during five subsequent weeks in the dose expansion part. The study was conducted at Pan American Cancer Treatment Center (Tijuana, Mexico) in 2020 and had a duration of 10 months. Results A total of eight patients (all white/Caucasian) were enrolled in both parts of the study. A total of four patients who participated in the dose escalation part were dosed twice weekly at 1, 2, and 4 mg/kg in two-week cycles for each dose level with the dose increased to the next higher level in the subsequent cycle. Dose-limiting toxicities (DLTs) were defined at dose level 4 mg/kg due to treatment-emergent reversible adverse events that required medications for symptomatic relief. The most common drug-related toxicities that occurred in two or more patients (≥25%) were weakness (five patients), fatigue (four patients), dizziness (three patients), nausea (two patients), poor sleep (two patients), and abdominal discomfort (two patients). In the dose expansion part, a dose of 2 mg/kg administered twice weekly was investigated for five continuous weeks in four patients and was established as recommended phase 1b/2 dose. Systemic exposure to KLS-1 (area under the curve (AUC) and maximum serum concentration (Cmax)) increased from 1 to 4 mg/kg and showed a linear relationship. Conclusions Multiple doses of KLS-1 ranging from 1 to 2 mg/kg administered twice a week via intravenous infusion for up to five continuous weeks were safe and well tolerated in patients with different types of therapeutic conditions including but not limited to a few forms of cancer and Parkinson's disease, and the evaluated pharmacokinetic parameters exhibited favorable profile.

PMID:36381721 | PMC:PMC9637427 | DOI:10.7759/cureus.29921

Health Sci Rep. 2022 Nov 14;5(6):e931. doi: 10.1002/hsr2.931. eCollection 2022 Nov.

ABSTRACT

BACKGROUND AND AIMS: Doxycycline is recommended for use in rickettsial diseases. The available evidence regarding its safety for rickettsial infection in pregnancy is limited. Our study aimed to describe the adverse events of doxycycline when used during pregnancy for any indication, in terms of adverse maternal and/or neonatal outcomes, using the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS: We used the OpenVigil software for extracting the safety reports from the United States submitted to the FAERS from 2004 to 2021. We manually reviewed reports of doxycycline use resulting in adverse pregnancy outcomes or congenital anomalies to describe the patient and safety event characteristics.

RESULTS: From 2004 to 2021, 59 individual case safety reports containing preferred terms indicative of drug exposure during pregnancy or drug-induced adverse fetal outcomes were identified in the FAERS database. Following deduplication and manual review, 20 relevant adverse event reports were obtained. Doxycycline was the suspect medication in 13/20 (65%) reports. The common adverse event terms reported were premature delivery/baby in 6 reports, spontaneous abortion in 6, intrauterine death in 2, and various congenital anomalies in the rest. Fifty percent of the safety reports contained other medications which could have potentially caused the outcome.

CONCLUSIONS: The number of reported events in the FAERS database of adverse pregnancy/neonatal outcomes following doxycycline use is small, similar to the numbers reported from large cohort or surveillance studies. Given the presence of concomitant medications that could have contributed to the outcome, there does not seem to be a strong signal of harm, although this needs to be confirmed by surveillance studies.

PMID:36381408 | PMC:PMC9662692 | DOI:10.1002/hsr2.931

Sci Rep. 2022 Nov 15;12(1):19555. doi: 10.1038/s41598-022-23834-1.

ABSTRACT

Osimertinib was a third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), which approved by the US Food and Drug Administration (FDA) in 2015 for treatment of non-small cell lung cancer (NSCLC). Our study was to explore the adverse events (AEs) caused by osimertinib through data mining of the US FDA Adverse Event Reporting System (FAERS), and provide reference for clinical safety. Data of osimertinib were collected from the FAERS database covering the period from first quarter of 2016 to the fourth quarter of 2021. Disproportionality analyses was employed to quantify the associated AE signals of osimertinib and detect the risk signals from the data in the FAERS database. Reporting odds ratio (ROR) was used to detect the risk signals from the data in the FAERS database. The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA). Totally, 9,704,33 reports were collected from the FAERS database, 10,804 reports of osimertinib were identified as the 'primary suspected (PS)' AEs. Osimertinib induced AEs occurred in 27 organ systems. 68 significant disproportionality PTs satisfying with the four algorithms were retained at the same time. Unexpected significant AEs such as scrotal volvulus, hepatic function abnormal, venous thromboembolisms might also occur. The median onset time of osimertinib-associated AEs was 58 days (interquartile range [IQR] 14-212 days), and the majority of the AEs occurred within the first 30 days after osimertinib initiation. Our study found significant new AEs signals of osimertinib and might provide support for clinical monitoring and risk identification of osimertinib.

PMID:36380085 | DOI:10.1038/s41598-022-23834-1

Saudi Med J. 2022 Nov;43(11):1248-1253. doi: 10.15537/smj.2022.43.11.20220493.

ABSTRACT

OBJECTIVES: To investigate the side effects of Pizer- BioNTech mRNA (BNT162b2) and Spikevax (mRNA- 1273) Coronavirus disease 2019 (COVID-19) vaccines on adolescents in Riyadh, Saudi Arabia.

METHODS: A cross-sectional study using an online questionnaire was carried out among COVID-19 vaccine adolescent recipients in Riyadh, Saudi Arabia. After receiving at least one dose of each vaccine, general and demographic data were collected, and vaccine-related side effects were evaluated.

RESULTS: The final sample consisted of 604 participants with a majority age group of 16-17 years old. Approximately 89.1% of the study participants were female. Most participants reported pain at the injection site (85.1% 1st dose, 79.8% 2nd dose), feeling tired, and headache (58.6% 1st dose, 64.2% 2nd dose). Moreover, we found that patients who took the first dose and had a chronic disease had 2.4 times higher odds of having menstrual disorder (females) than non-chronic disease patients (p=0.03) and 4.5 times higher odds of exhibiting breathing congestion (p=0.01). In addition, patients with chronic disease had 2.4 times higher odds of exhibiting muscle and joint pain and dizziness than non-chronic disease patients (p=0.01, p=0.02). Males were less likely to have dizziness after the first dose than females (OR=0.26, p=0.01).

CONCLUSION: This study investigates the adverse effects of COVID-19 vaccines among adolescents in Riyadh. As a result, this study creates a database to inform people about the risk of experiencing side effects based on their gender, age, and the vaccine type; more investigation is needed to better understand the link between risk factors and the development of adverse effects.

PMID:36379531 | DOI:10.15537/smj.2022.43.11.20220493