J Int Med Res. 2024 Mar;52(3):3000605241238993. doi: 10.1177/03000605241238077.

ABSTRACT

OBJECTIVE: The OpenVigil database can be used to assess medications that may cause supraventricular tachycardia (SVT) and to produce a reference for their safe use in clinical settings.

METHODS: We analyzed first-quarter data from 2004 to 2023, obtained by searching the OpenVigil database using the keyword "supraventricular tachycardia." Trade names and generic names were obtained by querying the RxNav database, and the proportions were summarized. The proportionate reporting ratio (PRR), reporting odds ratio, and chi-square values were also summarized. We created Asahi diagrams and set the screening criteria to drug events ≥30, PRR >2, and chi-square >4. Outcomes were evaluated using the Side Effect Resource database, several scientific literature databases, and the Hangzhou Yiyao Rational Medication System.

RESULTS: A total of 2435 distinct medications were found to induce SVT between the first quarter of 2004 and 2023, leading to 22,375 documented adverse events related to SVT. Further investigation revealed that salbutamol, paroxetine, formoterol, paclitaxel, venlafaxine, and theophylline were most likely to cause SVT.

CONCLUSION: We conducted signal mining of adverse drug events using the OpenVigil database and evaluated the six drugs most likely to cause SVT. The results of this research can serve as a drug safety reference in the clinic.

PMID:38530149 | DOI:10.1177/03000605241238077

BMC Pediatr. 2024 Mar 25;24(1):212. doi: 10.1186/s12887-024-04697-z.

ABSTRACT

OBJECTIVE: The clinical characteristics of hospitalized children with acute poisoning were analyzed to provide a reference for preventing poisoning and seeking effective prevention and treatment.

METHODS: The clinical data of 112 children with acute poisoning admitted to Qilu Hospital of Shandong University from January 1, 2018, to December 31, 2021, were collected and analyzed from different perspectives.

RESULTS: The majority of acute poisoning cases that occurred in children were in early childhood and preschool age (89 cases, accounting for 79.4%). The most common types of poisoning were pesticide poisoning and drug poisoning, and the main ways of poisoning were accidental administration via the digestive tract and accidental ingestion. Poisoning occurred slightly more in spring and summer all year round, and most children had a good prognosis after timely treatment.

CONCLUSION: Acute poisoning often occurs in children. Parental education and intensified child supervision are needed to prevent the incidence of unintentional poisoning.

PMID:38528509 | DOI:10.1186/s12887-024-04697-z

Sr Care Pharm. 2024 Apr 1;39(4):132-136. doi: 10.4140/TCP.n.2024.132.

ABSTRACT

Older people are over-represented among individuals that experience adverse drug reactions (ADR) and adverse drug events (ADE). Furthermore, older people are over-represented among individuals that visit emergency departments and are hospitalized because of ADRs. Moreover, older people are overrepresented among those who suffer ADEs while hospitalized. Finally, older people are among those most likely to have an anaphylactic response to prescription medications. Therefore, older people are prime candidates for efforts aimed at optimizing pharmacotherapeutic outcomes. Pharmacogenomics is an approach of using genetic data to optimize pharmacotherapeutic outcomes. Over the last two decades, pharmacogenomics grew from research initiatives into the current environment of pharmacogenomics implementation. Specifically, implementing pharmacogenomics into clinical settings or within health care systems has proven beneficial in optimizing pharmacotherapeutic outcomes. Therefore, pharmacists focused on optimizing pharmacotherapeutic outcomes for older people should be aware of the approaches to and resources available for implementing pharmacogenomics. KEY WORDS: Drug labeling biomarkers, Genes, Older adults, Pharmacogenomics.

PMID:38528338 | DOI:10.4140/TCP.n.2024.132

Comput Biol Med. 2024 Mar 20;173:108348. doi: 10.1016/j.compbiomed.2024.108348. Online ahead of print.

ABSTRACT

Drug-induced diseases are the most important component of iatrogenic disease. It is the duty of doctors to provide a reasonable and safe dose of medication. Gunqile-7 is a Mongolian medicine with analgesic and anti-inflammatory effects. As a foreign substance in the body, even with reasonable medication, it may produce varying degrees of adverse reactions or toxic side effects. Since the cost of collecting Gunqile-7 for pharmacological animal trials is high and the data sample is small, this paper employs transfer learning and data augmentation methods to study the toxicity of Gunqile-7. More specifically, to reduce the necessary number of training samples, the data augmentation approach is employed to extend the data set. Then, the transfer learning method and one-dimensional convolutional neural network are utilized to train the network. In addition, we use the support vector machine-recursive feature elimination method for feature selection to reduce features that have adverse effects on model predictions. Furthermore, due to the important role of the pre-trained model of transfer learning, we select a quantitative toxicity prediction model as the pre-trained model, which is consistent with the purpose of this paper. Lastly, the experimental results demonstrate the efficiency of the proposed method. Our method can improve accuracy by up to 9 percentage points compared to the method without transfer learning on a small sample set.

PMID:38531249 | DOI:10.1016/j.compbiomed.2024.108348

Front Oncol. 2024 Mar 11;14:1366532. doi: 10.3389/fonc.2024.1366532. eCollection 2024.

ABSTRACT

BACKGROUND: Novel therapies, immune checkpoint inhibitors (ICIs), and BRAF/MEK inhibitors (BRAFi/MEKi) provide unprecedented survival benefits for patients with advanced melanoma. However, the management of drug-induced adverse events is problematic for both agents and, although rare, can cause serious cardiac dysfunction.

CASE REPORT: A 42-year-old male patient with no significant medical history noticed a fading dark brown patch on his left anterior chest, which had been there for 20 years, after his second coronavirus disease 2019 (COVID-19) vaccination. The left axillary lymph node became swollen one week after a third booster vaccination. Thinking of it as an adverse reaction to the vaccine, but the swelling increased, so he visited a hospital. The patient presented with a brown macule with depigmentation on the left anterior chest and a 13 cm left axillary mass. A biopsy of the axillary mass showed a metastatic malignant melanoma. Positron emission tomography (PET) showed an accumulation only in the axillary lymph nodes. One month after the initial diagnosis, the axillary mass had further enlarged. In addition, pleural effusion, ascites, difficulty breathing, and systemic edema appeared, and he was diagnosed with heart failure (NYHA class III). Echocardiography showed an ejection fraction of 52% and electrocardiogram (ECG) showed no abnormal findings. Though it was (a life-threatening instead of the life-threatening) the life-threatening condition, we determined that the symptoms were associated with the current disease. Then nivolumab (nivo) plus ipilimumab (ipi) was initiated after explaining the risk of cardiac dysfunction associated with drug use to the patient. After initiation of ICIs, treatment was switched to BRAFi/MEKi (encorafenib/vinimetinib) after the patient tested positive for BRAF V600E. After one month of treatment, the tumor shrank significantly and achieved a complete remission after four months. Furthermore, as the tumor shrank, the patient's heart failure improved, and he was able to continue treatment without serious drug-induced cardiotoxicity.

CONCLUSION: Both ICI and BRAFi/MEKi carry a risk of cardiac dysfunction. However, without any underlying cardiac disease or severe cardiac dysfunction, their administration should not necessarily be excluded if careful follow-up is provided.

PMID:38529375 | PMC:PMC10961452 | DOI:10.3389/fonc.2024.1366532

Med Oncol. 2024 Mar 25;41(5):91. doi: 10.1007/s12032-024-02309-5.

ABSTRACT

The application of immune checkpoint inhibitors (ICIs) has changed the treatment of advanced hepatocellular carcinoma. Transcatheter arterial chemoembolization (TACE) is a first-line treatment for intermediate hepatocellular carcinoma. Serving as a local treatment modality that can induce immunogenic cell death, the efficacy and safety of combined use with ICI have not been evaluated. Although there have been prospective studies aimed at evaluating the efficacy and safety of ICI combined with TACE in BCLC stage B HCC patients, there are few reports on the evaluation of BCLC stage C patients with distant metastasis or portal vein cancer thrombus. Data of unresectable hepatocellular carcinoma patients received PD-1 inhibitor and TACE were collected in Xijing Hospital from June 2019 to December 2022. The tumor response was evaluated according to the Solid Tumor Modified Response Evaluation Standard (mRECIST), including complete response (CR), partial response (PR), disease stability (SD), disease progression (PD), objective response rate (ORR), and disease control rate (DCR). The progression-free survival (PFS) and overall survival (OS) were used to estimate therapy efficacy. The treatment-related adverse events were evaluated based on National Cancer Institute Common Adverse Event Evaluation Criteria (CTCAE) version 5.0. A total of 42 patients with unresectable hepatocellular carcinoma were included in this study, including 34 males (80.5%) and 8 females (19.5%). The average age is 54.5 years, ranging from 34 to 72. The median follow-up time was 12.3 months, with an ORR of 42.9% and a DCR of 90.5% as of the follow-up time. The median PFS is 7.5 months (95% CI: 5.76-9.23), and the median OS has not yet been reached; 6-month PFS was 62.2%. Safety analysis showed that 41 (97.6%) patients experienced treatment-related adverse reactions, mainly including elevated AST and ALT, fever, elevated bilirubin, hypothyroidism, nausea, abdominal pain, and rash. 40 patients had grade 1/2 adverse reactions, and only one patient had grade 3 adverse reactions, manifested as intolerable rash, nausea, and vomiting. Treatment is terminated when symptomatic treatment and drug suspension cannot be alleviated. In this study, thre patients with unresectable hepatocellular carcinoma were treated with PD-1 inhibitor combined with TACE to achieve good tumor reduction effect and underwent liver cancer resection surgery. For patients with unresectable hepatocellular carcinoma, whether in BCLC stage B or stage C, effective systemic therapy (PD-1 inhibitor) combined with local therapy (TACE) can achieve a high rate of tumor regression and objective response. Some patients may even pursue surgical treatment opportunities, and the treatment-related adverse reactions are controllable, which is expected to provide new options for extending the survival of unresectable hepatocellular carcinoma patients.

PMID:38526607 | DOI:10.1007/s12032-024-02309-5

Sci Rep. 2024 Mar 24;14(1):6993. doi: 10.1038/s41598-024-57892-4.

ABSTRACT

Iodine deficiency and excessive salt intake have adverse health effects. This study evaluated the iodine level and salt intake in Chinese adults aged 18-59 years after implementing the salt reduction program and compared with both the World Health Organization (WHO) and Chinese recommendations. Adults aged 18-59 years were randomly selected using multi-stage stratified random sampling in coastal urban area (CUA), non-coastal urban area (Non-CUA), coastal rural area (CRA), and non-coastal rural area (Non-CRA) of Fujian Province, China. Iodine, sodium, and creatinine concentrations in spot urine samples were measured. Knudsen equation was used to determine 24-h urinary iodine and sodium excretion. The median urinary iodine concentration (mUIC) and urinary sodium concentration (mUNaC) among adults (n = 3513) were 132.0 μg/L and 4.0 g/d, respectively. The mUIC and median daily iodine intake in CUA, Non-CUA, CRA and Non-CRA were 112.1, 127.5, 128.5, 167.5 μg/L and 189.6, 182.5, 199.4, 236.0 μg/d, respectively. The mUNaC and median daily salt intake (mDSI) in these four areas were 2.4, 2.8, 2.9, 2.9 g/L and 9.8, 10.4, 10.4, 10.6 g/d, respectively. The mUIC and DII of residents were higher in the Non-CRA than in the other three areas (P < 0.05). The UNaC and DSI of residents were lower in the CUA than in the other three areas (P < 0.05). The logistic regression demonstrated that the people living in CUA and Non-CUA consumed less salt compared with those in Non-CRA. Except for Non-CUA, the DII was lower (< 150 μg/d) among women of childbearing age in the low-salt intake group (< 5 g/d) compared with the high-salt intake group (≥ 5 g/d) (P < 0.05). Iodine nutrition in Chinese adults aged 18-59 years was sufficient, but the salt intake was substantially higher than the WHO and Chinese recommendations. Further policy implementation is needed to reduce salt intake and improve the monitoring of iodine levels in Chinese adults, especially in women of childbearing age.

PMID:38523151 | DOI:10.1038/s41598-024-57892-4

Drug Ther Bull. 2024 Mar 25;62(4):52. doi: 10.1136/dtb.2024.000016.

ABSTRACT

Overview of: Hanula R, Bortolussi-Courval É, Mendel A, et al. Evaluation of oseltamivir used to prevent hospitalization in outpatients with influenza: a systematic review and meta-analysis. JAMA Internal Medicine 2024;184:18-27.

PMID:38527768 | DOI:10.1136/dtb.2024.000016

Drug Ther Bull. 2024 Mar 25;62(4):54. doi: 10.1136/dtb.2024.000017.

ABSTRACT

Overview of: Bhasin S, Lincoff AM, Nissen SE, et al. Effect of testosterone on progression from prediabetes to diabetes in men with hypogonadism: a substudy of the TRAVERSE randomized clinical trial. JAMA Intern Med. 2024. doi: 10.1001/jamainternmed.2023.7862. [Epub ahead of print 5 February 2024].

PMID:38527767 | DOI:10.1136/dtb.2024.000017

Drug Ther Bull. 2024 Mar 25;62(4):51. doi: 10.1136/dtb.2024.000015.

ABSTRACT

Overview of: Copaescu AM, Vogrin S, James F, et al. Efficacy of a clinical decision rule to enable direct oral challenge in patients with low-risk penicillin allergy: The PALACE randomized clinical trial. JAMA Intern Med 2023;183:944-52.

PMID:38527765 | DOI:10.1136/dtb.2024.000015

J Toxicol Environ Health B Crit Rev. 2024 May 18;27(4):153-187. doi: 10.1080/10937404.2024.2330962. Epub 2024 Mar 22.

ABSTRACT

The widespread production and use of plastics have resulted in accumulation of plastic debris in the environment, gradually breaking down into smaller particles over time. Nano-plastics (NPs) and microplastics (MPs), defined as particles smaller than 100 nanometers and 5 millimeters, respectively, raise concerns due to their ability to enter the human body through various pathways including ingestion, inhalation, and skin contact. Various investigators demonstrated that these particles may produce physical and chemical damage to human cells, tissues, and organs, disrupting cellular processes, triggering inflammation and oxidative stress, and impacting hormone and neurotransmitter balance. In addition, micro- and nano-plastics (MNPLs) may carry toxic chemicals and pathogens, exacerbating adverse effects on human health. The magnitude and nature of these effects are not yet fully understood, requiring further research for a comprehensive risk assessment. Nevertheless, evidence available suggests that accumulation of these particles in the environment and potential human uptake are causes for concern. Urgent measures to reduce plastic pollution and limit human exposure to MNPLs are necessary to safeguard human health and the environment. In this review, current knowledge regarding the influence of MNPLs on human health is summarized, including toxicity mechanisms, exposure pathways, and health outcomes across multiple organs. The critical need for additional research is also emphasized to comprehensively assess potential risks posed by degradation of MNPLs on human health and inform strategies for addressing this emerging environmental health challenge. Finally, new research directions are proposed including evaluation of gene regulation associated with MNPLs exposure.

PMID:38517360 | DOI:10.1080/10937404.2024.2330962

Medicine (Baltimore). 2024 Mar 22;103(12):e37562. doi: 10.1097/MD.0000000000037562.

ABSTRACT

RATIONALE: Immune-related adverse events following treatment with immune checkpoint inhibitors can affect almost every organ. Tislelizumab, a novel humanized Ig G4 programmed death receptor 1 inhibitor, was started for bladder cancer in 2019, but the adverse effects of this drug may not yet be known due to its short time on the market, and there are still some clinical safety concerns. There are few reports of adrenal insufficiency after tislelizumab treatment, which is easily missed, misdiagnosed and life-threatening.

PATIENT CONCERNS: A 67-year-old male with bladder cancer who developed rash, water-sodium retention, electrolyte disturbances, hypoalbuminemia, low-grade fever, nausea and vomiting, and fatigue after 2 cycles of tislelizumab.

DIAGNOSIS: Immune checkpoint inhibitor-related adrenal hypofunction and Psoriasisby.

INTERVENTIONS: Suspended tislelizumab treatment and continued glucocorticoid therapy.

OUTCOMES: The patient showed significant improvement in the above symptoms. But bladder cancer reemerged at the same site.

CONCLUSIONS: The advent of immune-related adverse events has increased the complexity of the application of tislelizumab in the treatment of bladder cancer and further research is needed to develop the best treatment guidelines. Early diagnosis and treatment are crucial since the adverse events could endanger lives.

PMID:38518047 | PMC:PMC10956970 | DOI:10.1097/MD.0000000000037562

Clin Transl Sci. 2024 Mar;17(3):e13769. doi: 10.1111/cts.13769.

ABSTRACT

Tislelizumab, an anti-programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first-in-human, dose-finding BGB-A317-001 study (data cutoff [DCO]: August 2017) examined the following tislelizumab dosing regimens: 0.5-10 mg/kg every 2 weeks (q2w), 2-5 mg/kg q2w or q3w, and 200 mg q3w. Similar objective response rates (ORRs) were reported in the 2 and 5 mg/kg q2w or q3w cohorts. Safety outcomes (grade ≥3 adverse events [AEs], AEs leading to dose modification/discontinuation, immune-mediated AEs, and infusion-related reactions) were generally comparable across the dosing range examined. These results, alongside the convenience of a fixed q3w dose, formed the basis of choosing 200 mg q3w as the recommended dosing regimen for further clinical use. Pooled exposure-response (E-R) analyses by logistic regression using data from study BGB-A317-001 (DCO: August 2020) and three additional phase I/II studies (DCOs: 2018-2020) showed no statistically significant correlation between tislelizumab pharmacokinetic exposure and ORR across multiple solid tumor types or classical Hodgkin's lymphoma, nor was exposure associated with any of the safety end points evaluated over the dose range tested. Hence, tislelizumab showed a relatively flat E-R relationship. Overall, the totality of data, including efficacy, safety, and E-R analyses, together with the relative convenience of a fixed q3w dose, provided clinical rationale for the recommended dosing regimen of tislelizumab 200 mg q3w for multiple cancer indications.

PMID:38515348 | PMC:PMC10958174 | DOI:10.1111/cts.13769

MMW Fortschr Med. 2024 Mar;166(5):12-14. doi: 10.1007/s15006-024-3731-8.

NO ABSTRACT

PMID:38514537 | DOI:10.1007/s15006-024-3731-8

Drug Ther Bull. 2024 Mar 22:dtb-2024-000018. doi: 10.1136/dtb.2024.000018. Online ahead of print.

ABSTRACT

The BNF is jointly published by the Royal Pharmaceutical Society and BMJ. BNF is published in print twice a year and interim updates are issued and published monthly in the digital versions. The following summary provides a brief description of some recent key changes that have been made to BNF content.

PMID:38519120 | DOI:10.1136/dtb.2024.000018

Front Pharmacol. 2024 Mar 7;15:1346169. doi: 10.3389/fphar.2024.1346169. eCollection 2024.

ABSTRACT

Background: Recommended standard treatment for leprosy is multidrugtherapy (MDT/WHO), consisting Rifampicin+Dapsone+Clofazimine. Other medications are recommended in cases of resistance, adverse reactions and intolerances, including ROM regimen, Rifampicin+Ofloxacin+Minocycline. Therefore, pharmacovigilance is an important tool in understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. This study seeks to evaluate ADRs comparing two therapeutic regimens, MDT and ROM, used in treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety. Methods:A retrospective cohort study was performed by assessing medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil. They were subject to 24 months or more of treatment with MDT or ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity and the causality criteria of Naranjo and WHO. Results: The findings observed an average of 1.3 reactions/patient. Out of individuals experiencing reactions, 67.0% (69/103) were utilizing MDT/MB, while 33.0% (34/103) were using ROM. The median time for ADR of 79 days for MDT and 179 days for ROM. In first reaction, Dapsone was the most frequently involved medication; the most affected system was hematopoietic. As compared to Clofazimine, results indicated that use of Dapsone was associated with 7% increased risk of ADR occurrence (HR: 1.07; p = 0.866). Additionally, Rifampicin was linked to 31% increased risk of ADRs (HR: 1.31; p = 0.602); and Ofloxacin showed 35% elevated risk (HR: 1.35; p = 0.653). Conversely, results for Minocycline indicated 44% reduction in the risk of ADRs (HR: 0.56; p = 0.527), although statistical significance was not reached. The use of MDT conferred 2.51 times higher risk of developing ADRs in comparison to ROM. Conclusion: The comparison between MDT and ROM revealed that MDT caused more ADRs, and these reactions were more severe, indicating less safety for patients. Dapsone was the most common medication causing ADRs, followed by Rifampicin. The combination with Clofazimine was associated with an additional risk of ADRs, warranting further studies to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to monitor patients undergoing leprosy treatment with focus on pharmacovigilance.

PMID:38515839 | PMC:PMC10955366 | DOI:10.3389/fphar.2024.1346169

AIDS Res Ther. 2024 Mar 21;21(1):17. doi: 10.1186/s12981-024-00604-9.

ABSTRACT

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years).

METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis.

RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years.

CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities.

TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

PMID:38515183 | DOI:10.1186/s12981-024-00604-9

Neurology. 2024 Apr 23;102(8):e209316. doi: 10.1212/WNL.0000000000209316. Epub 2024 Mar 21.

NO ABSTRACT

PMID:38513190 | DOI:10.1212/WNL.0000000000209316

Prim Care Companion CNS Disord. 2024 Mar 14;26(2):23cr03631. doi: 10.4088/PCC.23cr03631.

NO ABSTRACT

PMID:38512205 | DOI:10.4088/PCC.23cr03631

Am J Nurs. 2024 Apr 1;124(4):23. doi: 10.1097/01.NAJ.0001010564.78302.59. Epub 2024 Mar 21.

NO ABSTRACT

PMID:38511705 | DOI:10.1097/01.NAJ.0001010564.78302.59