JBMR Plus. 2021 Sep 7;5(10):e10541. doi: 10.1002/jbm4.10541. eCollection 2021 Oct.

ABSTRACT

Atypical antipsychotic (AA) drugs, such as risperidone, are associated with endocrine and metabolic side effects, including impaired bone mineral density (BMD) acquisition and increased fracture risk. We have previously shown that risperidone causes bone loss through the sympathetic nervous system and that bone loss is associated with elevated markers of thermogenesis in brown and white adipose tissue. Because rodents are normally housed in sub-thermoneutral conditions, we wanted to test whether increasing housing temperature would protect against bone loss from risperidone. Four weeks of risperidone treatment in female C57BL/6J mice at thermoneutral (28°C) housing attenuated risperidone-induced trabecular bone loss and led to a low-turnover bone phenotype, with indices of both bone formation and resorption suppressed in mice with risperidone treatment at thermoneutrality, whereas indices of bone resorption were elevated by risperidone at room temperature. Protection against trabecular bone loss was not absolute, however, and additional evidence of cortical bone loss emerged in risperidone-treated mice at thermoneutrality. Taken together, these findings suggest thermal challenge may be in part responsible for bone loss with risperidone treatment and that housing temperature should be considered when assessing bone outcomes of treatments that impact thermogenic pathways. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

PMID:34693191 | PMC:PMC8520062 | DOI:10.1002/jbm4.10541

Emerg Med J. 2021 Nov;38(11):829-841. doi: 10.1136/emermed-2021-211335.

NO ABSTRACT

PMID:34686538 | DOI:10.1136/emermed-2021-211335

Pharmaceutics. 2021 Oct 13;13(10):1670. doi: 10.3390/pharmaceutics13101670.

ABSTRACT

The tumor microenvironment (TME) plays a central role in regulating antitumor immune responses. As an important part of the TME, alternatively activated type 2 (M2) macrophages drive the development of primary and secondary tumors by promoting tumor cell proliferation, tumor angiogenesis, extracellular matrix remodeling and overall immunosuppression. Immunotherapy approaches targeting tumor-associated macrophages (TAMs) in order to reduce the immunosuppressive state in the TME have received great attention. Although these methods hold great potential for the treatment of several cancers, they also face some limitations, such as the fast degradation rate of drugs and drug-induced cytotoxicity of organs and tissues. Nanomedicine formulations that prevent TAM signaling and recruitment to the TME or deplete M2 TAMs to reduce tumor growth and metastasis represent encouraging novel strategies in cancer therapy. They allow the specific delivery of antitumor drugs to the tumor area, thereby reducing side effects associated with systemic application. In this review, we give an overview of TAM biology and the current state of nanomedicines that target M2 macrophages in the course of cancer immunotherapy, with a specific focus on nanoparticles (NPs). We summarize how different types of NPs target M2 TAMs, and how the physicochemical properties of NPs (size, shape, charge and targeting ligands) influence NP uptake by TAMs in vitro and in vivo in the TME. Furthermore, we provide a comparative analysis of passive and active NP-based TAM-targeting strategies and discuss their therapeutic potential.

PMID:34683963 | PMC:PMC8540805 | DOI:10.3390/pharmaceutics13101670

Pharmaceutics. 2021 Oct 6;13(10):1628. doi: 10.3390/pharmaceutics13101628.

ABSTRACT

Eye injuries due to corneal abrasions, chemical spills, penetrating wounds, and microbial infections cause corneal scarring and opacification that result in impaired vision or blindness. However, presently available eye drop formulations of anti-inflammatory and antibiotic drugs are not effective due to their rapid clearance from the ocular surface or due to drug-related side effects such as cataract formation or increased intraocular pressure. In this article, we presented the development of a dextran sulfate-based polymer wafer (DS-wafer) for the effective modulation of inflammation and fibrosis and demonstrated its efficacy in two corneal injury models: corneal abrasion mouse model and alkali induced ocular burn mouse model. The DS-wafers were fabricated by the electrospinning method. We assessed the efficacy of the DS-wafer by light microscopy, qPCR, confocal fluorescence imaging, and histopathological analysis. These studies demonstrated that the DS-wafer treatment is significantly effective in modulating corneal inflammation and fibrosis and inhibited corneal scarring and opacification compared to the unsulfated dextran-wafer treated and untreated corneas. Furthermore, these studies have demonstrated the efficacy of dextran sulfate as an anti-inflammatory and antifibrotic polymer therapeutic.

PMID:34683921 | PMC:PMC8539456 | DOI:10.3390/pharmaceutics13101628

Pharmaceuticals (Basel). 2021 Oct 15;14(10):1049. doi: 10.3390/ph14101049.

ABSTRACT

Young adults had been widely perceived as a low-risk group for COVID-19 severity; therefore, they were deprioritised within the mass vaccination strategies as their prognosis of COVID-19 infection is relatively more favourable than older age groups. On the other hand, vaccination of this demographic group is indispensable to achieve herd immunity. A cross-sectional survey-based study was used to evaluate the side effects of mRNA-based COVID-19 vaccines among university students in the Czech Republic. The validated questionnaire was delivered in a digital form, and it consisted of demographic data; COVID-19 vaccine-related anamnesis; and local, systemic, orofacial, and skin-related side effects' prevalence, onset, and duration. Out of the 539 included participants, 70.1% were females and 45.8% were <23 years old. The vast majority (95.2%) reported at least one side effect. The most common side effect was injection site pain (91.8%), followed by fatigue (62.5%), headache (36.4%), and muscle pain (34.9%). The majority of local side effects occurred after both doses (74.4%), while most systemic side effects occurred after the second dose only (56.2%). Most local (94.2%) and systemic (93.3%) side effects resolved within three days after vaccination. Females participants' adjusted odds ratio (AOR) showed they were 2.566 (CI 95%: 1.103-5.970) times more likely to experience post-vaccination side effects, and the participants who received two doses reported an increased AOR of 1.896 (0.708-5.077) for experiencing side effects. The results of this study imply that mRNA-based COVID-19 vaccines are highly probably safe for young adults, and further studies are required to investigate the role of medical anamnesis, prior COVID-19 infection, and gender in side effects incidence.

PMID:34681273 | DOI:10.3390/ph14101049

BMC Bioinformatics. 2021 Oct 21;22(Suppl 11):330. doi: 10.1186/s12859-021-04249-7.

ABSTRACT

BACKGROUND: Extraction of adverse drug events from biomedical literature and other textual data is an important component to monitor drug-safety and this has attracted attention of many researchers in healthcare. Existing works are more pivoted around entity-relation extraction using bidirectional long short term memory networks (Bi-LSTM) which does not attain the best feature representations.

RESULTS: In this paper, we introduce a question answering framework that exploits the robustness, masking and dynamic attention capabilities of RoBERTa by a technique of domain adaptation and attempt to overcome the aforementioned limitations. With formulation of an end-to-end pipeline, our model outperforms the prior work by 9.53% F1-Score.

CONCLUSION: An end-to-end pipeline that leverages state of the art transformer architecture in conjunction with QA approach can bolster the performances of entity-relation extraction tasks in the biomedical domain. In particular, we believe our research would be helpful in identification of potential adverse drug reactions in mono as well as combination therapy related textual data.

PMID:34674630 | DOI:10.1186/s12859-021-04249-7

J Clin Endocrinol Metab. 2021 Oct 22:dgab750. doi: 10.1210/clinem/dgab750. Online ahead of print.

ABSTRACT

CONTEXT: Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction. Our previous trial showed improvement of key clinical and biochemical features during one year of treatment with the T3-analogue Triac. Long-term follow-up data are lacking.

METHODS: In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8 deficient patients in 33 sites. The primary endpoint was the change in serum T3 concentrations from baseline to last-available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action.

RESULTS: Between 15-Oct-2014 and 1-Jan-2021, sixty-seven patients with a median baseline age of 4.6 years (range:0.5-66 years) were treated up to 6 years, with a median of 2.2 years (range 0.2-6.2 years). Mean T3 concentrations decreased from 4.58 (SD:1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L, 95%CI:2.61-3.23, p<0.0001; target:1.4-2.5 nmol/L). Body weight-for-age exceeded that of untreated historical controls (mean difference 0.72 SDs, 95%CI:0.36-1.09, p=0.0002). Heart rate-for-age decreased (mean difference 0.64 SDs, 95%CI:0.29-0.98, p=0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L, 95%CI:16-57, p=0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) µmol/L (mean increase 7 µmol/L, 95%CI:6-9, p<0.0001). Mean CK concentrations did not significantly change. No drug-related severe adverse events were reported.

CONCLUSIONS: Key features were sustainably alleviated in patients with MCT8 deficiency across all ages and highlight the potential of Triac for MCT8 deficiency in real-life.

PMID:34679181 | DOI:10.1210/clinem/dgab750

J Med Internet Res. 2021 Oct 21;23(10):e27714. doi: 10.2196/27714.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) affect the health of hundreds of thousands of individuals annually in the United States, with associated costs of hundreds of billions of dollars. The monitoring and analysis of the severity of ADRs is limited by the current qualitative and categorical systems of severity classification. Previous efforts have generated quantitative estimates for a subset of ADRs but were limited in scope because of the time and costs associated with the efforts.

OBJECTIVE: The aim of this study is to increase the number of ADRs for which there are quantitative severity estimates while improving the quality of these severity estimates.

METHODS: We present a semisupervised approach that estimates ADR severity by using social media word embeddings to construct a lexical network of ADRs and perform label propagation. We used this method to estimate the severity of 28,113 ADRs, representing 12,198 unique ADR concepts from the Medical Dictionary for Regulatory Activities.

RESULTS: Our Severity of Adverse Events Derived from Reddit (SAEDR) scores have good correlations with real-world outcomes. The SAEDR scores had Spearman correlations of 0.595, 0.633, and -0.748 for death, serious outcome, and no outcome, respectively, with ADR case outcomes in the Food and Drug Administration Adverse Event Reporting System. We investigated different methods for defining initial seed term sets and evaluated their impact on the severity estimates. We analyzed severity distributions for ADRs based on their appearance in boxed warning drug label sections, as well as for ADRs with sex-specific associations. We found that ADRs discovered in the postmarketing period had significantly greater severity than those discovered during the clinical trial (P<.001). We created quantitative drug-risk profile (DRIP) scores for 968 drugs that had a Spearman correlation of 0.377 with drugs ranked by the Food and Drug Administration Adverse Event Reporting System cases resulting in death, where the given drug was the primary suspect.

CONCLUSIONS: Our SAEDR and DRIP scores are well correlated with the real-world outcomes of the entities they represent and have demonstrated utility in pharmacovigilance research. We make the SAEDR scores for 12,198 ADRs and the DRIP scores for 968 drugs publicly available to enable more quantitative analysis of pharmacovigilance data.

PMID:34673524 | DOI:10.2196/27714

Eur J Paediatr Neurol. 2021 Oct 7;35:111-122. doi: 10.1016/j.ejpn.2021.10.003. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to measure health-related quality of life (HRQOL) in children and adolescents with tuberous sclerosis complex (TSC) and quality of life (QOL) and depressive symptoms among caregivers.

METHODS: Adequate metrics were used to assess HRQOL in children and adolescents with TSC (4-18 years, KINDLR) as well as QOL (EQ-5D) and symptoms of depression (BDI-II) among caregivers. Predictors for reduced HRQOL and depressive symptoms were identified by variance analysis, ordinal regression, and bivariate correlation.

RESULTS: The mean HRQOL score was 67.9 ± 12.7, and significantly lower values were associated with increasing age, attending special needs education, TSC-associated psychiatric symptoms, and drug-related adverse events. The mean QOL of caregivers was 85.4 ± 15.7, and caregiver's sex, TSC mutation locus, familial TSC clustering, special needs education, degree of disability, care dependency, presence of TSC-associated psychiatric symptoms, and TSC severity were significant predictors of lower QOL. Depressive symptoms were identified in 45.7% of caregivers, associated with female sex of the caregiver, familial TSC clustering, special needs education, and presence of TSC-associated psychiatric symptoms of the child. Multivariate regression analysis revealed adolescence and drug-related adverse events as significant predictors for lower HRQOL in TSC children, and TSC2 variants predicted lower QOL and depressive symptoms in caregivers.

CONCLUSION: Compared with other chronic diseases, such as headache, diabetes or obesity, children with TSC have significantly lower HRQOL, which further decreases during adolescence. A decreased HRQOL of patients correlates with a lower QOL and increased symptoms of depression of their caregivers. These results may improve the comprehensive therapy and care of children and adolescents with TSC and their families and caregivers.

TRIAL REGISTRATION: DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.

PMID:34673401 | DOI:10.1016/j.ejpn.2021.10.003

Front Pharmacol. 2021 Oct 4;12:731757. doi: 10.3389/fphar.2021.731757. eCollection 2021.

ABSTRACT

Introduction: Pharmacovigilance studies include monitoring and preventing the occurrence of new, rare, or serious adverse drug reactions, making it possible to discover new safety issues without delay. Bibliometrics could assist scholars to analyze the development of pharmacovigilance. Methods: The MeSH terms of both pharmacovigilance and "adverse drug reaction reporting system" were retrieved in the Science Citation Index Expanded. The articles from 1974 to July 2021 in the pharmacology and pharmacy category were recruited. The citation reports including the publication numbers, h-index, and sum and average cited times in terms of annuals, countries, organizations, authors and journals were tabulated. The coauthorship relations in the analysis units of countries, organizations, and authors; the top 10 burst references; the document citation network; and the author's keywords co-occurrence overlay map were visualized by bibliometric software including the website (https://bibliometric.com/), VOSviewer, CiteSpace, and CitNetExplorer. Results: From 1974 to the present, the most high-yield publication year, country, institute, author, and journal were 2020 (n = 222), France (n = 522), Netherlands Pharmacovigilance Centre Lareb (n = 82), Jean-Louis Montastruc (n = 125), Drug Safety (n = 384), respectively, in all 2,128 articles. Similarly, the United States, Institut National de la Sante et de la Recherche Medicale, and Jean-Louis Montastruc had the most coauthorship strength at the macrolevel (global), mesolevel (local), and microlevel (individual). The topics of burst references covered are the development of methodology, issues of patients reporting and under-reporting, evaluation of methods and databases, assessment of causality, and perspectives in pharmacovigilance. Eight clusters were grouped in the document citation network. "Pharmacovigilance," "adverse drug reactions," "pharmacoepidemiology," "drug safety," and "signal detection" were the research priorities, while "drug-related side effects and adverse reactions," "VigiBase," "disproportionality analysis," "social media," "FAERS," "chemotherapy," "patient safety," "reporting odds ratio," and "preventability" might be the future research hotspots. Conclusion: Positive synergies can be observed in this study by employing the multiple software tools which established the relationship between the units of analysis. The bibliometric analysis can organize the thematic development and guide the hotspots of pharmacovigilance in pharmacology and pharmacy.

PMID:34671257 | PMC:PMC8521010 | DOI:10.3389/fphar.2021.731757

G Ital Nefrol. 2021 Sep 7;38(Suppl 77):2021-S77.

ABSTRACT

Traditional medicine is a widespread treatment method in the world. Despite the WHO's confirmation of the progressive spread of national policies responsible for controlling the production and distribution of phytotherapy, the risk of toxic side effects is high even if the real incidence is not known. These risks largely result from the self-prescription supported by the assumption that what is natural is not dangerous to health. The phytotherapic industry turnover is progressively increasing, favored by the ease with which products can be purchased without prescription in pharmacies in some countries or online. In particular, Chinese herbs can be nephrotoxic and clinicians should consider the possibility of their role in some cases of AKI or CKD with unknown etiology. Furthermore, in the collection of the pharmacological history of patients with CKD or kidney transplantation it is necessary to exclude the use of some phytotherapics of common use that may be contraindicated for possible interactions with drugs of conventional medicine.

PMID:34669303

Aliment Pharmacol Ther. 2021 Oct 20. doi: 10.1111/apt.16642. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-induced gastrointestinal injury has been increasingly reported, but its exact incidence is not known. The small and large intestines represent the most affected sites of injury, accounting for 20%-40% of all gastrointestinal side effects.

AIM: To provide an updated literature review detailing medications linked to the development of small bowel injury.

METHODS: We conducted a literature search on PubMed from its inception to May 1, 2021. We included English-language original studies, meta-analyses, systematic reviews, review articles and case reports.

RESULTS: Drug-induced enteropathy can range from asymptomatic histological changes resulting in a subtle, self-limited disease to a chronic inflammatory condition mimicking inflammatory bowel disease, or bowel perforation. Endoscopy can demonstrate erythema, mucosal friability, oedema, erosions, ulcers or strictures in severe cases. Histology may include mucosal erosions and ulcerations, focal active enteritis, villous atrophy, epithelial apoptosis or necrotising enteritis. A well-established association has been found with the use of nonsteroidal anti-inflammatory drugs, immunosuppressants, chemotherapeutic agents, antibiotics, immunotherapies, etanercept and olmesartan. Possible associations have been reported with other biologic agents, medications used for glycemic control, antihypertensives, cholinesterase inhibitors, potassium and iron supplements, with conflicting data regarding contraceptives/hormonal therapy and isotretinoin.

CONCLUSION: Physicians should be aware of the manifestations of drug-induced enteropathy as early recognition can lead to prompt discontinuation of the offending therapy and, therefore, a reduced risk of future complications.

PMID:34668591 | DOI:10.1111/apt.16642

Medicine (Baltimore). 2021 Sep 17;100(37):e27107. doi: 10.1097/MD.0000000000027107.

ABSTRACT

OBJECTIVE: Lymphoma is a hematological disease with high prevalence. Multi-cycle chemotherapy (CHT) or local radiotherapy is applied usually; however, adverse events have been reported, such as drug-induced lung disease (DILD). Positron emission tomography/computed tomography (PET/CT) is often used to evaluate the lesion, treatment effect, and prognosis of lymphoma. We investigated DILD and pulmonary infection (PI) after multi-cycle CHT in lymphoma patients, to identify DILD and PI, provide guidance for later treatment for them.

METHODS: In all, 677 patients diagnosed with lymphoma and who underwent CHT were included. These patients underwent 18fluorodeoxyglucose (18F-FDG) PET/CT before and after CHT at Shandong Cancer Hospital (affiliated with Shandong University) between April 2015 and November 2019. Fifty patients developed DILD, 41 patients had lung infections; lesion characteristics were analyzed based on clinical characteristics, laboratory examinations, and PET/CT imaging.

RESULTS: Among the 677 lymphoma patients, there were 50 cases of DILD, with an incidence rate of 7.4%. PET/CT showed an elevated 18fluorodeoxyglucose uptake lung background, septal thickening and reticulation, multiple ground glass-like shadows, and grid-shaped blur shadows, which were more common in the lung periphery and under the pleura. The maximum standardized uptake value in the lung was 2.45 ± 0.52. Pulmonary infections occurred in 41 patients, and the maximum standardized uptake value was 4.05 ± 1.42. Age, sex, CHT cycle, Ann-Arbor stage, and lymphocyte levels were not significantly different between DILD and PI patients. Leukocyte and neutrophils showed significant differences; the PI patients had increased laboratory indexes of leukocyte and neutrophils. The mean number of CHT cycles was 4 cycles for DILD and PI.

CONCLUSIONS: PET/CT imaging has high sensitivity and detection rates for primary and metastatic lymphoma lesions. DILD mostly occurs in the middle and late stages of CHT. Laboratory tests and PET/CT can evaluate the lesions and treatment effects, and provide guidance for subsequent treatment plans for patients.

PMID:34664833 | DOI:10.1097/MD.0000000000027107

Drug Ther Bull. 2021 Oct 18:dtb-2021-000058. doi: 10.1136/dtb.2021.000058. Online ahead of print.

ABSTRACT

Overview of: Shantsila E, Shahid F, Sun Y, et al Spironolactone to improve exercise tolerance in people with permanent atrial fibrillation and preserved ejection fraction: the IMPRESS-AF RCT. Efficacy Mech Eval 2020; 7(4).

PMID:34663577 | DOI:10.1136/dtb.2021.000058

Eur Rev Med Pharmacol Sci. 2021 Oct;25(19):5942-5946. doi: 10.26355/eurrev_202110_26871.

ABSTRACT

OBJECTIVE: The pandemic disease by SARS-CoV-2 infection does not have an effective treatment. To prevent the disease, scientists developed vaccines that the clinicians use as an emergency licensed vaccine. The objective of this study was to determine the side effects in personnel vaccinated at the Military Central Hospital of Mexico with the BNT162b2 vaccine.

PATIENTS AND METHODS: This study included the subjects who had received both doses of the BNT162b2 vaccine between December 2020 and February 2021. We asked about the side effects after the first and the second vaccine doses. One group had no history of COVID-19, and the second had a history of COVID-19. ANTI-SARS-CoV-2 antibodies were measured by the immunodetection technique in the second group only.

RESULTS: We included 946 participants, 62% were women, and 80% were without comorbidities; 680 were included in the first group, and only 266 were in the second group. After the first dose, 77% of the first group and 86% of the second group presented some side effects. After the second dose, 84% of the first group and 89% of the second group showed some side effects. The main side effect was mild pain. All participants (126) were IgG positive, and only 26.9% were IgM positive at 17.5 days (12.8 days, 20.3 days) after the second dose.

CONCLUSIONS: There is a positive correlation between side effects after the first dose in patients with a history of previous SARS-CoV-2 infection compared to those who did not. Nevertheless, this correlation is not present after the second dose. The low percentage of IgM could be related to the time interval between vaccination and sample measure.

PMID:34661253 | DOI:10.26355/eurrev_202110_26871

Front Pediatr. 2021 Oct 1;9:726769. doi: 10.3389/fped.2021.726769. eCollection 2021.

ABSTRACT

Objective: To evaluate the efficacy, safety, and fungal sensitivity of prophylactic fluconazole use in very premature infants. Methods: We performed a retrospective historical comparative analysis of 196 very premature infants (113 in the prophylaxis group and 83 in the rescue group). The incidence of nosocomial fungal infection (NCFI) and pathogenic fungi, their drug sensitivity, and the minimum inhibitory concentration (MIC) of fluconazole were compared between the two groups. We also analyzed differences in short-term adverse outcomes, such as drug-induced liver or renal function disruption, fungal-attributable death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC), between the groups. The effects of the prophylactic fluconazole strategy on NCFI and short-term adverse outcomes were assessed by multivariate logistic regression. Results: Candida albicans (46.7%) and Candida glabrata (43.3%) were the main culprit pathogens causing NCFI. The incidence of NCFI was significantly lower in the prophylaxis group than in the rescue group (15.9 vs. 45.8%, P < 0.001). However, fewer fungi were completely sensitive to fluconazole (40 vs. 85%, P < 0.05) and the MIC of fluconazole was higher [16.0 (3.5 ~ 16.0) vs. 3.0 (1.0 ~ 8.0) μg/ml, P < 0.001] in the prophylaxis group than in the rescue group. Compared with the rescue group, the prophylaxis group had a lower risk of NCFI (adjusted OR 0.25; 95% CI 0.11, 0.55). Additionally, the prophylaxis group had significantly lower risks of combined outcomes (one or more complications, such as BPD, ROP needing interventions, PVL/IVH (grade > 2), NEC stage ≥2, and fungal-attributable death) (adjusted OR 0.44; 95% CI 0.21, 0.92). There was no significant difference in serum alanine transferase (ALT), aspartate transaminase (AST), creatinine (Cr), or direct bilirubin (DBIL) levels between the two groups. Conclusions: Fluconazole prophylaxis reduced NCFI and improved combined clinical outcomes in very premature infants, with no increased risks of serious short-term adverse side effects; however, the MIC of fluconazole showed significant increases. Therefore, further optimization of preventive strategies is necessary to maintain the sensitivity of fluconazole against fungal isolates.

PMID:34660487 | PMC:PMC8517516 | DOI:10.3389/fped.2021.726769

Cureus. 2021 Sep 9;13(9):e17856. doi: 10.7759/cureus.17856. eCollection 2021 Sep.

ABSTRACT

Drug-induced liver injury (DILI) is the leading cause of acute liver failure in the United States. Azithromycin is a commonly used antibiotic for community-acquired pneumonia that causes liver injury in rare cases. Typically, cholestatic liver injury has been reported for azithromycin, but there have only been a few case reports addressing the association with direct hepatocellular liver injury. This is a case of a 66-year-old man, with no pre-existing liver disease, who was managed for Legionnaires' disease who sustained a hepatocellular pattern of liver injury associated with azithromycin. We report this case to highlight the importance of prompt recognition of these rare side effects associated with azithromycin and the discontinuation of the drug to facilitate rapid recovery.

PMID:34660061 | PMC:PMC8502755 | DOI:10.7759/cureus.17856

Hypertens Res. 2021 Oct 17. doi: 10.1038/s41440-021-00760-9. Online ahead of print.

ABSTRACT

Renal denervation is a potential alternative to antihypertensive drug therapy. However, data on patient preference for this treatment option are limited and there are no data specifically from Asian patients. This study evaluated patient preference for renal denervation in patients with hypertension from Japan. Patients were a subset of those who participated in a March 2020 online electronic survey of patients with hypertension who had regularly visited medical institutions for treatment, were receiving antihypertensive drug therapy and had home blood pressure recordings available. The survey included a question about patient preference for treatment with renal denervation. A total of 2,392 patients were included (66% male, mean age 59.8 ± 11.6 years, mean duration of hypertension 11.4 ± 9.5 years). Preference for renal denervation was expressed by 755 patients (31.6%), and was higher in males than in females, in younger compared with older patients, in those with higher versus lower blood pressure, in patients who were less adherent versus more adherent to antihypertensive drug therapy, and in those who did rather than did not have antihypertensive drug-related side effects. Significant predictors of preference for renal denervation on logistic regression analysis were younger patient age, male sex, higher home or office systolic blood pressure, poor antihypertensive drug adherence, the presence of heart failure, and the presence of side effects during treatment with antihypertensive drugs. Overall, a relevant proportion of Japanese patients with hypertension expressed a preference for renal denervation. This should be taken into account when making shared decisions about antihypertensive drug therapy.

PMID:34657136 | DOI:10.1038/s41440-021-00760-9

Gan To Kagaku Ryoho. 2021 Oct;48(10):1265-1267.

ABSTRACT

The patient was a 69-year-old man diagnosed with stage ⅣB lung adenocarcinoma with 95% programmed death- ligand 1 expression, and pembrolizumab monotherapy was initiated. The patient exhibited fatigue from the 12th course(36 weeks after treatment initiation) of treatment. Chest computed tomography revealed scattered ground-glass opacities in the upper lobes of both lungs, and he was subsequently diagnosed with interstitial pneumonia. Fatigue persisted even after a drug holiday from pembrolizumab, and the patient was diagnosed with hypopituitarism based on the results of endocrinological examinations. Rashes appeared on both legs 40 weeks after treatment initiation, which led to the patient being diagnosed with a drug-induced skin disorder. All the adverse events resolved upon treatment with hydrocortisone. Immune- related adverse events due to pembrolizumab may occur in multiple organs simultaneously.

PMID:34657060

Int J Med Inform. 2021 Dec;156:104611. doi: 10.1016/j.ijmedinf.2021.104611. Epub 2021 Oct 5.

ABSTRACT

BACKGROUND: The penicillin adverse drug reaction (ADR) label is common in electronic health records (EHRs). However, there is significant misclassification between allergy and intolerance within the EHR and most patients can be delabelled after an immunologic assessment. Machine learning natural language processing may be able to assist with the categorisation and risk stratification of penicillin ADRs.

OBJECTIVE: The aim of this study was to use text entered into an EHR to derive and evaluate machine learning models to classify penicillin ADRs and assess the risk of true allergy.

METHODS: Machine learning natural language processing was applied to free-text penicillin ADR data extracted from a public health system EHR. The model was developed by training on labelled dataset. ADR entries were split into training and testing datasets and used to develop and test a variety of machine learning models. These were compared to categorisation with a simple algorithm using keyword search.

RESULTS: The best performing model for the classification of penicillin ADRs as being consistent with allergy or intolerance was the artificial neural network (AUC 0.994, sensitivity 0.99, specificity 0.96). The artificial neural network also achieved the highest AUC in the classification of high- or low-risk of true allergy (AUC 0.988, sensitivity 0.99, specificity 0.99). All ADR labels were able to be classified using these machine learning models, whereas a small proportion were unclassifiable using the simple algorithm as they contained no keywords.

CONCLUSION: Machine learning natural language processing performed similarly to expert criteria in classifying and risk stratifying penicillin ADRs labels. These models outperformed simpler algorithms in their ability to interpret free-text data contained in the EHR. The automated evaluation of penicillin ADR labels may allow real-time risk stratification to facilitate delabelling and improve the specificity of prescribing alerts.

PMID:34653809 | DOI:10.1016/j.ijmedinf.2021.104611