Nutrients. 2022 Aug 17;14(16):3367. doi: 10.3390/nu14163367.

ABSTRACT

Nootropics, also known as "smart drugs" are a diverse group of medicinal substances whose action improves human thinking, learning, and memory, especially in cases where these functions are impaired. This review provides an up-to-date overview of the potential effectiveness and importance of nootropics. Based on their nature and their effects, this heterogeneous group of drugs has been divided into four subgroups: classical nootropic compounds, substances increasing brain metabolism, cholinergic, and plants and their extracts with nootropic effects. Each subgroup of nootropics contains several main representatives, and for each one, its uses, indications, experimental treatments, dosage, and possible side effects and contraindications are discussed. For the nootropic plant extracts, there is also a brief description of each plant representative, its occurrence, history, and chemical composition of the medicinal part. Lastly, specific recommendations regarding the use of nootropics by both ill and healthy individuals are summarized.

PMID:36014874 | PMC:PMC9415189 | DOI:10.3390/nu14163367

Int J Mol Sci. 2022 Aug 14;23(16):9103. doi: 10.3390/ijms23169103.

ABSTRACT

Recent pharmacological studies indicated that the modulation of tripartite-synaptic transmission plays important roles in the pathophysiology of schizophrenia, mood disorders and adverse reactions. Therefore, to explore the mechanisms underlying the clinical and adverse reactions to atypical antipsychotics, the present study determined the effects of the sub-chronic administration of quetiapine (QTP: 3~30 μM) on the protein expression of 5-HT7 receptor (5-HT7R), connexin43 (Cx43), cAMP level and intracellular signalling, Akt, Erk and adenosine monophosphate-activated protein kinase (AMPK) in cultured astrocytes and the rat hypothalamus, using ultra-high-pressure liquid chromatography with mass spectrometry and capillary immunoblotting systems. QTP biphasically increased physiological ripple-burst evoked astroglial D-serine release in a concentration-dependent manner, peaking at 10 μM. QTP enhanced the astroglial signalling of Erk concentration-dependently, whereas both Akt and AMPK signalling's were biphasically enhanced by QTP, peaking at 10 μM and 3 μM, respectively. QTP downregulated astroglial 5-HT7R in the plasma membrane concentration-dependently. Protein expression of Cx43 in astroglial cytosol and intracellular cAMP levels were decreased and increased by QTP also biphasically, peaking at 3 μM. The dose-dependent effects of QTP on the protein expression of 5-HT7R and Cx43, AMPK signalling and intracellular cAMP levels in the hypothalamus were similar to those in astrocytes. These results suggest several complicated pharmacological features of QTP. A therapeutically relevant concentration/dose of QTP activates Akt, Erk and AMPK signalling, whereas a higher concentration/dose of QTP suppresses AMPK signalling via its low-affinity 5-HT7R inverse agonistic action. Therefore, 5-HT7R inverse agonistic action probably plays important roles in the prevention of a part of adverse reactions of QTP, such as weight gain and metabolic complications.

PMID:36012369 | PMC:PMC9409360 | DOI:10.3390/ijms23169103

J Hypertens. 2022 Jun 1;40(Suppl 1):e306-e307. doi: 10.1097/01.hjh.0000838720.56735.68.

ABSTRACT

OBJECTIVE: One of the reasons for patients' poor medication compliance is the occurrence of drug-induced adverse events. The aim of this study was to determine the prevalence of Multiple Drug Intolerance Syndrome (MDIS), defined as adverse events after 3 or more drug classes, in a group of patients with arterial hypertension and to assess the predisposing factors.

DESIGN AND METHOD: The study population comprised hospitalized patients diagnosed with arterial hypertension as well as patients undergoing chronic treatment in an outpatient hypertension clinic. A structured proprietary questionnaire was used, which focused on demographic and clinical data, including current or past incidences of adverse drug reactions.

RESULTS: The study population comprised a total of 1000 patients, including 560 women. The mean age was 62.84 ± 14.96 years. Eighty patients (8%) suffered from MDIS. A significantly higher percentage of patients with MDIS were women (71% vs. 55%, p = 0.006) and patients with longer-lasting hypertension (median 15 vs. 10 years, p = 0.008). Moreover, among patients with MDIS, the following disorders were more frequent: respiratory (21% vs. 11%, p = 0.013), gastrointestinal (25% vs. 13%, p = 0.003), rheumatic (24% vs. 9%, p < 0.001) and endocrine (29% vs. 16%, p = 0.007). The risk of MDIS was highest in the case of concomitant use of analgesics, OR = 65.59, p < 0.001, followed by beta-blockers, OR = 48.42, p < 0.001, antiplatelet drugs, OR = 47.26, p < 0.001 and antibiotics OR = 30.04, p < 0.001.

CONCLUSIONS: MDIS in patients with hypertension is common and affects more frequently women and patients with a longer disease duration. Comorbidities increase risk of MDIS. The risk of MDIS is most strongly associated with the use of analgesics, beta-blockers, antiplatelet drugs and antibiotics.

PMID:36027449 | DOI:10.1097/01.hjh.0000838720.56735.68

Curr Drug Saf. 2022 Aug 25. doi: 10.2174/1574886317666220825104207. Online ahead of print.

ABSTRACT

BACKGROUND: Methotrexate is an antimetabolite anticancer drug frequently used in the treatment of extensive chronic plaque psoriasis. Psoriasis patients on treatment with immunosuppressants have an increased risk of developing malignancies.

OBJECTIVE: To present a rare case of oral squamous cell carcinoma (OSCC) in a psoriasis patient postacute methotrexate toxicity.

CASE REPORT: A 47-year-old female, known case of chronic plaque psoriasis for which she was on 15 mg/week methotrexate therapy and accidentally consumed 15 mg for 7 consecutive days. She was successfully treated for methotrexate toxicity and 45 days later she presented with exophytic growth on the tongue. Histopathology confirmed the diagnosis of squamous cell carcinoma and the patient underwent surgical resection.

CONCLUSION: There could be a causal association between psoriasis and OSCC in the setting of acute methotrexate toxicity, as in the present case.

PMID:36017826 | DOI:10.2174/1574886317666220825104207

Front Genet. 2022 Aug 9;13:894209. doi: 10.3389/fgene.2022.894209. eCollection 2022.

ABSTRACT

Drug-Induced Liver Injury (DILI), despite its low occurrence rate, can cause severe side effects or even lead to death. Thus, it is one of the leading causes for terminating the development of new, and restricting the use of already-circulating, drugs. Moreover, its multifactorial nature, combined with a clinical presentation that often mimics other liver diseases, complicate the identification of DILI-related (or "positive") literature, which remains the main medium for sourcing results from the clinical practice and experimental studies. This work-contributing to the "Literature AI for DILI Challenge" of the Critical Assessment of Massive Data Analysis (CAMDA) 2021- presents an automated pipeline for distinguishing between DILI-positive and negative publications. We used Natural Language Processing (NLP) to filter out the uninformative parts of a text, and identify and extract mentions of chemicals and diseases. We combined that information with small-molecule and disease embeddings, which are capable of capturing chemical and disease similarities, to improve classification performance. The former were directly sourced from the Chemical Checker (CC). For the latter, we collected data that encode different aspects of disease similarity from the National Library of Medicine's (NLM) Medical Subject Headings (MeSH) thesaurus and the Comparative Toxicogenomics Database (CTD). Following a similar procedure as the one used in the CC, vector representations for diseases were learnt and evaluated. Two Neural Network (NN) classifiers were developed: a baseline model that accepts texts as input and an augmented, extended, model that also utilises chemical and disease embeddings. We trained, validated, and tested the classifiers through a Nested Cross-Validation (NCV) scheme with 10 outer and 5 inner folds. During this, the baseline and extended models performed virtually identically, with F1-scores of 95.04 ± 0.61% and 94.80 ± 0.41%, respectively. Upon validation on an external, withheld, dataset that is meant to assess classifier generalisability, the extended model achieved an F1-score of 91.14 ± 1.62%, outperforming its baseline counterpart which received a lower score of 88.30 ± 2.44%. We make further comparisons between the classifiers and discuss future improvements and directions, including utilising chemical and disease embeddings for visualisation and exploratory analysis of the DILI-positive literature.

PMID:36017500 | PMC:PMC9395939 | DOI:10.3389/fgene.2022.894209

Arch Rheumatol. 2021 Dec 24;37(2):300-310. doi: 10.46497/ArchRheumatol.2022.9049. eCollection 2022 Jun.

ABSTRACT

OBJECTIVES: Biological medications have been used with an increasing frequency to treat rheumatological diseases. Autoimmune events can be induced by these drugs, such as psoriasiform lesions, alopecia, lupus and, vasculitis, which more often affects the skin (small-sized vessels) and eventually other organs. In this review, we describe the clinical profile of patients with vasculitis induced by the main biological agents used in rheumatology.

PATIENTS AND METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The PubMed database was used for searching eligible articles. We included case reports, case series, and letter to the editor of patients on anti-tumor necrosis factor-alpha (anti-TNF-a) molecules, as well as tocilizumab, ustekinumab, secukinumab, rituximab, and abatacept, who had vasculitis induced by these agents.

RESULTS: Eighty-one articles were included for final analysis (n=89). Twenty-seven patients were using infliximab, 20 adalimumab, 18 etanercept, seven secukinumab, four certolizumab, four rituximab, three golimumab, three ustekinumab, two abatacept, and one tocilizumab. Unspecific leukocytoclastic vasculitis (LCV) was the most common type of vasculitis (n=37), followed by anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (n=16). The medication was replaced with another biological molecule in 23 cases, with only four relapses. In six cases, the biological was maintained, but vasculitis worsened/persisted in one case, being necessary drug removal.

CONCLUSION: Infections, infusion reaction, cancer, and autoimmune events are well-known side effects of biological therapy. This review demonstrates that vasculitis is another adverse effect of this type of therapy, particularly the anti-TNF-a molecules, and LCV the most reported type of vasculitis.

PMID:36017201 | PMC:PMC9377167 | DOI:10.46497/ArchRheumatol.2022.9049

Rev Panam Salud Publica. 2022 Aug 18;46:e110. doi: 10.26633/RPSP.2022.110. eCollection 2022.

ABSTRACT

There is a lack of real-world surveillance studies on reports of adverse events associated with COVID-19 vaccination, as well as comparative analyses of adverse events from vaccines with different platforms. This observational, descriptive, retrospective study based on secondary data describes the adverse events following immunization (AEFIs) related to the first 145 000 doses of COVID-19 vaccines delivered in Aracaju municipality, Sergipe state, northeast Brazil. Records of AEFIs were collected using the e-SUS Notifica database for January 19 to April 30, 2021. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for AEFIs and the type of COVID-19 vaccine, either CoronaVac (Sinovac-Butantan) or Oxford-AstraZeneca (Fiocruz). A total of 474 AEFIs (32.7 events/10 000 doses) from 254 individuals were reported and analyzed, and all of them were classified as non-serious. There was an association between the use of the CoronaVac vaccine and headache (OR = 2.1; 95% CI: 1.4-3.2), pain at the injection site (OR = 9.6; 95% CI: 3.9-23.8), lethargy (OR = 5.2; 95% CI: 1.8-14.8), fatigue (OR = 10.1; 95% CI: 2.4-42.3), diarrhea (OR = 4.4; 95% CI: 1.5-12.5) and cold-like symptoms (OR = 8.0; 95% CI: 1.9-34.0). However, the proportion of individuals reporting fever was higher among those who received the Oxford-AstraZeneca vaccine (OR = 3.1; 95% CI 1.5-6.4). This population-based observational study strengthens the evidence for the safety and tolerability of the CoronaVac and Oxford-AstraZeneca vaccines used against COVID-19.

PMID:36016838 | PMC:PMC9395276 | DOI:10.26633/RPSP.2022.110

Front Oncol. 2022 Aug 9;12:963928. doi: 10.3389/fonc.2022.963928. eCollection 2022.

ABSTRACT

BACKGROUND: The frequent emergence of drug resistance to chemotherapy is a major obstacle for the treatment of ovarian cancer. There is a need for novel drugs to fulfill this challenge. Pyroptosis-inducing drugs can inhibit tumor growth. However, their roles in ovarian cancer have not been demonstrated.

METHODS: We tested the effectiveness of a novel drug, BI 2536, which we found in colorectal cancer. Cell proliferation, cell cycle, and drug-induced apoptosis and pyroptosis were tested. In vivo treatments were performed using a cell-derived xenograft model.

RESULTS: BI 2536 significantly inhibited the proliferation of ovarian cancer cells and induced cell cycle arrest at the G2/M phases. After BI 2536 treatment, DNA fragmentation and PS exposure on the outside of apoptotic cells were detected. Moreover, the pyroptotic phenotype of ovarian cancer cells along with the release of LDH and HMGB1 were observed, indicating the leakage of cells. Western blot analysis verified that BI 2536 induced GSDME-mediated pyroptosis. Pyroptosis was abolished after additional treatment with Z-DEVD-FMK, a caspase-3 inhibitor. Thus, BI 2536 induced pyroptosis in ovarian cancer through the caspase-3/GSDME pathway. In vivo experiments further demonstrated the antitumoral effect and ability of BI 2536 to accumulate CD8+ T cells in ovarian cancer.

CONCLUSION: In this study, we identified BI 2536 as an effective anti-ovarian cancer drug that inhibits proliferation, arrests the cell cycle, induces apoptosis and pyroptosis, and leads to the accumulation of CD8+ T cells in tumor sites. Drug-induced pyroptosis may have promising prospects for reducing side effects and activating immune responses.

PMID:36016611 | PMC:PMC9396031 | DOI:10.3389/fonc.2022.963928

Int J Geriatr Psychiatry. 2022 Sep;37(9). doi: 10.1002/gps.5800.

ABSTRACT

OBJECTIVES: Information on medication-related problems (MRPs) in elderly psychiatric patients is scarce. In the present study, we analyzed the frequency and characteristics of MRPs in patients ≥60 years treated on the gerontopsychiatric ward of Hannover Medical School in 2019.

METHODS: Taking advantage of an interdisciplinary approach, two independent investigators screened hospital discharge letters of 230 psychiatric inpatients for clinically relevant MRPs, followed by validation through an interdisciplinary expert panel. Drug interactions as a subset of MRPs were analyzed with the aid of two different drug interaction programs.

RESULTS: 230 patients (63.0% female, mean age 73.7 ± 8.4 years, median length of stay 18 days) were prescribed a median of 6 drugs. In total, 2180 MRPs were detected in the study population and 94.3% of the patients exhibited at least one MRP. Patients displayed a median of 7 MRPs (interquartile range 3-15). Pharmacodynamic interactions accounted for almost half of all MRPs (48.1%; 1048/2180). The number of drugs prescribed and the number of MRPs per patient showed a strong linear relationship (adjusted R2 = 0.747).

CONCLUSION: An exceedingly high proportion of elderly psychiatric inpatients displayed clinically relevant MRPs in the present study, which may be explained by the multimorbidity prevalent in the study population and the associated polypharmacy. The number of drug interactions was largely in accordance with previous studies. As a novel finding, we detected that a considerable proportion of elderly psychiatric inpatients were affected by potential prescribing omissions, potentially inappropriate duplicate prescriptions, and insufficient documentation.

PMID:36005273 | DOI:10.1002/gps.5800

J Med Chem. 2022 Sep 8;65(17):11433-11453. doi: 10.1021/acs.jmedchem.2c00833. Epub 2022 Aug 24.

ABSTRACT

Reactive metabolite (RM) formation is widely accepted as playing a pivotal role in causing adverse idiosyncratic drug reactions, with most attention paid to drug-induced liver injury. Mechanisms of RM formation are determined by the drug's properties in relation to human enzymes transforming the drug. This Perspective focuses on enzymatic oxidation of alkyl groups on aromatics leading to quinone methides and benzylic alcohol sulfates as RMs, a topic that has not received very much attention. Unlike previous overviews, we will include in our Perspective several fulvene-like methides such as 3-methyleneindole. We also speculate that a few older drugs may form non-reported methides of this class. In addition, we report a few guiding DFT calculations of changes in free energy on going from a benzylic alcohol to the corresponding methide. Particularly facile reactions of 2-aminothiazole-5-methanol and 4-aminobenzyl alcohol are noted.

PMID:36001003 | DOI:10.1021/acs.jmedchem.2c00833

Zhongguo Fei Ai Za Zhi. 2022 Aug 20;25(8):555-566. doi: 10.3779/j.issn.1009-3419.2022.101.39.

ABSTRACT

Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy. .

PMID:36002192 | DOI:10.3779/j.issn.1009-3419.2022.101.39

Ann Hematol. 2022 Aug 25. doi: 10.1007/s00277-022-04945-1. Online ahead of print.

ABSTRACT

Tyrosine kinase inhibitors (TKIs) have dramatically changed the way chronic myeloid leukemia (CML) is treated. Although TKI therapy improves the overall survival of patients with CML, the management of various adverse events (AEs) from the therapy has become a major barrier to its adherence. Bosutinib is a second-generation TKI and an effective first-line treatment for CML. The most frequent AE is diarrhea; however, liver toxicity is also a major complication. In general, drug-induced hepatic enzyme elevation occurs within 1-2 weeks after treatment initiation. However, we noticed that, in a certain number of patients, liver injury appeared late (4-7 weeks) and was accompanied by eosinophilia. Herein, we retrospectively analyzed patients with CML treated with bosutinib at the Juntendo University School of Medicine and observed five patients with CML who developed late-onset liver injury with an elevation of the eosinophil count. In all cases, the liver enzyme level was within the normal range or grade 1 during the first 3 weeks of the bosutinib treatment and then elevated steeply thereafter. The pattern of hepatic toxicity was hepatocellular injury. In addition, all cases of eosinophilia tended to precede or coincide with an elevated liver enzyme level. Thus, the elevation of the eosinophil count may be a predictor for bosutinib-induced liver injury. Careful attention should be paid to delayed-onset hepatic injury, especially at 4-6 weeks after bosutinib initiation.

PMID:36002756 | DOI:10.1007/s00277-022-04945-1

Reg Anesth Pain Med. 2022 Aug 24:rapm-2022-103683. doi: 10.1136/rapm-2022-103683. Online ahead of print.

ABSTRACT

INTRODUCTION: Liver resection patients may be at an increased risk of local anesthetic (LA) toxicity because the liver is essential for metabolizing LA and producing proteins (mainly α1-acid glycoprotein (AAG)) that bind to it and reduce the free (and pharmacologically active/toxic) levels in circulation. The liver resection itself, manipulation during surgery, and pre-existing liver disease may all interfere with normal hepatic protein synthesis and result in an attenuation of the increased AAG (a positive acute-phase protein) that normally occurs postoperatively. The purpose of this study was to determine whether the AAG response is attenuated postoperatively following liver resection and whether patients approach toxicity thresholds with continuous postoperative epidural infusion of bupivacaine.

METHODS: Prospective, observational study with blood drawn preoperatively, in the postanesthetic care unit, on postoperative day (POD) 2, and prior to discontinuation of epidural analgesia on POD3/POD4. Plasma was analyzed for total and unbound bupivacaine via liquid chromatography-mass spectrometry and AAG via ELISA. Signs/symptoms of local anesthetic systemic toxicity (LAST), pain, and sedation scores were also recorded.

RESULTS: For the 19 patients completed, total plasma bupivacaine was correlated with total administered, but unbound levels were not associated with the total administered. Unlike non-hepatectomy surgery where unbound LA plasma levels remain stable (or decrease) with continuous postoperative epidural administration, we observed an overall increase. Several patients approached toxicity thresholds and 47% reported at least one symptom of LAST, but no epidurals were discontinued because of LAST. In contrast to the AAG response reported following major non-liver surgery where AAG levels increase twofold, we observed a reduction until POD2 and the magnitude was proportional to resection weight.

DISCUSSION: Our results are supported by the literature in suggesting that major liver resection patients may be at an increased vulnerability for LAST. Factors such as the extent of liver disease, resection and intraoperative blood loss should be considered when using continuous postoperative epidural infusion of bupivacaine and vigilance should be used in monitoring, for signs/symptoms of LAST, even for those subtle and non-specific. Future research will be required to verify these findings.

TRIAL REGISTRATION NUMBER: NCT03145805.

PMID:36002226 | DOI:10.1136/rapm-2022-103683

Drug Ther Bull. 2022 Sep;60(9):135. doi: 10.1136/dtb.2022.000043.

ABSTRACT

Overview of: Ozieranski P, Martinon L, Jachiet PA, et al Accessibility and quality of drug company disclosures of payments to healthcare professionals and organisations in 37 countries: a European policy review. BMJ Open 2021;11:e053138.

PMID:36002155 | DOI:10.1136/dtb.2022.000043

Leuk Lymphoma. 2022 Aug 23:1-8. doi: 10.1080/10428194.2022.2113535. Online ahead of print.

ABSTRACT

For many years, intensive research has been carried out on the in-depth understanding of the pathogenesis of multiple myeloma (MM). Nevertheless, the multifactorial nature of the disease, the development of drug resistance, and the side effects of therapy, make it difficult to effectively treat patients. One of the many factors involved in the pathogenesis of MM is brain-derived neurotrophic factor (BDNF). This factor is widely described as a neuroregenerative and neuroprotective agent, but it also regulates non-neuronal cell functions, such as proliferation, apoptosis, and viability. Therefore, BDNF appears to be a good therapeutic target in MM. On the other hand, its decreased concentration during treatment closely correlates with the development of peripheral neuropathy (PN). BDNF dualism requires a detailed understanding of its action on individual molecular mechanisms. Perhaps the optimization of the BDNF level will contribute to the improvement of MM treatment and the reduction of chemotherapy side effects.

PMID:35999712 | DOI:10.1080/10428194.2022.2113535

PLoS One. 2022 Aug 23;17(8):e0269944. doi: 10.1371/journal.pone.0269944. eCollection 2022.

ABSTRACT

BACKGROUND: COVID-19 vaccination acceptance is important, and combating hesitancy which is generally based on the individuals' beliefs and perceptions is essential in the present pandemic. This study assesses COVID-19 vaccine hesitancy and associated factors, beliefs and barriers associated with COVID-19 vaccination.

METHODS: A cross-sectional study was carried out among 492 Bangladeshi residents (76% male; mean age = 24.21 ± 4.91 years; age range = 18-50 years) prior to the nationwide mass COVID-19 vaccination campaign (September 28, 2021). A semi-structured e-questionnaire included three sections (demographic variables, beliefs around the vaccination, and perceived barriers regarding COVID-19 vaccination).

RESULTS: More than a quarter of participants (26.42%) were hesitant, 70.33% reported to accept the vaccine, and 3.25% refused to be vaccinated. While (54%) believed that mass vaccination would be the most effective method to combat the COVID-19 pandemic, concerns regarding the side effects of the vaccine (58%), inadequate vaccine trials before human administration (43%), commercial profiteering (42%), and mistrust of the benefits of the vaccine (20%) were also reported. In addition, other barriers including a short supply of vaccines, unknown future adverse effects (55%), low confidence in the health system (51%), doubts regarding its effectiveness (50%) and safety (45%), and insufficient information regarding potential adverse effects (44.7%) were reported. In bivariate analysis, variables such as current political affiliation, previous vaccination history, and health status were significantly associated with the COVID-19 vaccine uptake variable (acceptance, hesitancy, refusal). Regression analysis showed that participants who identified with the opposing current political parties, and not having been vaccinated since the age of 18 years were significantly more likely to report vaccine hesitancy.

CONCLUSIONS: The current findings relating to COVID-19 vaccination demonstrate that government and policy makers need to take all necessary measures to ensure the effectiveness of the vaccination program among the Bangladeshi people.

PMID:35998135 | PMC:PMC9398020 | DOI:10.1371/journal.pone.0269944

BMC Psychiatry. 2022 Aug 22;22(1):563. doi: 10.1186/s12888-022-04207-4.

ABSTRACT

BACKGROUND: Polypharmacy increases the risk of potential drug-drug interactions (pDDIs). This retrospective analysis was conducted to detect pDDIs and adverse drug reactions (ADRs) among older adults with psychiatric disorder, and identify pDDIs with clinical significance.

METHODS: A retrospective analysis was carried out based on the medical records of older adults with psychiatric disorders. Data on demographic characteristics, substance abuse, medical history, and medications were extracted. The Lexi-Interact online database was used to detect pDDIs. The minimal clinically important difference (MCID) was set as the change in the Treatment Emergent Symptom Scale (TESS) score between admission and discharge. The median and interquartile ranges were used for continuous variables, and frequencies were calculated for dichotomous variables. Poisson regression was implemented to determine the factors influencing the number of ADR types. The influencing factors of each ADR and the clinical significance of the severity of the ADR were analysed using binary logistic regression. P < 0.05 was considered statistically significant.

RESULTS: A total of 308 older adults were enrolled, 171 (55.52%) of whom had at least 1 pDDI. Thirty-six types of pDDIs that should be avoided were found, and the most frequent pDDI was the coadministration of lorazepam and olanzapine (55.5%). A total of 26 ADRs induced by pDDIs were identified, and the most common ADR was constipation (26.05%). There was a 9.4 and 10.3% increase in the number of ADR types for each extra medical diagnosis and for each extra drug, respectively. There was a 120% increase in the number of ADR types for older adults hospitalized for 18-28 days compared with those hospitalized for 3-17 days. There was an 11.1% decrease in the number of ADR types for each extra readmission. The length of hospitalization was a risk factor for abnormal liver function (P < 0.05). The use of a large number of drugs was a risk factor for gastric distress (P < 0.05) and dizziness and fainting (P < 0.05). None of the four pDDIs, including coadministrations of olanzapine and lorazepam, quetiapine and potassium chloride, quetiapine and escitalopram, and olanzapine and clonazepam, showed clinical significance of ADR severity (P > 0.05).

CONCLUSIONS: pDDIs are prevalent in older adults, and the rate is increasing. However, many pDDIs may have no clinical significance in terms of ADR severity. Further research on assessing pDDIs, and possible measures to prevent serious ADRs induced by DDIs is needed to reduce the clinical significance of pDDIs.

PMID:35996119 | DOI:10.1186/s12888-022-04207-4

Front Med (Lausanne). 2022 Aug 3;9:888186. doi: 10.3389/fmed.2022.888186. eCollection 2022.

ABSTRACT

BACKGROUND: Antimicrobial resistance to metronidazole has emerged after several decades of worldwide use of the drug. The purpose of this study was to evaluate the effectiveness, safety and population pharmacokinetics of morinidazole plus levofloxacin in adult women with pelvic inflammatory disease (PID).

METHODS: Patients in 30 hospitals received a 14-day course of 500 mg intravenous morinidazole twice daily plus 500 mg of levofloxacin daily. A total of 474 patients were included in the safety analysis set (SS); 398 patients were included in the full analysis set (FAS); 377 patients were included in the per protocol set (PPS); 16 patients were included in the microbiologically valid (MBV) population.

RESULTS: The clinical resolution rates in the FAS and PPS populations at the test of cure (TOC, primary effectiveness end point, 7-30 days post-therapy) visit were 81.91 and 82.49% (311/377), respectively. There were 332 patients who did not receive antibiotics before treatment, and the clinical cure rate was 82.83%. Among 66 patients who received antibiotics before treatment, 51 patients were clinically cured 7-30 days after treatment, with a clinical cure rate of 77.27%. The bacteriological success rate in the MBV population at the TOC visit was 87.5%. The minimum inhibitory concentration (MIC) values of morinidazole for use against these anaerobes ranged from 1 to 8 μg/mL. The rate of drug-related adverse events (AEs) was 27.43%, and no serious AEs or deaths occurred during the study.

CONCLUSIONS: The study showed that treatment with a 14-day course of intravenous morinidazole, 500 mg twice daily, plus levofloxacin 500 mg daily, was effective and safe. The results of this study were consistent with the results of a phase III clinical trial, which verified the effectiveness and safety of morinidazole.

PMID:35991648 | PMC:PMC9382104 | DOI:10.3389/fmed.2022.888186

Korean J Intern Med. 2022 Aug 22. doi: 10.3904/kjim.2022.072. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Pulmonary toxicities of coronavirus disease 2019 (COVID-19) vaccination are exceedingly rare. However, there are a few reported cases after mRNA vaccination, especially from Asian countries. The purpose of this study was to report the clinical characteristics of patients with COVID-19 vaccine-related pneumonitis (CV-P) and to review cases reported in the literature.

METHODS: We performed a prospective, observational case series analysis.

RESULTS: Eleven patients with a median age of 80 years were enrolled. Ten patients developed CV-P after BNT162b2-mRNA vaccination and one after ChAdOx1 nCoV-19 vaccination. We identified various patterns of CV-P, including transient infiltration, life-threatening acute respiratory distress syndrome, and aggravation of underlying interstitial lung disease. Most patients showed favorable outcomes with good responses to corticosteroid therapy.

CONCLUSIONS: Identifying the mechanism of CV-P requires further investigation; however, radiological and laboratory findings in our case series support inflammatory dysregulation in the lung parenchyma after vaccination. Clinicians should consider CV-P in patients with atypical lung infiltration, no specific etiologies, and recent COVID-19 vaccination.

PMID:35989064 | DOI:10.3904/kjim.2022.072

BMC Pharmacol Toxicol. 2022 Aug 20;23(1):64. doi: 10.1186/s40360-022-00606-1.

ABSTRACT

BACKGROUND: Anecdotal experience and studies have shown that most pediatric patients fail to reach target therapeutic vancomycin trough levels (VTLs) and required higher total daily doses (TDD). This retrospective study aims to evaluate the frequency of hospitalized children who achieved target VTLs with a vancomycin (VNCO) dosing regimen of 40-60 mg/kg/d q6h and to assess the VNCO-TDD required to attain the target and their effects on clinical outcomes in pediatric patients.

METHODS: After ethical approval, patients of 3 month-12 years were evaluated in this chart review study who received ≥ 3 intravenous-VNCO doses and appropriately drawn blood samples of VTLs between October 2019 to June 2020. Data were retrieved for demographic and clinical characteristics, culture reports, VNCO-regimen, subsequent steady-state VTLs, concomitant nephrotoxic medications, and serum creatinine. Clinical pharmacists made interventions in VNCO therapy and higher VNCO-TDD were used. Safety of higher vs standard daily doses and their clinical impact on duration of therapy, hospital stay, and survival were evaluated.

RESULTS: A total of 89 (39.1%) patients achieved target VTLs (SD-group). The smallest proportion (18.2%) of 2-6 years patients achieved target VTLs and reported the lowest mean value of 10.1 ± 0.2 mg/L which was a significant difference (p < 0.05) from all subgroups. Subtherapeutic VTLs were observed in 139 (60.9%) cases (HD-group), who received higher VNCO-TDD of 72 ± 8.9 mg/kg/d q6h to achieve the targets. Duration of therapy in culture-proven septic patients was significantly (p = 0.025) longer in SD-group [18.4 ± 12.2 days] than HD-group [15.1 ± 8.9 days]. Nephrotoxicity and electrolyte imbalance were comparable in groups. Length of hospital stay was significantly (p = 0.011) longer [median 22 (range 8-55) days] in SD-group compared to HD-group [median 16 (range 8-37) days]. Number of patients survived in HD-group were significantly (p = 0.008) higher than SD-group [129 (92.8%) vs 75 (84.3%)].

CONCLUSION: Initial Vancomycin doses of 72 ± 8.9 mg/kg/day q6h are required to achieve therapeutic target in 3 months to 12 years patients. High doses are not associated with higher nephrotoxicity than reported with low doses. In addition, efficient pharmacist intervention for the use of higher VNCO-TDD may improve clinical outcomes in terms of duration of therapy, hospital stay, and survival.

PMID:35987842 | DOI:10.1186/s40360-022-00606-1