Z Gerontol Geriatr. 2023 Feb 27. doi: 10.1007/s00391-023-02173-4. Online ahead of print.

ABSTRACT

BACKGROUND: From a geriatric perspective, the use of antipsychotic drugs (AP) is associated with significant risks in addition to their known effects. These include unfavorable interactions with geriatric syndromes, such as immobility and risk of falling, and potentially increased mortality, at least in certain patient groups. With reference to this the current state of knowledge on treatment with AP in older people with schizophrenia spectrum disorders is summarized with a focus on the typical multimorbidity of geriatric patients.

METHODS: Narrative review with special consideration of guidelines and consensus papers from German speaking countries and a PubMed-supported literature search for current systematic reviews and meta-analyses.

RESULTS: Antipsychotic agents are an essential part of a comprehensive treatment concept for schizophrenia with well-documented evidence. In geriatric patients adaptations under gerontopharmacological aspects are necessary. A sufficient data basis for evidence-based recommendations for the treatment of multimorbid and frail geriatric patients does not exist.

CONCLUSION: An effective and as safe as possible treatment with AP requires a careful risk-benefit assessment, combined with an individual adaptation regarding the substance applied, dose and treatment duration in an interdisciplinary/multiprofessional context.

PMID:36847861 | DOI:10.1007/s00391-023-02173-4

Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(2):73-82. doi: 10.17116/jnevro202312302173.

ABSTRACT

OBJECTIVE: To evaluate the efficacy of Ipigrix in the complex treatment of patients with dorsalgia (DA) of the lumbosacral spine based on the results of the DORISS observational non-interventional multicenter study.

MATERIAL AND METHODS: Overall 3563 patients with verified diagnoses of DA at 200 clinical centers within the Russian Federation who received comparable baseline therapy according to nosological standards were examined, some of them additionally received oral or staggered treatment with Ipigrix. Baseline therapy for DA was given to 376 patients (treatment group 1), combination of baseline with oral Ipigrix was given to 1026 patients (group 2), and combination with staggered prescription of ipidacrine - to 2161 (group 3). Secondary endpoint of the study included analysis of the improvement of clinical symptoms, values of pain NRS and DN4 scales together with Roland-Morris questionnaire during the period of observation depending on the therapy with an assessment of its safety.

RESULTS: The results of the analysis of covariance allowed to exclude the influence of confounders (age and initial indicators of the utilized scales) on DA outcomes and demonstrated the greatest pain reduction in patients who additionally received Ipigrix via the staggered scheme. The inter-group comparison aligned by pseudorandomization showed statistically significant benefits of combined therapy regardless of the type of Ipigrix administration concerning main vertebral syndrome manifestations, sensory and motor disturbances, relief of pain, as well as neuropathic symptoms, improvement of neurophysiological parameters and restoration of life functioning without serious drug related adverse events.

CONCLUSION: Ipigrix (ipidacrine) can be considered an effective and safe adjuvant analgesic in the treatment of DA.

PMID:36843462 | DOI:10.17116/jnevro202312302173

Medicina (Kaunas). 2023 Feb 14;59(2):364. doi: 10.3390/medicina59020364.

ABSTRACT

Since vaccines are in fact manufactured chemical compounds such as drugs, the appearance of side effects following their use is not surprising. Similarly, as the main goal of vaccines is to stimulate the immune system bringing out the production of protective antibodies, autoimmune-related side effects as a consequence of increased immune activity do not seem irrational. Fortunately, the rate of such side effects is low; however, the importance of reporting adverse events following vaccinations, understanding the mechanisms behind their appearance, making early diagnosis, and appropriate treatment cannot be overemphasized. In fact, autoimmune-related side effects of vaccines, particularly those based on adjuvants, were reported long before the introduction of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Nevertheless, ASIA gathered and united the side effects of vaccines under one title, a step which helped organize the research and call for better immune stimulators than adjuvants. New technologies and methods of making vaccines were clearly noticed during the pandemic of COVID-19 after the introduction of mRNA-based vaccines. In our current paper, we introduce the notion of side effects to vaccines, particularly those of autoimmune nature, the mechanisms of ASIA, and the main vaccines linked with the syndrome including the recent COVID-19 vaccines. The transition from side effects to ASIA is the main idea behind our work.

PMID:36837564 | PMC:PMC9966463 | DOI:10.3390/medicina59020364

Int J Mol Sci. 2023 Feb 18;24(4):4116. doi: 10.3390/ijms24044116.

ABSTRACT

Analysis platforms to predict drug-induced seizure liability at an early phase of drug development would improve safety and reduce attrition and the high cost of drug development. We hypothesized that a drug-induced in vitro transcriptomics signature predicts its ictogenicity. We exposed rat cortical neuronal cultures to non-toxic concentrations of 34 compounds for 24 h; 11 were known to be ictogenic (tool compounds), 13 were associated with a high number of seizure-related adverse event reports in the clinical FDA Adverse Event Reporting System (FAERS) database and systematic literature search (FAERS-positive compounds), and 10 were known to be non-ictogenic (FAERS-negative compounds). The drug-induced gene expression profile was assessed from RNA-sequencing data. Transcriptomics profiles induced by the tool, FAERS-positive and FAERS-negative compounds, were compared using bioinformatics and machine learning. Of the 13 FAERS-positive compounds, 11 induced significant differential gene expression; 10 of the 11 showed an overall high similarity to the profile of at least one tool compound, correctly predicting the ictogenicity. Alikeness-% based on the number of the same differentially expressed genes correctly categorized 85%, the Gene Set Enrichment Analysis score correctly categorized 73%, and the machine-learning approach correctly categorized 91% of the FAERS-positive compounds with reported seizure liability currently in clinical use. Our data suggest that the drug-induced gene expression profile could be used as a predictive biomarker for seizure liability.

PMID:36835526 | PMC:PMC9963992 | DOI:10.3390/ijms24044116

Int J Mol Sci. 2023 Feb 16;24(4):4013. doi: 10.3390/ijms24044013.

ABSTRACT

Metabolic activation is the primary cause of chemical toxicity including hepatotoxicity. Cytochrome P450 2E (CYP2E) is involved in this process for many hepatotoxicants, including acetaminophen (APAP), one of the most common analgesics and antipyretics. Although the zebrafish is now used as a model for toxicology and toxicity tests, the CYP2E homologue in zebrafish has not been identified yet. In this study, we prepared transgenic zebrafish embryos/larvae expressing rat CYP2E1 and enhanced green fluorescent protein (EGFP) using a β-actin promoter. Rat CYP2E1 activity was confirmed by the fluorescence of 7-hydroxycoumarin (7-HC), a metabolite of 7-methoxycoumarin that was specific for CYP2 in transgenic larvae with EGFP fluorescence (EGFP [+]) but not in transgenic larvae without EGFP fluorescence (EGFP [-]). APAP (2.5 mM) caused reduction in the size of the retina in EGFP [+] larvae but not in EGFP [-] larvae, while APAP similarly reduced pigmentation in both larvae. APAP at even 1 mM reduced the liver size in EGFP [+] larvae but not in EGFP [-] larvae. APAP-induced reduction of liver size was inhibited by N-acetylcysteine. These results suggest that rat CYP2E1 is involved in some APAP-induced toxicological endpoints in the retina and liver but not in melanogenesis of the developing zebrafish.

PMID:36835425 | PMC:PMC9968093 | DOI:10.3390/ijms24044013

Int J Mol Sci. 2023 Feb 14;24(4):3791. doi: 10.3390/ijms24043791.

ABSTRACT

Drug-induced liver injury, also known as drug-induced hepatotoxicity (DILI), is a major cause of medicine withdrawal (prescription or over-the-counter) from the market [...].

PMID:36835204 | PMC:PMC9961832 | DOI:10.3390/ijms24043791

Int J Mol Sci. 2023 Feb 7;24(4):3291. doi: 10.3390/ijms24043291.

ABSTRACT

Lipid-lowering therapies are widely used to prevent the development of atherosclerotic cardiovascular disease (ASCVD) and related mortality worldwide. "Omics" technologies have been successfully applied in recent decades to investigate the mechanisms of action of these drugs, their pleiotropic effects, and their side effects, aiming to identify novel targets for future personalized medicine with an improvement of the efficacy and safety associated with the treatment. Pharmacometabolomics is a branch of metabolomics that is focused on the study of drug effects on metabolic pathways that are implicated in the variation of response to the treatment considering also the influences from a specific disease, environment, and concomitant pharmacological therapies. In this review, we summarized the most significant metabolomic studies on the effects of lipid-lowering therapies, including the most commonly used statins and fibrates to novel drugs or nutraceutical approaches. The integration of pharmacometabolomics data with the information obtained from the other "omics" approaches could help in the comprehension of the biological mechanisms underlying the use of lipid-lowering drugs in view of defining a precision medicine to improve the efficacy and reduce the side effects associated with the treatment.

PMID:36834701 | PMC:PMC9960554 | DOI:10.3390/ijms24043291

Int J Environ Res Public Health. 2023 Feb 20;20(4):3725. doi: 10.3390/ijerph20043725.

ABSTRACT

Adverse drug reaction (ADR) severity levels are mainly rated by healthcare professionals (HCPs), but patient ratings are limited. This study aimed to compare patient-rated and pharmacist-rated ADR severity levels and determined methods employed for ADR management and prevention by patients and HCPs. A cross-sectional survey was conducted in outpatients visiting two hospitals. Patients were asked about ADR experiences using a self-administered questionnaire, and additional information was retrieved from the medical records. In total, 617 out of 5594 patients had experienced ADRs (11.0%), but 419 patients were valid (68.0%). Patients commonly reported that their ADR severity level was moderate (39.4%), whereas pharmacists rated the ADRs as mild (52.5%). There was little agreement between patient-rated and pharmacist-rated ADR severity levels (κ = 0.144; p < 0.001). The major method of ADR management by physicians was drug withdrawal (84.7%), while for patients, it was physician consultation (67.5%). The main methods for ADR prevention by patients and HCPs were carrying an allergy card (37.2%) and recording drug allergy history (51.1%), respectively. A higher level of ADR bothersomeness was associated with higher ADR severity levels (p < 0.001). Patients and HCPs rated ADR severity and used ADR management and prevention methods differently. However, patient rating of ADR severity is a potential signal for severe ADR detection of HCPs.

PMID:36834422 | PMC:PMC9959449 | DOI:10.3390/ijerph20043725

Int J Environ Res Public Health. 2023 Feb 18;20(4):3639. doi: 10.3390/ijerph20043639.

ABSTRACT

There is no published evidence on the possible differences in multimorbidity, inappropriate prescribing, and adverse outcomes of care, simultaneously, from a sex perspective in older patients. We aimed to identify those possible differences in patients hospitalized because of a chronic disease exacerbation. A multicenter, prospective cohort study of 740 older hospitalized patients (≥65 years) was designed, registering sociodemographic variables, frailty, Barthel index, chronic conditions (CCs), geriatric syndromes (GSs), polypharmacy, potentially inappropriate prescribing (PIP) according to STOPP/START criteria, and adverse drug reactions (ADRs). Outcomes were length of stay (LOS), discharge to nursing home, in-hospital mortality, cause of mortality, and existence of any ADR and its worst consequence. Bivariate analyses between sex and all variables were performed, and a network graph was created for each sex using CC and GS. A total of 740 patients were included (53.2% females, 53.5% ≥85 years old). Women presented higher prevalence of frailty, and more were living in a nursing home or alone, and had a higher percentage of PIP related to anxiolytics or pain management drugs. Moreover, they presented significant pairwise associations between CC, such as asthma, vertigo, thyroid diseases, osteoarticular diseases, and sleep disorders, and with GS, such as chronic pain, constipation, and anxiety/depression. No significant differences in immediate adverse outcomes of care were observed between men and women in the exacerbation episode.

PMID:36834333 | PMC:PMC9964600 | DOI:10.3390/ijerph20043639

Int J Environ Res Public Health. 2023 Feb 17;20(4):3548. doi: 10.3390/ijerph20043548.

ABSTRACT

BACKGROUND: Pharmacovigilance (PV) is an essential activity to detect adverse drug reactions (ADRs) and ensure patient safety. Hence, we aimed to evaluate knowledge, attitudes, and practices (KAP) regarding PV among community pharmacists in Qassim, Saudi Arabia.

METHODS: A cross-sectional study was conducted by using a validated questionnaire after obtaining ethical approval from the Deanship of Scientific Research, Qassim University. The sample size was calculated based on the total number of pharmacists in the Qassim area by using Raosoft, Inc. Statistical Package for the Social Sciences version 20 was used for data entry and analysis. Ordinal logistic regression was performed to identify the predictors of KAP. A p-value of <0.05 was considered statistically significant.

RESULTS: A total of 209 community pharmacists participated in the study; 62.9% of them defined the PV correctly, and 59% of them defined ADRs correctly. However, only 17.2% knew where to report ADRs. Interestingly, the majority of participants (92.9%) reported that it is necessary to report ADRs, and 73.8% of them were willing to report ADRs. A total of 53.8% of the participants identified ADRs during their careers; however, only 21.9% reported ADRs. Barriers discourage ADR reporting; the majority of the participants (85.6%) do not know how to report ADRs.

CONCLUSION: Community pharmacists who participated in the study were knowledgeable about PV, and their attitude towards reporting ADRs was highly positive. However, the number of reported ADRs was low because of the lack of knowledge on how and where to report ADRs. Continuous education and motivation about ADRs reporting and PV are warranted among community pharmacists for the rational use of medications.

PMID:36834240 | PMC:PMC9958751 | DOI:10.3390/ijerph20043548

Int J Environ Res Public Health. 2023 Feb 16;20(4):3473. doi: 10.3390/ijerph20043473.

ABSTRACT

Physiologically Based Pharmacokinetic (PBPK) models are mechanistic tools generally employed in the pharmaceutical industry and environmental health risk assessment. These models are recognized by regulatory authorities for predicting organ concentration-time profiles, pharmacokinetics and daily intake dose of xenobiotics. The extension of PBPK models to capture sensitive populations such as pediatric, geriatric, pregnant females, fetus, etc., and diseased populations such as those with renal impairment, liver cirrhosis, etc., is a must. However, the current modelling practices and existing models are not mature enough to confidently predict the risk in these populations. A multidisciplinary collaboration between clinicians, experimental and modeler scientist is vital to improve the physiology and calculation of biochemical parameters for integrating knowledge and refining existing PBPK models. Specific PBPK covering compartments such as cerebrospinal fluid and the hippocampus are required to gain mechanistic understanding about xenobiotic disposition in these sub-parts. The PBPK model assists in building quantitative adverse outcome pathways (qAOPs) for several endpoints such as developmental neurotoxicity (DNT), hepatotoxicity and cardiotoxicity. Machine learning algorithms can predict physicochemical parameters required to develop in silico models where experimental data are unavailable. Integrating machine learning with PBPK carries the potential to revolutionize the field of drug discovery and development and environmental risk. Overall, this review tried to summarize the recent developments in the in-silico models, building of qAOPs and use of machine learning for improving existing models, along with a regulatory perspective. This review can act as a guide for toxicologists who wish to build their careers in kinetic modeling.

PMID:36834167 | PMC:PMC9966583 | DOI:10.3390/ijerph20043473

Int J Environ Res Public Health. 2023 Feb 15;20(4):3398. doi: 10.3390/ijerph20043398.

ABSTRACT

A relationship was found between the COVID-19 pandemic and depression among older adults and between depressed mood and increased use of antidepressant medication among older adults during the pandemic. With the aim of broadening the understanding of these relationships, the study examined whether COVID-19 perceived susceptibility mediates the relationship between psychosocial resources (optimism and perceived social support) and depressive symptoms and medication use. Participants included 383 older adults (M = 71.75, SD = 6.77) reporting on socio-demographics, health characteristics, depression, optimism, social support, and COVID-19 perceived susceptibility. Medication use was retrieved from participants medical files. Lower optimism, lower social support, and higher COVID-19 perceived susceptibility were associated with greater depression, related with higher medication use. The findings emphasize the buffering effect of psychosocial resources on the adverse effects of depression affecting older adults during the COVID-19 pandemic, and consequently, the increased use of medication in this population. Practitioners should focus interventions on enhancing optimism and expanding social support among older adults. Moreover, interventions focused on alleviating depression among older adults should aim at improving perceptions of perceived susceptibility in the older population.

PMID:36834090 | PMC:PMC9961318 | DOI:10.3390/ijerph20043398

Int J Environ Res Public Health. 2023 Feb 13;20(4):3289. doi: 10.3390/ijerph20043289.

ABSTRACT

Osteoporosis is a serious bone disease that affects many people worldwide. Various drugs have been used to treat osteoporosis. However, these drugs may cause severe adverse events in patients. Adverse drug events are harmful reactions caused by drug usage and remain one of the leading causes of death in many countries. Predicting serious adverse drug reactions in the early stages can help save patients' lives and reduce healthcare costs. Classification methods are commonly used to predict the severity of adverse events. These methods usually assume independence among attributes, which may not be practical in real-world applications. In this paper, a new attribute weighted logistic regression is proposed to predict the severity of adverse drug events. Our method relaxes the assumption of independence among the attributes. An evaluation was performed on osteoporosis data obtained from the United States Food and Drug Administration databases. The results showed that our method achieved a higher recognition performance and outperformed baseline methods in predicting the severity of adverse drug events.

PMID:36833984 | PMC:PMC9965583 | DOI:10.3390/ijerph20043289

Genes (Basel). 2023 Feb 10;14(2):456. doi: 10.3390/genes14020456.

ABSTRACT

Pharmacogenomic testing is a method to prevent adverse drug reactions. Pharmacogenomics could be relevant to optimize statin treatment, by identifying patients at high risk for adverse drug reactions. We aim to investigate the clinical validity and utility of pre-emptive pharmacogenomics screening in primary care, with SLCO1B1 c.521T>C as a risk factor for statin-induced adverse drug reactions. The focus was on changes in therapy as a proxy for adverse drug reactions observed in statin-users in a population-based Dutch cohort. In total, 1136 statin users were retrospectively genotyped for the SLCO1B1 c.521T>C polymorphism (rs4149056) and information on their statin dispensing was evaluated as cross-sectional research. Approximately half of the included participants discontinued or switched their statin treatment within three years. In our analyses, we could not confirm an association between the SLCO1B1 c.521T>C genotype and any change in statin therapy or arriving at a stable dose sooner in primary care. To be able to evaluate the predictive values of SLCO1B1 c.521T>C genotype on adverse drug reactions from statins, prospective data collection of actual adverse drug reactions and reasons to change statin treatment should be facilitated.

PMID:36833383 | PMC:PMC9957000 | DOI:10.3390/genes14020456

Trials. 2023 Feb 25;24(1):144. doi: 10.1186/s13063-023-07178-3.

ABSTRACT

BACKGROUND: Perioperative pain management is one of the most challenging issues for patients with spinal neoplasms. Inadequate postoperative analgesia usually leads to severe postsurgical pain, which could cause patients to suffer from many other related complications. Meanwhile, there is no appropriate analgesic strategy for patients with spinal neoplasms.

METHODS/DESIGN: This is a protocol for a randomized double-blind controlled trial to evaluate the effect of esketamine combined with pregabalin on postsurgical pain in spinal surgery. Patients aged 18 to 65 years scheduled for spinal neoplasm resection will be randomly allocated into the combined and control groups in a 1:1 ratio. In the combined group, esketamine will be given during the during the surgery procedure until 48-h postoperative period, and pregabalin will be taken from 2 h before the surgery to 2 weeks postoperatively. The control group will receive normal saline and placebo capsules at the same time points. Both groups received a background analgesic regimen by using patient-controlled intravenous analgesia (containing 100 μg sufentanil and 16 mg ondansetron) until 2 days after surgery. To ensure the accuracy and reliability of this trial, all the researchers and patients will be blinded until the completion of this study. The primary outcome will be the proportion of patients with acute moderate-to-severe postsurgical pain (visual analog scale, VAS ≥ 40, range: 0-100, with 0, no pain; 100, the worst pain) during the 48-h postoperative period. The secondary outcomes will include the maximal VAS scores (when the patients felt the most intense pain over the last 24 h before being interviewed) at 0-2 h, 2-24 h, 24-48 h, and 48-72 h after leaving the operating room and 24 h before discharge; the incidence of acute moderate-to-severe postsurgical pain at each other time point; chronic postsurgical pain assessment; neuropathic pain assessment; and the incidence of drug-related adverse events and other postoperative complications, such as postoperative delirium and postoperative nausea and vomiting (PONV).

DISCUSSION: The aim of this study was to evaluate the effect of esketamine combined with pregabalin on acute postsurgical pain in patients undergoing resection of spinal neoplasms. The safety of this perioperative pain management strategy will also be examined.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05096468. Registered on October 27, 2021.

PMID:36841794 | DOI:10.1186/s13063-023-07178-3

Molecules. 2023 Feb 20;28(4):1990. doi: 10.3390/molecules28041990.

ABSTRACT

The kidney is an important organ in the human body, with functions such as urine production, the excretion of metabolic waste, the regulation of water, electrolyte and acid-base balance and endocrine release. The morbidity and mortality of kidney diseases are increasing year by year worldwide, and they have become a serious public health problem. In recent years, natural products derived from fungi, plants and animals have become an important alternative source of treatment for kidney diseases because of their multiple pathways, multiple targets, safety, low toxicity and few side effects. Tanshinone IIA (Tan IIA) is a lipid-soluble diterpene quinone isolated from the Chinese herb Salvia miltiorrhiza, considered as a common drug for the treatment of cardiovascular diseases. As researchers around the world continue to explore its unknown biological activities, it has also been found to have a wide range of biological effects, such as anti-cancer, anti-oxidative stress, anti-inflammatory, anti-fibrotic, and hepatoprotective effects, among others. In recent years, many studies have elaborated on its renoprotective effects in various renal diseases, including diabetic nephropathy (DN), renal fibrosis (RF), uric acid nephropathy (UAN), renal cell carcinoma (RCC) and drug-induced kidney injury caused by cisplatin, vancomycin and acetaminophen (APAP). These effects imply that Tan IIA may be a promising drug to use against renal diseases. This article provides a comprehensive review of the pharmacological mechanisms of Tan IIA in the treatment of various renal diseases, and it provides some references for further research and clinical application of Tan IIA in renal diseases.

PMID:36838978 | DOI:10.3390/molecules28041990

Medicina (Kaunas). 2023 Feb 9;59(2):324. doi: 10.3390/medicina59020324.

ABSTRACT

Background and Objectives: The treatment of chronic lymphocytic leukemia (CLL) has acquired new targeted therapies. In clinical trials, ibrutinib improved outcomes safely. Real-world data called for a reappraisal of ibrutinib strategies. We report on a single center's experience with ibrutinib monotherapy, aiming to explore the outcomes, tolerability, and prognosis of CLL patients in routine clinical practice. Materials and Methods: Data were collected from all CLL patients treated with ibrutinib at Fundeni Clinical Institute, Bucharest, Romania, between January 2016 and June 2021. Results: A total of one hundred twenty-three CLL adult patients were treated with ibrutinib. Of the patients, 87% had relapsed/refractory CLL. The median age at ibrutinib initiation was 65 years; 44.7% of patients were staged Rai III/IV. At 32-month median follow-up, the median progression-free survival (PFS) was 50 months, the overall survival (OS) was not reached, and the overall response rate (ORR) was 86.2%. The age or number of previous therapies did not impact outcomes or tolerability. An Eastern Cooperative Oncology Group performance status (ECOG PS) score ≥ 2 and shorter time from initiation of last therapy (TILT) before ibrutinib predicted inferior PFS. Baseline characteristics had no impact on the OS except for TILT in R/R CLL patients. Drug-related adverse events (AEs) of any grade and grade ≥ 3 AEs were reported in 82.1% and 30.9% of the patients, respectively. Infections were the most common AEs (29.3%). Drug discontinuation was permanent in 43.9% of patients, mainly due to disease progression (17.1%) and toxicity (8.9%). Patients with a Cumulative Illness Rating Scale (CIRS) score ≥ 6 had a higher risk for toxicity-related discontinuation. An ECOG PS ≥ 2 predicted an increased rate of permanent discontinuation and grade ≥ 3 AEs. Conclusions: The outcomes of this study align with the results from ibrutinib clinical trials. Our study demonstrated that poor patient fitness, early relapse before ibrutinib, and permanent ibrutinib discontinuation are essential outcome determinants. Patient comorbidity burden and fitness were significant predictors for ibrutinib intolerance.

PMID:36837525 | DOI:10.3390/medicina59020324

J Clin Med. 2023 Feb 7;12(4):1320. doi: 10.3390/jcm12041320.

ABSTRACT

Adverse drug events (ADEs) and adverse drug reactions (ADRs) are leading causes of iatrogenic injury, which can result in emergency department (ED) visits or admissions to inpatient wards. The aim of this systematic review and meta-analysis was to provide up-to-date estimates of the prevalence of (preventable) drug-related ED visits and hospital admissions, as well as the type and prevalence of implicated ADRs/ADEs and drugs. A literature search of studies published between January 2012 and December 2021 was performed in PubMed, Medline, EMBASE, Cochrane Library, and Web of Science. Retrospective and prospective observational studies investigating acute admissions to EDs or inpatient wards due to ADRs or ADEs in the general population were included. Meta-analyses of prevalence rates were conducted using generalized linear mixed models (GLMM) with the random-effect method. Seventeen studies reporting ADRs and/or ADEs were eligible for inclusion. The prevalence rates of ADR- and ADE-related admissions to EDs or inpatient wards were estimated at 8.3% ([95% CI, 6.4-10.7%]) and 13.9% ([95% CI, 8.1-22.8%]), respectively, of which almost half (ADRs: 44.7% [95% CI: 28.1; 62.4]) and more than two thirds (ADEs: 71.0% [95% CI, 65.9-75.6%]) had been classified as at least possibly preventable. The ADR categories most frequently implicated in ADR-related admissions were gastrointestinal disorders, electrolyte disturbances, bleeding events, and renal and urinary disorders. Nervous system drugs were found to be the most commonly implicated drug groups, followed by cardiovascular and antithrombotic agents. Our findings demonstrate that ADR-related admissions to EDs and inpatient wards still represent a major and often preventable health care problem. In comparison to previous systematic reviews, cardiovascular and antithrombotic drugs remain common causes of drug-related admissions, while nervous system drugs appear to have become more commonly implicated. These developments may be considered in future efforts to improve medication safety in primary care.

PMID:36835854 | DOI:10.3390/jcm12041320

Int J Mol Sci. 2023 Feb 7;24(4):3345. doi: 10.3390/ijms24043345.

ABSTRACT

Duchenne Muscular Dystrophy (DMD) is a very severe X-linked dystrophinopathy. It is due to a mutation in the DMD gene and causes muscular degeneration in conjunction with several secondary co-morbidities, such cardiomyopathy and respiratory failure. DMD is characterized by a chronic inflammatory state, and corticosteroids represent the main therapy for these patients. To contradict drug-related side effects, there is need for novel and more safe therapeutic strategies. Macrophages are immune cells stringently involved in both physiological and pathological inflammatory processes. They express the CB2 receptor, one of the main elements of the endocannabinoid system, and have been proposed as an anti-inflammatory target in several inflammatory and immune diseases. We observed a lower expression of the CB2 receptor in DMD-associated macrophages, hypothesizing its involvement in the pathogenesis of this pathology. Therefore, we analyzed the effect of JWH-133, a CB2 receptor selective agonist, on DMD-associated primary macrophages. Our study describes the beneficial effect of JWH-133 in counteracting inflammation by inhibiting pro-inflammatory cytokines release and by directing macrophages' phenotype toward the M2 anti-inflammatory one.

PMID:36834757 | DOI:10.3390/ijms24043345

PLoS One. 2023 Feb 24;18(2):e0282096. doi: 10.1371/journal.pone.0282096. eCollection 2023.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) have continued to be a public health challenge with significant clinical and healthcare costs. However, little is known regarding the incidence of ADR in Ethiopia, particularly in the study setting. Thus, this study aimed to assess the incidence and patterns of ADRs in patients admitted to the University of Gondar comprehensive specialized hospital (UoGCSH).

METHODS: A prospective observational follow-up study was conducted on admitted patients at the medical ward in the UoGCSH from May to August 2022. A multifaceted approach involving daily chart review and patient interviews was employed to collect the data. A standard Naranjo ADR Probability Scale measuring tool was used to characterize the probability of existing ADR. The data was analyzed using the Statistical Package for Social Sciences (SPSS) version 25. Logistic regression analysis was employed to determine the association between the occurrence of ADRs and other variables. A p-value at the 95% confidence interval was considered statistically significant.

RESULTS: This study included 237 participants in total. The average length of follow-up was 16.4 (±5.2) days. Overall, 65 ADRs were identified, resulting an incidence rate of 27.4 (95% CI: 19.8-30.4) per 100 admissions. The most common ADRs were hypokalemia (10.7%), followed by constipation, diarrhea, hypotension, and rash (9.2% each). The majority of these ADRs (73.8%) were classified as "definite" by the Naranjo ADR probability scale. Gastrointestinal tract (GIT) (41.5%) and metabolic (18.6%) were the most frequently exposed systems for ADR. Antibiotics (26.2%) and cardiovascular medications (24.7%) were the most frequently implicated medications in existing ADRs. ADRs were significantly associated with age (p = 0.035), the presence of comorbidities (p = 0.021) and complications (p = 0.008), and receiving a higher number of medications (p = 0.04).

CONCLUSION: In this study, ADR was identified in about one-fourth of the participants. Older patients, patients with comorbidities and complications, and patients who received a higher number of medications were more likely exposed for ADRs. Healthcare providers should strictly follow the admitted patients to minimize ADRs.

PMID:36827307 | PMC:PMC9955665 | DOI:10.1371/journal.pone.0282096