Association of Pharmacist Interventions With Adverse Drug Events and Potential Adverse Drug Events.

BACKGROUND: Adverse drug events (ADEs) are a frequent cause of injury in patients. Our aim was to assess whether pharmacist interventions compared with no pharmacist intervention results in reduced ADEs and potential adverse drug events (PADEs). METHODS: We searched MEDLINE, Embase, and two other databases through September 19, 2022 for any RCT assessing the effect of a pharmacist intervention compared with no pharmacist intervention and reporting on ADEs or PADEs. The risk of bias was assessed using the Cochrane tool for RCTs. A random-effects model was used to pool summary results from individual RCTs. RESULTS: Fifteen RCTs met the inclusion criteria. The pooled results showed a statistically significant reduction in ADE associated with pharmacist intervention compared with no pharmacist intervention (RR = 0.86; [95% CI 0.80-0.94]; p = 0.0005) but not for PADEs (RR = 0.79; [95% CI 0.47-1.32]; p = 0.37). The heterogeneity was insignificant (I2 = 0%) for ADEs and substantial (I2 = 77%) for PADEs. Patients receiving a pharmacist intervention were 14% less likely for ADE than those who did not receive a pharmacist intervention. The estimated number of patients needed to prevent one ADE across all patient locations was 33. CONCLUSIONS: To our knowledge, this is the first systematic review and meta-analysis of RCTs seeking to understand the association of pharmacist interventions with ADEs and PADEs. The risk of having an ADE is reduced by a seventh for patients receiving a pharmacist care intervention versus no such intervention. The estimated number of patients needed to be followed across all patient locations to prevent one preventable ADE across all patient locations is 33.

bioTCIs: Middle-to-Macro Biomolecular Targeted Covalent Inhibitors Possessing Both Semi-Permanent Drug Action and Stringent Target Specificity as Potential Antibody Replacements.

Monoclonal antibody therapies targeting immuno-modulatory targets such as checkpoint proteins, chemokines, and cytokines have made significant impact in several areas, including cancer, inflammatory disease, and infection. However, antibodies are complex biologics with well-known limitations, including high cost for development and production, immunogenicity, a limited shelf-life because of aggregation, denaturation, and fragmentation of the large protein. Drug modalities such as peptides and nucleic acid aptamers showing high-affinity and highly selective interaction with the target protein have been proposed alternatives to therapeutic antibodies. The fundamental limitation of short in vivo half-life has prevented the wide acceptance of these alternatives. Covalent drugs, also known as targeted covalent inhibitors (TCIs), form permanent bonds to target proteins and, in theory, eternally exert the drug action, circumventing the pharmacokinetic limitation of other antibody alternatives. The TCI drug platform, too, has been slow in gaining acceptance because of its potential prolonged side-effect from off-target covalent binding. To avoid the potential risks of irreversible adverse drug effects from off-target conjugation, the TCI modality is broadening from the conventional small molecules to larger biomolecules possessing desirable properties (e.g., hydrolysis resistance, drug-action reversal, unique pharmacokinetics, stringent target specificity, and inhibition of protein-protein interactions). Here, we review the historical development of the TCI made of bio-oligomers/polymers (i.e., peptide-, protein-, or nucleic-acid-type) obtained by rational design and combinatorial screening. The structural optimization of the reactive warheads and incorporation into the targeted biomolecules enabling a highly selective covalent interaction between the TCI and the target protein is discussed. Through this review, we hope to highlight the middle to macro-molecular TCI platform as a realistic replacement for the antibody.

Relative Nuclease Resistance of a DNA Aptamer Covalently Conjugated to a Target Protein.

A major obstacle to the therapeutic application of an aptamer is its susceptibility to nuclease digestion. Here, we confirmed the acquisition of relative nuclease resistance of a DNA-type thrombin binding aptamer with a warhead (TBA3) by covalent binding to a target protein in the presence of serum/various nucleases. When the thrombin-inhibitory activity of TBA3 on thrombin was reversed by the addition of the complementary strand, the aptamer was instantly degraded by the nucleases, showing that the properly folded/bound aptamer conferred the resistance. Covalently binding aptamers possessing both a prolonged drug effect and relative nuclease resistance would be beneficial for in vivo translational applications.

The psychometric properties of the adolescent dissociative experiences scale (A-DES) in a sample of Portuguese at-risk adolescents.

Dissociation is a process that often occurs as a sequela of psychological trauma, and it is interrelated with psychological and behavioral problems. In the at-risk adolescent population, dissociation is often underdiagnosed and undertreated. Having reliable measures to assess this phenomenon can help in identifying adolescents at-risk and improve treatment outcomes. This study assessed the psychometric properties of the Adolescent Dissociative Experiences Scale (A-DES) with a sample of 402 Portuguese adolescents recruited from three at-risk populations. Participants completed self-report measures of trauma exposure, posttraumatic symptoms, psychological and behavioral problems, and the A-DES. A subset of the sample also completed test-retest measures. Confirmatory factor analyses revealed a best-fitting 3-factor model. Analyses revealed good internal consistencies and good agreement test-retest reliability for the scale overall and the factor-based sub-scales. Construct and predictive validity was supported with results showing that A-DES discriminates between youth reporting high versus low levels of cumulative trauma exposure and youth who meet or do not meet criteria for a probable PTSD diagnosis. Study findings replicate prior research supporting a 3-factor model of dissociation and the usefulness of A-DES to identify adolescents with dissociative symptoms. Clinical and research implications are discussed.

Comparative assessment of manual chart review and ICD claims data in evaluating immunotherapy-related adverse events.

BACKGROUND: The aim of this retrospective study was to demonstrate that irAEs, specifically gastrointestinal and pulmonary, examined through International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs, thereby concluding that ICD claims data are a poor approach to electronic health record (EHR) data mining for irAEs in immunotherapy clinical research. METHODS: This retrospective analysis was conducted in 1,063 cancer patients who received ICIs between 2011 and 2017. We identified irAEs by manual review of medical records to determine the incidence of each of our endpoints, namely colitis, hepatitis, pneumonitis, other irAE, or no irAE. We then performed a secondary analysis utilizing ICD claims data alone using a broad range of symptom and disease-specific ICD codes representative of irAEs. RESULTS: 16% (n = 174/1,063) of the total study population was initially found to have either pneumonitis 3% (n = 37), colitis 7% (n = 81) or hepatitis 5% (n = 56) on manual review. Of these patients, 46% (n = 80/174) did not have ICD code evidence in the EHR reflecting their irAE. Of the total patients not found to have any irAEs during manual review, 61% (n = 459/748) of patients had ICD codes suggestive of possible irAE, yet were not identified as having an irAE during manual review. DISCUSSION: Examining gastrointestinal and pulmonary irAEs through the International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs.

Prevalence of potentially harmful multidrug interactions on medication lists of elderly ambulatory patients.

BACKGROUND: It has been hypothesized that polypharmacy may increase the frequency of multidrug interactions (MDIs) where one drug interacts with two or more other drugs, amplifying the risk of associated adverse drug events (ADEs). The main objective of this study was to determine the prevalence of MDIs in medication lists of elderly ambulatory patients and to identify the medications most commonly involved in MDIs that amplify the risk of ADEs. METHODS: Medication lists stored in the electronic health record (EHR) of 6,545 outpatients ≥60 years old were extracted from the enterprise data warehouse. Network analysis identified patients with three or more interacting medications from their medication lists. Potentially harmful interactions were identified from the enterprise drug-drug interaction alerting system. MDIs were considered to amplify the risk if interactions could increase the probability of ADEs. RESULTS: MDIs were identified in 1.3 % of the medication lists, the majority of which involved three interacting drugs (75.6 %) while the remainder involved four (15.6 %) or five or more (8.9 %) interacting drugs. The average number of medications on the lists was 3.1 ± 2.3 in patients with no drug interactions and 8.6 ± 3.4 in patients with MDIs. The prevalence of MDIs on medication lists was greater than 10 % in patients prescribed bupropion, tramadol, trazodone, cyclobenzaprine, fluoxetine, ondansetron, or quetiapine and greater than 20 % in patients prescribed amiodarone or methotrexate. All MDIs were potentially risk-amplifying due to pharmacodynamic interactions, where three or more medications were associated with the same ADE, or pharmacokinetic, where two or more drugs reduced the metabolism of a third drug. The most common drugs involved in MDIs were psychotropic, comprising 35.1 % of all drugs involved. The most common serious potential ADEs associated with the interactions were serotonin syndrome, seizures, prolonged QT interval and bleeding. CONCLUSIONS: An identifiable number of medications, the majority of which are psychotropic, may be involved in MDIs in elderly ambulatory patients which may amplify the risk of serious ADEs. To mitigate the risk, providers will need to pay special attention to the overlapping drug-drug interactions which result in MDIs.

A Network Analysis to Identify Associations between PTSD and Dissociation among Teenagers.

We conducted a network analysis of measures of dissociation and posttraumatic symptoms (PTS) with a varied sample of adolescents (N = 312), some of them previously exposed to war scenarios. The global measure of dissociation (A-DES) was uniquely linked to the arousal PTS symptom cluster (CRIES-13), in particular sleep problems, but not to the reexperiencing and avoidance clusters. Three of four (i.e., depersonalization/derealization, amnesia, mental partition/compartmentalization) dissociation clusters were uniquely linked to PTS severity, but not absorption. The results with the pooled groups were generally representative of both groups. The DP/DR relation to PTS was based on data from both samples, whereas the link between amnesia and partition/parts might have been driven by the normative group, although the refugee sample had significantly higher scores in those variables. The results replicate some previous findings with adult samples and suggest new paths for research and theory.

Detecting high-quality signals of adverse drug-drug interactions from spontaneous reporting data.

As a medicine safety issue, Drug-Drug Interaction (DDI) may become an unexpected threat for causing Adverse Drug Events (ADEs). There is a growing demand for computational methods to efficiently and effectively analyse large-scale data to detect signals of Adverse Drug-drug Interactions (ADDIs). In this paper, we aim to detect high-quality signals of ADDIs which are non-spurious and non-redundant. We propose a new method which employs the framework of Bayesian network to infer the direct associations between the target ADE and medicines, and uses domain knowledge to facilitate the learning of Bayesian network structures. To improve efficiency and avoid redundancy, we design a level-wise algorithm with pruning strategy to search for high-quality ADDI signals. We have applied the proposed method to the United States Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) data. The result shows that 54.45% of detected signals are verified as known DDIs and 10.89% were evaluated as high-quality ADDI signals, demonstrating that the proposed method could be a promising tool for ADDI signal detection.

How do pediatric patients perceive adverse drug events of anticonvulsant drugs? A survey.

Anticonvulsant drugs have a high risk of adverse drug events. Little is known about the perception of those events by pediatric patients. We performed a survey in the neuropediatric departments of two university hospitals. Using a questionnaire, we interviewed patients aged 6-18 years with current anticonvulsant treatment regarding (i) their fears about potential adverse drug events, (ii) experienced adverse drug events, and (iii) perceived burden of experienced adverse drug events. One hundred patients took part in the interview. (i) 40 (40%) expressed fears that the medication could harm them. Eighteen of 40 (45%) named fears concerning specific adverse drug events. Of those, 12/18 (67%) feared neurologic or psychiatric symptoms. (ii) 37 (37%) of children described altogether 60 experienced adverse drug events. Of those, 38 (63%) concerned neurologic or psychiatric symptoms. (iii) 32/37 (82%) children who experienced adverse drug events felt bothered by the experienced event. Among others, they described an emotional burden (11/37, 30%), and restrictions in school performance (8/37, 22%) and favorite leisure activities (4/37, 11%).Conclusion: School-aged children are well able to describe adverse drug events of their anticonvulsant medication. Almost two thirds of the described events concern neurologic or psychiatric symptoms that cause an emotional burden and restrictions according to the patients. What is Known: • Anticonvulsants have a high potential of adverse drug events. • In an earlier survey, parents expressed fears of severe adverse drug events such as liver failure, which seldom occur, and reported a high number of neurological and psychological adverse drug events. What is New: • Many children fear that their anticonvulsants could harm them, and they fear and experience neurological and psychological adverse drug events. • According to the children, adverse drug events cause an emotional burden and restrictions in school performance and favorite leisure activities.

A cross-sectional study: medication safety among cancer in-patients in tertiary care hospitals in KPK, Pakistan.

BACKGROUND: Medication safety in cancer patients receiving complex medication regimens is an important problem in various settings. Medication related events, interceptions and interventions are not well described in this area. We intended to study incidence, types, settings and stages involved, root cause analysis, medication classes involved and the level of harm cause by medication errors in two hospitals providing oncology services comparatively. The severity of incidents and interventions are studied. METHODS: It was a prospective cross sectional study among cancer in-patients of two tertiary care hospitals of KPK. Scale by NCC-MERP was used for evaluation of all medication related incidents. The data obtained was analyzed by IBM SPSS statistics 22 with 95% confidence interval and used the same for other descriptive statistics. RESULTS: All medication orders were reviewed at both sites (Computerized Prescription Order Entry and HWP systems). Potential ADEs incidence was found high at site 2 (97.5%) while medication errors without harm was high at site 1 (97.5%). Most events occur at prescribing level 87.6 and 81.7% at both sites 1 and 2. Types highly reported involved improper dose 31.4 and 15.5%, monitoring error 14.6 and 15.2% at site 1 and 2. Medications involved in these incidents were antibiotics 44 and 12.7%, antiemetic 7.5 and 15.8% and antineoplastic 2.9 and 9.4% at site 1 and 2. Severity of 3.6 and 36.5% incidents had potential to cause harm at site 1 and 2. Root causes were human factors 62.6 and 72.3%, drug selection 33.6 and 38.8%, and dose selection 39.6 and 15.3% at sites 1 and 2. Contributing factors including staff training 33.6 and 24.3%, system for covering patient care 14.9 and 36.6%, communication system 2.4 and 20.3%, interruptions 9.7 and 7.3% and others 78.8 and 68.6% were highly reported. Preventability of medication errors was 99% at both sites. Intervention was taken in 90.5% events at site 1 (CPOE system) while the incidence lowest at site 2 (HWP system). CONCLUSION: Medication related events are high among cancer in-patients at the site lacking updated electronic system for medication prescribing. Proper training about medication safety, reporting and interventions are required.

Clinically relevant drug-drug interactions among elderly people with dementia.

PURPOSE: Increased numbers of drugs and changes in pharmacokinetic and pharmacodynamic parameters among elderly people contribute to increased prevalence of adverse drug reactions. Drug-drug interactions (DDIs) are an important reason for admission to hospital and elderly people with dementia are particularly vulnerable. The aims of the present study were to assess the occurrence and characteristics of clinically relevant DDIs and to investigate potential risk factors associated with DDIs among elderly people with dementia. METHODS: People ≥ 65 years with dementia, admitted to two hospitals in Northern Sweden, were included. The medical records of 458 patients were reviewed. Clinically relevant DDIs were identified using the Janusmed interactions database. Pharmacological classification was conducted using Stockley's classification system. RESULTS: A total of 401 DDIs were identified among 43.2% of the study population, of which 98.5% had interactions that may require dose adjustment and 7.6% had drug combinations that should be avoided. Pharmacodynamic interactions were most common, of which furosemide-citalopram (n = 35) were most frequently observed. Omeprazol-citalopram (n = 25) was the most common drug combination among pharmacokinetic interactions. Citalopram and warfarin were the most commonly involved drug substances. An association was found between a higher number of medications being prescribed and having at least one DDI. CONCLUSION: Clinically relevant drug-drug interactions are prevalent among elderly people with dementia living in Northern Sweden. Drug-drug interactions should be identified in order to manage and prevent adverse outcomes. This is particularly important among this group of people especially when multiple medications are being prescribed.

A data-driven method to detect adverse drug events from prescription data.

Drug safety issues such as Adverse Drug Events (ADEs) can cause serious consequences for the public. The clinical trials that are undertaken to assess medicine efficacy and safety prior to marketing, generally, may provide sufficient samples for discovering common ADEs. However, more samples are needed to detect infrequent and rare events. Additionally, clinical trials may not include all subgroups of patients. For these reasons, post-marketing surveillance of medicines is necessary for identifying drug safety issues. Most regulatory agencies use the Spontaneous Reporting Systems to identify associations between medicines and suspected ADEs. Data mining with effective analytical frameworks and large-scale medical data is potentially an alternative method to discover and monitor ADEs. In the present paper, we aim to detect potential ADEs from prescription data by discovering ADE associated prescription sequences. In an ADE associated prescription sequence 〈Dp→Ds〉, the prior medicine Dp leads to an ADE for which the succeeding medicine Ds is dispensed to treat. We propose a data-driven method which integrates (1) a constrained sequential pattern mining to uncover prescription sequences as potential signals of ADEs, (2) domain constraints to eliminate interference signals and (3) an adapted Self-Controlled Case Series model to evaluate the potential signals of ADEs. Despite ample prior works using Electronic Health Records (EHRs), our method utilises pure prescription data which does not contain additional information, e.g. symptoms or diagnoses as included in EHRs. To assess the performance of the proposed method, we apply it to a real-world dataset from the Pharmaceutical Benefits Scheme of Australia. The dataset contains over 50 million records covering approximately 2 million patients. The results demonstrate the effectiveness of our method in identifying both known ADEs and unknown yet suspicious ADEs with limited detection of false positive signals. Comparing to a recognised gold standard, our method successfully detects 67.4% of the positive adverse events while only 8.78% false positives exist.

AdeR-AdeS mutations & overexpression of the AdeABC efflux system in ciprofloxacin-resistant Acinetobacter baumannii clinical isolates.

Background & objectives: : Overexpression of efflux pumps is a cause of acquired resistance to fluoroquinolones in Acinetobacter baumannii. The present study was done to investigate the presence and overexpression of AdeABC efflux system and to analyze the sequences of AdeR-AdeS regulatory system in ciprofloxacin-resistant A. baumannii isolates. Methods: : Susceptibility of 50 clinical A. baumannii isolates to ciprofloxacin, imipenem, ceftazidime, cefepime and gentamicin antimicrobials was evaluated by agar dilution method. Isolates were screened for the evidence of active efflux pump. Isolates were also examined for adeR-adeS and adeB efflux genes by polymerase chain reaction (PCR). The adeR and adeS regulatory genes were sequenced to detect amino acid substitutions. Expression of adeB was evaluated by quantitative reverse-transcriptase PCR. Results: : There were high rates of resistance to ciprofloxacin (88%), ceftazidime (88%), cefepime (74%) and imipenem (72%) and less resistance rate to gentamicin (64%). Phenotypic assay showed involvement of active efflux in decreased susceptibility to ciprofloxacin among 16 isolates. The 12.27-fold increase and 4.25-fold increase were found in adeB expression in ciprofloxacin-full-resistant and ciprofloxacin-intermediate-resistant isolates, respectively. Several effective mutations, including A91V, A136V, L192R, A94V, G103D and G186V, were detected in some domains of AdeR-AdeS regulators in the overexpressed ciprofloxacin-resistant isolates. Interpretation & conclusions: The results of this study indicated that overexpression of the AdeABC efflux pump was important to reduce susceptibility to ciprofloxacin and cefepime in A. baumannii that, in turn, could be triggered by alterations in the AdeR-AdeS two-component system. However, gene expression alone does not seem adequate to explain multidrug resistance phenomenon. These results could help plan improved active efflux pump inhibitors.

Post-marketing safety surveillance and re-evaluation of Xueshuantong injection.

BACKGROUND: Traditional Chinese medicine injections (TCMIs) have been widely used to treat severe and acute diseases due to their high bioavailability, accurate curative effect, and rapid effect. However, incidence rates of adverse drug reactions (ADRs) of TCMIs have also increased in recent years. Xueshuantong injection (XSTI) is a commonly-used TCMI comprised of Panax notoginseng total sapiens for the treatment of stroke hemiplegia, chest pain, and central retinal vein occlusion. Its safety remains uncelar. Therefore, post-marketing safety of XSTI was studied in this research. METHODS: In present study, post-marketing safety surveillance and re-evaluation of XSTI were reported. Thirty thousand eight hundred eighty-four patients in 33 hospitals from 7 provinces participated in this study. Incidence rate, most common clinical manifestations, types, severity, occurrence time, and disposal of ADRs were calculated. RESULTS: Incidence rate of ADR of XSTI was 4.14‰ and the most common clinical manifestations were skin and its appendages damage. Type A accounts for 95.49% of ADRs of XSTI and most of them (41.41%) were occurred within 24 h after receiving XSTI treatment. Severities of most ADRs of XSTI were moderate reactions (86.72%). Main disposition of ADRs of XSTI was drug withdrawal and symptomatic treatment (54.69%). CONCLUSIONS: Our data provide basis for improvement of instructions of XSTI and clinical safety of XSTI. Post-marketing surveillance of TCMIs in this study is a powerful tool to identify types and manifestations of ADRs to improve safety and effectiveness of drugs in clinical applications. TRIAL REGISTRATION: This protocol has international registration in China clinical trial registration center ( ChiCTR~OPC~ 14,005,718 ) at December 22, 2014.

Pattern Of Presentation Among Adults Hospitalized With Dengue Disease.

BACKGROUND: Dengue is a mosquito born viral infection that has rapidly spread in the world particularly in Southeast Asia. The aim of this hospital based study was to see the demographic, clinical and laboratory characteristics in adults with dengue infection in Hazara region of Northern Pakistan. METHODS: This is a descriptive study. Clinical, laboratory and demographic information were collected from adult patients with suspected dengue infection (n=100) and then managed in one of medical units of tertiary care hospital in Abbottabad from August to October 2015. RESULTS: Total number of patients was 100, 78 were male and 22 were female. 49 patients were in age group from 21 to 40 years. Most patients were from Mansehra district (69), followed by Haripur (11), Abbottabad (11), Battagram (06) and Kohistan (03). Common clinical features were fever (100%), body aches (95%), headache (94%), chills (87%), and anorexia (86%), haemorrhagic tendencies (12%), rash (05%), and sore throat (03%). Thrombocytopenia was observed in 98%, leucopoenia in 25%, high Aminotransferases (ALT) in 67%, Ns1 antigen positive 66%, negative 18% and unknown 16%. IgM Antibodies against Dengue Virus was positive 67%, negative 19% and were unknown in 14%, IgG antibodies positive in 54%, negative 32% and were unknown in 14%. CONCLUSIONS: We concluded in our study that presentation of dengue infection is same as in other Southeast Asian countries; however, the disease is more prevalent in cities located on plain than hilly areas.

Prescription of potentially inappropriate medication in Korean older adults based on 2012 Beers Criteria: a cross-sectional population based study.

BACKGROUND: A high number of elderly people with multiple comorbidities are exposed to the risk of polypharmacy and prescription of potentially inappropriate medication (PIM). The purpose of this study was to determine the prevalence and patterns of PIM prescription in Korean older adults according to the 2012 Beers Criteria. METHODS: A retrospective study was conducted using data from the Korean Health Insurance Review and Assessment (KHIRA) database of outpatient prescription claims collected from January 1, 2009 to December 31, 2011. A total of 523,811 elderly subjects aged 65 years and older were included in the study, and several covariates related to the prescription of PIMs were obtained from the KHIRA database. These covariates were analyzed using Student's t test and the chi-square test; furthermore, multivariate logistic regression analysis was used to evaluate the risk factors associated with the prescription of PIMs. RESULTS: A total of 80.96 % subjects were prescribed at least one PIM independent of their diagnosis or condition according to the 2012 Beers Criteria. The most commonly prescribed medication class was first-generation antihistamines with anticholinergic properties (52.33 %). Pain medications (43.04 %) and benzodiazepines (42.53 %) were next in line. When considering subjects' diagnoses or conditions, subjects diagnosed with central nervous system conditions were most often prescribed PIMs. Female sex, severity of comorbidities, and polypharmacy were significant risk factors for PIM prescriptions. CONCLUSIONS: This study confirmed that PIM prescription is common among elderly Koreans. A clinical decision support system should be developed to decrease the prevalence of PIM prescriptions.

Validation of the Italian version of the dissociative experience scale for adolescents and young adults.

BACKGROUND: The Dissociative Experience Scale for adolescent (A-DES), a 30-item, multidimensional, self-administered questionnaire, was validated using a large sample of American young people sample. We reported the linguistic validation process and the metric validity of the Italian version of A-DES in the Italy. METHODS: A set of questionnaires was provided to a total of 633 participants from March 2015 to April 2016. The participants consisted of 282 boys and 351 girls, and their average age was between 18 and 24 years old. The translation process consisted of two consecutive steps: forward-backward translation and acceptability testing. The psychometric testing was applied to Italian students who were recruited from the Italian Public Schools and Universities in Sicily. Informed consent was obtained from all participants at the research. All individuals completed the A-DES. Reliability and validity were tested. RESULTS: The translated version was validated on a total of 633 Italian students. The reliability of A-DES total is .926. It is composed by 4 subscales: Dissociative amnesia, Absorption and imaginative involvement, Depersonalization and derealization, and Passive influence. The reliability of each subscale is: .756 for dissociative amnesia, .659 for absorption and imaginative involvement, .850 for depersonalization and derealization, and .743 for passive influence. CONCLUSIONS: The Italian version of the A-DES constitutes a useful instrument to measure dissociative experience in adolescents and young adults in Italy.

Psychometric properties of the Adolescent Dissociative Experiences Scale in a sample of Italian adolescents.

The purpose of this study was to examine the psychometric properties of the Italian translation of the Adolescent Dissociative Experiences Scale (A-DES). A sample of 1,806 high-school students between the ages of 13 and 18 years, recruited in 6 Italian cities, completed the A-DES. The A-DES showed high internal consistency, excellent item-to-scale homogeneity, good split-half reliability, and a single-factor structure. The scores of the Italian adolescents were comparable to those found in previous research with the measure. No gender differences were found in mean A-DES scores, but boys and girls showed different patterns of responses on A-DES items. Age differences were also found, with 13- and 18-year-old students scoring higher on the measure than the other participants. A cluster analysis showed that participants could be consistently grouped into 2 clusters of low- and high-dissociative adolescents. This study supports the A-DES as a reliable and valid screening measure for dissociative symptoms in adolescents.

Risk of drug-induced delirium in older patients- a pharmacovigilance study of FDA adverse event reporting system database.

BACKGROUND: Drug-induced delirium is known risk factors associated with increased morbidity and mortality in older patients. The objective was to evaluate the risk of drug-related delirium in older patients based on the FDA Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: Delirium reports in older patients (age ≥65) extracted from the FAERS database using Open Vigil 2.1. The reported odds ratio and the proportional reported ratio were calculated to detect the adverse reaction signal of delirium. Combined with published evidence, suspected drugs were categorized as known, possible, or new potential delirium-risk-increasing drugs. RESULTS: Of the 130,885 reports (including 28,850 delirium events and 1,857 drugs) analyzed for this study, 314 positive signal drugs were detected. Positive signal drugs are mainly concentrated on the drug of nervous system, cardiovascular system , alimentary tract and metabolism and anti-infectives for systemic use. Of the positive signal drugs, 26.11% (82/314) were known delirium-risk increasing drugs, 44.90% (141/314) were possible and 28.98% (91/314) were new potential. CONCLUSION: Drug-induced delirium risk is prevalent in older patients, according to the FAERS. The risk level of drug-induced delirium should be taken into account to optimize drug therapy in clinical practice.

A new diagnostic tool for brain disorders: extracellular vesicles derived from neuron, astrocyte, and oligodendrocyte.

Brain disorders are the leading cause of disability worldwide, affecting people's quality of life and causing economic burdens. The current clinical diagnosis of brain disorders relies solely on individual phenotypes and lacks accurate molecular biomarkers. An emerging field of research centers around extracellular vesicles (EVs), nanoscale membrane vesicles which can easily cross the blood-brain barrier. EVs in the blood are derived from various tissues, including the brain. Therefore, purifying central nervous system (CNS)-derived EVs from the blood and analyzing their contents may be a relatively non-invasive way to analyze brain molecular alterations and identify biomarkers in brain disorders. Recently, methods for capturing neuron-derived EVs (NDEs), astrocyte-derived EVs (ADEs), and oligodendrocyte-derived EVs (ODEs) in peripheral blood were reported. In this article, we provide an overview of the research history of EVs in the blood, specifically focusing on biomarker findings in six major brain disorders (Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, depression, and autism spectrum disorder). Additionally, we discuss the methodology employed for testing CNS-derived EVs. Among brain disorders, Alzheimer's disease has received the most extensive attention in EV research to date. Most studies focus on specific molecules, candidate proteins, or miRNAs. Notably, the most studied molecules implicated in the pathology of these diseases, such as Aß, tau, and α-synuclein, exhibit good reproducibility. These findings suggest that CNS-derived EVs can serve as valuable tools for observing brain molecular changes minimally invasively. However, further analysis is necessary to understand the cargo composition of these EVs and improve isolation methods. Therefore, research efforts should prioritize the analysis of CNS-derived EVs' origin and genome-wide biomarker discovery studies.