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International Journal of Molecular... Mar 2023According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones... (Review)
Review
According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones monitored by the EU EWS. They have a similar structure to cathinone, principally found in Catha Edulis; they have a phenethylamine related structure but also exhibit amphetamine-like stimulant effects. Illegal laboratories regularly develop new substances and place them on the market. For this reason, during the last decade this class of substances has presented a great challenge for public health and forensic toxicologists. Acting on different systems and with various mechanisms of action, the spectrum of side effects caused by the intake of these drugs of abuse is very broad. To date, most studies have focused on the substances' cardiac effects, and very few on their associated neurotoxicity. Specifically, synthetic cathinones appear to be involved in different neurological events, including increased alertness, mild agitation, severe psychosis, hyperthermia and death. A systematic literature search in PubMed and Scopus databases according to PRISMA guidelines was performed. A total of 515 studies published from 2005 to 2022 (350 articles from PubMed and 165 from Scopus) were initially screened for eligibility. The papers excluded, according to the criteria described in the Method Section (n = 401) and after full text analyses (n = 82), were 483 in total. The remaining 76 were included in the present review, as they met fully the inclusion criteria. The present work provides a comprehensive review on neurotoxic mechanisms of synthetic cathinones highlighting intoxication cases and fatalities in humans, as well as the toxic effects on animals (in particular rats, mice and zebrafish larvae). The reviewed studies showed brain-related adverse effects, including encephalopathy, coma and convulsions, and sympathomimetic and hallucinogenic toxidromes, together with the risk of developing excited/agitated delirium syndrome and serotonin syndrome.
Topics: Mice; Rats; Humans; Animals; Synthetic Cathinone; Zebrafish; Central Nervous System Stimulants; Fever; Amphetamine; Neurotoxicity Syndromes; Psychotropic Drugs
PubMed: 37047201
DOI: 10.3390/ijms24076230 -
Pediatric Critical Care Medicine : a... May 2023Pediatric delirium (PD) is a neuropsychiatric syndrome caused by a complex interplay between predisposing factors (e.g., age, cognitive impairment), acute illness, and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Pediatric delirium (PD) is a neuropsychiatric syndrome caused by a complex interplay between predisposing factors (e.g., age, cognitive impairment), acute illness, and environmental triggers. PD is associated with substantial morbidity and mortality. The objective of this study is to systematically review and evaluate factors associated with PD in hospitalized pediatric patients.
DATA SOURCES
A systematic search of PubMed, Embase, Ovid Medline, Web- of-Science, Cochrane, CIHNAL, and Google Scholar databases was conducted for relevant studies (1990-2022).
STUDY SELECTION
We included studies that compared pediatric patients with and without delirium. Reviews, editorials, congress abstracts, or studies that did not report factors for PD were excluded. No restrictions were imposed on language.
DATA EXTRACTION
Title and abstract were independently screened by two reviewers. Individual characteristics, study design, and outcomes were independently extracted.
DATA SYNTHESIS
Categorical dichotomous data were summarized across groups using Mantel-Haenszel odds ratios (ORs) with 95% 95% CIs. Either fixed-effect or random effects models were used as indicated by the results of a heterogeneity test. Of 1,846 abstracts, 24 studies were included. We identified 54 factors studied in univariate analyses, and 27 of these were associated with PD in multivariable analyses. In pooled analyses, greater odds of PD were associated with developmental delay (OR 3.98; 95% CI 1.54-10.26), need for mechanical ventilation (OR 6.02; 95% CI 4.43-8.19), use of physical restraints (OR 4.67; 95% CI 1.82-11.96), and receipt of either benzodiazepines (OR 4.10; 95% CI 2.48-6.80), opiates (OR 2.88; 95% CI 1.89-4.37), steroids (OR 2.02; 95% CI 1.47-2.77), or vasoactive medication (OR 3.68; 95% CI 1.17-11.60).
CONCLUSIONS
In this meta-analysis, we identified seven factors associated with greater odds of developing delirium during pediatric critical illness.
Topics: Humans; Child; Benzodiazepines; Cognitive Dysfunction; Critical Illness; Delirium
PubMed: 36790201
DOI: 10.1097/PCC.0000000000003196 -
Biomedicines Feb 2022(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules.... (Review)
Review
(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules. As current knowledge on the abuse of centrally acting anticholinergics is limited, the aim of the present study is to review the relevant published data, focusing on the following molecules: benztropine, biperiden, scopolamine, orphenadrine, and benzhexol/trihexyphenidyl (THP). (2) Methods: A systematic literature review was carried out using Pubmed, Scopus, and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Research methods were registered on PROSPERO (CRD42021257293). (3) Results: A total of 48 articles, including case reports, surveys, and retrospective case series analyses, were included. Most articles focused on benzhexol/THP ( = 25), and benztropine ( = 4). The routes of administration were mostly oral, and macrodoses together concomitant illicit drugs, e.g., cocaine, have been recorded. Toxidromes included both physical (e.g., tachycardia, tachypnoea, dilatated pupils, dry skin, urinary retention, ataxia, etc.) and psychiatric symptoms (e.g., anxiety, agitation, delirium, etc.). Fatal outcomes were very rare but reported. (4) Conclusion: Results from the present study show that anticholinergic misusing issues are both widespread worldwide and popular. Considering the potential adverse effects associated, healthcare professionals should be vigilant and monitor eventual misusing issues.
PubMed: 35203563
DOI: 10.3390/biomedicines10020355 -
Critical Care (London, England) Jul 2017Subsyndromal delirium (SSD) is a frequent condition and has been commonly described as an intermediate stage between delirium and normal cognition. However, the true... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Subsyndromal delirium (SSD) is a frequent condition and has been commonly described as an intermediate stage between delirium and normal cognition. However, the true frequency of SSD and its impact on clinically relevant outcomes in the intensive care unit (ICU) remains unclear.
METHODS
We performed a systematic search in PubMed, Embase, CINAHL, Cochrane Library, and PsychINFO, with no language restrictions, up to 1 October 2016 to identify publications that evaluated SSD in ICU patients.
RESULTS
The six eligible studies were evaluated. SSD was present in 950 (36%) patients. Four studies evaluated only surgical patients. Four studies used the Intensive Care Delirium Screening Checklist (ICDSC) and two used the Confusion Assessment Method (CAM) score to diagnose SSD. The meta-analysis showed an increased hospital length of stay (LOS) in SSD patients (0.31, 0.12-0.51, p = 0.002; I = 34%). Hospital mortality was described in two studies but it was not significant (hazard ratio 0.97, 0.61-1.55, p = 0.90 and 5% vs 9%, p = 0.05). The use of antipsychotics in SSD patients to prevent delirium was evaluated in two studies but it did not modify ICU LOS (6.5 (4-8) vs 7 (4-9) days, p = 0.66 and 2 (2-3) vs 3 (2-3) days, p = 0.517) or mortality (9 (26.5%) vs 7 (20.6%), p = 0.55).
CONCLUSIONS
SSD occurs in one-third of the ICU patients and has limited impact on the outcomes. The current literature concerning SSD is composed of small-sample studies with methodological differences, impairing a clear conclusion about the association between SSD and progression to delirium or worse ICU clinical outcomes.
Topics: Adult; Checklist; Critical Illness; Decision Support Techniques; Delirium; Hospital Mortality; Humans; Intensive Care Units; Length of Stay
PubMed: 28697802
DOI: 10.1186/s13054-017-1765-3 -
Revista Latino-americana de Enfermagem 2022to estimate the prevalence and synthesize diverse evidence about the relationship between frailty and delirium in hospitalized older adults. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
to estimate the prevalence and synthesize diverse evidence about the relationship between frailty and delirium in hospitalized older adults.
METHOD
a systematic review with meta-analysis in which observational studies conducted with older adults about frailty, delirium and hospitalization, were selected without time of language restrictions. The search was conducted in the MEDLINE, EMBASE, CINAHL, Scopus, Web of Science and CENTRAL databases during August 2021. The precepts set forth by the Joanna Briggs Institute (JBI) - Evidence Synthesis Groups were followed. The meta-analysis model estimated the relative risk corresponding to the prevalence of frailty and delirium. The inverse variance method for proportions was used to estimate the prevalence values and relative risks for binary outcomes.
RESULTS
initially, 1,244 articles were identified, of which 26 were included in the meta-analysis (n=13,502 participants), with 34% prevalence of frailty (95% CI:0.26-0.42; I 2=99%; t 2=0.7618, p=0) and 21% for delirium (95% CI:0.17-0,25; I 2=95%; t 2=0.3454, p<0.01). The risk for hospitalized older adults to develop delirium was 66% (RR: 1.66; 95% CI:1.23-2.22; I2=92%; t2=0.4154; p<0.01).
CONCLUSION
34% prevalence of frailty and 21% of delirium in hospitalized older adults, with frailty being an independent risk factor for developing delirium, with an increased chance of 66% when compared to non-frail individuals.
Topics: Humans; Aged; Frailty; Frail Elderly; Hospitalization; Risk Factors; Delirium
PubMed: 36287400
DOI: 10.1590/1518-8345.6120.3687 -
Journal of Anesthesia, Analgesia and... Nov 2021Postoperative delirium is a serious complication that can occur within the 5th postoperative day. In 2017, the European Society of Anesthesiologists delivered dedicated... (Review)
Review
BACKGROUND
Postoperative delirium is a serious complication that can occur within the 5th postoperative day. In 2017, the European Society of Anesthesiologists delivered dedicated guidelines that reported the need for routine monitoring using validated scales.
OBJECTIVE
Aim of this systematic review is to identify clinical studies related to postoperative delirium that included postoperative monitoring with validated scales.
DESIGN
Systematic review METHODS: Searched keywords included the following terms: postoperative, postsurgical, post anesthesia, anesthesia recovery, delirium, and confusion. Two researchers independently screened retrieved studies using a data extraction form.
RESULTS
Literature search led to retrieve 6475 hits; of these, 260 studies (5.6% of the retrieved), published between 1987 and 2021, included in their methods a diagnostic workup with the use of a postoperative delirium validated scale and monitored patients for more than 24 h, therefore are qualified to be included in the present systematic review.
CONCLUSION
In conclusion, available clinical literature on postoperative delirium relies on a limited number of studies, that included a validated diagnostic workup based on validated scales, extracted from a large series of studies that used inconsistent diagnostic criteria. In order to extract indications based on reliable evidence-based criteria, these are the studies that should be selectively considered. The analysis of these studies can also serve to design future projects and to test clinical hypothesis with a more standardized methodological approach.
PubMed: 37386536
DOI: 10.1186/s44158-021-00021-8 -
Geriatrics (Basel, Switzerland) Sep 2016Emergency care systems are at the core of modern healthcare and are the "point-of-entry/admission" into the hospital for many older/elderly patients. Among these, it is... (Review)
Review
BACKGROUND
Emergency care systems are at the core of modern healthcare and are the "point-of-entry/admission" into the hospital for many older/elderly patients. Among these, it is estimated that 15% to 30% will have delirium on admission and that over 50% will develop it during their stay. However, appropriate delirium diagnostic and screening still remains a critical area of need. The goal of this review is to update the field, exploring target areas in screening methods for delirium in the Emergency Department (ED), and/or acute care units, in the older population.
METHODS
A systematic review was conducted to search screening/diagnostic methods for delirium in the ED and/or acute care units within the ED.
RESULTS
Seven different scales were identified. Of the identified instruments, the Confusion Assessment Method (CAM) for the Intense Care Unit (CAM-ICU) was the most widely used. Of note, a brief two-step approach for delirium surveillance was defined with the Delirium Triage Screen (DTS) and the Brief Confusion Assessment Method (bCAM), and the diagnostic accuracy of the Richmond Agitation-Sedation Scale (RASS) for delirium had a good sensitivity and specificity in older patients.
CONCLUSION
The CAM-ICU appears as the potential reference standard for use in the ED, but research in a global approach of evaluation of actual and past cognitive changes is still warranted.
PubMed: 31022815
DOI: 10.3390/geriatrics1030022 -
Relationship of sleep disturbance and postoperative delirium: a systematic review and meta-analysis.Gland Surgery Jul 2022Studies have investigated the relationship between sleep disturbance and postoperative delirium (PD) but have controversial results. A systematic review and...
BACKGROUND
Studies have investigated the relationship between sleep disturbance and postoperative delirium (PD) but have controversial results. A systematic review and meta-analysis have a high level of evidence to comprehensively evaluate the effect of sleep disturbance on PD. Our study aims to provide available evidence regarding the effect of sleep disturbance on PD.
METHODS
PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant studies from database inception to April 28, 2021. The eligible studies were identified according to the "PICOS" principles. Odds ratio (OR) was used to indicate the effect index, and 95% confidence interval (CI) was applied to express the effect size. The heterogeneity was tested. Subgroup analyses, meta-regression, and sensitivity analysis were also applied. Begg's test was used to test potential publication bias. The modified Newcastle-Ottawa Scale (NOS) was used to evaluate the literature quality.
RESULTS
Totally, 18 articles including 2,714 patients were enrolled, with most of the included literature being of moderate to high quality. The results of systematic and meta-analysis suggested that sleep disturbance was associated with an increased risk of PD (OR: 3.731; 95% CI: 2.338 to 5.956). Subgroup analysis results demonstrated that sleep disturbance in patients aged <65 years (OR: 6.072; 95% CI: 3.054 to 12.071), aged ≥65 years (OR: 2.904; 95% CI: 1.487 to 5.671), and undergoing cardiac (OR: 3.390; 95% CI: 1.359 to 8.453), orthopedic (OR: 3.943; 95% CI: 2.219 to 7.008), or other surgeries (OR: 4.963; 95% CI: 2.156 to 11.420) increased the risk of PD (all P<0.005). Moreover, increased risk of PD was found for both preoperative (OR: 2.804; 95% CI: 1.517 to 5.184) and postoperative (OR: 6.302; 95% CI: 3.794 to 10.467) sleep disturbance (all P<0.005). No associations between obstructive sleep apnea (OSA; OR: 2.008; 95% CI: 0.753 to 5.354; P=0.164), insomnia (OR: 4.005; 95% CI: 0.636 to 25.203; P=0.139) and risk of PD were observed.
CONCLUSIONS
Our study indicated the relationship between sleep disturbance and the risk of PD. Patients undergoing surgical treatments should pay attention to their sleep quality. However, more research is needed to confirm its relationship.
PubMed: 35935571
DOI: 10.21037/gs-22-312 -
Cureus Jun 2022Delirium is defined by the DSM-5 as a fluctuating course of disturbance in attention, cognition, and awareness that develops over a short period without any... (Review)
Review
Delirium is defined by the DSM-5 as a fluctuating course of disturbance in attention, cognition, and awareness that develops over a short period without any pre-existing neurocognitive disorder. As people age, there is an increased risk of complications that may occur following a surgical procedure and one such acute complication is delirium. Studies are emerging to reduce the incidence of postoperative delirium, and one such preventive measures implemented in recent years include the administration of dexmedetomidine, a high selectivity α-2 adrenoceptor agonist. This study aims to review the efficacy of Dexmedetomidine in the prevention of postoperative delirium in randomized controlled trials in patients older than 18 years of age. The literature was explored in three online databases, namely, PubMed, Science Direct, and Scopus. Appropriate keywords and MesH terms were employed to scrutinize relevant articles that demonstrated the effects of dexmedetomidine in the prevention of postoperative delirium. The data was restricted to randomized controlled trials and clinical trials published from 2017 to 2021 in human patients older than >18 years of age undergoing non-cardiac-related procedures. The randomized clinical trials were critically assessed with the Cochrane risk of bias tool. We proceeded to screen 428 records with the assessment of the PRISMA chart and filtered out 420 papers to obtain a total of eight studies where we identified data such as sample size, types of surgeries in which the patients were involved, the delirium assessment tool, the plan of the administration of dexmedetomidine and the outcomes evaluated in each study. The Confusion Assessment Method (CAM) was the prevailing assessment tool used with the sole purpose to evaluate the incidence of postoperative delirium as the primary outcome, and assessment of inflammatory cytokines, sleep quality, and pain scales were considered as secondary outcomes. The dosage of dexmedetomidine varied among studies, and it displayed varying impacts on postoperative delirium and the secondary outcomes as well. Limitations include varying ages and ethnicities of the population. It was concluded that dexmedetomidine prevents the development of postoperative delirium in elderly patients undergoing non-cardiac surgical interventions by modulating important predisposing factors such as neuroinflammation, pain, and sleep quality. No funding was made for this study.
PubMed: 35812638
DOI: 10.7759/cureus.25639 -
Journal of the American Geriatrics... Jan 2021To identify whether delirium biomarkers aligned with the National Institute on Aging-Alzheimer's Association (NIA-AA) research framework, a conceptual model that...
OBJECTIVES
To identify whether delirium biomarkers aligned with the National Institute on Aging-Alzheimer's Association (NIA-AA) research framework, a conceptual model that describes the use of diagnostic biomarkers for Alzheimer's disease and other related dementias (ADRD).
DESIGN
Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
SETTING
Acute care and outpatient settings.
PARTICIPANTS
Adults diagnosed with delirium.
METHODS AND MEASUREMENTS
MEDLINE, PsycInfo, Embase, and the Cochrane Library were searched for English-language studies published from January 2010 to February 2020. Studies included adults older than 18 years, identified delirium with a standardized assessment tool, and measured an ADRD biomarker. Independent reviewers determined whether an association between delirium and ADRD biomarker was found, the quality of biomarker data based on the REMARK (REporting recommendations for tumor MARKer prognostic studies) checklist, and the study bias based on the Newcastle-Ottawa Scale.
RESULTS
A total of 61,256 citations were identified; 113 studies were included. Most studies did not examine amyloid, tau, or neurodegeneration biomarkers. Delirium may be associated with neurodegeneration biomarkers, but few to no studies found an association with amyloid and tau biomarkers. Delirium was not consistently associated with inflammatory biomarkers. The quality of biomarker data was moderate, and the risk of bias was moderate to high. Studies often did not collect prehospital and posthospital cognitive data.
CONCLUSION
Most delirium diagnostic biomarker studies did not measure amyloid, tau, and/or neurodegenerative biomarkers, making characterization of the relationship between delirium and ADRD difficult. Future delirium biomarker diagnostic studies could improve the understanding of pathophysiologic links between delirium with other conditions affecting cognition.
Topics: Amyloid beta-Peptides; Biomarkers; Delirium; Humans; National Institute on Aging (U.S.); Research; United States; tau Proteins
PubMed: 32975827
DOI: 10.1111/jgs.16836