Central Nervous System Medications Research Articles

Factors influencing central nervous system medication deprescribing and behavior change in hospitalized older adults.

Central nervous system (CNS) medications are linked to higher morbidity and mortality in older adults. Hospitalization allows for deprescribing opportunities. This qualitative study investigates clinician and patient perspectives on CNS medication deprescribing during hospitalization using a behavioral change framework, aiming to inform interventions and identify recommendations to enhance hospital deprescribing processes. This qualitative study focused on hospitalists, primary care providers, pharmacists, and patients aged ≥60 years hospitalized on a general medicine service and prescribed ≥1 CNS medications. Using semi-structured interviews and focus groups, we aimed to evaluate patient medication knowledge, prior deprescribing experiences, and decision-making preferences, as well as provider processes and tools for medication evaluation and deprescribing. Rapid qualitative analysis applying the Capability, Opportunity, Motivation, and Behavior (COM-B) framework revealed themes influencing deprescribing behavior in patients and providers. A total of 52 participants (20 patients and 32 providers) identified facilitators and barriers across deprescribing steps and generated recommended strategies to address them. Clinicians and patients highlighted the opportunity for CNS medication deprescribing during hospitalizations, facilitated by multidisciplinary teams enhancing clinicians' capability to make medication changes. Both groups also stressed the importance of intensive patient engagement, education, and monitoring during hospitalizations, acknowledging challenges in timing and extent of deprescribing, with some patients preferring decisions deferred to outpatient clinicians. Hospitalist and pharmacist recommendations centered on early pharmacist involvement for medication reconciliation, expanding pharmacy consultation and clinician education on deprescribing, whereas patients recommended enhancing shared decision-making through patient education on medication adverse effects, tapering plans, and alternatives. Hospitalists and PCPs also emphasized standardized discharge instructions and transitional care calls to improve medication review and feedback during care transitions. Clinicians and patients highlighted the potential advantages of hospital interventions for CNS medication deprescribing, emphasizing the necessity of addressing communication, education, and coordination challenges between inpatient and outpatient settings.

Central Nervous System Medications: Pharmacokinetic and Pharmacodynamic Considerations for Older Adults.

Most drugs have not been evaluated in the older population. Recognizing physiological alterations associated with changes in drug disposition and with the ultimate effect, especially in central nervous system-acting drugs, is fundamental. While considering pharmacokinetics, it should be noted that the absorption of most drugs from the gastrointestinal tract does not change in advanced age. There are only few data about the effect of age on the transdermal absorption of medications such as fentanyl. Absorption from an intramuscular injection may be similar in older adults as in younger patients. The distribution of lipophilic drugs (such as diazepam) is increased owing to a relative increase in the percentage of body fat, causing drug accumulation and prolonged drug elimination following cessation. Phase I drug biotransformation is variably decreased in aging, impacting elimination, and hepatic drug clearance has been shown to decrease in older individuals by 10-40% for most drugs studied. Lower doses of phenothiazines, butyrophenones, atypical antipsychotics, antidepressants (citalopram, mirtazapine, and tricyclic antidepressants), and benzodiazepines (such as diazepam) achieve the same extent of exposure. For renally cleared drugs with no prior metabolism (such as gabapentin), the glomerular filtration rate appropriately estimates drug clearance. Important pharmacodynamic changes in older adults include an increased sedative effect of benzodiazepines at a given drug exposure, and a higher sensitivity to mu opiate receptor agonists and to opioid adverse effects. Artificial intelligence, physiologically based pharmacokinetic modeling and simulation, and concentration-effect modeling enabling a differentiation between the pharmacokinetic and the pharmacodynamic effects of aging might help to close some of the gaps in knowledge.

Central nervous system medication use around hospitalization.

Central nervous system (CNS) medication use is common among older adults, yet the impact of hospitalizations on use remains unclear. This study details CNS medication use, discontinuations, and user profiles during hospitalization periods. Retrospective cohort study using electronic health records on patients ≥65 years, from three hospitals (2018-2020), and prescribed a CNS medication around hospitalization (90 days prior to 90 days after). Latent class transitions analysis (LCTA) examined profiles of CNS medication class users across four time points (90 days prior, admission, discharge, 90 days after hospitalization). Among 4666 patients (mean age 74.3 ± 9.3 years; 63% female; 70% White; mean length of stay 4.6 ± 5.6 days (median 3.0 [2.0, 6.0]), the most commonly prescribed CNS medications were antidepressants (56%) and opioids (49%). Overall, 74% (n = 3446) of patients were persistent users of a CNS medication across all four time points; 7% (n = 388) had discontinuations during hospitalization, but of these, 64% (216/388) had new starts or restarts within 90 days after hospitalization. LCTA identified three profile groups: (1) low CNS medication users, 54%-60% of patients; (2) mental health medication users, 30%-36%; and (3) acute/chronic pain medication users, 9%-10%. Probability of staying in same group across the four time points was high (0.88-1.00). Transitioning to the low CNS medication use group was highest from admission to discharge (probability of 9% for pain medication users, 5% for mental health medication users). Female gender increased (OR 2.4, 95% CI 1.3-4.3), while chronic kidney disease lowered (OR 0.5, 0.2-0.9) the odds of transitioning to the low CNS medication use profile between admission and discharge. CNS medication use stays consistent around hospitalization, with discontinuation more likely between admission and discharge, especially among pain medication users. Further research on patient outcomes is needed to understand the benefits and harms of hospital deprescribing, particularly for medications requiring gradual tapering.

Iatrogenic Epileptogenicity Caused by CNS Drugs: A Short Case Series and Narrative Review.

Multiple medications are known to increase epileptogenicity in patients with and without an underlying seizure disorder. Paradoxically, some of these medications include anti-seizure medications (ASMs) and other medications, such as psychotropics, that act on the central nervous system (CNS). This article aims to discuss 3 clinical cases that highlight the gamut of epileptogenic reactivity secondary to CNS drugs ranging from increased epileptogenicity in the form of interictal epileptiform discharges (IEDs) without seizures, increased epileptogenicity on electroencephalogram (EEG) with associated non-epileptic movement disorders, and frank, de novo seizures. We also analyze the relevant literature on the impact of CNS medications on epileptogenicity.

Psychostimulant Medications for Physical Function and Spasticity in Children With Cerebral Palsy: Protocol for a Randomized Controlled Trial.

Cerebral palsy (CP) is a prevalent nonprogressive disorder that leads to impaired movement (ie, spasticity), posture, and balance, which affects functions such as walking and upper extremity tasks. Current medical treatments show efficacy in improving motor performance but have considerable side effects. Emerging off-label use of central nervous system (CNS) medications for improving motor performance has shown promising results in children with CP and other populations. The aim of this study is to describe a protocol for a pilot randomized controlled trial (RCT) to examine the safety, tolerability, and efficacy of methylphenidate (MPH) and modafinil on spasticity and motor performance in children with CP. This will be a protocol study for a pilot, triple-masked, placebo-controlled RCT (a class I trial following the American Academy of Neurology criteria) with blinded patients, outcome assessors, and intervention delivery team. Eligible children should be diagnosed with CP levels I or II based on the Gross Motor Function Classification System and be aged between 7 and 12 years. Thirty-six children with CP will be randomized into 3 groups to receive (1) MPH (2.5 mg of MPH + 100 mg placebo), (2) modafinil (100 mg modafinil + 2.5 mg placebo), or (3) a placebo (2.5 mg placebo + 100 mg placebo), in addition to physical therapy for 12 weeks. Primary outcomes include the Gross Motor Function Measure-66 and the Modified Ashworth Scale. Secondary outcomes include the Timed Up and Go test, 5 Time Sit to Stand test, Modified Clinical Test for Sensory Interaction of Balance, and 10-Meter Walk Test. The protocol has been accepted by Kuwait University (VDR/EC-225) and the Ministry of Health of Kuwait (2022/2157). The inclusion of participants will start in June 2024. The combination of CNS stimulant medications and controlling for rehabilitation has not been studied yet. The findings of this study may determine if using CNS stimulant medications is beneficial for the reduction of spasticity and improvement of physical function in children with spastic CP. ClinicalTrials.gov NCT05675098; https://clinicaltrials.gov/study/NCT05675098. PRR1-10.2196/53728.

ANN multi-layer perceptron for prediction of blood–brain barrier permeable compounds for central nervous system therapeutics

Endothelial cells produce a semipermeable barrier known as the blood–brain barrier (BBB) to keep undesired chemicals out of the central nervous system (CNS). However, this barrier also restricts the exploration of potential new medications due to insufficient exposure. To address this challenge, machine learning (ML) algorithms can be useful to predict the BBB permeability of chemical compounds. Support vector machines, continuous neural networks, and deep learning approaches have been used to identify compounds that can penetrate the BBB. However, predicting BBB permeability based solely on chemical structure can be difficult. In the current research, we developed an ML model using a large dataset to predict BBB permeability, which could be used for early-stage drug screening of potential CNS medications. Our artificial neural network ANN algorithm exhibited an accuracy of 0.94, specificity of 0.83, sensitivity of 0.97, AUC of 0.96, and MCC of 0.83. These metrics suggest that our model has a high accuracy rate in predicting BBB permeability and therefore has the potential to advance drug discovery efforts in the CNS. This study’s outcomes demonstrate the potential for ML models to predict BBB permeability accurately, aiding in the identification of new CNS therapeutic options. Communicated by Ramaswamy H. Sarma

Who tests for lead and why? A 10-year analysis of blood lead screening, follow-up and CNS outcomes in a statewide US healthcare system

ObjectivesThis study aims to determine (1) which providers in US healthcare systems order lead tests, why and at what frequency and (2) whether current patient population lead levels are predictive...

RECURRENT FALLS IN OLDER ADULTS ARE ASSOCIATED WITH MORTALITY AND HOSPITALIZATION

Abstract Annually, 1 in 4 older adults fall and roughly half have a second fall within 6 months. We studied 57 hospitals in the TriNetX Network. We included all older adults discharged home from the emergency department (ED) after a fall in 2022 for a total of 89,061 patients. Of these, 13,389 (15%) patients returned to the ED for another fall within 6 months. Patients with repeat falls were older (78.7 vs 76.5 years), more likely to have hypertension (76 vs 56%), prior myocardial infarction (14 vs 3%), heart failure (29 vs. 15%), peripheral vascular disease (18 vs 10%), cerebrovascular event (19 vs 10%), chronic obstructive pulmonary disease (COPD) (23 vs 14%), diabetes (40 vs 23%), liver disease (17 vs 11%), chronic kidney disease (30 vs 16%), and cancer (45 vs 32%); P< 0.001. Patients with recurrent falls were more likely to be prescribed cardiovascular medications (84 vs. 66%), central nervous system medications (87 vs 69%), opioids (71 vs 52%), sedatives/hypnotics (59 vs 42%), antipsychotics (23 vs 12%), antidepressants (51 vs 32%), antiparkinsonian agents (9 vs 4%), and antivertigo agents (15 vs 9%); P< 0.001. Patients with a recurrent fall within 6 months had higher hospital admission rate (46.2 vs 15.8%, OR 4.6 [95%CI, 4.4-4.7]) and higher mortality rate (6.2 vs 3.5%, OR 1.83 [95%CI 1.7-2.0]). Older adults discharged home from the ED after falling are at high risk of a second fall and those who have a repeat fall within 6 months are at higher risk of hospital admission and mortality.

229 OPTI-3S (criteria for optimising medicines by stopping, stepping down, or switching to safer alternatives): consensus validation via a Delphi method

Abstract Background No consensus-based criteria set exists specifically for Potentially Inappropriate Medications (PIMs in hospitalised frail older adults. This study aimed to develop the OPTI-3S core criteria for optimising medicines, using a modified Delphi method. Methods The OPTI-3S preliminary list was developed by the research team based on an extensive literature review. A modified Delphi method was conducted to validate a subset (‘core list’) of these preliminary statements. The Clinical Frailty Scale (CFS) was used to differentiate between frailty levels. Eleven practising experts reviewed the core list and full preliminary list in the first round. Participants were asked to rate their agreement with the core list of statements, using a 5-point Likert scale, and suggest additional statements from the full list, or based on their own knowledge. Statements with a median rating of 1 or 2 (i.e. strongly agree or agree) and 75th percentile of 2 or less were included in the final set. Results Nine experts completed the three rounds, after which consensus was reached on the inclusion of 45 statements: 17 statements in the first round, 25 in the second round, and three in the third round. These statements suggest optimising and/or deprescribing antidiabetic agents (n = 7), central nervous system (CNS) medications (n = 7), genito-urinary medications (n = 7), antithrombotic agents (n = 5), statins (n = 4), antihypertensives (n = 4), osteoporosis medications (n = 3), heart failure medications (n = 2), perioperative analgesia (n = 2), diuretics (n = 1), proton-pump inhibitors (n = 1), vitamins and supplements (n = 1), and anticholinergic medications (n = 1). 22 statements apply to a specific CFS frailty level, while the remainder apply to all frail older persons (i.e. CFS of 4 or more). Conclusion: The literature- and consensus- based OPTI-3S core criteria comprise 45 statements relating to PIMsand suggest preferential medications in hospitalised frail older adults. The OPTI-3S criteria may be a useful guide for medication optimisation in frail older people.

Advances and Opportunities in Nanoparticle Drug Delivery for Central Nervous System Disorders: A Review of Current Advances.

This narrative review provides an overview of the current advances, challenges, and opportunities in nanoparticle drug delivery for central nervous system (CNS) disorders. The treatment of central nervous system disorders is challenging due to the blood-brain barrier (BBB), which limits the delivery of therapeutic agents to the brain. Promising approaches to address these issues and improve the efficacy of CNS disease therapies are provided by nanoparticle-based drug delivery systems. Nanoparticles, such as liposomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles, can be modified to enhance targeting, stability, and drug-release patterns. They allow for the encapsulation of a variety of therapeutic compounds and can be functionalized with ligands or antibodies for active targeting, minimizing off-target effects. Additionally, nanoparticles can circumvent drug resistance processes and provide versatile platforms for applications that combine therapeutic and diagnostic functions. Although the delivery of CNS medications using nanoparticles has advanced significantly, there are still challenges to be resolved. These include understanding the BBB interactions, doing long-term safety studies, and scaling up the production. However, improvements in nanotechnology and a deeper comprehension of CNS disorders provide opportunities to enhance treatment results and address unmet medical requirements. Future research and ongoing clinical trials are required to further explore the potential of nanoparticle drug delivery for CNS disorders.

Potentially inappropriate medication uses and associated factors among elderly primary health care clinics attendees: A call to action.

Polypharmacy is a significant risk factor for using potentially inappropriate medication (PIM), which is using drugs with more risks than benefits, especially for elders. This study aimed to estimate the prevalence of PIM using Beers Criteria, polypharmacy, and their related risk factors. A descriptive cross-sectional study was conducted in West Bank primary health care clinics (PHC)from December 2021 to March 2022. Data were collected from PHC clinic attendees aged 65 and above via an interviewer-administered questionnaire and a review of their medical records. We used the Beers Criteria 2019 update to identify PIM and performed a multivariable analysis to determine its associated factors. The study included 421 older people (197 men and 224 women) with an average age of 73.6 years. The prevalence of polypharmacy was 75.1% (95%CI: 70.6%-79.1%), with an average of six medications dispensed per patient. On the other hand, PIM was identified among 36.8% of the study participants (CI:95%CI: 32.2%- 41.6%). Sulfonylureas were the most common (24.2%) reported PIM, followed by peripheral alpha-blockers (4.3%), non-steroidal anti-inflammatory drugs (3.1%), proton pump inhibitors (2.9%), and central nervous system medications (2.1%). Hyperpolypharmacy (> 10 drugs) [aOR = 4.1, 95%CI: 1.6-10.7], polypharmacy [aOR = 2.8, 95%CI: 1.4-5.4], and Diabetes [aOR = 3.5, 95%CI: 2.0-6.0] are the main associated factors of PIM. This study found that over one-third of the older people attending PHC clinics have PIM, with polypharmacy and Diabetes being the main predicting variables. Improving physicians' awareness of clear and specific PIM lists can reduce the number of PIM prescribed and decrease their impact.

Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil

BackgroundThe increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil.MethodsCross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy.ResultsA total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4–54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2–17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2–52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy.ConclusionsWe found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients’ therapeutic regimens should be implemented.

The Impact of Comorbid Chronic Pain on Pharmacotherapy for Veterans with Post-Traumatic Stress Disorder.

Chronic pain can worsen PTSD symptomatology and may increase the risk of the prescription of multiple central nervous system (CNS)-active medications. The objective is to determine the impact of chronic pain on the number of CNS medications, including psychiatric medications, as well as the amount of medication changes. Veterans Affairs (VA) administrative data were used to identify VA-served Veterans with PTSD (N = 637,428) who had chronic pain (50.3%) and did not have chronic pain (49.7%) in 2020. The outcomes included the number of changes in psychiatric medications and the number of currently prescribed CNS-active mediations during a one-year observation period. The number of changes in psychiatric medications was significantly higher for those with chronic pain (mean (M) = 1.8) versus those without chronic pain (M = 1.6) (Z = 38.4, p < 0.001). The mean number of concurrent CNS-active medications were significantly higher for those with chronic pain (M = 2.7) versus those without chronic pain (M = 2.0) (Z = 179.7, p < 0.001). These differences persisted after adjustment for confounding factors using negative binomial regression. Veterans with comorbid chronic pain and PTSD are at increased risk for a higher number of medication changes and for receiving CNS-active polytherapy.

Prevalence of Outpatient Use of Medicines by the Elderly Population in Portugal: A Cross-Sectional Study

Like in other countries, the age pyramid in Portugal has been changing considerably, with a substantial increase in the size of the older population and a significant reduction in the number of young people. With aging, co-occurrence of several conditions becomes frequent, often leading to the use of multiple medications (polypharmacy). Polypharmacy in the older population is particularly relevant considering the physiological changes of the ageing process, which increase the risk of drug interactions, poor adherence to treatment, and adverse drug reactions, especially in the oldest-old population (85 years or older). As the size of the older population is likely to increase significantly, it is important to characterize the pattern of medicines' use by the elderly while also identifying cases of polypharmacy in order to obtain evidence that can be used to develop specific measures to tackle the high prevalence of use and its associated risks. To this end, the aim of this study was to characterize medication use by older individuals in Portugal. Cross-sectional study with data from the National Health System's Control and Monitoring Center on reimbursed medicines that were prescribed and dispensed to individuals aged 65 years or older in 2019 in all community pharmacies of the Portuguese mainland. We performed a demographic and geographic analysis of the data by international nonproprietary name and therapeutic group. The number of reimbursed packages and the number of reimbursed packages per capita were the metrics used (data from Instituto Nacional de Estatística). A higher consumption of medicines was observed in women, increasing with age, except in the oldest olds, in which the sex difference tended to shrink. Use per capita showed an opposite trend, with the oldest-old men surpassing the oldest-old women (mean reimbursed packages: 55.5 in men versus 55.1 in women). In women, consumption was led by cardiovascular medicines (31%), followed by central nervous system medications (30%) and antidiabetics (13%); in men, 37% of TOP 10 consumption was due to cardiovascular medications, antidiabetics (16%) and drugs for benign prostatic hypertrophy (14%). In the elderly, there were sex differences in the pattern of medicines' use, and there were also significant age-related differences in 2019. To the best of our knowledge, our study is the first nationwide analysis of reimbursed medicines' consumption data in the elderly, which is essential to characterize the use of medicines in this age group in Portugal.

Geriatricians, general internists, and potentially inappropriate medications for a national sample of older adults.

Older adults are often prescribed medications that are potentially dangerous and geriatricians have specialized training in treating polypharmacy that may benefit these patients. To examine this, we compared potentially inappropriate medication (PIM) prescribing rates between geriatricians and similar general internists in the United States. Using national cross-sectional data from 2013 to 2019, we compared annual PIM prescribing rates between 2815 outpatient geriatricians certified by the American Board of Internal Medicine in 1994-2018 and general internists matched 1:1 on IM certification exam score and year, residency exam pass rate, gender, and US birth and/or US medical school. PIM prescribing was based on the Healthcare Effectiveness Data and Information Set (HEDIS) PIM physician annual prescribing measures which consider medications flagged as potentially inappropriate in the American Geriatric Society Beers Criteria® guideline. We also examined prescribing of appropriate alternative medications. Prescribing rates were calculated as the percentage a physician's patients with Medicare fee-for-service part D enrollment seen in the outpatient setting in a given year (mean: 150 patients per physician) with a PIM prescription they prescribed. Across 30,677 physician-year observations, geriatricians were 16.7% less likely (95% confidence interval (CI): -19.8 to -13.7, p < 0.001) to prescribe a PIM (7.2% versus 8.7% of patients respectively) and 2.7% more likely (95% CI: 0.8 to 4.5, p = 0.004) to prescribe an appropriate alternative medication (52.0% versus 50.7% of patients respectively). Lower PIM prescribing was observed for most medication sub-types including central nervous system, anticholinergic, pain, and endocrine medications. In sensitivity analyses, differences in prescribing were similar when comparing recently trained physicians with more experienced physicians. Findings suggest geriatricians in the United States prescribe PIMs at lower rates than general internists. This highlights the value geriatricians provide as well as opportunities to embed key principles of geriatric care into internal medicine training and health care delivery systems.

Disrupted white matter integrity in primary insomnia and major depressive disorder: relationships to sleep quality and depression severity.

This study examined the integrity of white matter tracts in 25 participants with primary insomnia (PI), 50 participants with major depressive disorder (MDD), and 25 healthy controls. Seven white matter tracts, selected based on prior research, were quantified by fractional anisotropy (FA) as well as by related measures of diffusivity using diffusion tensor imaging (DTI) on a 3-T scanner. All 100 participants were free of significant medical, psychiatric (excluding the MDD group) and sleep disorders (excluding the PI group), were free of central nervous system medications, and completed an extensive clinical assessment. Subjective and objective sleep measures revealed significant sleep disruption in both the PI and MDD groups. Relative to the controls, both the PI and MDD groups demonstrated impaired integrity in three of the seven white matter tracts: the genu of the corpus callosum (GenuCC), the superior longitudinal fasciculus (SLF), and the inferior longitudinal fasciculus (ILF). We demonstrated reduced FA in the GenuCC, reduced FA and reduced axial diffusivity (AD) in the SLF, as well as reduced AD and radial diffusivity in the ILF. Finally, in an exploratory analysis of the combined cohorts, FA in the GenuCC and FA in the SLF were negatively correlated with depression severity and positively correlated with total sleep time. Abnormalities documented in the GenuCC, SLF and ILF, and present in both the PI and MDD groups may suggest some shared neurobiology.

Exposures and Suspected Intoxications to Pharmacological and Non-Pharmacological Agents in Children Aged 0–14 Years: Real-World Data from an Italian Reference Poison Control Centre

This study describes the exposures and suspected intoxications in children (0-14 years) managed by an Italian reference poison control center (PCC). A seven-year observational retrospective study was performed on the medical records of the Toxicology Unit and PCC, Careggi University Hospital, Florence (Italy). During the study period (2015-2021), a total of 27,212 phone call consultations were managed by the PCC, of which 11,996 (44%) involved subjects aged 0-14 years. Most cases occurred in males (54%) aged 1-5 years (73.8%), mainly at home (97.4%), and with an oral route of intoxication (93%). Cases mainly occurred involuntarily. Consultations were generally requested by caregivers; however, in the age group 12-14 years, 70% were requested by healthcare professionals due to voluntary intoxications. Cleaners (19.44%) and household products (10.90%) were the most represented suspected agents. Pharmacological agents accounted for 28.80% of exposures. Covariates associated with a higher risk of emergency department visit or hospitalization were voluntary intoxication (OR 29.18 [11.76-72.38]), inhalation route (OR 1.87 [1.09-3.23]), and pharmacological agents (OR 1.34 [1.23-1.46]), particularly central nervous system medications. Overall, consultations do not burden national and regional healthcare facilities, revealing the activity of PCCs as having a strategic role in reducing public health spending, even during the COVID-19 pandemic.

Development and Validation of an LC-MS/MS Method for the Quantitative Determination of Contezolid in Human Plasma and Cerebrospinal Fluid

To develop and verify a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determining contezolid in plasma and cerebrospinal fluid (CSF). Protein precipitation was performed on samples using linezolid as the internal standard. We used an Agilent EclipsePlus C18 column operating at 0.4 mL/min in conjunction with acetonitrile and water mobile phases for the LC-MS/MS analysis. Using the precursor-product ion pairs 409.15→269.14 (contezolid) and 338.14→195.1 (linezolid), multiple reaction monitoring was used to quantify the compounds. Plasma linearity range was 50.0 to 5000 ng/mL, and CSF was 20.0 to 1000 ng/mL (r2 = 0.999). The inter-batch and intra-batch precisions were ≤2.57% and ≤5.79%, respectively. Plasma recovered 92.94%, and CSF recovered 97.83%. Plasma, CSF, hemolytic plasma, and hyperlipidemic plasma all showed a coefficient of variation ≤ 7.44%. The stability and dilution integrity of this method were also acceptable. The study also demonstrated that artificial CSF can be used as a matrix for the preparation of standard curve samples. A simple and accurate method was developed and validated for the determination of contezolid concentrations in human plasma and CSF, which may be useful for monitoring the therapeutic effect of central nervous system medications.

Gabapentin utilization among older adults with different cognitive status: Results from the National Alzheimer’s Coordinating Center database (2006‐2019)

AbstractBackgroundAlthough gabapentin use has been increasing among older adults, its safety is understudied. We aimed to examine gabapentin utilization trends among older adults with different cognitive status and investigate potentially inappropriate concurrent medication use with gabapentin.MethodsData were extracted from National Alzheimer’s Coordinating Center Uniform Data Set (2006‐2019). We included participants (age 65+) with any medications reported at the time of visit. Within each study year, we estimated the prevalence of gabapentin use among the participants at each visit, both overall and within subgroups defined by cognitive status [normal, mild cognitive impairment, and dementia] and demographics [age and sex]. Additionally, we assessed prevalence of concurrent use of gabapentin with Central Nervous System (CNS) depressants, including opioid, combined opioid and benzodiazepine, antidepressant, and antipsychotic.ResultsOverall, participant‐reported gabapentin use nearly tripled (2.2 to 6.1%) from 2006 to 2019. Further, prevalence increased over this period in every participant subgroup. Among gabapentin users, the concurrent use of antidepressants or antipsychotics was more common in participants with a dementia diagnosis than those with normal cognition. Over half of gabapentin users with dementia also reported use of antidepressants. The concurrent use of gabapentin with opioids ranged from 10 to 30%, and the concurrent use of gabapentin, benzodiazepine, and opioids was below 8% throughout the study period.ConclusionsGiven increasing use among older adults, including those with cognitive impairment and dementia, rigorous studies are needed to examine the safety of gabapentin in this population, especially when using gabapentin with other CNS medications concurrently.

Three‐stage classification of Alzheimer's disease in MRI in clinical records of the Mass General Brigham Health Care System

AbstractBackgroundDiagnostic deep learning has frequently been applied to diagnosis of Alzheimer's and Mild Cognitive Impairment in brain MRIs collected in a controlled research setting, but due to the presence of confounding factors, similar methods have rarely been applied post‐hoc to clinical MRI. Data matching, or the matching of datasets across different classes with respect to a number of confounds, is a method of finding subsets of an overall dataset, that can be used to mitigate the confounding factor problem.Method467,464 multimodal clinical MRIs of the brain from 37,311 patients in the Mass General Brigham (MGB) Healthcare System were either excluded (based on presence of neoplasms or head trauma) or labeled as AD, MCI, or control, based on a previous prescription of rivastigmine, galantamine, or donepezil (MCI), or memantine (AD), or the lack of a history of central nervous system medications. A data matching algorithm was applied to 18 technical and demographic confounding factors to isolate an unconfounded matched dataset set to train an ensemble of five 3D ResNet‐50 deep learning models. Across the ensemble, the test set totaled 287,367 files. See Figure 1.ResultIn distinguishing controls from AD/MCI on a per‐patient basis, an AUROC of 0.82 was achieved, though with lower performance in distinguishing between AD and MCI. Variations in performance were seen with MRI modality, with MPRAGE having the highest performance overall (0.859 AUROC). See Figure 2.ConclusionWhen carefully accounting for confounds, the use of deep learning models is feasible in the analysis of highly‐confounded clinical MRI.