Treatment Of Disorders Research Articles

Значение видео-уродинамического исследования в выборе метода лечения детей с нейрогенными дисфункциями мочевого пузыря

Video urodynamics is the standard for assessment of the lower urinary tract in children with neurogenic urinary disorders aiming to provide more information about the condition of the lower urinary tract v. retrograde urethrocystography. Video urodynamics parameters are used as possible indicators for choosing various surgical treatment options, however, all work is focused on adult patients, and data for the pediatric cohort were not available as yet. The purpose of this research was the evaluation of the role of video urodynamics and retrograde urethrocystography in the selection of effective conservative and surgical treatment of neurogenic urinary disorders in children. Materials and methods used: 112 patients aged 1,8 to 18 y/o with neurogenic urinary disorders were included in the study, of whom 101 were those who had been proven effectively treated with conservative M-cholinoblockers or had successfully undergone minimally invasive surgery as follows: intradetrusor injection of botulinum toxin (n=21), transurethral correction of VUR (n=17), simultaneous execution of two of these interventions (n=22). Based on the results of video urodynamic and cystographic examination of these patients with the CHAID technique, the classification trees were built in order to evaluate the effective treatment (conservative/surgical). Results: the median age of patients was 9,0 years [7,8-12,0]. The first classification tree containing the parameter “presence of VUR according to the results of retrograde cystography.” The sensitivity of the obtained model for the effectiveness of surgical treatment was 83,3% v. 73,2% for conservative treatment. The accuracy was 79,2%. The ROC-AUC value was 0,783. The second classification tree contained the maximum Pves value according to the results of the video urodynamics, presence of hyperactivity, presence of VUR. The sensitivity of the obtained model for the effectiveness of surgical treatment was 93,3% v. 97,6% for conservative treatment. The accuracy was 95,0%. The ROC-AUC value was 0,972. Comparison of ROC-AUC values by the Delong test revealed statistically significant differences between these binary classification metrics (p<0.001). Conclusion: the parameters of video urodynamics have greater diagnostic accuracy in effective prediction of both conservative and surgical treatment methods compared to the retrograde urethrocystography.

Oral aripiprazole in the treatment of tic disorders in China: a cost-effectiveness analysis based on a mapping algorithm derived from a Chinese children and adolescents population

BackgroundOral aripiprazole exhibits favorable clinical efficacy and safety in the suppression of tics in children and adolescents with tic disorders. This study aims to evaluate and compare the cost-effectiveness of high-dose and low-dose aripiprazole in children and adolescents with tic disorders from the perspective of the Chinese healthcare system.MethodsA questionnaire survey was conducted on 146 patients with tic disorders, of whom 144 completed EQ-5D-Y and YGTSS. Four models were built to convert YGTSS onto EQ-5D-Y utility using two mapping algorithms. We constructed a decision tree model containing efficacy and safety to compare the cost-effectiveness of high-dose and low-dose aripiprazole based on our mapping function.ResultsThe GLM with model 1 (YGTSS total tic scores) was selected as the preferred function in our decision tree model. The base case cost-effectiveness analysis showed that compared to low-dose aripiprazole, high-dose aripiprazole improves effectiveness by 0.001QALYs and increases the overall cost by $197.99, resulting in an ICER of $174339.22 per QALY, which exceeds three times the gross domestic product per capita. Hence, high-dose aripiprazole is not likely to be a cost-effective option for child patients with tic disorders. One-way sensitivity analysis and probabilistic sensitivity analysis showed that these results is robust.ConclusionOn the basis of currently available data, low-dose aripiprazole may be a safe, effective, and economical dosage for children and adolescents with tic disorders.LimitationsThe main limitation of our study is the lack of utility directly used for cost-effectiveness analysis. We obtained the utility of patients with tic disorders indirectly by the mapping function. This may introduce some bias and uncertainty. And it is a limitation to use the direct medical costs of Germany in our model. Although we converted it to the equivalent value of China using purchasing power parities, caution should be exercised when interpreting the results of this study.

Clinical Features, Psychiatric Comorbidities and Treatments in Childhood OCD in terms of OCD Severity, Age and Gender

Objective: The aim of this study was to investigate the clinical features, psychiatric comorbidities, and treatments of childhood obsessive-compulsive disorder (OCD), with consideration given to OCD severity, gender and age. Method: The study included 104 children and adolescents between the ages of 6 and 17 who were diagnosed with OCD and followed up in Child and Adolescent Psychiatry outpatient clinics between 2016 and 2023. The study examined the sociodemographic characteristics, clinical features, comorbid psychiatric disorders, and treatment approaches of children and adolescents with OCD. Results: The sample had a mean age of 13.1 ± 2.7 years, and the mean age at onset of OCD was 11.9 ± 2.7 years (range: 5-17 years). Those with mild OCD had a significantly lower mean age at presentation and onset of OCD compared to those with moderate and severe OCD (p=0.012, p=0.02, respectively). Patients with severe OCD had longer illness duration (p=0.009) and outpatient follow-up (p=0.004) compared to those with moderate OCD. Boys had significantly higher rates of family history of psychiatric disorders (p=0.006), attention-deficit/hyperactivity disorder/oppositional defiant disorder (p=0.003), and tic disorder (p=0.035) comorbidity rates than girls, while girls had higher rates of anxiety disorders (p=0.022) comorbidity. The study found that repeating and counting compulsions were more common in adolescents than in preadolescents (p=0.003, all). Conclusion: These results suggest that clinical presentation and comorbidity may vary with disease severity, gender and age, in children and adolescents with OCD. Early intervention is crucial to prevent clinical progression, worsening, and mental health sequelae.

Knowledge and Attitude of Undergraduate Dental Students towards Research in a private dental institute, karachi

Abstract: Background: Scientific research in healthcare is crucial for maintaining oral health and for the prevention, diagnosis, and treatment of oral disorders. Actually, it is regarded as a basic skill and one of the important areas in the medical education curriculum related to health care. The objective of this study was to evaluation the knowledge and attitude of undergraduate students towards research Methodology: A cross sectional study was conducted from BDS students using non probability convenient sampling technique. Study was conducted from a private dental institute from December 2023-may 2024. The estimated sample size was 160 using Open epi version 3.01, after inserting the prevalence 88.2% participants feel that they can plan and prepare research, with 95% confidence interval and 5% margin of error. Results: The research was conducted on 168 students from different BDS years. The majority of participants were in the age group of 20-25years (73.8%). Of the students, 40.5% were familiar with the literature review procedure; the majority of participants were from BDS's second and third years. About 42.8% of students expressed interest in pursuing this research as part of their dental profession. Reasons given by students for not being interested in doing research, 27% of the student recommended lack of time and lack of resources as the limitation in pursing research study. Conclusion: Research culture needs to be promoted since it benefits patients' health and the community that students will serve in addition to their career paths. It takes a foundational understanding of research methodology to practice medicine and dentistry competently. Engagement in research is the most effective means of achieving this familiarity Keywords: biomedical research, curriculum, students, evidence based medicine, research design, developing countries

Early Change as a Predictor of Treatment Outcome in Patients with a Personality Disorder.

A significant proportion of patients with a personality disorder do not benefit from treatment. Monitoring treatment progress can help adjust ineffective treatments. This study examined whether early changes in symptoms and personality dysfunction during the first phase of therapy could predict treatment outcomes. Data from 841 patients who received specialized treatment for personality disorders were analyzed. The study focused on whether changes in the Outcome Questionnaire-45.2 (OQ-45.2) symptom distress scale (SD), the General Assessment of Personality Disorder (GAPD), and Severity Indices of Personality Problems (SIPP) in the early phase of therapy predicted post-treatment personality dysfunction, as measured by the SIPP and GAPD. Early changes within a specific SIPP domain were the strongest predictors of post-treatment outcomes in that same domain. Early changes in symptoms significantly predicted outcomes in Self-Control, Relational Functioning, and Identity Integration, while the GAPD predicted outcomes in Self-Control and Social Attunement on the SIPP. For the GAPD, early changes on the GAPD itself, followed by early changes on the OQ-45 SD and the SIPP domain Social Attunement, were significant predictors. Thus, when it comes to personality dysfunction, early changes in a specific domain or measure are the best predictors of outcomes in that same domain. While the OQ-45 predicted some aspects of personality dysfunction, it should not replace disorder-specific measures. Additionally, the SIPP domains and the GAPD should not be used interchangeably to predict each other. In sum, considering these factors, monitoring early change can be useful in assessing progress in the treatment of patients with personality disorders.

Retrospective Review of Postpartum Lithium Use Including During Lactation.

Introduction: Lithium remains a gold standard treatment for bipolar disorder including during peripartum. Historically, guidelines advised against breastfeeding while taking lithium though recent data suggest it is acceptable for a healthy infant. Lack of awareness of acceptability contributes to decreased patient and clinician comfort and low breastfeeding rates. We report current breastfeeding rates, monitoring practices, and infant outcomes with lithium exposure in breastmilk at our institution. Methods: A retrospective chart review was conducted at a single academic medical center using records from 2013 to 2023. Electronic medical records were queried to identify patients prescribed lithium postpartum. Data were collected on timing of lithium initiation, lithium dose and concentration, breastfeeding status, and infant outcomes. Results: A total of 18 cases of lithium use in the postpartum period were identified. A total of 39% (n = 7) of patients taking lithium postpartum breastfed. Most patients, 61% (n = 11), initiated lithium prior to pregnancy, 11% (n = 2) initiated during pregnancy and 27% (n = 5) started postpartum. Four infant charts were reviewed with no reports of adverse events. Of these infants,;average maternal lithium dose was 750 mg daily, with an average maternal serum lithium concentration of 0.62 mmol/L and average infant serum lithium concentration of 0.16 mmol/L. Conclusion: Our data demonstrate most patients using lithium postpartum have been taking lithium long-term and are not breastfeeding. Lithium exposure in breastmilk appears to be tolerated by healthy infants. There is a need for ongoing research and education on acceptability and infant monitoring recommendations to support patients who would like to breastfeed while on lithium.

Germacrone: A Multi-targeting Sesquiterpene with Promising Anti-cancer and Chronic Disease Applications.

Germacrone, a naturally occurring active compound found in essential oils extracted from medicinal plants within the Zingiberaceae family, has garnered attention for its potential therapeutic applications. Extensive research has highlighted its multi-targeting capabilities, positioning it as a promising treatment for various chronic diseases, including cancer, cardiovascular conditions, and neurodegenerative disorders like Alzheimer's disease. This review aims to provide a comprehensive overview of germacrone as a scaffold for developing multi-targeting drugs with therapeutic potential against a range of chronic disorders. The study delves into the molecular mechanisms that underlie the therapeutic effects of germacrone and explores its potential targets, including NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction. A systematic review of literature databases was conducted to gather relevant studies on germacrone and its therapeutic applications. The molecular mechanisms and potential targets of germacrone were examined to elucidate its multi-targeting capabilities. Germacrone exhibits significant potential in the management of chronic diseases, with demonstrated effects on various cellular pathways. The review highlights its impact on NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction, showcasing its versatility in targeting multiple pathways associated with chronic conditions. Germacrone has emerged as a promising candidate for the treatment of diverse chronic diseases. The understanding of its multi-targeting capabilities, coupled with its natural origin, positions it as a valuable scaffold for developing therapeutics. The exploration of germacrone as a structural framework for multi-targeting drugs offers a potential avenue to enhance efficacy while minimizing potential side effects. Further research and clinical trials are warranted to validate the therapeutic potential of germacrone in diverse medical contexts.

Closed-Loop Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder: An Open-Label Pilot Study.

Closed-Loop Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder: An Open-Label Pilot Study.

Impact of initiation of targeted therapy on the use of psoriatic arthritis-related treatments and healthcare consumption: a cohort study of 9793 patients from the French health insurance database (SNDS)

ObjectivesTo assess the potential impact of targeted therapies for psoriatic arthritis (PsA) on symptomatic treatments (non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, opioid analgesics), methotrexate and mood disorder treatments and on hospitalisation...

Hippocampal neurogenesis modulated by Quinic acid: A therapeutic strategy for the neurodegenerative disorders.

Neural progenitor cells (NPCs) reside in the brain and participate in the mechanism of neurogenesis that permits the brain to generate the building blocks for enhancement of cognitive abilities and acquisition of new skills. The existence of NPCs in brain has opened a novel dimension of research to explore their potential for treatment of various neurodegenerative disorders. The present study provides novel insights into the intracellular mechanisms in neuronal cells proliferation, maturation and differentiation regulated by Quinic acid (QA). Furthermore, this study might help in discovery and development of lead molecule that can overcome the challenges in the treatment of neurodegenerative diseases. The growth supporting effect of QA was studied using MTT assay. For that purpose, hippocampal cell cultures of neonatal rats were treated with different concentrations of QA and incubated for 24, 48 and 72 h. Gene and protein expressions of the selected molecular markers nestin, neuron-specific class III beta-tubulin (Tuj-1), neuronal nuclear protein (NeuN), neuronal differentiation 1 (NeuroD1), glial fibrillary acidic protein (GFAP), neuroligin (NLGN) and vimentin were analyzed. QA-induced cell proliferation and differentiation of hippocampal progenitor cells was also accompanied by significantly increased expression of progenitor and immature neuronal marker, mature neuronal marker and differentiating factor, that is, nestin, Tuj-1, NeuN and NeuroD1, respectively. On the other hand, vimentin downregulation and constant GFAP expression were observed following QA treatment. Additionally, the effects of QA on the recovery of stressed cells was studied using in vitro model of oxygen glucose deprivation (OGD). It was observed that hippocampal cells were able to recover from OGD following the treatment with QA. These findings suggest that QA treatment promotes hippocampal neurogenesis by proliferating and differentiating of NPCs and recovers neurons from stress caused by OGD. Thus, the neurogenic potential of QA can be explored for the treatment of neurodegenerative disorders.

The relationship between alcohol availability and drink-driving policies and admissions to substance use disorder treatment during pregnancy.

Pregnancy-specific alcohol policies are widely adopted yet have limited effectiveness and established risks. It is unknown whether general population alcohol policies are effective during pregnancy. This study investigated associations between general population policies and alcohol treatment admission rates for pregnant people specifically. Data are from the Treatment Episodes Data Set: Admissions and state-level policy data for 1992-2019 (n=1,331 state-years). The primary outcome was treatment admissions where alcohol was the primary substance, and the secondary outcome included admissions where alcohol was any substance. There were five policy predictors: 1) Government spirits monopoly, 2) Ban on Sunday sales, 3) Grocery store sales, 4) Gas station sales, and 5) Blood alcohol concentration (BAC) laws. Covariates included poverty, unemployment, per capita cigarette consumption, state and year fixed effects, and state-specific time trends. In models with alcohol as the primary substance, prohibiting spirits sales in grocery stores (vs. allowing heavy beer and spirits) had lower treatment admission rates [IRR=0.88, 95% CI: 0.78-0.99, p=0.028]. States with BAC laws at 0.10% (vs. no law) had higher treatment admission rates [IRR=1.24, 95% CI: 1.08-1.43, p=0.003]. When alcohol was any substance, prohibiting spirits sales in grocery stores (vs. allowing heavy beer and spirits) was again associated with lower treatment admission rates [IRR=0.89, 95% CI: 0.80-0.98, p=0.021], but there was no association for BAC laws. Restrictions on grocery store spirits sales and BAC laws were associated with lower and higher alcohol treatment admission rates among pregnant people, respectively, suggesting general population alcohol policies are relevant for pregnant people's treatment utilization.

Effects of high-intensity interval training on sleep disturbances associated with posttraumatic stress disorder.

Sleep disturbances are common in individuals with posttraumatic stress disorder. Exercise interventions are a promising approach in the treatment of sleep disorders, but little is known about the efficacy of exercise interventions for sleep disturbances associated with posttraumatic stress disorder. A total of 40 individuals with posttraumatic stress disorder were randomized to six sessions of either high-intensity interval training or low-to-moderate-intensity training, administered within 12 days. Sleep quality was assessed over 24 days from baseline to post with the Pittsburgh Sleep Quality Index, a sleep log, and a waist-worn actigraphy. Analyses revealed that, regardless of group allocation, Pittsburgh Sleep Quality Index score improved significantly by 2.28 points for high-intensity interval training and 1.70 points for low-to-moderate-intensity training (d = 0.56 for high-intensity interval training; 0.49 for low-to-moderate-intensity training) over time, while there were no significant changes in any sleep log or actigraphy measure. Analysis of a subsample of those affected by clinically significant sleep disturbances (n = 24) revealed a significant time effect with no difference between exercise interventions: Pittsburgh Sleep Quality Index improved significantly by 2.65 points for high-intensity interval training and 2.89 points for low-to-moderate-intensity training (d = 0.53 for high-intensity interval training; 0.88 for low-to-moderate-intensity training), and actigraphy measure of wake after sleep onset was reduced significantly by 14.39 minutes for high-intensity interval training and 6.96 minutes for low-to-moderate-intensity training (d = 0.47 for high-intensity interval training; 0.11 for low-to-moderate-intensity training) from baseline to post. In our pilot study, we found an improvement in sleep quality from pre- to post-assessment. There were no significant differences between exercise groups. Further studies are needed to investigate whether the found time effects reflect the exercise intervention or unrelated factors.

Understanding sex differences in extinction retention: Pre-extinction stress and sex hormone status

Difficulties in fear regulation can sometimes result in maladaptive fear responses. To better understand how to improve fear regulation, it is important to determine how known factors, such as sex hormone status and stress, might interact to influence fear memory. Research has shown that women with high estradiol levels (mid-cycle) and men exhibit better extinction retention compared to women with low estradiol levels (women in the early follicular cycle or using oral contraceptives). Stress has also been demonstrated to affect both the learning and retention of extinction. Despite documented interactions between stress and sex hormones, their combined effects have not been thoroughly studied. This study aims to examine the impact of stress as a function of sex hormone status on extinction learning and retention.A total of 168 non-clinical participants were studied, including men (n = 46), women using oral contraceptives (n = 38), women in the early follicular phase (n = 40), and women in mid-cycle (n = 44). On Day 1, fear acquisition training was performed. On day 2, prior to extinction training, half of the participants were exposed to a psychosocial stressor, while the other half performed a non-stressful control task. On day 3, extinction retention was tested. Fear was quantified using skin conductance responses, while stress hormones were quantified through saliva samples.Exposure to stress prior to extinction training did not affect extinction learning, regardless of sex hormone status. In contrast, pre-extinction stress exposure had different effects on extinction retention depending on hormone status. Stressed men showed impairment in extinction retention compared to controls, while the experimental condition had no effect on naturally cycling women. Regardless of stress exposure, early follicular women exhibited a deficit in fear regulation, while mid-cycle women showed effective fear regulation. Among women using oral contraceptives, the stress group demonstrated better extinction retention compared to the control group.These results demonstrate the importance of considering sex hormone status and stress exposure during extinction learning, as both components may modulate extinction retention. These results could help identifying hormonal conditions that may enhance the effectiveness of extinction-based psychological therapies used in the treatment of fear-related disorders.

Liraglutide improves follicle development in polycystic ovary syndrome by inhibiting CXCL10 secretion

BackgroundAt present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear.MethodsRNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation.ResultsIn the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation.ConclusionsThe present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS.Trial registrationNot applicable.

The Role of Proteomics in Identification of Key Proteins of Bacterial Cells with Focus on Probiotic Bacteria

Probiotics can affect human health, keep the balance between beneficial and pathogenic bacteria, and their colonizing abilities enable the enhancement of the epithelial barrier, preventing the invasion of pathogens. Health benefits of probiotics were related to allergy, depression, eczema, cancer, obesity, inflammatory diseases, viral infections, and immune regulation. Probiotic bacterial cells contain various proteins that function as effector molecules, and explaining their roles in probiotic actions is a key to developing efficient and targeted treatments for various disorders. Systematic proteomic studies of probiotic proteins (probioproteomics) can provide information about the type of proteins involved, their expression levels, and the pathological changes. Advanced proteomic methods with mass spectrometry instrumentation and bioinformatics can point out potential candidates of next-generation probiotics that are regulated under pharmaceutical frameworks. In addition, the application of proteomics with other omics methods creates a powerful tool that can expand our understanding about diverse probiotic functionality. In this review, proteomic strategies for identification/quantitation of the proteins in probiotic bacteria were overviewed. The types of probiotic proteins investigated by proteomics were described, such as intracellular proteins, surface proteins, secreted proteins, and the proteins of extracellular vesicles. Examples of pathological conditions in which probiotic bacteria played crucial roles were discussed.

The Role of Phytochemicals in The Management of Lifestyle Disorders

Phytochemicals are natural chemical constituents or bioactive compounds found in medicinal plants, aromatic plants, vegetables, fruits, leaves, flowers and roots which work in conjunction with nutrients and dietary fibers to act as defense against diseases and to slow the aging process. The medicinal values of plants lie in the abilities of these phytochemicals to produce definite physiological action on the human body. A variety of phytochemicals such as polyphenols, terpenoids, flavonoids, tannins, saponins, glycosides and steroids present in plants and their products are key factors in the treatment of several disorders including lifestyle disorders. Lifestyle disorders, also known as non-communicable diseases, are conditions associated with the way people live and behave. According to the World Health Organization (WHO) fact sheets, lifestyle disorders like obesity, diabetes, cancer, cardiovascular diseases, respiratory and gastrointestinal diseases account for 59 percent of the 56.5 million deaths annually and 45.9 percent of the global burden of disease (WHO, 2021). This review introduced and identified various phytochemicals reported with beneficial effects or roles and their functional classification or subclasses that have been identified to help prevent diseases associated with lifestyle changes.

40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice

The glymphatic-lymphatic system is increasingly recognized as fundamental for the homeostasis of the brain milieu since it defines cerebral spinal fluid flow in the brain parenchyma and eliminates metabolic waste. Animal and human studies have uncovered several important physiological factors regulating the glymphatic system including sleep, aquaporin-4, and hemodynamic factors. Yet, our understanding of the modulation of the glymphatic system is limited, which has hindered the development of glymphatic-based treatment for aging and neurodegenerative disorders. Here, we present the evidence from fluorescence tracing, two-photon recording, and dynamic contrast-enhanced magnetic resonance imaging analyses that 40 Hz light flickering enhanced glymphatic influx and efflux independently of anesthesia and sleep, an effect attributed to increased astrocytic aquaporin-4 polarization and enhanced vasomotion. Adenosine-A2A receptor (A2AR) signaling emerged as the neurochemical underpinning of 40 Hz flickering-induced enhancement of glymphatic flow, based on increased cerebrofluid adenosine levels, the abolishment of enhanced glymphatic flow by pharmacological or genetic inactivation of equilibrative nucleotide transporters-2 or of A2AR, and by the physical and functional A2AR–aquaporin-4 interaction in astrocytes. These findings establish 40 Hz light flickering as a novel non-invasive strategy of enhanced glymphatic flow, with translational potential to relieve brain disorders.

Designing a Measurement Feedback System for Personality Disorders: Should Outcome Monitoring be Based on Symptom Severity or Personality Functioning?

Measurement feedback systems (MFS) providing insight in treatment progress can improve mental healthcare outcomes. However, there is no uniform measurement feedback system that could be used to measure treatment progress for personality disorders (PD). This study compared two types of measures: a generic measure for symptom severity (Brief Symptom Index, BSI) and a specific measure for personality functioning (Severity Indices of Personality Problems, SIPP) at different points in time in order to provide insight in the most suitable measuring moment for a MFS for PD. This study is conducted in a sample of 996 Dutch PD patients (mean age 33.51 (SD 10.42), 73.1% female). Symptom severity and personality functioning were assessed before and multiple times during treatment, using a timespan of 24months. Outcomes were examined over time using multilevel modeling. Symptom severity (generic measure) and personality functioning (specific measure) improved equally after 24months. However, during these 24months, different patterns of change were observed for symptom severity compared to severity of personality problems. In general, symptom severity decreased most during the 1st months of treatment, whereas personality functioning improved only after 6months of treatment. A generic instrument of symptom severity is able to measure early changes in symptom distress but may not be able to measure longer term changes in personality functioning. The authors discuss policy implications for benchmarking using specific measures in the treatment of personality disorders.

The Impact of COVID-19 on Substance Use and Related Consequences among Patients in Office-Based Opioid Use Disorder Treatment.

The COVID-19 pandemic led to increased substance-related morbidity and mortality and transformed care for opioid use disorder (OUD). We assessed the perceived impacts of the pandemic on substance use and related consequences among patients in office-based addiction treatment (OBAT). We recruited patients with OUD on buprenorphine from July 2021 to July 2022, with data collection at baseline and 6 months. Exposures of interest were the following 6 domains potentially impacted by COVID-19: personal or family infection, difficulty accessing healthcare/medication, economic stressors, worsening physical or mental health, social isolation, and conflicts/disruptions in the home. Outcomes were past 30-day alcohol and other substance use, increased use, and substance-related consequences at baseline and 6 months. Generalized estimating equations Poisson regression models quantified associations between increasing impact domain scores and relative risks of each outcome. All participants (N = 150) reported at least one domain negatively impacted by COVID-19 at both time points. Higher "worsening physical or mental health" domain scores were associated with increased relative risk of recent alcohol or drug use (adjusted risk ratio [aRR] 1.04, 95% confidence interval [CI]: 1.01-1.07). Relative risks of experiencing substance-related consequences increased with higher scores in the domains of economic stressors (aRR 1.07, 95% CI: 1.02-1.13), difficulty accessing healthcare/medication (aRR 1.11, 95% CI: 1.04-1.19), and worsening physical or mental health (aRR 1.08, 95% CI: 1.04-1.12). Among patients with OUD, stressors from COVID-19 were common. Three life domains impacted by COVID-19 appeared to be associated with consequential substance use, highlighting opportunities to address barriers to healthcare access and economic stressors.

Off-Label Use of Lamotrigine and Naltrexone in the Treatment of Ketamine Use Disorder: A Case Report.

Ketamine is a dissociative anesthetic increasingly utilized in United States medical settings for the treatment of mental health conditions. Additionally, it is increasingly used in nonmedical settings for its dissociative properties. While nonmedical ketamine use and ketamine use disorder (KUD) have been observed internationally, KUD, and approaches to its treatment, have not been previously described in the US. We present the case of a 32-year-old man with KUD who experienced severe cravings despite receipt of residential and intensive outpatient substance use disorder treatment. He resumed use after an initial period of abstinence and was subsequently started on lamotrigine and naltrexone for treatment of depressive symptoms and cravings. This combination altered his experience while on ketamine, resulting in nausea and decreased hallucinogenic effects. In addition, it substantially decreased his cravings, aiding him in achieving longer-term abstinence in combination with receipt of dialectical behavioral therapy, familial support, and involvement in 12-step programming. KUD is a poorly described condition that may become more prevalent as US ketamine use increases. Combining treatment of depressive symptoms and cravings, in this case with lamotrigine and naltrexone, may be a promising pharmacotherapeutic strategy. Lamotrigine, an antiepileptic with glutamate modulating effects, has been utilized to decrease cravings in a variety of substance use disorders. Naltrexone is an opioid antagonist approved for alcohol use disorder and opioid use disorder and is used off-label for stimulant use disorder. This combination offers a possible pharmacotherapeutic option for KUD with more research needed to further evaluate.