Changes in Emergency Department Utilization in Vulnerable Populations After COVID-19 Shelter-in-Place Orders.

OBJECTIVES: This study aims to compare emergency department (ED) utilization and admission rates for patients with a history of mental health (MH) disorders, substance use disorders (SUDs), and social determinants of health (SDOH) before and after implementing COVID-19 shelter-in-place (SIP) orders. METHODS: This was a retrospective, multicenter study leveraging electronic medical record (EMR) data from 20 EDs across a large Midwest integrated healthcare system from 5/2/2019 to 12/31/2019 (pre-SIP) and from 5/2/2020 to 12/31/2020 (post-SIP). Diagnoses were documented in the patient's medical records. Poisson and logistic regression models were used to evaluate ED utilization and admission rate changes. RESULTS: A total of 871,020 ED encounters from 487,028 unique patients were captured. Overall, 2,572 (0.53%) patients had a documented Z code for SDOH. Patients with previously diagnosed MH disorders or SUDs were more likely to seek ED care after the SIP orders were implemented (risk ratio (RR): 1.20, 95% confidence interval (CI): 1.18-1.22, p<0.001), as were patients with SDOH (RR: 2.37, 95% CI: 2.19-2.55, p<0.001). Patients with both previously diagnosed MH disorders or SUDs and a documented SDOH had even higher ED utilization (RR: 3.31, 95% CI: 2.83-3.88, p<0.001) than those with either condition alone. Patients with MH disorders and SUDs (OR: 0.89, 95% CI: 0.86-0.92, p<0.001) or SDOH (OR: 0.67, 95% CI: 0.54-0.83, p<0.001) were less likely to be admitted post-SIP orders, while patients with a history of diseases of physiologic systems were more likely to be admitted. CONCLUSION: Vulnerable populations with a history of MH disorders, SUDs, and SDOH experienced increased ED utilization but a lower rate of hospital admissions after the implementation of SIP orders. The findings highlight the importance of addressing these needs to mitigate the impact of public health crises on these populations.

Efficacy of topiramate in reducing second-generation antipsychotic-associated weight gain among children: A systematic review and meta-analysis.

AIMS: To conduct a systematic review and meta-analysis with the aim of synthesizing existing data on the efficacy and safety of topiramate as an adjunctive treatment for reducing second-generation antipsychotic (SGA)-associated weight gain in children aged 4-18 years. METHODS: We conducted a comprehensive search of PubMed, Embase, PsychNet and Web of Science from time of their inception up to 12 February 2024, including randomized controlled trials that compared SGA treatment with and without topiramate co-administration in children. The primary outcomes were changes in body weight and body mass index (BMI). Heterogeneity was assessed using I2 statistics. RESULTS: This systematic review included five randomized trials, totalling 139 participants (43.9% female; mean [SD] age 11.9 [3.5] years). Four of these trials were included in the meta-analysis, comprising 116 subjects. We found that topiramate was significantly effective both in reducing SGA-associated weight gain, with a mean difference of -2.80 kg (95% confidence interval [CI] -5.28 to -0.31; p = 0.037, I2 = 86.7%) and a standardized mean difference (SMD) of -1.33 (95% CI -2.14 to -0.51; p = 0.014, I2 = 31.7%), and in reducing BMI change compared to placebo (SMD -1.90, 95% CI -3.09 to -0.70; p = 0.02, I2 = 0%). Sedation risk was lower with topiramate than with placebo (odds ratio 0.19, 95% CI 0.11-0.32; p < 0.01, I2 = 0%). No significant differences were found in dropouts, any other side effects, and metabolic parameters, such as triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, and glucose. None of the included studies reported assessments on cognitive side effects. CONCLUSION: This meta-analysis suggests that topiramate is an effective and safe option for mitigating SGA-associated weight gain in children.

Diagnosis and treatment of Wernicke's encephalopathy: A systematic literature review.

BACKGROUND: Wernicke's encephalopathy (WE) is a serious neurological disorder that is underdiagnosed. Despite limited clinical guidelines, the standard use of intravenous (IV) thiamine is underutilized and remains an area of research deserving much attention. OBJECTIVES: We conducted a systematic review using Medline, Embase, and CENTRAL databases to identify and summarize the literature on IV thiamine treatment in WE. Human studies with WE patients who received ≥100 mg of thiamine IV met inclusion criteria. Randomized controlled trials, cross-sectional studies, and case reports were included. RESULTS: A total of 27 studies were included: 20 case reports, five retrospective studies, one prospective study and one randomized control trial. Of the case reports, 11 (55%) cases were female, and the average age of all cases was 45 years (SD = 15). The other seven studies included 688 patients; the average age was 52 years (SD = 9), and 266 (38.7%) were female. Among the case reports, neurological and clinical findings were used to diagnose WE in 16 (80%) cases. MRI was utilized to diagnose 15 (75%) cases. 500 mg IV thiamine TID was reported in 12 case reports (60%). 18 (90%) of case reports had partial or complete resolution of symptoms following IV thiamine. CONCLUSION: IV thiamine can alleviate neurological symptoms, cognitive dysfunction, and brain imaging lesions associated with WE. We found key limitations in the evidence for IV thiamine and diagnostic standards for WE. Future targeted research should establish clear diagnostic and treatment guidelines for WE to prevent this serious condition from being underdiagnosed or undertreated.

The impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies.

Background: The relationship between cannabis use and the risk of returning to using opioids non-medically during treatment for opioid use disorder (OUD) remains unclear.Objective: We sought to quantify the impact of cannabis use on the risk of non-medical opioid use among people receiving pharmacotherapies for OUD.Methods: A comprehensive search was performed using multiple databases from March 1 to April 5 of 2023. Eligible studies longitudinally assessed the association between cannabis use and non-medical opioid use among people with OUD receiving treatment with buprenorphine, methadone, or naltrexone. We utilized a random-effects model employing the restricted maximum likelihood method. A sensitivity analysis was conducted to understand potential differences between each OUD treatment modality.Results: A total of 10 studies were included in the final meta-analysis. There were 8,367 participants (38% female). The average follow-up time across these studies was 9.7 months (SD = 3.77), ranging from 4 to 15 months. The pharmacotherapies involved were methadone (76.3%) buprenorphine (21.3%), and naltrexone (2.4%). The pooled odds ratio did not indicate that cannabis use significantly influenced non-medical opioid use (OR: 1.00, 95% CI: 0.97-1.04, p = .98). There is evidence of moderate heterogeneity and publication bias.Conclusion: There was no significant association between cannabis use and non-medical opioid use among patients receiving pharmacotherapies for OUD. These findings neither confirm concerns about cannabis increasing non-medical opioid use during MOUD, nor do they endorse its efficacy in decreasing non-medical opioid use with MOUD. This indicates a need for individualized approaches for cannabis use and challenges the requirement of cannabis abstinence to maintain OUD pharmacotherapies.

Emergency services utilization by patients with alcohol-associated hepatitis: An analysis of national trends.

BACKGROUND: Hospitalization and mortality in patients with alcohol-associated hepatitis (AH), a severe form of liver disease, continue to increase over time. Given the severity of the illness, most hospitalized patients with AH are admitted from the emergency department (ED). However, there are no data on ED utilization by patients with AH. Thus, the Nationwide Emergency Department Sample (NEDS) dataset was analyzed to determine the ED utilization for AH. METHODS: Temporal trends (2016-2019) and outcomes of ED visits for AH were determined. Primary or secondary AH diagnoses were based on coding priority. Numbers of patients evaluated in the ED, severity of disease, complications of liver disease, and discharge disposition were analyzed. Crude and adjusted rates were examined, and temporal trends evaluated using logistic regression with orthogonal polynomial contrasts for each year. RESULTS: There were 466,014,370 ED visits during 2016-2019, of which 448,984 (0.096%) were for AH, 85.0% of which required hospitalization. The rate of visits for AH (primary and secondary) between 2016 and 2019 increased from 85 to 106.8/100,000 ED visits. The rate of secondary AH increased more than the rate of primary AH (from 68.6 to 86.5 vs. from 16.4 to 20.3/100,000 ED visits). Patients aged 45-64 years had the highest rate of ED visits for AH, which decreased during the study period, while the rate of ED visits for AH increased in those aged 25-44 years (from 38.5% to 42.9%). The severity of disease (ascites, hepatic encephalopathy, and acute kidney injury) also increased over time. Medicaid and private insurance were the most common payors for patients seeking care in the ED for AH. CONCLUSIONS: Temporal trends show an overall increase in ED utilization rates for AH, more patients requiring hospitalization, and an increase in the proportion of younger patients presenting to the ED with AH.

Race, economic status, and disparities in the receipt of benzodiazepine prescriptions in a large primary care sample.

OBJECTIVE: To evaluate the relationship between race, economic status, and patient characteristics with benzodiazepine prescribing in an urban and suburban primary care context. METHOD: This retrospective study used data from a previously described cohort of patients seen in a large Ohio healthcare system's primary care clinics from 2019 to 2020. Associations and interactions between race, economic status (using median income of patient ZIP code as a proxy), patient characteristics, and prescription of benzodiazepines were assessed using multivariable logistic regression. RESULTS: 455,537 patients had 1,643,473 primary care visits, and 5.8% of patients were prescribed a benzodiazepine. White patients were prescribed benzodiazepines more often than Multiracial/Multicultural, African American and Asian American patients (6.5%, 3.8%, 2.7% and 2.0% respectively). Patients from lower income ZIP codes were less likely to receive a prescription. Interaction effects were observed between race, patient economic status, gender, insurance status, and diagnoses (general anxiety disorder, insomnia, and panic disorder). The largest prescribing disparities by race were among patients with these three diagnoses. The largest disparity in prescription by income was seen in African American patients. CONCLUSION: African American, Multicultural/Multiracial and Asian American patients were less likely than White patients to receive benzodiazepine prescriptions. Middle and lower-income patients are particularly susceptible to this prescribing disparity.

Prescribing of Z-Drugs With and Without Opioid Coprescribing to Primary Care Patients in a Large Health Care System From 2019-2020.

Objective: This study aimed to characterize Z-drug prescribing with and without opioid coprescribing pre- and post-COVID-19 lockdown in the primary care clinics of a large health care system.Methods: A retrospective, cross-sectional study was conducted that measured the prevalence of Z-drug prescribing with and without opioids for adults aged ≥ 18 years that were seen in the primary care clinics of a large health care system in 2019 and 2020. The pre-COVID time period was defined as March 24, 2019-December 31, 2019, and the post-lockdown time period was defined as March 24, 2020-December 31, 2020.Results: Among 455,537 adult patients, 6,743 (1.48%) were prescribed a Z-drug during the study period. In addition, 1,064 (0.2%) were coprescribed a Z-drug and an opioid at least once, constituting 15.78% of patients receiving a Z-drug prescription. There was no change in the rate of Z-drug prescription post-lockdown (odds ratio [OR] = 0.978, 95% confidence interval [CI] = 0.942-1.010, P = .233), though odds of coprescribing decreased (OR = 0.883, 95% CI = 0.789-0.988, P = .031). Important correlates of receiving a Z-drug prescription during the study period were older age, White race, and diagnosis of opioid use disorder. Older age and a diagnosis of opioid use disorder were also associated with coprescribing. Receiving a de novo Z-drug prescription post-lockdown was associated with increased age, White race, and diagnosis of bipolar disorder, generalized anxiety disorder, and insomnia.Conclusions: Rates of Z-drug prescribing were unchanged post-lockdown, while rates of Z-drug with opioid coprescribing decreased. Some patient populations vulnerable to Z-drug adverse effects were at heightened risk of Z-drug prescription, while racial disparities in Z-drug prescribing were observed.

Clinical Presentations and Treatment of Phenibut Toxicity and Withdrawal: A Systematic Literature Review.

OBJECTIVES: This systematic review aimed to identify published articles that evaluated all phenibut toxicity and withdrawal cases to understand better their clinical presentations and treatments. METHODS: A comprehensive literature search was conducted using Medline (Ovid), Embase (Ovid), and Cochrane Library databases to capture all published cases on the presentations and management of phenibut toxicity or withdrawal. RESULTS: Sixty-two cases from 36 studies on presentation and management of phenibut toxicity or phenibut withdrawal were identified. Of all subjects, 80.7% were male. The average age was 30.9 years (SD, 13.2 years; range, 0-71 years). A total of 86.8% reported obtaining phenibut online, and 63.2% reported concomitant substance use with other addictive agents; benzodiazepines and alcohol were the most combined drugs. The average length of hospital stay was 5.0 days (n = 25; SD, 5.4 days; range, 1-25 days) for phenibut toxicity and 7.7 days (n = 20; SD, 7.8 days; range, 0-30 days) for phenibut withdrawals. The most common symptoms reported during phenibut toxicity were altered mental status, somnolence, psychosis, and movement disorders. Of the phenibut toxicity cases, 48.7% required intubation. Benzodiazepines and antipsychotics were most used to treat phenibut toxicity. For phenibut withdrawal cases, 95.7% reported daily use. The most common symptoms reported during phenibut withdrawals were anxiety, irritability or agitation, insomnia, and psychosis. Sixteen (69.6%) of phenibut withdrawal cases required multiple medications for treatment. Benzodiazepines, baclofen, atypical antipsychotics, gabapentanoids, and barbiturates were commonly used to treat phenibut withdrawals. CONCLUSIONS: The seriousness of presentations, combined with the assortments of medications used for both syndromes, reflects the potential dangers of phenibut use and the need for systematized treatment protocols.

Cognitive, imaging, and psychiatric changes associated with chronic toluene use: case report and literature review.

Inhalant misuse and inhalant use disorder are global public health concern that impacts adolescents but can occur throughout life. Toluene is the most commonly misused inhalant. Toluene use leads to significant neuroanatomic, cognitive, and psychiatric deficits. The purpose of this study was to review and summarize the effects of toluene and present a case of a middle-aged patient with an inhalant use disorder. A literature review was conducted to evaluate imaging, neurocognitive, and psychiatric consequences of toluene misuse. The common imaging findings amongst those who misuse toluene were cerebral and cerebellar atrophy, ventricular dilation, loss of gray-white matter differentiation, corpus callosum thinning, and diffuse white matter changes. Concerning cognition, toluene misusers were shown to have deficits in intelligence, attention, memory, visuospatial function, and complex cognition. In addition, toluene users also commonly presented with apathy, flat affect, hallucinations, delusions, anxiety, depression, and insomnia. The neuroanatomical, neurocognitive, and psychiatric effects of toluene misuse are profound. These deficits can make inhalant use disorder difficult to treat. Therefore, evidence-based treatments that recognize and address these domain-specific neurocognitive deficits are needed.

Comment on Yang et al., 2020: Melatonergic agents in the prevention of delirium: A network meta-analysis of randomized controlled trials.

An analysis of delirium prevention considering only older adults is essential. Delirium markedly impacts the older adult population, as it is associated with inpatient occurrence rates from 14% to 56% and hospital mortality rates from 25% to 33% [2]. Ageing comes with a cumulative decline in physiological systems and is a relevant risk factor for chronic diseases [3,4]. Delirium causes in older adults can be multifactorial, including underlying medical conditions, medications, and environmental factors. Therefore, it is vital for healthcare providers to monitor for delirium symptoms in older adults and to implement appropriate interventions, such as addressing underlying medical conditions and addressing possible triggers [5]. Likewise, it is reasonable to think that eventual delirium preventive solutions for older patients would differentiate from the general population.

An Analysis of Benzodiazepine Prescribing to Primary Care Patients in a Large Healthcare System from 2019-2020.

We sought to quantify benzodiazepine prescribing by primary care providers from 2019 to 2020 and identify correlates of prescribing. We hypothesized prescribing would increase post-COVID-19 lockdown. We conducted a retrospective cohort study of adult patients with primary care visits in 2019 or 2020 in a large Ohio healthcare system. Demographics, diagnosis codes, and receipt of benzodiazepine prescriptions were collected. Using multivariable logistic regression, we examined factors associated with benzodiazepine prescription receipt during the whole study period and post-lockdown. 455,537 adult patients had 1,643,473 visits. Benzodiazepines were prescribed in 3.2% (53,049/1,643,473) of visits. Effect sizes for positive associations with benzodiazepine prescription were largest for anxiety disorders. For negative associations, they were largest for Black patients and patients with cocaine use disorder. Benzodiazepine prescribing was positively associated with multiple groups having contraindications, though effect sizes were small. Contrary to our hypothesis, odds of receiving a prescription were 8.8% lower post-lockdown. Benzodiazepine prescribing rates in our system compared favorably to national rates. Year over year odds of receiving a prescription were slightly lower post-lockdown. Racial disparities were present and deserve further study. Strategies to reduce benzodiazepine prescribing to patients with anxiety may yield the largest reductions for benzodiazepine prescribing in primary care settings.

Management of Phenibut Use Disorder and Withdrawal in a Geriatric Patient.

Phenibut is a misused substance which has shown an increase in use over the past decade. Marketed as a "dietary supplement," it is not approved in the United States for use and is not regulated by the Food and Drug Administration. The substance, however, is readily available for purchase through online markets. It has a similar drug profile as alcohol, gabapentin and benzodiazepines. Clinical effects of this drug include physiologic dependence, euphoria, anxiolysis, antispasticity, sedation, and possible nootropic properties. While there are emerging new cases of managing phenibut withdrawal, no cases currently feature phenibut addiction and withdrawal management in the geriatric population. Here we discuss such a case of phenibut addiction and withdrawal in a 68-year-old male who initially began misusing phenibut to alleviate anxiety and insomnia precipitated by worsening affective disorder, sedative, hypnotic, or anxiolytic use disorder, and alcohol use disorder.

Black Pepper (Piper nigrum) for Tobacco Withdrawal: A Case Report.

Tobacco use continues to be one of humanity's most significant public health concerns, causing more than 8-million deaths annually. Existing treatments for tobacco use disorder are limited in efficacy and there is a strong need for identifying effective novel treatments. Small clinical trials indicate that black pepper (Piper nigrum) essential oil may be helpful for treating nicotine withdrawal and craving. However, we are unaware of any cases reporting the use of black pepper for these purposes in nonresearch settings. Here we present the case of a patient who inhaled combusted black pepper to self-medicate nicotine withdrawal when lacking access to tobacco cigarettes while incarcerated. Based on our patient's report, inhalation of combusted black pepper may have alleviated his tobacco withdrawal and cravings by reducing his automatic motor urge to smoke, quelling withdrawal-associated anxiety, and mimicking the sensorimotor experience of smoking tobacco cigarettes. Notably, our patient reported that inhalation of combusted black pepper for treatment of nicotine craving and withdrawal was common in his correctional facility. Though combusted black pepper is highly unlikely to be an appealing treatment outside of a correctional setting, this case suggests that further investigation of vaporized black pepper essential oil for tobacco cessation may be warranted.

Treatment of Misophonia with Risperidone in a Patient with Autism Spectrum Disorder.

We report the case of a 32-year-old male with autism spectrum disorder (ASD) suffering from severe misophonia. After titrating risperidone to 2 mg twice a day, the patient reported a significant reduction in his symptoms and his Amsterdam misophonia scale-revised (AMISOS-R) score dropped by from 31 to 5. Upon discharge, the patient was noted to have decreased irritability and overall improved behavior and effect. This significant symptomatic improvement was likely not explained by inpatient admission alone or other simultaneous pharmacologic treatments, as the effect was seen during an isolated titration of risperidone with other treatments remaining constant. Although, unfortunately, follow-up findings indicated that the treatment was not curative for the patient, risperidone's potential for treating misophonia may warrant systematic investigation.

Drug Misuse in the Veterinary Setting: an Under-recognized Avenue.

PURPOSE OF REVIEW: Prescription drug misuse is a public health concern. Governments are attempting to restrict the incidence of medication diversion by establishing laws to curb drug access from human healthcare providers. Veterinarians, who also prescribe controlled substances and see hundreds of millions of patients annually in the USA, are often overlooked as a source of prescription drug misuse. RECENT FINDINGS: Evidence suggests that drug misuse occurs in the veterinary setting, and veterinarians acknowledge this as a common problem. Although analgesics are alleged to be the most common drug class diverted, a recent cross-sectional study suggests veterinarian opioid prescribing rate continues to increase. Prescription misuse in veterinarian settings is likely underestimated and needs to be better investigated. Human healthcare providers must familiarize themselves with this potential channel to prescription drugs and specifically question patients on veterinary drug misuse.

Surviving and thriving in terms of symbiotic performance of antibiotic and phage-resistant mutants of Bradyrhizobium of soybean [Glycine max (L.) Merrill].

Rhizobial inoculation plays an important role in yielding enhancement of soybean, but it is frequently disturbed by competition with bacterial population present in the soil. Identification of potential indigenous rhizobia as competitive inoculants for efficient nodulation and N(2)-fixation of soybean was assessed under laboratory and field conditions. Two indigenous bradyrhizobial isolates (MPSR033 and MPSR220) and its derived different antibiotic (streptomycin and gentamicin) and phage (RT5 and RT6)-resistant mutant strains were used for competition study. Nodulation occupancy between parent and mutant strains was compared on soybean cultivar JS335 under exotic condition. Strain MPSR033 Sm(r) V(r) was found highly competitive for nodule occupancy in all treatment combinations. On the basis of laboratory experiments four indigenous strains (MPSR033, MPSR033 Sm(r), MPSR033 Sm(r) V(r), MPSR220) were selected for their symbiotic performance along with two exotic strains (USDA123 and USDA94) on two soybean cultivars under field conditions. A significant symbiotic interaction between Bradyrhizobium strains and soybean cultivar was observed. Strain MPSR033 Sm(r) V(r) was found superior among the rhizobial treatments in seed yield production with both cultivars. The 16S rRNA region sequence analysis of the indigenous strains showed close relationship with Bradyrhizobium yuanmingense strain. These findings widen out the usefulness of antibiotic-resistance marked phage-resistant bradyrhizobial strains in interactive mode for studying their symbiotic effectiveness with host plant, and open the way to study the mechanism of contact-dependent growth inhibition in rhizobia.

Genotypic characterization of phage-typed indigenous soybean bradyrhizobia and their host range symbiotic effectiveness.

Analysis of genetic diversity among indigenous rhizobia and its symbiotic effectiveness with soybean cultivar is important for development of knowledge about rhizobial ecology. In India, little is known about the genetic resources and diversity of rhizobia nodulating soybean. Indigenous bradyrhizobia isolated from root nodules of soybean plants, collected from traditional cultivating regions of two states (Madhya Pradesh and Uttar Pradesh) of India, were screened for bacteriophage sensitivity to identify successful broad host range symbiotic effectivity. Of 172 rhizobial isolates, 91 showed sensitivities to eight lytic phages and form ten groups on the basis of sensitivity patterns. The genetic diversity of 23 isolates belonging to different phage groups was assessed along with that of strains USDA123 and USDA94 by the restriction fragment length polymorphism (RFLP) analysis of 16S rDNA, intergenic spacer (IGS) (16S-23S rDNA), and DnaK regions. RFLP analysis of 16S rDNA formed 5 groups, whereas 19 and 9 groups were revealed by IGS and the DnaK genes, respectively. The IGS regions showed many amplified polymorphic bands. Nine isolates which revealed high RFLP polymorphism in the abovementioned regions (16S rRNA, IGS, DnaK) were used for 16S rRNA sequence analyses. The results indicate that taxonomically, all isolates were related to Rhizobium etli, Bradyrhizobium spp., and Bradyrhizobium yuanmingense. The doubling time of isolates varied from 9 h (MPSR155) to 16.2 h (MPSR068) in YM broth. Five isolates which did not show cross infectivity with isolated phage strains were studied for symbiotic efficiency. All isolates showed broad host range symbiotic effectiveness forming effective nodules on Vigna mungo, Vigna radiata, Vigna unguiculata, and Cajanus cajan. The present study provides information on genetic diversity and host range symbiosis of indigenous soybean rhizobia typed by different phages.