Benzodiazepine receipt in adults with psychogenic non-epileptic seizures in the USA.

Background: Characterising benzodiazepine (BZD) prescribing to individuals with psychogenic non-epileptic seizures (PNES) is important for optimising PNES outcomes, but existing data is lacking. Methods: Using a nationwide administrative claims database (2016-2022), incident PNES was defined as an International classification of diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis in an inpatient or outpatient healthcare encounter after a 1-year period with no documented diagnosis. We described clinical characteristics of adults with incident PNES and estimated the prevalence of outpatient BZD treatment in the baseline year and 30-day follow-up period, with secondary analyses stratifying by baseline ES, anxiety and/or insomnia diagnoses, representing common indications for BZD receipt. We used logistic regression to evaluate predictors of post-PNES BZD receipt. Results: Among 20 848 adults with incident PNES diagnosis, 33.1% and 15.1% received BZDs in the year and month prior to PNES diagnosis, respectively, and 18.1% received BZDs in the month following a PNES diagnosis; 5.4% of those without prior BZD prescriptions received BZDs after diagnosis. The median days' supply was 30 days, with clonazepam, alprazolam and lorazepam representing the most common BZDs prescribed after PNES. Most people who received BZDs in the month prior to PNES diagnosis remained on BZDs in the month after PNES diagnosis (62.9%), with similar findings in the subcohorts without ES, anxiety and/or insomnia. Baseline BZD receipt and anxiety disorders, but not baseline ES diagnoses, were strong independent predictors of post-PNES BZD receipt. Conclusions: While new BZD initiation is rare after PNES, most individuals with BZD scripts 1 month before PNES continue scripts after diagnosis.

The brain-heart-immune axis: a vago-centric framework for predicting and enhancing resilient recovery in older surgery patients.

Nearly all geriatric surgical complications are studied in the context of a single organ system, e.g., cardiac complications and the heart; delirium and the brain; infections and the immune system. Yet, we know that advanced age, physiological stress, and infection all increase sympathetic and decrease parasympathetic nervous system function. Parasympathetic function is mediated through the vagus nerve, which connects the heart, brain, and immune system to form, what we have termed, the brain-heart-immune axis. We hypothesize that this brain-heart-immune axis plays a critical role in surgical recovery among older adults. In particular, we hypothesize that the brain-heart-immune axis plays a critical role in the most common surgical complication among older adults: postoperative delirium. Further, we present heart rate variability as a measure that may eventually become a multi-system vital sign evaluating brain-heart-immune axis function. Finally, we suggest the brain-heart-immune axis as a potential interventional target for bio-electronic neuro-immune modulation to enhance resilient surgical recovery among older adults.

Co-occurring autism, ADHD, and gender dysphoria in children, adolescents, and young adults with eating disorders: an examination of pre- vs. post-COVID pandemic outbreak trends with real-time electronic health record data.

Background: Incidence rates of autism, attention-deficit/hyperactivity disorder (ADHD), and gender dysphoria (GD) are rising not only in the general population, but particularly among children, adolescents, and young adults with eating disorders (EDs). While ED rates have risen during the COVID pandemic, trends in co-occurring autism, ADHD, and GD have yet to be investigated in detail or at scale by way of large electronic medical record data. Objectives: To investigate trends in rates of co-occurring autism, ADHD, and GD among children, adolescents, and young adults with EDs in years prior to and during the COVID-19 pandemic. Methods: We utilized a de-identified multinational electronic health records database (TriNetX) with 48,558 individuals aged 5-26 diagnosed with eating disorders (EDs) at least twice between 2017 and 2022. The primary predictor variable differentiated between the years of each person's index (first) ED diagnosis (2017-2019 vs. 2020-2022). The primary outcome variable was the rate of new co-occurring psychiatric diagnoses of autism, ADHD, and GD in the year following each patient's first ED diagnosis. We applied propensity score-matched multivariable logistic regressions to compare primary outcomes between 2017-2019 and 2020-2022. Results: Our analysis included 17,445 individuals diagnosed with EDs in 2017-2019 (8% autism, 13.5% ADHD, 1.9% GD) and 31,113 diagnosed with EDs in 2020-2022 (8% autism, 14.6% ADHD, 3.2% GD). After 1:1 propensity score matching, 17,202 individuals from the 2017-2019 cohort were matched to peers mirroring the 2020-2022 cohort. Those diagnosed in 2020-2022 showed a 19% (aOR[95%CI]=1.19[1.07-1.33]), 25% (aOR=1.25[1.04-1.49]), and 36% (aOR=1.36[1.07-1.74]) increase in odds for autism, ADHD, and GD diagnoses, respectively, within the 365 days after the index EDs diagnosis, compared to the 2017-2019 cohort. Discussion: Rates of autism, ADHD, and GD are significantly higher in individuals with ED in the post-pandemic 2020-2022 cohort in comparison to the pre-pandemic 2017-2019 cohort, even after controlling for baseline levels of co-occurring psychiatric diagnoses. Such findings reveal a critical gap in our current understanding of the totality of ways in which COVID-19 may have impacted the onset and clinical course of EDs, autism, ADHD, and GD among children, adolescents, and young adults.

Minimizing Survey Questions for PTSD Prediction Following Acute Trauma.

Traumatic experiences have the potential to give rise to post-traumatic stress disorder (PTSD), a debilitating psychiatric condition associated with impairments in both social and occupational functioning. There has been great interest in utilizing machine learning approaches to predict the development of PTSD in trauma patients from clinician assessment or survey-based psychological assessments. However, these assessments require a large number of questions, which is time consuming and not easy to administer. In this paper, we aim to predict PTSD development of patients 3 months post-trauma from multiple survey-based assessments taken within 2 weeks post-trauma. Our objective is to minimize the number of survey questions that patients need to answer while maintaining the prediction accuracy from the full surveys. We formulate this as a feature selection problem and consider 4 different feature selection approaches. We demonstrate that it is possible to achieve up to 72% accuracy for predicting the 3-month PTSD diagnosis from 10 survey questions using a mean decrease in impurity-based feature selector followed by a gradient boosting classifier.

Contraceptive uptake in postpartum people with and without opioid use disorder and opioid use with co-occurring substance use.

Background: Using contraception to delay pregnancy allows people with opioid use disorder (OUD) to choose when they are ready to continue their families. Yet, postpartum contraceptive uptake among people with OUD has not been well characterized. Methods: Analyses used 73,811 pregnancy episodes among 61,221 people (2016-2021) from the St. Louis University-SSM Virtual Data Warehouse. OUD was defined from the year prior and through pregnancy. Contraceptive uptake was defined within 90-days after delivery. We used Generalized Estimating Equations-type multinomial logit models to assess association of OUD +/- co-occurring substance use disorders (SUDs) with any contraception (yes/no) and type of contraception (effective - pills, patch, ring, injection; or highly effective - long-acting reversible, LARC methods [intrauterine device, implant] and sterilization). Results: The sample was 66.0 % white and average age was 27.7 years (±5.6). 32.5 % of pregnancies were followed by contraception initiation, 2.3 % had an OUD diagnosis, and 1.3 % OUD with co-occurring SUD. There was no association between OUD and postpartum contraception receipt, but OUD was associated with decreased highly effective compared to effective method initiation (aOR=0.76; 95 % CI: [0.64-0.91]). OUD plus co-occurring SUD was associated with decreased uptake across all contraception types (aOR=0.81[0.70-0.93]), specifically, highly-effective methods (aOR=0.48[0.38-0.61]). Conclusions: Overall postpartum contraception uptake among people with OUD is comparable to uptake in the non-OUD population. People with OUD plus co-occurring SUDs are particularly unlikely to receive contraception. The reasons people choose contraceptive methods are complex and may differ by SUD severity. More information is needed to understand factors that impact postpartum contraception initiation.

Co-occurring psychiatric disorders in young people with eating disorders: An multi-state and real-time analysis of real-world administrative data.

OBJECTIVE: We aimed to use real-world data to characterize the burden of psychiatric comorbidities in young people with eating disorders (EDs) relative to peers without EDs. METHOD: This retrospective cohort study used a large federated multi-national network of real-time electronic health records. Our cohort consisted of 124,575 people (14,524 people receiving their index, first-ever, ED diagnosis, compared to 110,051 peers without EDs initiating antidepressants). After 1:1 propensity score matching of the two cohorts by pre-existing demographic and clinical characteristics, we used multivariable logistic regression to compute the adjusted odds ratio (aOR) of psychiatric diagnoses arising in the year following the index event (either first ED diagnosis or first antidepressant script). RESULTS: Over 50% of people with EDs had prior psychiatric diagnoses in the year preceding the index EDs diagnosis, with mood disorders, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), specific phobia (SP), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) being the most common. Adjusted analyses showed higher odds for mood disorders (aOR = 1.20 [95% CI = 1.14-1.26]), GAD (aOR = 1.28 [1.21-1.35]), PTSD (aOR = 1.29 [1.18-1.40]), and SP (aOR = 1.45 [1.31-1.60]) in the EDs cohort compared to antidepressant-initiating peers without EDs, although rates of ADHD and ASD were similar in both cohorts. CONCLUSION: This large-scale real-time analysis of administrative data illustrates a high burden of co-occurring psychiatric disorders in people with EDs.

Treatment setting and buprenorphine discontinuation: an analysis of multi-state insurance claims.

BACKGROUND: Potential differences in buprenorphine treatment outcomes across various treatment settings are poorly characterized in multi-state administrative data. We thus evaluated the association of opioid use disorder (OUD) treatment setting and insurance type with risk of buprenorphine discontinuation among commercial insurance and Medicaid enrollees initiated on buprenorphine. METHODS: In this observational, retrospective cohort study using the Merative MarketScan databases (2006-2016), we analyzed buprenorphine retention in 58,200 US adults with OUD. Predictor variables included insurance status (Medicaid vs commercial) and treatment setting, operationalized as substance use disorder (SUD) specialty treatment facility versus outpatient primary care physicians (PCPs) versus outpatient psychiatry, ascertained by linking physician visit codes to buprenorphine prescriptions. Treatment setting was inferred based on timing of prescriber visit claims preceding prescription fills. We estimated time to buprenorphine discontinuation using multivariable cox regression. RESULTS: Among enrollees with OUD receiving buprenorphine, 26,168 (45.0%) had prescriptions from SUD facilities without outpatient buprenorphine treatment, with the remaining treated by outpatient PCPs (n = 23,899, 41.1%) and psychiatrists (n = 8133, 13.9%). Overall, 50.6% and 73.3% discontinued treatment at 180 and 365 days respectively. Buprenorphine discontinuation was higher among enrollees receiving prescriptions from SUD facilities (aHR = 1.03[1.01-1.06]) and PCPs (aHR = 1.07[1.05-1.10]). Medicaid enrollees had lower buprenorphine retention than those with commercial insurance, particularly those receiving buprenorphine from SUD facilities and PCPs (aHR = 1.24[1.20-1.29] and aHR = 1.39[1.34-1.45] respectively, relative to comparator group of commercial insurance enrollees receiving buprenorphine from outpatient psychiatry). CONCLUSION: Buprenorphine discontinuation is high across outpatient PCP, psychiatry, and SUD treatment facility settings, with potentially lower treatment retention among Medicaid enrollees receiving care from SUD facilities and PCPs.

Brain-Hazardous Medications and Potential Subadequate Antidepressant Dosing in Older Surgical Patients Receiving Home Antidepressants: An Observational Study of a Large US Health System.

BACKGROUND: Older surgical patients with depression often experience poor postoperative outcomes. Poor outcomes may stem from brain-hazardous medications and subadequate antidepressant dosing. METHODS: This was a retrospective, observational cohort study covering the period between January 1, 2021 and December 31, 2021. Patients ≥60 years of age who underwent inpatient surgery and had an overnight stay at an integrated academic health care system comprising 14 hospitals were eligible. We analyzed the prevalence of home central nervous system (CNS)-active potentially inappropriate medication (PIM) and potential subadequate antidepressant dosing in older surgical patients receiving home antidepressants. Univariable and multivariable regression models were used to identify factors associated with home CNS-active PIM prescribing and potential subadequate antidepressant dosing. Additionally, outcomes were compared among patients receiving and not receiving CNS-active PIMs and patients receiving and not receiving subadequate antidepressant dosing. RESULTS: A total of 8031 patients were included in this study (47% female, mean age = 70 years) of whom 2087 (26%) were prescribed antidepressants. Roughly one-half (49%, 95% confidence interval [CI], 46.5-50.1) of patients receiving home antidepressants were also receiving ≥1 CNS-active PIM and 29% (95% CI, 27.0-29.3) were receiving a potential subadequate dose. Factors associated with an increased likelihood of receiving a home CNS-active PIM included female sex (adjusted odds ratio [aOR], 1.46), anxiety (aOR, 2.43), asthma or chronic obstructive pulmonary disease (aOR, 1.39), and serotonin-norepinephrine reuptake inhibitor use (aOR, 1.54). Patients aged ≥75 years (aOR, 1.57), black race (aOR, 1.48) and those with congestive heart failure (aOR, 1.33) were more likely to be prescribed a potential subadequate antidepressant dose. Patients receiving potential subadequate antidepressant doses were discharged home less often (64% vs 73%), had a longer hospital length of stay (9 days vs 7 days), and a higher mortality rate (18% vs 10%) compared to patients receiving adequate home antidepressant doses (P-value for all <0.01). No differences in these outcomes were found among patients receiving home antidepressants with or without CNS-active PIMs. CONCLUSIONS: Older surgical patients receiving antidepressants are frequently prescribed brain-hazardous medications and potentially subadequate antidepressant doses. Those receiving subadequate antidepressant doses may be at risk for worse postoperative outcomes compared to patients receiving adequate doses. The role of preoperative medication optimization to improve outcomes for older surgical patients should be evaluated.

Pregnancy Rates Among Women Treated with Medication for Opioid Use Disorder.

BACKGROUND: Treatment-seeking people with opioid use disorder (OUD) who are capable of pregnancy need accurate information about the potential impact of medication to treat OUD (MOUD) on fertility to make informed choices about treatment that are consistent with their reproductive wishes. There is a dearth of research on fertility associated with MOUD receipt in birthing people with OUD. OBJECTIVE: To estimate the association between treatment with MOUD and odds of conception among birthing people using national administrative claims. DESIGN: Retrospective case-crossover study using multi-state US administrative data (2006-2016). Dates of conception were estimated from delivery dates and served as "case" days for which MOUD exposures were compared to those on all other ("control") days of insurance enrollment. PARTICIPANTS: Treatment-seeking people with OUD with a delivery during the observation period. MAIN MEASURES: Odds ratios for conception from within-person fixed effects models were modeled as a function of exposure to MOUD (buprenorphine, methadone, extended-release depot naltrexone, or oral naltrexone) using conditional logistic regression. KEY RESULTS: A total of 21,928 births among 19,133 people with OUD were identified. In the sample, 5873 people received buprenorphine, 1825 methadone, 486 extended-release naltrexone, and 714 oral naltrexone. Participants could receive more than one type of MOUD. Mean age was 28.2 years (SD = 2.2; range = 16-45), with 76.2% having Medicaid. vs. commercial insurance. Compared to no MOUD, periods of methadone (aOR = 0.55 [95% CI = 0.48-0.63]) or buprenorphine receipt (aOR = 0.84 [0.77-0.91]) were associated with fewer conceptions. Treatment periods with extended-release depot naltrexone compared to no medication were associated with higher odds of conception (aOR = 1.75 [1.22-2.50]) and there was no significant difference in conception with oral naltrexone (aOR = 1.02 [0.67-1.54]). CONCLUSIONS: The association between MOUD and odds of conception among birthing people varied by type of MOUD, with extended-release naltrexone associated with higher odds of conceiving compared to no treatment. Clinical studies are urgently needed to investigate these findings further.

County-level neonatal opioid withdrawal syndrome rates and real-world access to buprenorphine during pregnancy: An audit ("secret shopper") study in Missouri.

Background: Amid rising rates of neonatal opioid withdrawal syndrome (NOWS) worldwide and in many regions of the USA, we conducted an audit study ("secret shopper study") to evaluate the influence of county-level buprenorphine capacity and rurality on county-level NOWS rates. Methods: In 2019, up to three phone calls were made to buprenorphine prescribers in the state of Missouri (USA). County-level buprenorphine capacity was defined as the number of clinicians (across all specialties) accepting pregnant people divided by the number of births. Multivariable negative binomial regression models estimated associations between buprenorphine capacity, rurality, and county-level NOWS rates, controlling for potential confounders (i.e., poverty, unemployment, and physician shortages) that may correspond to higher rates of NOWS and lower rates of buprenorphine prescribing. Analyses were stratified using tertiles of county-level overdose rates (top, middle, and lowest 1/3 of overdose rates). Results: Of 115 Missouri counties, 81(70 %) had no buprenorphine capacity, 17(15 %) were low-capacity (<0.5-clinicians/1,000 births), and 17(15 %) were high-capacity (≥0.5/1,000 births). The mean NOWS rate was 6.5/1,000 births. In Missouri counties with both the highest and lowest opioid overdose rates, higher buprenorphine capacity did not correspond to decreases in NOWS rates (incidence rate ratio[IRR]=1.23[95 %-confidence-interval[CI]=0.65-2.32] and IRR=1.57[1.21-2.03] respectively). Rurality did not correspond to greater NOWS burden in both Missouri counties with highest and lowest opioid overdose rates. Conclusions: The vast majority of counties in Missouri have no capacity for buprenorphine prescribing during pregnancy. Rurality and lower buprenorphine capacity did not significantly predict elevated rates of NOWS.

Preoperative therapy in melanoma: Evolving perspectives in clinical trials.

We reviewed phase II and III trials beginning after 2010 studying preoperative therapy in melanoma (61 trials). Compared to standard adjuvant treatment, neoadjuvant immune checkpoint inhibitors (ICIs) show improved outcomes with approximately 70-80% recurrence free survival at 2 years. Several biomarkers demonstrate predictive value for pathological response (higher PD-L1 expression) and survival (IFN-γ signatures, CD8 + cell density). A number of 'non-standard' treatment mechanisms are being studied in combination with ICI therapies such as TLR-9 agonists, and anti-LAG3 checkpoint inhibitors, which show promise for alternative therapy options in the neoadjuvant setting. Finally, trials for advanced unresectable melanomas show improved survival compared to definitive systemic treatment when upfront systemic therapies lead to resectability. To conclude, in the preoperative setting for melanoma, ICIs have potential to improve outcomes for patients, and will likely change the standard treatment approach for advanced resectable disease.

Functional gallbladder disorder: Interim analysis of a prospective cohort study.

BACKGROUND: Functional gallbladder disorder (FGBD) remains a controversial indication for cholecystectomy. METHODS: A prospective cohort study enrolled patients strictly meeting Rome criteria for FGBD, and cholecystectomy was performed. They were assessed pre- and 3 and 6 months postoperatively with surveys of abdominal pain and quality of life (RAPID and SF-12 surveys, respectively). Interim analysis was performed. RESULTS: Although neither ejection fraction nor pain reproduction predicted success after cholecystectomy, the vast majority of enrolled patients had a successful outcome after undergoing cholecystectomy for FGBD: of a planned 100 patients, 46 were enrolled. Of 31 evaluable patients, 26 (83.9 â€‹%) reported RAPID improvement and 28 (93.3 â€‹%) SF12 improvement at 3- or 6-month follow-up. CONCLUSION: FGBD, strictly diagnosed, should perhaps no longer be a controversial indication for cholecystectomy, since its success rate for biliary pain in this study was similar to that for symptomatic cholelithiasis. Larger-scale studies or randomized trials may confirm these findings.

Screen Use and Social Media "Addiction" in the Era of TikTok: What Generalists Should Know.

While the term "screen addiction" or "social media addiction" is gaining steam in the popular media, preclinical, clinical, and population health research have not caught up with regards to the diagnosis and treatment of unhealthy screen use. The overarching goal of this article is to provide broad clinical tips to generalists, working outside the mental health specialty, on the evaluation and treatment of unhealthy screen exposure in children and young adults. We will clarify the difference between addiction and overuse, and why this distinction matters. Recognizing that screens are here to stay in the post-COVID era, we will provide guidance on how to reduce potential harms associated with screen exposure without necessarily requiring people to abstain or stop using screens.

Effects of spectral smearing on speech understanding and masking release in simulated bilateral cochlear implants.

Differences in spectro-temporal degradation may explain some variability in cochlear implant users' speech outcomes. The present study employs vocoder simulations on listeners with typical hearing to evaluate how differences in degree of channel interaction across ears affects spatial speech recognition. Speech recognition thresholds and spatial release from masking were measured in 16 normal-hearing subjects listening to simulated bilateral cochlear implants. 16-channel sine-vocoded speech simulated limited, broad, or mixed channel interaction, in dichotic and diotic target-masker conditions, across ears. Thresholds were highest with broad channel interaction in both ears but improved when interaction decreased in one ear and again in both ears. Masking release was apparent across conditions. Results from this simulation study on listeners with typical hearing show that channel interaction may impact speech recognition more than masking release, and may have implications for the effects of channel interaction on cochlear implant users' speech recognition outcomes.

Predicting kidney transplant survival using multiple feature representations for HLAs.

Kidney transplantation can significantly enhance living standards for people suffering from end-stage renal disease. A significant factor that affects graft survival time (the time until the transplant fails and the patient requires another transplant) for kidney transplantation is the compatibility of the Human Leukocyte Antigens (HLAs) between the donor and recipient. In this paper, we propose 4 new biologically-relevant feature representations for incorporating HLA information into machine learning-based survival analysis algorithms. We evaluate our proposed HLA feature representations on a database of over 100,000 transplants and find that they improve prediction accuracy by about 1%, modest at the patient level but potentially significant at a societal level. Accurate prediction of survival times can improve transplant survival outcomes, enabling better allocation of donors to recipients and reducing the number of re-transplants due to graft failure with poorly matched donors.