Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy.

BACKGROUND: Among women with epilepsy, studies regarding changes in seizure frequency during pregnancy have been limited by the lack of an appropriate nonpregnant comparator group to provide data on the natural course of seizure frequency in both groups. METHODS: In this prospective, observational, multicenter cohort study, we compared the frequency of seizures during pregnancy through the peripartum period (the first 6 weeks after birth) (epoch 1) with the frequency during the postpartum period (the following 7.5 months after pregnancy) (epoch 2). Nonpregnant women with epilepsy were enrolled as controls and had similar follow-up during an 18-month period. The primary outcome was the percentage of women who had a higher frequency of seizures that impaired awareness during epoch 1 than during epoch 2. We also compared changes in the doses of antiepileptic drugs that were administered in the two groups during the first 9 months of epoch 1. RESULTS: We enrolled 351 pregnant women and 109 controls with epilepsy. Among the 299 pregnant women and 93 controls who had a history of seizures that impaired awareness and who had available data for the two epochs, seizure frequency was higher during epoch 1 than during epoch 2 in 70 pregnant women (23%) and in 23 controls (25%) (odds ratio, 0.93; 95% confidence interval [CI], 0.54 to 1.60). During pregnancy, the dose of an antiepileptic drug was changed at least once in 74% of pregnant women and in 31% of controls (odds ratio, 6.36; 95% CI, 3.82 to 10.59). CONCLUSIONS: Among women with epilepsy, the percentage who had a higher incidence of seizures during pregnancy than during the postpartum period was similar to that in women who were not pregnant during the corresponding epochs. Changes in doses of antiepileptic drugs occurred more frequently in pregnant women than in nonpregnant women during similar time periods. (Funded by the National Institutes of Health; MONEAD ClinicalTrials.gov number, NCT01730170.).

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. Main Outcomes and Measures: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. Results: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Conclusions and Relevance: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03866174.

Opioid Overdose Deaths Among Formerly Incarcerated Persons and the General Population: North Carolina, 2000‒2018.

Objectives. To compare opioid overdose death (OOD) rates among formerly incarcerated persons (FIPs) from 2016 to 2018 with the North Carolina population and with OOD rates from 2000 to 2015. Methods. We performed a retrospective cohort study of 259 861 North Carolina FIPs from 2000 to 2018 linked with North Carolina death records. We used indirectly standardized OOD mortality rates and ratios and present 95% confidence intervals (CIs). Results. From 2017 to 2018, the OOD rates in the North Carolina general population decreased by 10.1% but increased by 32% among FIPs. During 2016 to 2018, the highest substance-specific OOD rate among FIPs was attributable to synthetic narcotics (mainly fentanyl and its analogs), while OOD rates for other opioids were half or less than that from synthetic narcotics. During 2016 to 2018, the OOD risk for FIPs from synthetic narcotics was 50.3 (95% CI = 30.9, 69.6), 20.2 (95% CI = 17.3, 23.2), and 18.2 (95% CI = 15.9, 20.5) times as high as that for the North Carolina population at 2-week, 1-year, and complete follow-up after release, respectively. Conclusions. While nationwide OOD rates declined from 2017 to 2018, OOD rates among North Carolina FIPs increased by about a third, largely from fentanyl and its analogs. (Am J Public Health. 2022;112(2):300-303. https://doi.org/10.2105/AJPH.2021.306621).

Mental health emergency department visits: An exploration of case definitions in North Carolina.

BACKGROUND: Mental health (MH) disorders comprise a high disease burden and have long-lasting impacts. To improve MH, it is important to define public health MH surveillance. METHODS: We compared MH related definitions using ICD-10-CM codes: The Council of State and Territorial Epidemiologists' (CSTE) surveillance indicators for all MH, mood or depressive, schizophrenic, and drug/alcohol-induced disorders; and North Carolina's (NC) syndromic surveillance system's definition for anxiety/mood/psychotic disorders, and suicide/self-harm. We compared code definitions and frequent codes in 2019 emergency department (ED) data for those age ≥ 10 years. RESULTS: CSTE's definition resulted in over one million MH-related visits (23% of all ED visits) and NC's definitions in 451,807 MH-related visits (9% of all ED visits). Using CSTE's broadest definition, nicotine use was the most common visit type; using NC's definitions, it was major depressive disorder. CONCLUSIONS: Standardizing population-level MH indicators benefits surveillance efforts. Given its prevalence, efforts should focus on documenting MH to improve treatment and prevention.

The Obstetrical Care and Delivery Experience of Women with Epilepsy in the MONEAD Study.

OBJECTIVE: We examined mode of delivery among pregnant women with epilepsy (PWWE) versus pregnant controls (PC). We hypothesize that PWWE are more likely to deliver by cesarean. STUDY DESIGN: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an observational, prospective, multicenter investigation of pregnancy outcomes funded by the National Institute of Health (NIH). MONEAD enrolled patients from December 2012 through January 2016. PWWE were matched to PC in a case:control ratio of 3:1. This analysis had 80% power to detect a 36% increase in cesarean frequency assuming a baseline rate of 30% among PC at an α = 0.05. RESULTS: This report analyzed 331 PWWE (76%) and 102 PC (24%) who gave birth while enrolled in the study. PWWE and PC had similar rates of cesarean delivery (34.7 vs. 28.6%; p = 0.27). Of women with cesarean, rates of cesarean without labor were similar between groups for those delivering in recruitment hospitals (48.2 vs. 50.0%) but in nonrecruitment hospitals, cesarean rates without labor were over two-fold higher among PWWE than those of PC (68.8 vs. 30.8%; p = 0.023). Receipt of a cesarean after labor did not differ for PWWE compared to PC or by type of antiepileptic drug among the PWWE. CONCLUSION: These findings suggest that the obstetrical experiences of PWWE and PC are similar. An interesting deviation from this observation was the mode of delivery with higher unlabored cesarean rates occurring among PWWE in nonrecruitment hospitals. As the study recruitment hospitals were tertiary academic centers and nonrecruitment hospitals tended to be community-based institutions, differences in perinatal expertise might contribute to this difference. KEY POINTS: · Unlabored cesarean rates higher among women with epilepsy.. · Provider preference may influence delivery mode among women with epilepsy.. · Type and amount of antiepileptic drug was not associated with mode of delivery..

Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN).

Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR) Acinetobacter baumannii Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of i.v. minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200-mg i.v. dose of minocycline. Plasma PK samples were collected predose and 1, 4, 12, 24, 36, and 48 h after initiation of minocycline. Total and unbound minocycline concentrations were determined at each time point. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (free area under the curve above the MIC [fAUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of A. baumannii were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (fub) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with fub). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with A. baumannii infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation.

IL-1B(3954) polymorphism and red complex bacteria increase IL-1ß (GCF) levels in periodontitis.

OBJECTIVE: The aim of this study was to compare IL-1ß levels in gingival crevicular fluid (GCF) from healthy and periodontitis sites of IL-1B(3954)-Single Nucleotide Polymorphism (SNP) positive and IL-1B(3954)-SNP negative periodontitis subjects in association with their bacterial profiles. BACKGROUND: Susceptibility to periodontitis has been associated with several risk factors, including allelic variants at multiple gene loci. Variations in the IL-1 gene cluster have been linked with increased risk for periodontitis. IL-1B(3954)-SNP has been previously associated with increased levels of IL-1ß in GCF or periodontal tissues in chronic periodontitis patients, as well as higher levels of specific periodontal pathogens. There is insufficient evidence to conclude if IL-1B gene polymorphisms affect the susceptibility to periodontitis by ultimately modulating the levels of IL-1ß in GCF, the subgingival microbial profile or both. MATERIALS AND METHODS: GCF, subgingival plaque, and buccal epithelial cells were collected from 32 individuals with periodontitis. GCF IL-1ß levels were measured by an enzyme-linked immunosorbent assay (ELISA). Bacterial plaque samples were analyzed for 11 periodontal pathogens using polymerase chain reaction (PCR) analysis with specific primers for the 16SrRNA gene of each bacterium. IL-1B(3954)-SNP status was determined by identifying the carriers of the polymorphic T allele. RESULTS: A significant association was shown between IL-1B(3954)-SNP and IL-1ß GCF levels (amount and concentration). The concomitant presence of two or three red complex bacterial species was associated with increased IL-1ß GCF levels in periodontitis sites (site-level analysis). The concurrent presence of all three red complex periodontal pathogens and IL-1B(3954)-SNP was associated with the highest IL-1ß GCF levels in periodontitis sites. CONCLUSIONS: Our results indicate an independent association of both IL-1B(3954)-SNP and red complex bacterial species with increased IL-1ß levels in GCF of periodontitis sites. A better understanding of the interaction between genetics, bacteria, and inflammation is essential to develop more effective diagnostic, prognostic, and therapeutic tools for periodontitis.

Assessing recovery rate methods: A review and application for human skeletal assemblages.

OBJECTIVES: Recovery rates reflect the amount of recovered skeletal materials based on expectations about the total number of elements or individuals that should be present in an assemblage. It is an underlying concept that reflects analytical potential, wherein high recovery rates typically indicate high analytical capabilities. However, numerous methods are available to calculate different types of recovery rates, and each method addresses various types of research questions and utilizes different variables. Therefore, recovery rates cannot be applied and compared directly, and the appropriate recovery rate for any given research question must be considered thoughtfully. MATERIALS AND METHODS: Several methods of determining individual and element recovery rates are applied to the USS Oklahoma commingled human remains assemblage and discussed with regard to their utility. RESULTS: Depending on which method is used, recovery rates range from 91 to 102% for the recovery of individuals and 0.02 to 91% for the recovery of elements within this assemblage. DISCUSSION: These results emphasize the need to carefully consider which recovery rate is most appropriate based on associated research questions and project contexts. We introduce the idea of the analytical recovery rate, a flexible concept to determine the potential assessment of biological profile parameters once individuation of commingled remains has occurred, wherein elements are selected based on the needs of the project as well as element preservation.

Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase 3 Clinical Trial.

Background: Studies indicate that the prevalence of multidrug-resistant infections, including hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), has been rising. There are many challenges associated with these disease conditions and the ability to develop new treatments. Additionally, HABP/VABP clinical trials are very costly to conduct given their complex protocol designs and the difficulty in recruiting and retaining patients. Methods: With input from clinicians, representatives from industry, and the US Food and Drug Administration, we conducted a study to (1) evaluate the drivers of HABP/VABP phase 3 direct and indirect clinical trial costs; (2) to identify opportunities to lower these costs; and (3) to compare (1) and (2) to endocrine and oncology clinical trials. Benchmark data were gathered from proprietary and commercial databases and used to create a model that calculates the fully loaded (direct and indirect) cost of typical phase 3 HABP/VABP endocrine and oncology clinical trials. Results: Results indicate that the cost per patient for a 200-site, 1000-patient phase 3 HABP/VABP study is $89600 per patient. The cost of screen failures and screen failure rates are the main cost drivers. Conclusions: Results indicate that biopharmaceutical companies and regulatory agencies should consider strategies to improve screening and recruitment to decrease HABP/VABP clinical trial costs.

Prevalence of Metabolic Syndrome and Its Individual Components Among Midwestern University Students.

Michigan has the 17th highest adult obesity rate in the United States. Among college-aged adults between 18 and 25 years old, the rate of obesity was 11.6%. Obesity is a key precedent for the development of metabolic syndrome. Accordingly, the purpose of this study was to examine the prevalence of metabolic syndrome and its individual components among a sample of students at Central Michigan University. A cross-sectional survey was conducted among 462 students, aged 18-25 years, in Spring 2015 and Fall/Spring 2016 semesters. Students were recruited throughout the campus via flyers, in-class, and Blackboard announcements. Biochemical, anthropometric, and blood pressure measurements were taken for all students. Prevalence of metabolic syndrome was estimated based on the National Cholesterol Education Program's Adult Treatment Panel III guidelines. Multivariable analysis was used to assess the prevalence of metabolic risk components. To explore the association between metabolic risk factors and lifestyle behaviors, students filled out a validated online questionnaire related to their eating habits, physical activity, and sleep patterns. Metabolic syndrome was not prevalent in our sample. However, about one-third of the students had at least one metabolic abnormality, and 6.0% had two metabolic abnormalities. The most common metabolic abnormalities were low HDL-cholesterol levels (22.0%) and high waist circumference (12.6%), and elevated serum triglyceride (5.8%). Adjusting for other factors, excess adiposity and high visceral fat scores were associated with increased risk of metabolic risk factors, whereas healthy lifestyle practices such as daily breakfast consumption, eating three meals a day, being active, and not smoking were associated with lower risks for MetS. Given the adverse consequences of undiagnosed metabolic abnormalities, efforts to identify and manage MetS among asymptomatic college students, particularly women, is essential and warrants further research.

Night eating syndrome and its association with weight status, physical activity, eating habits, smoking status, and sleep patterns among college students.

BACKGROUND: Night eating syndrome (NES) is characterized by evening hyperphagia and/or nocturnal ingestion. OBJECTIVE: The main objective of this study was to assess the percentage of students complying with symptoms and behaviors consistent with the diagnostic criteria for NES, and explore its association with body mass index (BMI), dietary habits, physical activity, smoking status, and sleep patterns, among a sample of college students. METHODS: A cross-sectional survey was conducted among a sample of 413 undergraduate students, mean age of 20.6 ± 1.68 SD, at Central Michigan University. Students completed an online survey including demographic information and the Night Eating Diagnostic Questionnaire (NEDQ) and Pittsburgh Sleep Quality Index Questionnaire (PSQI). Participants were grouped based on self-reporting of the presence and frequency of night eating-related symptoms and behaviors related to the diagnostic criteria for NES as follows: normal, mild night eater, moderate night eater, and full-syndrome night eater. Pearson's Chi-squared, Student's t test, and Wilcoxon rank-sum test were used to test the association between students with and without any night eating behavior in relation to BMI, lifestyle variables, and sleep duration/quality. RESULTS: Results showed that the proportion of students complying with symptoms and behaviors consistent with full-syndrome of NES was 1.2%. There were no significant differences between students complying with symptoms and behaviors consistent with any level of NES and those without any night eating behavior regarding BMI, eating habits, physical activity, and smoking status. NES was significantly related to sleep duration (P = 0.023). Students complying with symptoms consistent with any level of NES reported shorter sleep time and had higher total PSQI score (6.73 ± 4.06) than students without the syndrome (5.61 ± 2.61) (P = 0.007). CONCLUSION: Although the percentage of students complying with full-syndrome NES was relatively low in our student sample, those students had shorter sleep time and poorer sleep quality than the other groups. However, it is unclear whether evening hyperphagia is a response to a lack of sleep or vice versa, and further research is needed. LEVEL OF EVIDENCE: Level III, case-control analytic study.

A Randomized Controlled Trial Offering Higher- Compared with Lower-Dairy Second Meals Daily in Preschools in Guinea-Bissau Demonstrates an Attendance-Dependent Increase in Weight Gain for Both Meal Types and an Increase in Mid-Upper Arm Circumference for the Higher-Dairy Meal.

BACKGROUND: Controversy remains over the most effective approaches to prevent childhood malnutrition. OBJECTIVES: We tested the feasibility and effectiveness of delivering ready-to-use supplementary foods (RUSFs) as a second daily meal in preschool children aged 3-5 y in Guinea-Bissau, and compared RUSFs with different levels of dairy protein. METHODS: This study was a 3 mo cluster-randomized controlled pilot trial of 2 RUSFs differing in dairy protein in 533 boys and girls from 9 preschools. Children receiving RUSFs were compared with wait-listed controls, and all students received a daily school lunch. The RUSFs were delivered 5 d/wk for 3 mo and contained 478 kcal and 11.5 g protein per 92-g daily serving. Deliveries included a ready-to-use supplementary food with 15% of protein from dairy sources (RUSF-15%) or one with 33% of protein from dairy sources (RUSF-33%). Intention-to-treat (ITT) and per-protocol analyses (>50 d of RUSF consumption) were conducted. Changes in the weight-for-age z score (WAZ) and height-for-age z score were primary outcomes. Additional outcomes included changes in mid-upper arm circumference (MUAC), hemoglobin, and retinol binding protein. RESULTS: Baseline anthropometry was not different between groups (WAZ, -0.48 ± 1.04) and increased significantly over time (P < 0.01) with no effects of the RUSFs in ITT analyses. However, children consuming RUSFs for >50 d had a significantly greater increase in WAZ relative to the increase in controls (+0.40 and +0.32 for RUSF-15% and RUSF-33%, respectively, compared with +0.24 in controls, P < 0.01 and P < 0.05, respectively). RUSF-33%, but not RUSF-15%, also eliminated a decrease in MUAC observed in controls (-0.01 cm in RUSF-33% compared with -0.34 cm in controls, P < 0.05). The only difference between RUSF-15% and RUSF-33% was a mean decrease in hemoglobin in children receiving RUSF-15% (-0.5 compared with -0.002 g/dL, P = 0.05). CONCLUSIONS: Implementation of 2-meal preschool feeding programs is feasible in low-income countries, and there are measurable benefits relative to 1-meal programs in children attending preschool regularly. In addition, MUAC and hemoglobin measurements indicate that meals with 33% compared with 15% of protein from dairy may help prevent wasting and anemia.

Level of nutrition knowledge and its association with fat consumption among college students.

BACKGROUND: Intake of saturated fat, trans fat, and cholesterol has been associated with increased risk of coronary heart disease. The aim of this study was to explore whether increased nutrition knowledge is associated with a reduction in the consumption of unhealthy fats in a sample of university students. METHODS: A sample of 231 students, with a mean age of 20 years, was recruited from university campus during spring 2012. Students completed a validated questionnaire related to students' demographic, nutrition knowledge, and daily fat consumption. Weight, height, and waist circumference were measured. Data were analyzed using one-way ANOVA, chi-square, and student's t-test. RESULTS: Results indicate that female students have greater nutrition knowledge than male students (the mean nutrition score for women was 5 points higher than that of men (P = 0.01)). Nutrition knowledge was negatively correlated with fat and cholesterol intake. Students who consumed more than 35 % calories from fat or >300 mg of cholesterol daily had lower mean nutrition scores than those students with lower fat or cholesterol intake (8 points lower and 7.9 points lower, respectively). Using linear regression for nutrition scores on estimated saturated fat intake and cholesterol intake (controlling for gender, height, weight, age, and dieting), nutrition scores were negatively associated with saturated fat intake (-0.15, P <0.0001) and cholesterol intake (-1.38, P <0.0001). CONCLUSION: Students with greater nutritional knowledge consumed less unhealthy fats and cholesterol. This finding magnifies the role of nutrition education as a potential tool in health campaigns to promote healthy eating patterns among college students. Results of this pilot study can inform the design of future nutrition education intervention studies to assess the efficacy of nutrition knowledge on pattern of fat consumption among college students.

Predictors of hypophosphatemia during refeeding of patients with severe anorexia nervosa.

OBJECTIVE: Hypophosphatemia of refeeding is one of the most dangerous complications seen during the treatment of patients with anorexia nervosa. Although easily detectable and treatable, hypophosphatemia is under-recognized as a complication of refeeding. Specific risk factors for the development of hypophosphatemia are likely to exist among patients with severe anorexia nervosa. The purpose of this study was to identify clinically useful markers that may predict the development of or protection from hypophosphatemia during refeeding. METHODS: We conducted a retrospective case-control study of 123 patients with severe anorexia nervosa admitted for medical stabilization at the ACUTE Center for Eating Disorders between October 1, 2008 and December 31, 2013. Risk factors for refeeding hypophosphatemia were determined by multivariate logistic regression from clinical parameters and laboratory values measured at the time of admission. RESULTS: The prevalence of hypophosphatemia was 33.3% (41 of 123 patients). Higher hemoglobin was the only risk factor associated with a higher odds of developing hypophosphatemia (adjusted odds ratio [aOR], 1.56 [95% confidence interval [CI], 1.12-2.18]). Statistically significant protective factors against the development of hypophosphatemia were observed with higher body mass index (aOR, 0.54 [95% CI, 0.39-0.75]), higher serum potassium (aOR, 0.29 [95% CI, 0.14-0.62]), and higher serum prealbumin (aOR, 0.91 [95% CI, 0.84-0.99]). DISCUSSION: Four independent factors associated with refeeding hypophosphatemia were identified. Identification of findings which correlate with hypophosphatemia, or the lack thereof, has the potential to facilitate appropriate triage of patients with anorexia nervosa for closer monitoring during refeeding.

Medical complications of anorexia nervosa and their treatments: an update on some critical aspects.

Anorexia nervosa has the highest mortality rate of any psychiatric disorder. Many of the deaths are attributable to medical complications which arise as the malnutrition and weight loss worsens. Every body system may be adversely affected by anorexia nervosa. Yet, remarkably, most of the medical complications of anorexia nervosa are treatable and reversible with optimal medical care, as part of a multidisciplinary team who are often involved in the care of these patients. Herein, we will describe the medical complications of anorexia nervosa and their treatments.

Anorexia nervosa complicated by diabetes mellitus: the case for permissive hyperglycemia.

The coexistence of Type 1 Diabetes Mellitus and anorexia nervosa results in an increased incidence of known diabetic complications such as retinopathy and nephropathy, presumably because blood glucose is difficult to control within the throes of comorbid anorexia nervosa. In addition, even when a diabetic patient with anorexia nervosa has committed to resolving his or her eating disorder, glucose control is again difficult and fraught with complexity and peril as will be highlighted in the following case report. Prudence dictates that strict glucose control is not indicated for the relatively short period of time that constitutes the early stage of refeeding in a patient with severe anorexia nervosa. Rather, "permissive hyperglycemia" may be the more optimal course to pursue, as a clinical strategy which is considerate of both the criticality of the refeeding treatment plan and of the long-term nature of the diabetic illness.

Refining the referral criteria of persons who have been burned to palliative care: A modified Delphi approach.

A paucity of evidence is available to guide integration of specialist palliative care into burn care. This study's purpose was to develop consensus on referral criteria using a modified Delphi process. Content experts were defined as burn or palliative care providers in locations where the teams have collaborative history; published at least one manuscript or presented nationally on burn and palliative care collaboration; or nomination as having equivalent expertise. N = 202 eligible persons were identified; n = 43 participated in Iteration 1 and Iteration 3 retained 79%. Iteration 1 invited participants to rank published referral criteria on a 9-point Likert-style scale. Consensus was defined as an interquartile range ≤ 2. Consensus items with median scores ≤ 3 were dropped from further consideration. Consensus items with median scores ≥ 7 were considered to be important and excluded in Iteration 2. Iteration 2 which presented non-consensus items with their associated median (interquartile range) and the participant's own ranking from Iteration 1. Iteration 3 presented three models; participants ranked in order of preference and suggested revisions. Consensus was achieved on a final set of criteria for specialist palliative care for persons who sustain burn injuries. Future research should prospectively evaluate the criteria against meaningful outcomes.

Behavioral Outcomes and Neurodevelopmental Disorders Among Children of Women With Epilepsy.

Importance: The association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated. Objective: To examine the association of fetal ASM exposure with subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age. Design, Setting, and Participants: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023. Exposures: Exposures included mother's epilepsy status as well as mother's ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrolled regardless of ASM regimen. Main Outcomes and Measures: The primary outcome was the Adaptive Behavior Assessment System, Third Edition (ABAS-3) General Adaptive Composite (GAC) score among children at 4.5 years of age. Children of women with epilepsy and children of women without epilepsy were compared, and the associations of ASM exposures with outcomes among exposed children were assessed. Secondary outcomes involved similar analyses of other related measures. Results: Primary analysis included 302 children of women with epilepsy (143 boys [47.4%]) and 84 children of women without epilepsy (45 boys [53.6%]). Overall adaptive functioning (ABAS-3 GAC score at 4.5 years) did not significantly differ between children of women with epilepsy and children of women without epilepsy (parameter estimate [PE], 0.4 [95% CI, -2.5 to 3.4]; P = .77). However, in adjusted analyses, a significant decrease in functioning was seen with increasing third-trimester maximum ASM blood concentrations (PE, -7.8 [95% CI, -12.6 to -3.1]; P = .001). This decrease in functioning was evident for levetiracetam (PE, -18.9 [95% CI, -26.8 to -10.9]; P < .001) and lamotrigine (PE, -12.0 [95% CI, -23.7 to -0.3]; P = .04), the ASMs with sample sizes large enough for analysis. Results were similar with third-trimester maximum daily dose. Conclusions and Relevance: This study suggests that adaptive functioning of children of women with epilepsy taking commonly used ASMs did not significantly differ from that of children of women without epilepsy, but there was an exposure-dependent association of ASMs with functioning. Thus, psychiatric or psychological screening and referral of women with epilepsy and their offspring are recommended when appropriate. Additional research is needed to confirm these findings.

Association of Prenatal Exposure to Antiseizure Medications With Creative and Executive Function at Age 4.5 Years.

BACKGROUND AND OBJECTIVES: Neurodevelopmental effects of fetal antiseizure medication (ASM) exposure on creativity and executive functions are poorly understood. We previously found fetal valproate exposure to adversely affect measures of creativity and executive functions. In this study, we examine fetal exposure of newer ASMs on these functions in children of women with epilepsy (WWE) compared with children of healthy women (HW). METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a multicenter NIH-funded prospective observational cohort study of WWE and HW enrolled in pregnancy and their offsprings. This report examines blindly assessed creativity and executive functions in 4.5-year-old children of WWE vs HW. In addition, exposure-dependent ASM effects during the third trimester were examined in children of WWE, using a ratio of maximum observed ASM concentrations and ratio of defined daily dose (ratio DDD). For polytherapy, ratios were summed across ASMs. Linear regression models adjusted for multiple potential confounding factors were conducted for all analyses. The primary outcome for 4.5-year-old children was the Torrance Test of Creative Thinking-Figural Creativity Index. Secondary outcomes included the Global Executive Composite Score from the Behavior Rating Inventory of Executive Function-Preschool Version and subscales and other indexes of both measures. RESULTS: The primary analysis included 251 children of WWE and 73 of HW. No differences in creativity or executive function were found between children of WWE vs HW. No ASM exposure-dependent effects were found for the creativity measures, but exposure-dependent effects for executive function were present for ratio ASM concentration and ratio DDD. DISCUSSION: Our findings at 4.5 years show no differences in creative thinking between children of WWE vs HW (-3.2 [-9.0 to 2.7], p = 0.286) or associations with fetal exposure to ASMs (-2.6 [-11.0 to 5.7], p = 0.530). Secondary analyses revealed fetal exposure-dependent effects for executive function in children of WWE (7.0 [2.9-11.2], p = 0.001), which are most marked for levetiracetam (12.9 [4.2-21.6], p = 0.004). Our findings suggest that even for relatively safe ASMs, dosing needs to be adjusted to concentrations that prevent seizures, but balance risks to the fetus that high concentrations may pose. TRIAL REGISTRATION INFORMATION: The study is registered at ClinicalTrials.gov as NCT01730170.