NDF is a transcription factor that stimulates elongation by RNA polymerase II.

RNA polymerase II (Pol II) elongation is a critical step in gene expression. Here we found that NDF, which was identified as a bilaterian nucleosome-destabilizing factor, is also a Pol II transcription factor that stimulates elongation with plain DNA templates in the absence of nucleosomes. NDF binds directly to Pol II and enhances elongation by a different mechanism than that used by transcription factor TFIIS. Moreover, yeast Pdp3, which is related to NDF, binds to Pol II and stimulates elongation. Thus, NDF is a Pol II binding transcription elongation factor that is localized over gene bodies and is conserved from yeast to humans.

Nanoblot: an R-package for visualization of RNA isoforms from long-read RNA-sequencing data.

RT-PCR and northern blots have long been used to study RNA isoforms usage for single genes. Recent advancements in long-read sequencing have yielded unprecedented information about the usage and abundance of these RNA isoforms. However, visualization of long-read sequencing data remains challenging due to the high information density. To alleviate these issues, we have developed NanoBlot, an open-source R-package that generates northern blot and RT-PCR-like images from long-read sequencing data. NanoBlot requires aligned, positionally sorted and indexed BAM files. Plotting is based around ggplot2 and is easily customizable. Advantages of NanoBlot include a robust system for designing probes to visualize isoforms including excluding reads based on the presence or absence of a specified region, an elegant solution to representing isoforms with continuous variations in length, and the ability to overlay multiple genes in the same plot using different colors. We present examples of nanoblots compared to actual northern blot data. In addition to traditional gel-like images, the NanoBlot package can also output other visualizations such as violin plots and 3'-RACE-like plots focused on 3'-end isoforms visualization. The use of the NanoBlot package should provide a simple answer to some of the challenges of visualizing long-read RNA-sequencing data.

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.

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.

Recent advances in pharmacotherapy for epilepsy.

PURPOSE OF REVIEW: Epilepsy affects 70 million people worldwide and is a significant cause of morbidity and early mortality. The mainstay of therapy is oral medications. Epilepsy drug development is escalating, driven by continued drug resistance in up to a third of epilepsy patients. Treatment development now focuses on discovery of novel mechanisms of action and syndrome-specific therapies. RECENT FINDINGS: Difficult-to-treat epilepsy related to conditions including tuberous sclerosis complex (TSC), Lennox Gastaut syndrome (LGS) and Dravet syndrome (DS) have been the target of recent developments. Disease-modifying therapy for epilepsy related to TSC with vigabatrin at onset of first electroencephalographic epileptiform changes, rather than after first clinical seizure, has demonstrated strongly positive seizure and developmental outcomes. Fenfluramine, approved for DS and, more recently, LGS, has robust data supporting efficacy, safety/tolerability, as well as mortality, quality of life and cognitive function. Rescue therapy has expanded to include better tolerated benzodiazepines in the form of nasal midazolam and valium. Cenobamate, a first-in-class inactivator of the persistent voltage-gated sodium channel and approved for adult partial onset epilepsy, has exceptional efficacy and tolerability and will be expanded to children and to generalized onset epilepsy in adults. SUMMARY: The repertoire of available and developmental therapies for epilepsy is rapidly expanding, and now includes disease-modifying vigabatrin in TSC and agents with extraordinary efficacy, fenfluramine and cenobamate.

Racial and Ethnic Inequities in Buprenorphine and Methadone Utilization Among Reproductive-Age Women with Opioid Use Disorder: an Analysis of Multi-state Medicaid Claims in the USA.

BACKGROUND: Associations between race/ethnicity and medications to treat OUD (MOUD), buprenorphine and methadone, in reproductive-age women have not been thoroughly studied in multi-state samples. OBJECTIVE: To evaluate racial/ethnic variation in buprenorphine and methadone receipt and retention in a multi-state U.S. sample of Medicaid-enrolled, reproductive-age women with opioid use disorder (OUD) at the beginning of OUD treatment. DESIGN: Retrospective cohort study. SUBJECTS: Reproductive-age (18-45 years) women with OUD, in the Merative™ MarketScan® Multi-State Medicaid Database (2011-2016). MAIN MEASURES: Differences by race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, "other" race/ethnicity) in the likelihood of receiving buprenorphine and methadone during the start of OUD treatment (yes/no) were estimated using multivariable logistic regression. Differences in time to medication discontinuation (days) by race/ethnicity were evaluated using multivariable Cox regression. RESULTS: Of 66,550 reproductive-age Medicaid enrollees with OUD (84.1% non-Hispanic White, 5.9% non-Hispanic Black, 1.0% Hispanic, 5.3% "other"), 15,313 (23.0%) received buprenorphine and 6290 (9.5%) methadone. Non-Hispanic Black enrollees were less likely to receive buprenorphine (adjusted odds ratio, aOR = 0.76 [0.68-0.84]) and more likely to be referred to methadone clinics (aOR = 1.78 [1.60-2.00]) compared to non-Hispanic White participants. Across both buprenorphine and methadone in unadjusted analyses, the median discontinuation time for non-Hispanic Black enrollees was 123 days compared to 132 days and 141 days for non-Hispanic White and Hispanic enrollees respectively (χ2 = 10.6; P = .01). In adjusted analyses, non-Hispanic Black enrollees experienced greater discontinuation for buprenorphine and methadone (adjusted hazard ratio, aHR = 1.16 [1.08-1.24] and aHR = 1.16 [1.07-1.30] respectively) compared to non-Hispanic White peers. We did not observe differences in buprenorphine or methadone receipt or retention for Hispanic enrollees compared to the non-Hispanic White enrollees. CONCLUSIONS: Our data illustrate inequities between non-Hispanic Black and non-Hispanic White Medicaid enrollees with regard to buprenorphine and methadone utilization in the USA, consistent with literature on the racialized origins of methadone and buprenorphine treatment.

Formation of multicellular colonies by choanoflagellates increases susceptibility to capture by amoeboid predators.

Many heterotrophic microbial eukaryotes are size-selective feeders. Some microorganisms increase their size by forming multicellular colonies. We used choanoflagellates, Salpingoeca helianthica, which can be unicellular or form multicellular colonies, to study the effects of multicellularity on vulnerability to predation by the raptorial protozoan predator, Amoeba proteus, which captures prey with pseudopodia. Videomicrography used to measure the behavior of interacting S. helianthica and A. proteus revealed that large choanoflagellate colonies were more susceptible to capture than were small colonies or single cells. Swimming colonies produced larger flow fields than did swimming unicellular choanoflagellates, and the distance of S. helianthica from A. proteus when pseudopod formation started was greater for colonies than for single cells. Prey size did not affect the number of pseudopodia formed and the time between their formation, pulsatile kinematics and speed of extension by pseudopodia, or percent of prey lost by the predator. S. helianthica did not change swimming speed or execute escape maneuvers in response to being pursued by pseudopodia, so size-selective feeding by A. proteus was due to predator behavior rather than prey escape. Our results do not support the theory that the selective advantage of becoming multicellular by choanoflagellate-like ancestors of animals was reduced susceptibility to protozoan predation.

Using machine learning to predict gamma passing rate in volumetric-modulated arc therapy treatment plans.

PURPOSE: This study aims to develop an algorithm to predict gamma passing rate (GPR) in the volumetric-modulated arc therapy (VMAT) technique. MATERIALS AND METHODS: A total of 118 clinical VMAT plans, including 28 mediastina, 25 head and neck, 40 brains intensity-modulated radiosurgery, and 25 prostate cases, were created in RayStation treatment planning system for Edge and TrueBeam linacs. In-house scripts were developed to compute Modulation indices such as plan-averaged beam area (PA), plan-averaged beam irregularity (PI), total monitor unit (MU), leaf travel/arc length, mean dose rate variation, and mean gantry speed variation. Pretreatment verifications were performed on ArcCHECK phantom with SNC software. GPR was calculated with 3%/2 mm and 10% threshold. The dataset was randomly split into a training (70%) and a test (30%) dataset. A random forest regression (RFR) model and support vector regression (SVR) with linear kernel were trained to predict GPR using the complexity metrics as input. The prediction performance was evaluated by calculating the mean absolute error (MAE), R2 , and root mean square error (RMSE). RESULTS: RMSEs at γ 3%/2 mm for RFR and SVR were 1.407 ± 0.103 and 1.447 ± 0.121, respectively. MAE was 1.14 ± 0.084 for RFR and 1.101 ± 0.09 for SVR. R2 was equal to 0.703 ± 0.027 and 0.689 ± 0.053 for RFR and SVR, respectively. GPR of 3%/2 mm with a 10% threshold can be predicted with an error smaller than 3% for 94% of plans using RFR and SVR models. The most important metrics that had the greatest impact on how accurately GPR can be predicted were determined to be the PA, PI, and total MU. CONCLUSION: In terms of its prediction values and errors, SVR (linear) appeared to be comparable with RFR for this dataset. Based on our results, the PA, PI, and total MU calculations may be useful in guiding VMAT plan evaluation and ultimately reducing uncertainties in planning and radiation delivery.

Therapeutic Antibodies in Medicine.

Antibody engineering has developed into a wide-reaching field, impacting a multitude of industries, most notably healthcare and diagnostics. The seminal work on developing the first monoclonal antibody four decades ago has witnessed exponential growth in the last 10-15 years, where regulators have approved monoclonal antibodies as therapeutics and for several diagnostic applications, including the remarkable attention it garnered during the pandemic. In recent years, antibodies have become the fastest-growing class of biological drugs approved for the treatment of a wide range of diseases, from cancer to autoimmune conditions. This review discusses the field of therapeutic antibodies as it stands today. It summarizes and outlines the clinical relevance and application of therapeutic antibodies in treating a landscape of diseases in different disciplines of medicine. It discusses the nomenclature, various approaches to antibody therapies, and the evolution of antibody therapeutics. It also discusses the risk profile and adverse immune reactions associated with the antibodies and sheds light on future applications and perspectives in antibody drug discovery.

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.

Synergistic bactericidal effects of pairs of photosensitizer molecules activated by ultraviolet A light against bacteria in plasma.

BACKGROUND: The current approach to reducing bacterial contamination in blood transfusion products is through detection or pathogen reduction methods, some of which utilize ultraviolet (UV) light photosensitizers. A small number of photosensitizers are being used as single agents in combination with UV light, but their efficacy can be limited against some pathogens. Benzophenone (BP) and vitamins B1, B6, and K3 have been identified as effective UVA photosensitizers for inactivation of bacteria. We evaluated whether combining pairs of photosensitizers in this group would have synergistic bactericidal effects on Gram-negative and Gram-positive bacteria. STUDY DESIGN AND METHODS: Bacteria species of Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Klebsiella pneumoniae were mixed with 0 to 100 mM concentrations of photosensitizers and exposed to UVA irradiation at 18 J/cm2 to assess their bactericidal effects. RESULTS: Single photosensitizers irradiated with UVA produced a range of bactericidal activity. When combined in pairs, all demonstrated some synergistic bactericidal effects with up to 4-log reduction above the sum of activities of individual molecules in the pair against bacteria in plasma. Photosensitizer pairs with BP had the highest synergism across all bacteria. With vitamin K3 in the pair, synergism was evident for Gram-positive but not for Gram-negative bacteria. Vitamin B1 and vitamin B6 had the least synergism. These results indicate that a combination approach with multiple photosensitizers may extend effectiveness of pathogen reduction in plasma. CONCLUSIONS: Combining photosensitizers in pathogen reduction methods could improve bactericidal efficacy and lead to use of lower concentrations of photosensitizers to reduce toxicities and unwanted side effects.

The transcription factor NKX1-2 promotes adipogenesis and may contribute to a balance between adipocyte and osteoblast differentiation.

Although adipogenesis is mainly controlled by a small number of master transcription factors, including CCAAT/enhancer-binding protein family members and peroxisome proliferator-activated receptor γ (PPARγ), other transcription factors also are involved in this process. Thyroid cancer cells expressing a paired box 8 (PAX8)-PPARγ fusion oncogene trans-differentiate into adipocyte-like cells in the presence of the PPARγ ligand pioglitazone, but this trans-differentiation is inhibited by the transcription factor NK2 homeobox 1 (NKX2-1). Here, we tested whether NKX family members may play a role also in normal adipogenesis. Using quantitative RT-PCR (RT-qPCR), we examined the expression of all 14 NKX family members during 3T3-L1 adipocyte differentiation. We found that most NKX members, including NKX2-1, are expressed at very low levels throughout differentiation. However, mRNA and protein expression of a related family member, NKX1-2, was induced during adipocyte differentiation. NKX1-2 also was up-regulated in cultured murine ear mesenchymal stem cells (EMSCs) during adipogenesis. Importantly, shRNA-mediated NKX1-2 knockdown in 3T3-L1 preadipocytes or EMSCs almost completely blocked adipocyte differentiation. Furthermore, NKX1-2 overexpression promoted differentiation of the ST2 bone marrow-derived mesenchymal precursor cell line into adipocytes. Additional findings suggested that NKX1-2 promotes adipogenesis by inhibiting expression of the antiadipogenic protein COUP transcription factor II. Bone marrow mesenchymal precursor cells can differentiate into adipocytes or osteoblasts, and we found that NKX1-2 both promotes ST2 cell adipogenesis and inhibits their osteoblastogenic differentiation. These results support a role for NKX1-2 in promoting adipogenesis and possibly in regulating the balance between adipocyte and osteoblast differentiation of bone marrow mesenchymal precursor cells.

Effects of Spectral Resolution and Frequency Mismatch on Speech Understanding and Spatial Release From Masking in Simulated Bilateral Cochlear Implants.

OBJECTIVES: Due to interaural frequency mismatch, bilateral cochlear-implant (CI) users may be less able to take advantage of binaural cues that normal-hearing (NH) listeners use for spatial hearing, such as interaural time differences and interaural level differences. As such, bilateral CI users have difficulty segregating competing speech even when the target and competing talkers are spatially separated. The goal of this study was to evaluate the effects of spectral resolution, tonotopic mismatch (the frequency mismatch between the acoustic center frequency assigned to CI electrode within an implanted ear relative to the expected spiral ganglion characteristic frequency), and interaural mismatch (differences in the degree of tonotopic mismatch in each ear) on speech understanding and spatial release from masking (SRM) in the presence of competing talkers in NH subjects listening to bilateral vocoder simulations. DESIGN: During testing, both target and masker speech were presented in five-word sentences that had the same syntax but were not necessarily meaningful. The sentences were composed of five categories in fixed order (Name, Verb, Number, Color, and Clothes), each of which had 10 items, such that multiple sentences could be generated by randomly selecting a word from each category. Speech reception thresholds (SRTs) for the target sentence presented in competing speech maskers were measured. The target speech was delivered to both ears and the two speech maskers were delivered to (1) both ears (diotic masker), or (2) different ears (dichotic masker: one delivered to the left ear and the other delivered to the right ear). Stimuli included the unprocessed speech and four 16-channel sine-vocoder simulations with different interaural mismatch (0, 1, and 2 mm). SRM was calculated as the difference between the diotic and dichotic listening conditions. RESULTS: With unprocessed speech, SRTs were 0.3 and -18.0 dB for the diotic and dichotic maskers, respectively. For the spectrally degraded speech with mild tonotopic mismatch and no interaural mismatch, SRTs were 5.6 and -2.0 dB for the diotic and dichotic maskers, respectively. When the tonotopic mismatch increased in both ears, SRTs worsened to 8.9 and 2.4 dB for the diotic and dichotic maskers, respectively. When the two ears had different tonotopic mismatch (e.g., there was interaural mismatch), the performance drop in SRTs was much larger for the dichotic than for the diotic masker. The largest SRM was observed with unprocessed speech (18.3 dB). With the CI simulations, SRM was significantly reduced to 7.6 dB even with mild tonotopic mismatch but no interaural mismatch; SRM was further reduced with increasing interaural mismatch. CONCLUSIONS: The results demonstrate that frequency resolution, tonotopic mismatch, and interaural mismatch have differential effects on speech understanding and SRM in simulation of bilateral CIs. Minimizing interaural mismatch may be critical to optimize binaural benefits and improve CI performance for competing speech, a typical listening environment. SRM (the difference in SRTs between diotic and dichotic maskers) may be a useful clinical tool to assess interaural frequency mismatch in bilateral CI users and to evaluate the benefits of optimization methods that minimize interaural mismatch.

Risk of readmission for suicide attempt after epilepsy hospitalization.

OBJECTIVE: The objective of this study was to examine if epilepsy admissions are associated with a higher readmission risk for suicide attempt, independent of psychiatric comorbidity, compared with index admissions for other medical causes. METHODS: The Nationwide Readmissions Database is a nationally representative dataset containing data from roughly 15 million hospital discharges. Analysis of International Classification of Disease Clinical Modification 9 (ICD-9-CM) codes in the year 2013 revealed 58,278 index admissions for epilepsy; this group was compared with admissions for stroke (N=215,821) and common medical causes (N=973,078). Ninety-day readmission rates for suicide attempts were calculated. Cox regression tested for associations between admission type and suicide attempt readmissions up to 1year following index admission. RESULTS: There were 402/100,000 readmissions for suicide attempt within 90days from index admission in the group with epilepsy; 43/100,000 in the stroke group; and between 37 and 89/100,000 in the medical group. Unadjusted hazard ratios (HR) for suicide readmissions within 1year in the group with epilepsy compared with the stroke group were 9.61 (95% confidence interval (CI): 7.69-11.90, p<2.0×10-16) and 5.02 compared with the medical group (95% CI: 4.40-5.73, p<2.0×10-16). The HR for readmission in the group with epilepsy, after adjustment for sociodemographic and psychiatric variables, were elevated at 4.91 compared with the stroke group (95% CI: 3.83-6.27, p<2.0×10-16), and 2.66 compared with the medical group (95% CI: 2.32-3.05, p<2.0×10-16). CONCLUSION: Independent of psychiatric comorbidities, epilepsy admissions may be independently associated with more than a threefold increased risk of hospital readmission for suicide in the year following index admission in comparison with patients recently hospitalized because of stroke or other common medical disorders.

Assessing the association of obesity and asthma morbidity in older adults.

BACKGROUND: Obesity is a robust predictor of poor asthma control in younger adults. Given the high prevalence of asthma and obesity in older Americans, weight reduction could benefit asthma management in this population. OBJECTIVE: To assess the association between obesity and asthma outcomes among older adults. METHODS: We recruited from urban primary care clinics a prospective cohort of nonsmoking individuals with asthma who were 60 years or older without a history of other respiratory diseases. At baseline, body mass index (BMI) measurements were classified as normal (BMI, 18-25), overweight (BMI, 25-30), or obese (BMI, >30). Measures of asthma morbidity (Asthma Control Questionnaire [ACQ], and Mini Asthma Quality of Life Questionnaire [Mini-AQLQ]) and asthma-related resource utilization (inpatient or outpatient) were taken at baseline and at 3- and 12-month interviews. We used generalized estimating equation models to assess associations between obesity and asthma outcomes after controlling for potential confounders. RESULTS: Of the 437 older adults with asthma in the study, 17% had a normal BMI, 32% were overweight, and 51% were obese. Unadjusted analyses revealed that obesity was associated with lower ACQ scores (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.09-1.31) and poorer Mini-AQLQ scores (OR, 1.21; 95% CI, 1.11-1.33). Adjusted analyses revealed no significant association between obesity and ACQ (OR, 1.05; 95% CI, 0.96-1.15) and Mini-AQLQ (OR, 1.08; 95% CI, 0.99-1.19). CONCLUSION: Our study suggests that obesity is not independently associated with worse asthma outcomes in older adults, reflecting potential differences in the mechanisms that link obesity with asthma control in older vs younger populations.

Risk of hyperglycemia attributable to everolimus in cancer patients: A meta-analysis.

Everolimus has been used widely in cancer patients and is associated with the development of hyperglycemia. Due to confounding factors, its specific impact on hyperglycemia has not been well understood. We performed a meta-analysis of randomized controlled trials to determine the risk of hyperglycemia attributable to everolimus in cancer patients of varying tumor types. MATERIAL AND METHODS: PubMed and American Society of Clinical Oncology conference abstracts up to June 2015 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which everolimus was compared to placebo in cancer patients with or without other agents. Heterogeneity tests were performed to examine between-study differences in hyperglycemia, and the incidence and relative risk of all- and high-grade hyperglycemia attributable to everolimus were determined using both random- or fixed-effects models. RESULTS: A total of seven phase III and two phase II RCTs with various tumors, encompassing a total of 3879 cancer patients, were included in our analysis. Everolimus significantly increased the risk of all-grade (RR =2.60, 95% CI 2.03-3.31, p < 0.001) and high-grade (RR =3.0, 95% CI 1.72-5.23; p < 0.001) hyperglycemia. The incidences of all- and high-grade hyperglycemia attributable to everolimus were 6.8% (95% CI 3.4-13.2%) and 2.5% (95% CI 1.2-4.9%), respectively. The everolimus-specific risk of all-grade hyperglycemia varied significantly with tumor types (p < 0.001), with the highest incidence seen in renal cell carcinoma (RCC) (27.2%, 95% CI 22.2-32.8%) and the lowest in breast cancer (3.3%, 95% CI 1.3-8.2%). No significant variation was found between everolimus alone or everolimus in combination with other agents. Similar results were also found for the risk of high-grade hyperglycemia attributable to everolimus. CONCLUSION: The specific risk of hyperglycemia attributable to everolimus may vary significantly with tumor types. Close monitoring should be given to patients at high risk, such as RCC.

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.