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Increased use of oral anticancer agents (OAAs) has empowered adults with multiple myeloma (MM) to manage their oncolytic therapy, but such a shift may result in issues with medication use, particularly among patients being concurrently treated for pre-existing, multiple chronic conditions.

This retrospective cohort study used 2013-2018 commercial and Medicare claims data to assess medication use in adults with MM. To be included, adults (18 years and older) must have been diagnosed with and had 2+ claims for an OAA, had continuous enrollment for 12 months before and after OAA initiation, and have been previously diagnosed with and had prescription fills for 2+ select chronic conditions. The proportion of days covered metric assessed medication adherence and was compared for 12 months before and after the OAA initiation by Wilcoxon signed-rank tests, McNemar's tests, and difference-in-differences models.

The mean OAA adherence in the first year of therapy was 58.3% (standard deviation 24.5) and 65.1% (standard deviation 27.01) for commercial and Medicare patients, respectively. Adherence and the proportion adherent (proportion of days covered ≥ 80%) to comorbid therapies generally declined in the first year after OAA initiation. Changes in medication use were particularly noticeable among those on antihypertensive therapy adjusted analyses uncovered a 2.5% (Medicare) and 5.2% (commercial) difference in adherence to these medications between those initially adherent and nonadherent to OAA therapy (both

< .05).

Initiating OAA therapy in adults with MM may complicate an already complex treatment regimen, resulting in poor overall medication adherence in patients with multiple comorbid conditions.

Initiating OAA therapy in adults with MM may complicate an already complex treatment regimen, resulting in poor overall medication adherence in patients with multiple comorbid conditions.Lipid nanoparticles (LNPs) are the most widely investigated delivery systems for nucleic acid-based therapeutics and vaccines. Loading efficiency of nucleic acids may vary with formulation conditions, and it is considered one of the critical quality attributes of LNP products. Current analytical methods for quantification of cargo loading in LNPs often require external standard preparations and preseparation of unloaded nucleic acids from LNPs; therefore, they are subject to tedious and lengthy procedures, LNP stability, and unpredictable recovery rates of the separated analytes. Here, we developed a modeling approach, which was based on locally weighted regression (LWR) of ultraviolet (UV) spectra of unpurified samples, to quantify the loading of nucleic acid cargos in LNPs in-situ. We trained the model to automatically tune the training library space according to the spectral features of a query sample so as to robustly predict the nucleic acid cargo concentration and rank loading capacity with similar performance as the more complicated experimental approaches. Furthermore, we successfully applied the model to a wide range of nucleic acid cargo species, including antisense oligonucleotides, single-guided RNA, and messenger RNA, in varied lipid matrices. The LWR modeling approach significantly saved analytical time and efforts by facile UV scans of 96-well sample plates within a few minutes and with minimal sample preprocessing. Our proof-of-concept study presented the very first data mining and modeling strategy to quantify nucleic acid loading in LNPs and is expected to better serve high-throughput screening workflows, thereby facilitates early-stage optimization and development of LNP formulations.Modified nucleoside triphosphates (NTPs) are powerful probes and medicines, but their anionic character impedes membrane permeability. As such, invasive delivery techniques, transport carriers, or prodrug strategies are required for their in vivo use. Here, we present a fluorescent 2'-deoxyribonucleoside triphosphate "TAMRA-dATP" that exhibits surprisingly high bioavailability in vivo. TAMRA-dATP spontaneously forms nanoparticles in Mg+2-containing buffers that are taken into the vesicles of living cells and animals by energy-dependent processes. In cell cultures, photochemical activation with yellow laser light (561 nm) facilitated endosomal escape of TAMRA-dATP, resulting in its metabolic incorporation into DNA in vitro. In contrast, in vivo studies revealed that TAMRA-dATP is extensively trafficked by active pathways into cellular DNA of zebrafish (Danio rerio) and Caenorhabditis elegans where DNA labeling was observed in live animals, even without photochemical release. Metabolic labeling of DNA in whole, living animals can therefore be achieved by simply soaking animals in a buffer containing TAMRA-dATP or a structurally related compound, Cy3-dATP.Biallelic variants in DI3SL2 cause Perlman Syndrome, associated increased risk for Wilms tumor. Cutis Mamorata Telangiectatica Congenita (CMTC) is a rare congenital disorder characterized by cutaneous vascular anomalies. We report a 2-year-old boy with both Wilms tumor and CMTC. Genetic testing, prompted by his complex presentation, revealed 1 somatic mutation and 1 familial germline mutation in the DIS3L2 gene, suggesting a 2-hit causation of Wilms tumor. Separately, a single GNA11 somatic mutation was identified to explain the CMTC. We suggest that genetic testing for germline mutations associated with Wilms tumor susceptibility be considered even in cases without known family history.Idiopathic purpura fulminans (PF) is rare but has been reported in pediatric patients, commonly following infections. We present a case of a 5-year-old boy, heterozygous for factor V Leiden, with no history of recent infections, who presented with PF secondary to acquired protein S deficiency. Despite initial supportive treatment, the patient required surgical fasciotomy and extensive skin grafts. The protein S level normalized 4 months following the presentation. In this context, an autoimmune component with transient anti-protein S antibodies was believed to be involved. This case report highlights the course of idiopathic PF due to noninfectious acquired protein S deficiency.While there has been considerable interest in debates about right wing ideas in LGBT movements-military service, marriage, nationalism, white supremacy-there has been comparatively little attention to self-proclaimed right wing LGBT organizations, what I call the "gay right." Social theory to date offers a fragmented set of theoretical tools to explain them, including homonationalism, post-gay identity, additive intersectionality, and systems justification theory. I propose a two axis framework to unify these theories and map wide ranging diversity within the gay right. This framework is based on both a review of existing theories, and also analysis of 38 gay right organizations in 14 countries. I illustrate the framework with an extended analysis of three gay-right organizations which share a context-the contemporary UK-but have very different politics.Frasier syndrome (FS) is a rare condition, caused by splice-site mutations of intron 9 in the Wilms' tumor suppressor gene 1 (WT1 gene). The WT1 protein is essential for urogenital development and patients with 46XY karyotype present with female (FS type 1) or male phenotype, gonadal dysgenesis, progressive glomerulopathy, and high risk of gonadoblastoma. We describe a female patient with an IVS9+4C>T donor splice-site mutation, who underwent a preventive gonadectomy at the age of 6 years due to imaging findings of dysplastic gonads. The biopsy revealed bilateral gonadoblastoma, emphasizing the need for early gonadectomy in 46XY FS patients.The central complex in the brain of insects provides a neural network for sensorimotor processing that is essential for spatial navigation and locomotion and plays a role in sleep control. Studies on the neurochemical architecture of the central complex have been performed especially in the fruit fly Drosophila melangoaster and the desert locust, Schistocerca gregaria. In several insect species, myoinhibitory peptides (MIPs) are involved in circadian control and sleep-wake regulation. To identify neurons that might underlie these functions, we investigated the distribution of MIPs in the central complex of the locust. In silico transcript analysis suggests the presence of eight different MIPs in the desert locust. Through immunolabeling, we identified five systems of central-complex neurons that express MIP-like peptides. Two systems constitute columnar neurons of the protocerebral bridge and the lower division of the central body, while the other three systems are columnar neurons (two systems) and tangential neurons (one system) of the upper division of the central body. The innervation pattern and cell count of two systems of columnar neurons revealed the existence of 18 instead of 16 columns of the protocerebral bridge. Immunostaining of preparations containing intracellularly stained single cells allowed us to further specify subtypes of labeled columnar neurons. Double-label experiments showed that three systems of MIP-immunostained columnar neurons are also locustatachykinin-immunoreactive. No colocalization was found with serotonin immunostaining. The data provide novel insights into the architecture of the locust central complex and suggest that MIPs play a prominent role within the central-complex network.To date, the optimal management of displaced midshaft clavicle fractures remains unknown. Operatively, plate or nail fixation may be used. Nonoperatively, the options are sling or harness. Given the equivocal effectiveness between approaches, the costs to the health care system and the patient become critical considerations. A decision tree model was constructed to study plate and sling management of displaced midshaft clavicle fractures. Primary analysis used 6 randomized controlled trials that directly compared open reduction and internal fixation with a plate to sling. Lanifibranor mw Secondary analysis included 18 studies that studied either plate, sling, or both. Incremental cost-effectiveness ratios (ICERs) were calculated using quality-adjusted life-years (QALYs). Second-order Monte Carlo probabilistic sensitivity analysis (PSA) was subsequently conducted. In primary analysis, at a willingness-to-pay (WTP) threshold of $100,000, operative management was found to be less cost-effective relative to nonoperative management, with an ICER of $606,957/QALY (0.03 additional QALYs gained for an additional $16,120). In PSA, sling management was cost-effective across all WTP ranges. In secondary analysis, the ICER decreased to $75,230/QALY. Primary analysis shows that plate management is not a cost-effective option. In secondary analysis, the incremental effectiveness of plate management increased enough that the calculated ICER is below the WTP threshold of $100,000; however, the strength of evidence in secondary analysis is lower than in primary analysis. Thus, because neither option is dominant in this model, both plate and sling remain viable approaches, although the cost-conscious decision will be to treat these fractures with a sling until future data suggest otherwise. [Orthopedics. 2022;45(5)e243-e251.].