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IMPORTANCE: Progressive multifocal leukoencephalopathy (PML) is a life-threatening viral infection with no approved antiviral treatment. OBJECTIVE: To determine whether restoring the compromised immune system of patients with PML with directly isolated allogeneic virus–specific (DIAVIS) T cells is a promising therapeutic strategy, especially if other curative options are absent. DESIGN, SETTING, AND PARTICIPANTS: A retrospective case series of patients with PML who were treated with DIAVIS T cells was conducted between March 2020 and February 2022. T cells were isolated from healthy donors within 24 hours and targeted against the BK polyomavirus. Patients with PML were treated monocentrically. Eligibility for treatment with DIAVIS T cells was assessed for patients with confirmed PML, and exclusion criteria included stable PML disease and previous treatment with natalizumab. EXPOSURE: Fresh DIAVIS T cells were administered with a maximum dose of 2 × 104 CD3+ cells/kg body weight. Remaining T cells were cryopreserved in divided doses and administered in additional treatments approximately 2 and 6 weeks later. MAIN OUTCOMES AND MEASURES: Primary outcome measures were clinical response and survival of patients, compared with the outcomes of a historical reference group of PML cases receiving best supportive treatment (BST) and with recently published real-world data of patients with PML who were treated with immune checkpoint inhibition. RESULTS: The study cohort consisted of 28 patients (median [IQR] age, 60 [51-72] years; 20 male [71.4%]). Twenty-two patients (79%) treated with DIAVIS T cells showed response, resulting in significant clinical stabilization or improvement and a reduction in viral load. Six individuals (21%) were classified as nonresponders, deteriorated rapidly, and died, as did 2 other patients during a 12-month follow-up. Older age was the only predictor of a poor treatment response. Survival analysis revealed better 12-month survival rates (hazard ratio, 0.42; 95% CI, 0.24-0.73; P =.02) from diagnosis for patients treated with DIAVIS T cells (18 of 26 [69%]; 12-mo survival rate, 69%) compared with historical controls with BST (57 of 113 [50%]; 12-mo survival rate, including censored data, 45%). CONCLUSION AND RELEVANCE: This case series of DIAVIS T-cell therapy in PML provides first class IV evidence suggesting efficacy to reduce mortality and improve functional outcome. Further prospective studies are required to confirm these results.

Abstract.Objective:We examined predictors and moderators of treatment outcome in mothers and children diagnosed with ADHD in a large multicentre RCT. Method:In total, 144 mother-child dyads with ADHD were randomly assigned to either a maternal ADHD treatment (group psychotherapy and open methylphenidate medication, TG) or to a control treatment (individual counselling without psycho- or pharmacotherapy, CG). After maternal ADHD treatment, parent-child training (PCT) for all mother-child dyads was added. The final analysis set was based on 123 dyads with completed primary outcome assessments (TG: n= 67, CG: n= 56). The primary outcome was the change in each child’s externalizing symptoms. Multiple linear regression analyses were performed. Results:The severity of the child’s externalizing problem behaviour in the family at baseline predicted more externalizing symptoms in the child after PCT, independent of maternal treatment. When mothers had a comorbid depression, TG children showed more externalizing symptoms after PCT than CG children of depressive mothers. No differences between the treatment arms were seen in the mothers without comorbid depression. Conclusions:Severely impaired mothers with ADHD and depressive disorder are likely to need additional disorder-specific treatment for their comorbid psychiatric disorders to effectively transfer the contents of the PCT to the home situation (CCTISRCTN73911400).

Hintergrund: Der positive Einfluss pharmazeutischer Betreuung auf die Verbesserung der Arzneimitteltherapiesicherheit gilt als belegt. Zum ökonomischen Nutzen klinisch pharmazeutischer Dienstleistungen in Deutschland ist bisher wenig bekannt. Ziel der Arbeit: Im Klinikum Ernst von Bergmann wurde 2020 ein Pilotprojekt zur Einführung von Stationsapotheker:innen in der Intensivmedizin gestartet, in dem auch der finanzielle Nutzen des angebotenen Medikationsmanagements ermittelt werden sollte. Methodik: Jeder pharmazeutischen Intervention (PI) wurde durch ein Team aus erfahrenen Intensivmediziner:innen und Stationsapotheker:innen im Konsensprinzip ein Wahrscheinlichkeitswert (Nesbit-probability-Score) zugeordnet, mit dem ein unerwünschtes Arzneimittelereignis (UAE) aufgetreten wäre. Unter der Annahme, dass pro UAE eine verlängerte Liegedauer resultiert, wurden die durchschnittlichen Fallkosten der Intensivstation/Tag als Einsparungspotenzial herangezogen. Das Modell kombiniert dabei die Ergebnisse zweier internationaler Publikationen, um eine ökonomische Bilanzierung pharmazeutischer Dienstleistungen zu ermöglichen. Ergebnisse: Im Untersuchungszeitraum wurden 177 PI ausgewertet und entsprechende Wahrscheinlichkeitswerte für das Eintreten von UAE ermittelt. Daraus wurden durch vermiedene Kosten jährliche Einsparungen von 80.000 € berechnet. Schlussfolgerung: In diesem Projekt konnte der ökonomische Nutzen pharmazeutischer Dienstleistungen in der Intensivmedizin belegt werden. Stationsapotheker:innen sind nun fester Bestandteil des intensivmedizinischen Behandlungsteams im Klinikum Ernst von Bergmann.

Hintergrund: Patientenberichtete Endpunkte („patient-reported outcomes“ [PRO]) sind wichtige Zielgrößen für die Bewertung des Nutzens eines Medikaments. Für das vom Gemeinsamen Bundesausschuss (G-BA) in Deutschland neu eingeführte Instrument der Anwendungsbegleitenden Datenerhebungen (AbD) wird gefordert, dass Vergleichsdaten für PRO aus Registern zur Verfügung stehen. Fragestellung: Wie kann es gelingen, PRO in einem europäischen Register zu implementieren? Methode: Im Rahmen der AbD für ein CAR-T-Zell-Produkt hat das europäische Mantelzell-Lymphom-Netzwerk (European Mantle Cell Lymphoma Network, EMCL) im Herbst 2023 die Erfassung von PRO in seinem Register eingeführt. Dabei mussten Lösungen für Fragen unter anderem der Vertragsgestaltung, des Datenschutzes, der Logistik der Datenerhebung, der Arbeitsbelastung für die Zentren und des Datentransfers gefunden werden. Dieser Beitrag berichtet über die ersten Erfahrungen bei der Implementierung. Ergebnisse und Schlussfolgerung: Die PRO-Erfassung im Rahmen von medizinischen Registern ist möglich, aber mit hohem Aufwand verbunden. Eine Regelfinanzierung der PRO-Erfassung in Registern erscheint sinnvoll, beispielsweise im Rahmen von AbD.

Background: Systematic reviews indicated that home treatment is an effective and cost-saving alternative to conventional acute psychiatric treatment options. Treatment success has often been defined as a reduction of hospital admissions. In the current study, symptoms and well-being are assessed regularly during treatment as an indicator for treatment success. Patients’ characteristics such as diagnosis, age, substance use, and motivation for treatment were discussed as predictors for treatment success. A second focal point of the study lies in the examination of the therapeutic relationship in terms of the outcome, which has not yet been systematically investigated in home treatment. Methods: This is an observational study with a prospective naturalistic design. Measurements are carried out at baseline, during and at the end of treatment as well as at the 3‑month follow-up. Patients’ characteristics as potential predictors for treatment success will be assessed at baseline. In addition, the perceived relationship between the patients and the team will be measured daily and weekly throughout the treatment. Treatment success is by the changes in symptoms and general well-being assessed weekly. We aim to include 82 participants assigned to home treatment. Variance analyses with repeated measurements will be conducted to evaluate treatment success. Conclusion: By examining potential patient- and relationship-related predictors of treatment success, insights into relevant determining variables of treatment success in this setting are expected. The results might help to better identify who benefits the most from home treatment.

This study proposes a hierarchically integrated framework for safe task and motion planning (TAMP) of bipedal locomotion in a partially observable environment with dynamic obstacles and uneven terrain. The high-level task planner employs linear temporal logic for a reactive game synthesis between the robot and its environment and provides a formal guarantee on navigation safety and task completion. To address environmental partial observability, a belief abstraction model is designed by partitioning the environment into multiple belief regions and employed at the high-level navigation planner to estimate the dynamic obstacles' location. This additional location information of dynamic obstacles offered by belief abstraction enables less conservative long-horizon navigation actions beyond guaranteeing immediate collision avoidance. Accordingly, a synthesized action planner sends a set of locomotion actions to the middle-level motion planner while incorporating safe locomotion specifications extracted from safety theorems based on a reduced-order model (ROM) of the locomotion process. The motion planner employs the ROM to design safety criteria and a sampling algorithm to generate nonperiodic motion plans that accurately track high-level actions. At the low level, a foot placement controller based on an angular-momentum linear inverted pendulum model is implemented and integrated with an ankle-actuated passivity-based controller for full-body trajectory tracking. To address external perturbations, this study also investigates the safe sequential composition of the keyframe locomotion state and achieves robust transitions against external perturbations through reachability analysis. The overall TAMP framework is validated with extensive simulations and hardware experiments on bipedal walking robots Cassie and Digit designed by Agility Robotics.

AbstractWe present a simple inductive proof of the Lagrange Inversion Formula.

BackgroundMRI guided laser interstitial thermal therapy (M-LITT) capsulotomy has proven to be efficacious in decreasing refractory obsessive-compulsive disorder (OCD) related symptomatology yet capsulotomy either via radiosurgery or radiofrequency ablation has in some patients led to increased apathy following surgery. The current case series aims to investigate objective patient-reported change in apathy, disinhibition, depression, and executive dysfunction following anterior capsulotomy via M-LITT for OCD. MethodsTen consecutive patients pre- and post-M-LITT completed measures of OCD, apathy, disinhibition, executive dysfunction, and depression (Mtime between= 1.3 years; 0.42-3.7 years). Reliable Change Index (RCI) was used to evaluate change in pre- and post-M-LITT. OCD symptom response was evaluated using percent change (Y-BOCS scores: 24-34 % reduction indicating partial response; ≥35% reduction indicating full response).ResultsPositive post-surgical change was noted in OCD symptomatology with >65% reporting a partial or full response. However, six patients endorsed increased apathy with half of the non-responders (e.g., less than <24% score reduction on Y-BOCS) reporting increases in apathy. Patients reported relatively stable disinhibition and executive dysfunction, while over half reported a decrease in depression symptoms. Two of the non-responders and one responder endorsed increased apathy despite stable or improved depression symptoms, disinhibition, and executive dysfunction.ConclusionsMost patients in the current cohort achieved full-or-partial OCD recovery. Yet, 60% of patients also reported significant increases in apathy, despite experiencing a decrease in depression symptoms, with stable disinhibition and executive dysfunction. Despite these promising improvements in OCD symptomatology following M-LITT, further investigations of the impact of surgery and lesion location on apathy levels is clearly warranted using objective, quantifiable methods.

Waveform adaptation is a key-feature for modern radar systems and essential for cognitive radar. In this article, we present a concept for the enhancement of the classification performance by using optimized transmit waveforms and a Gaussian template matching high range resolution profile classifier. A straight forward approach is presented, aiming to improve specific parts of the confusion matrix, which will be exploited within a cognitive framework. The optimization includes different types of uncertainties and is designed during a training process to be accessed by a library. Taking different uncertainties into account, the calculation of the expected performance, the optimization, the range side lobe constraint and the time-domain realisation is explained. A nonlinear frequency modulation waveform is used since it provides a compression gain with range resolution and a constant envelope. Based on an electromagnetic simulation, the concept is validated for different ground targets and aspect angle uncertainties. The adaptation is compared to a commonly used linear frequency modulation. The results of the mean performance improvement reached an enhancement between $8.8 \,\%$ and $20.9 \,\%$.

Gäbler, M, Prieske, O, Elferink-Gemser, MT, Hortobágyi, T, Warnke, T, and Granacher, U. Measures of physical fitness improve prediction of kayak and canoe sprint performance in young kayakers and canoeists. J Strength Cond Res37(6): 1264–1270, 2023—Markers of talent selection and predictors of performance in canoe and kayak sprint are not yet well defined. We aimed to determine the combination of variables (i.e., demographic, anthropometric, and physical fitness) that most accurately predicts sprint performance (i.e., 500- and 2000-m race time) in semielite, young kayakers and canoeists (n= 39, age 13 year, 10F). The level of significance was set at p< 0.05. Linear regression analyses identified boat type (i.e., kayak or canoe), skeletal muscle mass, and average power during a 2-minute bench pull test, normalized to body mass, as predictors of 2000-m race time (R22000 m= 0.69, Akaike information criterion [AIC] = 425) and together with vertical jump height, as predictors of 500-m race time (R2500 m= 0.87, AIC = 255). This was an improvement over models containing solely demographic variables (R2500 m= 0.66, AIC = 293; R22000 m= 0.44, AIC = 446) and over models containing demographic and anthropometric variables (R2500m= 0.79, AIC = 277; R22000 m= 0.56, AIC = 437). Race time showed the strongest semipartial correlations with the 2-minute bench pull test (0.7 ≤ r≤ 0.9). Adding physical fitness data (i.e., 2-minute bench pull test) to demographic and anthropometric data improves the prediction accuracy of race times in young kayak and canoe athletes. The characteristics of physical fitness tests should resemble as much as possible the biomechanical (e.g., prime movers) and metabolic (e.g., duration) demands of the sport.

The structural elucidation of metabolite molecules is important in many branches of the life sciences. However, the isomeric and isobaric complexity of metabolites makes their identification extremely challenging, and analytical standards are often required to confirm the presence of a particular compound in a sample. We present here an approach to overcome these challenges using high-resolution ion mobility spectrometry in combination with cryogenic vibrational spectroscopy for the rapid separation and identification of metabolite isomers and isobars. Ion mobility can separate isomeric metabolites in tens of milliseconds, and cryogenic IR spectroscopy provides highly structured IR fingerprints for unambiguous molecular identification. Moreover, our approach allows one to identify metabolite isomers automatically by comparing their IR fingerprints with those previously recorded in a database, obviating the need for a recurrent introduction of analytical standards. We demonstrate the principle of this approach by constructing a database composed of IR fingerprints of eight isomeric/isobaric metabolites and use it for the identification of these isomers present in mixtures. Moreover, we show how our fast IR fingerprinting technology allows to probe the IR fingerprints of molecules within just a few seconds as they elute from an LC column. This approach has the potential to greatly improve metabolomics workflows in terms of accuracy, speed, and cost.

Colonial bentgrass (Agrostis capillaris) is a tetraploid rhizomatous bentgrass that generally exhibits improved resistance to the important fungal disease dollar spot and has more tolerance to water‐deficit stress than the more widely grown creeping bentgrass (Agrostis stolonifera). Interspecific hybridization between these two species is possible and efforts to understand the genetic mechanisms of enhanced biotic and abiotic stress resistance in colonial bentgrass are proceeding. To gain a better understanding of the level of genetic diversity in cultivated colonial bentgrasses and to determine if genotypes with improved interspecific hybridization potential can be identified, nine colonial bentgrass cultivars and one creeping bentgrass cultivar were screened with 48 colonial bentgrass‐derived simple sequence repeat markers. Twenty‐one primer pairs were found to produce reliable amplification, and these markers were scored using high‐resolution melt analysis to generate haplotypes that were used to evaluate cultivar relationships. The nine colonial bentgrass cultivars could be placed into two groups and overall showed limited levels of diversity. The creeping bentgrass cultivar was distinct and individual genotypes within each species exhibited haplotypes more common in the alternate species, suggesting that these markers may be useful for selecting genotypes with enhanced interspecific hybridization potential. The use of SSR loci with high‐resolution melt analysis and haplotype scoring is an effective method for assessing the genetic diversity of outcrossing grasses.The colonial bentgrass cultivars tested seperated into only two groups indicating that additional genetic diversity could enhance breeding efforts.The SSR haplotypes may help identify germplasm with enhanced interspecific hybidization potential.

Folate intake and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene may affect folate metabolism in infants.

Supplemental Digital Content is Available in the Text.

Costas arrays are useful in radar and sonar engineering, and many other settings in which optimal 2-D autocorrelation is needed: they are permutation matrices in which the vectors joining different pairs of ones are all distinct. We prove that the density of Costas arrays among permutation matrices decays exponentially, solving a core problem in the theory of Costas arrays. The proof combines ideas from random graph theory with tools from probabilistic combinatorics.

The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture1. The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate2–4. Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans—including 278 individuals from England—alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present-day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age France5,6.

Religion ist ein diskursiv komplexes Wort der deutschen Sprache. Sein Gebrauch wird hier im Kontext des deutschen Kolonialismus genauer untersucht. Einerseits betrachtet der Aufsatz den diskurslinguistischen Status des Nomens näher und andererseits legt er auf der Grundlage der Digitalen Sammlung deutscher Kolonialismuseine korpuspragmatische Analyse konkreter epistemischer Situiertheit des Nomens vor.

Glycan analysis has evolved considerably during the last decade. The advent of high-resolution ion-mobility spectrometry has enabled the separation of isomers with only the slightest of structural differences. However, the ability to separate such species raises the problem of identifying all the mobility-resolved peaks that are observed, especially when analytical standards are not available. In this work, we report an approach based on the combination of IMSnwith cryogenic vibrational spectroscopy to identify N-glycan reducing-end anomers. By identifying the reducing-end α and β anomers of diacetyl-chitobiose, which is a disaccharide that forms part of the common core of all N-glycans, we are able to assign mobility peaks to reducing anomers of a selection of N-glycans of different sizes, starting from trisaccharides such as Man-1 up to glycans containing nine monosaccharide units, such as G2. By building an infrared fingerprint database of the identified N-glycans, our approach allows unambiguous identification of mobility peaks corresponding to reducing-end anomers and distinguishes them from positional isomers that might be present in a complex mixture.

Background: Colombian indigenous Wiwas are exposed to a variety of partly complex medical conditions with a predominance of infectious diseases. The study provided here aims at verifying of falsifying previous suspicions on therapeutic shortcomings and neglect of disease categories. Material and methods: Local diagnoses within various subpopulations of indigenous Wiwas obtained by a study physician and local health brigades and health points between 2017 and 2018 were coded following the ICD 10 classification from 2019. Proportions of diagnoses per ICD-10 sub-chapter were evaluated to find diseases and to rank the occurrence of diagnoses in the population of indigenous people. Thereafter, the available medication provided by the indigenous health care provider Dusakawi for the treatment of the indigenous patients was analyzed in regard of its sufficiency to cover the recorded diseases. Results: The majority of the diseases found in the communities cannot at all (32%) or only partially (56%) be treated according to available guidelines. Only few (12%), predominantly infectious diseases, were covered completely by the provided medication. Notably, there are some ICD chapters with diseases that do only rarely appear at all in the gained datasets, e.g., complications during birth, mental disorders or cancer. Conclusions: An expansion and revision of the medical supply for the indigenous population of the Sierra Nevada de Santa Marta is needed. An emergency kit for medical brigades and health points should be provided and in place. Awareness for neglected diseases needs to be created.

•Cohort study in MS patients treated with natalizumab.•The cohort was enriched for individuals with high anti-JCV antibody levels in sera.•JCV DNA was undetectable in stool samples using sensitive methods.•Stool samples seem not suitable for PML risk stratification in persons with MS.

Tarlov cysts are a rare condition. While they appear asymptomatic mostly, some patients develop severe clinical symptoms. Tarlov cysts can grow over time and may result from disturbances within the spinal CSF system. Due to the rare character, the disease can be a burden for both patients and physicians. Treat or not to treat, and if yes, how to treat is a relevant question. Here, a retrospective, observational study on 49 patients suffering from symptomatic Tarlov cysts treated with a combined endoscopic-microsurgical approach was performed. The microsurgical resection was combined with thecaloscopy inside the lower lumbosacral subarachnoidal space to improve the CSF flow and pressure regulation capability. The purpose was to prove that the surgical method was able to prevent recurrence and gives a major relief of symptoms. Our data suggest that combined interventional treatment of symptomatic Tarlov Cysts is helpful to treat the long-standing symptoms. In all patients we found signs for inflammatory processes at the level of the lumbar leptomeningeal sheets, involving the pia mater and the arachnoid. We found evidence that patients suffering from a slow inflammatory process within the leptomeninges might have increase risk of developing Tarlov cysts. We hypothesized that local CSF flow and pressure regulation mechanism become invalid by the morphological changes at the arachnoid and lose the capability to regulate CSF pressure down by pressing minimal volumes of CSF out of the dural sac at the nerve root exits.

Buffalograss [Buchloë dactyloides(Nutt.) Engelm. syn. Bouteloua dactyloides(Nutt.) Columbus] is a stoloniferous low input turfgrass species native to the central Great Plains of the United States. Several molecular marker techniques have been used to compare relationships among elite buffalograss germplasm, but most rely on random amplification, are transferred from other species, or are developed from limited DNA sequence information. The objectives of this study were to develop buffalograss derived simple sequence repeat markers (SSRs) from buffalograss sequence data using an in‐silico bioinformatics pipeline and use high resolution melt analysis to screen the SSRs based on their melt profiles on buffalograss cultivars and germplasm. Transcriptomes from buffalograss cultivars ‘378’ and ‘Prestige’ were mined for SSRs using the MIcroSAtellite tool. There were 259 conserved SSRs that were polymorphic between 378 and Prestige. Of those, 96 were tested by HRM on a panel of eight genotypes and 24 were selected for producing melt profiles that could distinguish the genotypes. The selected reactions produced 356 distinct melt profiles when tested on a panel of 96 genotypes, including 88 buffalograss germplasm selections, six buffalograss cultivars, and two blue grama [Bouteloua gracilis(H. B. K.) Lag. ex Steud.] selections, with melt profile frequencies ranging from 0.01 to 0.97. A subset of 86 melt profiles segregating among the blue grama and elite buffalograss cultivars distinguished each genotype. The buffalograss‐specific SSR markers presented here will be useful to study buffalograss genetic diversity, line purity maintenance, and for marker supported plant breeding strategies. Buffalograss transcriptome‐derived simple sequence repeat markers can distinguish cultivars.Simple sequence repeat markers can support cultivar purity and maintenance.Coupled with high resolution melt, buffalograss SSRs are a rapid molecular diagnostic tool.

The diagnosis of angioimmunoblastic T-cell lymphoma (AITL) is complex and requires the demonstration of a T-follicular helper (TFH) phenotype. Immunophenotypic markers that detect the TFH phenotype are highly variable, thereby necessitating the use of 3 to 5 TFH markers to substantiate a TFH phenotype. We tested the utility of germinal center markers human germinal center–associated lymphoma (HGAL) and LIM-domain only 2 (LMO2) in detecting a TFH phenotype. We compared their staining to that of 6 TFH markers in current use, PD-1, ICOS, CXCL13, SAP, CD10, and BCL6, in a cohort of 23 AITL. Our results show that although both markers can detect a TFH phenotype, HGAL was superior to LMO2 in the percent of cells stained and the intensity of staining, 2 variables used to generate H-scores. Using H-scores as the metric, HGAL was most comparable to BCL6 among the currently used TFH markers and was more sensitive than CXCL13, SAP, CD10, and LMO2. PD-1 and ICOS emerged as the most robust of the 8 markers tested in this study in detecting a TFH phenotype. We conclude that HGAL is a reliable marker of TFH cells and can aid in the diagnosis of lymphomas of TFH derivation, particularly in the recognition of early patterns of AITL.

The aim was to assess the pharmacokinetics of tolterodine released from vaginal rings and of its active metabolite 5‐hydroxymethyl tolterodine (5‐HMT) compared to the respective pharmacokinetics resulting from oral administration of extended‐release tolterodine in healthy, postmenopausal women. In this single‐center, open‐label trial, subjects received 4 treatments in a fixed sequence: fasted oral extended‐release tolterodine 2.74 mg/d (reference, 5 days), single vaginal rings; tolterodine releasing rates: 0.95 mg/d (test 1, 13 days), 1.40 mg/d (test 2, 28 days), 1.90 mg/d (test 3, 28 days). Systemic exposure of tolterodine, 5‐HMT, and the molar sum of unbound tolterodine/5‐HMT (active moiety [AM]) in steady state was determined. Sixteen of 18 included women completed the study. For the oral formulation, peak‐trough fluctuations of tolterodine, 5‐HMT, and AM plasma concentrations (AM: mean maximum/minimum concentration, 2580/574 pmol/L = 4.5) were large. Intravaginal application led to steadier plasma concentrations (AM, test 3: mean maximum/minimum concentration, 1880/814 pmol/L = 2.3; fluctuation due to initial peak), which is the result of constant releasing rates after ring insertion over the 28‐day application period. The vaginal rings demonstrated a favorable local tolerability. The most common adverse events with oral and vaginal tolterodine were headache (n = 11) and dry mouth (n = 8). Vaginal rings releasing tolterodine represent a promising new formulation for overactive bladder treatment with little fluctuation of drug plasma levels. This is expected to lead to a more predictable and continuous therapeutic effect and a reduced frequency of side effects compared to oral tolterodine.

A quality improvement project conducted at 3 Texas hospitals to implement a new systematic process to address maternal marijuana use among breastfeeding mothers. The new process was created using the evidence-based Screening, Brief Intervention, Referral to Treatment (SBIRT) model to address maternal marijuana use. Nurses screened all postpartum mothers for marijuana use at each of the 3 hospitals. Mothers who reported ever using marijuana were advised to abstain while breastfeeding and given educational materials and a treatment referral card. Among all 3 hospitals, the mean nurses’ adherence to the SBIRT process was 69 percent, exceeding the project aim of 50 percent adherence. SBIRT, which has been used extensively with other populations and settings, was easily translated into practice for use with postpartum mothers who reported using marijuana. A systematic process using SBIRT may help mitigate the risk of harm for infants of mothers who use marijuana.