Risk factors for recurrent urinary tract infections among women in a large integrated health care organization in the United States.

BACKGROUND: Urinary tract infections (UTIs) occur commonly and often recur. However, recent data on the epidemiology of recurrent UTI (rUTI) are scarce. METHODS: Between 01/01/2016-31/12/2020, index uncomplicated UTIs (uUTI) from office, emergency department (ED), hospital, and virtual care settings were identified from electronic health records of women at Kaiser Permanente Southern California. We defined rUTI as ≥3 UTI within 365 days or ≥2 UTI within 180 days. We determined the proportion of women with cystitis index uUTI who had rUTI and examined factors associated with rUTIs using modified multivariable Poisson regression. RESULTS: Among 374,171 women with cystitis index uUTI, 54,318 (14.5%) had rUTI. A higher proportion of women with rUTI compared to those without rUTI were age 18-27 or ≥78 years at index uUTI (19.7% vs 18.7% and 9.0% vs 6.0%, respectively), were immunocompromised, or had a positive urine culture at index uUTI. In multivariable analyses, characteristics associated with rUTI included younger or older age (48-57 vs 18-27 years aRR=0.83 [95% CI: 0.80-0.85]; ≥78 vs 18-27 years aRR=1.07 [95%CI=1.03-1.11]), Charlson Comorbidity Index (≥3 vs 0, aRR=1.12 [95%CI:1.08-1.17]), and diabetes mellitus (aRR=1.07 [95%CI:1.04-1.10]). More frequent prior year outpatient and ED encounters, oral antibiotic prescriptions, oral contraceptive prescriptions, positive culture at index uUTI, and antibiotic resistant organisms were also associated with increased risk of rUTI. CONCLUSIONS: The high risk of rUTI among women with cystitis is concerning, especially given previous reports of increasing UTI incidence. Current assessment of the epidemiology of rUTI may guide the development of preventive interventions against UTI.

Antibiotic resistance of urinary tract infection recurrences in a large U.S. integrated health care system.

BACKGROUND: Data on antibiotic resistance of uropathogens for UTI recurrences are lacking. METHODS: In a retrospective cohort of adults at Kaiser Permanente Southern California with culture-confirmed index uncomplicated UTI (uUTI) between 01/2016 and 12/2020, we examined the number and characteristics of subsequent culture-confirmed UTIs through 2021. RESULTS: We identified 148,994 individuals with a culture-confirmed index uUTI (88% female, 44% Hispanic, mean age 51 years [s.d. 19]), of whom 19% developed a subsequent culture-confirmed UTI after a median 300 days (IQR: 126-627). The proportion of UTI due to E. coli was highest for index uUTI (79%) and decreased to 73% for sixth UTI (UTI 6) (p-for trend <0.001), while the proportion due to Klebsiella spp increased from index UTI (7%) to UTI 6 (11%) (p-for-trend <0.001). Non-susceptibility to ≥1 and ≥3 antibiotic classes was observed in 57% and 13% of index uUTIs, respectively, and was higher for subsequent UTIs (65% and 20%, respectively, for UTI 6). Most commonly observed antibiotic non-susceptibility patterns included penicillins alone (12%), and penicillins, trimethoprim-sulfamethoxazole plus ≥1 additional antibiotic class (9%). CONCLUSIONS: Antibiotic non-susceptibility is common in UTIs and increases with subsequent UTIs. Continuous monitoring of UTI recurrences and susceptibility patterns are needed to guide treatment decisions.

Heteropolyaromatic Covalent Organic Frameworks via One-Pot Multicomponent Reactions.

Multicomponent reactions (MCRs) offer a platform to create different chemical structures and linkages for highly stable covalent organic frameworks (COFs). As an illustrative example, the multicomponent Povarov reaction generates 2,4-phenylquinoline from aldehydes and amines in the presence of electron-rich alkenes. In this study, we introduce a new domino reaction to generate unprecedented 2,3-phenylquinoline COFs in the presence of epoxystyrene. This work thus presents, for the first time, structural isomeric COFs produced by multicomponent domino and Povarov reactions. Furthermore, 2,3-phenylquinolines can undergo a Scholl reaction to form extended aromatic linkages. With this approach, we synthesize two thermally and chemically stable MCR-COFs and two heteropolyaromatic COFs using both domino and in situ domino and Scholl reactions. The structure and properties of these COFs are compared with the corresponding 2,4-phenylquinoline-linked COF and imine-COF, and their activity toward benzene and cyclohexane sorption and separation is investigated. The position of the pendant phenyl groups within the COF pore plays a crucial role in facilitating the industrially important sorption and separation of benzene over cyclohexane. This study opens a new avenue to construct heteropolyaromatic COFs via MCR reactions.

Stabilizing Monoatomic Two-Coordinate Bismuth(I) and Bismuth(II) Using a Redox Noninnocent Bis(germylene) Ligand.

The formation of isolable monatomic BiI complexes and BiII radical species is challenging due to the pronounced reducing nature of metallic bismuth. Here, we report a convenient strategy to tame BiI and BiII atoms by taking advantage of the redox noninnocent character of a new chelating bis(germylene) ligand. The remarkably stable novel BiI cation complex 4, supported by the new bis(iminophosphonamido-germylene)xanthene ligand [(P)GeII(Xant)GeII(P)] 1, [(P)GeII(Xant)GeII(P) = Ph2P(NtBu)2GeII(Xant)GeII(NtBu)2PPh2, Xant = 9,9-dimethyl-xanthene-4,5-diyl], was synthesized by a two-electron reduction of the cationic BiIIII2 precursor complex 3 with cobaltocene (Cp2Co) in a molar ratio of 1:2. Notably, owing to the redox noninnocent character of the germylene moieties, the positive charge of BiI cation 4 migrates to one of the Ge atoms in the bis(germylene) ligand, giving rise to a germylium(germylene) BiI complex as suggested by DFT calculations and X-ray photoelectron spectroscopy (XPS). Likewise, migration of the positive charge of the BiIIII2 cation of 3 results in a bis(germylium)BiIIII2 complex. The delocalization of the positive charge in the ligand engenders a much higher stability of the BiI cation 4 in comparison to an isoelectronic two-coordinate Pb0 analogue (plumbylone; decomposition below -30 °C). Interestingly, 4[BArF] undergoes a reversible single-electron transfer (SET) reaction (oxidation) to afford the isolable BiII radical complex 5 in 5[BArF]2. According to electron paramagnetic resonance (EPR) spectroscopy, the unpaired electron predominantly resides at the BiII atom. Extending the redox reactivity of 4[OTf] employing AgOTf and MeOTf affords BiIII(OTf)2 complex 7 and BiIIIMe complex 8, respectively, demonstrating the high nucleophilic character of BiI cation 4.

Dynamical Criticality of Magnetization Transfer in Integrable Spin Chains.

Recent studies have found that fluctuations of magnetization transfer in integrable spin chains violate the central limit property. Here, we revisit the problem of anomalous counting statistics in the Landau-Lifshitz field theory by specializing to two distinct anomalous regimes featuring a dynamical critical point. By performing optimized numerical simulations using an integrable space-time discretization, we extract the algebraic growth exponents of time-dependent cumulants which attain their threshold values. The distinctly non-Gaussian statistics of magnetization transfer in the easy-axis regime is found to converge toward the universal distribution of charged single-file systems. At the isotropic point, we infer a weakly non-Gaussian distribution, corroborating the view that superdiffusive spin transport in integrable spin chains does not belong to any known dynamical universality class.

Computational Performance of Deep Reinforcement Learning to Find Nash Equilibria.

We test the performance of deep deterministic policy gradient-a deep reinforcement learning algorithm, able to handle continuous state and action spaces-to find Nash equilibria in a setting where firms compete in offer prices through a uniform price auction. These algorithms are typically considered "model-free" although a large set of parameters is utilized by the algorithm. These parameters may include learning rates, memory buffers, state space dimensioning, normalizations, or noise decay rates, and the purpose of this work is to systematically test the effect of these parameter configurations on convergence to the analytically derived Bertrand equilibrium. We find parameter choices that can reach convergence rates of up to 99%. We show that the algorithm also converges in more complex settings with multiple players and different cost structures. Its reliable convergence may make the method a useful tool to studying strategic behavior of firms even in more complex settings.

An Alkyne-Bridged Covalent Organic Framework Featuring Interactive Pockets for Bromine Capture.

The high degree of corrosivity and reactivity of bromine, which is released from various sources, poses a serious threat to the environment. Moreover, its coexistence with iodine forming an equilibrium compound, iodine monobromide (IBr) necessitates the selective capture of bromine from halogen mixtures. The electrophilicity of halogens to π-electron rich structures enabled us to strategically design a covalent organic framework for halogen capture, featuring a defined pore environment with localized sorption sites. The higher capture capacity of bromine (4.6 g g-1) over iodine by ~41 % shows its potential in selective capture. Spectroscopic results uncovering the preferential interaction sites are supported by theoretical investigations. The alkyne bridge is a core functionality promoting the selectivity in capture by synergistic physisorption, rationalized by the higher orbital overlap of bromine due to its smaller atomic size as well as reversible chemical interactions. The slip stacking in the structure has further promoted this phenomenon by creating clusters of molecular interaction sites with bromine intercalated between the layers. The inclusion of unsaturated moieties, i.e. triple bonds and the complementary pore geometry offer a promising design strategy for the construction of porous materials for halogen capture.

The Role of AI in Serious Games and Gamification for Health: Scoping Review.

BACKGROUND: Artificial intelligence (AI) and game-based methods such as serious games or gamification are both emerging technologies and methodologies in health care. The merging of the two could provide greater advantages, particularly in the field of therapeutic interventions in medicine. OBJECTIVE: This scoping review sought to generate an overview of the currently existing literature on the connection of AI and game-based approaches in health care. The primary objectives were to cluster studies by disease and health topic addressed, level of care, and AI or games technology. METHODS: For this scoping review, the databases PubMed, Scopus, IEEE Xplore, Cochrane Library, and PubPsych were comprehensively searched on February 2, 2022. Two independent authors conducted the screening process using Rayyan software (Rayyan Systems Inc). Only original studies published in English since 1992 were eligible for inclusion. The studies had to involve aspects of therapy or education in medicine and the use of AI in combination with game-based approaches. Each publication was coded for basic characteristics, including the population, intervention, comparison, and outcomes (PICO) criteria; the level of evidence; the disease and health issue; the level of care; the game variant; the AI technology; and the function type. Inductive coding was used to identify the patterns, themes, and categories in the data. Individual codings were analyzed and summarized narratively. RESULTS: A total of 16 papers met all inclusion criteria. Most of the studies (10/16, 63%) were conducted in disease rehabilitation, tackling motion impairment (eg, after stroke or trauma). Another cluster of studies (3/16, 19%) was found in the detection and rehabilitation of cognitive impairment. Machine learning was the main AI technology applied and serious games the main game-based approach used. However, direct interaction between the technologies occurred only in 3 (19%) of the 16 studies. The included studies all show very limited quality evidence. From the patients' and healthy individuals' perspective, generally high usability, motivation, and satisfaction were found. CONCLUSIONS: The review shows limited quality of evidence for the combination of AI and games in health care. Most of the included studies were nonrandomized pilot studies with few participants (14/16, 88%). This leads to a high risk for a range of biases and limits overall conclusions. However, the first results present a broad scope of possible applications, especially in motion and cognitive impairment, as well as positive perceptions by patients. In future, the development of adaptive game designs with direct interaction between AI and games seems promising and should be a topic for future reviews.

Disease-Agnostic Electronic Adherence Aid for Subcutaneous at-Home and Self-Administration Devices-The Lowest Common Denominator Based on a Cross-Indication Survey.

The value of connected devices and health apps with features such as adherence trackers, dosing reminders, and remote communication tools for users and healthcare providers has been assessed to support home-based subcutaneous administration. A comprehensive survey was conducted with 605 participants, including users and caregivers, from eight countries. Medical conditions encompassed ankylosing spondylitis, asthma, cerebral palsy, cluster headaches, Crohn's disease, hemophilia, lupus, migraine, multiple sclerosis, Parkinson's disease, plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, spasticity, spondyloarthritis, and ulcerative colitis. Utilizing a maximum difference scaling methodology, the survey gauged participant preferences regarding specific attributes and features of connected drug delivery devices. Irrespective of demographic factors like age, gender, nationality, or the specific medical condition, the device's ability to verify a successful injection stood out as universally valued. The second and third most valued attributes pertained to temperature-related indicators or warnings. These features do not necessitate the use of a connected device and can be integrated into existing autoinjector platforms. The survey findings support the development of a universal adherence tool for at-home subcutaneous dosing, independent of a specific medical condition. This tool may be gradually improved with disease-specific features. Once established as a platform, manufacturers can launch any subcutaneous medication and later integrate real-world evidence for enhanced educational, treatment, and diagnostic capabilities. This approach is crucial for advancing connected adherence tools in decentralized healthcare, aligning with user and healthcare system needs while translating scientific innovation into practical solutions.

The stress for surgeons: exploring stress entities with the robotic senhance surgical system.

Robotic surgery is on its way to revolutionizing traditional surgical procedures, offering precise and minimally invasive techniques hypothesized to shorten recovery times and improve patient outcomes. While there have been multiple publications on robotic systems' medical and procedural achievements, more emphasis should be put on the surgeon's experience, especially in comparison with laparoscopic surgery. The present report aims to systematically examine the stress impact on surgeons by comparing the robotic Senhance Surgical System (Asensus Surgical, Durham, North Carolina, U.S.A) to laparoscopic surgery. The well-established "SURG-TLX" survey is used to measure distinct stress entities. The "SURG-TLX" survey is a modified version of the NASA-TLX, validated for surgery by M. Willson. Based on a comprehensive database from six centers encompassing various disciplines and surgical procedures, our analysis indicates significantly reduced "overall stress" levels for robotic (cockpit) compared to laparoscopic surgeons. Exploring the "SURG-TLX" stress dimensions further between methods (robotic vs. laparoscopic) and surgeon position (laparoscopic, (robotic) bedside, or (robotic) cockpit) resulted in significantly more Mental (p.value < 0.015), less Physical Demands (p.value < 0.001) and less Distraction (p.value < 0.009) for robotic surgery, especially regarding the robotic cockpit surgeons. This finding suggests that robotic surgery with the Senhance Surgical System contributes to a favorable stress profile for surgeons, potentially enhancing their overall well-being and performance.

Adjuvant Treatment with S-1 in Patients after R0-Resection of Adenocarcinoma of the Stomach and Esophagogastric Junction: A Multicenter Phase I/II Feasibility Study (GMBH-STO-0114).

INTRODUCTION: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability, and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients. METHODS: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30 mg/m2 bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the Common Toxicity Criteria Adverse Events (CTCAE) version 4.0. Secondary endpoints were 1-year relapse-free survival (RFS) rate, RFS, and overall survival (OS). RESULTS: Between October 2015 and February 2018, 32 patients were enrolled in 12 German centers, and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment early due to adverse events (AEs), 7 due to patient's or investigator's decision, and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m2 in 9 patients and to 20 mg/m2 in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥3 AEs were neutropenia, diarrhea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia, and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year RFS rate was 77%. Data on OS were still premature at the end of the study. CONCLUSION: Adjuvant treatment with S-1 for 1 year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ after R0-resection.

Excess resource use and cost of drug-resistant infections for six key pathogens in Europe: a systematic review and Bayesian meta-analysis.

BACKGROUND: Quantifying the resource use and cost of antimicrobial resistance establishes the magnitude of the problem and drives action. OBJECTIVES: Assessment of resource use and cost associated with infections with six key drug-resistant pathogens in Europe. METHODS: A systematic review and Bayesian meta-analysis. DATA SOURCES: MEDLINE (Ovid), Embase (Ovid), Econlit databases, and grey literature for the period 1 January 1990, to 21 June 2022. STUDY ELIGIBILITY CRITERIA: Resource use and cost outcomes (including excess length of stay, overall costs, and other excess in or outpatient costs) were compared between patients with defined antibiotic-resistant infections caused by carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, CR or third-generation cephalosporin Escherichia coli (3GCREC) and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium, and patients with drug-susceptible or no infection. PARTICIPANTS: All patients diagnosed with drug-resistant bloodstream infections (BSIs). INTERVENTIONS: NA. ASSESSMENT OF RISK OF BIAS: An adapted version of the Joanna Briggs Institute assessment tool, incorporating case-control, cohort, and economic assessment frameworks. METHODS OF DATA SYNTHESIS: Hierarchical Bayesian meta-analyses were used to assess pathogen-specific resource use estimates. RESULTS: Of 5969 screened publications, 37 were included in the review. Data were sparse and heterogeneous. Most studies estimated the attributable burden by, comparing resistant and susceptible pathogens (32/37). Four studies analysed the excess cost of hospitalization attributable to 3GCREC BSIs, ranging from -€ 2465.50 to € 6402.81. Eight studies presented adjusted excess length of hospital stay estimates for methicillin-resistant S. aureus and 3GCREC BSIs (4 each) allowing for Bayesian hierarchical analysis, estimating means of 1.26 (95% credible interval [CrI], -0.72 to 4.17) and 1.78 (95% CrI, -0.02 to 3.38) days, respectively. CONCLUSIONS: Evidence on most cost and resource use outcomes and across most pathogen-resistance combinations was severely lacking. Given the importance of this evidence for rational policymaking, further research is urgently needed.