Co-resistance Among Escherichia coli and Klebsiella pneumoniae Urine Isolates from Female Outpatients with Presumed UTI: A Retrospective US Cohort Study.

INTRODUCTION: Urinary tract infections (UTIs) caused by antimicrobial-resistant Enterobacterales are a global health threat. There are limited surveillance data available to characterize the prevalence of antimicrobial resistance among outpatients in the United States (US). METHODS: This retrospective cohort (database) study investigated co-resistance among Escherichia coli and Klebsiella pneumoniae urinary isolates from US female outpatients aged ≥ 12 years with presumed uncomplicated UTI (uUTI), ≥ 3 months of data (2011-2019), and antimicrobial susceptibility testing results. Eligible isolates were the first urinary E. coli or K. pneumoniae isolate per patient collected within 30 days; classified as not susceptible (NS) if antimicrobial susceptibility testing results were intermediate or resistant to each antibiotic tested. Four resistance phenotypes were identified: NS to fluoroquinolones (FQ), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NTF), and extended-spectrum ß-lactamase+/third-generation cephalosporin (ESBL+/3GC NS). Co-resistance phenotypes included all possible combinations of resistance to ≥ 2 drug classes. RESULTS: Of 1,513,882 E. coli isolates and 250,719 K. pneumoniae isolates, 856,918 and 187,459 isolates with ≥ 1 resistance phenotype were included in the analysis, respectively. The most common resistance phenotypes were SXT NS for the E. coli isolates (44.8%) and NTF NS for the K. pneumoniae isolates (75.5%), while ESBL+/3GC NS comprised 11.2 and 5.9%, respectively. Among ESBL+/3GC NS E. coli isolates, 72.4, 56.7, and 46.6% were co-resistant to FQ, SXT, and FQ + SXT, respectively. For ESBL+/3GC NS K. pneumoniae isolates, 65.7 and 45.7% were co-resistant to SXT and FQ + SXT. CONCLUSION: Both species exhibited high rates of co-resistance, emphasizing the need to raise awareness of co-resistance and of the unmet need for effective treatment options for uUTI.

Treatment Patterns and Adherence to Guidelines for Uncomplicated Urinary Tract Infection in Germany: A Retrospective Cohort Study.

INTRODUCTION: Understanding antibiotic prescribing for uncomplicated urinary tract infection (uUTI) could help to optimize management. However, data on uUTI treatment patterns in the European Union are scarce. We used real-world data to evaluate adherence to antibiotic prescribing guidelines for femalepatients with uUTI in Germany. METHODS: This retrospective cohort study used anonymized German statutory health insurance claims data from the Wissenschaftliches Institut für Gesundheitsökonomie und Gesundheitssystemforschung from January 2013 to December 2019. Patients were female, aged ≥ 12 years, with an index uUTI diagnosis. Patient characteristics and treating physician specialties were examined overall and in sub-cohorts for recommended/non-recommended treatment (based on initial therapy adherence to German uUTI treatment guidelines) and optimal/sub-optimal outcome (based on a prescription of different antibiotics or a urinary tract infection-related episode). RESULTS: Overall, 144,645 uUTI cases in 124,971 patients were analyzed; 51,230 (35.4%) and 93,415 (64.6%) cases were assigned to the recommended/non-recommended treatment sub-cohorts, respectively. Clinically meaningful differences in age and comorbidities were observed between these sub-cohorts. Most cases had an optimal outcome (n = 122,823; 84.9%); of these, a higher proportion received antibiotics that were recommended but not as first-choice versus first-choice therapies as their initial treatment (58.6% vs. 35.3%). In the sub-optimal outcome cohort, 49.1% received antibiotics that were recommended but not as first-choice and 41.1% received first-choice therapies as their initial treatment. Most uUTIs were treated by general practitioners (GPs; 82.3%), followed by gynecologists (13.3%), and urologists (6.8%). Notably, 64.5% of initial therapy prescriptions filled by gynecologists and 32.1% by GPs were first-choice antibiotics. CONCLUSION: A high proportion of prescribed treatments for the initial uUTI episode were not recommended by German uUTI guidelines as first-choice antibiotics. Prescribing adherence varied by physician specialty; specialists showed greater adherence to treatment guidelines versus GPs. This study provides a novel and multi-dimensional picture of uUTI treatment in Germany.

Uncomplicated urinary tract infections are one of the most common infections in women. Doctors around the world use different types of antibiotics to treat people with uncomplicated urinary tract infections. We performed this study to find out more about how doctors in Germany use antibiotics to treat uncomplicated urinary tract infections. We looked at health records from female patients (aged 12+) in Germany. Overall, we examined 144,645 records. We found that around one in ten women use antibiotics to treat an uncomplicated urinary tract infection every year. We then checked to see if the doctors were giving people the right type of antibiotic, the right dose, and the right length of course. To do this, we checked against guidelines that were written by experts in Germany. We found that only one in three patients (35%) received treatment that met the guidelines. We also looked to see what differences there were between different types of doctors. For example, if general practitioners (family doctors) used different antibiotics to specialist doctors in hospitals. Four out of five patients (82%) were treated by general practitioners. We found that specialists were more likely to stick to the guidelines than general practitioners. Finally, we looked at how many patients recovered well after their first course of antibiotics. More than four out of five patients (80%) recovered well. Interestingly, more than half of the patients who had a good recovery (59%) received antibiotics that were not recommended by the guidelines.

Alarming Incidence of Gastric Outlet Obstruction Related to NSAIDS and Synthetic Opioid in North West India.

BACKGROUND: In recent years, there has been an alarming increase in cases of gastric outlet obstruction (GOO) at our center due to drug abuse. So, we conducted this study to know the incidence of nonsteroidal anti-inflammatory drugs (NSAIDs) and synthetic opioid abuse in cases of GOO. METHODS: This was an observational study involving consecutive cases of GOO diagnosed from September 2017 to February 2019. A detailed history, including drug addiction history and clinical examination, was done. Investigations included routine biochemical and hematological tests, upper gastrointestinal endoscopy (UGIE), ultrasonography, rapid urease test (RUT), and histopathology of the diseased area. RESULTS: Among the 102 cases diagnosed with GOO, 62 (60.78%) cases had a history of drug addiction. The drug addiction history was as follows: NSAIDs and opioids in 56, opioids alone in four, and NSAIDs alone in two cases. The most common site of stricture was the second part of the duodenum. The features on histopathology were ulcerations of the mucosa infiltrated by eosinophils, plasma cells, and lymphocytes. CONCLUSION: There is an alarming increase in the incidence of GOO due to NSAIDs and opioid abuse at our center. Efforts should be made to control the indiscriminate use of these over-the-counter drugs to prevent dreaded complications.

The Efficacy of Paxman Scalp Cooling System in Preventing Hair Loss in Breast Cancer Patients Receiving Chemotherapy in Western India - Multi-centre Retrospective Cohort Study.

Aim: Chemotherapy-induced alopecia (CIA) is the most common side effect of systemic treatment in breast cancer patients. Scalp cooling gained worldwide acceptance in preventing or mitigating CIA in patients undergoing chemotherapy. The objective of this study was to evaluate the efficacy and safety of the Paxman scalp cooling system (PSCS) in Indian breast cancer patients. Materials and Methods: This is a multi-centre, retrospective-observational study including patients registered from 1st March, 2019 to 30th April, 2021 undergoing chemotherapy for breast cancer by using PSCS. The primary end-point was the incidence of CIA after completing cycles of chemotherapy. Results: A total of 91 female patients were enrolled in the study, with a median age of 53 years (IQR: 44-62 years). The prevention of alopecia (grade 0 and grade I) was seen in 81%, while more than 50% hair loss (grade 2) was seen in 16.48% after completion of treatment. The univariate analysis results showed that CIA was significantly higher in patients who received anthracyclines (OR: 2.69; 95% CI: 1.04-6.958; P = 0.041) and in patients with a post-infusion cooling time of >150 minutes (OR: 8.409; 95% CI: 2.295-30.787; P = 0.001). The incidence of grade 2 (>50% hair loss) alopecia was 81.3% in patients <6 weeks and was 18.8% at >6 weeks of start of chemotherapy (P < 0.0001). No adverse events were reported in 71.4% of patients, and the most common adverse event was headache (18.7%). Conclusion: PSCS is an effective and well-tolerated treatment modality for preventing CIA among breast cancer patients undergoing chemotherapy.

Development of Predictive Models to Inform a Novel Risk Categorization Framework for Antibiotic Resistance in E. coli-Causing Uncomplicated Urinary Tract Infection.

BACKGROUND: In clinical practice, challenges in identifying patients with uncomplicated urinary tract infections (uUTIs) at risk of antibiotic non-susceptibility may lead to inappropriate prescribing and contribute to antibiotic resistance. We developed predictive models to quantify risk of non-susceptibility to four commonly prescribed antibiotic classes for uUTI, identify predictors of non-susceptibility to each class, and construct a corresponding risk categorization framework for non-susceptibility. METHODS: Eligible females aged ≥12 years with E. coli-caused uUTI were identified from Optum's de-identified Electronic Health Record dataset (10/1/2015‒2/29/2020). Four predictive models were developed to predict non-susceptibility to each antibiotic class and a risk categorization framework was developed to classify patients' isolates as low, moderate, and high risk of non-susceptibility to each antibiotic class. RESULTS: Predictive models were developed among 87487 patients. Key predictors of having a non-susceptible isolate to ≥3 antibiotic classes included number of previous UTI episodes, prior ß-lactam non-susceptibility, prior fluoroquinolone treatment, census bureau region, and race. The risk categorization framework classified 8.1%, 14.4%, 17.4%, and 6.3% of patients as having isolates at high risk of non-susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, ß-lactams, and fluoroquinolones, respectively. Across classes, the proportion of patients categorized as having high-risk isolates was 3-12 folds higher among patients with non-susceptible isolates versus susceptible isolates. CONCLUSIONS: Our predictive models highlight factors that increase risk of non-susceptibility to antibiotics for uUTIs, while the risk categorization framework contextualizes risk of non-susceptibility to these treatments. Our findings provide valuable insight to clinicians treating uUTIs and may help inform empiric prescribing in this population.

Likelihood of Antimicrobial Resistance in Urinary E coli Isolates among US Female Patients with Recurrent vs Non-Recurrent Uncomplicated Urinary Tract Infection.

OBJECTIVE: To assess the relative likelihood of antimicrobial resistance (AMR) and multi-drug resistance (MDR) among E coli isolates from outpatients with recurrent versus non-recurrent uncomplicated urinary tract infection (uUTI). METHODS: In this retrospective observational US cohort study, female outpatients (≥12 years) with uUTI, positive E coli culture, and treated with ≥1 oral antibiotic within ±5 days of diagnosis were grouped into recurrent and non-recurrent uUTI cohorts per their UTI history (past 12 months). AMR to specific drug classes was evaluated at index. Univariable and multivariable logistic regression models estimated the likelihood of not-susceptible E coli isolates (AMR/MDR) among patients with recurrent uUTI versus non-recurrent uUTI. RESULTS: Recurrent (N = 12,234) and non-recurrent (N = 68,033) uUTI cohorts had similar distributions (race, ethnicity, region). Patients with recurrent uUTI had a higher prevalence of E coli resistance to trimethoprim-sulfamethoxazole (21.8% vs 18.7%) and fluoroquinolones (14.2% vs 8.6%), and more isolates were extended-spectrum ß-lactamase-producing (5.9% vs 4.1%) compared to non-recurrent uUTI patients. Patients with recurrent uUTI had a higher likelihood (odds ratio [95% confidence interval]) of any AMR (1.28 [1.22-1.34]), single drug-class resistance (1.18 [1.12-1.24]), and resistance to 2 (1.53 [1.41-1.67]) or ≥3 drug classes (1.70 [1.48-1.96]) (all P <.001). CONCLUSION: This study delineated the likelihood of AMR and MDR among E coli isolates from patients with recurrent versus non-recurrent uUTI. While some treatment guidelines support empiric therapy in recurrent uUTI, the increased likelihood of resistance among these patients suggests that culture and susceptibility testing should be undertaken to inform recurrent uUTI treatment.

Prevalence, regional distribution, and trends of antimicrobial resistance among female outpatients with urine Klebsiella spp. isolates: a multicenter evaluation in the United States between 2011 and 2019.

BACKGROUND: Antimicrobial resistance research in uncomplicated urinary tract infection typically focuses on the main causative pathogen, Escherichia coli; however, little is known about the antimicrobial resistance burden of Klebsiella species, which can also cause uncomplicated urinary tract infections. This retrospective cohort study assessed the prevalence and geographic distribution of antimicrobial resistance among Klebsiella species and antimicrobial resistance trends for K. pneumoniae in the United States (2011-2019). METHODS: K. pneumoniae and K. oxytoca urine isolates (30-day, non-duplicate) among female outpatients (aged ≥ 12 years) with presumed uUTI at 304 centers in the United States were classified by resistance phenotype(s): not susceptible to nitrofurantoin, trimethoprim/sulfamethoxazole, or fluoroquinolone, extended-spectrum ß-lactamase-positive/not susceptible; and multidrug-resistant based on ≥ 2 and ≥ 3 resistance phenotypes. Antimicrobial resistance prevalence by census division and age, as well as antimicrobial resistance trends over time for Klebsiella species, were assessed using generalized estimating equations. RESULTS: 270,552 Klebsiella species isolates were evaluated (250,719 K. pneumoniae; 19,833 K. oxytoca). The most frequent resistance phenotypes in 2019 were nitrofurantoin not susceptible (Klebsiella species: 54.0%; K. pneumoniae: 57.3%; K. oxytoca: 15.1%) and trimethoprim/sulfamethoxazole not susceptible (Klebsiella species: 10.4%; K. pneumoniae: 10.6%; K. oxytoca: 8.6%). Extended-spectrum ß-lactamase-positive/not susceptible prevalence was 5.4%, 5.3%, and 6.8%, respectively. K. pneumoniae resistance phenotype prevalence varied (p < 0.0001) geographically and by age, and increased over time (except for the nitrofurantoin not susceptible phenotype, which was stable and > 50% throughout). CONCLUSIONS: There is a high antimicrobial resistance prevalence and increasing antimicrobial resistance trends among K. pneumoniae isolates from female outpatients in the United States with presumed uncomplicated urinary tract infection. Awareness of K. pneumoniae antimicrobial resistance helps to optimize empiric uncomplicated urinary tract infection treatment.

Designing and evaluating a Nutritional Assessment and Intervention Kiosk for mother-child dyad to combat double burden of malnutrition.

The study protocol focuses on DBM, proposing a preventive strategy for mother-child pairs that would be accessible, affordable, sustainable, and human-centred. The aim is to guide the development of tools and technologies, passing through stages for gathering a process and presenting health data. The initial stage identifies the rules and models synthesising existing digital interventions combating forms of malnourishment, followed by designing and developing a Nutrition Informatics Intervention, i.e. NAIK. The last stage includes evaluation of the effectiveness and utility of NAIK. The system aims to address malnutrition by assessing different associated elements, with the participants. An SMS system will provide follow-up assistance. Overall, this study is an amalgamation of technology, data collection, personalised interventions, growth monitoring, and education to address malnutrition effectively by promoting positive health-behaviours within the community. So, a computerised health kiosk will help provide preventive strategies from the healthcare professional, especially in circumstances requiring immediate attention.

A Real-World Molecular Epidemiological Study of Non-Small-Cell Lung Cancer (NSCLC) Patients from Western India.

Ashish JoshiBackground The molecular characterization of advanced non-small-cell lung cancer (NSCLC) has unveiled genomic alterations such as EGFR gene mutations, KRAS gene mutations, ROS1 gene rearrangements, EML4-ALK rearrangements, and altered MET signaling. The objective of this molecular epidemiological study was to report the clinical, pathological, and molecular profile of NSCLC patients from western India. Materials and Methods This real-world study of NSCLC patients was performed at a chemotherapy day-care center in western India. The clinical, pathological, and molecular data were collected from the patient's medical records after obtaining the Ethics Committee permission for the study. The study was conducted according to the ethical principles stated in the latest version of Helsinki Declaration, and the applicable guidelines for good clinical practice. Results A total of 182 (58.7%) men and 128 (41.3%) women with a median age of 63 years (range: 22-93 years) were included in the study. Of the total 310 patients, 195 (62.9%) were nonsmokers whereas 81 (26.1%) had a past history of smoking. EGFR , EML4-ALK Fusion Gene, KRAS , ROS1 gene rearrangement, and PD-L1 were positive in 42 (22.3%), 12 (9%), 2 (28.6%), 3 (12.5%), and 3 (25%) patients, respectively. One patient had concurrent EGFR mutation along with ROS1 gene rearrangement. Conclusion Oncogenic driver mutations are present in Indian NSCLC patients. Molecular testing should be performed for all patients of advanced NSCLC to identify those that can benefit from newer generation of targeted or immunotherapies.

Single-molecule FRET unmasks structural subpopulations and crucial molecular events during FUS low-complexity domain phase separation.

Biomolecular condensates formed via phase separation of proteins and nucleic acids are thought to be associated with a wide range of cellular functions and dysfunctions. We dissect critical molecular events associated with phase separation of an intrinsically disordered prion-like low-complexity domain of Fused in Sarcoma by performing single-molecule studies permitting us to access the wealth of molecular information that is skewed in conventional ensemble experiments. Our single-molecule FRET experiments reveal the coexistence of two conformationally distinct subpopulations in the monomeric form. Single-droplet single-molecule FRET studies coupled with fluorescence correlation spectroscopy, picosecond time-resolved fluorescence anisotropy, and vibrational Raman spectroscopy indicate that structural unwinding switches intramolecular interactions into intermolecular contacts allowing the formation of a dynamic network within condensates. A disease-related mutation introduces enhanced structural plasticity engendering greater interchain interactions that can accelerate pathological aggregation. Our findings provide key mechanistic underpinnings of sequence-encoded dynamically-controlled structural unzipping resulting in biological phase separation.

Expectations of employers in the United States for entry-level public health job skills with a bachelor's degree: an analysis of the positions advertised in an online job portal.

Objectives: To analyze the current public health labor market for bachelor's-level graduates. Methods: Public health-related job postings (N = 365) from across the United States were collected from an online job portal, Indeed.com, from November 7-14, 2022. Job titles, organization type, degree requirements, work experience, job location, and preferred skills for bachelor's-level public health positions were analyzed. Results: Thirty-one job titles were identified. Approximately one-third (32.33%) of postings were from the Northeastern US; 23.56% were from the Southeastern region. Thirty-five job skill categories were identified. Most jobs (92.33%) required oral and written communication skills, and 85.21% specified educational skills for public health promotion. Cultural competency, project management, and case management abilities were also highly sought. Conclusion: This study revealed the needs of the public health workforce and bolstered the case that public health degree-seekers should be equipped with a set of strategic skills applicable to a range of multisectoral and multidisciplinary public health jobs. Policy implications: Given the rapid changes in the field of public health, ongoing analysis of the labor market benefits educators, employers, and policymakers alike.

Ru(II)/Ru(IV)-catalyzed C(sp2)-H allylation with alkene difunctionalization to access isochroman-1-imines.

Merging C(sp2)-H allylation and alkene difunctionalization events to access isochroman-1-imines, using N-aroyl aminoesters, MBH acetates, and NBS, under Ru(II)/Ru(IV) catalysis has been developed. Using 1H NMR, ESI-MS, HRMS, control reactions, deuterium labeling experiments, and DFT analysis, the allyl transfer (redox) process was proven to involve in C-H allylation rather than olefin insertion. Scale-up and synthetic transformations demonstrated the sustainability of this method.

Escherichia coli resistance, treatment patterns and clinical outcomes among females with uUTI in Germany: a retrospective physician-based chart review study.

Real-world data were collected to examine antimicrobial resistance (AMR) prevalence, treatment patterns, and clinical outcomes among female patients with uncomplicated urinary tract infection (uUTI) in Germany. Data were from a retrospective physician-based chart review completed by physicians treating patients with uUTI. Non-pregnant women aged ≥ 12 years, with a uUTI diagnosis, an E. coli-positive urine culture between January 2017-December 2019, and susceptibility test results for ≥ 4 drug classes were eligible. Patients were stratified into three cohorts by drug class susceptibility: susceptible to all (SUS), resistant to one or two drug classes (DR1/2), and resistant to ≥ 3 (MDR) drug classes tested. Among 386 eligible patients [SUS (67.1%); DR1/2 (29.0%); MDR (3.9%)], AMR prevalence was highest for FMIs (18.3%) and lowest for fluoroquinolones (5.2%). The most prescribed drugs were fosfomycin in SUS (44.0%), DR1/2 (41.4%), and fluoroquinolones in MDR (40.0%). Treatment for uUTI failed for 8.8% of patients; failure was more likely in MDR versus SUS [adjusted odds ratio [95% CI] = 4.21 [1.14-1.50]; P = 0.031); incidence of recurrent infection in the 6-months post-index period was higher in DR1/2 versus SUS. These findings may have implications for empiric prescribing, suggesting an unmet need for new treatments.

Hydrogen-Deuterium Exchange Vibrational Raman Spectroscopy Distinguishes Distinct Amyloid Polymorphs Comprising Altered Core Architecture.

Amyloid fibrils are ordered protein aggregates comprising a hydrogen-bonded central cross-ß core displaying a structural diversity in their supramolecular packing arrangements within the core. Such an altered packing results in amyloid polymorphism that gives rise to morphological and biological strain diversities. Here, we show that vibrational Raman spectroscopy coupled with hydrogen/deuterium (H/D) exchange discerns the key structural features that are responsible for yielding diverse amyloid polymorphs. Such a noninvasive and label-free methodology allows us to structurally distinguish distinct amyloid polymorphs displaying altered hydrogen bonding and supramolecular packing within the cross-ß structural motif. By using quantitative molecular fingerprinting and multivariate statistical analysis, we analyze key Raman bands for the protein backbone and side chains that allow us to capture the conformational heterogeneity and structural distributions within distinct amyloid polymorphs. Our results delineate the key molecular factors governing the structural diversity in amyloid polymorphs and can potentially simplify studying amyloid remodeling by small molecules.

Older patient age and prior antimicrobial use strongly predict antimicrobial resistance in Escherichia coli isolates recovered from urinary tract infections among female outpatients.

BACKGROUND: Increasing prevalence of antimicrobial resistance (AMR), including multidrug resistance (MDR), among Escherichia coli (E. coli) makes treatment of uncomplicated urinary tract infection (uUTI) difficult. We assessed risk factors for fluoroquinolone (FQ)-not-susceptible (NS) and MDR E. coli among US female outpatients. METHODS: This retrospective cohort study utilized data from female outpatients aged ≥ 12 years with E. coli positive urine culture and oral antimicrobial prescription ± 1 day from index. We assessed patient-level factors within 90 and 91-360 days prior to index as predictors of FQ NS (intermediate/resistant) and MDR (NS to ≥ 1 drug across ≥ 3 classes) E. coli: age, prior oral antimicrobial dispensing, prior AMR phenotypes, prior urine culture, and prior hospitalization. RESULTS: Among 1,858 outpatients with urine-isolated E. coli, 369 (19.9%) had FQ NS and 59 (3.2%) had MDR isolates. After multivariable adjustment, independent risk factors (p < 0.03) for FQ NS E. coli were older age, prior FQ NS isolates, prior dispensing of FQ, and dispensing of any oral antibiotic. Independent risk factors (p < 0.02) for MDR were prior extended-spectrum ß-lactamase-producing isolates (ESBL+), prior FQ dispensing, and prior oral antibiotic dispensing. CONCLUSIONS: In women with uUTI due to E. coli, prior dispensing of FQ or any oral antibiotic within 90 days predicted FQ NS and MDR urine E. coli. Prior urine culture with FQ NS isolates and older age were predictive of FQ NS E. coli. Prior ESBL+ was predictive of MDR E. coli. These data could help identify patients at risk for AMR E. coli and inform empiric prescribing.

Unmet needs in uncomplicated urinary tract infection in the United States and Germany: a physician survey.

BACKGROUND: Uncomplicated urinary tract infections (uUTIs/acute cystitis) are among the most common infections in women worldwide. There are differences in uUTI treatment guidelines between countries and understanding the needs of physicians in diverse healthcare systems is important for developing new treatments. We performed a survey of physicians in the United States (US) and Germany to understand their perceptions of, and management approaches to uUTI. METHODS: This was a cross-sectional online survey of physicians in the US and Germany who were actively treating patients with uUTI (≥ 10 patients/month). Physicians were recruited via a specialist panel and the survey was piloted with 2 physicians (1 US, 1 Germany) prior to study commencement. Data were analyzed with descriptive statistics. RESULTS: A total of 300 physicians were surveyed (n = 200 US, n = 100 Germany). Across countries and specialties, physicians estimated 16-43% of patients did not receive complete relief from initial therapy and 33-37% had recurrent infections. Urine culture and susceptibility testing was more common in the US and among urologists. The most commonly selected first-line therapy was trimethoprim-sulfamethoxazole in the US (76%) and fosfomycin in Germany (61%). Ciprofloxacin was the most selected following multiple treatment failures (51% US, 45% Germany). Overall, 35% of US and 45% of German physicians agreed with the statement "I feel there is a good selection of treatment options" and ≥ 50% felt that current treatments provided good symptom relief. More than 90% of physicians included symptom relief amongst their top 3 treatment goals. The overall impact of symptoms on patients' lives was rated "a great deal" by 51% of US and 38% of German physicians, increasing with each treatment failure. Most physicians (> 80%) agreed that antimicrobial resistance (AMR) is serious, but fewer (56% US, 46% Germany) had a high level of confidence in their knowledge of AMR. CONCLUSIONS: Treatment goals for uUTI were similar in the US and Germany, although with nuances to disease management approaches. Physicians recognized that treatment failures have a significant impact on patients' lives and that AMR is a serious problem, though many did not have confidence in their own knowledge of AMR.

Measuring the Burden of Infodemics: Summary of the Methods and Results of the Fifth WHO Infodemic Management Conference.

Background: An infodemic is excess information, including false or misleading information, that spreads in digital and physical environments during a public health emergency. The COVID-19 pandemic has been accompanied by an unprecedented global infodemic that has led to confusion about the benefits of medical and public health interventions, with substantial impact on risk-taking and health-seeking behaviors, eroding trust in health authorities and compromising the effectiveness of public health responses and policies. Standardized measures are needed to quantify the harmful impacts of the infodemic in a systematic and methodologically robust manner, as well as harmonizing highly divergent approaches currently explored for this purpose. This can serve as a foundation for a systematic, evidence-based approach to monitoring, identifying, and mitigating future infodemic harms in emergency preparedness and prevention. Objective: In this paper, we summarize the Fifth World Health Organization (WHO) Infodemic Management Conference structure, proceedings, outcomes, and proposed actions seeking to identify the interdisciplinary approaches and frameworks needed to enable the measurement of the burden of infodemics. Methods: An iterative human-centered design (HCD) approach and concept mapping were used to facilitate focused discussions and allow for the generation of actionable outcomes and recommendations. The discussions included 86 participants representing diverse scientific disciplines and health authorities from 28 countries across all WHO regions, along with observers from civil society and global public health-implementing partners. A thematic map capturing the concepts matching the key contributing factors to the public health burden of infodemics was used throughout the conference to frame and contextualize discussions. Five key areas for immediate action were identified. Results: The 5 key areas for the development of metrics to assess the burden of infodemics and associated interventions included (1) developing standardized definitions and ensuring the adoption thereof; (2) improving the map of concepts influencing the burden of infodemics; (3) conducting a review of evidence, tools, and data sources; (4) setting up a technical working group; and (5) addressing immediate priorities for postpandemic recovery and resilience building. The summary report consolidated group input toward a common vocabulary with standardized terms, concepts, study designs, measures, and tools to estimate the burden of infodemics and the effectiveness of infodemic management interventions. Conclusions: Standardizing measurement is the basis for documenting the burden of infodemics on health systems and population health during emergencies. Investment is needed into the development of practical, affordable, evidence-based, and systematic methods that are legally and ethically balanced for monitoring infodemics; generating diagnostics, infodemic insights, and recommendations; and developing interventions, action-oriented guidance, policies, support options, mechanisms, and tools for infodemic managers and emergency program managers.

The Design, Development, and Implementation of a Web-Enabled Informatics Platform to Enhance the Well-being of Individuals Aged 18-24 Years: Protocol for an Experimental Study.

BACKGROUND: Well-being is multidimensional, complex, and dynamic in nature. It is an amalgam of physical and mental health, essential for disease prevention and the promotion of a healthy life. OBJECTIVE: This study aims to explore the features that impact the well-being of individuals between 18 and 24 years of age in an Indian setting. It further aims to design, develop, and evaluate the usefulness and effectiveness of a web-based informatics platform or stand-alone intervention to enhance the well-being of individuals aged 18-24 years in an Indian setting. METHODS: This study follows a mixed method approach to identify factors influencing the well-being of individuals in the age group of 18-24 years in an Indian setting. The college-going students in this age group from the states of Uttarakhand (urban settings of Dehradun) and Uttar Pradesh (urban settings of Meerut) will be enrolled. They will be randomly allocated to the control and intervention groups. The participants in the intervention group will have access to the web-based well-being platform. RESULTS: This study will examine the factors that influence the well-being of individuals aged 18-24 years. It will also facilitate the design and development of the web-based platform or stand-alone intervention, which will enhance the well-being of individuals in the age group of 18-24 years in an Indian setting. Furthermore, the results of this study will help generate a well-being index for individuals to plan tailored interventions. The 60 in-depth interviews have been conducted as of September 30, 2022. CONCLUSIONS: The study will help understand the factors that influence the well-being of individuals. The findings of this study will help in the design and development of the web-based platform or stand-alone intervention to enhance the well-being of individuals in the age group of 18-24 years in an Indian setting. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/38632.

The bacterial nucleoid-associated proteins, HU and Dps, condense DNA into context-dependent biphasic or multiphasic complex coacervates.

The bacterial chromosome, known as its nucleoid, is an amorphous assemblage of globular nucleoprotein domains. It exists in a state of phase separation from the cell's cytoplasm, as an irregularly-shaped, membrane-less, intracellular compartment. This state (the nature of which remains largely unknown) is maintained through bacterial generations ad infinitum. Here, we show that HU and Dps, two of the most abundant nucleoid-associated proteins (NAPs) of Escherichia coli, undergo spontaneous complex coacervation with different forms of DNA/RNA, both individually and in each other's presence, to cause accretion and compaction of DNA/RNA into liquid-liquid phase separated condensates in vitro. Upon mixing with nucleic acids, HU-A and HU-B form (a) biphasic heterotypic mixed condensates in which HU-B helps to lower the Csat of HU-A and also (b) multiphasic heterotypic condensates, with Dps, in which demixed domains display different contents of HU and Dps. We believe that these modes of complex coacervation that are seen in vitro can serve as models for the in vivo relationships among NAPs in nucleoids, involving local and global variations in the relative abundances of the different NAPs, especially in demixed subdomains that are characterized by differing grades of phase separation. Our results clearly demonstrate some quantitative, and some qualitative, differences in the coacervating abilities of different NAPs with DNA, potentially explaining (i) why E. coli has two isoforms of HU, and (ii) why changes in the abundances of HU and Dps facilitate the lag, logarithmic, and stationary phases of E. coli growth.