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Activity impairment, health-related quality of life, productivity, and self-reported resource use and associated costs of uncomplicated urinary tract infection among women in the United States
Uncomplicated urinary tract infections (uUTIs) are among the most common infections in the US. Only a few studies, however, describe the impact of uUTIs from the patient perspective.
A cross-sectional online survey of US women aged ≥18 years was performed assessing uUTI burden regarding activity impairment, health-related quality of life (HRQoL), workplace productivity, healthcare resource use (HRU), and costs. Participants who self-reported a uUTI in the prior 60 days treated with ≥1 oral antibiotic were included. Activity impairment was assessed with the Activity Impairment Assessment scale. HRQoL was assessed using a modified Short Form 36 (SF-36). Direct costs were sum of out-of-pocket expenditures and monetized HRU; indirect costs were calculated using Work Productivity and Activity Impairment (WPAI). Participants were stratified by uUTI recurrence, number of prescribed antibiotics for recent uUTI and therapy appropriateness (1 first-line/1 second-line/multiple antibiotics). Multivariable regression analysis assessed the relationship between stratifications and outcomes while controlling for demographic/clinical characteristics. Propensity score matching was used to compare participants to a matched population from the 2020 National Health and Wellness Survey (NHWS), to control for any impact of COVID-19 on responses.
Among 375 participants, impaired activities included sexual intercourse (66.9%), sleep (60.8%) and exercise (52.3%). HRQoL was worse (p<0.0001) than the NHWS population (46.4 vs. 51.3 [physical component score]; 40.0 vs. 46.9 [mental component score]; 0.63 vs. 0.72 [health utility index]). All included WPAI assessments were worse for uUTI cohort vs. NHWS (p<0.0001). Adjusted direct costs were higher for participants receiving 2 vs. 1 antibiotic ($2090 vs. $776; p<0.0001) and receiving multiple antibiotics vs. 1 first-line ($1642 vs. $875; p = 0.002). Recurrent uUTI was associated with increased activity impairment, worse HRQoL, and costs vs. non-recurrent.
uUTIs were associated with increased activity impairment, worse productivity, and reduced HRQoL. Higher costs were found vs. a matched population.
Journal Article
Treatment patterns, healthcare resource use, and costs associated with uncomplicated urinary tract infection among female patients in the United States
We evaluated associations between antibiotic prescription and healthcare resource use and costs (Part A), and between antibiotic switching and healthcare resource use, costs, and uncomplicated urinary tract infection recurrence (Part B) in female patients with uncomplicated urinary tract infection in the United States.
This retrospective cohort study of linked Optum and Premier Healthcare Database data included female patients ≥12 years old with an uncomplicated urinary tract infection diagnosis (index date), who were prescribed antibiotics during an outpatient/emergency department visit between January 1, 2013 and December 31, 2018. In Part A, patients were stratified by antibiotic prescription appropriateness: appropriate and optimal (compliant with Infectious Diseases Society of America 2011 guidelines for drug class/treatment duration) versus inappropriate/suboptimal (inappropriate drug class/treatment duration per Infectious Diseases Society of America 2011 guidelines, and/or treatment failure). In Part B, patients were stratified by treatment pattern (antibiotic switch vs no antibiotic switch). Healthcare resource use and costs during index episode (within 28 days of index date) and 12-month follow-up were compared.
Of 5870 patients (mean age 44.5 years), 2762 (47.1%) had inappropriate/suboptimal prescriptions and 567 (9.7%) switched antibiotic. Inappropriate/suboptimal prescriptions were associated with higher healthcare resource use (mean number of ambulatory care and pharmacy claims [both p < 0.001]), and higher total mean cost (inpatient, outpatient/emergency department, ambulatory visits, and pharmacy costs) per patient ($2616) than appropriate and optimal prescriptions ($649; p < 0.001) (Part A). Antibiotic switching was associated with more pharmacy claims and higher total mean costs (p ≤ 0.01), and a higher incidence of recurrent uncomplicated urinary tract infection (18.9%) than no antibiotic switching (14.2%; p < 0.001) (Part B).
Inappropriate/suboptimal prescriptions and antibiotic switching were associated with high costs, ambulatory care, and pharmacy claims, suggesting a need for improved uncomplicated urinary tract infection prescribing practices in the United States.
Journal Article
Allergies to antibiotics among US women with uncomplicated urinary tract infection
Uncomplicated urinary tract infections (uUTI) are generally treated empirically with antibiotics. However, antibiotic allergies limit the available oral treatment options for some patients. We assessed the proportion of self-reported antibiotic allergies among US women with uUTI. We performed a cross-sectional survey of US women (≥18 years) with a self-reported uUTI in the previous 60 days and an oral antibiotic prescription. Participants completed an online questionnaire about their most recent uUTI episode. Descriptive self-reported allergy data were stratified into subgroups by whether the participant had recurrent UTI (≥2 uUTIs in the past 6 months or ≥3 uUTIs in past 12 months, including the index episode), the number of different antibiotics given for the index episode (1, 2, ≥3), and whether the treatment was clinically aligned according to Infectious Diseases Society of America uUTI guidelines. Overall, 375 participants completed the questionnaire. The most commonly prescribed antibiotics were trimethoprim-sulfamethoxazole (SXT; 38.7%), ciprofloxacin (22.7%), and nitrofurantoin (18.9%). Most participants (62.7%) received only 1 antibiotic for their uUTI, and most (56.5%) were classified as having a non-recurrent uUTI. No antibiotic allergies were reported for most participants (69.3%), with 24.0% reporting 1 antibiotic allergy and 6.7% reporting ≥2 antibiotic allergies. Allergies to ≥2 antibiotic types were more common among participants classified as having recurrent uUTI, or who used multiple antibiotics to treat their uUTI. The most common allergy was to SXT (15.7%), followed by amoxicillin-clavulanate (8.3%) and ciprofloxacin (5.3%). Similar allergy trends were seen across subgroups, except higher rates of ciprofloxacin allergy were seen in participants given multiple antibiotics. Antibiotic allergies were relatively frequent in this uUTI cohort and the most common allergy was to SXT, which was the most prescribed antibiotic. Allergies to antibiotics reduce the available treatment options for uUTI in some patients.
Journal Article
Activity impairment, work productivity, health-related quality-of-life, and costs associated with uncomplicated urinary tract infection among females in Germany
Uncomplicated urinary tract infections (uUTIs) represent a sizable healthcare burden with a substantial negative impact on patients’ health-related quality-of-life (HRQoL). However, the HRQoL impact of uUTI from the patient perspective is under-represented in research. A cross-sectional online survey assessed activity impairment and work productivity, HRQoL, costs, and treatment satisfaction of female patients with uUTIs in the US; the current study applies this earlier methodology to Germany to provide a European perspective. We examined: activity impairment and work productivity using Activity Impairment Assessment (AIA), and Work Productivity and Activity Impairment (WPAI) questionnaires, respectively; HRQoL using a modified Short Form-36, and participants completed the treatment satisfaction questionnaire for medication. Participants (≥ 12 years) self-reported a uUTI treated with oral antibiotics in the last 60 days, had no evidence of complicated UTI, and were recruited via a consumer panel. In the patient (N = 200) survey, bladder pain (70%), dysuria (69%), and frequent urination (66%) were the most common uUTI symptoms reported. Activities frequently affected by uUTI were sexual activity (56%) and exercise (48%), resulting in an overall AIA score of 8.2 indicating that activities among patients were impaired ‘most of the time’ during their recent uUTI. Absenteeism was 29% (of a 40-hour work week); presenteeism, 34%; and overall work impairment, 41%. Indirect costs due to impact of uUTI were €7.62/hour/participant, representing a loss for the employer. The lowest HRQoL scores were for mental (44%) and physical components (43%); emotional and physical functioning scores were 71% and 70%, respectively. Mean direct costs of €20.10 for medical treatments and €11.30 for other treatment costs were reported. Overall, most participants were satisfied with the uUTI treatment (76% satisfaction score). Results demonstrate the patient-reported burden of uUTI for patients and employers, with activities and ability to work impacted, resulting in a notable indirect burden in Europe.
Journal Article
Single-droplet surface-enhanced Raman scattering decodes the molecular determinants of liquid-liquid phase separation
Biomolecular condensates formed via liquid-liquid phase separation (LLPS) are involved in a myriad of critical cellular functions and debilitating neurodegenerative diseases. Elucidating the role of intrinsic disorder and conformational heterogeneity of intrinsically disordered proteins/regions (IDPs/IDRs) in these phase-separated membrane-less organelles is crucial to understanding the mechanism of formation and regulation of biomolecular condensates. Here we introduce a unique single-droplet surface-enhanced Raman scattering (SERS) methodology that utilizes surface-engineered, plasmonic, metal nanoparticles to unveil the inner workings of mesoscopic liquid droplets of Fused in Sarcoma (FUS) in the absence and presence of RNA. These highly sensitive measurements offer unprecedented sensitivity to capture the crucial interactions, conformational heterogeneity, and structural distributions within the condensed phase in a droplet-by-droplet manner. Such an ultra-sensitive single-droplet vibrational methodology can serve as a potent tool to decipher the key molecular drivers of biological phase transitions of a wide range of biomolecular condensates involved in physiology and disease.
The authors introduce a unique single-droplet surface-enhanced Raman scattering (SERS) methodology that illuminates a wealth of molecular information within the mesoscopic liquid condensed phase of Fused in Sarcoma in the absence and presence of RNA.
Journal Article
Sjögren’s syndrome and hepatitis C virus infection presenting as hypokalemic quadriparesis: A case report
Distal renal tubular acidosis can present with acute-onset quadriparesis caused by severe hypokalemia, and primary Sjögren’s syndrome is a significant potential cause of distal renal tubular acidosis in such patients. The extrahepatic manifestations of chronic hepatitis C virus infection can mimic those of primary Sjögren’s syndrome, creating a diagnostic dilemma. Here, we present the case of a woman in her mid-20s who presented with sudden-onset quadriparesis. Laboratory investigations showed severe hypokalemia, normal anion gap metabolic acidosis, and positivity for antinuclear and anti-Ro/Sjögren’s syndrome–related antigen A antibodies. Further evaluation confirmed a positive hepatitis C virus antibody test but a negative viral load. A diagnosis of primary Sjögren’s syndrome with distal renal tubular acidosis was established, accounting for the hypokalemia. Potassium supplementation and correction of acid–base disturbances led to significant patient improvement. This case highlights the importance of including autoimmune conditions such as primary Sjögren’s syndrome in the differential diagnosis of patients presenting with hypokalemic quadriparesis and distal renal tubular acidosis, even in the absence of glandular symptoms. Early diagnosis and management are essential to improve outcomes.
Journal Article
Periprosthetic Joint Infection: The Incidence, Timing, and Predisposing Factors
Periprosthetic joint infection is one of the most challenging complications of joint arthroplasty. We identified current risk factors of periprosthetic joint infection after modern joint arthroplasty, and determined the incidence and timing of periprosthetic joint infection. We reviewed prospectively collected data from our database on 9245 patients undergoing primary hip or knee arthroplasty between January 2001 and April 2006. Periprosthetic joint infections developed in 63 patients (0.7%). Sixty-five percent of periprosthetic joint infections developed within the first year of the index arthroplasty. The infecting organism was isolated in 57 of 63 cases (91%). The most common organisms identified were Staphylococcus aureus and Staphylococcus epidermidis. We identified the following independent predictors for periprosthetic joint infection: higher American Society of Anesthesiologists score, morbid obesity, bilateral arthroplasty, knee arthroplasty, allogenic transfusion, postoperative atrial fibrillation, myocardial infarction, urinary tract infection, and longer hospitalization. This study confirmed some previously implicated factors and identified new variables that predispose patients to periprosthetic joint infection.
Level of Evidence:
Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
Journal Article
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.
Using single-molecule FRET, the authors discover hidden structural subpopulations of the intrinsically disordered prion-like low-complexity domain of FUS and dissect key molecular events that drive dynamic network formation during phase separation.
Journal Article
Older patient age and prior antimicrobial use strongly predict antimicrobial resistance in Escherichia coli isolates recovered from urinary tract infections among female outpatients
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.
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.
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 β-lactamase-producing isolates (ESBL+), prior FQ dispensing, and prior oral antibiotic dispensing.
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.
Journal Article