The fate of coronary dissections left after sirolimus-coated balloon angioplasty: A prespecified subanalysis of the EASTBOURNE study.

OBJECTIVES: We sought to understand the clinical outcomes of dissections left untreated after sirolimus drug-coated balloon (DCB) angioplasty. BACKGROUND: DCB may be a valuable alternative to stents for the treatment of native coronary lesions, but the risk of having a dissection after DCB-angioplasty is not negligible. While type A and B dissections can be safely treated conservatively, some debate exists regarding type C dissections. We previously showed the safety of dissections left untreated after second-generation paclitaxel-DCB. However, the fate of dissections after sirolimus-DCB angioplasty has not been investigated so far. METHODS: EASTBOURNE is a prospective, multicenter, international, investigator-driven study aiming to explore the safety and efficacy of a novel sirolimus-DCB. This study enrolled a consecutive, all-comer population of coronary artery disease patients and is the largest prospective study on DCB so far. Primary endpoints of the study, target-lesion revascularization (TLR), and other clinical endpoints at 12 months, have been presented elsewhere. This is a prespecified subgroup analysis of the patients left with not-flow limiting dissection after DCB angioplasty, with complete 12 months follow-up and comparison between patients left with a dissection versus patients with DCB used for de novo lesions. RESULTS: Between September 2016 and November 2020, a total of 2123 patients were enrolled at 38 study centers. Seventy-three patients were left with nonflow limiting dissections (43 type A, 27 type B, 3 type C) and underwent complete 1-year clinical follow-up. In the nondissection group, 1110 patients had de-novo coronary artery disease while 900 had in-stent restenosis. Baseline characteristics were similar between the groups, while the dissection group was associated with longer lesions (23.8 vs. 18.4 mm, p < 0.001) and more frequent use of predilation (100 vs. 91.4%, p = 0.016). At 12-month follow-up, no significant differences among the groups were found, with a total of 1.25% TLR in the dissection cohort versus 5.6% in the de-novo cohort (p = 0.13), and an overall rate of major adverse cardiovascular events of 4.4% versus 10.1% (p = 0.18). Total death (1.5 vs. 2.6, p = 0.87), cardiac death, myocardial infarction (0% vs. 2.5%, p = 0.35), and bleedings did not differ significantly among the groups as well. CONCLUSIONS: In this subgroup analysis of the EASTBOURNE study of consecutive patients treated with new-generation sirolimus DCB, dissections left untreated after angioplasty did not lead to an increase in adverse events.

Clinical burden of invasive Escherichia coli disease among older adult patients treated in hospitals in the United States.

BACKGROUND: Invasive extraintestinal pathogenic Escherichia coli disease (IED) can lead to severe outcomes, particularly among older adults. However, the clinical burden of IED in the U.S. has not been well characterized. METHODS: IED encounters among patients ≥ 60 years old were identified using the PINC AI™ Healthcare Database (10/01/2015-03/31/2020) by either a positive E. coli culture in blood or another normally sterile body site and ≥ 1 sign of systemic inflammatory response syndrome or signs of sepsis, or a positive E. coli culture in urine with urinary tract infection and signs of sepsis. Medical resource utilization, clinical outcomes, and E. coli isolate characteristics were descriptively reported during the first IED encounter and during the following year (observation period). RESULTS: Overall, 19,773 patients with IED were included (mean age: 76.8 years; 67.4% female; 78.5% with signs of sepsis). Most encounters involved community-onset IED (94.3%) and required hospitalization (96.5%; mean duration: 6.9 days), with 32.4% of patients being admitted to the intensive care unit (mean duration: 3.7 days). Most E. coli isolates were resistant to ≥ 1 antibiotic category (61.7%) and 34.4% were resistant to ≥ 3 antibiotic categories. Following their first IED encounter, 34.8% of patients were transferred to a skilled nursing/intermediate care facility, whereas 6.8% had died. During the observation period, 36.8% of patients were rehospitalized, 2.4% had IED recurrence, and in-hospital death increased to 10.9%. CONCLUSIONS: IED is associated with substantial clinical burden at first encounter with considerable long-term consequences. Findings demonstrate the need for increased IED awareness and highlight potential benefits of prevention.

Healthcare Resource Utilization and Costs Among Patients With Schizophrenia Switching From Oral Risperidone/Paliperidone to Once-Monthly Paliperidone Palmitate: A Veterans Health Administration Claims Analysis.

BACKGROUND: Schizophrenia is associated with high health care resource utilization and treatment costs. OBJECTIVE: This study compared treatment patterns, health care resource utilization, and medical costs before and after a switch from oral antipsychotic drug (risperidone or paliperidone [RIS/PALI]) therapy to the long-acting injectable once-monthly paliperidone palmitate (PP1M) in patients with schizophrenia. METHODS: Data for adult patients (aged ≥18 years) with at least 1 diagnosis of schizophrenia who initiated treatment with oral RIS/PALI ≥6 months before switching and had continuous health plan enrollment during the study period before and after the switch were extracted from the Veterans Health Administration database. Treatment patterns, health care resource utilization, and costs were compared between the period 6 or 12 months before and after switching directly from oral RIS/PALI to PP1M. RESULTS: The analysis included 676 and 493 patients in the 6-month and 12-month cohorts, respectively. Adherence to oral RIS/PALI during the 12 months preswitch was 11.0% and 22.1% as measured by proportion of days covered and medication possession ratio ≥80%, respectively. During the 12 months postswitch, adherence to PP1M was 27.0% and 35.9%, respectively. Among patients treated with oral RIS/PALI, from 12 months pre- to 12 months post-PP1M switch, fewer all-cause inpatient stays (2.2 vs 1.1, respectively; P < 0.05) and a shorter mean length of inpatient stay (28.1 and 14.0 days, respectively; P < 0.05) were observed. This pattern was similar for both the number of mental health- and schizophrenia-related inpatient stays and length of stay. Compared with 12 months pre-PP1M switch, significantly higher mean numbers of all-cause outpatient visits and pharmacy visits were observed at 12 months postswitch. In line with health care resource utilization findings, at 12 months pre- versus 12 months post-PP1M switch we observed decreases in all-cause inpatient stay costs ($41,886 vs $20,489; P < 0.05) and increases in outpatient visit costs ($22,005 vs $29,069; P < 0.05). Findings for the 6-month cohort followed a similar pattern. CONCLUSIONS: Post-PP1M switch, a decrease in total medical costs fully offset an increase in pharmacy costs, resulting in similar total costs. The findings suggest potential economic benefits of switching patients with schizophrenia from oral RIS/PALI to PP1M in the Veterans Health Administration.

The Predicted Long-Term Benefits of Ensuring Timely Treatment and Medication Adherence in Early Schizophrenia.

The impact of initiatives aimed at reducing time in untreated psychosis during early-stage schizophrenia will be unknown for many years. Thus, we simulate the effect of earlier treatment entry and better antipsychotic drug adherence on schizophrenia-related hospitalizations, receipt of disability benefits, competitive employment, and independent/family living over a ten-year horizon. We predict that earlier treatment entry reduces hospitalizations by 12.6-14.4% and benefit receipt by 7.0-8.5%, while increasing independent/family living by 41.5-46% and employment by 42-58%. We predict larger gains if a pro-adherence intervention is also used. Our findings suggest substantial benefits of timely and consistent early schizophrenia care.

Current perspectives on biosimilars.

In this work, an overview of the biosimilars market, pipeline and industry targets is discussed. Biosimilars typically have a shorter timeline for approval (8 years) compared to 12 years for innovator drugs and the development cost can be 10-20% of the innovator drug. The biosimilar pipeline is reviewed as well as the quality management system (QMS) that is needed to generate traceable, trackable data sets. One difference between developing a biosimilar compared to an originator is that a broader analytical foundation is required for biosimilars and advances made in developing analytical similarity to characterize these products are discussed. An example is presented on the decisions and considerations explored in the development of a biosimilar and includes identification of the best process parameters and methods based on cost, time, and titer. Finally factors to consider in the manufacture of a biosimilar and approaches used to achieve the target-directed development of a biosimilar are discussed.

A Reanalysis of the RIVUR Trial Using a Risk Classification System.

PURPOSE: The RIVUR (Randomized Intervention for Children with Vesicoureteral Reflux) trial showed a 50% decrease in the risk of urinary tract infection recurrence in children with reflux receiving continuous antibiotic prophylaxis. We reanalyzed the RIVUR data with the purpose of using a risk classification system to identify children who are more likely to benefit from continuous antibiotic prophylaxis. MATERIALS AND METHODS: Data from 607 children enrolled in the RIVUR trial were obtained from the National Institute of Diabetes and Digestive and Kidney Diseases Central Repository and analyzed. We stratified these children into low and high risk categories. The proportion of children and risk of urinary tract infection recurrence in the stratified treatment groups were compared. RESULTS: Of the children 385 (63.9%) were stratified into the low risk and 217 (36.1%) into the high risk category. The proportions of children with urinary tract infection recurrence were not significantly different in the low risk category between the placebo and continuous antibiotic prophylaxis groups (p = 0.151), while urinary tract infection recurrence was significantly higher in the placebo group (31.5% vs 11.4%, p = 0.001) for high risk children. Furthermore, high risk children on placebo had a 3.7-fold increased risk of urinary tract infection recurrence during 2 years of followup compared to those on continuous antibiotic prophylaxis. CONCLUSIONS: Although the RIVUR trial concluded that children with vesicoureteral reflux benefit from continuous antibiotic prophylaxis, our reanalysis of the data demonstrates that high risk children benefit more, with a number needed to treat of 5 compared to 18 in low risk children. The clinical implications of these findings suggest a need to refine current indications for continuous antibiotic prophylaxis in children with reflux, supporting a shift toward a "selective" risk based approach for management.

Home Urodynamic Pressures and Volume Measurement for the Neurogenic Bladder: Initial Validation Study.

PURPOSE: We evaluated the ability of a bladder pressure/volume diary to identify patients at risk for increased intravesical pressures. MATERIALS AND METHODS: Patients dependent on clean intermittent catheterization used ruler based manometry to measure intravesical pressures before leakage or scheduled drainage at home. We prospectively collected clinical, urodynamic and bladder pressure/volume diary data in patients with spina bifida who were optimized on anticholinergic therapy and clean intermittent catheterization. Measurements were taken with patients in the supine position with relaxed abdominal muscles. We defined increased pressure as detrusor pressure greater than 30 cm water as measured by urodynamics. ROCs were plotted to correlate bladder pressure/volume diary variables with abnormal intravesical pressures, and the most sensitive variable in determining abnormal intravesical pressures was sought as the end point. RESULTS: A total of 30 patients with a mean age of 10 years (range 1 to 20) were included. Home pressures measured at maximal clean intermittent catheterization volume and mean bladder pressure/volume diary pressures were most reliable in predicting urodynamic pressures greater than 30 cm water (AUC 0.93 and 0.87, respectively). Home pressures measured at maximal clean intermittent catheterization volumes less than 20 cm water were associated with normal bladder pressures (less than 30 cm water) on urodynamics, with a sensitivity of 100% and a specificity of 80%. CONCLUSIONS: Home manometry less than 20 cm water provides a reliable measurement of safe pressures. A bladder pressure/volume diary is feasible and can aid in monitoring pressures at home without the additional cost and morbidity of urodynamics. A bladder pressure/volume diary may be a useful tool to help identify patients who would benefit from urodynamic testing.

Prospective evaluation of Peristeen® transanal irrigation system with the validated neurogenic bowel dysfunction score sheet in the pediatric population.

AIMS: To determine the ability of Peristeen® transanal irrigation system to reduce symptoms of neurogenic bowel dysfunction (NBD) in patients using the validated neurogenic bowel dysfunction scoring system for the pediatric population. METHODS: Patients 3-21 years with NBD whose current bowel program was unsuccessful were given the Neurogenic Bowel Dysfunction (NBoDS) score sheet before initiating Peristeen®, and at 2 weeks, 2 months, and 6 months after. All patients were started on Peristeen® with tap water (20 ml/kg) per daily irrigation. Mean and paired t-tests were completed. RESULTS: 24 patients were enrolled and had follow-up. Mean age was 10.5 years (range 3-21 years), 25%, 50%, 25% had thoracic, lumbar and sacral level lesions respectively. Mean NBoDS score at initiation of Peristeen® was 20.21 (±5.56), n = 24. The mean score after two weeks of use was 12.75 (±4.40), n = 24. There was a statistically significant decrease of 7.46 (95%CI, 5.07-9.84) points, t(23) = 6.47, P < 0.0005 after two weeks. There was a statistically significant decrease in their scores from initiation to the 2 month time period of 7.00 (95%CI, 2.18-11.82) points, t(9) = 3.29, P = 0.009. By the sixth month of daily use the mean NBoDS score was 9.67 (n = 12). This was an average decrease of 8.83 (95%CI, 5.39-12.28) points from initiation score, t(11) = 5.641, P < 0.005. CONCLUSION: The Peristeen® transanal irrigation system provides a significant reduction in NBoDS scores in pediatric patients with NBD. Peristeen® should be considered when other conservative bowel management options have been unsuccessful. Neurourol. Urodynam. 36:632-635, 2017. © 2016 Wiley Periodicals, Inc.

Health outcomes of bedaquiline in the treatment of multidrug-resistant tuberculosis in selected high burden countries.

BACKGROUND: Less than one-third of patients who are estimated to be infected with multidrug-resistant tuberculosis (MDR-TB) receive MDR-TB treatment regimens, and only 48% of those who received treatment have successful outcomes. Despite current regimens, newer, more effective and cost-effective approaches to treatment are needed. The aim of the study was to project health outcomes and impact on healthcare resources of adding bedaquiline to the treatment regimen of MDR-TB in selected high burden countries: Estonia, Russia, South Africa, Peru, China, the Philippines, and India. METHODS: This study adapted an existing Markov model to estimate the health outcomes and impact on total healthcare costs of adding bedaquiline to current MDR-TB treatment regimens. A price threshold analysis was conducted to determine the price range at which bedaquiline would be cost-effective. RESULTS: Adding bedaquiline to the background regimen (BR) resulted in increased disability-adjusted life years (DALYs) averted, and reduced total healthcare costs (excluding treatment acquisition costs) compared with BR alone in all countries analyzed. Addition of bedaquiline to BR resulted in savings to healthcare costs compared with BR alone in all countries analyzed, with the highest impact expected in Russia (US$194 million) and South Africa (US$43 million). The price per regimen at which bedaquiline would be cost-effective ranged between US$23,904-US$203,492 in Estonia, Russia, Peru, South Africa, and China (high and upper middle-income countries) and between US$6,996-US$20,323 in the Philippines and India (lower middle-income countries); however, these cost-effective prices do not necessarily address concerns about affordability. CONCLUSIONS: Adding bedaquiline to BR provides improvements in health outcomes and reductions in healthcare costs in high MDR-TB burden countries. The range of prices per regimen for which bedaquiline would be cost-effective varied between countries.

Environmental enrichment rescues the effects of early life inflammation on markers of synaptic transmission and plasticity.

Environmental enrichment (EE) has been successful at rescuing the brain from a variety of early-life psychogenic stressors. However, its ability to reverse the behavioral and neural alterations induced by a prenatal maternal infection model of schizophrenia is less clear. Moreover, the specific interactions between the components (i.e. social enhancement, novelty, physical activity) of EE that lead to its success as a supportive intervention have not been adequately identified. In the current study, standard housed female Sprague-Dawley rats were administered either the inflammatory endotoxin lipopolysaccharide (LPS; 100µg/kg) or pyrogen-free saline (equivolume) on gestational day 15. On postnatal day 50, offspring were randomized into one of three conditions: EE (group housed in a large multi-level cage with novel toys, tubes and ramps), Colony Nesting (CN; socially-housed in a larger style cage), or Standard Care (SC; pair-housed in standard cages). Six weeks later we scored social engagement and performance in the object-in-place task. Afterwards hippocampus and prefrontal cortex (n=7-9) were collected and evaluated for excitatory amino acid transporter (EAAT) 1-3, brain-derived neurotrophic factor (BDNF), and neurotrophic tyrosine kinase, receptor type 2 (TrkB) gene expression (normalized to GAPDH) using qPCR methods. Overall, we show that gestational inflammation downregulates genes critical to synaptic transmission and plasticity, which may underlie the pathogenesis of neurodevelopmental disorders such as schizophrenia and autism. Additionally, we observed disruptions in both social engagement and spatial discrimination. Importantly, behavioral and neurophysiological effects were rescued in an experience dependent manner. Given the evidence that schizophrenia and autism may be associated with infection during pregnancy, these data have compelling implications for the prevention and reversibility of the consequences that follow immune activation in early in life.

Development, reliability and validation of a neurogenic bowel dysfunction score in pediatric patients with spina bifida.

OBJECTIVE: To develop a reliable and valid questionnaire to monitor neurogenic bowel symptoms in children. PATIENTS: Thirty-four children aged 6-18 with neurogenic bowel and their caregivers. Eighteen control patients. METHODS: An expert panel generated a domain of observables and formative/reflective content. Response options were scaled following Likert-type items. Key informant interviews revised the measures. A final questionnaire was given to patients twice to calculate intra-rater reliability using Cohen's Kappa Coefficient (k) and paired t-test. Blinded interviews were conducted after physical examination and health assessment and questionnaires completed by a nurse to determine construct validity and inter-rater reliability using k and Spearman's rank-order correlation. Control patients completed the questionnaire once, their results were used to determine discriminate validity and a receiver operating characteristic (ROC) curve. RESULTS: Intra-rater reliability showed 85% of the questionnaires having k >0.6. Paired t-test results of t(33) = 1.997, P = 0.054, d = 0.53, confirmed there was not a significant difference between the scores of the two completed questionnaires. Inter-rater reliability showed 97% of the questionnaires having k >0.6 between the nurse and the patient/caregiver responses. Scores had a strong positive correlation at rs (32) = 0.943, P < 0.0005. Mean score with neurogenic bowel was 15.18(STD ± 5.77) and control group 4.68(STD ± 2.98). ROC analysis showed an area under the curve of 0.9. A score of 8.5 correlated with presence of neurogenic bowel with sensitivity of 94% and specificity of 87%. CONCLUSION: The questionnaire shows positive reliability and validity when used for pediatric neurogenic bowel patients. The questionnaire differentiates between normal and neurogenic patients. Larger studies are necessary to conduct further validation.

Predicting the Risk of Breakthrough Urinary Tract Infections: Primary Vesicoureteral Reflux.

PURPOSE: We constructed a risk prediction instrument stratifying patients with primary vesicoureteral reflux into groups according to their 2-year probability of breakthrough urinary tract infection. MATERIALS AND METHODS: Demographic and clinical information was retrospectively collected in children diagnosed with primary vesicoureteral reflux and followed for 2 years. Bivariate and binary logistic regression analyses were performed to identify factors associated with breakthrough urinary tract infection. The final regression model was used to compute an estimation of the 2-year probability of breakthrough urinary tract infection for each subject. Accuracy of the binary classifier for breakthrough urinary tract infection was evaluated using receiver operator curve analysis. Three distinct risk groups were identified. The model was then validated in a prospective cohort. RESULTS: A total of 252 bivariate analyses showed that high grade (IV or V) vesicoureteral reflux (OR 9.4, 95% CI 3.8-23.5, p <0.001), presentation after urinary tract infection (OR 5.3, 95% CI 1.1-24.7, p = 0.034) and female gender (OR 2.6, 95% CI 0.097-7.11, p <0.054) were important risk factors for breakthrough urinary tract infection. Subgroup analysis revealed bladder and bowel dysfunction was a significant risk factor more pronounced in low grade (I to III) vesicoureteral reflux (OR 2.8, p = 0.018). The estimation model was applied for prospective validation, which demonstrated predicted vs actual 2-year breakthrough urinary tract infection rates of 19% vs 21%. Stratifying the patients into 3 risk groups based on parameters in the risk model showed 2-year risk for breakthrough urinary tract infection was 8.6%, 26.0% and 62.5% in the low, intermediate and high risk groups, respectively. CONCLUSIONS: This proposed risk stratification and probability model allows prediction of 2-year risk of patient breakthrough urinary tract infection to better inform parents of possible outcomes and treatment strategies.

Renal medullary carcinoma in a white adolescent with sickle cell trait.

Renal medullary carcinoma (RMC) is a rare neoplasm of the kidney that has been recently described. It is almost exclusive to young patients of African descent and associated with sickle cell hemoglobinopathy, mainly sickle cell trait and hemoglobin sickle cell disease. The prognosis of RMC is very poor because of the highly aggressive behavior of this neoplasm and its resistance to conventional chemotherapy. Metastatic disease is almost universal at the time of presentation, and the malignancy is minimally responsive to a variety of regimens and/or modalities, including surgery, radiotherapy, chemotherapy, and biological immune-modulation therapy. We report the seventh case of a left RMC occurring in a white child with sickle cell trait, but with a localization of the tumor in the left kidney, considered a nonpredominant side for this type of tumor.

Health-related quality of life in patients with hepatitis C virus infection in Brazil.

OBJECTIVE: To quantify the health-related quality of life (HRQoL) burden of hepatitis C virus (HCV) infection among a broad sample of adults in Brazil, particularly among those 40 years of age and older. METHODS: This was a retrospective observational study of data from the 2011 Brazil National Health and Wellness Survey, a large (n = 12 000) cross-sectional survey that includes information on medical conditions and health outcomes, including the Medical Outcomes Study Short-form 12 health questionnaire, version 2 (SF-12v2). Respondents who reported a physician diagnosis of HCV infection were compared with those who reported never experiencing HCV on the Mental (MCS) and Physical (PCS) Component Summary scores and SF-6D health utility scores. Unadjusted comparisons were conducted with chi-square tests for categorical variables and t-tests for continuous variables. Regression was used to adjust outcomes for potential confounds. Subgroup analyses were conducted on those 40 years of age and older. RESULTS: Unadjusted comparisons between respondents infected with HCV (n = 100) and controls (n = 11 694) revealed similar MCS and PCS scores, but HCV patients had lower SF-6D utility scores (0.70 vs. 0.73, P < 0.05). Regressions adjusting for demographic and health characteristics provided similar results to unadjusted comparisons. Subgroup analyses of respondents 40 years of age and older revealed decrements in both MCS (45.95 vs. 49.72, P < 0.05) and SF-6D (0.71 vs. 0.76, P < 0.05). PCS scores were comparable in HCV patients and controls. CONCLUSIONS: HCV infection in Brazil causes significant HRQoL burden, especially among the older population. Prevention measures to curtail the spread of the virus in Brazil should provide societal benefits in terms of quality of life, in addition to preventing morbidity and mortality from chronic infection.

Performance of sodium-glucose cotransporter 2 inhibitors in cardiovascular disease.

AIMS: The use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as a new class of drug in treating type 2 diabetes has expanded beyond its original framework. Positive results have been achieved in reducing symptoms in patients with cardiovascular disease (CVD). The aim of this article is to present an in-depth review of the basic principles of this class of medications and how it has brought benefits to patients affected particularly by heart failure. METHODS: Following a thorough PubMed search, this review includes 62 studies published between 2015 and 2023. Keywords searched included 'sodium-glucose cotransporter 2 inhibitors', 'cardiovascular disease', 'heart failure', 'chronic kidney disease', and 'type 2 diabetes'. The most recent and comprehensive data were used. RESULTS: Positive results have been achieved in reducing symptoms in patients with CVD. SGLT2 inhibitors have also been shown to be useful in other contexts such as nonalcoholic fatty liver disease (NAFLD) by reducing liver fat accumulation, kidney benefits by improving body weight and vascular endothelium, improving eGFR, and reducing progression to end stage kidney disease (ESKD). SGLT2 inhibitors are also effective in reducing the need for heart failure hospitalizations and the risk of serious cardiac adverse events, including cardiovascular and all-cause mortality, in patients with reduced or preserved left ventricular (LV) ejection fraction and in acute or decompensated settings. CONCLUSION: SGLT2 inhibitors have evolved into metabolic drugs because of their multisystem action and are indicated for the treatment of all spectrums of heart failure, type 2 diabetes, and chronic kidney disease.

Insurer costs of COVID-19 by disease severity and duration.

OBJECTIVES: To analyze US commercial insurance payments associated with COVID-19 as a function of severity and duration of disease. STUDY DESIGN: Retrospective database analysis. METHODS: Patients with COVID-19 between April 1, 2020, and June 30, 2021, in the Merative MarketScan Commercial database were identified and stratified as having asymptomatic, mild, moderate (with and without lower respiratory disease), or severe/critical (S/C) disease based on the severity of the acute COVID-19 infection. Duration of disease (DOD) was estimated for all patients. Patients with DOD longer than 12 weeks were defined as having post-COVID-19 condition (PCC). Outcomes were all-cause payments (ACP) and disease-specific payments (DSP) for the entire DOD. Variables included demographic and comorbidities at the time of acute disease. Adjusted payments by disease severity were estimated using generalized linear models (γ distribution with log link). RESULTS: A total of 738,339 patients were included (374,401 asymptomatic, 156,220 mild, 180,213 moderate, and 27,505 S/C cases). DSP increased from $217 (95% CI, $214-221) for asymptomatic cases to $2744 (95% CI, $2678-$2811) for moderate cases with lower respiratory disease and $28,250 (95% CI, $26,963-$29,538) for S/C cases. ACP increased from $505 (95% CI, $497-$512) for asymptomatic cases to $46,538 (95% CI, $44,096-$48,979) for S/C cases. The DSP and ACP further increased by $50,736 (95% CI, $45,337-$56,136) and $94,839 (95% CI, $88,029-$101,649), respectively, in S/C cases with PCC vs a DOD of fewer than 4 weeks. CONCLUSIONS: COVID-19 payments for S/C cases were more than 10-fold greater than those of moderate cases and further increased by nearly $95,000 in S/C cases with PCC vs a DOD of fewer than 4 weeks.

Perceptions and Acceptance of a Prophylactic Vaccine for Human Immunodeficiency Virus (HIV): A Qualitative Study.

BACKGROUND: Despite advances in human immunodeficiency virus (HIV) prevention methods, such as the advent of pre-exposure prophylaxis (PrEP), the number of people with newly acquired HIV remains high, particularly in at-risk groups. A prophylactic HIV vaccine could contribute to reduced disease prevalence and future transmission and address limitations of existing options, such as suboptimal long-term adherence to PrEPs. METHODS: This qualitative study aimed to capture perceptions towards and acceptance of prophylactic HIV vaccination in three adult populations in the United States: the general population, 'at-risk' individuals (e.g. men who have sex with men, transgender individuals, gender-nonconforming individuals, and individuals in a sexual relationship with a person living with HIV), and parents/caregivers of children aged 9-17 years. Interviews were conducted with 55 participants to explore key drivers and barriers to HIV vaccine uptake, and a conceptual model was developed. RESULTS: The sample was diverse; participants were 51% female, aged 20-57 years (mean 37 years), 33% with high school diploma as highest education level, and identified as White (42%), Black or African American (35%), of Hispanic, Latino, or Spanish origin (22%), or other races/ethnicities (8%) [groupings are not mutually exclusive]. Perceptions were influenced by individual, interpersonal, community, institutional, and structural factors. Overall, 98% of participants thought vaccination would be beneficial in preventing HIV. Key considerations/barriers included perceived susceptibility, i.e. whether participants felt there was a risk of contracting HIV (discussed by 90%); the clinical profile of the vaccine (e.g. the adverse effect profile [98%], and vaccine efficacy [85%], cost [73%] and administration schedule [88%]); and concerns around potential vaccine-induced seropositivity (VISP; 62%). Stigma was not found to be an important barrier, with a general view that vaccination status was personal. Participants in the 'at-risk' group were the most likely to accept an HIV vaccine (70%). Unique concerns in the subgroups included how a potential vaccine's clinical profile compared with PrEP, voiced by those receiving/considering PrEP, and considerations of children's views on the topic, voiced by parents/caregivers. CONCLUSIONS: Understanding these factors could help develop HIV vaccine research strategies and contribute toward public health messaging to support future HIV vaccination programs.

Endoscopic treatment of primary obstructive megaureter with high pressure balloon dilation in infants.

INTRODUCTION AND OBJECTIVE: Ureteral reimplantation of the dilated ureter in infants is challenging; however, some patients with primary obstructive megaureter (POM) in this age group require intervention due to clinical or radiological progression. We sought to determine if high pressure balloon dilation (HPBD) can serve as a definitive treatment for POM in children under one year of age, or as a temporizing measure until later reimplantation. MATERIALS AND METHODS: All patients from a single institution who underwent HPBD between October 2009 and May 2022 were retrospectively reviewed. Patients were excluded if older than 12 months or diagnosed with neurogenic bladder, posterior urethral valves, or obstructed refluxing megaureter. Patients with prior surgical intervention at the ureterovesical junction were excluded. Indications for surgery included progressive hydroureteronephrosis or urinary tract infection (UTI). Balloon dilation was performed via cystoscopy with fluoroscopic guidance, followed by placement of two temporary ureteral stents. Primary outcomes were improvement or resolution of megaureter and rates of subsequent reimplantation. Secondary outcomes included total number of anesthetics and postoperative UTIs. RESULTS: Fifteen infants with median age of 7.6 months (IQR 3.8-9.7) underwent HPBD. Twelve (80%) patients were detected prenatally and 3 (20%) after a UTI. Indication for surgery was progressive hydroureteronephrosis in 10 patients (67%) and UTI in five (33%). All had SFU grade 3 or 4 hydronephrosis on preoperative ultrasound and median distal ureteral diameter was 13 mm. Median follow up was 2.9 years. Twelve (80%) succeeded with endoscopic treatment: 7 patients had an undetectable distal ureter on ultrasound at last follow-up, 5 were improved with median distal ureteral diameter of 7 mm. Three patients (20%) required ureteral reimplantation due to progressive dilation, all with grade 4 hydronephrosis and distal ureteral diameters were 11, 15, and 21 mm. Six patients (40%) required two anesthetics to complete endoscopic treatment. Among those, 4 patients required initial stent placement for passive dilation followed by a second anesthetic for HPBD weeks later. Two patients underwent repeat HPBD following postoperative proximal migration of the ureteral stents. All 15 patients had an additional anesthetic for removal of stents. Five patients (33%) were treated for a symptomatic UTI (4 febrile, 1 afebrile) with the stents indwelling but there were no UTIs in the group following stent removal. CONCLUSION: Balloon dilation is a practical option for treatment of POM in infants, and in most cases (80%) avoids subsequent open surgery (over median 2.9 years of follow-up).

Impact of Invasive Escherichia Coli Disease on Clinical Outcomes and Medical Resource Utilization Among Asian Patients in the United States.

INTRODUCTION: Invasive Escherichia coli disease (IED) can lead to sepsis and death and is associated with a substantial burden. Yet, there is scarce information on the burden of IED in Asian patients. METHODS: This retrospective study used US hospital data from the PINC AI™ Healthcare database (October 2015-March 2020) to identify IED cases among patients aged ≥ 60 years. IED was defined as a positive E. coli culture in blood or other normally sterile body site (group 1 IED) or positive culture of E. coli in urine with signs of sepsis (group 2 IED). Eligible patients with IED were classified into Asian and non-Asian cohorts based on their reported race. Entropy balancing was used to create cohorts with similar characteristics. Outcomes following IED were descriptively reported in the balanced cohorts. RESULTS: A total of 646 Asian and 19,127 non-Asian patients with IED were included (median age 79 years; 68% female after balancing). For both cohorts, most IED encounters had community-onset (> 95%) and required hospitalization (Asian 96%, mean duration 6.9 days; non-Asian 95%, mean duration 6.8 days), with frequent admission to intensive care (Asian 35%, mean duration 3.3 days; non-Asian 34%, mean duration 3.5 days), all standardized differences [SD] < 0.20. Compared to non-Asian patients, Asian patients were more likely to be discharged home (54% vs. 43%; SD = 0.22), and less likely to be discharged to a skilled nursing facility (24% vs. 31%; SD = 0.16). In-hospital fatality rates during the IED encounter were similar across cohorts (Asian 9%, non-Asian 10%; SD = 0.01). Most E. coli isolates showed resistance to ≥ 1 antibiotic (Asian 61%; non-Asian 64%) and 36% to ≥ 3 antibiotic classes (all SD < 0.20). CONCLUSION: IED is associated with a substantial burden, including need for intensive care and considerable mortality, in Asian patients in the USA that is consistent with that observed for non-Asian patients.