Association Between Social Vulnerability and Streptococcus pneumoniae Antimicrobial Resistance in US Adults.

BACKGROUND: Growing evidence indicates antimicrobial resistance disproportionately affects individuals living in socially vulnerable areas. This study evaluated the association between Streptococcus pneumoniae (SP) antimicrobial resistance (AMR) and the CDC/ATSDR Social Vulnerability Index (SVI) in the United States. METHODS: Adult patients ≥ 18 years with 30-day nonduplicate SP isolates from ambulatory/hospital settings from January 2011-December 2022 with zip codes of residence were evaluated across 177 facilities in the BD Insights Research Database. Isolates were identified as SP AMR if they were non-susceptible to ≥ 1 antibiotic class (macrolide, tetracycline, extended-spectrum cephalosporins, or penicillin). Associations between SP AMR and SVI score (overall and themes) were evaluated using generalized estimating equations with repeated measurements within county to account for within-cluster correlations. RESULTS: Of 8,008 unique SP isolates from 574 US counties across 39 states, the overall proportion of AMR was 49.9%. A significant association between socioeconomic status (SES) theme and SP AMR was detected with higher SES theme SVI score (indicating greater social vulnerability) associated with greater risk of AMR. On average, a decile increase of SES, indicating greater vulnerability, was associated with a 1.28% increased risk of AMR (95% confidence interval [CI], 0.61%, 1.95%; P=0.0002). A decile increase of household characteristic score was associated with a 0.81% increased risk in SP AMR (95% CI,0.13%, 1.49%; P=0.0197). There was no association between racial/ethnic minority status, housing type and transportation theme, or overall SVI score and SP AMR. CONCLUSIONS: SES and household characteristics were the SVI themes most associated with SP AMR.

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection.

Background: Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI. Methods: A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results. Results: The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY). Conclusions: Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI.

Prevalence of metabolic syndrome and obesity-associated hypertension in the racial ethnic minorities of the United States.

Metabolic syndrome (MetS) is a clinical condition that includes multiple cardiovascular disease risk factors, including obesity, high blood pressure or hypertension, dyslipidemia, and abnormal glucose metabolism. The core metabolic abnormality in MetS is insulin resistance, or impaired insulin-mediated glucose regulation that results in elevated plasma insulin concentration. MetS greatly increases the risk for diabetes, atherosclerosis, and adverse metabolic and cardiovascular outcomes. The syndrome is present in over 25 % of adults in the U.S., with higher rates among racial/ethnic minority groups. Although commonly associated with adult diseases and aging, MetS has also been described in children and adolescents, but at a much lower prevalence of approximately 4-5 %. Because obesity is a key component of the syndrome, the growing childhood epidemic has raised awareness of MetS in children. The rate of MetS among obese children and adolescents is approximately 30 %, with similar racial/ethnic disparity among minority groups as among adults.

Evaluating the health and economic outcomes of a PCV15 vaccination program for adults aged 65 years-and-above in Switzerland.

OBJECTIVE: To assess the health and economic outcomes of a PCV13 or PCV15 age-based (65 years-and-above) vaccination program in Switzerland. INTERVENTIONS: The three vaccination strategies examined were:Target population: All adults aged 65 years-and-above. Perspective(s): Switzerland health care payer. TIME HORIZON: 35 years. Discount rate: 3.0%. Costing year: 2023 Swiss Francs (CHF). STUDY DESIGN: A static Markov state-transition model. DATA SOURCES: Published literature and publicly available databases or reports. OUTCOME MEASURES: Pneumococcal diseases (PD) i.e., invasive pneumococcal diseases (IPD) and non-bacteremic pneumococcal pneumonia (NBPP); total quality-adjusted life-years (QALYs), total costs and incremental cost-effectiveness ratios (CHF/QALY gained). RESULTS: Using an assumed coverage of 60%, the PCV15 strategy prevented a substantially higher number of cases/deaths than the PCV13 strategy when compared to the No vaccination strategy (1,078 IPD; 21,155 NBPP; 493 deaths). The overall total QALYs were 10,364,620 (PCV15), 10,364,070 (PCV13), and 10,362,490 (no vaccination). The associated overall total costs were CHF 741,949,814 (PCV15), CHF 756,051,954 (PCV13) and CHF 698,329,579 (no vaccination). Thus, the PCV13 strategy was strongly dominated by the PCV15 strategy. The ICER of the PCV15 strategy (vs. no vaccination) was CHF 20,479/QALY gained. In two scenario analyses where the vaccine effectiveness for serotype 3 were reduced (75% to 39.3% for IPD; 45% to 23.6% for NBPP) and NBPP incidence was increased (from 1,346 to 1,636/100,000), the resulting ICERs were CHF 29,432 and CHF 13,700/QALY gained, respectively. The deterministic and probabilistic sensitivity analyses demonstrated the robustness of the qualitative results-the estimated ICERs for the PCV15 strategy (vs. No vaccination) were all below CHF 30,000/QALYs gained. CONCLUSIONS: These results demonstrate that using PCV15 among adults aged 65 years-and-above can prevent a substantial number of PD cases and deaths while remaining cost-effective over a range of inputs and scenarios.

Clinical and economic burden of invasive pneumococcal disease and noninvasive all-cause pneumonia in hospitalized US adults: A multicenter analysis from 2015 to 2020.

OBJECTIVES: To evaluate the clinical and economic outcomes in adults hospitalized with invasive pneumococcal disease (IPD) and noninvasive all-cause pneumonia (ACP) overall and by antimicrobial resistance (AMR) status. METHODS: Hospitalized adults from the BD Insights Research Database with an ICD10 code for IPD, noninvasive ACP or a positive Streptococcus pneumoniae culture/urine antigen test were included. Descriptive statistics and multivariable analyses were used to evaluate outcomes (in-hospital mortality, length of stay [LOS], cost per admission, and hospital margin [costs - payments]). RESULTS: The study included 88,182 adult patients at 90 US hospitals (October 2015-February 2020). Most (98.6%) had noninvasive ACP and 40.2% were <65 years old. Of 1450 culture-positive patients, 37.7% had an isolate resistant to ≥1 antibiotic class. Observed mortality, median LOS, cost per admission, and hospital margins were 8.3%, 6 days, $9791, and $11, respectively. Risk factors for mortality included ≥50 years of age, higher risk of pneumococcal disease (based on chronic or immunocompromising conditions), and intensive care unit admission. Patients with IPD had similar mortality rates and hospital margins compared with noninvasive ACP, but greater costs per admission and LOS. CONCLUSION: IPD and noninvasive ACP are associated with substantial clinical and economic burden across all adult age groups. Expanded pneumococcal vaccination programs may help reduce disease burden and decrease hospital costs.

Comment on Chandler et al. 23-Valent Pneumococcal Polysaccharide Vaccination Does Not Prevent Community-Acquired Pneumonia Hospitalizations Due to Vaccine-Type Streptococcus pneumoniae. Microorganisms 2022, 10, 560.

The 23-valent pneumococcal polysaccharide vaccine (PPSV23) targets 23 common serotypes and is recommended for use in adults in various countries to protect against pneumococcal infection. Test-negative design (TND) studies aim to include cases and controls from the same healthcare facilities; however, design choices or limitations associated with conducting real-world research can affect the study results. Here, we highlight how some methodological limitations may have affected results and conclusions of a published study described by Chandler et al.

CMV viral load kinetics as surrogate endpoints after allogeneic transplantation.

BACKGROUNDViral load (VL) surrogate endpoints transformed development of HIV and hepatitis C therapeutics. Surrogate endpoints for CMV-related morbidity and mortality could advance development of antiviral treatments. Although observational data support using CMV VL as a trial endpoint, randomized controlled trials (RCTs) demonstrating direct associations between virological markers and clinical endpoints are lacking.METHODSWe performed CMV DNA PCR on frozen serum samples from the only placebo-controlled RCT of ganciclovir for early treatment of CMV after hematopoietic cell transplantation (HCT). We used established criteria to assess VL kinetics as surrogates for CMV disease or death by weeks 8, 24, and 48 after randomization and quantified antiviral effects captured by each marker. We used ensemble-based machine learning to assess the predictive ability of VL kinetics and performed this analysis on a ganciclovir prophylaxis RCT for validation.RESULTSVL suppression with ganciclovir reduced cumulative incidence of CMV disease and death for 20 years after HCT. Mean VL, peak VL, and change in VL during the first 5 weeks of treatment fulfilled the Prentice definition for surrogacy, capturing more than 95% of ganciclovir's effect, and yielded highly sensitive and specific predictions by week 48. In the prophylaxis trial, the viral shedding rate satisfied the Prentice definition for CMV disease by week 24.CONCLUSIONSOur results support using CMV VL kinetics as surrogates for CMV disease, provide a framework for developing CMV preventative and therapeutic agents, and support reductions in VL as the mechanism through which antivirals reduce CMV disease.FUNDINGMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Prediction of Recurrent Clostridium Difficile Infection Using Comprehensive Electronic Medical Records in an Integrated Healthcare Delivery System.

BACKGROUND Predicting recurrent Clostridium difficile infection (rCDI) remains difficult. METHODS: We employed a retrospective cohort design. Granular electronic medical record (EMR) data had been collected from patients hospitalized at 21 Kaiser Permanente Northern California hospitals. The derivation dataset (2007-2013) included data from 9,386 patients who experienced incident CDI (iCDI) and 1,311 who experienced their first CDI recurrences (rCDI). The validation dataset (2014) included data from 1,865 patients who experienced incident CDI and 144 who experienced rCDI. Using multiple techniques, including machine learning, we evaluated more than 150 potential predictors. Our final analyses evaluated 3 models with varying degrees of complexity and 1 previously published model. RESULTS Despite having a large multicenter cohort and access to granular EMR data (eg, vital signs, and laboratory test results), none of the models discriminated well (c statistics, 0.591-0.605), had good calibration, or had good explanatory power. CONCLUSIONS Our ability to predict rCDI remains limited. Given currently available EMR technology, improvements in prediction will require incorporating new variables because currently available data elements lack adequate explanatory power. Infect Control Hosp Epidemiol 2017;38:1196-1203.

Estimating the Prevalence of Binge Eating Disorder in a Community Sample From the United States: Comparing DSM-IV-TR and DSM-5 Criteria.

OBJECTIVE: To estimate binge eating disorder (BED) prevalence according to DSM-5 and DSM-IV-TR criteria in US adults and to estimate the proportion of individuals meeting DSM-5 BED criteria who reported being formally diagnosed. METHODS: A representative sample of US adults who participated in the National Health and Wellness Survey were asked to respond to an Internet survey (conducted in October 2013). Assessments included 3-month, 12-month, and lifetime BED prevalence based on DSM-5 and DSM-IV-TR criteria and demographics, psychiatric comorbidities, and self-esteem (Rosenberg Self-Esteem Scale). Descriptive statistics are provided. Prevalence estimates were calculated using poststratification sampling weights. RESULTS: Of 22,397 respondents, 344 (women, n = 242; men, n = 102) self-reported symptoms consistent with DSM-5 BED symptom criteria. The 3-month, 12-month, and lifetime DSM-5 prevalence estimates (95% CIs) projected to the US population were 1.19% (1.04%-1.37%), 1.64% (1.45%-1.85%), and 2.03% (1.83%-2.26%), respectively. The 12-month and lifetime projected DSM-IV-TR prevalence estimates were 1.15% (1.00%-1.32%) and 1.52% (1.35%-1.70%), respectively. Of respondents meeting DSM-5 BED criteria in the past 12 months, 3.2% (11/344) reported receiving a formal diagnosis. Compared with non-BED respondents, respondents meeting DSM-5 BED criteria in the past 12 months were younger (mean ± SD age = 46.01 ± 14.32 vs 51.59 ± 15.80 years; P < .001), had a higher body mass index (mean ± SD = 33.71 ± 9.36 vs 27.96 ± 6.68 kg/m²; P < .001), and had lower self-esteem (mean ± SD score = 16.47 ± 6.99 vs 23.33 ± 6.06; P < .001). CONCLUSIONS: DSM-5 BED criteria resulted in higher BED prevalence estimates than with DSM-IV-TR criteria. Most BED respondents did not report being formally diagnosed, indicating an unmet need in BED recognition and diagnosis.

Race/ethnic issues in obesity and obesity-related comorbidities.

The prevalence of obesity is increasing among all age and racial groups in the United States. There is, however, a disproportionate rise in the prevalence of obesity among African-Americans and Hispanic/Mexican Americans. Obesity is a major contributor to the insulin resistant syndrome (IRS), a condition of multiple metabolic abnormalities that is a precursor to type 2 diabetes, and confers a high risk for cardiovascular events. The estimated prevalence of IRS is also greater in Mexican Americans and African-Americans than in Caucasians. The IRS is identifiable in children, and as with adults, there are racial differences in its expression even at a young age. The obesity-associated diseases, including diabetes and hypertension, are found at higher rates within the minority races compared with Caucasians. However, there are differences, in that obesity-related hypertension occurs at higher rates among African-Americans, and obesity-related diabetes occurs at higher rates among Mexican Americans. Race/ethnic differences in lifestyle behaviors and economic disadvantage may account for some of the race disparity in obesity-related diseases and disease outcomes. Environmental factors, however, do not explain all of the race disparity in disease expression, indicating that there are genetic/molecular factors that are operational as well.

Plasma homocysteine concentration and blood pressure in young adult African Americans.

BACKGROUND: An association of plasma homocysteine concentration ([Hcy]) with cardiovascular events has been described, but the role of [Hcy] in the early phase of cardiovascular disease is uncertain. The purpose of this study was to determine whether [Hcy] is related to blood pressure (BP) or other risk factors in African Americans, a population at high risk for cardiovascular disease. METHODS: This cross-sectional study was conducted on a sample of premenopausal African American women (N = 119) and men (N = 56), 30 to 40 years of age. Each subject was classified as normotensive or hypertensive. Fasting blood samples were obtained for serum lipids, insulin, glucose, Hcy, folate, and B-12, followed by an oral glucose tolerance test. RESULTS: Mean [Hcy] was higher in hypertensives compared to normotensives, but the difference was statistically significant only in women (10.5 +/- 5.3 v 8.2 +/- 2.3; P <.01). In women, the simple correlation analysis revealed a statistically significant relationship of [Hcy] with systolic BP (r = 0.22, P =.02) and diastolic BP (r = 0.240, P =.01). However, after adjusting for age and body mass index (BMI), the correlations were attenuated and no longer significant. There was a significant inverse relationship of [Hcy] with plasma folate (r = -0.35, P <.001) and B-12 (r = -0.29, P <.01) in women. CONCLUSIONS: Although the simple correlation coefficient suggests a significant relationship of [Hcy] with BP in women, this relationship was no longer statistically significant after adjustment for age and BMI. The significant inverse relationship of plasma folate and B-12 with [Hcy] suggest that diet factors may affect the crude [Hcy]-BP relationship identified in this sample.

Parental correlates of physical activity in a racially/ethnically diverse adolescent sample.

PURPOSE: To evaluate relationships between parents' and adolescents' physical activity and television usage and whether these relationships differed among adolescents from different racial/ethnic backgrounds. METHODS: Adolescents and their parents were separately asked to report information about their eating, exercising, and weight-related behaviors. Among the 900 adolescents, 477 were girls and 423 were boys; 60% were in high school; 29% were white, 23% were black, 21% were Asian, 14% were Hispanic, and 13% were considered mixed or other race/ethnicity. RESULTS: Parents' reported encouragement was positively related to physical activity in white (r = 0.39; p <.001) and black boys (r = 0.26; p =.007), and girls (all race/ethnic groups combined: r = 0.15; p <.001). Parents' television time was positively related to television time in Hispanic boys (r = 0.40; p =.009) but negatively related to television time in black boys (r = -0.23; p =.036). Parents' concern about their own fitness was negatively related to television time in white girls (r = -0.19; p =.029) but positively related in black girls (r = 0.23; p =.030). CONCLUSION: This study found significant, although modest, relationships between parents' and adolescents' physical activity attitudes and behaviors. Many of these relationships differed by race/ethnicity. Results from the present and previous studies suggest that factors other than parents' behavior and support explain adolescents' physical activity behaviors.

Characterization of treatment resistant depression episodes in a cohort of patients from a US commercial claims database.

CONTEXT: Treatment Resistant Depression (TRD) is a significant and burdensome health concern. OBJECTIVE: To characterize, compare and understand the difference between TRD and non-TRD patients and episodes in respect of their episode duration, treatment patterns and healthcare resource utilization. DESIGN AND SETTING: Patients between 18 and 64 years with a new diagnosis of major depressive disorder (MDD) and without a previous or comorbid diagnosis of schizophrenia or bipolar disease were included from PharMetrics Integrated Database, a claims database of commercial insurers in the US. Episodes of these patients in which there were at least two distinct failed regimens involving antidepressants and antipsychotics were classified as TRD. PATIENTS: 82,742 MDD patients were included in the analysis; of these patients, 125,172 episodes were identified (47,654 of these were drug-treated episodes). MAIN OUTCOME MEASURES: Comparison between TRD and non-TRD episodes in terms of their duration, number and duration of lines of treatment, comorbidities, and medical resource utilization. RESULTS: Of the treated episodes, 6.6% (N = 3,134) met the criteria for TRD. The median time to an episode becoming TRD was approximately one year. The mean duration of a TRD episode was 1,004 days (vs. 452 days for a non-TRD episode). More than 75% of TRD episodes had at least four lines of therapy; half of the treatment regimens included a combination of drugs. Average hospitalization costs were higher for TRD than non-TRD episodes: $6,464 vs. $1,734, as were all other health care utilization costs. CONCLUSIONS: While this study was limited to relatively young and commercially covered patients, used a rigorous definition of TRD and did not analyze for cause or consequence, the results highlight high unmet medical need and burden of TRD on patients and health care resources.