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Rationale: Although IFN-γ release assays (IGRAs) are widely used to screen for Mycobacterium tuberculosis infection in high-income countries, published data on repeatability are limited.Objectives: To determine IGRA repeatability.Methods: The study population included consecutive patients referred to The Methodist Hospital (Houston, TX) between August 1, 2010 and July 31, 2011 for latent tuberculosis (TB) infection screening with an IGRA (QuantiFERON-TB Gold In-Tube; Cellestis, Carnegie, Australia). We performed multiple IGRA tests using leftover stimulated plasma according to a prospectively formulated quality control protocol. We analyzed agreement in interpretation of test results classified according to manufacturer-recommended criteria and repeatability of quantitative TB response.Measurements and Main Results: During the study period, 1,086 test results were obtained from 543 subjects. Per the manufacturer's cut-point, the result of the second test was discordant from that of the first in 28 (8%) of 366 patients with valid test results, including 13 with an initial negative result and 15 with an initial positive result. Although agreement between repeat test results was high (κ = 0.84; 95% confidence interval, 0.79-0.90), the normal expected range of within-subject variability in TB response on retesting included differences of ± 0.60 IU/ml for all individuals (coefficient of variation, 14%), and ± 0.24 IU/ml (coefficient of variation, 27%) for individuals whose initial TB response was between 0.25 and 0.80 IU/ml.Conclusions: There is substantial variability in TB response when IGRAs are repeated using the same patient sample. IGRA results should be interpreted cautiously when TB response is near interpretation cut-points. [ABSTRACT FROM AUTHOR]

Objective: To analyze knee trabecular bone structure and spatial cartilage T(1ρ) and T(2) relaxation times using 3-T magnetic resonance imaging (MRI) in subjects with and without tears of posterior horn of the medial meniscus (PHMM).Design: 3-T MRI from 59 subjects (>18 years), were used to evaluate PHMM tears based on modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring; and to calculate apparent trabecular bone-volume over total bone volume fraction (app. BV/TV), apparent trabecular number (app. Tb.N), apparent trabecular separation (app. Tb.Sp) and apparent trabecular thickness (app. Tb.Th) for overall femur/tibia and medial/lateral femur/tibia; and relaxation times for deep and superficial layers of articular cartilage. A repeated measures analysis using Generalized Estimating Equation (GEE) was performed to compare trabecular bone and cartilage relaxation time parameters between people with (n = 35) and without (n = 24) PHMM tears, while adjusting for age and knee OA presence.Results: Subjects with PHMM tears had lower app. BV/TV and app. Tb.N, and greater app. Tb.Th, and app. Tb.Sp. They also had higher T(1ρ) times in the deep cartilage layer for lateral tibia and medial femur and higher T(2) relaxation times for the deep cartilage layer across all compartments.Conclusions: PHMM tears are associated with differences in underlying trabecular bone and deep layer of cartilage. Over-load of subchondral bone can lead to its sclerosis and stress shielding of trabecular bone leading to the resorptive changes observed in this study. The results underline the importance of interactions of trabecular bone and cartilage in the pathogenesis of knee OA in people with PHMM tears. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to determine whether the mean and heterogeneity of magnetic resonance (MR) knee cartilage T(2) relaxation time measurements at baseline are associated with morphologic degeneration of cartilage, meniscus, and bone marrow tissues over 3 years in subjects with risk factors for osteoarthritis (OA).Design: Subjects with risk factors for OA (n=289) with an age range of 45-55 years were selected from the Osteoarthritis Initiative (OAI) database. 3.0 Tesla MR images were analyzed using morphological gradings of cartilage, bone marrow and menisci whole-organ magnetic resonance imaging scores (WORMS scoring). A T(2) mapping sequence was used to assess the mean and heterogeneity of cartilage T(2) (gray level co-occurrence matrix texture analysis). Regression models were used to assess the relationship between baseline T(2) parameters and changes in morphologic knee WORMS scores over 3 years.Results: The prevalence of knee abnormalities in the cartilage (P<0.0005), meniscus (P<0.00001), and bone marrow significantly (P<0.00001) increased from baseline to 3 years in all compartments combined. The baseline mean and heterogeneity of cartilage T(2) were significantly (P<0.05) associated with morphologic joint degeneration in the cartilage, meniscus and bone marrow over 3 years.Conclusions: The prevalence of knee abnormalities significantly increased over 3 years; increased cartilage T(2) at baseline predicted longitudinal morphologic degeneration in the cartilage, meniscus, and bone marrow over 3 years in subjects with risk factors for OA. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of BMI on the prevalence, severity, and 36-month progression of early degenerative changes in the knee by using 3T MRI in middle-aged subjects without radiographic osteoarthritis (OA).Materials and Methods: We examined baseline and 36-month follow-up MR studies from 137 middle-aged individuals (45-55 years old) with risk factors for knee OA but no radiographic OA from the Osteoarthritis Initiative. Subjects were grouped into three categories: normal BMI (BMI < 25 kg/m(2), n = 38), overweight (BMI 25-29.9 kg/m(2), n = 37), and obese (BMI ≥ 30 kg/m(2), n = 62). Using 3T MRI, cartilage, meniscus, and bone marrow abnormalities were graded using the OA Whole-organ MR Imaging Score (WORMS). The statistical analysis was corrected as necessary for differences in age, sex, and OA risk factors other than BMI.Results: The overall prevalence of lesions was 64% for meniscus and 79% for cartilage (including low grade lesions). At baseline, the prevalence and severity of knee lesions was positively associated with BMI, with a nearly fourfold increase in meniscal tears and more than twofold increase in high-grade cartilage defects in obese individuals relative to normal-weight subjects. Over the 36-month follow-up period, the number of new or worsening cartilage lesions of any grade was significantly higher in obese subjects (p = 0.039), while there was no significant difference in meniscal lesion progression.Conclusion: Obesity was associated with both higher prevalence and severity of early degenerative changes in the knee in middle-aged individuals without radiographic OA and with significantly increased cartilage lesion progression (of any grade) over 36 months. [ABSTRACT FROM AUTHOR]

Objective: To study the role of vastus lateralis/vastus medialis cross-sectional area CSA ratio (VL/VM CSA ratio) in preclinical knee osteoarthritis (OA) using magnetic resonance imaging (MRI)-based cartilage T2 mapping technique and morphological analysis at 3.0T in non-symptomatic, middle-aged subjects.Material and Methods: 174 non-symptomatic individuals aged 45-55 years with OA risk factors were selected from the Osteoarthritis Initiative (OAI) incidence cohort. OA-related knee abnormalities were analyzed using the whole-organ magnetic resonance imaging score (WORMS). Knee cartilage T2 maps were generated using sagittal 2D multi-echo spin-echo images of the right knee. CSA of thigh muscles was measured using axial T1W images of the right mid thigh. Spline-based segmentation of cartilage and muscles was performed on a SUN/SPARC workstation. Muscle measurements were normalized to body size using body surface area (BSA). Statistical significance was determined using Student's t-test, Pearson correlation test, and multiple regression models. To correct for multiple testing, Bonferroni adjustments were applied across all tests within each of the primary results tables (Tables III-VII).Results: Higher T2 values were associated with increased prevalence and severity of cartilage degeneration. In our study, male and female subjects with higher VL/VM CSA ratio demonstrated significantly lower mean cartilage T2 values (all compartments combined) (mean 44.10 vs 45.17, P=0.0017), and significantly lower WORMS scores (mean 14.12 vs 18.68, P=0.0316). Regression analyses of combined mean cartilage T2 using VL/VM CSA ratio as a continuous predictor showed a significant curvilinear relationship between these two variables (P=0.0082).Conclusion: Our results suggested that higher VL/VM CSA ratio is associated with lower T2 values and decreased presence and severity of OA-related morphological changes. Additional studies will be needed to determine causality. [ABSTRACT FROM AUTHOR]

Patients who have undergone angioplasty experience difficulty modifying at-risk behaviors for subsequent cardiac events. The purpose of this study was to test whether an innovative approach to framing of risk, based on 'net present value' economic theory, would be more effective in behavioral intervention than the standard 'future value approach' in reducing cardiovascular morbidity and mortality following angioplasty. At baseline, all patients completed a health assessment, received an individualized risk profile and selected risk factors for modification. The intervention randomized patients into two varying methods for illustrating positive effects of behavior change. For the experimental group, each selected risk factor was assigned a numeric biologic age (the net present value) that approximated the relative potential to improve current health status and quality of life when modifying that risk factor. In the control group, risk reduction was framed as the value of preventing future health problems. Ninety-four percent of patients completed 2-year follow-up. There was no difference between the rates of death, stroke, myocardial infarction, Class II-IV angina or severe ischemia (on non-invasive testing) between the net present value group and the future value group. Our results show that a net present risk communication intervention did not result in significant differences in health outcomes. [ABSTRACT FROM AUTHOR]

Background: Although the majority of studies examining racial/ethnic disparities in health care have focused on the characteristics of the individual, more recently there has been growing attention to the notion that an individual's health practices could be influenced by the characteristics of the place where they reside.Objective: The objective of this study was to examine whether access to care for individuals of different racial/ethnic groups varies by the prevalence of blacks and the prevalence of Latinos in their county of residence.Study Design: We conducted a cross-sectional cohort.Participants: Individuals from the 1996 Medical Expenditure Panel Survey, a nationally representative sample of U.S. households, who described their race/ethnicity as white, black, or Latino, and who resided in 1 of 677 counties (n = 14740) were studied.Measures: Counties were assigned to 6 groups based on the prevalence of blacks and Latinos who resided there (<6% referred to as "low prevalence," 6-39% referred to as "midprevalence," >or=40% referred to as "high prevalence" separately for both blacks and Latinos). Outcomes included whether during the past year any family members: 1). experienced difficulty obtaining any type of health care, delayed obtaining care, or did not receive health care they thought they needed (referred to as "difficulty obtaining care"); or (2). did not receive a doctor's care or a prescription medication because the family needed money to buy food, clothing, or pay for housing (referred to as "financial barriers").Results: After controlling for other individual and area-level covariates, blacks reported lower rates of both outcome variables when they lived in a county with a high prevalence of blacks compared with blacks who lived in a county with a low prevalence of blacks (difficulty obtaining care: 4.3% vs. 18.8%, P <0.005; financial barriers: 1.6% vs. 10.5%, P <0.005). There was a similar association for Latinos by the prevalence of Latinos in the county for difficulty obtaining care (high: 5.0% vs. low: 13.4%, P <0.05), but not the financial barriers outcome (high: 2.2% vs. low: 2.4%, P = 0.90). Whites who lived in an area with a high prevalence of Latinos were more likely to report both outcomes compared with whites who lived in a county with a low prevalence of Latinos (difficulty obtaining care: 17.7% vs. 9.4%, P <0.05; financial barriers: 8.5% vs. 3.2%, P <0.005) .Conclusions: Blacks and Latinos may perceive fewer barriers to care when they live in a county with a high prevalence of people of similar race/ethnicity. Conversely, whites may perceive more difficulty receiving care when they live in an area with a high prevalence of Latinos. Diminishing disparities in access to health care may require interventions that extend beyond the individual. [ABSTRACT FROM AUTHOR]

Background: End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined.Methods: We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization.Results: The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m2 (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m2 (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m2 (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern.Conclusions: An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic led to dramatic changes in the lives of children that impact cardiometabolic health. Cities and counties had varying policies with respect to school closure, recreational programs, and efforts to mitigate food insecurity and economic distress. Our objective was to evaluate changes in BMI-z score and prevalence of overweight/obesity prior to and during the pandemic among children in San Francisco, CA, where public schools were closed for 18-months., Methods: This was an electronic medical record-based retrospective cohort study. We included 15,401 children, 4-17 years of age at study onset. Our exposure was time into each of three time periods: (1) March 2018-February 2019; (2) March 2019-February 2020; (3) March 2020-August 2021 (the pandemic period of school closure). Generalized estimating equations (GEE) were used to assess changes in BMI-z score and overweight/obesity across the three time periods. We assessed for effect modification by age-category, insurance status, and race/ethnicity., Results: Mean BMI-z score increased by 0.06 per year in time period 2, the year prior to the pandemic (p < 0.001, 95% CI: 0.04, 0.09), and by 0.12 per year during time period 3, the first 18 months of the pandemic (p < 0.001, 95% CI 0.10, 0.13). The proportion of children with overweight/obesity increased by 1.4% points per year during time period 2 (p = 0.012, 95% CI: 0.03, 2.46) and by 4.9% points per year during the first 18 months of the pandemic (p < 0.001, 95% CI: 4.11, 5.67). The effect modification analysis demonstrated that the youngest age group, publicly insured children (versus privately insured), and Black, Latino, and Asian children (versus White children) experienced greater increases in BMI-z score during the pandemic (p < 0.01 for all comparisons). The youngest age group (p = 0.022) and publicly insured children (versus privately insured children) (p < 0.001) also experienced greater increases in the proportion of children with overweight/obesity during the pandemic., Conclusions: Among children in San Francisco, increases in BMI-z score and overweight/obesity were greater during the pandemic compared to prior changes, with the most pronounced increases among younger and publicly insured children. These findings support the need for more targeted and effective policies for addressing childhood overweight/obesity, especially among these high-risk populations., (© 2024. The Author(s).)

Importance: Patient to staff ratios vary across US dialysis facilities and have been associated with patient outcomes in older adults., Objective: To determine whether patient to nurse or patient to social worker staff ratios are associated with access to kidney transplant for adolescents and young adults., Design, Setting, and Participants: Retrospective cohort study including patients aged 12 to 30 years who started dialysis between 2005 and 2019 at 8490 US facilities according to the US Renal Data System, the national end-stage kidney disease registry., Exposures: Time-updated quartile of patient to nurse and patient to social worker ratios at dialysis facilities., Main Outcomes and Measures: Fine-Gray models were used to relate the exposure to the incidence of waitlisting and kidney transplant, accounting for the competing risk of death. Subgroup analysis by age at dialysis initiation (<22 vs ≥22 years) was performed. Follow-up was censored in January 2020., Results: A total of 54 141 participants were included (median age, 25 years [IQR, 21-28]; 54.4% male; 4.3% of Asian race, 35.3% of non-Hispanic Black race). The median patient to staff ratios were 14.4 patients per nurse (IQR, 10.3-18.9) and 91.0 patients per social worker (IQR, 65.2-115.0). During a median follow-up of 2.6 years, 39.9% of patients (n = 21 598) received a transplant. In adjusted analysis, the highest (vs lowest) quartile of patient to nurse ratios was associated with 14% lower incidence of transplant (subhazard ratio [SHR], 0.86 [95% CI, 0.82-0.91]). The highest (vs lowest) quartile of patient to social worker ratios was associated with lower incidence of waitlisting (SHR, 0.95 [95% CI, 0.91-0.99]) and transplant (SHR, 0.85 [95% CI, 0.81-0.89]). For both staff ratios, there was an interaction with age at dialysis initiation, such that the association was more pronounced in patients starting dialysis at younger than 22 years (SHR, 0.71 [95% CI, 0.65-0.78] for the highest vs lowest quartile for nursing; SHR, 0.74 [95% CI, 0.68-0.80] for social work) compared with those 22 years and older (SHR, 1.00 [95% CI, 0.94-1.06] for nursing; SHR, 0.96 [95% CI, 0.91-1.02] for social work) for the outcome of transplant., Conclusions and Relevance: Adolescents and young adults receiving care at dialysis facilities with higher patient to staff ratios had reduced access to waitlisting and transplant, particularly if they were younger than 22 years of age at dialysis initiation.

Rationale & Objective: Optimal blood pressure (BP) targets in advanced CKD are controversial. More intensive BP lowering in the setting of advanced CKD is thought to be associated with risk of acute kidney injury, hyperkalemia, and ESKD. We aimed to conduct a pilot trial of intensive BP control to determine if lower SBP targets can be safely achieved for patients with CKD through titration of BP medications using in-home measured BP., Study Design: Non-blinded randomized controlled trial., Settings & Participants: 108 patients with advanced CKD (eGFR ≤30 mL/min/1.73 m 2 ) and hypertension., Interventions: Participants were randomized either to a target home SBP goal of <120 mmHg (N=66) or a less intensive SBP goal (N=42). Antihypertensive medications were titrated to achieve the target home SBP range in the first 4 months of the study and maintained until the end of the study. Home BP was measured using a wireless Bluetooth-enabled monitor that transmitted readings to providers in real-time., Outcomes: The primary efficacy outcome was the difference in achieved clinic SBP between the two study arms from months 4-12. Safety outcomes included hyperkalemia, a composite outcome of falls or syncope, and onset of need for dialysis or kidney transplantation., Results: The mean clinic SBP at month 12 was 124.7 mmHg in the intensive SBP group vs. 138.2 mmHg in the less intensive SBP group. Averaged over months 4-12, the achieved mean clinic SBP in the intensive SBP arm was 11.7 mmHg (95% CI 7.5 to 16 mmHg, p<0.001) lower than the mean SBP achieved in the less intensive SBP arm. Primary safety outcomes were not statistically significantly different between the two arms (all p>0.05)., Limitations: Small sample size which may limit our ability to detect clinically significant differences in rates of adverse outcomes; single-center design., Conclusions: A clinic SBP goal of <120 mmHg is feasible to achieve with the help of real-time home BP monitoring and appears to be safe in this study population with advanced CKD. Larger trials to determine optimal BP targets in advanced CKD and the risks and benefits associated with more intensive BP control are warranted., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Racial and ethnic healthcare disparities require innovative solutions. Patient portals enable online access to health records and clinician communication and are associated with improved health outcomes. Nevertheless, a digital divide in access to such portals persist, especially among people of minoritized race and non-English-speakers. This study assesses the impact of automatic enrollment (autoenrollment) on patient portal activation rates among adult patients at the University of California, San Francisco (UCSF), with a focus on disparities by race, ethnicity, and primary language., Materials and Methods: Starting March 2020, autoenrollment offers for patient portals were sent to UCSF adult patients aged 18 or older via text message. Analysis considered patient portal activation before and after the intervention, examining variations by race, ethnicity, and primary language. Descriptive statistics and an interrupted time series analysis were used to assess the intervention's impact., Results: Autoenrollment increased patient portal activation rates among all adult patients and patients of minoritized races saw greater increases in activation rates than White patients. While initially not statistically significant, by the end of the surveillance period, we observed statistically significant increases in activation rates in Latinx (3.5-fold, p = < 0.001), Black (3.2-fold, p = 0.003), and Asian (3.1-fold, p = 0.002) patient populations when compared with White patients. Increased activation rates over time in patients with a preferred language other than English (13-fold) were also statistically significant (p = < 0.001) when compared with the increase in English preferred language patients., Conclusion: An organization-based workflow intervention that provided autoenrollment in patient portals via text message was associated with statistically significant mitigation of racial, ethnic, and language-based disparities in patient portal activation rates. Although promising, the autoenrollment intervention did not eliminate disparities in portal enrollment. More work must be done to close the digital divide in access to healthcare technology., (© 2024. The Author(s).)

Importance: Preterm birth (PTB) (gestational age <37 weeks) is a major cause of infant mortality and morbidity in the US and is marked by racial and ethnic and socioeconomic inequities. Further research is needed to elucidate the association of risk and protective factors with trends in PTB rates and with related inequities., Objective: To describe the association of PTB rates with inequities as well as related risk and protective factors over the past decade in a US population-based cohort., Design, Setting, and Participants: This retrospective cohort study of singleton live births in California from January 1, 2011, to December 31, 2022, was conducted using vital statistics records and hospital records. The cohort included births with a gestational age of 22 to 44 weeks., Main Outcomes and Measures: Preterm birth rates by racial and ethnic group and by public and nonpublic insurance (considered as a proxy for socioeconomic status) were studied across years. Log-linear regression (relative risks with 95% CIs) was used to evaluate risk and protective factors within groups. Associations of PTB rates with risk and protective factors were assessed., Results: This study included 5 431 018 singleton live births to individuals who identified as American Indian or Alaska Native (0.3%), Asian (14.2%), Black (4.9%), Hispanic (47.8%), or White (27.0%). A total of 43.1% of births were to individuals with public health insurance. From 2011 to 2022, the overall PTB rate increased from 6.8% to 7.5% (change [SE], 10.6% [0.6%]; z score of 18.5; P < .001). Differences in PTB rates and associated changes were observed for racial and ethnic groups and insurance groups. For example, 2022 PTB rates ranged from 5.8% among White individuals with nonpublic insurance to 11.3% among Black individuals with public health insurance. From 2011 to 2022, PTB rates decreased from 9.1% to 8.8% (change [SE], -3.5% [4.2]; z score of -0.8; P = .42) among Black individuals with nonpublic insurance, whereas they increased from 6.4% to 9.5% (change [SE], 49.8% [16.0%]; z score of 3.1; P = .002) among American Indian or Alaska Native individuals with nonpublic insurance. Increases in some risk factors (eg, preexisting diabetes, sexually transmitted infections, mental health conditions) were observed in most groups, and decreases in some protective factors (eg, participation in the California Women, Infants, and Children program) (P for trend < .001 from 2011 to 2021) were observed mostly in low-income groups., Conclusions and Relevance: In this cohort study of singleton live births in California, PTB rates increased in many groups. Persistent racial and ethnic and socioeconomic inequities were also observed. Changes in risk and protective factors provided clues to patterns of PTB. These data point to an urgent need to address factors associated with PTB at both the individual and population levels.

Objectives: To investigate the association between magnetic resonance imaging (MRI)-based ligamentum teres lesions (LTL) and structural hip degeneration., Methods: Bilateral 3-T hip MRIs of participants (n = 93 [36 men]; mean age ( ± SD) 51 years ± 15.4) recruited from the community and the orthopedic clinic of a single medical center were included. Clinical and imaging data acquired included hip disability and osteoarthritis outcome scores, semi-quantitative scoring of hip osteoarthritis on MRI (SHOMRI) scores on fluid-sensitive sequences, and cartilage T 1ρ /T 2 compositional sequences. An MRI-based LTL scoring system, incorporating continuity, thickening, and signal intensity, ranging from 0 (normal) to 4 (complete tear) was constructed. Hip morphological features associated with LTL, based on functional or anatomical relationships to LT, were defined. Relationships between MRI-LT scores and SHOMRI, global/regional cartilage T 1ρ /T 2 , and proposed morphological abnormalities and LTL were explored by mixed effects linear and logistic regression models., Results: In 82 (46.1%) hips, no pain was documented; 118 (63.4%) and 68 (36.6%) hips were graded as KL-grade ≤ 1 and ≥ 2, respectively. Compared to MRI-LT score = 0 (normal), score = 4 (complete tear) revealed significantly worse subchondral bony degenerative changes for bone marrow lesions (SHOMRI-BML) and subchondral cysts (SHOMRI-sc) (p < 0.001, p = 0.015, respectively). Global acetabular T 1ρ , femoral T 2 were significantly increased for abnormal MRI-LT scores (p-range = 0.005-0.032). Regional analyses revealed significantly increased T 1ρ /T 2 in central acetabular/increased T 2 in off-central femoral regions (p-range = 0.005-0.046). Pulvinar effusion-synovitis, shallow fovea, and foveal osteophytes were significantly associated with abnormal LT MRI findings (p-range = < 0.001-0.044)., Conclusion: MRI abnormalities of LT are associated with worse SHOMRI-sc/BML scores, indicative of hip osteoarthritis and higher T 1ρ and T 2 that differ by region. Pulvinar effusion-synovitis and changes in femoral head morphology are associated with LTL., Clinical Relevance Statement: Abnormal ligamentum teres findings identified via MRI are associated with structural degenerative changes of the hip joint and alterations in acetabular and femoral cartilage compositions show spatial differences in relation to LTL., Key Points: The clinical significance of common ligamentum teres lesions (LTL) on MRI is not well understood. LTL identified by an MRI-based scoring system is associated with worse biomarkers, indicating more advanced degenerative hip changes. Effusion-synovitis signal at pulvinar, shallow fovea capitis, and foveal osteophytes are associated with LTL on imaging., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Asthma, pneumonia, and bronchiolitis are the top causes of childhood hospitalization in the United States, leading to over 350,000 hospitalizations and ≈$2 billion in costs annually. The majority of these hospitalizations occur in general/community hospitals. Poor guideline adoption by clinicians contributes to poor health outcomes for children hospitalized with these illnesses, including longer recovery time/hospital stay, higher rates of intensive care unit transfer, and increased risk of hospital readmission. A prior single-center study at a children's hospital tested a multicondition clinical pathway intervention (simultaneous implementation of multiple pathways for multiple pediatric conditions) and demonstrated improved clinician guideline adherence and patient health outcomes. This intervention has not yet been studied in community hospitals, which face unique implementation barriers., Objective: To study the implementation and effectiveness of a multicondition pathway intervention for children hospitalized with asthma, pneumonia, or bronchiolitis in community hospitals., Methods: We will conduct a pragmatic, hybrid effectiveness-implementation, cluster-randomized trial in community hospitals around the United States (1:1 randomization to intervention vs. wait-list control). Our primary outcome will be the adoption of 2-3 evidence-based practices for each condition over a sustained period of 2 years. Secondary outcomes include hospital length of stay, ICU transfer, and readmission., Discussion: This hybrid trial will lead to a comprehensive understanding of how to pragmatically and sustainably implement a multicondition pathway intervention in community hospitals and an assessment of its effects. Enrollment began in July 2022 and is projected to be completed in September 2024. Primary analysis completion is anticipated in March 2025, with reporting of results following., (© 2024 Society of Hospital Medicine.)

Background: Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin-converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin-converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear., Methods and Results: We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow-up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus <15%) were associated with a 26% higher hazard of cardiovascular outcomes (95% CI, 1.07-1.48). In spline-based analysis, risk for cardiovascular outcomes was higher in the hydrochlorothiazide arm at every level of decline in eGFR compared with the same magnitude of eGFR decline in the amlodipine arm., Conclusion: Combined use of benazepril and amlodipine remains superior to benazepril and hydrochlorothiazide for cardiovascular outcomes, regardless of the magnitude of the decline in eGFR that occurred with initiation of therapy.

Background: Promoting physical activity among young individuals with cardiovascular disease (CVD) risk factors such as hypertension, diabetes, or chronic kidney disease can lower systolic blood pressure (BP). We sought to determine whether a 6-month intervention using a physical activity tracker was feasible and effective, compared with usual care., Methods: Participants were recruited at a single academic medical center. Those aged 8-30 years were randomized in a 2:1 ratio to either the intervention (use of a Fitbit physical activity tracker coupled with feedback regarding the participant's step count) or usual care. The primary feasibility outcomes were screening-to-enrollment ratio and 6-month retention rates; the primary clinical outcome was a change in systolic BP from 0-6 months., Results: Sixty-three participants were enrolled (57% male; mean age: 18 ± 4 years). The screening-to-enrollment ratio was 1.8:1. Six-month retention was 62% in the intervention group and 86% in the control group (p = 0.08). Mean change in systolic BP in the intervention group was not significantly different from the control group at 6 months (- 2.3 mmHg; 95% CI - 6.5, 1.8 vs. 3.0 mmHg; 95% CI - 2.5, 8.4, respectively, p = 0.12)., Conclusions: Among children and young adults at elevated CVD risk, the use of a physical activity tracker coupled with tailored feedback regarding their step count progress was feasible but not sustained over time. Physical activity tracker use did not have a statistically significant effect on BP after 6 months. Augmented strategies to mitigate risk in young patients at high risk for early-onset CVD should be explored. This trial is registered at ClinicalTrials.gov (NCT03325426)., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Improving perinatal mental health and care experiences and preventing adverse maternal and infant outcomes are essential prenatal care components, yet existing services often miss the mark, particularly for low-income populations. An enhanced group prenatal care program, "Glow! Group Prenatal Care and Support," was developed in California's Central Valley in response to poor perinatal mental health, disrespectful care experiences, and high rates of adverse birth outcomes among families with low incomes., Methods: Engaging Mothers & Babies; Reimagining Antenatal Care for Everyone (EMBRACE) is a pragmatic, two-arm, randomized, comparative-effectiveness study designed to assess depression (primary outcome), the experience of care (secondary outcome), and preterm birth (exploratory outcome) among Medi-Cal (California's Medicaid program)-eligible pregnant and birthing people, comparing those assigned to Glow! Group Prenatal Care and Support (Glow/GC) with those assigned to enhanced, individual prenatal care through the California Department of Public Health's Comprehensive Perinatal Services Program (CPSP/IC). Participating clinical practices offer the two comparators, alternating between comparators every 6 weeks, with the starting comparator randomized at the practice level. Participant-reported outcomes are assessed through interviewer-administered surveys at study entry, during the participant's third trimester, and at 3 months postpartum; preterm birth and other clinical outcomes are abstracted from labor and delivery records. Patient care experiences are further assessed in qualitative interviews. The protocol complies with the Standard Protocol Items for Randomized Trials., Conclusions: This comparative-effectiveness study will be used to determine which of two forms of enhanced prenatal care is more effective, informing future decisions regarding their use., Trial Registration: ClinicalTrials.gov: NCT04154423., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mean arterial blood pressure (MAP), which decreases as portal hypertension progresses, may be a modifiable risk factor among patients with cirrhosis. We included adults enrolled in the Functional Assessment in Liver Transplantation study. We completed latent class trajectory analyses to define MAP trajectories. We completed time-dependent Cox-regression analyses to test the association between outpatient MAP and 3 cirrhosis-related outcomes: (1) stage 2 acute kidney injury (AKI), defined as a ≥200% increase in serum creatinine from baseline; (2) a 5-point increase in the MELD-Na score, defined as the incidence of increase from initial MELD-Na; (3) waitlist mortality, defined as death on the waitlist. For each outcome, we defined MAP cut points by determining the maximally selected Log-rank statistic after univariable Cox-regression analyses. Among the 1786 patients included in this analysis, our latent class trajectory analyses identified 3 specific outpatient MAP trajectories: "stable-low," "stable-high," and "increasing-to-decreasing." However, >80% of patients were in a "stable-low" trajectory. We found in adjusted analyses that outpatient MAP was associated with each of our outcomes: Stage 2 AKI (adjusted hazard ratio 0.88 per 10 mm Hg increase in MAP [95% CI: 0.79-0.99]); 5-point increase in MELD-Na (adjusted hazard ratio: 0.91 [95% CI: 0.86-0.96]; waitlist mortality (adjusted hazard ratio: 0.89 [95% CI: 0.81-0.96]). For each outcome, we found that an outpatient MAP of 82 mm Hg was most associated with outcomes ( p <0.05 for all). Our study informs the association between outpatient MAP and cirrhosis-related outcomes. These findings, coupled with the identification of specific thresholds, lay the foundation for the trial of targeted outpatient MAP modulation in patients with cirrhosis., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear., Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non-ACEi or ARB comparator, with rates of KFRT and death., Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023., Study Selection: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m 2 ., Data Extraction: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m 2 ), albuminuria (urine albumin-creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes., Data Synthesis: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m 2 , of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes ( P for interaction > 0.05 for all)., Limitation: Individual participant-level data for hyperkalemia or acute kidney injury were not available., Conclusion: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD., Primary Funding Source: National Institutes of Health. (PROSPERO: CRD42022307589)., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-3236.

Objective: To investigate the associations of thigh muscle and fat volumes with structural abnormalities on MRI related to knee osteoarthritis., Materials and Methods: MRI studies of the thighs and knees from 100 individuals were randomly selected from the Osteoarthritis Initiative Cohort. Whole Organ MR Scoring (WORMS) and effusion-synovitis scoring were performed in all knee MRI. Thigh muscles, intermuscular fat, and subcutaneous fat were manually segmented in 15 consecutive MR thigh images. Radiographic Kellgren-Lawrence grades (KLG) were also obtained in all knee radiographs. Independent t-tests were used to investigate the associations between thigh muscle and fat volumes, and sex. Mixed-effects analyses were obtained to investigate the associations between thigh muscle and fat volumes, KLG, WOMAC pain score, cartilage and bone marrow WORMS, as well as effusion-synovitis scores., Results: Women had higher subcutaneous fat volume than men (616.82 vs. 229.13 cm 3 , p < 0.01) and men had higher muscle volumes than women (p < 0.01). Quadriceps (coef = -2.15, p = 0.01) and vastus medialis (coef = -1.84, p = 0.03) volumes were negatively associated with the WORMS cartilage scores. Intermuscular fat volume (coef = 0.48, p = 0.01) was positively associated with WORMS bone marrow edema-like lesion (BMEL) scores. The quadriceps (coef = -0.99, p < 0.01) and hamstring (coef = -0.59, p = 0.01) volumes were negatively associated with WORMS BMEL scores. No evidence of an association was found between thigh muscle and fat volumes with KLG and effusion-synovitis grading (p > 0.05)., Conclusion: Increased quadriceps and hamstring volumes were negatively associated with cartilage lesion and BMEL scores while no evidence of an association was found between thigh muscle and fat volumes, and radiographic knee osteoarthritis or effusion-synovitis grading., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objective: While risk factors for osteoarthritis (OA) are well known, it is not well understood why certain individuals maintain high mobility and joint health throughout their life while others demonstrate OA at older ages. The purpose of this study was to assess which demographic, clinical and MRI quantitative and semi-quantitative factors are associated with preserving healthy knees in older individuals., Methods: This study analyzed data from the OA Initiative (OAI) cohort of individuals at the age of 65 years or above. Participants without OA at baseline (BL) (Kellgren-Lawrence (KL) ≤ 1) were followed and classified as incident cases (KL ≥ 2 during follow-up; n = 115) and as non-incident (KL ≤ 1 over 96-month; n = 391). Associations between the predictor-variables sex, age, BMI, race, clinical scoring systems, T 2 relaxation times and Whole-Organ Magnetic Resonance Imaging-Score (WORMS) readings at BL and the preservation of healthy knees (KL ≤ 1) during a 96-month follow-up period were assessed using logistic regression models., Results: Obesity and presence of pain showed a significant inverse association with maintaining radiographically normal joints in patients aged 65 and above. T 2 relaxation times of the lateral femur and tibia as well as the medial femur were also significantly associated with maintaining radiographically normal knee joints. Additionally, absence of lesions of the lateral meniscus and absence of cartilage lesions in the medial and patellofemoral compartments were significantly associated with maintaining healthy knee joints., Conclusion: Overall, this study provides protective clinical parameters as well as quantitative and semi-quantitative MR-imaging parameters associated with maintaining radiographically normal knee joints in an older population over 8 years., (© 2024. The Author(s).)

Background: Scalable PTSD screening strategies must be brief, accurate and capable of administration by a non-specialized workforce., Methods: We used PTSD as determined by the structured clinical interview as our gold standard and considered predictors sets of (a) Posttraumatic Stress Checklist-5 (PCL-5), (b) Primary Care PTSD Screen for the DSM-5 (PC-PTSD) and, (c) PCL-5 and PC-PTSD questions to identify the optimal items for PTSD screening for public sector settings in Kenya. A logistic regression model using LASSO was fit by minimizing the average squared error in the validation data. Area under the receiver operating characteristic curve (AUROC) measured discrimination performance., Results: Penalized regression analysis suggested a screening tool that sums the Likert scale values of two PCL-5 questions-intrusive thoughts of the stressful experience (#1) and insomnia (#21). This had an AUROC of 0.85 (using hold-out test data) for predicting PTSD as evaluated by the MINI, which outperformed the PC-PTSD. The AUROC was similar in subgroups defined by age, sex, and number of categories of trauma experienced (all AUROCs>0.83) except those with no trauma history- AUROC was 0.78., Conclusion: In some East African settings, a 2-item PTSD screening tool may outperform longer screeners and is easily scaled by a non-specialist workforce., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Meffert, Mathai, Ongeri, Neylan, Mwai, Onyango, Akena, Rota, Otieno, Obura, Wangia, Opiyo, Muchembre, Oluoch, Wambura, Mbwayo, Kahn, Cohen, Bukusi, Aarons, Burger, Jin, McCulloch and Njuguna Kahonge.)

Background: Evidence links lifestyle factors with Alzheimer's disease (AD). We report the first randomized, controlled clinical trial to determine if intensive lifestyle changes may beneficially affect the progression of mild cognitive impairment (MCI) or early dementia due to AD., Methods: A 1:1 multicenter randomized controlled phase 2 trial, ages 45-90 with MCI or early dementia due to AD and a Montreal Cognitive Assessment (MoCA) score of 18 or higher. The primary outcome measures were changes in cognition and function tests: Clinical Global Impression of Change (CGIC), Alzheimer's Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating-Sum of Boxes (CDR-SB), and Clinical Dementia Rating Global (CDR-G) after 20 weeks of an intensive multidomain lifestyle intervention compared to a wait-list usual care control group. ADAS-Cog, CDR-SB, and CDR-Global scales were compared using a Mann-Whitney-Wilcoxon rank-sum test, and CGIC was compared using Fisher's exact test. Secondary outcomes included plasma Aβ42/40 ratio, other biomarkers, and correlating lifestyle with the degree of change in these measures., Results: Fifty-one AD patients enrolled, mean age 73.5. No significant differences in any measures at baseline. Only two patients withdrew. All patients had plasma Aβ42/40 ratios <0.0672 at baseline, strongly supporting AD diagnosis. After 20 weeks, significant between-group differences in the CGIC (p= 0.001), CDR-SB (p= 0.032), and CDR Global (p= 0.037) tests and borderline significance in the ADAS-Cog test (p= 0.053). CGIC, CDR Global, and ADAS-Cog showed improvement in cognition and function and CDR-SB showed significantly less progression, compared to the control group which worsened in all four measures. Aβ42/40 ratio increased in the intervention group and decreased in the control group (p = 0.003). There was a significant correlation between lifestyle and both cognitive function and the plasma Aβ42/40 ratio. The microbiome improved only in the intervention group (p <0.0001)., Conclusions: Comprehensive lifestyle changes may significantly improve cognition and function after 20 weeks in many patients with MCI or early dementia due to AD., Trial Registration: Approved by Western Institutional Review Board on 12/31/2017 (#20172897) and by Institutional Review Boards of all sites. This study was registered retrospectively with clinicaltrials.gov on October 8, 2020 (NCT04606420, ID: 20172897)., (© 2024. The Author(s).)