Blood pressure control according to clinical practice guidelines is associated with decreased mortality and cardiovascular events among liver transplant recipients.

Data for liver transplant recipients (LTRs) regarding the benefit of care concordant with clinical practice guidelines for management of blood pressure (BP) are sparse. This paper reports on clinician adherence with BP clinical practice guideline recommendations and whether BP control is associated with mortality and cardiovascular events (CVEs) among LTRs. We conducted a longitudinal cohort study of adult LTRs who survived to hospital discharge at a large tertiary care network between 2010 and 2016. The primary exposure was a BP of <140/<90 mm Hg within year 1 of LT. Among 602 LTRs (mean age 56.7 years, 64% men), 92% had hypertension and 38% had new onset hypertension. Less than 30% of LTRs achieved a BP of <140/<90 mm Hg over a mean of 43.2 months. In multivariable models, adjusted for key confounders, BP control post-LT compared with lack of control was associated with a significantly lower hazard of mortality (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.39, 0.87) and of CVEs (HR 0.65, 95% CI 0.43, 0.97). The association between BP control of <140/<90 mm Hg with improved survival and decreased CVEs in LTRs suggests that efforts to improve clinician adherence to BP clinical practice recommendations should be intensified.

Effectiveness and Efficiency of Observationally Assessing Fidelity to a Family-Centered Child Intervention: A Quasi-Experimental Study.

Assessment of fidelity that is effective, efficient, and differentiates from usual practices is critical for effectively implementing evidence-based programs for families. This quasi-experiemntal study sought to determine whether observational ratings of fidelity to the Family Check-Up (FCU) could differentiate between levels of clinician training in the model, and from services as usual, and whether rating segments of sessions could be equivalent to rating complete sessions. Coders rated 75 videotaped sessions-complete and 20-min segments-for fidelity, using a valid and reliable rating system across three groups: (a) highly trained in FCU with universal, routine monitoring; (b) minimally trained in FCU with optional, variable monitoring; and (c) services as usual with no training in the FCU. We hypothesized that certain dimensions of fidelity would differ by training, whereas others would not. The results indicated that, as expected, one dimension of fidelity to the FCU, Conceptually accurate to the FCU, was reliably different between the groups (χ2 = 44.63, p < .001). The differences observed were in the expected direction, showing higher scores for therapists with more training. The rating magnitude of session segments largely did not differ from those of complete session ratings; however, interrater reliabilities were low for the segments. Although observational ratings were shown to be sensitive to the degree of training in the FCU on a unique and theoretically critical dimension, observational coding of complete sessions is resource intensive and limits scalability. Additional work is needed to reduce the burden of assessing fidelity to family-centered programs.

Addressing Methodologic Challenges and Minimizing Threats to Validity in Synthesizing Findings from Individual-Level Data Across Longitudinal Randomized Trials.

Integrative Data Analysis (IDA) encompasses a collection of methods for data synthesis that pools participant-level data across multiple studies. Compared with single-study analyses, IDA provides larger sample sizes, better representation of participant characteristics, and often increased statistical power. Many of the methods currently available for IDA have focused on examining developmental changes using longitudinal observational studies employing different measures across time and study. However, IDA can also be useful in synthesizing across multiple randomized clinical trials to improve our understanding of the comprehensive effectiveness of interventions, as well as mediators and moderators of those effects. The pooling of data from randomized clinical trials presents a number of methodological challenges, and we discuss ways to examine potential threats to internal and external validity. Using as an illustration a synthesis of 19 randomized clinical trials on the prevention of adolescent depression, we articulate IDA methods that can be used to minimize threats to internal validity, including (1) heterogeneity in the outcome measures across trials, (2) heterogeneity in the follow-up assessments across trials, (3) heterogeneity in the sample characteristics across trials, (4) heterogeneity in the comparison conditions across trials, and (5) heterogeneity in the impact trajectories. We also demonstrate a technique for minimizing threats to external validity in synthesis analysis that may result from non-availability of some trial datasets. The proposed methods rely heavily on latent variable modeling extensions of the latent growth curve model, as well as missing data procedures. The goal is to provide strategies for researchers considering IDA.

Two-Year Impact of Prevention Programs on Adolescent Depression: an Integrative Data Analysis Approach.

This paper presents the first findings of an integrative data analysis of individual-level data from 19 adolescent depression prevention trials (n = 5210) involving nine distinct interventions across 2 years post-randomization. In separate papers, several interventions have been found to decrease the risk of depressive disorders or elevated depressive/internalizing symptoms among youth. One type of intervention specifically targets youth without a depressive disorder who are at risk due to elevated depressive symptoms and/or having a parent with a depressive disorder. A second type of intervention targets two broad domains: prevention of problem behaviors, which we define as drug use/abuse, sexual risk behaviors, conduct disorder, or other externalizing problems, and general mental health. Most of these latter interventions improve parenting or family factors. We examined the shared and unique effects of these interventions by level of baseline youth depressive symptoms, sociodemographic characteristics of the youth (age, sex, parent education, and family income), type of intervention, and mode of intervention delivery to the youth, parent(s), or both. We harmonized eight different measures of depression utilized across these trials and used growth models to evaluate intervention impact over 2 years. We found a significant overall effect of these interventions on reducing depressive symptoms over 2 years and a stronger impact among those interventions that targeted depression specifically rather than problem behaviors or general mental health, especially when baseline symptoms were high. Implications for improving population-level impact are discussed.

Individualized Relative-Intensity Physical Activity Accelerometer Cut Points.

PURPOSE: Physical activity (PA) intensity is expressed as either absolute or relative intensity. Absolute intensity refers to the energy required to perform an activity. Relative intensity refers to a level of effort that takes into account how hard an individual is working relative to their maximum capacity. We sought to develop methods for obtaining individualized relative-intensity accelerometer cut points using data from a maximal graded exercise treadmill test (GXT) so that each individual has their own cut point. METHODS: A total of 2363 men and women 38 to 50 yr old from the CARDIA fitness study wore ActiGraph 7164 accelerometers during a maximal GXT and for seven consecutive days in 2005-2006. Using mixed-effects regression models, we regressed accelerometer counts on heart rate as a percentage of maximum (%HRmax) and on RPE. Based on these two models, we obtained a moderate-intensity (%HRmax = 64% or RPE = 12) count cut point that is specific to each participant. We applied these subject-specific cut points to the available CARDIA accelerometer data. RESULTS: Using RPE, the mean moderate-intensity accelerometer cut point was 4004 (SD = 1120) counts per minute. On average, cut points were higher for men (4189 counts per minute) versus women (3865 counts per minute) and were higher for Whites (4088 counts per minute) versus African Americans (3896 counts per minute). Cut points were correlated with body mass index (rho = -0.11) and GXT duration (rho = 0.33). Mean daily minutes of absolute- and relative-intensity moderate to vigorous PA were 34.1 (SD = 31.1) min·d and 9.1 (SD = 18.2) min·d, respectively. RPE cut points were higher than those based on %HRmax. This is likely due to some participants ending the GXT before achieving their HRmax. CONCLUSIONS: Accelerometer-based relative-intensity PA may be a useful measure of intensity relative to maximal capacity.

The Hispanic Paradox in Patients With Liver Cirrhosis: Current Evidence From a Large Regional Retrospective Cohort Study.

BACKGROUND: Despite lower socioeconomic status, Hispanics in the United States paradoxically maintain equal or higher average survival rates compared to non-Hispanic Whites (NHW). METHODS: We used multivariable Cox regression to assess whether this "Hispanic paradox" applies to patients with liver cirrhosis using a retrospective cohort of twenty 121 patients in a Chicago-wide electronic health record database. RESULTS: Our study population included 3279 (16%) Hispanics, 9150 (45%) NHW, 4432 (22%) African Americans, 529 (3%) Asians, and 2731 (14%) of other races/ethnic groups. Compared to Hispanics, NHW (hazard ratio [HR] 1.26; 95% confidence interval [CI], 1.16-1.37), African American (HR 1.26; 95% CI, 1.15-1.39), and other races/ethnic groups (HR 1.55; 95% CI, 1.40-1.71) had an increased risk of death despite adjustment for age, sex, insurance status, etiology of cirrhosis, and comorbidities. On stratified analyses, a mortality advantage for Hispanics compared to NHW was seen for alcohol cirrhosis (HR for NHW 1.35; 95% CI, 1.19-1.52), hepatitis B (HR for NHW 1.35; 95% CI, 0.98-1.87), hepatitis C (HR for NHW 1.21; 95% CI, 1.06-1.38), and nonalcoholic steatohepatitis (HR for NHW 1.14; 95% CI, 0.94-1.39). There was no advantage associated with Hispanic race over NHW in cases of hepatocellular carcinoma or cholestatic liver disease. CONCLUSIONS: Hispanic patients with cirrhosis experience a survival advantage over many other racial groups despite adjustment for multiple covariates.

Real-World Study of Once-Daily, Extended-Release Tacrolimus Versus Twice-Daily, Immediate-Release Tacrolimus in Kidney Transplantation: Clinical Outcomes and Healthcare Resource Utilization.

INTRODUCTION: Real-world data with extended-release tacrolimus (ER-T) are lacking in the USA. This study examined clinical outcomes and healthcare resource utilization in kidney transplant patients receiving ER-T in clinical practice. METHODS: This was a retrospective, single-center analysis (February-June 2016) using data from Northwestern University's Enterprise Data Warehouse. Adult patients receiving a kidney transplant in the preceding 4 years, treated de novo or converted to ER-T from immediate-release tacrolimus (IR-T) within 10 days post-transplantation, and maintained on ER-T (at least 3 months) were included. Patients were matched for demographic and clinical characteristics with IR-T-treated control patients. Endpoints included clinical outcomes and healthcare resource utilization up to 1 year post-transplantation. RESULTS: A total of 19 ER-T-treated patients were matched with 55 IR-T-treated patients. No ER-T-treated patients experienced biopsy-confirmed acute rejection (BCAR) or graft failure versus 3 (5.5%) and 3 (5.5%) IR-T-treated patients, respectively. Mean estimated glomerular filtration rate (eGFR), the number of all-cause outpatient visits, readmissions, and all-cause hospitalization days were comparable between groups. Tacrolimus trough levels, days to target level (6-10 ng/mL), and number of required dose adjustments were also similar. CONCLUSION: Real-world clinical outcomes and healthcare resource utilization were similar with ER-T and IR-T. Larger studies will need to investigate the trend toward fewer BCAR events, and increased graft survival with ER-T. FUNDING: Astellas Pharma Global Development, Inc. Plain language summary available for this article.

Pre-pregnancy blood pressure and body mass index trajectories and incident hypertensive disorders of pregnancy.

There are few studies examining patterns in body mass index (BMI) and blood pressure (BP) and subsequent hypertensive disorders of pregnancy (HDPs). We examined the association of BMI (n = 1342) or BP (n = 2266) trajectories in the 5 years preceding birth with HDPs using adjusted logistic regression. Compared to normal-weight BMI and low-normal BP groups, membership to the overweight BMI group (OR: 2.95, 95%CI: 1.57-5.53, p = 0.001) and higher-normal (OR: 2.74, 95%CI:1.49-5.04, p = 0.001) and prehypertensive (OR:7.27, 95%CI: 3.29-16.06, p < 0.001) BP groups were associated with higher odds of HDPs. Our data suggest maintaining normal-weight and low-normal BP in the years preceding pregnancy may help avoid HDPs.

FGF23 (Fibroblast Growth Factor-23) and Incident Hypertension in Young and Middle-Aged Adults: The CARDIA Study.

Blacks have the highest prevalence of hypertension in the United States. Higher levels of FGF23 (fibroblast growth factor-23) have been associated with worse cardiovascular outcomes. Whether FGF23 is associated with rising blood pressure (BP) and racial differences in incident hypertension is unclear. We studied 1758 adults (45.0±3.7 years; 57.8% female; 36.9% black) without hypertension or cardiovascular disease who participated in the year 20 (2005-2006) follow-up examination of the CARDIA study (Coronary Artery Risk Development in Young Adults). We investigated the associations of baseline (year 20) cFGF23 (C-terminal FGF23) levels with longitudinal BP patterns and incident hypertension (defined as being on antihypertensive medication, systolic BP ≥130 or diastolic BP ≥80 mm Hg) during 2 follow-up visits (years 25 and 30). During follow-up, 35.2% of participants developed hypertension. In multivariable linear mixed models, there were greater increases in systolic BP from year 20 to 25 and year 25 to 30 in the highest FGF23 quartile relative to the lowest quartile (+2.1 mm Hg, P=0.0057 and +2.2 mm Hg, P=0.0108, respectively for each time period), whereas there were greater increases in diastolic BP from year 20 to 25 in the highest quartile relative to the lowest (+1.6 mm Hg; P=0.0024). In multivariable modified Poisson regression analyses, the highest FGF23 quartile was associated with a 45% greater risk of developing hypertension during follow-up compared with the lowest quartile (relative risk, 1.45 [1.18-1.77]). Results did not vary by race (Pinteraction=0.1523). Higher FGF23 levels are independently associated with rising BP over time and an increased risk of incident hypertension but not racial differences in hypertension.

Cardiovascular Disease Outcomes Related to Early Stage Renal Impairment After Liver Transplantation.

BACKGROUND: In the general population, even mild renal disease is associated with increased cardiovascular (CV) complications. Whether this is true in liver transplant recipients (LTR) is unknown. METHODS: This was a retrospective cohort study of 671 LTR (2002-2012) from a large urban tertiary care center and 37 322 LTR using Vizient hospitalization data linked to the United Network for Organ Sharing. The 4-variable Modification of Diet in Renal Disease equation estimated glomerular filtration rate (eGFR). Outcomes were 1-year CV complications (death/hospitalization from myocardial infarction, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, or stroke) and mortality. Latent mixture modeling identified trajectories in eGFR in the first liver transplantation (LT) year in the 671 patients. RESULTS: Mean (SD) eGFR was 72.1 (45.7) mL/min per 1.73 m. Six distinct eGFR trajectories were identified in the local cohort (n = 671): qualitatively normal-slow decrease (4% of cohort), normal-rapid decrease (4%), mild-stable (18%), mild-slow decrease (35%), moderate-stable (30%), and severe-stable (9%). In multivariable analyses adjusted for confounders and baseline eGFR, the greatest odds of 1-year CV complications were in the normal-rapid decrease group (odds ratio, 10.6; 95% confidence interval, 3.0-36.9). Among the national cohort, each 5-unit lower eGFR at LT was associated with a 2% and 5% higher hazard of all-cause and CV-mortality, respectively (P < 0.0001), independent of multiple confounders. CONCLUSIONS: Even mild renal disease at the time of LT is a risk factor for posttransplant all-cause and CV mortality. More rapid declines in eGFR soon after LT correlate with risk of adverse CV outcomes, highlighting the need to study whether early renal preservation interventions also reduce CV complications.

Association of sleep characteristics with cardiovascular and metabolic risk factors in a population sample: the Chicago Area Sleep Study.

OBJECTIVES: To investigate the association of sleep characteristics with prevalent hypertension, diabetes, and obesity in a multiethnic cohort. DESIGN: This study used a population-based cross-sectional study design. SETTING: Participants were recruited between 2009 and 2011 from Chicago, Illinois, and the surrounding suburbs. PARTICIPANTS: Participants were 492 adults aged 35 to 64years who self-reported as white, black, Hispanic, or Asian and who had a low likelihood of sleep apnea based on the apnea screening questionnaires and 1 night of apnea screening using an in-home device (apnea hypopnea index <15 or oxygen desaturation index <10). MEASUREMENTS: Participants wore a wrist actigraphy monitor (Actiwatch™) for 7days. During a clinical examination, participants completed questionnaires about sleep, other health behaviors, and medical history and had their blood pressure, anthropometric measures, and fasting blood glucose measured; metabolic risk factors were determined based on standard clinical guidelines. RESULTS: The prevalence of hypertension, obesity, and diabetes was 17.1%, 5.5%, and 35.4%, respectively. Sleep duration was not associated with any cardiovascular risk factor. There was a significantly increased odds for hypertension (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.08) and obesity (OR, 1.03; 95% CI, 1.00-1.05) associated with higher sleep fragmentation (per 1%). There was also a significantly increased odds for hypertension associated with poorer self-reported sleep quality (OR, 1.14 [95% CI, 1.05-1.24] per 1-unit higher Pittsburgh Sleep Quality Index global score). CONCLUSION: Objective and self-reported sleep quality may be more important than duration in relation to prevalent hypertension.

The Mediation of Racial Differences in Hypertension by Sleep Characteristics: Chicago Area Sleep Study.

BACKGROUND: Racial disparities in hypertension prevalence in the United States are established. Given our understanding of racial and ethnic disparities in sleep characteristics and demonstrated associations between sleep characteristics and hypertension, we tested whether sleep characteristics mediated racial disparities in hypertension. METHODS: Analyses were performed in the Chicago Area Sleep Study, a population-based cohort study of 154 Blacks, 128 Whites, 103 Hispanics, and 109 Asians without obstructive sleep apnea. Participants underwent 7 days of wrist actigraphy monitoring. Algorithms were used to determine sleep duration and sleep maintenance (the percent of sleep in the sleep period). Hypertension was determined as systolic blood pressure >140mm Hg or diastolic blood pressure >90mm Hg or the use of antihypertensive medications. We estimated sample prevalence ratios for hypertension before and after adjustment for sleep characteristics and also conducted mediation analysis. RESULTS: The sample prevalence of hypertension was highest in Blacks (36%), followed by Hispanics (14%), Asians (8%), and Whites (5%). The sample prevalence ratio for hypertension for Blacks vs. Whites was 5.52 (95% confidence interval (CI): 2.36, 13.23) after adjusting for age, sex, and education. Adjustment for sleep duration had no influence on the effect estimate, but adjustment for sleep maintenance attenuated the sample prevalence ratio to 4.55 (95% CI: 1.91, 11.14). Sleep maintenance mediated 11.4% of the difference in hypertension prevalence between Blacks and Whites in this sample. CONCLUSIONS: Sleep maintenance mediated a small but significant portion of the disparity in hypertension between Blacks and Whites. Future research should investigate the mechanisms underlying these findings.