Incident Proteinuria by HIV Serostatus Among Men With Pre--Diabetes Mellitus: The Multicenter AIDS Cohort Study.

BACKGROUND: Pre-diabetes mellitus (DM) is associated with proteinuria, a risk factor for chronic kidney disease. While people with human immunodeficiency virus (HIV; PWH) have a higher risk of proteinuria than people without HIV (PWOH), it is unknown whether incident proteinuria differs by HIV serostatus among prediabetic persons. METHODS: The urine protein-to-creatinine ratio was measured at semiannual visits among men in the Multicenter AIDS Cohort Study since April 2006. Men with pre-DM on or after April 2006 and no prevalent proteinuria or use of antidiabetic medications were included. Pre-DM was defined as a fasting glucose level of 100-125 mg/dL confirmed within a year by a repeated fasting glucose or hemoglobin A1c measurement of 5.7%-6.4%. Incident proteinuria was defined as a urine protein-to-creatinine ratio (UPCR) >200 mg/g, confirmed within a year. We used Poisson regression models to determine whether incident proteinuria in participants with pre-DM differed by HIV serostatus and, among PWH, whether HIV-specific factors were related to incident proteinuria. RESULTS: Between 2006 and 2019, among 1276 men with pre-DM, proteinuria developed in 128 of 613 PWH (21%) and 50 of 663 PWOH (8%) over a median 10-year follow-up. After multivariable adjustment, the incidence of proteinuria in PWH with pre-DM was 3.3 times (95% confidence interval, 2.3-4.8 times) greater than in PWOH (P < .01). Among PWH, current CD4 cell count <50/µL (P < .01) and current use of protease inhibitors (P = .03) were associated with incident proteinuria, while lamivudine and integrase inhibitor use were associated with a lower risk. CONCLUSIONS: Among men with pre-DM, the risk of incident proteinuria was 3 times higher in PWH. Strategies to preserve renal function are needed in this population.

Prevalence of dry eye and Meibomian gland dysfunction in Central and South America: a systematic review and meta-analysis.

BACKGROUND: Dry eye is one of the most common ophthalmic conditions and can significantly impact quality of life. Meibomian gland dysfunction (MGD) is a major cause of evaporative dry eye. We sought to conduct a systematic review and meta-analysis to estimate the prevalence and incidence of dry eye and MGD in Central and South America and to identify factors associated with disease burden. METHODS: Data sources Ovid MEDLINE and Embase. STUDY SELECTION: A search conducted on August 16, 2021, identified studies published between January 1, 2010, and August 16, 2021, with no restrictions regarding participant age or language of publication. Case reports, case series, case-control studies, and interventional studies were excluded. DATA EXTRACTION AND SYNTHESIS: The review was based on a protocol registered on PROSPERO (CRD42021256934). Risk of bias was assessed in duplicate using a risk of bias tool designed for the purposes of descriptive epidemiological studies. Data were extracted by one investigator and verified by another for accuracy. Prevalence of dry eye and MGD were grouped based on study participant characteristics. MAIN OUTCOMES AND MEASURES: Prevalence and incidence of dry eye and MGD in Central and South America. Summary estimates from meta-analysis with 95% confidence intervals (CI). RESULTS: Fourteen studies (11,594 total participants) were included. The population prevalence of dry eye was 13% (95% CI, 12%-14%) in Brazil and 41% (95% CI, 39%-44%) in Mexico based on one study each. Meta-analyses suggested that dry eye prevalence was 70% among indoor workers (95% CI, 56%-80%; I2, 82%; 3 studies), 71% among students (95% CI, 65%-77%; I2, 92%; 3 studies), and 83% in general ophthalmology clinics (95% CI, 77%-88%; I2, 88%; 2 studies). MGD prevalence ranged from 23% among indoor workers (95% CI, 16%-31%; 1 study) to 68% in general ophthalmology clinics (95% CI, 62%-72%; 1 study). No studies reported incidence of dry eye or MGD. CONCLUSIONS: This systematic review and meta-analysis demonstrated considerable variation in the published prevalence of dry eye and MGD among the general population and subpopulations in Central and South America. Local and subpopulation estimates of dry eye disease burden may be valuable to assist needs assessments and implementation of measures to mitigate the condition.

Patient barriers and facilitators for making environmental and behavioral modifications for dry eye in the United States.

BACKGROUND: Managing dry eye disease (DED) is expensive. Often, prescribed treatments improve clinical signs but not patient-reported symptoms. In large surveys, clinicians and patients ranked environmental and behavioral modifications among the most important DED-related research priorities. Our purpose was to investigate the barriers to and facilitators of use of these modifications by patients with DED in the United States and how their use may be impacted by socioeconomic status (SES). METHODS: Using Qualtrics, we conducted an anonymous online survey of adults with DED living in the United States in August to September 2022. Patients were identified through the Dry Eye Foundation, Sjögren's Foundation, and a DED clinic in Colorado. We used an established index for classifying respondent SES based on education, household income, and employment. Outcomes included use of environmental and behavioral modifications and barriers to and facilitators of their use. RESULTS: We included 754 respondents (SES: 382 low, 275 high, and 97 unclear). Most were aged 18 to 49 years (67%), female (68%), and White (76%) and reported dealing with DED for ≤5 years (67%). The most frequent modifications were taking breaks to rest eyes (68%), increasing water intake (68%), and using hot/cold compresses (52%). For these three, the biggest facilitators were as follows: belief that the modification works (27 to 37%), being recommended it (24 to 26%), and ease of use/performance (21 to 32%). Across modifications, the biggest barriers were difficulty of use (55%), lack of family/employer/social/community support (33%), and lack of awareness (32%). The data do not suggest discernible patterns of differences in barriers or facilitators by SES. CONCLUSIONS: Greater emphasis should be placed on explaining to patients how environmental and behavioral modifications might mitigate DED. Employers and members of patients' support systems should be guided regarding how best to support patients in managing DED symptoms.

Plasma Metabolomics of Dietary Intake of Protein-Rich Foods and Kidney Disease Progression in Children.

OBJECTIVE: Evidence regarding the efficacy of a low-protein diet for patients with CKD is inconsistent and recommending a low-protein diet for pediatric patients is controversial. There is also a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein and to assess whether protein-related metabolites are associated with CKD progression. METHODS: Nontargeted metabolomics was conducted in plasma samples from 484 Chronic Kidney Disease in Children (CKiD) participants. Multivariable linear regression estimated the cross-sectional association between 949 known, nondrug metabolites and dietary intake of total protein, animal protein, plant protein, chicken, dairy, nuts and beans, red and processed meat, fish, and eggs, adjusting for demographic, clinical, and dietary covariates. Cox proportional hazards models assessed the prospective association between protein-related metabolites and CKD progression defined as the initiation of kidney replacement therapy or 50% eGFR reduction, adjusting for demographic and clinical covariates. RESULTS: One hundred and twenty-seven (26%) children experienced CKD progression during 5 years of follow-up. Sixty metabolites were significantly associated with dietary protein intake. Among the 60 metabolites, 10 metabolites were significantly associated with CKD progression (animal protein: n = 1, dairy: n = 7, red and processed meat: n = 2, nuts and beans: n = 1), including one amino acid, one cofactor and vitamin, 4 lipids, 2 nucleotides, one peptide, and one xenobiotic. 1-(1-enyl-palmitoyl)-2-oleoyl-glycerophosphoethanolamine (GPE, P-16:0/18:1) was positively associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 88% higher risk of CKD progression. 3-ureidopropionate was inversely associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 48% lower risk of CKD progression. CONCLUSIONS: Untargeted plasma metabolomic profiling revealed metabolites associated with dietary intake of protein and CKD progression in a pediatric population.

Effect of Adopting the New Race-Free 2021 Chronic Kidney Disease Epidemiology Collaboration Estimated Glomerular Filtration Rate Creatinine Equation on Racial Differences in Kidney Disease Progression Among People With Human Immunodeficiency Virus: An Observational Study.

BACKGROUND: The impact of adopting a race-free estimated glomerular filtration rate (eGFR) creatinine (eGFRcr) equation on racial differences in chronic kidney disease (CKD) progression among people with human immunodeficiency virus (PWH) is unknown. METHODS: We defined eGFR stages using the original race-adjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr equation and the new race-free CKD-EPI eGFRcr equation. We then estimated 5-year probabilities of transitioning from baseline kidney function to more advanced eGFR stages and examined the association of race (black vs white) with rates of CKD progression using Markov models. RESULTS: With the race-adjusted eGFRcr equation, black participants (n = 31 298) had a lower risk of progressing from eGFR stage 1 to 2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], .73-.82), an equal risk of progressing from stage 2 to 3 (1.00; .92-.07) and a 3-fold risk of progressing from stage 3 to 4 or 5 (3.06; 2.60-3.62), compared with white participants (n = 27 542). When we used the race-free eGFRcr equation, 16% of black participants were reclassified into a more severe eGFR stage at baseline. The reclassified black individuals had a higher prevalence of CKD risk factors than black PWH who were not reclassified. With the race-free eGFRcr equation, black participants had a higher risk of disease progression across all eGFR stages than white participants. CONCLUSIONS: The original eGFRcr equation systematically masked a subgroup of black PWH who are at high-risk of CKD progression. The new race-free eGFRcr equation unmasks these individuals and may allow for earlier detection and management of CKD.

Prolonged facemask wearing among hospital workers and dry eye - a mixed-methods study.

BACKGROUND: Prolonged facemask wearing may have negatively affected essential workers with dry eye. We conducted a mixed-methods study to examine and understand the associations of the ocular surface, periocular environment, and dry eye-related symptoms among hospital workers across the job spectrum with prolonged facemask use. METHODS: We recruited clinical and non-clinical hospital workers with self-reported symptoms of dry eye and prolonged facemask use. We measured symptoms using the 5-item Dry Eye Questionnaire and the Ocular Surface Disease Index (OSDI). Objective ocular signs included corneal and conjunctival staining, fluorescein tear break up time (TBUT), meibography, tear film interferometry, and periocular humidity. We compared symptoms and signs across levels of periocular humidity, dry eye severity, facemask type, and job type. Participants with moderate or severe dry eye symptoms (OSDI > = 23) were invited for a semi-structured, one-on-one interview. RESULTS: We enrolled 20 clinical and 21 non-clinical hospital workers: 27% were 40 years or older, 76% were female, 29% reported a race other than White, and 20% were Hispanic. Seventeen individuals participated in the semi-structured interviews. From the quantitative analyses, we found that 90% of participants reported worsened severity of dry eye at work due to facemasks. Although wearing facemasks resulted in higher periocular humidity levels compared with not wearing facemasks, 66% participants reported increased airflow over their eyes. Findings from the qualitative interviews supported the finding that use of facemasks worsened dry eye symptoms, especially when facemasks were not fitted around the nose. The data did not suggest that non-clinical hospital workers experienced a greater impact of dry eye than clinical workers. CONCLUSIONS: Healthcare providers and patients with dry eye should be educated about the discomfort and the ocular surface health risks associated with inadequately fitted facemasks. Wearing a fitted facemask with a pliable nose wire appears to mitigate the upward airflow.

Using Machine Learning to Identify Metabolomic Signatures of Pediatric Chronic Kidney Disease Etiology.

BACKGROUND: Untargeted plasma metabolomic profiling combined with machine learning (ML) may lead to discovery of metabolic profiles that inform our understanding of pediatric CKD causes. We sought to identify metabolomic signatures in pediatric CKD based on diagnosis: FSGS, obstructive uropathy (OU), aplasia/dysplasia/hypoplasia (A/D/H), and reflux nephropathy (RN). METHODS: Untargeted metabolomic quantification (GC-MS/LC-MS, Metabolon) was performed on plasma from 702 Chronic Kidney Disease in Children study participants (n: FSGS=63, OU=122, A/D/H=109, and RN=86). Lasso regression was used for feature selection, adjusting for clinical covariates. Four methods were then applied to stratify significance: logistic regression, support vector machine, random forest, and extreme gradient boosting. ML training was performed on 80% total cohort subsets and validated on 20% holdout subsets. Important features were selected based on being significant in at least two of the four modeling approaches. We additionally performed pathway enrichment analysis to identify metabolic subpathways associated with CKD cause. RESULTS: ML models were evaluated on holdout subsets with receiver-operator and precision-recall area-under-the-curve, F1 score, and Matthews correlation coefficient. ML models outperformed no-skill prediction. Metabolomic profiles were identified based on cause. FSGS was associated with the sphingomyelin-ceramide axis. FSGS was also associated with individual plasmalogen metabolites and the subpathway. OU was associated with gut microbiome-derived histidine metabolites. CONCLUSION: ML models identified metabolomic signatures based on CKD cause. Using ML techniques in conjunction with traditional biostatistics, we demonstrated that sphingomyelin-ceramide and plasmalogen dysmetabolism are associated with FSGS and that gut microbiome-derived histidine metabolites are associated with OU.

The Measurement Error Elephant in the Room: Challenges and Solutions to Measurement Error in Epidemiology.

Measurement error, although ubiquitous, is uncommonly acknowledged and rarely assessed or corrected in epidemiologic studies. This review offers a straightforward guide to common problems caused by measurement error in research studies and a review of several accessible bias-correction methods for epidemiologists and data analysts. Although most correction methods require criterion validation including a gold standard, there are also ways to evaluate the impact of measurement error and potentially correct for it without such data. Technical difficulty ranges from simple algebra to more complex algorithms that require expertise, fine tuning, and computational power. However, at all skill levels, software packages and methods are available and can be used to understand the threat to inferences that arises from imperfect measurements.

Topical corticosteroids for dry eye.

BACKGROUND: Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks). OBJECTIVES: To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA). DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. MAIN RESULTS: We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED.  Study characteristics and risk of bias All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (median 79%, interquartile range [IQR] 76% to 80%). On average, each trial enrolled 86 participants (IQR 40 to 158). The treatment duration of topical steroids ranged between one week and three months; trial duration lasted between one week and six months. Eight trials were sponsored exclusively by industry, and four trials were co-sponsored by industry and institutional or governmental funds. We assessed the risk of bias of both subjective and objective outcomes using RoB 2, finding nearly half of the trials to be at high risk of bias associated with selective outcome reporting. Findings Of the 22 trials, 16 evaluated effects of topical steroids, alone or in combination with tobramycin, as compared with lubricants (AT, vehicle), AT plus tobramycin, or no treatment. Corticosteroids probably have a small to moderate effect on improving patient-reported symptoms by 0.29 standardized mean difference (SMD) (95% confidence interval [CI] 0.16 to 0.42) as compared with lubricants (moderate certainty evidence). Topical steroids also likely have a small to moderate effect on lowering corneal staining scores by 0.4 SMDs (95% CI 0.18 to 0.62) (moderate certainty evidence). However, steroids may increase tear film break-up time (TBUT) slightly (mean difference [MD] 0.70 s, 95% CI 0.06 to 1.34; low certainty evidence) but not tear osmolarity (MD 1.60 mOsm/kg, 95% CI -10.47 to 13.67; very low certainty evidence).  Six trials examined topical steroids, either alone or in combination with CsA, against CsA alone. Low certainty evidence indicates that steroid-based interventions may have a small to moderate effect on improving participants' symptoms (SMD -0.33, 95% CI -0.51 to -0.15), but little to no effect on corneal staining scores (SMD 0.05, 95% CI -0.25 to 0.35) as compared with CsA. The effect of topical steroids compared to CsA alone on TBUT (MD 0.37 s, 95% CI -0.13 to 0.87) or tear osmolarity (MD 5.80 mOsm/kg, 95% CI -0.94 to 12.54; loteprednol etabonate alone) is uncertain because the certainty of the evidence is low or very low. None of the included trials reported on quality of life scores. Adverse effects The evidence for adverse ocular effects of topical corticosteroids is very uncertain. Topical corticosteroids may increase participants' risk of intraocular pressure (IOP) elevation (risk ratio [RR] 5.96, 95% CI 1.30 to 27.38) as compared with lubricants. However, when compared with CsA, steroids alone or combined with CsA may decrease or increase IOP elevation (RR 1.45, 95% CI 0.25 to 8.33). It is also uncertain whether topical steroids may increase risk of cataract formation when compared with lubricants (RR 0.34, 95% CI 0.01 to 8.22), given the short-term use and study duration (four weeks or less) to observe longer-term adverse effects.  AUTHORS' CONCLUSIONS: Overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. For dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond CsA. However, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. The available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on IOP elevation or cataract formation or progression. Future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile.

Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in Children.

BACKGROUND: Novel urine biomarkers may improve identification of children at greater risk of rapid kidney function decline, and elucidate the pathophysiology of CKD progression. METHODS: We investigated the relationship between urine biomarkers of kidney tubular health (EGF and α-1 microglobulin), tubular injury (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in Children Study enrolled children aged 6 months to 16 years with an eGFR of 30-90ml/min per 1.73m2. Urine biomarkers were assayed a median of 5 months [IQR: 4-7] after study enrollment. We indexed the biomarker to urine creatinine by dividing the urine biomarker concentration by the urine creatinine concentration to account for the concentration of the urine. The primary outcome was CKD progression (a composite of a 50% decline in eGFR or kidney failure) during the follow-up period. RESULTS: Overall, 252 of 665 children (38%) reached the composite outcome over a median follow-up of 6.5 years. After adjustment for covariates, children with urine EGF concentrations in the lowest quartile were at a seven-fold higher risk of CKD progression versus those with concentrations in the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and α-1 microglobulin concentrations in the highest quartile were also at significantly higher risk of CKD progression versus those with biomarker concentrations in the lowest quartile. Addition of the five biomarkers to a clinical model increased the discrimination and reclassification for CKD progression. CONCLUSIONS: After multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, MCP-1, and α-1 microglobulin concentrations were each associated with CKD progression in children.

Changes in Cytomegalovirus Seroprevalence Among U.S. Children Aged 1-5 Years: The National Health and Nutrition Examination Surveys.

Data from the cross-sectional National Health and Nutrition Examination Surveys (NHANES) indicate that the seroprevalence of cytomegalovirus immunoglobulin G (IgG) antibodies among US children aged 1-5 years was 20.7% (95% confidence interval [CI]: 14.0, 29.0) in 2011-2012 and 28.2% (95% CI: 23.1-34.0) in 2017-2018 (adjusted prevalence difference, +7.6% [95% CI: -.4, +15.6]).

A New Panel-Estimated GFR, Including ß2-Microglobulin and ß-Trace Protein and Not Including Race, Developed in a Diverse Population.

RATIONALE AND OBJECTIVE: Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-cys requires specification of a person's race. ß2-Microglobulin (B2M) and ß-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is. STUDY DESIGN: Study of diagnostic test accuracy. SETTING AND PARTICIPANTS: Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants. TESTS COMPARED: Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race. OUTCOMES: GFR measured as the urinary clearance of iothalamate, plasma clearance of iohexol, or plasma clearance of [51Cr]EDTA. RESULTS: Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m2, and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFRcys (percentage of estimates greater than 30% different from measured GFR [1 - P30] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFRcr-cys (1 - P30 of 8.6% vs 9.4%; P = 0.2). Results were generally consistent across subgroups. LIMITATIONS: No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe. CONCLUSIONS: The 4-marker panel eGFR is as accurate as eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

Social inequalities contribute to racial/ethnic disparities in depressive symptomology among men who have sex with men.

PURPOSE: Racial/ethnic minorities experience disproportionate rates of depressive symptoms in the United States. The magnitude that underlying factors-such as social inequalities-contribute to these symptoms is unknown. We sought to identify exposures that explain racial/ethnic differences in clinically significant depressive symptomology among men who have sex with men (MSM). METHODS: Data from the Multicenter AIDS Cohort Study (MACS), a prospective cohort study, were used to examine clinically significant symptoms of depression (Center for Epidemiologic Studies Depression Scale score ≥ 20) among non-Latinx White, non-Latinx Black, and Latinx MSM. We included 44,823 person-visits by 1729 MSM seen in the study sites of Baltimore/Washington, DC; Chicago; Pittsburgh/Columbus; and Los Angeles from 2000 to 2017. Regression models estimated the percentage of depressive symptom risk explained by social, treatment, and health-related variables related to race/ethnicity. Machine-learning methods were used to predict the impact of mitigating differences in determinants of depressive symptoms by race/ethnicity. RESULTS: At the most recent non-missing MACS visit, 16% of non-Latinx White MSM reported clinically significant depressive symptoms, compared to 22% of non-Latinx Black and 25% of Latinx men. We found that income and social-environmental stress were the largest contributors to racial/ethnic disparities in risk for depressive symptoms. Similarly, setting the prevalence of these two exposures to be equal across racial/ethnic groups was estimated to be most effective at reducing levels of clinically significant depressive symptoms. CONCLUSION: Results suggested that reducing socioeconomic inequalities and stressful experiences may be effective public health targets to decrease racial/ethnic disparities in depressive symptoms among MSM.

Plasma Biomarkers of Tubular Injury and Inflammation Are Associated with CKD Progression in Children.

BACKGROUND: After accounting for known risk factors for CKD progression in children, clinical outcomes among children with CKD still vary substantially. Biomarkers of tubular injury (such as KIM-1), repair (such as YKL-40), or inflammation (such as MCP-1, suPAR, TNF receptor-1 [TNFR-1], and TNFR-2) may identify children with CKD at risk for GFR decline. METHODS: We investigated whether plasma KIM-1, YKL-40, MCP-1, suPAR, TNFR-1, and TNFR-2 are associated with GFR decline in children with CKD and in subgroups defined by glomerular versus nonglomerular cause of CKD. We studied participants of the prospective CKiD Cohort Study which enrolled children with an eGFR of 30-90 ml/min per 1.73 m2 and then assessed eGFR annually. Biomarkers were measured in plasma collected 5 months after study enrollment. The primary endpoint was CKD progression, defined as a composite of a 50% decline in eGFR or incident ESKD. RESULTS: Of the 651 children evaluated (median age 11 years; median baseline eGFR of 53 ml/min per 1.73 m2), 195 (30%) had a glomerular cause of CKD. Over a median follow-up of 5.7 years, 223 children (34%) experienced CKD progression to the composite endpoint. After multivariable adjustment, children with a plasma KIM-1, TNFR-1, or TNFR-2 concentration in the highest quartile were at significantly higher risk of CKD progression compared with children with a concentration for the respective biomarker in the lowest quartile (a 4-fold higher risk for KIM-1 and TNFR-1 and a 2-fold higher risk for TNFR-2). Plasma MCP-1, suPAR, and YKL-40 were not independently associated with progression. When stratified by glomerular versus nonglomerular etiology of CKD, effect estimates did not differ significantly. CONCLUSIONS: Higher plasma KIM-1, TNFR-1, and TNFR-2 are independently associated with CKD progression in children.

Hearing impairment and missing cognitive test scores in a population-based study of older adults: The Atherosclerosis Risk in Communities neurocognitive study.

INTRODUCTION: Hearing impairment is associated with poor cognitive test performance in older adults. However, hearing's impact on cognitive test completion is poorly described, and missing cognitive data due to hearing impairment could misestimate the association. METHODS: We investigated if hearing impairment is associated with missing neurocognitive scores in 3678 adults (72-94 years). Hearing impairment was defined by the better-ear pure tone average of speech-frequency thresholds (0.5-4 kHz) >25 decibels. RESULTS: Hearing impairment was associated with greater missingness on all auditory-only tests, including Logical Memory (prevalence ratio [PR] comparing ≥ moderate impairment vs normal hearing:1.68, 95% confidence interval [CI] 1.26, 2.25) and Digits Backwards (PR 1.62; 95% CI 1.21, 2.17); and two non-auditory tests, Boston Naming (PR 1.61; 95% CI 1.21, 2.17) and Trail Making B (PR 1.55; 95% CI 1.29, 1.86). Models that imputed missing cognitive scores showed the strongest hearing-cognition associations. DISCUSSION: Older adults with hearing impairment are less likely to complete cognitive testing, thereby underestimating the hearing impairment-cognition relationship.

Plasma Soluble Urokinase Plasminogen Activator Receptor (suPAR) and CKD Progression in Children.

RATIONALE & OBJECTIVE: Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker associated with incident chronic kidney disease (CKD) and has been identified as an independent risk factor for CKD progression in children, although these findings remain preliminary, limited to a single point in time, and unreplicated in pediatric cohorts. STUDY DESIGN: Prospective longitudinal cohort study. SETTING & PARTICIPANTS: 565 participants aged 1 to 16 years enrolled in the Chronic Kidney Disease in Children (CKiD) Study. EXPOSURE: Plasma suPAR levels, categorized by quartiles, measured at study entry and a 6-month follow-up interval. OUTCOME: CKD progression, defined as the initiation of kidney replacement therapy (dialysis or transplantation) or >50% decline in estimated glomerular filtrate rate (eGFR). ANALYTIC APPROACH: Associations between plasma suPAR quartiles and risk for CKD progression were estimated using lognormal survival models, adjusting for potential confounders. RESULTS: Participants in the highest suPAR quartile experienced 54% faster progression compared with the lowest quartile after adjustment for demographic and traditional CKD risk factors (P < 0.001). Addition of eGFR to the model attenuated the risk, although those in the highest quartile experienced 33% faster progression compared with the lowest quartile (P = 0.008). Plasma suPAR levels showed little change over 6 months. LIMITATIONS: Potential for residual confounding, reliance on observational data, relatively fewer patients with higher eGFRs for subgroup analysis. CONCLUSIONS: Higher suPAR levels are associated with shorter time to kidney replacement therapy or halving of eGFR in children with CKD. This association is attenuated slightly with inclusion of eGFR in regression modeling but remains a significant association for participants with the highest suPAR levels.

Inflammation and Risk of Depression in HIV: Prospective Findings From the Multicenter AIDS Cohort Study.

Studies suggest that inflammation might be involved in the pathogenesis of depression. Individuals with human immunodeficiency virus (HIV) have a higher risk of depression and elevated inflammatory profiles. Despite this, research on the link between inflammation and depression among this high-risk population is limited. We examined a sample of men who have sex with men from the Multicenter AIDS Cohort Study in prospective analyses of the association between inflammation and clinically relevant depression symptoms, defined as scores >20 on Center for Epidemiological Studies Depression Scale. We included 1,727 participants who contributed 9,287 person-visits from 1984 to 2010 (8,218 with HIV (HIV+) and 1,069 without (HIV-)). Exploratory factor analysis (EFA) was used to characterize underlying inflammatory processes from 19 immune markers. Logistic regression with generalized estimating equations was used to evaluate associations between inflammatory processes and depressive symptoms stratified by HIV serostatus. Three EFA-identified inflammatory processes (EIPs) were identified. EIP-1 scores-described by soluble tumor necrosis factor receptor 2 (sTNF-R2), soluble interleukin-2 receptor α (sIL-2Rα), sCD27, B-cell activating factor, interferon γ-induced protein 10 (IP-10), soluble interleukin-6 receptor (sIL-6R), sCD14, and sGP130-were significantly associated with 9% higher odds of depressive symptoms in HIV+ participants (odds ratio = 1.09; 95% confidence interval: 1.03, 1.16) and 33% higher odds in HIV- participants (odds ratio = 1.33; 95% confidence interval: 1.09, 1.61). Findings suggest that immune activation might be involved in depression risk among both HIV+ and HIV- men who have sex with men.

The Impact of Past and Current Alcohol Consumption Patterns on Progression of Carotid Intima-Media Thickness Among Women and Men Living with HIV Infection.

BACKGROUND: The relationship between alcohol consumption and atherosclerosis has not been sufficiently examined among people living with HIV (PLWH). METHODS: We analyzed data from PLWH in the Women's Interagency HIV Study (WIHS; n = 1,164) and the Multicenter AIDS Cohort Study (MACS; n = 387) with no history of cardiovascular disease (CVD). Repeated measures of intima-media thickness of the right common carotid artery (CCA-IMT) were assessed using B-mode ultrasound from 2004 to 2013. Current alcohol consumption was collected at time of CCA-IMT measurement and was categorized according to gender-specific weekly limits. Group-based trajectory models categorized participants into past 10-year consumption patterns (1994 to 2004). Multivariate generalized estimating equations were conducted to assess the association of past and current alcohol use patterns on change in CCA-IMT by cohort, controlling for age, race, cigarette and illicit drug use, probable depression, HIV RNA viral load, antiretroviral therapy exposure, and hepatitis C coinfection. RESULTS: Among the WIHS, past heavy alcohol consumption was associated with increased CCA-IMT level over time (ß = 8.08, CI 0.35, 15.8, p = 0.04), compared to abstinence. Among the MACS, compared to abstinence, all past consumption patterns were associated with increased CCA-IMT over time (past low: ß = 15.3, 95% CI 6.46, 24.2, p < 0.001; past moderate: ß = 14.3, CI 1.36, 27.2, p = 0.03; past heavy: ß = 21.8, CI 4.63, 38.9, p = 0.01). Current heavy consumption was associated with decreased CCA-IMT among the WIHS (ß = -11.4, 95% CI -20.2, -2.63, p = 0.01) and MACS (ß = -15.4, 95% CI -30.7, -0.13, p = 0.04). No statistically significant time by consumption pattern effects were found. CONCLUSIONS: In both cohorts, 10-year heavy consumption was associated with statistically significant increases in carotid artery thickness, compared to abstinence. Long-term patterns of drinking at any level above abstinence were particularly significant for increases in IMT among men, with heavy consumption presenting with the greatest increase. Our results suggest a potentially different window of risk among past and current heavy drinkers. Further studies are needed to determine whether alcohol consumption level is associated with intermediate measures of atherosclerosis. Alcohol screening and interventions to reduce heavy consumption may benefit PLWH who are at risk of CVD.

Optimal metrics for identifying long term patterns of depression in older HIV-infected and HIV-uninfected men who have sex with men.

OBJECTIVES: Center of Epidemiologic Studies-Depression Scale (CES-D) provides a snapshot of symptom severity at a single point in time. However, the best way of using CES-D to classify long-term depression is unclear. METHOD: To identify long-term depression among HIV-infected and HIV-uninfected 50+ year-old men who have sex with men (MSM) with at least 5 years of follow-up, we compared sensitivities and specificities of CES-D-based metrics (baseline CES-D; four consecutive CES-Ds; group-based trajectory models) thresholded at 16 and 20 to a clinician's evaluation of depression phenotype based on all available data including CES-D history, depression treatment history, drug use history, HIV disease factors, and demographic characteristics. RESULTS: A positive depressive phenotype prevalence was common among HIV-infected (prevalence = 33.1%) and HIV-uninfected MSM (prevalence = 23.2%). Compared to the depressive phenotype, trajectory models of CES-D≥20 provided highest specificities among HIV-infected (specificity = 99.9%, 95% Confidence Interval [CI]:99.4%-100.0%) and HIV-uninfected MSM (specificity = 99.0%, 95% CI:97.4%-99.7%). Highest sensitivities resulted from classifying baseline CES-D ≥ 16 among HIV-infected MSM (sensitivity = 75.0%, 95% CI:67.3%-81.7%) and four consecutive CES-Ds ≥ 16 among HIV-uninfected MSM (sensitivity = 81.0%, 95% CI:73.7%-87.0%). CONCLUSION: Choice of method should vary, depending on importance of false positive or negative rate for long-term depression in HIV-infected and HIV-uninfected MSM.

Multimorbidity Among Persons Living with Human Immunodeficiency Virus in the United States.

Background: Age-associated conditions are increasingly common among persons living with human immunodeficiency virus (HIV) (PLWH). A longitudinal investigation of their accrual is needed given their implications on clinical care complexity. We examined trends in the co-occurrence of age-associated conditions among PLWH receiving clinical care, and differences in their prevalence by demographic subgroup. Methods: This cohort study was nested within the North American AIDS Cohort Collaboration on Research and Design. Participants from HIV outpatient clinics were antiretroviral therapy-exposed PLWH receiving clinical care (ie, ≥1 CD4 count) in the United States during 2000-2009. Multimorbidity was irreversible, defined as having ≥2: hypertension, diabetes mellitus, chronic kidney disease, hypercholesterolemia, end-stage liver disease, or non-AIDS-related cancer. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) comparing demographic subgroups were obtained by Poisson regression with robust error variance, using generalized estimating equations for repeated measures. Results: Among 22969 adults, 79% were male, 36% were black, and the median baseline age was 40 years (interquartile range, 34-46 years). Between 2000 and 2009, multimorbidity prevalence increased from 8.2% to 22.4% (Ptrend < .001). Adjusting for age, this trend was still significant (P < .001). There was no difference by sex, but blacks were less likely than whites to have multimorbidity (aPR, 0.87; 95% CI, .77-.99). Multimorbidity was the highest among heterosexuals, relative to men who have sex with men (aPR, 1.16; 95% CI, 1.01-1.34). Hypertension and hypercholesterolemia most commonly co-occurred. Conclusions: Multimorbidity prevalence has increased among PLWH. Comorbidity prevention and multisubspecialty management of increasingly complex healthcare needs will be vital to ensuring that they receive needed care.