Maternal and Child Mortality: Analysis of Nurse Home Visiting in 3 RCTs.

INTRODUCTION: The impact of intensive prenatal and infant/toddler nurse home visiting on low-income mothers' and children's survival was examined in 3 RCTs following participants over 2-decade periods after trial registration during pregnancy (data gathered between 1978 and 2015 and analyzed between 2016 and 2020). METHODS: All-cause and external-cause maternal mortality and preventable-cause child mortality were examined using National Death Index data. Survival rates were calculated for all the 1,138 mothers randomized and 1,076 live-born children in the second RCT (conducted in Memphis, TN) and for all the 1,135 mothers randomized and 1,087 live-born children in the first and third RCTs combined (conducted in Elmira, NY and Denver, CO). RESULTS: There were no significant nurse home visiting-control differences in maternal mortality in Memphis or Elmira and Denver. Posthoc analysis, combining all 3 trials, suggested a reduction in external-cause maternal mortality among nurse-visited mothers (p=0.054). There was a marginally significant nurse home visiting-control difference in preventable-cause child mortality (p=0.09) in Memphis. CONCLUSIONS: These results support examining maternal and child mortality in additional nurse home visiting trials with larger samples living in disadvantaged contexts. Intensive prenatal and infant/toddler home visiting by nurses for mothers and children living in poverty may decrease premature death.

Prenatal and Infancy Nurse Home Visiting Effects on Mothers: 18-Year Follow-up of a Randomized Trial.

BACKGROUND: Prenatal and infancy home-visiting by nurses is promoted as a means of improving maternal life-course, but evidence of long-term effects is limited. We hypothesized that nurse-visitation would lead to long-term reductions in public-benefit costs, maternal substance abuse and depression, and that cost-savings would be greater for mothers with initially higher psychological resources. METHODS: We conducted an 18-year follow-up of 618 out of 742 low-income, primarily African-American mothers with no previous live births enrolled in an randomized clinical trial of prenatal and infancy home visiting by nurses. We compared nurse-visited and control-group women for public-benefit costs, rates of substance abuse and depression, and examined possible mediators of intervention effects. RESULTS: Nurse-visited women, compared with controls, incurred $17 310 less in public benefit costs (P = .03), an effect more pronounced for women with higher psychological resources ($28 847, P = .01). These savings compare with program costs of $12 578. There were no program effects on substance abuseor depression. Nurse-visited women were more likely to be married from child age 2 through 18 (19.2% vs 14.8%, P = .04), and those with higher psychological resources had 4.64 fewer cumulative years rearing subsequent children after the birth of the first child (P = .03). Pregnancy planning was a significant mediator of program effects on public benefit costs. CONCLUSIONS: Through child age 18, the program reduced public-benefit costs, an effect more pronounced for mothers with higher psychological resources and mediated by subsequent pregnancy planning. There were no effects on maternal substance abuse and depression.

Prenatal and Infancy Nurse Home Visiting and 18-Year Outcomes of a Randomized Trial.

OBJECTIVES: Given earlier effects found in randomized clinical trials of the Nurse-Family Partnership, we examined whether this program would improve 18-year-old first-born youths' cognition, academic achievement, and behavior and whether effects on cognitive-related outcomes would be greater for youth born to mothers with limited psychological resources (LPR) and on arrests and convictions among females. METHODS: We enrolled 742 pregnant, low-income women with no previous live births and randomly assigned them to receive either free transportation for prenatal care plus child development screening and referral (control; n = 514) or prenatal and infant home nurse visit (NV) plus transportation and screening (n = 228). Assessments were completed on 629 18-year-old first-born offspring to evaluate these primary outcomes: (1) cognitive-related abilities (nonverbal intelligence, receptive language, and math achievement) and (2) behavioral health (internalizing behavioral problems, substance use and abuse, sexually transmitted infections, HIV risk, arrests, convictions, and gang membership). RESULTS: Compared with control-group counterparts, NV youth born to mothers with LPR had better receptive language (effect size = 0.24; 95% confidence interval [CI]: 0.00 to 0.47; P = .05), math achievement (effect size = 0.38; 95% CI: 0.14 to 0.61; P = .002), and a number of secondary cognitive-related outcomes. NV females, as a trend, had fewer convictions (incidence ratio = 0.47; 95% CI: 0.20 to 1.11; P = .08). There were no intervention effects on other behaviors. CONCLUSIONS: The program improved the cognitive-related skills of 18-year-olds born to mothers with LPR and, as a trend, reduced female convictions but produced no other effects on youth behavioral health.

Cluster Randomized Controlled Trial of Intervention to Increase Participant Retention and Completed Home Visits in the Nurse-Family Partnership.

We conducted a cluster-based randomized controlled trial of an intervention designed to improve participant retention in community replication sites of the Nurse-Family Partnership (NFP). We registered 26 sites and randomized them into three groups: retention intervention (RI, N = 9), delayed RI (DRI, N = 6), or control (C, NFP as usual, N = 11). The RI consisted of training nurses to give more explicit control over the frequency of visits and content of the program to the parent participants. Two of the sites assigned to the RI, two assigned to the DRI, and two out of four nurses in one other site assigned to the DRI chose not to participate in the intervention. Primary analyses (intention to treat) contrasted changes in participant retention and completed visits (the primary outcomes) in the two intervention groups (RI and DRI) compared to control sites, focusing on differences in performance among baseline cohorts compared to cohorts enrolled during the first year during which the retention intervention was implemented. Compared to baseline, retention declined in the control sites over time but stayed the same in the RI and DRI sites (p value for interaction = 0.099). Compared to baseline, the number of completed home visits declined over time in the control sites but did not in the RI and DRI sites, producing a significant treatment difference in change in mean completed home visits over time (2.71 visits, SE = 1.164, p = 0.020). The intervention offset a decline over time in retention and completed home visits found in the control group during the time covered by this trial. Quantitative and qualitative evaluation of the intervention indicated that improvements are needed to promote its uptake.

Effect of home visiting by nurses on maternal and child mortality: results of a 2-decade follow-up of a randomized clinical trial.

IMPORTANCE: Mothers and children living in adverse contexts are at risk of premature death. OBJECTIVE: To determine the effect of prenatal and infant/toddler nurse home visiting on maternal and child mortality during a 2-decade period (1990-2011). DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was designed originally to assess the home visiting program's effect on pregnancy outcomes and maternal and child health through child age 2 years. The study was conducted in a public system of obstetric and pediatric care in Memphis, Tennessee. Participants included primarily African American women and their first live-born children living in highly disadvantaged urban neighborhoods, who were assigned to 1 of 4 treatment groups: treatment 1 (transportation for prenatal care [n = 166]), treatment 2 (transportation plus developmental screening for infants and toddlers [n = 514]), treatment 3 (transportation plus prenatal/postpartum home visiting [n = 230]), and treatment 4 (transportation, screening, and prenatal, postpartum, and infant/toddler home visiting [n = 228]). Treatments 1 and 3 were included originally to increase statistical power for testing pregnancy outcomes. For determining mortality, background information was available for all 1138 mothers assigned to all 4 treatments and all but 2 live-born children in treatments 2 and 4 (n = 704). Inclusion of children in treatments 1 and 3 was not possible because background information was missing on too many children. INTERVENTIONS: Nurses sought to improve the outcomes of pregnancy, children's health and development, and mothers' health and life-course with home visits beginning during pregnancy and continuing through child age 2 years. MAIN OUTCOMES AND MEASURES: All-cause mortality in mothers and preventable-cause mortality in children (sudden infant death syndrome, unintentional injury, and homicide) derived from the National Death Index. RESULTS: The mean (SE) 21-year maternal all-cause mortality rate was 3.7% (0.74%) in the combined control group (treatments 1 and 2), 0.4% (0.43%) in treatment 3, and 2.2% (0.97%) in treatment 4. The survival contrast of treatments 1 and 2 combined with treatment 3 was significant (P = .007); the contrast of treatments 1 and 2 combined with treatment 4 was not significant (P = .19), and the contrast of treatments 1 and 2 combined with treatments 3 and 4 combined was significant (post hoc P = .008). At child age 20 years, the preventable-cause child mortality rate was 1.6% (0.57%) in treatment 2 and 0.0% (SE not calculable) in treatment 4; the survival contrast was significant (P = .04). CONCLUSIONS AND RELEVANCE: Prenatal and infant/toddler home visitation by nurses is a promising means of reducing all-cause mortality among mothers and preventable-cause mortality in their first-born children living in highly disadvantaged settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00708695.

Effects of home visits by paraprofessionals and by nurses on children: follow-up of a randomized trial at ages 6 and 9 years.

IMPORTANCE: The Nurse-Family Partnership delivered by nurses has been found to produce long-term effects on maternal and child health in replicated randomized trials. A persistent question is whether paraprofessional home visitors might produce comparable effects. OBJECTIVE: To examine the impact of prenatal and infancy/toddler home visits by paraprofessionals and by nurses on child development at child ages 6 and 9 years. DESIGN, SETTING, AND PARTICIPANTS: Randomized trial in public and private care settings in Denver, Colorado, of 735 low-income women and their first-born children (85% of the mothers were unmarried; 47% were Hispanic, 35% were non-Hispanic white, 15% were African American, and 3% were American Indian/Asian). INTERVENTIONS: Home visits provided from pregnancy through child age 2 years delivered in one group by paraprofessionals and in the other by nurses. MAIN OUTCOMES AND MEASURES: Reports of children's internalizing, externalizing, and total emotional/behavioral problems, and tests of children's language, intelligence, attention, attention dysfunction, visual attention/task switching, working memory, and academic achievement. We hypothesized that program effects on cognitive-related outcomes would be more pronounced among children born to mothers with low psychological resources. We report paraprofessional-control and nurse-control differences with P < .10 given similar effects in a previous trial, earlier effects in this trial, and limited statistical power. RESULTS: There were no significant paraprofessional effects on emotional/behavioral problems, but paraprofessional-visited children born to mothers with low psychological resources compared with control group counterparts exhibited fewer errors in visual attention/task switching at age 9 years (effect size = -0.30, P = .08). There were no statistically significant paraprofessional effects on other primary outcomes. Nurse-visited children were less likely to be classified as having total emotional/behavioral problems at age 6 years (relative risk [RR] = 0.45, P = .08), internalizing problems at age 9 years (RR = 0.44, P = .08), and dysfunctional attention at age 9 years (RR = 0.34, P = .07). Nurse-visited children born to low-resource mothers compared with control-group counterparts had better receptive language averaged over ages 2, 4, and 6 years (effect size = 0.30, P = .01) and sustained attention averaged over ages 4, 6, and 9 years (effect size = 0.36, P = .006). There were no significant nurse effects on externalizing problems, intellectual functioning, and academic achievement. CONCLUSIONS AND RELEVANCE: Children born to low-resource mothers visited by paraprofessionals exhibited improvement in visual attention/task switching. Nurse-visited children showed improved behavioral functioning, and those born to low-resource mothers benefited in language and attention but did not improve in intellectual functioning and academic achievement. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438282 and NCT00438594.

Does severity of physical neglect moderate the impact of an efficacious preventive intervention for maltreated children in foster care?

Physically neglected youth are at increased risk of mental health problems, but there are few interventions that have demonstrated efficacy in reducing mental health symptoms for this vulnerable population. The Fostering Healthy Futures (FHF) program, which consists of mentoring and skills groups, was developed for preadolescent youth in foster care. In a published randomized controlled trial with 156 youth, FHF demonstrated positive impacts on mental health functioning. The current study sought to determine whether FHF might be particularly effective in ameliorating the impact of neglectful family environments. Because it was not possible to isolate a neglected-only subgroup, as most children with physical neglect histories had experienced other types of maltreatment, we tested the hypothesis that intervention effects would be stronger among children with more severe physical neglect. Findings did not support this hypothesis, however, as severity of physical neglect did not significantly moderate the impact of the intervention on psychosocial outcomes.

Relationship of blood pressure and other factors to serial retinal arteriolar diameter measurements over time: the beaver dam eye study.

OBJECTIVE: To describe the relationship of blood pressure (BP), antihypertensive medication use, and other factors to serial measurements of retinal arteriolar diameters over time in the Beaver Dam Eye Study. METHODS: Retinal arteriolar diameter was measured by computer-assisted methods and summarized as central retinal arteriolar equivalent (CRAE) in 4573 persons aged 43 to 99 years at 4 examinations (each separated by 5 years) during a 15-year period. Associations of CRAE with risk factors measured concurrently and 5 years previously were determined using multivariate analyses. RESULTS: While adjusting for image quality, refraction, and lens status, age (per 10 years: ß estimate, -0.73; P < .001), systolic BP (per 10 mm Hg: concurrent examination, -2.74; P < .001; previous examination, -1.75; P < .001), smoking status (smoker vs nonsmoker: concurrent examination, 4.29; P < .001; previous examination, 1.63; P = .004), body mass index (per category: concurrent examination, -0.51; P = .05; previous examination, -0.22; P = .44), and heavy alcohol consumption (drinking) (current vs past/never heavy drinker: concurrent examination, -2.54; P = .03; previous examination, -2.42; P = .02) were associated with CRAE. In the same model, there were significant interactions between concurrent and previous systolic BP (0.11; P = .003) and between concurrent and previous body mass index (0.12; P = .04). Use of calcium channel blockers at both the concurrent and past examination (vs neither examination, 1.59; P = .01), but not other classes of antihypertensive drugs, was associated with CRAE. CONCLUSIONS: Retinal arteriolar diameter is independently associated with past and current systolic BP, calcium channel blocker use, smoking status, body mass index, and heavy drinking during 5-year intervals. The relationships with CRAE are stronger for concurrent than for past measures of these variables.

Determinants of retinal venular diameter: the Beaver Dam Eye Study.

OBJECTIVE: To describe how retinal venular diameter changes over time for an individual and to examine differences in these changes among people with different risk profiles. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 4600 persons aged 43 to 86 years from the Beaver Dam Eye Study (BDES) who participated in at least 1 examination and had venular diameter measured in the right eye. METHODS: Data from 4 examinations during a 15-year period were analyzed. Retinal venular diameter was measured from photographs at each examination by computer-assisted methods and summarized as the central retinal venular equivalent (CRVE). Associations of risk factors with concurrent CRVE measurements and changes in CRVE over time were determined using multivariate analyses. MAIN OUTCOME MEASURES: Central retinal venular equivalent. RESULTS: The CRVE tended to narrow with age. Mean CRVE was approximately 5 µm smaller (225 vs. 230 µm) for the average 70-year-old compared with the average 50-year-old, and was approximately 13 µm smaller (217 vs. 230 µm) for the average 85-year-old compared with the average 50-year-old. Male sex (beta estimate [ß] = 5.24; 95% confidence interval [CI], 3.58-6.90), history of current cigarette smoking (ß = 9.38; 95% CI, 8.26-10.49), and higher white blood cell (WBC) count (per 1000/µL: ß = 0.95; 95% CI, 0.74-1.16) were independently associated with larger concurrent CRVE, whereas higher mean arterial blood pressure (per 5 mmHg: ß = -0.36; 95% CI, -0.50 to -0.23) and higher serum high-density lipoprotein (HDL) cholesterol (per 10 mg/dl: ß = 0.89; 95% CI, -1.15 to -0.63) were independently associated with smaller concurrent CRVE. History of cardiovascular disease (CVD) (ß = -0.16; 95% CI, -0.26 to -0.06) and presence of chronic kidney disease (CKD) (ß = -0.20; 95% CI, -0.34 to -0.05) were associated with a greater decrease in CRVE over time. CONCLUSIONS: These data show that retinal venular diameter tends to narrow with age; concurrent venular diameter is independently associated with sex, blood pressure, serum HDL cholesterol, WBC count, and history of current cigarette smoking; and change in CRVE is independently associated with a history of CVD and presence of CKD. The different independent effects of these interrelated factors on CRVE highlight the complex relationship between CRVE and systemic diseases and conditions and the difficulty in determining specific causes of change in CRVE over time. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

RCT of a mentoring and skills group program: placement and permanency outcomes for foster youth.

OBJECTIVE: To examine the impact of a mentoring and skills group intervention for preadolescent children in foster care on placement stability and permanence at 1-year postintervention. METHODS: A randomized controlled trial was conducted with 9- to 11-year-old children who were maltreated and placed in foster care (n = 54 control; n = 56 intervention). State child welfare records provided information on number of placement changes, placement in residential treatment, and case closure (ie, permanency). Rates of adoption and reunification were also examined. Analysis was by intention to treat. RESULTS: After controlling for baseline functioning and preintervention placement history, intervention youth were 71% less likely to be placed in residential treatment (odds ratio [OR] = 0.29, 95% confidence interval [CI] 0.09-0.98). There were no significant treatment differences in predicting placement changes or permanency for the total sample. Among a subsample of children living in nonrelative foster care at baseline, intervention youth had 44% fewer placement changes (incidence ratio = 0.56, 95% CI 0.34-0.93), were 82% less likely to be placed in a residential treatment center (OR = 0.18, 95% CI 0.03-0.96), and were 5 times more likely to have attained permanency at 1 year postintervention (OR = 5.14, 95% CI 1.55-17.07). More intervention youth had reunified 1-year postintervention [χ(2)(1, N = 78) = 3.99; P < .05], and the pattern of findings suggested that intervention youth had higher rates of adoption. A significant interaction [χ(2)(1, N = 110) = 5.43; P = .02] demonstrated that the intervention attenuated the impact of baseline behavior problems on placement changes. CONCLUSIONS: The findings suggest that participation in a 9-month mentoring and skills group intervention leads to greater placement stability and permanence, especially for children in nonrelative foster care.

Enduring effects of prenatal and infancy home visiting by nurses on maternal life course and government spending: follow-up of a randomized trial among children at age 12 years.

OBJECTIVE: To test, among an urban primarily African American sample, the effects of prenatal and infancy home visiting by nurses on mothers' fertility, partner relationships, and economic self-sufficiency and on government spending through age 12 years of their firstborn child. DESIGN: Randomized controlled trial. SETTING: Public system of obstetric and pediatric care in Memphis, Tennessee. PARTICIPANTS: A total of 594 urban primarily African American economically disadvantaged mothers (among 743 who registered during pregnancy). Intervention Prenatal and infancy home visiting by nurses. MAIN OUTCOME MEASURES: Mothers' cohabitation with and marriage to the child's biological father, intimate partner violence, duration (stability) of partner relationships, role impairment due to alcohol and other drug use, use and cost of welfare benefits, arrests, mastery, child foster care placements, and cumulative subsequent births. RESULTS: By the time the firstborn child was 12 years old, nurse-visited mothers compared with control subjects reported less role impairment owing to alcohol and other drug use (0.0% vs 2.5%, P = .04), longer partner relationships (59.58 vs 52.67 months, P = .02), and greater sense of mastery (101.04 vs 99.60, P = .005). During this 12-year period, government spent less per year on food stamps, Medicaid, and Aid to Families with Dependent Children and Temporary Assistance for Needy Families for nurse-visited than control families ($8772 vs $9797, P = .02); this represents $12 300 in discounted savings compared with a program cost of $11 511, both expressed in 2006 US dollars. No statistically significant program effects were noted on mothers' marriage, partnership with the child's biological father, intimate partner violence, alcohol and other drug use, arrests, incarceration, psychological distress, or reports of child foster care placements. CONCLUSION: The program improved maternal life course and reduced government spending among children through age 12 years.

Enduring effects of prenatal and infancy home visiting by nurses on children: follow-up of a randomized trial among children at age 12 years.

OBJECTIVE: To test the effect of prenatal and infancy home visits by nurses on 12-year-old, firstborn children's use of substances, behavioral adjustment, and academic achievement. DESIGN: Randomized controlled trial. SETTING: Public system of obstetric and pediatric care in Memphis, Tennessee. PARTICIPANTS: We studied 12-year-old, firstborn children (n = 613) of primarily African American, economically disadvantaged women (743 randomized during pregnancy). INTERVENTION: Program of prenatal and infancy home visits by nurses. OUTCOME MEASURES: Use of cigarettes, alcohol, and marijuana; internalizing, externalizing, and total behavioral problems; and academic achievement. RESULTS: By the time the firstborn child was 12 years of age, those visited by nurses, compared with those in the control group, reported fewer days of having used cigarettes, alcohol, and marijuana during the 30-day period before the 12-year interview (0.03 vs 0.18, P = .02) and were less likely to report having internalizing disorders that met the borderline or clinical threshold (22.1% vs 30.9%, P = .04). Nurse-visited children born to mothers with low psychological resources, compared with their control group counterparts, scored higher on the Peabody Individual Achievement Tests in reading and math (88.78 vs 85.70, P = .009) and, during their first 6 years of education, scored higher on group-administered standardized tests of math and reading achievement (40.52 vs 34.85, P = .02). No statistically significant program effects were found on children's externalizing or total behavioral problems. CONCLUSIONS: Through age 12, the program reduced children's use of substances and internalizing mental health problems and improved the academic achievement of children born to mothers with low psychological resources.

Emphysema, airflow limitation, and early age-related macular degeneration.

OBJECTIVE: To describe the associations of lung function and emphysema, measured with spirometry and computed tomography (CT), with early age-related macular degeneration (AMD) in a sample of white, black, Hispanic, and Chinese subjects. METHODS: Three thousand three hundred ninety-nine persons aged 45 to 84 years residing in 6 US communities participated in a period cross-sectional study. Age-related macular degeneration was measured from digital retinal photographs at the second Multi-Ethnic Study of Atherosclerosis (MESA) examination. Forced expiratory volume in 1 second (FEV(1)) and FEV(1) to forced vital capacity (FVC) ratio were measured at the third or fourth MESA examination. Percent emphysema was measured from cardiac CT scans at baseline. Apical and basilar lung segments were defined as the cephalad or caudal regions of the lung on the cardiac CT scan. Logistic regression models were used to examine the association of lung function and structure with AMD, controlling for age, sex, and other factors. RESULTS: The prevalence of early AMD was 3.7%. Early AMD was not associated with FEV(1) (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.58-1.15; P = .25), FEV(1):FVC ratio (OR, 0.92; 95% CI, 0.76-1.12; P = .43), percent emphysema (OR, 1.13; 95% CI, 0.91-1.40; P = .26), and apical-basilar difference in percent emphysema (OR, 1.14; 95% CI, 0.95-1.37; P = .17). Associations were stronger in smokers. Apical-basilar difference in percent emphysema was significantly associated with early AMD among those who ever smoked (OR, 1.28; 95% CI, 1.02-1.60; P = .03). Associations were not modified by race/ethnicity. CONCLUSIONS: Lung function and emphysema on CT scan were not cross-sectionally associated with AMD; this might be explained by the relatively low smoking exposure in this cohort.

Stability of 35-mm scanners as used in ophthalmologic research.

BACKGROUND AND OBJECTIVE: To assess the consistency of digitization of 35-mm slides as practiced in ophthalmologic research and estimate the impact of variation on semi-automated retinal vessel width measurements. PATIENTS AND METHODS: A single retina slide was repeatedly digitized under various conditions on three scanner models. Average color levels were extracted from the resulting images, from which vessel widths were graded. The color channel level variations and possible correlation with width were analyzed. RESULTS: The Nikon 5000 scanner (Nikon Corp., Tokyo, Japan) had average coefficients of variation of 0.4, 2.3, and 0.5 for the red, green, and blue channel levels across all runs. The P values of the correlation between the red, green, and blue color channel levels and the width of the large retinal arteriole were .89, .27, and .58, respectively. CONCLUSION: The results suggest that the tested scanners digitize the 35-mm slides in a reliable manner without biasing the retinal vessel measurements.

The relation of markers of inflammation and endothelial dysfunction to the prevalence and progression of diabetic retinopathy: Wisconsin epidemiologic study of diabetic retinopathy.

OBJECTIVE: To determine the relation of glycemia, blood pressure, and serum total cholesterol level as systemic markers of inflammation and endothelial dysfunction to the prevalence and incidence of diabetic retinal outcomes in persons with long-duration type 1 diabetes mellitus. METHODS: Longitudinal population-based study of persons with type 1 diabetes mellitus who received care for their diabetes in south central Wisconsin from July 1, 1979, to June 30, 1980. Data for this investigation were obtained from the 1990-1992 through the 2005-2007 follow-up examinations. Main outcome measures included the severity of diabetic retinopathy (DR) and macular edema (ME). RESULTS: In the 1990-1992 prevalence data, soluble vascular cell adhesion molecule, tumor necrosis factor, and homocysteine levels were associated with increased odds of more severe DR (odds ratios [highest vs lowest quartile], 3.95 [95% confidence interval, 1.66-9.39], 5.46 [2.38-12.52], and 7.46 [2.91-19.16], respectively) in those with kidney disease while controlling for relevant confounders. Similar odds were found for proliferative DR. Only total homocysteine level was associated with increased odds of ME (3.80 [95% confidence interval, 1.91-7.54]), irrespective of kidney disease. None of the markers were associated with incidence of proliferative DR, ME, or progression of DR 15 years later. CONCLUSIONS: A limited number of markers are associated with increased odds of prevalent retinal outcomes in persons with type 1 diabetes mellitus and kidney disease. Only homocysteine level is associated with ME in those with and without kidney disease. In the absence of kidney disease, the markers do not add to the more conventional descriptors and predictors of DR in persons with type 1 diabetes mellitus. This may reflect the close association of DR and kidney disease in diabetic persons.

Changes in visual impairment prevalence by period of diagnosis of diabetes: the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

OBJECTIVE: To examine relationships of period of diagnosis of type 1 diabetes mellitus (T1DM) to the prevalence of visual impairment (VI). DESIGN: Population-based longitudinal study. PARTICIPANTS: Nine hundred fifty-five persons (3719 participant visits) 4 to 80 years of age at baseline who lived in an 11-county area in southern Wisconsin who were diagnosed with T1DM before 30 years of age contributed to the prevalence of VI. METHODS: Five eye examination visits occurred in the following periods: 1980 through 1982, 1984 through 1986, 1990 through 1992, 1995 through 1996, and 2005 through 2007. Age of diagnosis of T1DM was grouped as before 1960, 1960 through 1969, 1970 through 1974, and 1975 through 1979. Best-corrected visual acuity (VA) using a modification of the Early Treatment Diabetic Retinopathy protocol was measured. MAIN OUTCOME MEASURES: Visual impairment was defined as best-corrected VA in the better eye of 20/40 or worse. RESULTS: While controlling for duration of T1DM, there was a lower prevalence of VI for more recent periods of diagnosis of diabetes (odds ratio per category, 0.91; 95% confidence interval, 0.88-0.93; P<0.001). This remained while controlling for glycosylated hemoglobin, blood pressure, and other related factors. CONCLUSIONS: More recently diagnosed T1DM was associated with a lower prevalence of VI. This is likely because of the diminishing incidence of proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME) resulting from better glycemic control and more timely interventions with photocoagulation for CSME and PDR in those with more recently diagnosed T1DM.

Serum cystatin C level, kidney disease markers, and incidence of age-related macular degeneration: the Beaver Dam Eye Study.

OBJECTIVE: To examine the associations of the serum cystatin C level and chronic kidney disease with the incidence of age-related macular degeneration (AMD) over 15 years. METHODS: In this population-based cohort study of 4926 individuals aged 43 to 86 years at baseline, 3779 participated in 1 or more follow-up examinations. Age-related macular degeneration was determined by grading photographs of the macula. Individuals were defined as having mild or moderate to severe chronic kidney disease based on a value of more than 45 mL/min/1.73 m(2) to 60 mL/min/1.73 m(2) or less and 45 mL/min/1.73 m(2) or less, respectively, according to the Modification of Diet in Renal Disease Study equation. RESULTS: While controlling for age and other risk factors, the level of serum cystatin C at baseline was associated with the incidence of early AMD (odds ratio per log standard deviation [95% confidence interval], 1.16 [1.01-1.35]) and exudative AMD (1.42 [1.03-1.96]) but not geographic atrophy (0.89 [0.56-1.41]) or progression of AMD (1.02 [0.88-1.18]). Mild chronic kidney disease was associated with the 15-year cumulative incidence of early AMD (odds ratio per log standard deviation, 1.36 [95% confidence interval, 1.00-1.86]) but not the incidence of other AMD end points. CONCLUSION: There is a relationship between the level of serum cystatin C and chronic kidney disease with the incidence of AMD. The underlying biological processes remain to be determined.

The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1 diabetes.

OBJECTIVE: To examine the 25-year cumulative incidence of macular edema (ME) and its relation to various risk factors. DESIGN: Population-based study. PARTICIPANTS: A total of 955 insulin-taking persons living in an 11-county area in southern Wisconsin with type 1 diabetes diagnosed before age 30 years who participated in baseline examinations (1980-1982) and at least 1 of 4 follow-up (4-, 10-, 14-, and 25-year) examinations (n=891) or died before the first follow-up examination (n=64). METHODS: Stereoscopic color fundus photographs were graded using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme. Competing risk of death was included in statistical models. MAIN OUTCOME MEASURES: Incidence of ME and clinically significant ME (CSME). RESULTS: The 25-year cumulative incidence was 29% for ME and 17% for CSME. Annualized incidences of ME were 2.3%, 2.1%, 2.3%, and 0.9% in the first, second, third, and fourth follow-up periods of the study, respectively. In univariate analyses, the incidence of ME was associated with male sex, more severe diabetic retinopathy, higher glycosylated hemoglobin, proteinuria, higher systolic and diastolic blood pressure, and more pack-years of smoking. Multivariate analyses showed that the incidence of ME was related to higher baseline glycosylated hemoglobin (hazard ratio [HR] per 1% 1.17; 95% confidence interval [CI], 1.10-1.25; P<0.001) and higher systolic blood pressure (HR per 10 mmHg 1.15; 95% CI, 1.04-1.26; P=0.004) and marginally to proteinuria (HR 1.43; 95% CI, 0.99-2.08; P=0.06). CONCLUSIONS: These data show that relatively high 25-year cumulative rates of incidence of ME were related to glycemia and blood pressure. The lower risk of incident ME in the last period of the study may reflect recent improvement in care.

Biomarkers of aging and falling: the Beaver Dam eye study.

Falls are an important cause of morbidity in older adults and are an important source of health care spending. We hypothesize that falls are associated with systemic biomarkers of aging. The following functions, measured at the 1998-2000 and 2003-2005 examinations of the Beaver Dam eye study, were considered to be biomarkers of aging (frailties): poorer visual acuity, contrast sensitivity or discrepant vision between the eyes, inability to rise from a chair, slower gait time, poorer hand grip strength, and lower peak expiratory flow rate. We found that poorer values on biomarkers of aging (frailties) at the 1998-2000 examination were associated with two or more reported falls in the past year at the 2003-2005 examination (p<0.05 for all markers except peak expiratory flow rate). When the markers were combined as an index of biological aging (frailty), the index was significantly associated with falls after controlling for significant confounders (odds ratio per one step increase in the index: 1.33; 95% confidence interval=CI=1.13-1.57). We conclude that biomarkers of aging, including any of three measures of visual function, are associated with falls. Improvement in these functional measures may lead to decreased risk of falls.

Patient self-report of prior laser treatment reliably indicates presence of severe diabetic retinopathy.

PURPOSE: To determine whether patient self-report of prior laser treatment can be used as a reliable tool for assessing the presence of severe diabetic retinopathy. DESIGN: This was a retrospective study on two groups of diabetic subjects. METHODS: One hundred patients with diabetes were recruited from the general eye and retina clinics at the University of Chicago Hospitals. The patients were asked, "Have you ever received laser treatment for your diabetic eye disease (DED)?" A chart review was then conducted noting if the patient had received either focal laser treatment for diabetic macular edema or panretinal photocoagulation for proliferative diabetic retinopathy. Data from the Wisconsin Epidemiological Study of Diabetic Retinopathy (WESDR) were also analyzed. Participant responses to the question "Have you had laser photocoagulation treatment for your eyes?" were analyzed with documentation of photocoagulation scars determined by grading seven-standard field color fundus photographs. RESULTS: In the University of Chicago group, 96 of 100 (96%) of patients were accurate in reporting whether they had received previous laser treatment for DED (sensitivity 95.8%, specificity 96.1%, and positive predictive value 88.5%). In the WESDR analysis, 2,329 of 2,348 (99%) of participants were accurate in reporting whether they had prior laser treatment for DED (sensitivity 96.0%, specificity 99.5%, and positive predictive value 95.6%). CONCLUSIONS: The high sensitivity and specificity of our results validate the use of patient self-report as a useful tool in assessing past laser treatment for severe diabetic retinopathy. Patient self-report may be a useful surrogate to clinical examination or medical record review to determine the presence of severe diabetic retinopathy.