Background/Aims

Three types of open-angle glaucoma (OAG) – primary, pigmentary, and pseudoexfoliative – are frequently encountered. The aim of this study was to compare demographic, ocular, and systemic medical information collected on people with these three OAG types at diagnosis, and determine if the OAG type affected prognosis.

Methods

Information on 607 participants of the Collaborative Initial Glaucoma Treatment Study was accessed. Descriptive statistics characterized their demographic, ocular, and medical status at diagnosis. Comparisons were made using analysis of variance (ANOVA), and chi-square or Fisher exact tests. Multinomial, mixed, and logistic regression analyses were also performed.

Results

Relative to people with primary OAG, those with pigmentary OAG were younger, more likely to be white, less likely to have a family history of glaucoma, and were more myopic. Those with pseudoexfoliative OAG were older, more likely to be white, more likely to be female, less likely to have bilateral disease, and presented with higher IOP and better VA. The type of glaucoma was not associated with intraocular pressure or visual field progression during follow-up.

Conclusion

Characteristics of newly-diagnosed enrollees differed by the type of OAG. While some of these differences relate to the pathogenesis of OAG type, other differences are noteworthy for further evaluation within population-based samples of subjects with newly-diagnosed OAG.

Purpose

To compare drivers and non-drivers, and describe the specific concerns of drivers, among individuals with glaucoma.

Methods

607 newly-diagnosed glaucoma patients from 14 clinical centers of the Collaborative Initial Glaucoma Treatment Study were randomly assigned to initial medicine or surgery and followed every six months for < 5 years. Driving status (drivers vs. non-drivers) as well as patient-reported visual function was determined by the Visual Activities Questionnaire and the National Eye Institute Visual Function Questionnaire. Clinical evaluation included visual field mean deviation (MD) and visual acuity. Statistical comparisons were made using t, Chi-square, and exact tests, regression, and Rasch analyses.

Results

Drivers were more likely than non-drivers to be male, white, married, employed, and have more education, higher income, and fewer co-morbidities. Over 50% of drivers reported at least “some” difficulty performing tasks involving glare, whereas 22% reported at least “some” difficulty with tasks requiring peripheral vision. At 54 months, drivers with moderate/severe bilateral visual field loss (VFL) reported greater difficulty with night driving and tasks involving visual search and visual processing speed than drivers with less bilateral VFL (all p-values <0.05). While those who remained drivers over follow-up had better MD in both eyes than those who became non-drivers due to eyesight, a number of drivers had marked VFL.

Conclusion

Inquiring about specific difficulties with tasks related to glare, visual processing speed, visual search and peripheral vision in driving, especially among patients with substantial bilateral VF damage, will enable physicians to more effectively counsel patients regarding driving.

Objective

To determine if A2ALL (Adult-to-Adult Living Donor Liver Transplantation Cohort Study) findings are reflected in the national experience, and further define risk factors for patient mortality and graft loss in living donor liver transplantation (LDLT).

Background

A2ALL previously identified risk factors for mortality after LDLT, including early center experience, older recipient age and duration of cold ischemia.

Methods

LDLTs at the 9 A2ALL centers (n=702) and 67 non-A2ALL centers (n=1664) from 1/1/98 to 12/31/07 in the Scientific Registry of Transplant Recipients database were analyzed. Potential predictors of time to death or graft failure were tested using multivariable Cox regression, starting at time of transplant.

Results

There was no significant difference in overall mortality between A2ALL and non-A2ALL centers. Higher mortality hazard ratios (HR) were associated with donor age (HR=1.13/10 years, P<0.001), recipient age (HR=1.20/10 years, P<0.001), serum creatinine (HR=1.52 (log scale), P<0.001), diagnosis of HCC (HR=2.12, P<0.001) or HCV (HR=1.18, P=0.03), ICU (HR=2.52, P<0.001) or hospitalized (HR=1.62, P<0.001) vs home, and earlier center experience (LDLT case number ≤15, HR=1.61, P<0.001; HR=2.24, P<0.001 among A2ALL centers, HR=1.45, P=0.005 among non-A2ALL centers). Cold ischemia time (CIT) >4.5 hours was also associated with higher mortality (HR=1.79, P<0.001). Other than for center experience, comparisons of risk factor effects between A2ALL and non-A2ALL centers were not significant. Increased risk of graft failure in early experience was comparable in both groups.

Conclusions

Mortality risk factors were similar at A2ALL and non-A2ALL centers. Variables associated with graft loss were identified and showed similar trends, with some minor differences in degree of significance. These analyses demonstrate that the findings from the A2ALL consortium are relevant to other centers in the U.S. performing LDLT, and conclusions and recommendations from A2ALL may help guide clinical decision making.

Introduction

Information on long-term health among living liver donors is incomplete. Because changes in standard laboratory tests may reflect underlying health among donors, pre- and post- donation results were examined in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL).

Methods

A2ALL followed 487 living liver donors who donated at nine U.S. transplant centers between 1998 and 2009. Aminotransferase and alkaline phosphatase activities (AST, ALT, AP), bilirubin, INR, albumin, white blood cell count (WBC), hemoglobin, platelet count, ferritin, serum creatinine and BUN were measured at evaluation and post-donation: 1 week, 1 month, 3 months, 1 year and yearly thereafter. Repeated measures models were used to estimate median lab values at each time point and test for differences between values at evaluation (baseline) and post-donation time points.

Results

Platelet counts were significantly decreased at every time point compared to baseline, and at three years were 19% lower. Approximately 10% of donors had a platelet count ≤150 (×1000/mm3) at 2–3 years post-donation. Donors with a platelet count ≤150 (×1000/mm3) at one year had had significantly lower mean platelet counts (189±32) vs. the remainder of the cohort (267±56, p<0.0001) at evaluation. Statistically significant differences from evaluation were noted for AST, AP, INR and albumin through the first year, although most measurements were in the normal range. Median values for WBC, hemoglobin, ferritin, albumin, serum creatinine, BUN, and INR were not substantially outside the normal range at any time point.

Conclusions

After three months, most laboratory values return to normal among right hepatic lobe liver donors, with slower return to baseline levels for AST, AP, INR and albumin. Persistently decreased platelet counts warrant further investigation.

Purpose

To evaluate factors associated with visual field (VF) progression, using all available follow-up through nine years after treatment initiation, in the Collaborative Initial Glaucoma Treatment Study (CIGTS).

Design

Longitudinal follow-up of participants enrolled in a randomized clinical trial.

Participants

607 newly diagnosed glaucoma patients.

Methods

In a randomized clinical trial, 607 subjects with newly diagnosed open-angle glaucoma were initially treated with either medication or trabeculectomy. After treatment initiation and early follow-up, subjects were evaluated clinically at 6-month intervals. Study participants in both arms of the CIGTS were treated aggressively in an effort to reduce intraocular pressure (IOP) to a level at or below a predetermined, eye-specific target pressure. VF progression was analyzed using repeated measures models.

Main outcome measures

VF progression, measured by Humphrey 24-2 full threshold testing and assessed by the change in the mean deviation (MD), and an indicator of substantial worsening of the VF (MD decrease of ≥3 dB from baseline), assessed at each follow-up visit.

Results

Follow-up indicates minimal change from baseline in each initial treatment group’s average MD. However, at the eight year follow-up examination, substantial worsening (≥3 dB) of MD from baseline was found in 21.3% and 25.5% of the initial surgery and initial medicine groups, respectively. The effect of initial treatment on subsequent VF loss was modified by time (P<0.0001), baseline MD (P=0.03), and diabetes (P=0.01). Initial surgery led to less VF progression than initial medicine in subjects with advanced VF loss at baseline, whereas subjects with diabetes had more VF loss over time if treated initially with surgery.

Conclusions

The CIGTS intervention protocol led to a lowering of IOP that persisted over time in both treatment groups. Progression in VF loss was seen in a subset increasing to over 20% of the subjects. Our findings regarding initial surgery being beneficial for subjects who present at diagnosis with more advanced VF loss, but detrimental for patients with diabetes, are noteworthy and warrant independent confirmation.

Background and Aims

More than 2000 adult-to-adult living donor liver transplants (LDLT) have been performed in the U.S., yet the potential benefit to liver transplant candidates of undergoing LDLT compared to waiting for deceased donor liver transplant (DDLT) is unknown. The aim of this study was to determine if there is a survival benefit of adult LDLT

Methods

Adults with chronic liver disease who had a potential living donor evaluated from 1/98 to 2/03 at nine university-based hospitals were analyzed. Starting at the time of a potential donor’s evaluation, we compared mortality after LDLT to mortality among those who remained on the waitlist or received DDLT. Median follow-up was 4.4 years. Comparisons were made by hazard ratios (HR) adjusted for LDLT candidate characteristics at the time of donor evaluation.

Results

Among 807 potential living donor recipients, 389 received LDLT, 249 received DDLT, 99 died without transplant, and 70 were awaiting transplant at last follow-up. Receipt of LDLT was associated with an adjusted mortality HR of 0.56 (95% confidence interval [CI] 0.42–0.74; P<0.001) relative to candidates who did not receive LDLT. As centers gained greater experience (> 20 LDLT), LDLT benefit was magnified, with a mortality HR of 0.35 (CI 0.23–0.53; P<0.001).

Conclusions

Adult LDLT was associated with lower mortality than the alternative of waiting for DDLT. This reduction in mortality was magnified as centers gained experience with living donor liver transplantation. This reduction in transplant candidate mortality must be balanced against the risks undertaken by the living donors themselves.

Purpose

To compare two vision-specific functional status measures to each other and to clinical parameters in the Collaborative Initial Glaucoma Treatment Study (CIGTS).

Methods

CIGTS participants completed the Visual Activities Questionnaire (VAQ) and the National Eye Institute-Visual Function Questionnaire (NEI-VFQ) and were tested for visual field (VF) and visual acuity (VA). 426 subjects contributed VAQ and NEI-VFQ scores at 54 months. Pearson correlations were used to assess associations.

Results

The VAQ subscales (range 0–100) that assessed light-dark adaptation (mean=66.1), glare disability (66.4), and acuity/spatial vision (67.7) indicated vision-related functions that CIGTS participants found most difficult. On the NEI-VFQ, subjects reported high levels of visual functioning, with mean ≥90 (out of 100) on the total score and in 9 of 12 subscales. General vision (mean=82.6) received the lowest subscale score. Two subscales common to both questionnaires were highly correlated: VA (r=0.68) and peripheral vision (r=0.77) (both p<.0001). Correlations between participants’ perceptions and clinical measures of visual function were in the expected direction, but weaker. Stronger associations were found between clinical measures and the NEI-VFQ than the VAQ. Better eye VF and worse eye VA had the highest number of significant correlations with subjects’ perceptions of their visual function. Increasing VF loss was associated with a significant decrease in the overall and peripheral vision subscale scores from both questionnaires, as well as several other subscales.

Conclusions

These findings will help researchers interested in assessing patients’ perceptions of their visual function make an informed selection when choosing between the VAQ and the NEI-VFQ.

Context

Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls that have toxic equivalency factors (TEFs) were measured in serum of 946 subjects in five Michigan counties. The study was motivated by concerns about human exposure to dioxin-contaminated sediments in the Tittabawassee River (TR). Most of the toxic equivalency in TR sediments is from two furan congeners, 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-pentaCDF).

Case presentation

The individual with the highest adjusted (for age, age squared, and body mass index) serum level of 2,3,4,7,8-pentaCDF in the study (42.5 ppt) reported a unique history of raising cattle and vegetables in the floodplain of the TR. Interviews and serum samples were obtained from the index case and 15 other people who ate beef and vegetables raised by the index case. 2,3,4,7,8-pentaCDF in beef lipid was estimated to have been more than three orders of magnitude greater than background (1,780 vs. 1.1 ppt). The mean, median, and 95th percentile for serum 2,3,4,7,8-pentaCDF in the study control population were 6.0, 5.4, and 13.0 ppt, respectively, and were 9.9, 8.4, and 20.5 ppt among beef and vegetable consumers, respectively. Back extrapolation for the index case suggests that his increase in serum concentration of 2,3,4,7,8-pentaCDF above background may have been as high as 146 ppt.

Discussion

Consumption of beef and/or vegetables raised on dioxin-contaminated soil may be an important completed pathway of exposure.

Relevance to public health practice

Animals and crops should not be raised for human consumption in areas contaminated with dioxins.

Purpose

To evaluate, both at initial glaucoma diagnosis and during treatment, the role of demographic and clinical factors on intraocular pressure (IOP).

Design

Cohort study of patients enrolled in a randomized clinical trial.

Participants

607 patients with newly diagnosed, open-angle glaucoma (OAG) were enrolled at 14 U.S. centers.

Methods

After randomization to initial surgery or medications, patients were followed at six-month intervals. IOP was measured by Goldmann applanation tonometry. Predictive factors for IOP at baseline and during follow-up were analyzed using linear mixed models.

Main Outcome Measure

IOP at baseline and during follow-up.

Results

The mean baseline IOP was 27.5 mmHg (standard deviation, 5.6 mmHg). Predictive factors for higher baseline IOP included younger age (0.7 mmHg per 10 years), male sex (2.4 mmHg higher than females), pseudoexfoliative glaucoma (5.4 mmHg higher than primary OAG), and pupillary defect (2.2 mmHg higher than those without a defect). During nine years of follow-up, both surgery and medications dramatically reduced IOP from baseline levels, but the extent of IOP reduction was consistently greater in the surgery group. Over follow-up years 2–9, mean IOP was 15.0 vs. 17.2 mmHg for surgery vs. medicine, respectively. Predictive associations with higher IOP during follow-up included higher baseline IOP (P<0.0001), worse baseline visual field (mean deviation; P<0.0001), and lower level of education (P=0.0019). Treatment effect was modified by smoking status: non-smokers treated surgically had lower IOP than smokers treated surgically (14.6 vs. 16.7 mmHg, respectively; P=0.0013). Clinical center effects were significant (P<0.0001) in both the baseline and follow-up models.

Conclusions

In this large cohort of newly diagnosed glaucoma patients, predictors of pre-treatment IOP and IOP measurements over nine years of follow-up were identified. Our findings lend credence to the postulate that sociodemographic, economic, compliance, or other environmental influences play a role in IOP control during treatment.

Background

We conducted a population-based human exposure study in response to concerns among the population of Midland and Saginaw counties, Michigan, that discharges by the Dow Chemical Company of dioxin-like compounds into the nearby river and air had led to an increase in residents’ body burdens of polychlorinated dibenzofurans (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs), here collectively referred to as “dioxins.”

Objectives

We sought to identify factors that explained variation in serum dioxin concentrations among the residents of Midland and Saginaw counties. Exposures to dioxins in soil, river sediments, household dust, historic emissions, and contaminated fish and game were of primary interest.

Methods

We studied 946 people in four populations in the contaminated area and in a referent population, by interview and by collection of serum, household dust, and residential soil. Linear regression was used to identify factors associated with serum dioxins.

Results

Demographic factors explained a large proportion of variation in serum dioxin concentrations. Historic exposures before 1980, including living in the Midland/Saginaw area, hunting and fishing in the contaminated areas, and working at Dow, contributed to serum dioxin levels. Exposures since 1980 in Midland and Saginaw counties contributed little to serum dioxins.

Conclusions

This study provides valuable insights into the relationships between serum dioxins and environmental factors, age, sex, body mass index, smoking, and breast-feeding. These factors together explain a substantial proportion of the variation in serum dioxin concentrations in the general population. Historic exposures to environmental contamination appeared to be of greater importance than recent exposures for dioxins.

Background

The University of Michigan Dioxin Exposure Study was undertaken to address concerns that the discharge of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo furans (PCDFs) from the Dow Chemical Company in the Midland, Michigan, area had resulted in contamination of soils in the Tittabawassee River floodplain and the city of Midland, leading to an increase in residents’ body burdens of these compounds.

Objective

In this article we present descriptive statistics from the resident survey and sampling of human serum, household dust, and soil and compare them with other published values.

Methods

From a multistage random sample of populations in four areas of Midland and Saginaw counties and from a distant referent population, we interviewed 946 adults, who also donated blood for analysis of PCDDs, PCDFs, and polychlorinated biphenyls (PCBs). Samples of household dust and house perimeter soil were collected from consenting subjects who owned their property.

Results

All five study populations were comparable in age, race, sex, and length of residence in their current home. Regional differences existed in employment history, personal contact with contaminated soils, and consumption of fish and game from contaminated areas. Median soil concentrations were significantly increased around homes in the Tittabawassee River floodplain (11.4 ppt) and within the city of Midland (58.2 ppt) compared with the referent population (3.6 ppt). Median serum toxic equivalencies were significantly increased in people who lived in the floodplain (23.2 ppt) compared with the referent population (18.5 ppt).

Conclusions

Differences in serum dioxin concentrations among the populations were small but statistically significant. Regression modeling is needed to identify whether the serum concentrations of PCDDs, PCDFs, and PCBs are associated with contaminated soils, household dust, and other factors.

Background

The University of Michigan Dioxin Exposure Study (UMDES) was undertaken in response to concerns that the discharge of dioxin-like compounds from the Dow Chemical Company facilities in Midland, Michigan, resulted in contamination of soils in the Tittabawassee River floodplain and areas of the city of Midland, leading to an increase in residents’ body burdens of polychlorinated dibenzodioxins and polychlorinated dibenzofurans.

Objectives

The UMDES is a hypothesis-driven study designed to answer important questions about human exposure to dioxins in the environment of Midland, where the Dow Chemical Company has operated for > 100 years, and in neighboring Saginaw, Michigan. In addition, the UMDES includes a referent population from an area of Michigan in which there are no unusual sources of dioxin exposure and from which inferences regarding the general Michigan population can be derived. A central goal of the study is to determine which factors explain variation in serum dioxin levels and to quantify how much variation each factor explains.

Conclusions

In this article we describe the study design and methods for a large population-based study of dioxin contamination and its relationship to blood dioxin levels. The study collected questionnaire, blood, dust, and soil samples on 731 people. This study provides a foundation for understanding the exposure pathways by which dioxins in soils, sediments, fish and game, and homegrown produce lead to increased body burdens of these compounds.

Objective

In this study we reviewed the half-life data in the literature for the 29 dioxin, furan, and polychlorinated biphenyl congeners named in the World Health Organization toxic equivalency factor scheme, with the aim of providing a reference value for the half-life of each congener in the human body and a method of half-life estimation that accounts for an individual’s personal characteristics.

Data sources and extraction

We compared data from > 30 studies containing congener-specific elimination rates. Half-life data were extracted and compiled into a summary table. We then created a subset of these data based on defined exclusionary criteria.

Data synthesis

We defined values for each congener that approximate the half-life in an infant and in an adult. A linear interpolation of these values was used to examine the relationship between half-life and age, percent body fat, and absolute body fat. We developed predictive equations based on these relationships and adjustments for individual characteristics.

Conclusions

The half-life of dioxins in the body can be predicted using a linear relationship with age adjusted for body fat, smoking, and breast-feeding. Data suggest an alternative method based on a linear relationship between half-life and total body fat, but this approach requires further testing and validation with individual measurements.

A key component in any investigation of cause-effect relationships between point source pollution, such as an incinerator, and human health is the availability of measurements and/or accurate models of exposure at the same scale or geography as the health data. Geostatistics allows one to simulate the spatial distribution of pollutant concentrations over various spatial supports while incorporating both field data and predictions of deterministic dispersion models. This methodology was used in a companion paper to identify the census blocks that have a high probability of exceeding a given level of dioxin TEQ (Toxic Equivalents) around an incinerator in Midland, Michigan. This geostatistical model, along with population data, provided guidance for the collection of 51 new soil data, which permits the verification of the geostatistical predictions, and calibration of the model. Each new soil measurement was compared to the set of 100 TEQ values simulated at the closest grid node. The correlation between the measured concentration and the averaged simulated value is moderate (0.44), and the actual concentrations are clearly overestimated in the vicinity of the plant property line. Nevertheless, probability intervals computed from simulated TEQ values provide an accurate model of uncertainty: the proportion of observations that fall within these intervals exceeds what is expected from the model. Simulation-based probability intervals are also narrower than the intervals derived from the global histogram of the data, which demonstrates the greater precision of the geostatistical approach. Lognormal ordinary kriging provided fairly similar estimation results for the small and well-sampled area used in this validation study, however, the model of uncertainty was not always accurate. The regression analysis and geostatistical simulation were then conducted using the combined set of 53 original and 51 new soil samples, leading to an updated model for the spatial distribution of TEQ in Midland, MI.

Background

Death of an infant in utero or at birth has always been a devastating experience for the mother and of concern in clinical practice. Infant mortality remains a challenge in the care of pregnant women worldwide, but particularly for developing countries and the need to understand contributory factors is crucial for addressing appropriate perinatal health.

Methods

Using information available in obstetric records for all deliveries (17,072 births) at Harare Maternity Hospital, Zimbabwe, we conducted a cross-sectional retrospective analysis of a one-year data, (1997–1998) to assess demographic and obstetric risk factors for stillbirth and early neonatal death. We estimated risk of stillbirth and early neonatal death for each potential risk factor.

Results

The annual frequency of stillbirth was 56 per 1,000 total births. Women delivering stillbirths and early neonatal deaths were less likely to receive prenatal care (adjusted relative risk [RR] = 2.54; 95% confidence intervals [CI] 2.19–2.94 and RR = 2.52; 95% CI 1.63–3.91), which for combined stillbirths and early neonatal deaths increased with increasing gestational age (Hazard Ratio [HR] = 3.98, HR = 7.49 at 28 and 40 weeks of gestation, respectively). Rural residence was associated with risk of infant dying in utero, (RR = 1.33; 95% CI 1.12–1.59), and the risk of death increased with increasing gestational age (HR = 1.04, HR = 1.69, at 28 and 40 weeks of gestation, respectively). Older maternal age was associated with risk of death (HR = 1.50; 95% CI 1.21–1.84). Stillbirths were less likely to be delivered by Cesarean section (RR = 0.64; 95% CI 0.51–0.79), but more likely to be delivered as breech (RR = 4.65; 95% CI 3.88–5.57, as were early neonatal deaths (RR = 3.38; 95% CI 1.64–6.96).

Conclusion

The frequency of stillbirth, especially macerated, is high, 27 per 1000 total births. Early prenatal care could help reduce perinatal death linking the woman to the health care system, increasing the probability that she would seek timely emergency care that would reduce the likelihood of death of her infant in utero. Improved quality of obstetric care during labor and delivery may help reduce the number of fresh stillbirths and early neonatal deaths.