A process evaluation of the childhood lead poisoning prevention program in Houston, Texas, 1992--1995

A process evaluation of the Houston Childhood Lead Poisoning Prevention Program, 1992-1995, was conducted. The Program's goal is to reduce lead poisoning prevalence. The study proposed to determine to what extent the Program was implemented as planned by measuring how well Program services were actually: (1) received by the intended target population; (2) delivered to children with elevated blood lead levels; (3) delivered in compliance with the Centers for Disease Control and Prevention and Program guidelines and timetables; and (4) able to reduce lead poisoning prevalence among those rescreened. Utilizing a program monitoring design, the Program's pre-collected computer records were reviewed. The study sample consisted of 820 children whose blood lead levels were above 15 micrograms per deciLiter, representing approximately 2.9% of the 28,406 screened over this period. Three blood lead levels from each participant were examined: the initial elevated result; the confirmatory result; and the next rescreen result, after the elevated confirmatory level. Results showed that the Program screened approximately 18% (28,406 of 161,569) of Houston's children under age 6 years for lead poisoning. Based on Chi-square tests of significance, results also showed that lead-poisoned participants were more likely to be younger than 3 years, male and Hispanic, compared to those not lead poisoned. The age, gender and ethnic differences observed were statistically significant (p =.01, p =.00, p =.00). Four of the six Program services: medical evaluations, rescreening, environmental inspections and confirmation, had satisfactory delivery completion rates of 71%-98%. Delivery timetable compliance rates for three of the six services examined: outreach contacts, home visits and environmental inspections were below 32%. However, dangerously elevated blood lead levels fell and lead poisoning prevalence dropped from 3.3% at initial screening to 1.2% among those rescreened, after intervention. From a public health perspective, reductions in lead poisoning prevalence are very meaningful. Based on these findings, the following are recommendations for future research: (1) integrate Program database files by utilizing a computer database management program; (2) target services at Hispanic male children under age 3 years living in the highest risk neighborhoods; (3) increase resources to: improve tracking and documentation of service delivery and provide more non-medical case management and environmental services; and (4) share the evaluation methodology/findings with the Centers for Disease Control and Prevention administrators; the implications may be relevant to other program managers conducting such assessments. ^

The diagnostic value of a 12-lead electrocardiogram in patients with cardiac tamponade due to a malignant pericardial effusion

Background. Cardiac tamponade can occur when a large amount of fluid, gas, singly or in combination, accumulating within the pericardium, compresses the heart causing circulatory compromise. Although previous investigators have found the 12-lead ECG to have a poor predictive value in diagnosing cardiac tamponade, very few studies have evaluated it as a follow up tool for ruling in or ruling out tamponade in patients with previously diagnosed malignant pericardial effusions. ^ Methods. 127 patients with malignant pericardial effusions at the MD Anderson Cancer Center were included in this retrospective study. While 83 of these patients had a cardiac tamponade diagnosed by echocardiographic criteria (Gold standard), 44 did not. We computed the sensitivity (Se), specificity (Sp), positive (PPV) and negative predictive values (NPV) for individual and combinations of ECG abnormalities. Individual ECG abnormalities were also entered singly into a univariate logistic regression model to predict tamponade. ^ Results. For patients with effusions of all sizes, electrical alternans had a Se, Sp, PPV and NPV of 22.61%, 97.61%, 95% and 39.25% respectively. These parameters for low voltage complexes were 55.95%, 74.44%, 81.03%, 46.37% respectively. The presence of all three ECG abnormalities had a Se = 8.33%, Sp = 100%, PPV = 100% and NPV = 35.83% while the presence of at least one of the three ECG abnormalities had a Se = 89.28%, Sp = 46.51%, PPV = 76.53%, NPV = 68.96%. For patients with effusions of all sizes electrical alternans had an OR of 12.28 (1.58–95.17, p = 0.016), while the presence of at least one ECG abnormality had an OR of 7.25 (2.9–18.1, p = 0.000) in predicting tamponade. ^ Conclusions. Although individual ECG abnormalities had low sensitivities, specificities, NPVs and PPVs with the exception of electrical alternans, the presence of at least one of the three ECG abnormalities had a high sensitivity in diagnosing cardiac tamponade. This could point to its potential use as a screening test with a correspondingly high NPV to rule out a diagnosis of tamponade in patients with malignant pericardial effusions. This could save expensive echocardiographic assessments in patients with previously diagnosed pericardial effusions. ^

GMZ27 is a new organic arsenic derivative with anti-leukemic activity, via the induction of reactive oxygen species through NADPH oxidase and mitochondrial pathway that lead to leukemia cell apoptosis

Arsenic trioxide (ATO) is an inorganic arsenic derivative that is very effective against relapsed acute promyelocytic leukemia. It is being investigated as therapy for other cancers, but the risk/benefit ratio is questionable due to significant side effects. In contrast, organic arsenic derivatives (OAD) are known to be much less toxic than ATO. Based on high activity, we selected GMZ27 (dipropil-s-glycerol arsenic) for further study and have confirmed its potent activity against human acute leukemia cell lines. This anti-leukemic activity is significantly higher than that of ATO. Both in vivo and in vitro tests have shown that GMZ27 is significantly less toxic to normal bone marrow mononuclear cells and normal mice. Therefore, further study of the biological activity of GMZ27 was undertaken. ^ GMZ27, in contrast to ATO, can only marginally induce maturation of leukemic cells. GMZ27 has no effect on cell cycle. The anti-leukemic activity of GMZ27 against acute myeolocytic leukemia cells is not dependent upon degradation of PML-RARα fusion protein. GMZ27 causes dissipation of mitochondrial transmembrane potential, cleavage of caspase 9, caspase 3 activation. Further studies indicated that GMZ27 induces intracellular reactive oxygen species (ROS) production, and modification of intracellular ROS levels had profound effect on its potential to inhibit proliferation of leukemic cells. Therefore ROS production plays a major role in the anti-leukemic activity of GMZ27. ^ To identify how GMZ27 induces ROS, our studies focused on mitochondria and NADPH oxidase. The results indicated that the source of ROS generation induced by GMZ27 is dose dependent. At the low dose (0.3 uM) GMZ27 induces NADPH oxidase activity that leads to late ROS production, while at the high dose (2.0 uM) mitochondria function is disrupted and early ROS production is induced leading to dramatic cell apoptosis. Therefore, late, ROS production can be detected in mitochondria are depleted Rho-0 cells. Our work not only delineates a major biologic pathway for the anti-leukemic activity of GMZ27, but also discusses possible ways of enhancing the effect by the co-application of NADPH oxidase activator. Further study of this interaction may lead to achieving better therapeutic index.^

Secondary data analysis of lead screening compliance in high-risk children

Introduction. Despite the ban of lead-containing gasoline and paint, childhood lead poisoning remains a public health issue. Furthermore, a Medicaid-eligible child is 8 times more likely to have an elevated blood lead level (EBLL) than a non-Medicaid child, which is the primary reason for the early detection lead screening mandate for ages 12 and 24 months among the Medicaid population. Based on field observations, there was evidence that suggested a screening compliance issue. Objective. The purpose of this study was to analyze blood lead screening compliance in previously lead poisoned Medicaid children and test for an association between timely lead screening and timely childhood immunizations. The mean months between follow-up tests were also examined for a significant difference between the non-compliant and compliant lead screened children. Methods. Access to the surveillance data of all childhood lead poisoned cases in Bexar County was granted by the San Antonio Metropolitan Health District. A database was constructed and analyzed using descriptive statistics, logistic regression methods and non-parametric tests. Lead screening at 12 months of age was analyzed separately from lead screening at 24 months. The small portion of the population who were also related were included in one analysis and removed from a second analysis to check for significance. Gender, ethnicity, age of home, and having a sibling with an EBLL were ruled out as confounders for the association tests but ethnicity and age of home were adjusted in the nonparametric tests. Results. There was a strong significant association between lead screening compliance at 12 months and childhood immunization compliance, with or without including related children (p<0.00). However, there was no significant association between the two variables at the age of 24 months. Furthermore, there was no significant difference between the median of the mean months of follow-up blood tests among the non-compliant and compliant lead screened population for at the 12 month screening group but there was a significant difference at the 24 month screening group (p<0.01). Discussion. Descriptive statistics showed that 61% and 56% of the previously lead poisoned Medicaid population did not receive their 12 and 24 month mandated lead screening on time, respectively. This suggests that their elevated blood lead level may have been diagnosed earlier in their childhood. Furthermore, a child who is compliant with their lead screening at 12 months of age is 2.36 times more likely to also receive their childhood immunizations on time compared to a child who was not compliant with their 12 month screening. Even though there was no statistical significant association found for the 24 month group, the public health significance of a screening compliance issue is no less important. The Texas Medicaid program needs to enforce lead screening compliance because it is evident that there has been no monitoring system in place. Further recommendations include a need for an increased focus on parental education and the importance of taking their children for wellness exams on time.^

Impact of environmental regulations on lead concentrations in Texas ambient air and water: 1970--1990

In the last two decades, the significance of lead has been addressed in a number of environmental regulations at the national and state levels. This project investigated the environmental regulations (Clean Air Act and Amendments, 1970-1990 and Clean Water Act of 1977) and their cumulative effects on lead in ambient air and water in the state of Texas. For this purpose, historical records from the Texas Water Development Board, Texas Natural Resources Conservation Commission, and the United States Geological Survey have been assembled and analyzed for temporal and spatial trends. These trends might correspond to the phase out of lead in gasoline and other regulations.^ This study concluded that there is a significant correlation (p $\leq$.001) between environmental regulations of lead in gasoline and the concentration of lead in ambient air. Lead concentrations in ambient air have been reduced by over 90 percent in the past twenty years. An overall significant difference (p $\leq$.001) was found in mean (94, 15 respectively) lead concentrations in surface water between two time periods, one at the beginning of the twenty year period and one at the end of the study period. There has been an overall reduction of lead concentrations in surface water in Texas of approximately 84 percent. However, this reduction cannot be statistically associated with any one regulation. Groundwater data could not be analyzed for lead concentrations because of limitations of reporting data as "less than". Approximately two percent of the groundwater data was analyzed by Oneway ANOVA and no significant difference was found between the means (18, 19 respectively) of two time periods, 1977-1979 and 1988-1990. This data is consistent with the regulations having a contributory affect on declining concentrations, but other factors cannot be ruled out as having added to these declines. This study can also serve as a starting point for a more in-depth study of environmental regulations and their impact on the environment. ^

APPLICATION OF THE BRAINSTEM EVOKED RESPONSE (BER) TO NEUROTOXICITY EVALUATION OF THE AUDITORY SYSTEM: ASSESSMENT OF INORGANIC LEAD-INDUCED OTOTOXICITY

An experimental procedure was developed using the Brainstem Evoked Response (BER) electrophysiological technique to assess the effect of neurotoxic substances on the auditory system. The procedure utilizes Sprague-Dawley albino rats who have had dural electrodes implanted in their skulls, allowing neuroelectric evoked potentials to be recorded from their brainstems. Latency and amplitude parameters derived from the evoked potentials help assess the neuroanatomical integrity of the auditory pathway in the brainstem. Moreover, since frequency-specific auditory stimuli are used to evoke the neural responses, additional audiometric information is obtainable. An investigation on non-exposed control animals shows the BER threshold curve obtained by tests at various frequencies very closely approximates that obtained by behavioral audibility tests. Thus, the BER appears to be a valid measure of both functional and neuroanatomical integrity of the afferent auditory neural pathway.^ To determine the usefulness of the BER technique in neurobehavioral toxicology research, a known neurotoxic agent, Pb, was studied. Female Sprague-Dawley rats were dosed for 45 days with low levels of Pb acetate in their drinking water, after which BER recordings were obtained. The Pb dosages were determined from the findings of an earlier pilot study. One group of 6 rats received normal tap water, one group of 7 rats received a solution of 0.1% Pb, and another group of 7 rats received a solution of 0.2% Pb. After 45 days, the three groups exhibited blood Pb levels of 4.5 (+OR-) 0.43 (mu)g/100 ml, 37.8 (+OR-) 4.8 (mu)g/100 ml and 47.3 (+OR-) 2.7 (mu)g/100 ml, respectively.^ The results of the BER recording indicated evoked response waveform latency abnormalities in both the Pb-treated groups when midrange frequency (8 kHz to 32 kHz) stimuli were used. For the most part, waveform amplitudes did not vary significantly from control values. BER recordings obtained after a 30-day recovery period indicated the effects seen in the 0.1% Pb group had disappeared. However, those anomalies exhibited by the 0.2% Pb group either remained or increased in number. This outcome indicates a longer lasting or possibly irreversible effect on the auditory system from the higher dose of Pb. The auditory pathway effect appears to be in the periphery, at the level of the cochlea or the auditory (VIII) nerve. The results of this research indicate the BER technique is a valuable and sensitive indicator of low-level toxic effects on the auditory system.^

Attention-deficit hyperactivity disorder symptoms and lead exposure in children: A systematic review of literature

Blood lead levels > 10 µg/dL are known to affect various areas of the brain that influence behavior and cause many other health problems in children. As a result, the Centers for Disease Control and Prevention (CDC) set the blood lead action level at 10 µg/dL. However, recent research provides evidence that blood lead levels <10 µg/dL also may lead to behavioral problems in children. With the recent increase in diagnosis of Attention-Deficit Hyperactivity Disorder (ADHD) in children in the U.S. it is important to determine possible environmental toxins such as lead that may play a role in causing ADHD symptoms. The aim of this systematic review of the literature was to identify recent published studies that examine an association between blood lead levels < 10 µg/dL and ADHD symptoms in children in order to summarize their findings and describe major gaps in the literature. Although available research is limited, the articles reviewed indicate that blood lead at levels much below the CDC action level of 10 µg/dL may affect a child's level of attention, hyperactivity, impulsivity and ADHD diagnosis. Additional prospective research is warranted in order to inform the revision of current blood lead action levels as well as better elucidate the relationship between lead and ADHD diagnoses.^

Left, right and interval bivariate censored data: Evaluating screening mammography in the presence of lead -time bias, length bias and over-detection

Of the large clinical trials evaluating screening mammography efficacy, none included women ages 75 and older. Recommendations on an upper age limit at which to discontinue screening are based on indirect evidence and are not consistent. Screening mammography is evaluated using observational data from the SEER-Medicare linked database. Measuring the benefit of screening mammography is difficult due to the impact of lead-time bias, length bias and over-detection. The underlying conceptual model divides the disease into two stages: pre-clinical (T0) and symptomatic (T1) breast cancer. Treating the time in these phases as a pair of dependent bivariate observations, (t0,t1), estimates are derived to describe the distribution of this random vector. To quantify the effect of screening mammography, statistical inference is made about the mammography parameters that correspond to the marginal distribution of the symptomatic phase duration (T1). This shows the hazard ratio of death from breast cancer comparing women with screen-detected tumors to those detected at their symptom onset is 0.36 (0.30, 0.42), indicating a benefit among the screen-detected cases. ^