BACKGROUND:Oxidative stress is thought to be related to many diseases. Furthermore, it is hypothesized that radiofrequency electromagnetic fields (RF-EMF) may induce excessive oxidative stress in various cell types and thereby have the potential to compromise human and animal health. The objective of this systematic review (SR) is to summarize and evaluate the literature on the relation between the exposure to RF-EMF in the frequency range from 100 kHz to 300 GHz and biomarkers of oxidative stress. METHODS:The SR framework was developed following the guidelines established in the WHO Handbook for Guideline Development and NTP/OHAT's Handbook for Conducting a Literature-Based Health Assessment. We used the latter handbook's methodology for implementing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for environmental health assessments. We searched the following databases up until June 30, 2023: PubMed, Embase, Web of Science Core Collection, Scopus, and the EMF-Portal. The reference lists of included studies and retrieved review articles were also manually searched. We rated Risk of Bias (RoB) using the OHAT RoB Rating Tool and assessed publication bias using funnel plots of included studies. We assessed the certainty of the evidence (high, moderate, low, or very low) for an association between RF-EMF and oxidative stress using an adapted version of the GRADE framework. Data were extracted according to a predefined set of forms developed in DistillerSR. Data were analysed after grouping them first as in vitro or in vivo and then according to outcome category, species category, and exposed tissue. We synthesized study results using a random effects meta-analysis when study characteristics were judged sufficiently similar to be combined and heterogeneity (I2) was lower than 75 %, otherwise we describe the findings narratively. RESULTS:Fifty-six (56) studies, 45 in vivo and 11 in vitro, in which cells (in vitro) or animals (in vivo) were exposed to frequencies in the range 800-2450 MHz, were included in the systematic review after eliminating 12,353 publications because they did not meet the criteria defined in the published protocol (Henschenmacher et al., 2022). Of 56 studies 52 studies with 169 individual results were included in the meta-analysis. Together, these studies examined six human in vitro samples and fifty animal samples, including rodents (mice, rats, hamsters, and guinea pigs, (n = 46)) and rabbits (n = 4). RF-EMF were predominantly applied as continuous wave exposures in these studies. The outcome biomarkers for modified proteins and amino acids were measured in n = 30 studies, for oxidized DNA bases in n = 26 studies, for oxidized lipids in n = 3 studies and hydrogen peroxide production in 2 studies. Outcomes were mostly measured in the brain (n = 22), liver (n = 9), cells (n = 9), blood (n = 6), and testis (n = 2). RoB in studies was high, mainly due to biases in exposure and outcome assessment. IN VIVO STUDIES:Brain: The effect on biomarkers for oxidized DNA bases in the rodent brain (five studies, n = 98) had an inconsistent effect, varying from a large decrease with a standardized mean difference (SMD) of -3.40 (95 % CI [-5.15, -1.64]) to a large increase with an SMD of 2.2 (95 % CI [0.78, 3.62]). In the brain of rabbits (two studies, n = 44), the effect sizes also varied, from an SMD of -1.06 (95 % CI [-2.13, 0.00]) to an SMD of 5.94 (95 % CI [3.14, 8.73]). The effect on biomarkers for modified proteins and amino acids in the rodent brain (15 studies, n = 328) also varied from a large decrease with an SMD of -6.11 (95 % CI [-8.16, -4.06]) to a large increase with an SMD of 5.33 (95 % CI [2.49, 8.17]). The effect on biomarkers for oxidized lipids in the brain of rodents (one study, n = 56) also varied from a large decrease with SMD = -4.10 (95 % CI [-5.48, -2.73]) to SMD = 1.27 (95 % CI [0.45, 2.10]). Liver: The effect on biomarkers for oxidized DNA bases in the rodent liver (two studies, n = 26) was inconsistent with effect sizes in both directions: SMD = -0.71 (95 % CI [-1.80, 0.38]) and SMD = 1.56 (95 % CI [0.19, 2.92]). The effect on biomarkers for oxidized DNA bases in the rabbits' liver (two studies, n = 60) was medium with a pooled SMD of 0.39 (95 % CI [-0.79, 1.56]). Biomarkers for modified proteins and amino acids in the liver of rodents (six studies, n = 159) increased with a pooled SMD of 0.55 (95 % CI [0.06, 1.05]). Blood: The effect of RF-EMF on biomarkers for oxidized DNA bases in rodent blood (four studies, n = 104) was inconsistent, with SMDs ranging from -1.14 (95 % CI [-2.23, -0.06]) to 1.71 (95 % CI [-0.10, 3.53]). RF-EMF had no effect on biomarkers for modified proteins and amino acids in rodent blood (three studies, n = 40), with a pooled SMD of -0.08 (95 % CI [-1.32, 1.16]). There was a large increase in biomarkers for oxidized DNA bases in rodent plasma (two studies, n = 38) with a pooled SMD of 2.25 (95 % CI [1.27, 3.24]). Gonads: There was an increase in biomarkers for oxidized DNA bases in the rodent testis (two studies, n = 24) with a pooled SMD of 1.60 (95 % CI [0.62, 2.59]). The effect of RF-EMF on biomarkers for modified proteins and amino acids in the ovary of rodents (two studies, n = 52) was inconsistent with a medium effect, SMD = 0.24 (95 % CI [-0.74, 1.23])) and a large effect (SMD = 2.08 (95 % CI [1.22, 2.94])). Thymus: RF-EMF increased biomarkers for modified proteins and amino acids in the thymus of rodents (one study, n = 42) considerably with a pooled SMD of 6.16 (95 % CI [3.55, 8.76]). Cells: RF-EMF increased oxidized DNA bases in rodent cells with SMD of 2.49 (95 % CI [1.30, 3.67]) (one study, n = 27). There was a medium effect in oxidized lipids (one study, n = 18) but not statistically significant with SMD = 0.34 (95 % CI [-0.62, 1.29]). IN VITRO STUDIES:In in vitro studies in human cells (three studies, n = 110), there were inconsistent increases in biomarkers for oxidized DNA bases, where the SMDs varied between 0.01 (95 % CI [-0.59, 0.62]) and 7.12 (95% CI [0.06, 14.18]) in 4 results (2 of them statistically significant). In rodent cells (three studies, n = 24), there was a not statistically significant large effect in biomarkers for oxidized DNA bases with SMD = 2.07 (95 % CI [-1.38, 5.52]). The RF-EMF biomarkers for modified proteins and amino acids in human cells (one study, n = 18) showed a large effect with SMD = 1.07 (95 % CI [-0.05, 2.19]). In rodent cells (two studies, n = 24) a medium effect of SMD = 0.56 (95 % CI [-0.29, 1.41]) was observed. DISCUSSION:The evidence on the relation between the exposure to RF-EMF and biomarkers of oxidative stress was of very low certainty, because a majority of the included studies were rated with a high RoB level and provided high heterogeneity. This is due to inaccurate measurements of exposure and/or of measurement of oxidative stress biomarkers and missing information on the blinding of research personnel to exposure conditions or outcome measurements. There may be no or an inconsistent effect of RF-EMF on biomarkers of oxidative stress in the brain, liver, blood, plasma and serum, and in the female reproductive system in animal experiments but the evidence is of very low certainty. There may be an increase in biomarkers of oxidative stress in testes, serum and thymus of rodents but the evidence is of very low certainty. Future studies should improve experimental designs and characterization of exposure systems as well as the use of validated biomarker measurements with positive controls. Other: This review was partially funded by the World Health Organization. The protocol for this review is registered in PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235573) and published in Environment International (https://doi.org/10.1016/j.envint.2021.106932) (Henschenmacher et al., 2022).

BACKGROUND:Oxidative stress is conjectured to be related to many diseases. Furthermore, it is hypothesized that radiofrequency fields may induce oxidative stress in various cell types and thereby compromise human and animal health. This systematic review (SR) aims to summarize and evaluate the literature related to this hypothesis. OBJECTIVES:The main objective of this SR is to evaluate the associations between the exposure to radiofrequency electromagnetic fields and oxidative stress in experimental models (in vivo and in vitro). METHODS:The SR framework has been developed following the guidelines established in the WHO Handbook for Guideline Development and the Handbook for Conducting a Literature-Based Health Assessment). We will include controlled in vivo and in vitro laboratory studies that assess the effects of an exposure to RF-EMF on valid markers for oxidative stress compared to no or sham exposure. The protocol is registered in PROSPERO. We will search the following databases: PubMed, Embase, Web of Science Core Collection, Scopus, and the EMF-Portal. The reference lists of included studies and retrieved review articles will also be manually searched. STUDY APPRAISAL AND SYNTHESIS METHOD:Data will be extracted according to a pre-defined set of forms developed in the DistillerSR online software and synthesized in a meta-analysis when studies are judged sufficiently similar to be combined. If a meta-analysis is not possible, we will describe the effects of the exposure in a narrative way. RISK OF BIAS:The risk of bias will be assessed with the NTP/OHAT risk of bias rating tool for human and animal studies. We will use GRADE to assess the certainty of the conclusions (high, moderate, low, or inadequate) regarding the association between radiofrequency electromagnetic fields and oxidative stress. FUNDING:This work was funded by the World Health Organization (WHO). REGISTRATION:The protocol was registered on the PROSPERO webpage on July 8, 2021.

Originally developed to inform the acute toxicity of chemicals on fish, the zebrafish embryotoxicity test (ZET) has also been proposed for assessing the prenatal developmental toxicity of chemicals, potentially replacing mammalian studies. Although extensively evaluated in primary studies, a comprehensive review summarizing the available evidence for the ZET's capacity is lacking. Therefore, we conducted a systematic review of how well the presence or absence of exposure-related findings in the ZET predicts prenatal development toxicity in studies with rats and rabbits. A two-tiered systematic review of the developmental toxicity literature was performed, a review of the ZET literature was followed by one of the mammalian literature. Data were extracted using DistillerSR, and study validity was assessed with an amended SYRCLE's risk-of-bias tool. Extracted data were analyzed for each species and substance, which provided the basis for comparing the 2 test methods. Although limited by the number of 24 included chemicals, our results suggest that the ZET has potential to identify chemicals that are mammalian prenatal developmental toxicants, with a tendency for overprediction. Furthermore, our analysis confirmed the need for further standardization of the ZET. In addition, we identified contextual and methodological challenges in the application of systematic review approaches to toxicological questions. One key to overcoming these challenges is a transition to more comprehensive and transparent planning, conduct and reporting of toxicological studies. The first step toward bringing about this change is to create broad awareness in the toxicological community of the need for and benefits of more evidence-based approaches.

Drug-induced liver injury (DILI) causes one in three market withdrawals due to adverse drug reactions, causing preventable human suffering and massive financial loss. We applied evidence-based methods to investigate the role of preclinical studies in predicting human DILI using two anti-diabetic drugs from the same class, but with different toxicological profiles: troglitazone (withdrawn from US market due to DILI) and rosiglitazone (remains on US market). Evidence Stream 1: A systematic literature review of in vivo studies on rosiglitazone or troglitazone was conducted (PROSPERO registration CRD42018112353). Evidence Stream 2: in vitro data on troglitazone and rosiglitazone were retrieved from the US EPA ToxCast database. Evidence Stream 3: troglitazone- and rosiglitazone-related DILI cases were retrieved from WHO Vigibase. All three evidence stream analyses were conducted according to evidence-based methodologies and performed according to pre-registered protocols. Evidence Stream 1: 9288 references were identified, with 42 studies included in analysis. No reported biomarker for either drug indicated a strong hazard signal in either preclinical animal or human studies. All included studies had substantial limitations, resulting in “low” or “very low” certainty in findings. Evidence Stream 2: Troglitazone was active in twice as many in vitro assays (129) as rosiglitazone (60), indicating a strong signal for more off-target effects. Evidence Stream 3: We observed a fivefold difference in both all adverse events and liver-related adverse events reported, and an eightfold difference in fatalities for troglitazone, compared to rosiglitazone. In summary, published animal and human trials failed to predict troglitazone’s potential to cause severe liver injury in a wider patient population, while in vitro data showed marked differences in the two drugs’ off-target activities, offering a new paradigm for reducing drug attrition in late development and in the market. This investigation concludes that death and disability due to adverse drug reactions may be prevented if mechanistic information is deployed at early stages of drug development by pharmaceutical companies and is considered by regulators as a part of regulatory submissions.

This column describes a project funded by the initiative to develop online learning modules for researchers, clinicians, and informationists/librarians on aspects of next-generation sequencing projects. The modules describe a framework for next-generation sequencing projects, with particular emphasis placed on experimental design, ethical considerations, data storage, and data sharing. The author outlines how the modules were developed and summarizes their contents.

Abstract Systematic review methodology is a means of addressing specific questions through structured, consistent, and transparent examinations of the relevant scientific evidence. This methodology has been used to advantage in clinical medicine, and is being adapted for use in other disciplines. Although some applications to toxicology have been explored, especially for hazard identification, the present preparatory study is, to our knowledge, the first attempt to adapt it to the assessment of toxicological test methods. As our test case, we chose the zebrafish embryotoxicity test (ZET) for developmental toxicity and its mammalian counterpart, the standard mammalian prenatal development toxicity study, focusing the review on how well the ZET predicts the presence or absence of chemical-induced prenatal developmental toxicity observed in mammalian studies. An interdisciplinary team prepared a systematic review protocol and adjusted it throughout this piloting phase, where needed. The final protocol was registered and will guide the main study (systematic review), which will execute the protocol to comprehensively answer the review question. The goal of this preparatory study was to translate systematic review methodology to the assessment of toxicological test method performance. Consequently, it focused on the methodological issues encountered, whereas the main study will report substantive findings. These relate to numerous systematic review steps, but primarily to searching and selecting the evidence. Applying the lessons learned to these challenges can improve not only our main study, but may also be helpful to others seeking to use systematic review methodology to compare toxicological test methods. We conclude with a series of recommendations that, if adopted, would help improve the quality of the published literature, and make conducting systematic reviews of toxicological studies faster and easier over time.

Systematic review methodology is a means of addressing specific questions through structured, consistent, and transparent examinations of the relevant scientific evidence. Thismethodology has been used to advantage in clinical medicine, and is being adapted for use in other disciplines. Although some applications to toxicology have been explored, especially for hazard identification, the present preparatory study is, to our knowledge, the first attempt to adapt it to the assessment of toxicological test methods. As our test case, we chose the zebrafish embryotoxicity test (ZET) for developmental toxicity and its mammalian counterpart, the standard mammalian prenatal development toxicity study, focusing the review on how well the ZET predicts the presence or absence of chemical-induced prenatal developmental toxicity observed in mammalian studies. An interdisciplinary team prepared a systematic review protocol and adjusted it throughout this piloting phase, where needed. The final protocol was registered and will guide the main study (systematic review), which will execute the protocol to comprehensively answer the review question. The goal of this preparatory study was to translate systematic review methodology to the assessment of toxicological test method performance. Consequently, it focused on the methodological issues encountered, whereas the main study will report substantive findings. These relate to numerous systematic review steps, but primarily to searching and selecting the evidence. Applying the lessons learned to these challenges can improve not only our main study, but may also be helpful to others seeking to use systematic review methodology to compare toxicological test methods. We conclude with a series of recommendations that, if adopted, would help improve the quality of the published literature, and make conducting systematic reviews of toxicological studies faster and easier over time.

Clozapine is the only medication indicated for treating refractory schizophrenia, due to its superior efficacy among all antipsychotic agents, but its mechanism of action is poorly understood. To date, no studies of human postmortem brain have characterized the gene expression response to clozapine. Therefore, we addressed this question by analyzing expression data extracted from published microarray studies involving brains of patients on antipsychotic therapy. We first performed a systematic review and identified four microarray studies of postmortem brains from antipsychotic-treated patients, then extracted the expression data. We then performed generalized linear model analysis on each study separately, and identified the genes differentially expressed in response to clozapine compared to other atypical antipsychotic medications, as well as their associated canonical pathways. We also found a number of genes common to all four studies that we analyzed: GCLM, ZNF652, and GYPC. In addition, pathway analysis highlighted the following processes in all four studies: clathrin-mediated endocytosis, SAPK/JNK signaling, 3-phosphoinositide synthesis, and paxillin signaling. Our analysis yielded the first comprehensive compendium of genes and pathways differentially expressed upon clozapine treatment in the human brain, which may provide insight into the mechanism and unique efficacy of clozapine, as well as the pathophysiology of schizophrenia.

Assessments of methodological and reporting quality are critical to adequately judging the credibility of a study's conclusions and to gauging its potential reproducibility. To aid those seeking to assess the methodological or reporting quality of studies relevant to toxicology, we conducted a scoping review of the available guidance with respect to four types of studies: in vivo and in vitro, (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and human observational studies. Our aims were to identify the available guidance in this diverse literature, briefly summarize each document, and distill the common elements of these documents for each study type. In general, we found considerable guidance for in vivo and human studies, but only one paper addressed in vitro studies exclusively. The guidance for (Q)SAR studies and physico-chemical studies was scant but authoritative. There was substantial overlap across guidance documents in the proposed criteria for both methodological and reporting quality. Some guidance documents address toxicology research directly, whereas others address preclinical research generally or clinical research and therefore may not be fully applicable to the toxicology context without some translation. Another challenge is the degree to which assessments of methodological quality in toxicology should focus on risk of bias – as in clinical medicine and healthcare – or be broadened to include other quality measures, such as confirming the identity of test substances prior to exposure. Our review is intended primarily for those in toxicology and risk assessment seeking an entry point into the extensive and diverse literature on methodological and reporting quality applicable to their work.

A National Research Council report recently addressed the need for enhanced education and training in the interdisciplinary field of forensic science. The Institute of Medicine and the American Psychological Association, among others, have also expressed the importance of interdisciplinary education. This article describes a unique partnership at a Regional Higher Education Center using an interdisciplinary, inter-institutional approach to the development of an introductory forensic science course engaging both health and non-health majors. Few examples of this kind of partnership exist in the literature. This article offers a detailed description of the development of this course, including challenges faced and successes achieved. As such, it provides a potential model for the development and implementation of similar courses. Furthermore, it offers an example of how to model in an academic setting the integration of disciplines that exists or is needed in the workplace.

Objective – The aim of this article is to present evidence based methods for the selection of chemistry monographs, particularly for librarians lacking a background in chemistry. These methods will be described in detail, their practical application illustrated, and their efficacy tested by analyzing circulation data. Methods – Two hundred and ninety-five chemistry monographs were selected between 2005 and 2007 using rigorously-applied evidence based methods involving the Library's integrated library system (ILS), Google, and SciFinder Scholar. The average circulation rate of this group of monographs was compared to the average circulation rate of 254 chemistry monographs selected between 2002 and 2004 when the methods were not used or were in an incomplete state of development. Results – Circulations/month were on average 9% greater in the cohort of monographs selected with the rigorously-applied evidence based methods. Further statistical analysis, however, finds that this result can not be attributed to the different application of these methods. Conclusion – The methods discussed in this article appear to provide an evidence base for the selection of chemistry monographs, but their application does not change circulation rates in a statistically significant way. Further research is needed to determine if this lack of statistical significance is real or a product of the organic development and application of these methods over time, making definitive comparisons difficult.

OBJECTIVE:To examine the attitudes, beliefs, and behaviors of parents whose children were underimmunized with respect to > or =2 vaccines that have recently received negative attention, compared with parents whose children were fully immunized with respect to the recommended vaccines. DESIGN:Case-control study. SETTING:A sample of households that participated in the National Immunization Survey were recontacted in 2001. MAIN OUTCOME MEASURE:Vaccination status was assessed. Case subjects were underimmunized with respect to > or =2 of 3 vaccines (diphtheria-tetanus-pertussis or diphtheria-tetanus-acellular pertussis, hepatitis B, or measles-containing vaccines), and control subjects were fully immunized. RESULTS:The response rate was 52.1% (2315 of 4440 subjects). Compared with control households, case households were more likely to make 0 dollar to 30,000 dollars (adjusted odds ratio [OR]: 2.7; 95% confidence interval [CI]: 1.5-4.6) than at least 75,000 dollars, to have > or =2 providers (OR: 2.0; 95% CI: 1.3-3.1) than 1, and to have > or =4 children (OR: 3.1; 95% CI: 1.5-6.3) than 1 child. With control for demographic and medical care factors, case subjects were more likely than control subjects to not want a new infant to receive all shots (OR: 3.8; 95% CI: 1.5-9.8), to score vaccines as unsafe or somewhat safe (OR: 2.0; 95% CI: 1.2-3.4), and to ask the doctor or nurse not to give the child a vaccine for reasons other than illness (OR: 2.7; 95% CI: 1.2-6.1). Among case subjects, 14.8% of underimmunization was attributable to parental attitudes, beliefs, and behaviors. CONCLUSIONS:Attitudes, beliefs, and behaviors indicative of vaccine safety concerns contribute substantially to underimmunization in the United States. Although concerns were significantly more common among parents of underimmunized children, many parents of fully immunized children demonstrated similar attitudes, beliefs, and behaviors, suggesting a risk to the currently high vaccination levels. Efforts to maintain and improve immunization coverage need to target those with attitudes/beliefs/behaviors indicative of vaccine safety concerns, as well as those with socioeconomic and health care access problems.

Background The National Immunization Survey provides coverage estimates for children aged 19 to 35 months in each of 78 state and urban areas designated as Immunization Action Plan (IAP) areas by the National Immunization Program in the Centers for Disease Control and Prevention (CDC). Coverage-level estimates for the 78 areas and for the nation as a whole are published in Morbidity and Mortality Weekly Report (MMWR), U. S. Department of Health and Human Services/Public Health Service (Ezzati-Rice et al., 1995). The NIS uses a list-assisted random-digit-dial (RDD) sample design. A randomly generated sample of telephone numbers is screened to determine whether each number is a working or nonworking telephone line; if working, whether the number is for a household or some nonresidential entity (business, fax/modem line); and, if a household, whether it contains any NIS-eligible children in the target age range of 19-35 months. Households with eligible children are invited to participate in the survey by providing immunization data about each eligible child in the household. In addition to the telephone survey of households, an equally important data collection component of the NIS is the Provider Record Check Study. In the telephone survey of households, respondents are encouraged to rely on shot cards given to them by physicians and other immunization providers. More than half of the respondents do use these records as they respond to the survey, but a significant proportion do not. Respondents who rely on memory alone are likely to misrepresent the immunization history of their children, because they may forget a vaccination or may misremember the date of a particular shot. Even when respondents do refer to shot records during the interview, they may have incomplete records. Parents can lose a copy of the shot card and be given a new one that omits earlier vaccinations, or they may have changed physicians and kept only the shot card from the newer provider. The Provider Record Check Study was designed to address these shortcomings in the household data by obtaining vaccination records from providers themselves. Procedures for the NIS Provider Record Check Study follow generally the model suggested by Dillman for mail questionnaires (Dillman, 1978; Dillman, 1991; Paxson, Dillman, and Tamai, 1995)--that is, repeated mail requests, including special handling, and telephone follow-up. The initial request, sent by Federal Express, contains the following items:

The National Immunization Survey (NIS) is a large federally funded survey designed to estimate vaccination coverage rates for children residing in the United States aged 19 to 35 months. In 1999, over 8 million telephone call attempts were made to obtain provider-reported vaccination histories on 22,521 children in the age range of interest.

The introduction in a random-digit-dialing (RDD) survey is the initial interaction point between the sample household and the interviewer. It often represents the initial request for participation in the survey and is therefore an important survey design component in the process of gaining cooperation and achieving a high response rate (Meegama and Blair, 1999). The relationship of the survey introduction and data quality has been studied by Couper (1997). In an RDD survey that screens for an eligible population, the survey introduction may also start the process of defining the target population to the respondent. In a screening survey the introduction can impact not only the response rate but also the household eligibility rate observed in the sample. Modest changes in a large-scale RDD screening operation can enhance a survey’s ability to sample a rare eligible population, such as in the National Immunization Survey (NIS), which samples households containing children ages 19-35 months. This paper presents the experimental methods and results of a field test designed to measure whether new versions of a CATI screener introduction in the NIS improved household eligibility rates and other data quality indicators. Potential cost savings and effects on immunization estimates due to the screener treatments are also discussed.

PROBLEM/CONDITION:High vaccination levels in the population are necessary to decrease disease transmission and prevent disease; therefore, an important component of the U.S. vaccination program is the assessment of vaccination coverage. Current goals are for > or = 90% coverage with recommended vaccines during the first 2 years of life.REPORTING PERIOD:January-December 1998.DESCRIPTION OF SYSTEMS:The National Immunization Survey (NIS) is an ongoing, random-digit-dialed telephone survey that gathers vaccination coverage data for children aged 19-35 months in all 50 states and 28 urban areas. Vaccination coverage rates derived from NIS data are adjusted statistically for households with multiple telephone lines, household nonresponse, the proportion of households without telephones, and vaccination provider nonresponse. The results were also adjusted to match the known total population of children in each survey area.RESULTS:On the basis of NIS data, national coverage was > or = 90% for three doses of poliovirus vaccine (Polio), three doses of Haemophilus influenzae type b vaccine (Hib), and one dose of measles-containing vaccine (MCV). Coverage was the highest ever reported for four doses of any diphtheria and tetanus toxoids and pertussis vaccine (DTP) (i.e., diphtheria and tetanus toxoids and pertussis vaccine, diphtheria and tetanus toxoids [DT], or diphtheria and tetanus toxoids and acellular pertussis vaccine [DTaP]) (83.9%), three doses of hepatitis B vaccine (Hep B, 87.0%), and one dose of varicella vaccine (43.2%). The number of states achieving the > or = 90% goal was 47 for three doses of Hib, 40 for three doses of Polio, 40 for one dose of MCV, nine for three doses of Hep B, and seven for four doses of DTP. Proportionally fewer urban areas achieved the > or = 90% goal: 23 of 28 for three doses of Hib, 13 for three doses of Polio, 16 for one dose of MCV, five for three doses of Hep B, and one for four doses of DTP. No state or urban area has yet achieved the > or = 90% goal for varicella.INTERPRETATION:Findings from the 1998 NIS indicate that national vaccination coverage levels for routinely recommended childhood vaccines are at the highest levels ever reported. However, substantial variation in coverage remains at the state and urban area levels.PUBLIC HEALTH ACTIONS:The public health community and vaccination providers in areas with low coverage should intensify their efforts to implement recommended strategies for increasing vaccination coverage to ensure that children are equally well protected throughout the United States.

Trena M. Ezzati-Ricea, Martin R. Frankelb, David C. Hoaglinb, John D. Loftc, Victor G. Coronadod and Robert A. Wrighta aCenters for Disease Control and Prevention, National Center for Health Statistics, 6525 Belcrest Road, Room 915, Hyattsville, MD 20782, USA bAbt Associates Inc., 55 Wheeler Street, Cambridge, MA 02138, USA cResearch Triangle Institute, 203 North Wabash, Suite 1220, Chicago, IL 60601, USA dCenters for Disease Control and Prevention, National Immunization Program, Corporate Square Boulevard, Atlanta, GA 30329, USA

The rationale for the use of an advance respondent letter is based on the experience of survey researchers that contact before an actual interview attempt “warmsup” respondents, hopefully making them more positively disposed toward participation than if they were only to receive a “cold call.” The logic is that using advance respondent letters will increase response rates, thereby reducing the potential size of nonresponse-related total survey error. For example, Traugott, Groves, and Lepkowski (1987) reported an experiment in which advance contact in a telephone survey of the public increased response rates by 10 percentage points. To the extent that advance letters reduce nonresponse, they also are likely to be highly cost effective by decreasing the need for far more expensive refusal conversion attempts (Frey, 1989; Lavrakas, 1993). For the typical RDD telephone survey, the first attempt made to contact a household is always a “cold call.” Since numbers are randomly generated, the person who answers the telephone does not expect the call, and may have never heard of the government agency sponsoring the survey or the survey organization collecting the dam. This lack of familiarity is one reason that RDD surveys typically achieve lower response rates than face-to-face household surveys. Another problem in RDD surveys is the proportion of individuals who simply hang up during the introduction without saying anything (HUDIs), often as soon as the interviewer begins to speak. Wulfsberg and Battaglia (1992), and Traugott, Groves, and Lepkowski (1987) discuss the potential for increasing response to surveys by using an advance respondent letter combined with RDD sampling methodology. To obtain addresses that correspond to the RDD-generated telephone numbers, a file containing the RDD-generated telephone numbers is crossreferenced against a computerized database containing directory-listed residential telephone numbers, names, and addresses. It is possible that an advance letter may unintentionally increase both total survey error and survey costs. If potential survey respondents learn from advance contact what makes one ineligible or eligible to be interviewed, some may answer the survey’s screening sequence inaccurately so as to avoid being interviewed. If this occurs, the potential respondent is actually refusing to participate and will be incorrectly coded as ineligible. Conversely, if potentially eligible survey respondents are not sufficiently persuaded as to the benefits that will accrue through survey participation, or if they do not see the relevance of the survey topic to their own circumstances, they may refuse to participate. An appeal to potential respondents to screening surveys that is too weak could possibly result in lower than predicted eligibility rates, since eligible respondents may participate at lower rates than ineligible households, especially since it is much easier to screen out ineligible households than enlist eligible households to participate.