Jennifer Nelson - Academia.edu (original) (raw)

Papers by Jennifer Nelson

Research paper thumbnail of Safety of repeated doses of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine in adults and adolescents

Pharmacoepidemiology and drug safety, Jan 3, 2018

In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria ... more In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.

Research paper thumbnail of Sequential surveillance for drug safety in a regulatory environment

Pharmacoepidemiology and drug safety, Jan 5, 2018

Research paper thumbnail of The impact of selection bias on vaccine effectiveness estimates from test-negative studies

Vaccine, Jan 15, 2017

Estimates of vaccine effectiveness (VE) from test-negative studies may be subject to selection bi... more Estimates of vaccine effectiveness (VE) from test-negative studies may be subject to selection bias. In the context of influenza VE, we used simulations to identify situations in which meaningful selection bias can occur. We also analyzed observational study data for evidence of selection bias. For the simulation study, we defined a hypothetical population whose members are at risk for acute respiratory illness (ARI) due to influenza and other pathogens. An unmeasured "healthcare seeking proclivity" affects both probability of vaccination and probability of seeking care for an ARI. We varied the direction and magnitude of these effects and identified situations where meaningful bias occurred. For the observational study, we reanalyzed data from the United States Influenza VE Network, an ongoing test-negative study. We compared "bias-naïve" VE estimates to bias-adjusted estimates, which used data from the source populations to correct for sampling bias. In the sim...

Research paper thumbnail of Design and analysis choices for safety surveillance evaluations need to be tuned to the specifics of the hypothesized drug-outcome association

Pharmacoepidemiology and drug safety, Sep 14, 2016

We reviewed the results of the Observational Medical Outcomes Research Partnership (OMOP) 2010 Ex... more We reviewed the results of the Observational Medical Outcomes Research Partnership (OMOP) 2010 Experiment in hopes of finding examples where apparently well-designed drug studies repeatedly produce anomalous findings. OMOP had applied thousands of designs and design parameters to 53 drug-outcome pairs across 10 electronic data resources. Our intent was to use this repository to elucidate some sources of error in observational studies. From the 2010 OMOP Experiment, we sought drug-outcome-method combinations (DOMCs) that met consensus design criteria, yet repeatedly produced results contrary to expectation. We set aside DOMCs for which we could not agree on the suitability of the designs, then selected for an in-depth scrutiny one drug-outcome pair analyzed by a seemingly plausible methodological approach, whose results consistently disagreed with the a priori expectation. The OMOP "all-by-all" assessment of possible DOMCs yielded many combinations that would not be chosen ...

Research paper thumbnail of Post licensure surveillance of influenza vaccines in the Vaccine Safety Datalink in the 2013-2014 and 2014-2015 seasons

Pharmacoepidemiology and Drug Safety, 2016

Purpose The changes in each year in influenza vaccine antigenic components as well as vaccine adm... more Purpose The changes in each year in influenza vaccine antigenic components as well as vaccine administration patterns may pose new risks of adverse events following immunization (AEs). To evaluate the safety of influenza vaccines annually administered to people ≥ 6 months, we conducted weekly post licensure surveillance for seven pre-specified adverse events following receipt of influenza vaccines during the 2013-2014 and 2014-2015 seasons in the Vaccine Safety Datalink (VSD). Methods We used both a historically-controlled cohort design with the Poisson-based maximized sequential probability ratio test (maxSPRT) and a self-controlled risk interval (SCRI) design with the binomial-based maxSPRT. For each adverse event outcome, we defined the risk interval on the basis of biologic plausibility and prior literature. For the historical cohort design, numbers of expected adverse events were calculated from the prior seven seasons, adjusted for age and site. For the SCRI design, a comparison window was defined either before vaccination or after vaccination, depending on each specific outcome. Results An elevated risk of febrile seizures 0-1 days following trivalent inactivated influenza vaccine (IIV3) was identified in children aged 6-23 months during the 2014-2015 season using the SCRI design. We found the relative risk (RR) of febrile seizures following concomitant administration of IIV3 and PCV13 was 5.3 with a 95% CI 1.87-14.75. Without concomitant PCV 13 administration, the estimated risk decreased and was no longer statistically significant (RR: 1.4; CI: 0.54-3.61).

Research paper thumbnail of Prophylaxis with acetaminophen or ibuprofen for prevention of local reactions to the fifth diphtheria-tetanus toxoids-acellular pertussis vaccination: a randomized, controlled trial

Pediatrics, 2006

The frequency of local vaccination reactions increases with successive doses of diphtheria-tetanu... more The frequency of local vaccination reactions increases with successive doses of diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccine, and local reactions occur for the majority of children receiving the fifth DTaP vaccination. It is not known whether these reactions can be prevented with prophylactic use of acetaminophen or ibuprofen. In this 3-group, randomized, blinded, controlled trial, 372 children were assigned randomly, in a 2:2:1 ratio, to receive 3 doses of acetaminophen, ibuprofen, or placebo. The first dose of study medication was administered within 2 hours before the fifth DTaP vaccination, and the remaining 2 doses were given at 6-hour intervals. The primary outcome measures included a local reaction with an area of redness or discoloration > or =5 cm in diameter on the evening of or during the 2 days after vaccination, an increase in mid-limb circumference of > or =2 cm on the evening of or during the 2 days after vaccination, and a persistent local reac...

Research paper thumbnail of Safety of varying dosages of 7-valent pneumococcal protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine

Vaccine, 2005

In a phase I/II dose escalation study, varying volumes (0.1 ml, 0.5 ml, 1.0 ml and 2.0 ml) of 7-v... more In a phase I/II dose escalation study, varying volumes (0.1 ml, 0.5 ml, 1.0 ml and 2.0 ml) of 7-valent pneumococcal conjugate vaccine (PCV) (Prevnar or 0.5 ml of 23-valent pneumococcal polysaccharide vaccine (PPV) were administered to 220 adults 70 through 79 years of age previously vaccinated with 0.5 ml PPV at age 65 years or above and at least 5 years previously. Fever was uncommon and did not vary by study group. The rate of local reactions increased with higher volumes of PCV and the rate following 2.0 ml of PCV was comparable to that following 0.5 ml PPV.

Research paper thumbnail of Immunogenicity of varying dosages of 7-valent pneumococcal polysaccharide–protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine

Vaccine, 2007

In this dose-ranging study 220 seniors who had received the 23-valent pneumococcal polysaccharide... more In this dose-ranging study 220 seniors who had received the 23-valent pneumococcal polysaccharide (PnPS) vaccine at least 5 years prior to enrollment were assigned to receive one of four volumes (0.1, 0.5, 1 or 2 ml) of 7-valent pneumococcal conjugate (PnC) vaccine or a 0.5 ml dose of 23-valent PnPS vaccine. All participants received a reduced challenge dose of 0.1 ml of PnPS vaccine 1 year after enrollment. There was evidence of a dose response to PnC vaccine and antibody levels in the 1 ml PnC group tended to be significantly higher than in the PnPS group. A booster response to the challenge vaccination was not observed. Administration of a 1 ml dose of PnC vaccine is more immunogenic than 0.5 ml of PnPS vaccine in elderly adults previously vaccinated with PnPS vaccine.

Research paper thumbnail of Assessment of the safety of a third dose of pneumococcal polysaccharide vaccine in the Vaccine Safety Datalink population

Vaccine, 2006

There is little information on the safety of administration of a third dose of pneumococcal polys... more There is little information on the safety of administration of a third dose of pneumococcal polysaccharide vaccine (PPV). The authors conducted a retrospective assessment of 316,995 adult members of three health maintenance organizations who had received one, two, or three PPV doses. Medical encounters associated with diagnosis codes potentially indicative of an injection site reaction in the week following a first, second, or third PPV dose were identified. These presumptive events occurred in 0.3% (911/279504) of the first PPV group, 0.7% (257/36888) of the second PPV group, and 0.5% (3/603) of the third PPV group (p>0.5 for both comparisons with the third PPV group). These findings do not suggest that a third PPV dose is associated with an increased risk of medically attended injection site reactions compared with a first or second PPV dose.

Research paper thumbnail of Vaccines and changes in coagulation parameters in adults on chronic warfarin therapy: a cohort study

Pharmacoepidemiology and Drug Safety, 2007

Purpose Warfarin is commonly used among patients who receive influenza, pneumococcal, and tetanus... more Purpose Warfarin is commonly used among patients who receive influenza, pneumococcal, and tetanus and diphtheria toxoid vaccines, and persons on warfarin therapy may also receive Hepatitis A vaccine. There has been concern that vaccinations could potentially alter coagulation parameters in patients on warfarin therapy. We sought to determine whether vaccinations are associated with changes in International Normalized Ratio (INR) in persons on long-term warfarin therapy. Methods We conducted a retrospective cohort study of 5167 members of Group Health, a health maintenance organization (HMO) in western Washington State, who were aged 18 years and older and who were on stable long-term warfarin therapy between 1 January 1992 and 31 December 2003. We made within-person comparisons between mean INR values in the 28 days after receipt of influenza, pneumococcal, tetanus, or hepatitis A vaccine versus mean INR values during other times. Results Receipt of influenza vaccine was not associated with a change in INR value (mean change, 0.01; 95% confidence interval (CI) À0.01 to 0.03); similar results were observed for pneumococcal (mean change 0.01; 95%CI À0.07 to 0.09), tetanus (mean change 0.03; 95%CI À0.03 to 0.10), and hepatitis A vaccines (mean change 0.03; 95%CI À0.10 to 0.14). Conclusions Our results do not suggest that vaccinations lead to clinically significant alterations in coagulation measures among adults on chronic warfarin therapy.

Research paper thumbnail of Accuracy of reporting maternal in-hospital diagnoses and intrapartum procedures in Washington State linked birth records

Paediatric and Perinatal Epidemiology, 2005

While the impact of maternal morbidities and intrapartum procedures is a common topic in perinata... more While the impact of maternal morbidities and intrapartum procedures is a common topic in perinatal outcomes research, the accuracy of the reporting of these variables in the large administrative databases (birth certificates, hospital discharges) often utilised for such research is largely unknown. We conducted this study to compare maternal diagnoses and procedures listed on birth certificates, hospital discharge data, and birth certificate and hospital discharge data combined, with those documented in a stratified random sample of hospital medical records of 4541 women delivering liveborn infants in Washington State in 2000. We found that birth certificate and hospital discharge data combined had substantially higher true positive fractions (TPF, proportion of women with a positive medical record assessment who were positive using the administrative databases) than did birth certificate data alone for labour induction (86% vs. 52%), cephalopelvic disproportion (83% vs. 35%), abruptio placentae (85% vs. 68%), and forceps-assisted delivery (89% vs. 55%). For procedures available only in hospital discharge data, TPFs were generally high: episiotomy (85%) and third and fourth degree vaginal lacerations (91%). Except for repeat caesarean section without labour (TPF, 81%), delivery procedures available only in birth certificate data had low TPFs, including augmentation (34%), repeat caesarean section with labour (61%), and vaginal birth after caesarean section (62%). Our data suggest that researchers conducting perinatal epidemiological studies should not rely solely on birth certificate data to detect maternal diagnoses and intrapartum procedures accurately.

Research paper thumbnail of Induction of Labor in the Absence of Standard Medical Indications

Medical Care, 2007

Background: Induction of labor is an increasingly common obstetrical procedure, with approximatel... more Background: Induction of labor is an increasingly common obstetrical procedure, with approximately 20-34% of women undergoing labor induction in the United States annually. Objective: To determine the extent of labor induction in the absence of standard medical indications and to assess possible associations with maternal and infant characteristics and hospital factors. Methods: We ascertained induction of labor and associated details as part of a medical record validation study of 4541 women with live, singleton births in 2000 in Washington State using medical record, birth certificate, and hospital discharge data. In this analysis, we report findings for the 1473 women (33% of original cohort) whose medical records indicated that their labors were induced. Results: Among women with induced labor, 7.9% had no clinical information providing an indication for the induction, and 6.4% had only "nonstandard" indications recorded. Compared with women delivering in moderate volume hospitals, women who delivered at lower volume (odds ratios ͓OR͔ 3.9; 95% confidence intervals ͓CI͔ 1.8-8.6) or higher volume hospitals (OR 4.2; 95% CI 2.4-7.2) had significantly increased risk for undocumented indication of labor. Women who had undocumented indication for induction were at significantly decreased risk of giving birth at a teaching hospital and a public nonfederally owned hospital, and were at greater risk to give birth at a private religious hospital. Factors that remained independently associated with nonstandard indication for induction of labor were primiparas (OR 2.4; 95% CI 1.3-4.2); multiparas (OR 4.3; 95% CI 2.5-7.4), pregnancyinduced hypertension (OR 0.2; 95% CI 0.1-0.4), hospital volume Ն2000 births annually (OR 19.9; 95% CI 6.7-58.6), primary (OR 11.7; 95% CI 4.1-33.6), and tertiary level hospital (OR 0.4; 95% CI 0.2-0.7). Conclusions: Our findings suggest that nearly 15% of inductions either were not clinically indicated according to standard protocols or indications were incompletely documented. At minimum, further studies are needed to explore how best to improve documentation of indications of labor because accurately describing, among other things, the process of labor induction, is a basic benchmark of care.

Research paper thumbnail of New strategies are needed to improve the accuracy of influenza vaccine effectiveness estimates among seniors

Journal of Clinical Epidemiology, 2009

Objective: The magnitude of the benefit of influenza vaccine among elderly individuals has been r... more Objective: The magnitude of the benefit of influenza vaccine among elderly individuals has been recently debated. Existing vaccine effectiveness estimates derive primarily from observational studies, which may be biased. In this paper, we provide a methodological examination of the potential sources of bias in observational studies of influenza vaccine effectiveness in seniors and propose design and analysis strategies to reduce bias in future studies. Study Design and Setting: We draw parallels to bias documented in observational studies of therapies in other areas of medical research including pharmacoepidemiology, discuss reasons why existing adjustment methods in influenza studies may not adequately control for the bias, and evaluate statistical approaches that may yield more accurate estimation of influenza vaccine effectiveness. Results: There is strong evidence for the presence of bias in existing observational estimates of influenza vaccine effectiveness in the elderly and the failure of current adjustment methods to reduce bias. Conclusion: Promising approaches for reducing bias include obtaining more accurate information on confounders, such as functional status, avoiding all-cause death in favor of outcomes, such as pneumonia or influenza-related pneumonia, and evaluating the extent to which bias is reduced by these and other methods using the 'control' period before influenza season.

Research paper thumbnail of Stress, depressive symptoms, and smoking cessation among pregnant women

Health Psychology, 2000

Perceived stress and depressive symptoms were examined as correlates and predictors of smoking ce... more Perceived stress and depressive symptoms were examined as correlates and predictors of smoking cessation during pregnancy in a sample of 819 pregnant smokers (454 baseline smokers and 365 baseline quitters). Women who quit early in pregnancy had lower levels of stress and depressive symptoms than baseline smokers. Adjusting for level of addiction and other demographic factors related to stress and depressive symptoms eliminated the significant association between depressive symptoms and smoking cessation. Lower levels of stress and depressive symptoms were not predictive of cessation in later pregnancy. Prenatal healthcare providers should continue to assess level of addiction and provide targeted intensive cessation interventions. Interventions that reduce stress and depression may also be of benefit to women who are continuing smokers in early pregnancy.

Research paper thumbnail of Partner smoking status and pregnant smoker's perceptions of support for and likelihood of smoking cessation

Health Psychology, 1998

Perceptions of support for cessation of smoking during pregnancy, likelihood of quitting, and par... more Perceptions of support for cessation of smoking during pregnancy, likelihood of quitting, and partner smoking status were explored in a sample of 688 pregnant smokers (372 baseline smokers and 316 baseline quitters). Women with nonsmoking partners were significantly more likely to be baseline quitters than women with partners who smoked. Baseline quitters reported significantly more positive support from their partners than did continuing smokers (p = .02). Neither partner smoking status nor partner support at baseline was associated with cessation or relapse later in pregnancy. Women reported greater support, both positive and negative, from nonsmoking partners than from partners who smoked (p = .001). Among partner smokers, those who were trying to quit were perceived to be particularly supportive. Cessation interventions for expectant fathers may increase pregnant women's success at quitting.

Research paper thumbnail of Differences in preconceptional and prenatal behaviors in women with intended and unintended pregnancies

American Journal of Public Health, 1998

OBJECTIVES: This study examined whether pregnancy intention was associated with cigarette smoking... more OBJECTIVES: This study examined whether pregnancy intention was associated with cigarette smoking, alcohol drinking, use of vitamins, and consumption of caffeinated drinks prior to pregnancy and in early pregnancy. METHODS: Data from a telephone survey of 7174 pregnant women were analyzed. RESULTS: In comparison with women whose pregnancies were intended, women with unintended pregnancies were more likely to report cigarette smoking and less likely to report daily vitamin use. Women with unintended pregnancies were also less likely to decrease consumption of caffeinated beverages or increase daily vitamin use. CONCLUSIONS: Pregnancy intention was associated with health behaviors, prior to pregnancy and in early pregnancy, that may influence pregnancy course and birth outcomes.

Research paper thumbnail of Prevention of relapse in women who quit smoking during pregnancy

American Journal of Public Health, 1999

OBJECTIVES: This study is an evaluation of relapse prevention interventions for smokers who quit ... more OBJECTIVES: This study is an evaluation of relapse prevention interventions for smokers who quit during pregnancy. METHODS: Pregnant smokers at 2 managed care organizations were randomized to receive a self-help booklet only, prepartum relapse prevention, or prepartum and postpartum relapse prevention. Follow-up surveys were conducted at 28 weeks of pregnancy and at 8 weeks, 6 months, and 12 months postpartum. RESULTS: The pre/post intervention delayed but did not prevent postpartum relapse to smoking. Prevalent abstinence was significantly greater for the pre/post intervention group than for the other groups at 8 weeks (booklet group, 30%; prepartum group, 35%; pre/post group, 39%; P = .02 [different superscripts denote differences at P < .05]) and at 6 months (booklet group, 26%, prepartum group, 24%; pre/post group, 33%; P = .04) postpartum. A nonsignificant reduction in relapse among the pre/post group contributed to differences in prevalent abstinence. There was no differenc...

Research paper thumbnail of The reporting of pre-existing maternal medical conditions and complications of pregnancy on birth certificates and in hospital discharge data

American Journal of Obstetrics and Gynecology, 2005

The purpose of this study was to determine the accuracy of live-birth certificates and hospital d... more The purpose of this study was to determine the accuracy of live-birth certificates and hospital discharge data that reported of pre-existing maternal medical conditions and complications of pregnancy. Study design: We conducted a population-based validation study in 19 non-federal short-stay hospitals in Washington state with a stratified random sample of 4541 women who had live births between January 1, 2000, and December 31, 2000. True-and false-positive fractions were calculated. Results: Birth certificate and hospital discharge data combined had substantially higher truepositive fractions than did birth certificate data alone for cardiac disease (54% vs 29%), acute or chronic lung disease (24% vs 10%), gestational diabetes mellitus (93% vs 64%), established diabetes mellitus (97% vs 52%), active genital herpes (77% vs 38%), chronic hypertension (70% vs 47%), pregnancy-induced hypertension (74% vs 49%), renal disease (13% vs 2%), and placenta previa (70% vs 33%). For the 2 medical risk factors that are available only on birth certificates, true-positive fractions were 37% for established genital herpes and 68% for being seropositive for hepatitis B surface antigen. Conclusion: In Washington, most medical conditions and complications of pregnancy that affect mothers are substantially underreported on birth certificates, but hospital discharge data are accurate in the reporting of gestational and established diabetes mellitus and placenta previa.

Research paper thumbnail of The association between the length of the QT interval and mortality in the cardiovascular health study

The American Journal of Medicine, 2003

A long QT interval is a risk factor for arrhythmic events and sudden death. Whether moderate QT p... more A long QT interval is a risk factor for arrhythmic events and sudden death. Whether moderate QT prolongation is associated with clinical events in community-dwelling elderly patients is uncertain. METHODS: We measured the QT interval in a populationbased sample of 5888 men and women at least 65 years of age who were participants in the Cardiovascular Health Study. The association between Bazett's rate-corrected QT (QTc, in ms) and mortality during the subsequent 10 years was evaluated. We stratified participants by the presence or absence of coronary heart disease status at baseline, and adjusted for coronary heart disease risk factors. RESULTS: The rates of all-cause and coronary heart disease mortality were greater in participants with longer QTc intervals. Among participants without known coronary heart disease, those whose QTc interval was Ͼ450 ms were at increased risk of all-cause mortality (relative risk [RR] ϭ 1.34; 95% confidence interval [CI]: 1.07 to 1.67) and coronary heart disease mortality (RR ϭ 1.6; 95% CI: 1.0 to 2.5) when compared with participants whose QTc interval was Ͻ410 ms. The associations were stronger among those with known coronary heart disease (RR for all-cause mortality ϭ 2.3; 95% CI: 1.6 to 3.3; and RR for coronary heart disease mortality ϭ 2.0; 95% CI: 1.1 to 3.7). CONCLUSION: The QT interval from the standard electrocardiograms is of value for identification of elderly persons at increased risk of coronary heart disease and total mortality. A QTc interval Ͼ450 ms should prompt clinical evaluation and possible interventions to reduce the risk of coronary events.

Research paper thumbnail of Comparison of Mortality Risk for Electrocardiographic Abnormalities in Men and Women With and Without Coronary Heart Disease (from the Cardiovascular Health Study)

The American Journal of Cardiology, 2006

Mortality risk associated with electrocardiographic (ECG) abnormalities has been commonly reporte... more Mortality risk associated with electrocardiographic (ECG) abnormalities has been commonly reported to be lower in women than in men. We compared coronary heart disease (CHD) and all-cause mortality risk for ECG variables during a mean 9.1-year follow-up in 4,912 participants in the Cardiovascular Health Study who were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 65 years of age. The hypothesis was that mortality risk for ECG abnormalities is not lower in women than in men. Five ECG variables were significant mortality predictors in Cox regression models that were adjusted for demographic, clinical, and medication variables. Gender differences were significant and mortality risk was higher in women for ECG estimates of left ventricular mass for both end points and for nondipolar QRS voltage for all-cause mortality. When evaluated simultaneously in multiple ECG variable risk models in subgroups that were stratified by baseline CHD status, no gender difference was significant. In the latter models, ST depression was a strong predictor of CHD mortality in groups with and without previous CHD. Other significant ECG predictors were previous myocardial infarction in the previous CHD group and nondipolar QRS voltage in the CHD-free group. Four ECG abnormalities were significant predictors of all-cause mortality in the CHD-free group, with risk increases of 18% to 50%. The risk of all-cause mortality in the previous CHD group was significantly increased for ST depression (by 64%), the ECG estimate of left ventricular mass (by 48%), and previous myocardial infarction (by 34%). In conclusion, we found no evidence that the relative risk of mortality for ECG abnormalities is lower in women than in men.

Research paper thumbnail of Safety of repeated doses of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine in adults and adolescents

Pharmacoepidemiology and drug safety, Jan 3, 2018

In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria ... more In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.

Research paper thumbnail of Sequential surveillance for drug safety in a regulatory environment

Pharmacoepidemiology and drug safety, Jan 5, 2018

Research paper thumbnail of The impact of selection bias on vaccine effectiveness estimates from test-negative studies

Vaccine, Jan 15, 2017

Estimates of vaccine effectiveness (VE) from test-negative studies may be subject to selection bi... more Estimates of vaccine effectiveness (VE) from test-negative studies may be subject to selection bias. In the context of influenza VE, we used simulations to identify situations in which meaningful selection bias can occur. We also analyzed observational study data for evidence of selection bias. For the simulation study, we defined a hypothetical population whose members are at risk for acute respiratory illness (ARI) due to influenza and other pathogens. An unmeasured "healthcare seeking proclivity" affects both probability of vaccination and probability of seeking care for an ARI. We varied the direction and magnitude of these effects and identified situations where meaningful bias occurred. For the observational study, we reanalyzed data from the United States Influenza VE Network, an ongoing test-negative study. We compared "bias-naïve" VE estimates to bias-adjusted estimates, which used data from the source populations to correct for sampling bias. In the sim...

Research paper thumbnail of Design and analysis choices for safety surveillance evaluations need to be tuned to the specifics of the hypothesized drug-outcome association

Pharmacoepidemiology and drug safety, Sep 14, 2016

We reviewed the results of the Observational Medical Outcomes Research Partnership (OMOP) 2010 Ex... more We reviewed the results of the Observational Medical Outcomes Research Partnership (OMOP) 2010 Experiment in hopes of finding examples where apparently well-designed drug studies repeatedly produce anomalous findings. OMOP had applied thousands of designs and design parameters to 53 drug-outcome pairs across 10 electronic data resources. Our intent was to use this repository to elucidate some sources of error in observational studies. From the 2010 OMOP Experiment, we sought drug-outcome-method combinations (DOMCs) that met consensus design criteria, yet repeatedly produced results contrary to expectation. We set aside DOMCs for which we could not agree on the suitability of the designs, then selected for an in-depth scrutiny one drug-outcome pair analyzed by a seemingly plausible methodological approach, whose results consistently disagreed with the a priori expectation. The OMOP "all-by-all" assessment of possible DOMCs yielded many combinations that would not be chosen ...

Research paper thumbnail of Post licensure surveillance of influenza vaccines in the Vaccine Safety Datalink in the 2013-2014 and 2014-2015 seasons

Pharmacoepidemiology and Drug Safety, 2016

Purpose The changes in each year in influenza vaccine antigenic components as well as vaccine adm... more Purpose The changes in each year in influenza vaccine antigenic components as well as vaccine administration patterns may pose new risks of adverse events following immunization (AEs). To evaluate the safety of influenza vaccines annually administered to people ≥ 6 months, we conducted weekly post licensure surveillance for seven pre-specified adverse events following receipt of influenza vaccines during the 2013-2014 and 2014-2015 seasons in the Vaccine Safety Datalink (VSD). Methods We used both a historically-controlled cohort design with the Poisson-based maximized sequential probability ratio test (maxSPRT) and a self-controlled risk interval (SCRI) design with the binomial-based maxSPRT. For each adverse event outcome, we defined the risk interval on the basis of biologic plausibility and prior literature. For the historical cohort design, numbers of expected adverse events were calculated from the prior seven seasons, adjusted for age and site. For the SCRI design, a comparison window was defined either before vaccination or after vaccination, depending on each specific outcome. Results An elevated risk of febrile seizures 0-1 days following trivalent inactivated influenza vaccine (IIV3) was identified in children aged 6-23 months during the 2014-2015 season using the SCRI design. We found the relative risk (RR) of febrile seizures following concomitant administration of IIV3 and PCV13 was 5.3 with a 95% CI 1.87-14.75. Without concomitant PCV 13 administration, the estimated risk decreased and was no longer statistically significant (RR: 1.4; CI: 0.54-3.61).

Research paper thumbnail of Prophylaxis with acetaminophen or ibuprofen for prevention of local reactions to the fifth diphtheria-tetanus toxoids-acellular pertussis vaccination: a randomized, controlled trial

Pediatrics, 2006

The frequency of local vaccination reactions increases with successive doses of diphtheria-tetanu... more The frequency of local vaccination reactions increases with successive doses of diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccine, and local reactions occur for the majority of children receiving the fifth DTaP vaccination. It is not known whether these reactions can be prevented with prophylactic use of acetaminophen or ibuprofen. In this 3-group, randomized, blinded, controlled trial, 372 children were assigned randomly, in a 2:2:1 ratio, to receive 3 doses of acetaminophen, ibuprofen, or placebo. The first dose of study medication was administered within 2 hours before the fifth DTaP vaccination, and the remaining 2 doses were given at 6-hour intervals. The primary outcome measures included a local reaction with an area of redness or discoloration > or =5 cm in diameter on the evening of or during the 2 days after vaccination, an increase in mid-limb circumference of > or =2 cm on the evening of or during the 2 days after vaccination, and a persistent local reac...

Research paper thumbnail of Safety of varying dosages of 7-valent pneumococcal protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine

Vaccine, 2005

In a phase I/II dose escalation study, varying volumes (0.1 ml, 0.5 ml, 1.0 ml and 2.0 ml) of 7-v... more In a phase I/II dose escalation study, varying volumes (0.1 ml, 0.5 ml, 1.0 ml and 2.0 ml) of 7-valent pneumococcal conjugate vaccine (PCV) (Prevnar or 0.5 ml of 23-valent pneumococcal polysaccharide vaccine (PPV) were administered to 220 adults 70 through 79 years of age previously vaccinated with 0.5 ml PPV at age 65 years or above and at least 5 years previously. Fever was uncommon and did not vary by study group. The rate of local reactions increased with higher volumes of PCV and the rate following 2.0 ml of PCV was comparable to that following 0.5 ml PPV.

Research paper thumbnail of Immunogenicity of varying dosages of 7-valent pneumococcal polysaccharide–protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine

Vaccine, 2007

In this dose-ranging study 220 seniors who had received the 23-valent pneumococcal polysaccharide... more In this dose-ranging study 220 seniors who had received the 23-valent pneumococcal polysaccharide (PnPS) vaccine at least 5 years prior to enrollment were assigned to receive one of four volumes (0.1, 0.5, 1 or 2 ml) of 7-valent pneumococcal conjugate (PnC) vaccine or a 0.5 ml dose of 23-valent PnPS vaccine. All participants received a reduced challenge dose of 0.1 ml of PnPS vaccine 1 year after enrollment. There was evidence of a dose response to PnC vaccine and antibody levels in the 1 ml PnC group tended to be significantly higher than in the PnPS group. A booster response to the challenge vaccination was not observed. Administration of a 1 ml dose of PnC vaccine is more immunogenic than 0.5 ml of PnPS vaccine in elderly adults previously vaccinated with PnPS vaccine.

Research paper thumbnail of Assessment of the safety of a third dose of pneumococcal polysaccharide vaccine in the Vaccine Safety Datalink population

Vaccine, 2006

There is little information on the safety of administration of a third dose of pneumococcal polys... more There is little information on the safety of administration of a third dose of pneumococcal polysaccharide vaccine (PPV). The authors conducted a retrospective assessment of 316,995 adult members of three health maintenance organizations who had received one, two, or three PPV doses. Medical encounters associated with diagnosis codes potentially indicative of an injection site reaction in the week following a first, second, or third PPV dose were identified. These presumptive events occurred in 0.3% (911/279504) of the first PPV group, 0.7% (257/36888) of the second PPV group, and 0.5% (3/603) of the third PPV group (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.5 for both comparisons with the third PPV group). These findings do not suggest that a third PPV dose is associated with an increased risk of medically attended injection site reactions compared with a first or second PPV dose.

Research paper thumbnail of Vaccines and changes in coagulation parameters in adults on chronic warfarin therapy: a cohort study

Pharmacoepidemiology and Drug Safety, 2007

Purpose Warfarin is commonly used among patients who receive influenza, pneumococcal, and tetanus... more Purpose Warfarin is commonly used among patients who receive influenza, pneumococcal, and tetanus and diphtheria toxoid vaccines, and persons on warfarin therapy may also receive Hepatitis A vaccine. There has been concern that vaccinations could potentially alter coagulation parameters in patients on warfarin therapy. We sought to determine whether vaccinations are associated with changes in International Normalized Ratio (INR) in persons on long-term warfarin therapy. Methods We conducted a retrospective cohort study of 5167 members of Group Health, a health maintenance organization (HMO) in western Washington State, who were aged 18 years and older and who were on stable long-term warfarin therapy between 1 January 1992 and 31 December 2003. We made within-person comparisons between mean INR values in the 28 days after receipt of influenza, pneumococcal, tetanus, or hepatitis A vaccine versus mean INR values during other times. Results Receipt of influenza vaccine was not associated with a change in INR value (mean change, 0.01; 95% confidence interval (CI) À0.01 to 0.03); similar results were observed for pneumococcal (mean change 0.01; 95%CI À0.07 to 0.09), tetanus (mean change 0.03; 95%CI À0.03 to 0.10), and hepatitis A vaccines (mean change 0.03; 95%CI À0.10 to 0.14). Conclusions Our results do not suggest that vaccinations lead to clinically significant alterations in coagulation measures among adults on chronic warfarin therapy.

Research paper thumbnail of Accuracy of reporting maternal in-hospital diagnoses and intrapartum procedures in Washington State linked birth records

Paediatric and Perinatal Epidemiology, 2005

While the impact of maternal morbidities and intrapartum procedures is a common topic in perinata... more While the impact of maternal morbidities and intrapartum procedures is a common topic in perinatal outcomes research, the accuracy of the reporting of these variables in the large administrative databases (birth certificates, hospital discharges) often utilised for such research is largely unknown. We conducted this study to compare maternal diagnoses and procedures listed on birth certificates, hospital discharge data, and birth certificate and hospital discharge data combined, with those documented in a stratified random sample of hospital medical records of 4541 women delivering liveborn infants in Washington State in 2000. We found that birth certificate and hospital discharge data combined had substantially higher true positive fractions (TPF, proportion of women with a positive medical record assessment who were positive using the administrative databases) than did birth certificate data alone for labour induction (86% vs. 52%), cephalopelvic disproportion (83% vs. 35%), abruptio placentae (85% vs. 68%), and forceps-assisted delivery (89% vs. 55%). For procedures available only in hospital discharge data, TPFs were generally high: episiotomy (85%) and third and fourth degree vaginal lacerations (91%). Except for repeat caesarean section without labour (TPF, 81%), delivery procedures available only in birth certificate data had low TPFs, including augmentation (34%), repeat caesarean section with labour (61%), and vaginal birth after caesarean section (62%). Our data suggest that researchers conducting perinatal epidemiological studies should not rely solely on birth certificate data to detect maternal diagnoses and intrapartum procedures accurately.

Research paper thumbnail of Induction of Labor in the Absence of Standard Medical Indications

Medical Care, 2007

Background: Induction of labor is an increasingly common obstetrical procedure, with approximatel... more Background: Induction of labor is an increasingly common obstetrical procedure, with approximately 20-34% of women undergoing labor induction in the United States annually. Objective: To determine the extent of labor induction in the absence of standard medical indications and to assess possible associations with maternal and infant characteristics and hospital factors. Methods: We ascertained induction of labor and associated details as part of a medical record validation study of 4541 women with live, singleton births in 2000 in Washington State using medical record, birth certificate, and hospital discharge data. In this analysis, we report findings for the 1473 women (33% of original cohort) whose medical records indicated that their labors were induced. Results: Among women with induced labor, 7.9% had no clinical information providing an indication for the induction, and 6.4% had only "nonstandard" indications recorded. Compared with women delivering in moderate volume hospitals, women who delivered at lower volume (odds ratios ͓OR͔ 3.9; 95% confidence intervals ͓CI͔ 1.8-8.6) or higher volume hospitals (OR 4.2; 95% CI 2.4-7.2) had significantly increased risk for undocumented indication of labor. Women who had undocumented indication for induction were at significantly decreased risk of giving birth at a teaching hospital and a public nonfederally owned hospital, and were at greater risk to give birth at a private religious hospital. Factors that remained independently associated with nonstandard indication for induction of labor were primiparas (OR 2.4; 95% CI 1.3-4.2); multiparas (OR 4.3; 95% CI 2.5-7.4), pregnancyinduced hypertension (OR 0.2; 95% CI 0.1-0.4), hospital volume Ն2000 births annually (OR 19.9; 95% CI 6.7-58.6), primary (OR 11.7; 95% CI 4.1-33.6), and tertiary level hospital (OR 0.4; 95% CI 0.2-0.7). Conclusions: Our findings suggest that nearly 15% of inductions either were not clinically indicated according to standard protocols or indications were incompletely documented. At minimum, further studies are needed to explore how best to improve documentation of indications of labor because accurately describing, among other things, the process of labor induction, is a basic benchmark of care.

Research paper thumbnail of New strategies are needed to improve the accuracy of influenza vaccine effectiveness estimates among seniors

Journal of Clinical Epidemiology, 2009

Objective: The magnitude of the benefit of influenza vaccine among elderly individuals has been r... more Objective: The magnitude of the benefit of influenza vaccine among elderly individuals has been recently debated. Existing vaccine effectiveness estimates derive primarily from observational studies, which may be biased. In this paper, we provide a methodological examination of the potential sources of bias in observational studies of influenza vaccine effectiveness in seniors and propose design and analysis strategies to reduce bias in future studies. Study Design and Setting: We draw parallels to bias documented in observational studies of therapies in other areas of medical research including pharmacoepidemiology, discuss reasons why existing adjustment methods in influenza studies may not adequately control for the bias, and evaluate statistical approaches that may yield more accurate estimation of influenza vaccine effectiveness. Results: There is strong evidence for the presence of bias in existing observational estimates of influenza vaccine effectiveness in the elderly and the failure of current adjustment methods to reduce bias. Conclusion: Promising approaches for reducing bias include obtaining more accurate information on confounders, such as functional status, avoiding all-cause death in favor of outcomes, such as pneumonia or influenza-related pneumonia, and evaluating the extent to which bias is reduced by these and other methods using the 'control' period before influenza season.

Research paper thumbnail of Stress, depressive symptoms, and smoking cessation among pregnant women

Health Psychology, 2000

Perceived stress and depressive symptoms were examined as correlates and predictors of smoking ce... more Perceived stress and depressive symptoms were examined as correlates and predictors of smoking cessation during pregnancy in a sample of 819 pregnant smokers (454 baseline smokers and 365 baseline quitters). Women who quit early in pregnancy had lower levels of stress and depressive symptoms than baseline smokers. Adjusting for level of addiction and other demographic factors related to stress and depressive symptoms eliminated the significant association between depressive symptoms and smoking cessation. Lower levels of stress and depressive symptoms were not predictive of cessation in later pregnancy. Prenatal healthcare providers should continue to assess level of addiction and provide targeted intensive cessation interventions. Interventions that reduce stress and depression may also be of benefit to women who are continuing smokers in early pregnancy.

Research paper thumbnail of Partner smoking status and pregnant smoker's perceptions of support for and likelihood of smoking cessation

Health Psychology, 1998

Perceptions of support for cessation of smoking during pregnancy, likelihood of quitting, and par... more Perceptions of support for cessation of smoking during pregnancy, likelihood of quitting, and partner smoking status were explored in a sample of 688 pregnant smokers (372 baseline smokers and 316 baseline quitters). Women with nonsmoking partners were significantly more likely to be baseline quitters than women with partners who smoked. Baseline quitters reported significantly more positive support from their partners than did continuing smokers (p = .02). Neither partner smoking status nor partner support at baseline was associated with cessation or relapse later in pregnancy. Women reported greater support, both positive and negative, from nonsmoking partners than from partners who smoked (p = .001). Among partner smokers, those who were trying to quit were perceived to be particularly supportive. Cessation interventions for expectant fathers may increase pregnant women&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s success at quitting.

Research paper thumbnail of Differences in preconceptional and prenatal behaviors in women with intended and unintended pregnancies

American Journal of Public Health, 1998

OBJECTIVES: This study examined whether pregnancy intention was associated with cigarette smoking... more OBJECTIVES: This study examined whether pregnancy intention was associated with cigarette smoking, alcohol drinking, use of vitamins, and consumption of caffeinated drinks prior to pregnancy and in early pregnancy. METHODS: Data from a telephone survey of 7174 pregnant women were analyzed. RESULTS: In comparison with women whose pregnancies were intended, women with unintended pregnancies were more likely to report cigarette smoking and less likely to report daily vitamin use. Women with unintended pregnancies were also less likely to decrease consumption of caffeinated beverages or increase daily vitamin use. CONCLUSIONS: Pregnancy intention was associated with health behaviors, prior to pregnancy and in early pregnancy, that may influence pregnancy course and birth outcomes.

Research paper thumbnail of Prevention of relapse in women who quit smoking during pregnancy

American Journal of Public Health, 1999

OBJECTIVES: This study is an evaluation of relapse prevention interventions for smokers who quit ... more OBJECTIVES: This study is an evaluation of relapse prevention interventions for smokers who quit during pregnancy. METHODS: Pregnant smokers at 2 managed care organizations were randomized to receive a self-help booklet only, prepartum relapse prevention, or prepartum and postpartum relapse prevention. Follow-up surveys were conducted at 28 weeks of pregnancy and at 8 weeks, 6 months, and 12 months postpartum. RESULTS: The pre/post intervention delayed but did not prevent postpartum relapse to smoking. Prevalent abstinence was significantly greater for the pre/post intervention group than for the other groups at 8 weeks (booklet group, 30%; prepartum group, 35%; pre/post group, 39%; P = .02 [different superscripts denote differences at P < .05]) and at 6 months (booklet group, 26%, prepartum group, 24%; pre/post group, 33%; P = .04) postpartum. A nonsignificant reduction in relapse among the pre/post group contributed to differences in prevalent abstinence. There was no differenc...

Research paper thumbnail of The reporting of pre-existing maternal medical conditions and complications of pregnancy on birth certificates and in hospital discharge data

American Journal of Obstetrics and Gynecology, 2005

The purpose of this study was to determine the accuracy of live-birth certificates and hospital d... more The purpose of this study was to determine the accuracy of live-birth certificates and hospital discharge data that reported of pre-existing maternal medical conditions and complications of pregnancy. Study design: We conducted a population-based validation study in 19 non-federal short-stay hospitals in Washington state with a stratified random sample of 4541 women who had live births between January 1, 2000, and December 31, 2000. True-and false-positive fractions were calculated. Results: Birth certificate and hospital discharge data combined had substantially higher truepositive fractions than did birth certificate data alone for cardiac disease (54% vs 29%), acute or chronic lung disease (24% vs 10%), gestational diabetes mellitus (93% vs 64%), established diabetes mellitus (97% vs 52%), active genital herpes (77% vs 38%), chronic hypertension (70% vs 47%), pregnancy-induced hypertension (74% vs 49%), renal disease (13% vs 2%), and placenta previa (70% vs 33%). For the 2 medical risk factors that are available only on birth certificates, true-positive fractions were 37% for established genital herpes and 68% for being seropositive for hepatitis B surface antigen. Conclusion: In Washington, most medical conditions and complications of pregnancy that affect mothers are substantially underreported on birth certificates, but hospital discharge data are accurate in the reporting of gestational and established diabetes mellitus and placenta previa.

Research paper thumbnail of The association between the length of the QT interval and mortality in the cardiovascular health study

The American Journal of Medicine, 2003

A long QT interval is a risk factor for arrhythmic events and sudden death. Whether moderate QT p... more A long QT interval is a risk factor for arrhythmic events and sudden death. Whether moderate QT prolongation is associated with clinical events in community-dwelling elderly patients is uncertain. METHODS: We measured the QT interval in a populationbased sample of 5888 men and women at least 65 years of age who were participants in the Cardiovascular Health Study. The association between Bazett's rate-corrected QT (QTc, in ms) and mortality during the subsequent 10 years was evaluated. We stratified participants by the presence or absence of coronary heart disease status at baseline, and adjusted for coronary heart disease risk factors. RESULTS: The rates of all-cause and coronary heart disease mortality were greater in participants with longer QTc intervals. Among participants without known coronary heart disease, those whose QTc interval was Ͼ450 ms were at increased risk of all-cause mortality (relative risk [RR] ϭ 1.34; 95% confidence interval [CI]: 1.07 to 1.67) and coronary heart disease mortality (RR ϭ 1.6; 95% CI: 1.0 to 2.5) when compared with participants whose QTc interval was Ͻ410 ms. The associations were stronger among those with known coronary heart disease (RR for all-cause mortality ϭ 2.3; 95% CI: 1.6 to 3.3; and RR for coronary heart disease mortality ϭ 2.0; 95% CI: 1.1 to 3.7). CONCLUSION: The QT interval from the standard electrocardiograms is of value for identification of elderly persons at increased risk of coronary heart disease and total mortality. A QTc interval Ͼ450 ms should prompt clinical evaluation and possible interventions to reduce the risk of coronary events.

Research paper thumbnail of Comparison of Mortality Risk for Electrocardiographic Abnormalities in Men and Women With and Without Coronary Heart Disease (from the Cardiovascular Health Study)

The American Journal of Cardiology, 2006

Mortality risk associated with electrocardiographic (ECG) abnormalities has been commonly reporte... more Mortality risk associated with electrocardiographic (ECG) abnormalities has been commonly reported to be lower in women than in men. We compared coronary heart disease (CHD) and all-cause mortality risk for ECG variables during a mean 9.1-year follow-up in 4,912 participants in the Cardiovascular Health Study who were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 65 years of age. The hypothesis was that mortality risk for ECG abnormalities is not lower in women than in men. Five ECG variables were significant mortality predictors in Cox regression models that were adjusted for demographic, clinical, and medication variables. Gender differences were significant and mortality risk was higher in women for ECG estimates of left ventricular mass for both end points and for nondipolar QRS voltage for all-cause mortality. When evaluated simultaneously in multiple ECG variable risk models in subgroups that were stratified by baseline CHD status, no gender difference was significant. In the latter models, ST depression was a strong predictor of CHD mortality in groups with and without previous CHD. Other significant ECG predictors were previous myocardial infarction in the previous CHD group and nondipolar QRS voltage in the CHD-free group. Four ECG abnormalities were significant predictors of all-cause mortality in the CHD-free group, with risk increases of 18% to 50%. The risk of all-cause mortality in the previous CHD group was significantly increased for ST depression (by 64%), the ECG estimate of left ventricular mass (by 48%), and previous myocardial infarction (by 34%). In conclusion, we found no evidence that the relative risk of mortality for ECG abnormalities is lower in women than in men.