Kenneth J Rothman

RTI Health Solutions, Durham, North Carolina, United States

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Publications (243)1697.11 Total impact

  • Morten Schmidt, Kenneth J Rothman
    International journal of cardiology. 10/2014; 177(3):1089-1090.
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    ABSTRACT: Background Several studies indicate that female obesity increases the risk of spontaneous abortion (SAB). Central adiposity, height, and location of typical weight gain have not been examined as risk factors for SAB.Methods We examined the associations between selected anthropometric factors and risk of SAB among 5132 women enrolled in a Danish Internet-based prospective cohort study of pregnancy planners. We used Cox proportional hazards regression models, with gestational weeks as the time scale, to compute hazard ratios (HRs) of SAB and 95% confidence intervals (CIs).ResultsAfter adjustment for potential confounders, the HRs for SAB among underweight (body mass index (BMI, kg/m2) <20), overweight (BMI: 25–29) and obese (BMI ≥30) women were 1.00 [95% CI: 0.81, 1.24], 0.90 [95% CI: 0.73, 1.09] and 1.23 [95% CI: 0.98, 1.54], respectively, compared with normal weight women (BMI 20–24). The association between obesity and SAB was stronger for early SAB (<8 weeks gestation); HR: 1.34 95% CI: 1.01, 1.77. The HR for height ≥174 cm vs. <166 cm was 0.81 [95% CI: 0.66, 1.00]. Increased waist-to-hip ratio (WHR) was inversely associated with risk of SAB (HR: 0.81; 95% CI: 0.63, 1.05). Waist circumference and location of typical weight gain were not appreciably associated with SAB risk.Conclusions This study confirms previous studies that have shown a small positive association between obesity and SAB risk. Our results suggest that obesity is a stronger risk factor for early pregnancy losses, and that small stature and low WHR are associated with an increased risk of SAB.
    Paediatric and Perinatal Epidemiology 09/2014; 28(5). · 2.16 Impact Factor
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    ABSTRACT: Prenatal termination of pregnancy may underestimate risks or cause bias in epidemiological studies of birth defects if such studies measure only defects diagnosed postnatally. We aimed to estimate the proportion of all fetuses with birth defects terminated in the second trimester of pregnancy-overall and for specific defects.
    Epidemiology (Cambridge, Mass.) 08/2014; · 5.51 Impact Factor
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    ABSTRACT: In longitudinal studies, the onset of the index condition (e.g. exposure) does not always coincide with the start of a study's observation period, leading to the possibility of bias in estimation that derives from studying prevalent exposure rather than new exposure. We investigate the possible role of this bias in the relationship between periodontitis progression and coronary heart disease (CHD) among a cohort of men participating in the Veterans Administration Dental Longitudinal Study.
    Annals of Epidemiology 07/2014; · 2.48 Impact Factor
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    ABSTRACT: Maternal diabetes preceding pregnancy may increase the risk of birth defects in the offspring, but not all studies confirm this association, which has shown considerable variation over time, and the effect of having type 1 versus type 2 diabetes is unclear. We conducted a population-based cohort study in the Northern Italy Emilia-Romagna region linking administrative databases with a Birth Defects Registry. From hospital discharge records we identified all diabetic pregnancies during 1997-2010, and a population of non-diabetic parturients matched for age, residence, year and delivery hospital. We collected available information on education, smoking and drug prescriptions, from which we inferred the type of diabetes. We found 62 malformed infants out of 2,269 births among diabetic women, and 162 out of 10,648 births among non-diabetic women. The age-standardized prevalence ratio (PR) of malformation associated with maternal pregestational diabetes was 1.79 (95 % confidence interval 1.34-2.39), a value that varied little by age. Type of diabetes strongly influenced the PR, with higher values related to type 2 diabetic women. Most major subgroups of anomalies had PRs above 1, including cardiovascular, genitourinary, musculoskeletal, and chromosomal abnormalities. There was an unusually high PR for the rare defect 'extra-ribs', but it was based on only two cases. This study indicates that maternal pregestational type 2 diabetes is associated with a higher prevalence of specific birth defects in offspring, whereas for type 1 diabetic mothers, particularly in recent years, the association was unremarkable.
    European Journal of Epidemiology 05/2014; · 5.12 Impact Factor
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    ABSTRACT: To investigate the extent to which fecundability is associated with active smoking, time since smoking cessation, and passive smoking. Prospective cohort study. Denmark, 2007-2011. A total of 3,773 female pregnancy planners aged 18-40 years. None. Self-reported pregnancy. Fecundability ratios (FRs) and 95% confidence intervals (CIs) were estimated using a proportional probabilities model that adjusted for menstrual cycle at risk and potential confounders. Among current smokers, smoking duration of ≥10 years was associated with reduced fecundability compared with never smokers (FR, 0.85, 95% CI 0.72-1.00). Former smokers who had smoked ≥10 pack-years had reduced fecundability regardless of when they quit smoking (1-1.9 years FR, 0.83, 95% CI 0.54-1.27; ≥2 years FR, 0.73, 95% CI 0.53-1.02). Among never smokers, the FRs were 1.04 (95% CI 0.89-1.21) for passive smoking in early life and 0.92 (95% CI 0.82-1.03) for passive smoking in adulthood. Among Danish pregnancy planners, cumulative exposure to active cigarette smoking was associated with delayed conception among current and former smokers. Time since smoking cessation and passive smoking were not appreciably associated with fecundability.
    Fertility and sterility 04/2014; · 3.97 Impact Factor
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    ABSTRACT: First marketed in the USA in 1996, topiramate (TPM) is an antiepileptic drug later approved for migraine prophylaxis, and in 2012 for weight loss in combination with phentermine. Some studies indicate an elevated prevalence of oral cleft (OC) in infants exposed to TPM in utero. We evaluated the association between TPM use in early pregnancy and the risk of OC. This retrospective cohort study used 1997-2011 automated data from four sources: HealthCore and OptumInsight (commercial insurance claims), Truven Health (Medicaid claims), and Kaiser Permanente Northern California Region (electronic medical records). We compared the prevalence of OCs in infants of women exposed to TPM in the first trimester (TPM cohort) with the prevalence in infants of women formerly exposed to TPM or other antiepileptic drugs (formerly exposed [FE] cohort) and infants of women with similar medical profiles (SMPs) to the TPM cohort that were not exposed to TPM (SMP cohort). To control for confounding, we used stratification and standardization for individual variables and propensity score deciles. The birth prevalence of OCs was 0.36% (7/1945) in the TPM cohort, 0.14% (20/13 512) in the FE cohort, and 0.07% (9/13 614) in the SMP cohort. Standardized by site, the prevalence ratio (PR) for TPM versus FE was 2.5 (95% CI: 1.0-6.0) and for TPM versus SMP was 5.4 (95% CI: 2.0-14.6). Adjustment for covariates one at a time or by propensity score yielded similar results. Consistent with other recent epidemiologic research, first-trimester TPM exposure was associated with an elevated birth prevalence of OC. Copyright © 2014 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 04/2014; · 2.90 Impact Factor
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    ABSTRACT: The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma (EXCELS) assessed the long-term safety of omalizumab in a clinical practice setting as part of a phase IV US Food and Drug Administration postmarketing commitment. We sought to evaluate long-term safety in omalizumab-treated and nonomalizumab-treated patients. Primary outcome measures focused on assessment of malignancies. EXCELS was a prospective observational cohort study in patients (≥12 years of age) with moderate-to-severe allergic asthma. There were 2 cohorts: omalizumab (taking omalizumab at baseline) and nonomalizumab (no history of omalizumab treatment). Primary outcomes included all confirmed, incident, study-emergent primary malignancies (malignancies), including and excluding nonmelanoma skin cancer (NMSC); all malignancies were externally adjudicated. The omalizumab cohort had a higher proportion of patients with severe asthma compared with the nonomalizumab cohort (50.0% vs 23.0%). Median follow-up was approximately 5 years for both cohorts. Crude malignancy rates were similar in the omalizumab and nonomalizumab cohorts, with a rate ratio of 0.84 (95% CI, 0.62-1.13) for all malignancies and 0.98 (95% CI, 0.71-1.36) for all malignancies excluding NMSC. Kaplan-Meier plots of time to first confirmed study-emergent primary malignancy were similar for the 2 treatment cohorts. Cox proportional hazards modeling, adjusting for confounders and risk factors, resulted in a hazard ratio (omalizumab vs nonomalizumab) of 1.09 (95% CI, 0.87-1.38) for all malignancies and 1.15 (95% CI, 0.83-1.59) for all malignancies excluding NMSC. Results from EXCELS suggest that omalizumab therapy is not associated with an increased risk of malignancy.
    The Journal of allergy and clinical immunology 03/2014; · 12.05 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting 1% to 2% of the population and raising the risk of stroke 5-fold. Until recently, the only treatment choices for stroke prevention in patients with AF have been vitamin K antagonists (VKA) or antiplatelet drugs. With approval of novel oral anticoagulants (NOACs) antithrombotic treatment, patterns are changing. The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation is designed to investigate patient characteristics influencing choice of antithrombotic treatment of stroke prevention in patients with nonvalvular AF and to collect data on outcomes of antithrombotic therapy in clinical practice. The GLORIA-AF is a large, international, observational registry involving patients with newly diagnosed nonvalvular AF at risk for stroke, enrolling up to 56,000 patients in nearly 50 countries. We will collect and analyze data from routine care using an inception cohort design. Phase I includes patients before approval of NOACs. Phase II, beginning early after approval of dabigatran, monitors dabigatran safety and addresses potential channeling across treatment options based on propensity scoring to assess comparability of baseline characteristics of patients treated with dabigatran or VKA. Phase III entails analysis of large treatment groups, adjusting for differences in propensity score, to provide information about the relative effectiveness and safety of NOACs and VKA in routine clinical care. Novel features of this registry program will add data from clinical practice to those from randomized trials to expand knowledge of antithrombotic treatment in patients with AF.
    American heart journal 03/2014; 167(3):329-34. · 4.65 Impact Factor
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    Kenneth J Rothman
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    ABSTRACT: Scientific knowledge changes rapidly, but the concepts and methods of the conduct of research change more slowly. To stimulate discussion of outmoded thinking regarding the conduct of research, I list six misconceptions about research that persist long after their flaws have become apparent. The misconceptions are: 1) There is a hierarchy of study designs; randomized trials provide the greatest validity, followed by cohort studies, with case-control studies being least reliable. 2) An essential element for valid generalization is that the study subjects constitute a representative sample of a target population. 3) If a term that denotes the product of two factors in a regression model is not statistically significant, then there is no biologic interaction between those factors. 4) When categorizing a continuous variable, a reasonable scheme for choosing category cut-points is to use percentile-defined boundaries, such as quartiles or quintiles of the distribution. 5) One should always report P values or confidence intervals that have been adjusted for multiple comparisons. 6) Significance testing is useful and important for the interpretation of data. These misconceptions have been perpetuated in journals, classrooms and textbooks. They persist because they represent intellectual shortcuts that avoid more thoughtful approaches to research problems. I hope that calling attention to these misconceptions will spark the debates needed to shelve these outmoded ideas for good.
    Journal of General Internal Medicine 01/2014; · 3.28 Impact Factor
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    ABSTRACT: To examine the association between a woman's birth weight and her subsequent fecundability. In this prospective cohort study, we included 2,773 Danish pregnancy planners enrolled in the internet-based cohort study "Snart-Gravid", conducted during 2007-2012. Participants were 18-40 years old at study entry, attempting to conceive, and were not receiving fertility treatment. Data on weight at birth were obtained from the Danish Medical Birth Registry and categorized as <2,500 grams, 2,500-2,999 grams, 3,000-3,999 grams, and ≥4,000 grams. In additional analyses, birth weight was categorized according to z-scores for each gestational week at birth. Time-to-pregnancy measured in cycles was used to compute fecundability ratios (FR) and 95% confidence intervals (CI), using a proportional probabilities regression model. Relative to women with a birth weight of 3,000-3,999 grams, FRs adjusted for gestational age, year of birth, and maternal socio-demographic and medical factors were 0.99 (95% CI: 0.73;1.34), 0.99 (95% CI: 0.87;1.12), and 1.08 (95% CI: 0.94;1.24) for birth weight <2,500 grams, 2,500-2,999 grams, and ≥4,000 grams, respectively. Estimates remained unchanged after further adjustment for markers of the participant's mother's fecundability. We obtained similar results when we restricted to women who were born at term, and to women who had attempted to conceive for a maximum of 6 cycles before study entry. Results remained similar when we estimated FRs according to z-scores of birth weight. Our results indicate that birth weight appears not to be an important determinant of fecundability.
    PLoS ONE 01/2014; 9(4):e95257. · 3.53 Impact Factor
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    Pharmacoepidemiology and Drug Safety 01/2014; 23(1):109-10. · 2.90 Impact Factor
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    ABSTRACT: Study Objective To estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials—amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin—compared with nonusers of these antimicrobials. DesignRetrospective, observational cohort study with a nested case-control analysis. Data SourceHealthCore Integrated Research Database. PatientsAdults with continuous health plan enrollment for at least 6 months before study entry who had a new dispensing of a study antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses indicating noninfectious liver injury during follow-up. To control for potentially confounding risk factors, 10 controls at risk for liver injury during follow-up were matched to each case by age, sex, and event date (liver injury date of the case), and analyses were adjusted for medical history, concomitant drugs, and health care service use. Measurements and Main ResultsTwo physician reviewers (blind to exposure) validated the cases. Among 1.3 million antimicrobial users, we identified 607 cases of liver injury, including 82 cases of severe hepatocellular injury and 11 cases of liver failure. Liver injury incidence in nonusers of study antimicrobials was 35/100,000 person-years (95% confidence interval [CI] 29–42/100,000 person-years). For valid cases, the adjusted relative risk among current users of multiple antimicrobials was 3.2 (95% CI 1.6–6.7). Levofloxacin had the highest relative risk for current single use (3.2, 95% CI 1.8–5.8). Relative risks were also elevated for amoxicillin-clavulanic acid (2.5, 95% CI 1.3–5.0), doxycycline (2.5, 95% CI 1.2–5.2), moxifloxacin (2.3, 95% CI 1.1–4.7), and amoxicillin (2.3, 95% CI 1.1–4.7). Conclusion The results support a comparatively high adjusted relative risk of liver injury among patients exposed concurrently to multiple antimicrobials and modest elevations in the risk for several antimicrobials used alone; however, we found little evidence of any strong effect of commonly used antimicrobials on the risk of liver injury.
    Pharmacotherapy 11/2013; · 2.31 Impact Factor
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    ABSTRACT: We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRDSM) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis. Liver test results were used to confirm case status according to published criteria. Two physician reviewers experienced in studying acute liver injury (blinded to study drug exposures) evaluated data abstracted from hospital and emergency department records to validate potential cases. Of 715 potential cases having claims associated with any of the primary screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295 (41%) were of uncertain status (records inadequate for validation). Among potential cases with adequate medical records, the PPV for presence of any of the primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%). Evaluation of cases of noninfectious liver injury using hospital and emergency department medical records continues to represent the preferred approach in studies using insurance claims data.
    Current drug safety. 10/2013;
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    Nathan Schachtman, Kenneth J. Rothman, Timothy L. Lash
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    ABSTRACT: This Amicus Brief challenged the United States government's use of a questionable statistical orthodoxy to maintain a Wire Fraud Act prosecution and conviction against a scientist for describing the results of a body of empirical data as "demonstrating" causality. The Brief, filed in support of Dr. Harkonen's petition for writ of certiorari in the U.S. Supreme Court, shows that the government misrepresented factual and theoretical aspects of statistical significance testing, as well as how significance testing is used in practice by government, academic, and private sector scientists in biological and medical research.
  • Fertility and Sterility 09/2013; 100(3):S336. · 4.17 Impact Factor
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    ABSTRACT: The U.S. Food and Drug Administration (FDA)'s Mini‐Sentinel pilot has created a distributed data system with over 125 million lives and nearly 350 million person‐years of observation time. The pilot allows the FDA to use modular analytic programs to assess suspected safety signals quickly. The FDA convened a committee to assess the implications of such rapid assessments on subsequent analyses of the same product–outcome pair using the same data. The committee offers several non‐binding recommendations based on the strength of the knowledge of the suspected association before running the analysis: signal generation (an analysis with no prior), signal refinement (an analysis with a weak or moderate prior), and signal evaluation (an analysis with a strong prior). The committee believes that modular programs (MPs) are most useful for signal refinement. If MPs are used for analyses with no or weak/moderate priors, the committee members generally agree that the data may be re‐used if certain conditions are met. When there is a strong prior, the committee recommends that a protocol‐based assessment be used; Mini‐Sentinel data may be analyzed by MPs and re‐used only under very uncommon circumstances. The committee agrees that any subsequent assessment of the same product–outcome pair that follows an MP analysis should not be interpreted as independent confirmation of the association, such as would be established via replication of the same product–outcome association in two different populations. Instead, the follow‐up assessment should be interpreted as an analysis that has reduced insofar as possible systematic errors that may have been present or residual in the original MP analysis. The committee also discussed how this general framework may apply to two completed rapid assessments of dabigatran and bleeding risk and of olmesartan and celiac disease risk. Copyright © 2013 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 08/2013; · 2.90 Impact Factor
  • Kenneth J Rothman, John Ej Gallacher, Elizabeth E Hatch
    International Journal of Epidemiology 08/2013; 42(4):1012-4. · 6.98 Impact Factor
  • Kenneth J Rothman, John Ej Gallacher, Elizabeth E Hatch
    International Journal of Epidemiology 08/2013; 42(4):1026-8. · 6.98 Impact Factor
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    ABSTRACT: MF59-adjuvanted trivalent influenza vaccine (Novartis Vaccines and Diagnostics, Siena, Italy) has been shown to be more effective than nonadjuvanted vaccine in the elderly population. Here we present results from a large-scale, observational, noninterventional, prospective postlicensure study that evaluated the safety of MF59-adjuvanted vaccine in elderly subjects aged 65 years or more. The study was performed in 5 northern Italian health districts during the 2006-2007, 2007-2008, and 2008-2009 influenza seasons. The choice of vaccine-either adjuvanted vaccine or a nonadjuvanted influenza vaccine-was determined by individual providers on the basis of local influenza vaccination policy. Hospitalizations for potential adverse events of special interest (AESIs) were identified from hospital databases and then reviewed against recognized case definitions to identify confirmed cases of AESI. Cumulative incidences were calculated for AESIs in predefined biologically plausible time windows, as well as in a 6-month window following vaccination. During the 3-year study period, 170,988 vaccine doses were administered to a total of 107,661 persons. Despite the large study size, cases of AESI resulting in hospitalization were rare, and risks of AESI were similar in both the MF59-adjuvanted and nonadjuvanted vaccination groups. In conclusion, similar safety profiles were observed for both nonadjuvanted and MF59-adjuvanted seasonal influenza vaccines in elderly recipients.
    American journal of epidemiology 07/2013; · 5.59 Impact Factor

Publication Stats

5k Citations
1,697.11 Total Impact Points


  • 2007–2014
    • RTI Health Solutions
      Durham, North Carolina, United States
  • 2005–2014
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Division of Pharmacoepidemiology and Pharmacoeconomics
      Boston, Massachusetts, United States
  • 1997–2014
    • Boston University
      • • Department of Epidemiology
      • • Department of Medicine
      • • Section of Preventive Medicine and Epidemiology
      Boston, Massachusetts, United States
  • 1989–2014
    • University of Massachusetts Boston
      • Clinical Epidemiology Research and Training Unit
      Boston, Massachusetts, United States
  • 2013
    • Cardiff University
      Cardiff, Wales, United Kingdom
  • 1997–2013
    • Aarhus University Hospital
      • Department of Clinical Epidemiology
      Århus, Central Jutland, Denmark
  • 2009–2012
    • The University of Manchester
      • School of Translational Medicine
      Manchester, ENG, United Kingdom
    • University of Chichester
      Chichester, England, United Kingdom
    • Research Triangle Park Laboratories, Inc.
      Raleigh, North Carolina, United States
    • University of Rochester
      • Division of Epidemiology
      Rochester, NY, United States
  • 2006–2012
    • RTI International
      Durham, North Carolina, United States
  • 2011
    • Health Effects Institute
      Boston, Massachusetts, United States
  • 2009–2011
    • Amgen
      Thousand Oaks, California, United States
  • 2005–2011
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States
  • 1999–2011
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
    • Oulu University Hospital
      Uleoborg, Oulu, Finland
  • 2001–2009
    • Aalborg University Hospital
      • Department of Cardiology
      Aalborg, Region North Jutland, Denmark
  • 2008
    • CSU Mentor
      Long Beach, California, United States
    • Outcomes Insights
      Westlake Village, California, United States
  • 1981–2005
    • Boston Medical Center
      Boston, Massachusetts, United States
  • 2003
    • Harvard University
      • Department of Epidemiology
      Cambridge, MA, United States
  • 1997–2003
    • Aarhus University
      • Department of Epidemiology and Social Medicine
      Aars, Region North Jutland, Denmark
  • 1987
    • University of Massachusetts Medical School
      • Department of Family Medicine and Community Health
      Worcester, Massachusetts, United States