Timothy L Lash

McGill University, Montréal, Quebec, Canada

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Publications (238)1156.43 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Many prostate cancer patients die of other causes, but it remains unknown whether comorbidity interacts synergistically with prostate cancer to increase the mortality rate beyond that explained by the individual risks of comorbidity and prostate cancer. Methods: A nationwide cohort study of 45 326 Danish prostate cancer patients diagnosed during 1995-2011, each matched to approximately five men from the general population on age and individual comorbidities in the Charlson Comorbidity Index (CCI). We calculated five-year mortality rates and interaction contrasts as a measure of the excess mortality rate explained by synergy between prostate cancer and comorbidity. Results: Five-year mortality was 46.8% in prostate cancer patients and 25.8% in matched men from the general population. For prostate cancer patients with a CCI score of 2-3, the mortality rate was 250 per 1000 person-years [95% confidence interval (CI): 236, 263], and interaction between comorbidity and prostate cancer accounted for 20% of the total mortality rate (50 deaths per 1000 person-years, 95% CI 35, 65) in the first year following cancer diagnosis. The interaction was mainly present for patients with metastatic disease and those not treated with prostatectomy. Conclusion: Up to 20% of all deaths among men who had both prostate cancer and comorbidities could be explained by the comorbidity-prostate cancer interaction. The mortality attributable to comorbidity itself and the mortality attributable to the interaction may be reduced by successful treatment of the comorbidity.
    Acta Oncologica 11/2015; DOI:10.3109/0284186X.2015.1105382 · 3.00 Impact Factor
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    ABSTRACT: Objective: Assessment of the joint and independent relationships of gestational weight gain and prepregnancy body mass index (BMI) on risk of infant mortality was performed. Methods: This study used Pennsylvania linked birth-infant death records (2003-2011) from infants without anomalies born to mothers with prepregnancy BMI categorized as underweight (n = 58,973), normal weight (n = 610,118), overweight (n = 296,630), grade 1 obesity (n = 147,608), grade 2 obesity (n = 71,740), and grade 3 obesity (n = 47,277). Multivariable logistic regression models stratified by BMI category were used to estimate dose-response associations between z scores of gestational weight gain and infant death after confounder adjustment. Results: Infant mortality risk was lowest among normal-weight women and increased with rising BMI category. For all BMI groups except for grade 3 obesity, there were U-shaped associations between gestational weight gain and risk of infant death. Weight loss and very low weight gain among women with grades 1 and 2 obesity were associated with high risks of infant mortality. However, even when gestational weight gain in women with obesity was optimized, the predicted risk of infant death remained higher than that of normal-weight women. Conclusions: Interventions aimed at substantially reducing preconception weight among women with obesity and avoiding very low or very high gestational weight gain may reduce risk of infant death.
    Obesity 11/2015; DOI:10.1002/oby.21335 · 3.73 Impact Factor
  • Timothy L Lash ·

    Epidemiology (Cambridge, Mass.) 09/2015; 26(6). DOI:10.1097/EDE.0000000000000382 · 6.20 Impact Factor

  • European geriatric medicine 09/2015; 6:S98. DOI:10.1016/S1878-7649(15)30347-8 · 0.73 Impact Factor
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    ABSTRACT: Longitudinal outcomes following stress or trauma diagnoses are receiving attention, yet population-based studies are few. The aims of the present cohort study were to examine the cumulative incidence of traumatic events and psychiatric diagnoses following diagnoses of severe stress and adjustment disorders categorized using International Classification of Diseases, Tenth Revision, codes and to examine associations of these diagnoses with all-cause mortality and suicide. Data came from a longitudinal cohort of all Danes who received a diagnosis of reaction to severe stress or adjustment disorders (International Classification of Diseases, Tenth Revision, code F43.x) between 1995 and 2011, and they were compared with data from a general-population cohort. Cumulative incidence curves were plotted to examine traumatic experiences and psychiatric diagnoses during the study period. A Cox proportional hazards regression model was used to examine the associations of the disorders with mortality and suicide. Participants with stress diagnoses had a higher incidence of traumatic events and psychiatric diagnoses than did the comparison group. Each disorder was associated with a higher rate of all-cause mortality than that seen in the comparison cohort, and strong associations with suicide were found after adjustment. This study provides a comprehensive assessment of the associations of stress disorders with a variety of outcomes, and we found that stress diagnoses may have long-lasting and potentially severe consequences. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
    American journal of epidemiology 08/2015; 182(5). DOI:10.1093/aje/kwv066 · 5.23 Impact Factor
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    ABSTRACT: The risk of colorectal cancer (CRC) is reportedly increased two-fold if at least one first-degree relative (FDR) is affected with CRC, increasing to three- to four-fold if multiple FDRs are affected or if one FDR was diagnosed at a young age. We evaluated familial risk of CRC, systematically excluding monogenetic high-risk families with polyposis or Lynch syndrome/hereditary non-polyposis colorectal cancer (HNPCC). FDRs of 1196 Danish CRC patients diagnosed between 1995 and 1998 (baseline) were identified and the family history of cancer was assessed at baseline using Danish medical registries; 4182 FDRs without CRC from 1060 of the families were matched on age and gender with ten individuals from the general population and followed from baseline to 2010. Family history was updated with any new cancer event during follow-up. Using Cox proportional hazard modeling the risk estimates were: at least one relative with CRC: hazard ratio (HR)=1.78 (95%CI: 1.45, 2.17), one relative with CRC diagnosed after the age of 50: HR=1.68 (95%CI: 1.32, 2.14), one relative with CRC diagnosed before the age of 50: HR=1.86 (95%CI: 0.70, 4.94), and multiple affected relatives: HR=2.04 (95%CI: 1.38, 3.00). Although the overall risk in FDRs of CRC patients in our study was comparable with the results of previous studies, the risk in families with multiple relatives with CRC or one CRC patient diagnosed young may be lower than reported previously. Copyright © 2015. Published by Elsevier Ltd.
    07/2015; 39(5). DOI:10.1016/j.canep.2015.07.004
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    ABSTRACT: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. Patients with incident, early stage breast cancer who were diagnosed during 1996 through 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months of continuous exposure), and cumulative morphine-equivalent dose, adjusting for confounders. In total, 34,188 patients were identified who, together, contributed 283,666 person-years of follow-up. There was no association between ever-use of opioids and breast cancer recurrence (crude hazard ratio, 0.98; 95% confidence interval, 0.90-1.1; adjusted hazard ratio, 1.0; 95% confidence interval, 0.92-1.1), regardless of opioid type, strength, chronicity of use, or cumulative dose. Breast cancer recurrence rates were lower among users of strongly (but not weakly) immunosuppressive opioids, possibly because of channeling bias among those with a high competing risk, because mortality was higher among users of this drug type. This large, prospective cohort study provided no clinically relevant evidence of an association between opioid prescriptions and breast cancer recurrence. The current findings are important to cancer survivorship, because opioids are frequently used to manage pain associated with comorbid conditions. Cancer 2015. © 2015 American Cancer Society. © 2015 American Cancer Society.
    Cancer 07/2015; 121(19). DOI:10.1002/cncr.29532 · 4.89 Impact Factor
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    ABSTRACT: Venous thromboembolism (VTE) is a serious complication of cancer. It is unknown whether comorbidity interacts clinically with prostate cancer (PC) to increase the VTE rate beyond that explained by PC and comorbidity alone, for example, by delaying diagnosis or precluding treatment. A nationwide, registry-based cohort study of all 44,035 Danish patients diagnosed with PC from 1995 to 2011 and 213,810 men from the general population matched 5:1 on age, calendar time, and comorbidities. The authors calculated VTE rate ratios and the interaction contrast as a measure on the additive scale of the excess VTE rate explained by synergy between PC and comorbidity. In total, 849 patients in the PC cohort and 2360 men from the general population had VTE during 5 years of follow-up, and their risk of VTE was 2.2% and 1.3%, respectively. The 1-year VTE standardized rate among PC patients who had high comorbidity levels was 15 per 1000 person-years (PYs) (95% confidence interval, 6.8-24 per 1000 PYs), and 29% of that rate was explained by an interaction between PC and comorbidity. The VTE risk was increased among older patients, those with metastases, those with high Gleason scores, those in the D'Amico high-risk group, and those who underwent surgery. PC interacted clinically with high comorbidity levels and increased the VTE rate. Because of the large PC burden, reducing VTEs associated with comorbidities may have an impact on VTE risk and the potential to improve prognosis. Clinical interactions between high levels of comorbidity and PC on the risk of VTE were observed. Almost 30% of all episodes of VTE occurred among patients who had high levels of comorbidity. Cancer 2015. © 2015 American Cancer Society. © 2015 American Cancer Society.
    Cancer 07/2015; 121(20). DOI:10.1002/cncr.29535 · 4.89 Impact Factor
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    ABSTRACT: Although asthma has recently been established as a risk factor for pneumococcal disease (PD), few studies have specifically evaluated this association in children. We conducted a nation-wide population-based cohort study of the effect of asthma on childhood PD among all singleton live births in Denmark from 1994 to 2007, before the introduction of the 7-valent pneumococcal conjugate vaccine. All data were abstracted from Danish medical registries. Because underlying comorbidity substantially increases the PD risk in children, standard methods were used to assess the evidence of biologic interaction between comorbidity and asthma on the risk of PD. There were 2,253 cases of childhood PD among 888,655 children born in Denmark from 1994 to 2007. The adjusted incidence rate ratio of the effect of asthma on childhood PD was 2.2 (95% confidence interval [CI]: 2.0, 2.5). Age-stratified incidence rate ratios were 2.1 (95% CI: 1.8, 2.9) in children 6 months to <24 months, 4.1 (95% CI: 3.3, 5.1) in children 24 months to <60 months, and 2.3 (95% CI: 1.6, 3.2) in children ≥60 months. Evaluation of the biologic interaction between asthma and comorbidity in older children revealed that 55% (24 months to <60 months) to 73% (≥60 months) of cases among asthma-exposed children can be accounted for by the interaction between asthma and comorbidity. These results confirm that asthma is an important risk factor for PD in children and suggest that children with underlying comorbidities are more sensitive to the effect of asthma on PD than children without comorbidities.
    Clinical Epidemiology 07/2015; 7:325-34. DOI:10.2147/CLEP.S78619
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    ABSTRACT: The monogenic Lynch syndrome (LS) is associated with better survival in colorectal cancer (CRC) patients. Whether family history of CRC affects CRC prognosis in general remains unclear. We evaluated overall mortality in a Danish cohort of CRC patients comparing patients with a family history (FHpos) to those without (FHneg) with focus on patients from non-syndromic families, thus FHpos patients were further divided into a non-syndromic group (FHNS) and a HNPCC/LS group (FHHNPCC). We included CRC patients diagnosed 1995-1998. First degree relatives were identified using Danish population registries and family history was obtained by linkage to Danish medical registries. 1- and 5-year mortality were evaluated using the Kaplan-Meier method and Cox regression, with adjustment for age, sex, cancer site, cancer stage, and comorbidity. 1196 CRC patients were included in the study, 219 FHpos patients of whom 197 were FHNS patients. 1- and 5-year adjusted Mortality Rate Ratios comparing FHpos patients to FHneg patients were 0.99 (95 % CI 0.69, 1.42) and 1.07 (95 % CI 0.87, 1.32), respectively. For FHNS patients, the corresponding MRRs were 1.01 (95 % CI 0.69, 1.47) and 1.15 (95 % CI 0.93, 1.43). For the FHHNPCC patients MRRs were 0.84 (95 % CI 0.29, 2.44) and 0.66 (95 % CI 0.33, 1.31), respectively. In contrast to the lower mortality in LS patients, other types of familial CRC do not seem to affect the survival after CRC diagnosis.
    Familial Cancer 05/2015; 14(4). DOI:10.1007/s10689-015-9812-1 · 1.98 Impact Factor
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    ABSTRACT: The association between stress and cancer incidence has been studied for more than seven decades. Despite plausible biological mechanisms and evidence from laboratory studies, findings from clinical research are conflicting. The objective of this study was to examine the association between PTSD and various cancer outcomes. This nation-wide cohort study included all Danish-born residents of Denmark from 1995 to 2011. The exposure was PTSD diagnoses (n = 4131). The main outcomes were cancer diagnoses including: (1) all malignant neoplasms; (2) hematologic malignancies; (3) immune-related cancers; (4) smoking- and alcohol-related cancers; (5) cancers at all other sites. Standardized incidence ratios (SIR) were calculated. Null associations were found between PTSD and nearly all cancer diagnoses examined, both overall [SIR for all cancers = 1.0, 95 % confidence interval (CI) = 0.88, 1.2] and in analyses stratified by gender, age, substance abuse history and time since PTSD diagnosis. This study is the most comprehensive examination to date of PTSD as a predictor of many cancer types. Our data show no evidence of an association between PTSD and cancer in this nationwide cohort.
    European Journal of Epidemiology 05/2015; 30(7). DOI:10.1007/s10654-015-0032-7 · 5.34 Impact Factor
  • Timothy L Lash · Jay S Kaufman ·

    Epidemiology (Cambridge, Mass.) 05/2015; 26(4). DOI:10.1097/EDE.0000000000000318 · 6.20 Impact Factor
  • S A J Schmidt · T L Lash ·
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    ABSTRACT: Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.
    Bone marrow transplantation 03/2015; 50(6). DOI:10.1038/bmt.2015.66 · 3.57 Impact Factor
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    ABSTRACT: It remains unknown whether incident chronic diseases are more often fatal among breast cancer survivors than among women free of breast cancer. We conducted a nationwide matched cohort study of all Danish breast cancer patients diagnosed between 1994 and 2007, who survived for five years. We compared their long-term mortality with five times as many women from the general population without breast cancer, matched on age. We used time-varying methods to compute mortality rate ratios (MRRs) for incident diseases included in the Charlson Comorbidity Index (CCI). One third of five-year breast cancer survivors developed incident diseases during 14years of follow-up, with about the same incidence as women without breast cancer. Mortality associated with any incident disease was similar among breast cancer survivors (MRR=7.1, 95% confidence interval (CI): 6.7, 7.4) and comparison women (MRR=7.5, 95% CI: 7.3, 7.7). Among breast cancer patients, relative mortality associated with incident diseases was higher among patients treated with chemotherapy (MRR=10, 95% CI: 8.7, 12) and radiotherapy (MRR=9.8, 95% CI: 8.8, 11) than among patients who received surgery (MRR=7.0, 95% CI: 6.7, 7.4) or hormonal therapy (MRR=6.3, 95% CI: 5.8, 6.9). There were no marked differences in mortality of diseases among breast cancer survivors and women from the general population. Among breast cancer patients, new diseases were more often fatal in patients treated with chemotherapy and radiotherapy. Five-year breast cancer survivors have similar risk of dying from new chronic medical conditions as women from the general population without breast cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 03/2015; 47(6). DOI:10.1016/j.ejca.2015.02.001 · 5.42 Impact Factor
  • Timothy L Lash ·

    Epidemiology (Cambridge, Mass.) 03/2015; 26(2):141-2. DOI:10.1097/EDE.0000000000000250 · 6.20 Impact Factor
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    ABSTRACT: To assess the validity of reaction to severe stress and adjustment disorder diagnoses registered in the Danish Psychiatric Central Research Register (DPCRR), to examine the documentation of stressful and traumatic events in the medical records, and to investigate the occurrence of stress diagnoses among persons not registered in the DPCRR. Among 101,633 patients diagnosed with International Classification of Diseases, 10th Edition (ICD-10) F43 diagnoses between 1995 and 2011, we selected 50 patients from two hospitals (100 total), comprising one above and one below median age for each diagnosis for five time periods, and reviewed their medical records. We calculated the positive predictive value, comparing registration in the DPCRR with the original medical records, and captured data on stressful life events. Two general practitioners were queried about 50 patients without a stress diagnosis in the DPCRR, regarding whether they had ever received a stress diagnosis. The positive predictive value was 58% for acute stress reaction, 83% for posttraumatic stress disorder, 94% for adjustment disorder, 71% for other reactions to severe stress, and 68% for reaction to severe stress, unspecified. In 80% of the records, a stressful or traumatic event was noted. Of 100 patients without an F43 diagnosis in the DPCRR, seven had a stress diagnosis. The DPCRR represents a valid and comprehensive resource for research on reaction to severe stress and adjustment disorders, particularly for posttraumatic stress disorder and adjustment disorder.
    Clinical Epidemiology 03/2015; 7:235. DOI:10.2147/CLEP.S80514
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    ABSTRACT: Autoimmune diseases (ADs) comprise a large group of heterogeneous diseases in which the immune system attacks healthy organs. Both intrinsic changes in the body and AD treatment can compromise immune function. Impaired immune function could increase the risk of recurrent cancer. We aimed to investigate this hypothesis in a population-based epidemiological study. We examined the risk of breast cancer (BC) recurrence associated with an AD diagnosis among patients with incident stages I–III BC diagnosed during 1980–2007. Data were obtained from Danish population-based medical registries. ADs were categorized dichotomously and according to organ system of origin. Follow-up was up to 10 years or until 31 December 2009. Multivariate Cox proportional hazard regression was used to compute hazard ratios (HRs) and associated 95 % confidence intervals (95 % CIs) to evaluate the association between AD diagnosis and BC recurrence. 78,095 women with stages I–III BC were identified. Median age-at-diagnosis was 61 years (19–102 years), median follow-up was 5.7 years, and 13,545 women had a recurrence during follow-up. 6,716 women had at least one AD. In adjusted models, the association between ADs and BC recurrence was near null: HRadjusted 0.96 (95 % CI 0.89, 1.04). These results held in all AD subcategories, except for central nervous/neuromuscular system ADs, with HRadjusted 0.56 (95 % CI 0.40, 0.78). Among women with BC, a history of at least one AD diagnosis was not associated with BC recurrence, with the possible exception of ADs of the central nervous/neuromuscular system.
    Breast Cancer Research and Treatment 01/2015; 149(2). DOI:10.1007/s10549-014-3258-2 · 3.94 Impact Factor
  • Lisa M. Bodnar · Barbara Abrams · Lara Siminerio · Timothy L. Lash ·
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    ABSTRACT: Birth certificates are an important source of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) data for surveillance and aetiologic studies, but little is known about their validity in twin pregnancies. Twins experience high rates of adverse perinatal outcomes that have been associated with BMI and GWG in singletons. Our objective was to evaluate the accuracy of birth certificate-derived pre-pregnancy BMI and GWG compared with medical record-derived data in a sample of 186 twin pregnancies at a teaching hospital in Pennsylvania (2003–2010). Twelve strata were created by simultaneous stratification on pre-pregnancy BMI (underweight, normal weight/overweight, obese class 1, obese classes 2 and 3) and GWG (<20th, 20–80th, >80th percentile). The agreement of birth certificate-derived pre-pregnancy BMI category with medical record BMI category was lowest among underweight mothers [75% (95% confidence interval 51–91%) ] and highest among normal/overweight [97% (90–99%) ] and obese classes 2 and 3 mothers [97% (85–99%) ]. Agreement for GWG category from the birth certificate varied from 57% (41–70%) for GWG >80th percentile to 80% (65–91%) and 82% (72–89%) for GWG <20th and 20th–80th percentiles, respectively. The misclassification of BMI and GWG was primarily due to error in pre-pregnancy weight rather than weight at delivery or height. Agreement proportions for twins were not meaningfully different from the proportions in a comparable sample of singleton pregnancies. These data suggest that birth certificate-based BMI and GWG data are prone to error in twin pregnancies. Those who use these data should conduct internal validation studies and adjust their results using bias analyses.
    Maternal and Child Nutrition 01/2015; DOI:10.1111/mcn.12160 · 3.06 Impact Factor
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    Timothy L. Lash ·

    Paediatric and Perinatal Epidemiology 01/2015; 29(1). DOI:10.1111/ppe.12167 · 3.13 Impact Factor
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    ABSTRACT: Several studies have shown that uncertainty about disease and fear of disease progression affects psychosocial adjustment and quality of life. The purpose of this study was to validate a Norwegian short version of the "The Mishel Uncertainty in Illness Scale" (SF-MUIS) and to examine the impact of uncertainty in illness in breast cancer patients. 209 patients in breast cancer treatment completed questionnaires for SF-MUIS, Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Cancer Therapy-Breast (FACT-ES), and eight questions concerning quality of the patient information provided (IQP). Relationship between scores on uncertainty in illness and anxiety, depression, social support, emotional well-being, the quality of patient information provided, and age were studied by multiple regression analyses. Ordinal coefficient alpha for the Norwegian version of SF-MUIS was 0.70. Scores on SF-MUIS correlated significantly with scores on HADS (P = 0.001), FACT-ES (P = 0.001), and IQP (P = 0.001) indicating good convergent validity. The patients reported a moderate degree of uncertainty in illness. However, those who had been diagnosed with breast cancer for a year, reported higher scores than those newly diagnosed (P=<0.0001). Information provided was the sole significant predictor of illness uncertainty (P=<0.0001). The results of the present study confirm that the Norwegian version of the SF-MUIS is a suitable tool for assessment of uncertainty in breast cancer patients, who reported a moderate degree of uncertainty in illness. Copyright © 2014 Elsevier Ltd. All rights reserved.
    European journal of oncology nursing: the official journal of European Oncology Nursing Society 12/2014; 19(2). DOI:10.1016/j.ejon.2014.10.009 · 1.43 Impact Factor

Publication Stats

5k Citations
1,156.43 Total Impact Points


  • 2015
    • McGill University
      Montréal, Quebec, Canada
  • 2013-2015
    • Emory University
      • Department of Epidemiology
      Atlanta, Georgia, United States
  • 2008-2015
    • Aarhus University Hospital
      • Department of Clinical Epidemiology
      Aarhus, Central Jutland, Denmark
    • University of California, Los Angeles
      • Department of Epidemiology
      Los Ángeles, California, United States
  • 2014
    • Wake Forest School of Medicine
      • Division of Public Health Sciences
      Winston-Salem, North Carolina, United States
  • 2010-2014
    • Aarhus University
      • Department of Clinical Epidemiology
      Aarhus, Central Jutland, Denmark
  • 1998-2012
    • Boston University
      • • Department of Medicine
      • • Department of Epidemiology
      • • School of Public Health
      Boston, Massachusetts, United States
  • 1999-2009
    • Boston Medical Center
      Boston, Massachusetts, United States
  • 2007
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
  • 1999-2007
    • University of Massachusetts Boston
      • Clinical Epidemiology Research and Training Unit
      Boston, Massachusetts, United States