Publications by authors named "Laura Hester"

14 Publications

  • Page 1 of 1

Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study.

Lancet Rheumatol 2020 Nov 21;2(11):e698-e711. Epub 2020 Aug 21.

Janssen Research and Development, Titusville, NJ, USA.

Background: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis.

Methods: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the value was less than 0·4.

Findings: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12-2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22-3·95]), chest pain or angina (1·15 [1·05-1·26]), and heart failure (1·22 [1·02-1·45]).

Interpretation: Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment.

Funding: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations.
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http://dx.doi.org/10.1016/S2665-9913(20)30276-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442425PMC
November 2020

Acute pancreatitis risk in type 2 diabetes patients treated with canagliflozin versus other antihyperglycemic agents: an observational claims database study.

Curr Med Res Opin 2020 07 14;36(7):1117-1124. Epub 2020 May 14.

Cardiovascular and Metabolism, Janssen Research & Development, LLC, Raritan, NJ, USA.

Observational evidence suggests that patients with type 2 diabetes mellitus (T2DM) are at increased risk for acute pancreatitis (AP) versus those without T2DM. A small number of AP events were reported in clinical trials of the sodium glucose co-transporter 2 inhibitor canagliflozin, though no imbalances were observed between treatment groups. This observational study evaluated risk of AP among new users of canagliflozin compared with new users of six classes of other antihyperglycemic agents (AHAs). Three US claims databases were analyzed based on a prespecified protocol approved by the European Medicines Agency. Propensity score adjustment controlled for imbalances in baseline covariates. Cox regression models estimated the hazard ratio of AP with canagliflozin compared with other AHAs using on-treatment (primary) and intent-to-treat approaches. Sensitivity analyses assessed robustness of findings. Across the three databases, there were between 12,023-80,986 new users of canagliflozin; the unadjusted incidence rates of AP (per 1000 person-years) were between 1.5-2.2 for canagliflozin and 1.1-6.6 for other AHAs. The risk of AP was generally similar for new users of canagliflozin compared with new users of glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sulfonylureas, thiazolidinediones, insulin, and other AHAs, with no consistent between-treatment differences observed across databases. Intent-to-treat and sensitivity analysis findings were qualitatively consistent with on-treatment findings. In this large observational study, incidence rates of AP in patients with T2DM treated with canagliflozin or other AHAs were generally similar, with no evidence suggesting that canagliflozin is associated with increased risk of AP compared with other AHAs.
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http://dx.doi.org/10.1080/03007995.2020.1761312DOI Listing
July 2020

Diabetic ketoacidosis in patients with type 2 diabetes treated with sodium glucose co-transporter 2 inhibitors versus other antihyperglycemic agents: An observational study of four US administrative claims databases.

Pharmacoepidemiol Drug Saf 2019 12 27;28(12):1620-1628. Epub 2019 Aug 27.

Janssen Research & Development, LLC, Raritan, New Jersey.

Purpose: To compare the incidence of diabetic ketoacidosis (DKA) among patients with type 2 diabetes mellitus (T2DM) who were new users of sodium glucose co-transporter 2 inhibitors (SGLT2i) versus other classes of antihyperglycemic agents (AHAs).

Methods: Patients were identified from four large US claims databases using broad (all T2DM patients) and narrow (intended to exclude patients with type 1 diabetes or secondary diabetes misclassified as T2DM) definitions of T2DM. New users of SGLT2i and seven groups of comparator AHAs were matched (1:1) on exposure propensity scores to adjust for imbalances in baseline covariates. Cox proportional hazards regression models, conditioned on propensity score-matched pairs, were used to estimate hazard ratios (HRs) of DKA for new users of SGLT2i versus other AHAs. When I <40%, a combined HR across the four databases was estimated.

Results: Using the broad definition of T2DM, new users of SGLT2i had an increased risk of DKA versus sulfonylureas (HR [95% CI]: 1.53 [1.31-1.79]), DPP-4i (1.28 [1.11-1.47]), GLP-1 receptor agonists (1.34 [1.12-1.60]), metformin (1.31 [1.11-1.54]), and insulinotropic AHAs (1.38 [1.15-1.66]). Using the narrow definition of T2DM, new users of SGLT2i had an increased risk of DKA versus sulfonylureas (1.43 [1.01-2.01]). New users of SGLT2i had a lower risk of DKA versus insulin and a similar risk as thiazolidinediones, regardless of T2DM definition.

Conclusions: Increased risk of DKA was observed for new users of SGLT2i versus several non-SGLT2i AHAs when T2DM was defined broadly. When T2DM was defined narrowly to exclude possible misclassified patients, an increased risk of DKA with SGLT2i was observed compared with sulfonylureas.
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http://dx.doi.org/10.1002/pds.4887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916409PMC
December 2019

Comparison of Medicare Claims-based Proxy Measures of Poor Function and Associations With Treatment Receipt and Mortality in Older Colon Cancer Patients.

Med Care 2019 04;57(4):286-294

Department of Epidemiology, Gillings School of Global Public Health.

Background: Multiple claims-based proxy measures of poor function have been developed to address confounding in observational studies of drug effects in older adults. We evaluated agreement between these measures and their associations with treatment receipt and mortality in a cohort of older colon cancer patients.

Methods: Medicare beneficiaries age 66+ diagnosed with stage II-III colon cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare database (2004-2011). Poor function was operationalized by: (1) summing the total poor function indicators for each model; and (2) estimating predicted probabilities of poor function at diagnosis. Agreement was evaluated using Fleiss' κ and Spearman's correlation. Associations between proxy measures and: (1) laparoscopic versus open surgery; (2) chemotherapy versus none; (3) 5-fluorouracil (5FU)+oxaliplatin (FOLFOX) versus 5FU monotherapy; and (4) 1-year mortality were estimated using log-binomial regression, controlling for age, sex, stage, and comorbidity. Survival estimates were stratified by functional group, age, and comorbidity.

Results: Among 29,687 eligible colon cancer patients, 67% were 75+ years and 45% had stage III disease. Concordance across the poor function indicator counts was moderate (κ: 0.64) and correlation of predicted probability measures varied (ρ: 0.21-0.74). Worse function was associated with lower chemotherapy and FOLFOX receipt, and higher 1-year mortality. Within age and comorbidity strata, poor function remained associated with mortality.

Conclusions: While agreement varied across the claims-based proxy measures, each demonstrated anticipated associations with treatment receipt and mortality independent of comorbidity. Claims-based comparative effectiveness studies in older populations should consider applying one of these models to improve confounding control.
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http://dx.doi.org/10.1097/MLR.0000000000001073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417959PMC
April 2019

Cause-specific mortality among Medicare beneficiaries with newly diagnosed non-Hodgkin lymphoma subtypes.

Cancer 2019 04 11;125(7):1101-1112. Epub 2018 Dec 11.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background: As the US population ages and non-Hodgkin lymphoma (NHL)-specific mortality declines, deaths from causes other than NHL will become increasingly important in treatment decision making for older patients with NHL. The objective of the current study was to describe how the 5-year cumulative incidence of NHL-specific and other-cause mortality varies by subtype, age, comorbidity level, and time since diagnosis in older patients.

Methods: Using the Surveillance, Epidemiology, and End Results cancer registry data linked to Medicare claims, patients aged ≥66 years were identified at the time of diagnosis with a first, primary NHL diagnosis from 2004 through 2013. Death certificate data and Fine-Gray competing risks models were used to estimate the 5-year cumulative incidence of NHL-specific and other-cause mortality by NHL subtype, age, and comorbidity level. Estimates were displayed over time using stacked cumulative incidence curves.

Results: Among 30,666 patients with NHL, 32% died of NHL and 13% died of other causes within 5 years of diagnosis. The cumulative incidence of other-cause mortality increased with age and comorbidity level for all subtypes. Among patients with aggressive NHL subtypes, NHL-specific mortality exceeded other-cause mortality across all age groups, comorbidity levels, and number of years after diagnosis. For patients with indolent NHL subtypes, other-cause mortality was similar to or exceeded NHL-specific mortality, especially among older patients with severe comorbidity or with the indolent marginal zone, lymphoplasmacytic, and mycosis fungoides subtypes.

Conclusions: The findings of the current study suggest that mortality from causes other than NHL are important for patients of an older age, with a higher comorbidity level, and with indolent disease. Evidence from the current study can guide the development of tools for estimating individual prognosis that inform treatment discussions in patients with NHL.
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http://dx.doi.org/10.1002/cncr.31821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719299PMC
April 2019

Reply to: comparative effectiveness medicines research cannot assess efficacy.

J Clin Epidemiol 2017 12 12;92:130-132. Epub 2017 Sep 12.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, 135 Dauer Drive, 2101 McGavran-Greenberg Hall, CB #7435, Chapel Hill, NC 1-609-703-6927, USA.

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http://dx.doi.org/10.1016/j.jclinepi.2017.09.009DOI Listing
December 2017

Methodologic Issues When Estimating Risks in Pharmacoepidemiology.

Curr Epidemiol Rep 2016 Dec 13;3(4):285-296. Epub 2016 Sep 13.

Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA.

Risk is an important parameter to describe the occurrence of health outcomes over time. However, many outcomes of interest in healthcare settings, such as disease incidence, treatment initiation, and cause-specific mortality, may be precluded from occurring by other events, often referred to as competing events. Here, we review straightforward approaches to estimate risk in the presence of competing events. We illustrate the application of these methods using timely examples in pharmacoepidemiologic research and compare results to those obtained using analytic simplifications commonly used to handle competing events. These examples demonstrate how the analytic methods used to account for competing events affect the interpretation of results from pharmacoepidemiologic studies.
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http://dx.doi.org/10.1007/s40471-016-0089-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557056PMC
December 2016

Publication of comparative effectiveness research has not increased in high-impact medical journals, 2004-2013.

J Clin Epidemiol 2017 Apr 8;84:185-187. Epub 2017 Feb 8.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, 135 Dauer Drive, 2101 McGavran-Greenberg Hall, CB #7435, Chapel Hill, NC 27599, USA.

Objective: To explore the impact of increasing interest and investment in patient-centered research, this study sought to describe patterns of comparative effectiveness research (CER) and patient-reported outcomes (PROs) in pharmacologic intervention studies published in widely read medical journals from 2004-2013.

Design And Setting: We identified 2335 articles published in five widely read medical journals from 2004-2013 with ≥1 intervention meeting the US Food and Drug Administration's definitions for a drug, biologic, or vaccine. Six trained reviewers extracted characteristics from a 20% random sample of articles (468 studies). We calculated the proportion of studies with CER and PROs. Trends were summarized using locally-weighted means and 95% confidence intervals.

Results: Of the 468 sampled studies, 30% used CER designs and 33% assessed PROs. The proportion of studies using CER designs did not meaningfully increase over the study period. However, we observed an increase in the use of PROs.

Conclusions: Among pharmacological intervention studies published in widely read medical journals from 2004-2013, we identified no increase in CER. Randomized, placebo-controlled trials continue to be the dominant study design for assessing pharmacologic interventions. Increasing trends in PRO use may indicate greater acceptance of these outcomes as evidence for clinical benefit.
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http://dx.doi.org/10.1016/j.jclinepi.2017.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441956PMC
April 2017

Applying the Social Ecological Model to Creating Asthma-Friendly Schools in Louisiana.

J Sch Health 2016 Mar;86(3):225-32

Air Pollution and Respiratory Health Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Hwy, Mailstop F60, Atlanta, GA 30341.

Background: In 2010, the Louisiana Asthma Management and Prevention Program (LAMP) implemented the Asthma-Friendly Schools Initiative in high-risk Louisiana populations. The social ecological model (SEM) was used as a framework for an asthma program implemented in 70 state K-12 public schools over 2 years.

Methods: Activities included a needs assessment, identification of students with asthma, individualized asthma action plans (AAP), staff trainings, environmental quality improvement, and school system policy changes to address the asthma burden.

Results: There were 522 new or existing asthma cases recognized. Asthma knowledge/awareness was measurably improved among school personnel. School indoor air quality was improved across all locations. School-level policies were adopted that improved AAP collection, compliance to bus-idling restrictions, and asthma medication self-carry.

Conclusions: The SEM framework can be used for school-based programs to address successfully and improve asthma-related issues from the individual through policy levels.
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http://dx.doi.org/10.1111/josh.12369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754781PMC
March 2016

Roles of the state asthma program in implementing multicomponent, school-based asthma interventions.

J Sch Health 2013 Dec;83(12):833-41

Environmental Health Scientist, ORISE/CDC Research Program, Air Pollution and Respiratory Health Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Hwy, Mailstop F60, Atlanta, GA 30341.

Background: Asthma is a leading chronic childhood disease in the United States and a major contributor to school absenteeism. Evidence suggests that multicomponent, school-based asthma interventions are a strategic way to address asthma among school-aged children. The Centers for Disease Control and Prevention (CDC) encourages the 36 health departments (34 states, District of Columbia, and Puerto Rico) in the National Asthma Control Program (NACP) to implement multicomponent, school-based asthma interventions on a larger scale.

Methods: To gain a better understanding of replicable best practices for state-coordinated asthma interventions in schools, an NACP evaluation team conducted evaluability assessments of promising interventions run by state asthma programs in Louisiana, Indiana, and Utah.

Results: The team found that state asthma programs play a critical role in implementing school-based asthma interventions due to their ability to (1) use statewide surveillance data to identify asthma trends and address disparities; (2) facilitate connections between schools, school systems, and school-related community stakeholders; (3) form state-level connections; (4) translate policies into action; (5) provide resources and public health practice information to schools and school systems; (6) monitor and evaluate implementation.

Conclusions: This article presents evaluability assessment findings and illustrates state roles using examples from the 3 participating state asthma programs.
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http://dx.doi.org/10.1111/josh.12101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555870PMC
December 2013

An examination of spatial concentrations of sex exchange and sex exchange norms among drug users in Baltimore, Maryland.

Ann Assoc Am Geogr 2012 09 15;102(5):1058-1066. Epub 2012 May 15.

Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, 2213 McElderry Street, Second floor, Baltimore, Maryland 21205, 410-502-5368, 410-502-5385 (fax).

Baltimore, Maryland consistently ranks highest nationally in rates of sexually transmitted diseases and HIV infection. Prior studies have identified geographic areas where STI and HIV infection in the city is most prevalent. It is well established that sex exchange behavior is associated with HIV and STIs, yet it is not well understood how sex exchangers are spatially distributed within the high-risk areas. We sought to examine the spatial distribution of individuals who report sex exchange compared to those who do not exchange. Additionally we examined the spatial context of perceived norms about sex exchange. Data for the study came from a baseline sample of predominately injection drug users (n=842). Of these, 21% reported sex exchange in the prior 90 days. All valid baseline residential addresses of participants living within Baltimore city boundaries were geocoded. The Multi-Distance Spatial Cluster Analysis (Ripley's K-function) was used to separately calculate the K-functions for the addresses of participants reporting sex exchange or non-sex exchange, relative to the recruited population. Evidence of spatial clustering of sex exchangers was observed and norms aligned with these clusters. Of particular interest was the high density of sex exchangers in one specific housing complex of East Baltimore, which happens to be the oldest in Baltimore. These findings can inform targeted efforts for screening and testing for HIV and STIs and placement of both individual and structural level interventions that focus on increasing access to risk reduction materials and changing norms about risk behaviors.
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http://dx.doi.org/10.1080/00045608.2012.674902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636531PMC
September 2012

Social network characteristics and heavy episodic drinking among women at risk for HIV/sexually transmitted infections.

J Stud Alcohol Drugs 2011 Nov;72(6):1041-7

Department of Health, Behavior, and Society, Johns Hopkins Bloomberg School of Public Health, 2213 McElderry Street, 2nd Floor, Baltimore, Maryland 21205, USA.

Objective: Social networks can either negatively or positively influence a variety of behaviors, including alcohol use. This study examined social network characteristics that are risk factors for and protective factors against heavy episodic drinking among a sample of women at risk for HIV/sexually transmitted infections.

Method: This was a cross-sectional study using baseline data from 567 impoverished women participating in an HIV prevention study in Baltimore, MD. Data were collected through face-to-face interviews at a community-based research clinic. Heavy episodic drinking was defined as six or more drinks per drinking episode on at least a weekly basis. We examined network characteristics, including structure and function and their association with heavy episodic drinking. Multivariate logistic regression was used, adjusting for individual-level factors, such as drug use, demographics, and depression.

Results: Approximately 21% of the sample engaged in heavy episodic drinking at least weekly. Controlling for individual-level factors, women who engaged in heavy episodic drinking had fewer social network members (a) who were in drug treatment, adjusted odds ratio (AOR) = 0.65, 95% CI [0.49, 0.88]; (b) who were employed, AOR = 0.89, 95% CI [0.79, 0.99]; and (c) with whom the participant socialized, AOR = 0.74, 95% CI [0.63, 0.96]. Women who engaged in heavy episodic drinking had a significantly higher number of social network members with whom they drank alcohol, AOR = 1.71, 95% CI [1.43, 2.03].

Conclusions: Social network characteristics are both protective and risk factors for heavy episodic drinking among women. Interpersonal interventions, such as peer education, may be a useful strategy to decrease heavy episodic drinking and its subsequent outcomes among women.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3211958PMC
http://dx.doi.org/10.15288/jsad.2011.72.1041DOI Listing
November 2011

Rabies in bats from Alabama.

J Wildl Dis 2007 Apr;43(2):291-9

Department of Biological Sciences, 331 Funchess Hall, Auburn University, AL 36849, USA.

Data on rabies virus infection in bats that were submitted to the Alabama Department of Public Health from 1995-2005 were analyzed. Demographic factors, such as species and sex, and temporal aspects, such as yearly and monthly trends, were investigated. Thirteen species of bats were submitted, and of those, individuals from seven species were rabid; prevalence was highest in Lasiurus borealis and Pipistrellus subflavus and lowest in Eptesicus fuscus and Nycticeius humeralis. There was no difference in prevalence of rabies between sexes or years. Statistically, more rabid bats were submitted in August, September, and November; and fewer were submitted in March, June, and July. Results were similar to those from other regions of North America; these data from Alabama can help to present a more complete view of rabies in bats in North America.
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http://dx.doi.org/10.7589/0090-3558-43.2.291DOI Listing
April 2007