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Article ; Online: Identifying individuals with physician-diagnosed chronic obstructive pulmonary disease in primary care electronic medical records: a retrospective chart abstraction study.

Lee, Theresa M / Tu, Karen / Wing, Laura L / Gershon, Andrea S

2017 Volume 27, Issue 1, Page(s) 34

Abstract: Little is known about using electronic medical records to identify patients with chronic obstructive pulmonary disease to improve quality of care. Our objective was to develop electronic medical record algorithms that can accurately identify patients ... ...

Abstract	Little is known about using electronic medical records to identify patients with chronic obstructive pulmonary disease to improve quality of care. Our objective was to develop electronic medical record algorithms that can accurately identify patients with obstructive pulmonary disease. A retrospective chart abstraction study was conducted on data from the Electronic Medical Record Administrative data Linked Database (EMRALD Chronic lung disease: NOVEL ALGORITHM SEARCH TECHNIQUE: Researchers develop an algorithm that can accurately search through electronic health records to find patients with chronic lung disease. Mining population-wide data for information on patients diagnosed and treated with chronic obstructive pulmonary disease (COPD) in primary care could help inform future healthcare and spending practices. Theresa Lee at the University of Toronto, Canada, and colleagues used an algorithm to search electronic medical records and identify patients with COPD from doctors' notes, prescriptions and symptom histories. They carefully adjusted the algorithm to improve sensitivity and predictive value by adding details such as specific medications, physician codes related to COPD, and different combinations of terminology in doctors' notes. The team accurately identified 364 patients with COPD in a randomly-selected cohort of 5889 people. Their results suggest opportunities for broader, informative studies of COPD in wider populations.
MeSH term(s)	Adult ; Aged ; Algorithms ; Canada ; Databases, Factual ; Electronic Health Records ; Female ; Humans ; Male ; Middle Aged ; Primary Health Care ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Retrospective Studies ; Sensitivity and Specificity
Language	English
Publishing date	2017-05-15
Publishing country	England
Document type	Journal Article ; Validation Study
ZDB-ID	2780812-9
ISSN	2055-1010 ; 2055-1010
ISSN (online)	2055-1010
ISSN	2055-1010
DOI	10.1038/s41533-017-0035-9
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Article ; Online: ADHD Treatment in Primary Care: Demographic Factors, Medication Trends, and Treatment Predictors.

Hauck, Tanya S / Lau, Cindy / Wing, Laura Li Foa / Kurdyak, Paul / Tu, Karen

Canadian journal of psychiatry. Revue canadienne de psychiatrie

2017 Volume 62, Issue 6, Page(s) 393–402

Abstract: Background: The aim of this study is to determine the prevalence and characteristics of youth with attention-deficit hyperactivity disorder (ADHD) in Ontario, Canada, and to determine the predictors of psychotropic medication prescriptions in youth with ...

Abstract	Background: The aim of this study is to determine the prevalence and characteristics of youth with attention-deficit hyperactivity disorder (ADHD) in Ontario, Canada, and to determine the predictors of psychotropic medication prescriptions in youth with ADHD. Method: This is a cross-sectional retrospective chart abstraction of more than 250 000 medical records from youth aged 1 to 24 years in a large geographical region in Ontario, Canada, linked to population-based health administrative data. A total of 10 000 charts were randomly selected and manually reviewed using predetermined criteria for ADHD and comorbidities. Prevalence, comorbidities, demographic indicators, and health service utilization characteristics were calculated. Predictors of treatment characteristics were determined using logistic regression modelling. Results: The prevalence of ADHD was 5.4% (7.9% males, 2.7% females). Youth with ADHD had significant psychiatric comorbidities. The majority (70.0%) of ADHD patients received prescriptions for stimulant or nonstimulant ADHD medication. Antipsychotic prescriptions were provided to 11.9% of ADHD patients versus 0.9% of patients without ADHD. Antidepressant prescriptions were provided to 19.8% versus 5.4% of patients with and without ADHD, respectively. Predictors of antidepressant prescriptions were increasing age (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.07 to 1.21), psychiatric consultation (OR, 2.04; 95% CI, 1.16 to 3.58), and diagnoses of both anxiety and depression (OR, 18.4; 95% CI, 8.03 to 42.1), whereas the only predictor of antipsychotic prescriptions was psychiatric consultation (OR, 3.85; 95% CI, 2.11 to 7.02). Conclusions: Youth with ADHD have more psychiatric comorbidities than youth without ADHD. The majority of youth with ADHD received stimulant medications, and a significant number received additional psychotropic medications, with psychiatric consultation predicting medication use.
MeSH term(s)	Adolescent ; Adult ; Anxiety/drug therapy ; Anxiety/epidemiology ; Attention Deficit Disorder with Hyperactivity/drug therapy ; Attention Deficit Disorder with Hyperactivity/epidemiology ; Central Nervous System Stimulants/therapeutic use ; Child ; Child, Preschool ; Comorbidity ; Cross-Sectional Studies ; Depression/drug therapy ; Depression/epidemiology ; Female ; Humans ; Infant ; Male ; Ontario/epidemiology ; Primary Health Care/statistics & numerical data ; Psychotropic Drugs/therapeutic use ; Retrospective Studies ; Young Adult
Chemical Substances	Central Nervous System Stimulants ; Psychotropic Drugs
Language	English
Publishing date	2017-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	304227-3
ISSN	1497-0015 ; 0008-4824 ; 0706-7437
ISSN (online)	1497-0015
ISSN	0008-4824 ; 0706-7437
DOI	10.1177/0706743716689055
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Article ; Online: Identifying Patients With Atrial Fibrillation in Administrative Data.

Tu, Karen / Nieuwlaat, Robby / Cheng, Stephanie Y / Wing, Laura / Ivers, Noah / Atzema, Clare L / Healey, Jeff S / Dorian, Paul

The Canadian journal of cardiology

2016 Volume 32, Issue 12, Page(s) 1561–1565

Abstract: Background: Identifying patients with atrial fibrillation (AF) using administrative data is important for epidemiologic and outcomes research. Although administrative data cover large populations, it is necessary to assess their validity in identifying ... ...

Abstract	Background: Identifying patients with atrial fibrillation (AF) using administrative data is important for epidemiologic and outcomes research. Although administrative data cover large populations, it is necessary to assess their validity in identifying AF patients. Methods: We used Ontario family physician electronic medical records from the Electronic Medical Record Administrative data Linked Database (EMRALD) as a reference standard to assess the accuracy of administrative data algorithms in identifying patients with AF. From a random sample of 7500 adult patients, patients with AF as recorded in family physician records were identified. Results: The optimal algorithm consisted of any of: hospitalization or an emergency room code for AF or prescription for an AF-specific antiarrhythmic agent or billing code for cardioversion, or prescription for an anticoagulant that was accompanied by a physician billing code. for arrhythmia. The algorithm sensitivity was 80.7% (95% confidence interval [CI], 75.1-86.3), specificity 99.1% (95% CI, 98.9-99.3), positive predictive value 71.1% (95% CI, 65.1-77.1), and negative predictive value 99.5% (95% CI, 99.3-99.7). This algorithm, applied to the Ontario population, resulted in a calculated increase in AF prevalence from 1.68% to 2.36% over the years 2000-2014. Anticoagulation rates for AF patients increased from 53% in 2011 to 60% in 2014. Among AF patients receiving anticoagulants, novel oral anticoagulant utilization increased from < 5% in 2011 to > 50% in 2014. Conclusions: Identifying patients with AF can be done using administrative data, and the algorithm can be used to assess trends in disease burden over time and patterns of care in large populations.
MeSH term(s)	Aged ; Algorithms ; Anticoagulants/therapeutic use ; Atrial Fibrillation/epidemiology ; Atrial Fibrillation/therapy ; Data Accuracy ; Databases, Factual ; Electronic Health Records/statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Ontario/epidemiology ; Patient Care Management/organization & administration ; Prevalence
Chemical Substances	Anticoagulants
Language	English
Publishing date	2016-12
Publishing country	England
Document type	Journal Article
ZDB-ID	632813-1
ISSN	1916-7075 ; 0828-282X
ISSN (online)	1916-7075
ISSN	0828-282X
DOI	10.1016/j.cjca.2016.06.006
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Article ; Online: Rotavirus vaccine coverage and factors associated with uptake using linked data: Ontario, Canada.

Wilson, Sarah E / Chung, Hannah / Schwartz, Kevin L / Guttmann, Astrid / Deeks, Shelley L / Kwong, Jeffrey C / Crowcroft, Natasha S / Wing, Laura / Tu, Karen

PloS one

2018 Volume 13, Issue 2, Page(s) e0192809

Abstract: Background: In August 2011, Ontario, Canada introduced a rotavirus immunization program using Rotarix™ vaccine. No assessments of rotavirus vaccine coverage have been previously conducted in Ontario.: Methods: We assessed vaccine coverage (series ... ...

Abstract	Background: In August 2011, Ontario, Canada introduced a rotavirus immunization program using Rotarix™ vaccine. No assessments of rotavirus vaccine coverage have been previously conducted in Ontario. Methods: We assessed vaccine coverage (series initiation and completion) and factors associated with uptake using the Electronic Medical Record Administrative data Linked Database (EMRALD), a collection of family physician electronic medical records (EMR) linked to health administrative data. Series initiation (1 dose) and series completion (2 doses) before and after the program's introduction were calculated. To identify factors associated with series initiation and completion, adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) were calculated using logistic regression. Results: A total of 12,525 children were included. Series completion increased each year of the program (73%, 79% and 84%, respectively). Factors associated with series initiation included high continuity of care (aOR = 2.15; 95%CI, 1.61-2.87), maternal influenza vaccination (aOR = 1.55; 95%CI,1.24-1.93), maternal immmigration to Canada in the last five years (aOR = 1.47; 95% CI, 1.05-2.04), and having no siblings (aOR = 1.62; 95%CI,1.30-2.03). Relative to the first program year, infants were more likely to initiate the series in the second year (aOR = 1.71; 95% CI 1.39-2.10) and third year (aOR = 2.02; 95% CI 1.56-2.61) of the program. Infants receiving care from physicians with large practices were less likely to initiate the series (aOR 0.91; 95%CI, 0.88-0.94, per 100 patients rostered) and less likely to complete the series (aOR 0.94; 95%CI, 0.91-0.97, per 100 patients rostered). Additional associations were identified for series completion. Conclusions: Family physician delivery achieved moderately high coverage in the program's first three years. This assessment demonstrates the usefulness of EMR data for evaluating vaccine coverage. Important insights into factors associated with initiation or completion (i.e. high continuity of care, smaller roster sizes, rural practice location) suggest areas for research and potential program supports.
MeSH term(s)	Child, Preschool ; Cohort Studies ; Confidence Intervals ; Electronic Health Records ; Family Practice ; Female ; Health Information Interoperability ; Humans ; Immunization Programs/statistics & numerical data ; Infant ; Infant, Newborn ; Information Storage and Retrieval ; Logistic Models ; Male ; Multivariate Analysis ; Odds Ratio ; Ontario ; Rotavirus Infections/prevention & control ; Rotavirus Vaccines/therapeutic use
Chemical Substances	Rotavirus Vaccines
Language	English
Publishing date	2018-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0192809
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Article ; Online: Primary Care Screening and Comorbidity Management in Rheumatoid Arthritis in Ontario, Canada.

Widdifield, Jessica / Ivers, Noah M / Bernatsky, Sasha / Jaakkimainen, Liisa / Bombardier, Claire / Thorne, J Carter / Ahluwalia, Vandana / Paterson, J Michael / Young, Jacqueline / Wing, Laura / Tu, Karen

Arthritis care & research

2017 Volume 69, Issue 10, Page(s) 1495–1503

Abstract: Objective: Quality measurement for rheumatoid arthritis (RA) patients has largely focused on care provided by rheumatologists. Our aim was to develop and assess quality measures related to the screening and management of comorbidity in RA patients in ... ...

Abstract	Objective: Quality measurement for rheumatoid arthritis (RA) patients has largely focused on care provided by rheumatologists. Our aim was to develop and assess quality measures related to the screening and management of comorbidity in RA patients in primary care. Methods: We used the primary care Electronic Medical Record Administrative data Linked Database in Ontario, Canada. We harmonized Canadian general population and RA clinical recommendations to develop and assess screening, process, and outcome measures. For each RA patient, 10 non-RA patients were matched by age and sex. Stratified analyses were performed, comparing patients with RA to those without RA, to assess the performance of quality measures. Results: We compared 1,405 RA patients to 14,050 matched non-RA patients (72.8% female; mean age 62.5 years). Compared to non-RA patients, RA patients more frequently had influenza (44.9% versus 40.0%) and pneumococcal (40.4% versus 34.1%) vaccinations and bone mineral density testing (67.4% versus 58.1%). Herpes zoster vaccinations were less frequent among RA patients (13.8% versus 19.5%), as was screening for cervical cancer (58.6% versus 64.0%). No significant differences were observed between RA and non-RA patients in screenings for breast (70.7% versus 73.8%) or colorectal (31.7% versus 34.5%) cancers. Only a quarter of RA patients had a comprehensive cardiovascular risk assessment. No definitive differences were detected in the management of patients who had co-occurring cardiovascular disease or diabetes mellitus. Conclusion: For both RA and non-RA patients, compliance with Canadian recommendations for preventive medical services and screening for comorbid conditions in primary care was less than optimal. This indicates key targets for improvement.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/epidemiology ; Arthritis, Rheumatoid/therapy ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/therapy ; Communicable Diseases/diagnosis ; Communicable Diseases/epidemiology ; Communicable Diseases/therapy ; Comorbidity ; Databases, Factual ; Diabetes Mellitus/diagnosis ; Diabetes Mellitus/epidemiology ; Diabetes Mellitus/therapy ; Electronic Health Records ; Female ; Guideline Adherence ; Humans ; Male ; Mass Screening/methods ; Middle Aged ; Neoplasms/diagnosis ; Neoplasms/epidemiology ; Neoplasms/therapy ; Ontario/epidemiology ; Physicians, Primary Care ; Practice Patterns, Physicians' ; Predictive Value of Tests ; Primary Health Care ; Process Assessment (Health Care) ; Quality Indicators, Health Care ; Retrospective Studies ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2017-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	645059-3
ISSN	2151-4658 ; 0893-7524 ; 2151-464X
ISSN (online)	2151-4658
ISSN	0893-7524 ; 2151-464X
DOI	10.1002/acr.23178
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Article ; Online: Patterns of Care Among Patients Referred to Rheumatologists in Ontario, Canada.

Widdifield, Jessica / Tu, Karen / Carter Thorne, J / Bombardier, Claire / Michael Paterson, J / Liisa Jaakkimainen, R / Wing, Laura / Butt, Debra A / Ivers, Noah / Hofstetter, Catherine / Lyddiatt, Anne / Ahluwalia, Vandana / Bernatsky, Sasha

Arthritis care & research

2017 Volume 69, Issue 1, Page(s) 104–114

Abstract: Objective: Our aim was to characterize referrals to rheumatologists, the early care management of patients with rheumatic diseases, and timeliness of care and treatment.: Methods: We conducted a retrospective observational study involving patients ... ...

Abstract	Objective: Our aim was to characterize referrals to rheumatologists, the early care management of patients with rheumatic diseases, and timeliness of care and treatment. Methods: We conducted a retrospective observational study involving patients with first-time rheumatology referrals between 2000 and 2013 in the primary care Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Referrals were characterized in terms of diagnoses, patient demographics, diagnostic tests, treatment initiated by family physicians and rheumatologists, and other specialists seen prior to rheumatology consultation. Timeliness of referrals, rheumatologist consultations, and treatment were determined overall and for each diagnostic category. Results: Among 2,430 patients referred to a rheumatologist, 69% were female, with an average age of 53 years. The principal diagnosis associated with the referral included osteoarthritis (32%), systemic inflammatory rheumatic diseases (31%), regional musculoskeletal conditions (16%), chronic pain conditions (14%), osteoporosis (2%), and other/miscellaneous (5%). Family physicians most frequently prescribed nonsteroidal antiinflammatory drugs/cyclooxygenase 2 inhibitors (38%), and their pre-referral diagnostic testing practice varied considerably. The duration of time from symptom onset to rheumatology consultation varied by diagnoses, with the shortest being for patients with systemic rheumatic diseases; for rheumatoid arthritis (RA), the median time to consultation was 327 days. Most of the delay occurred prior to referral; 36% of RA patients initiated a disease-modifying antirheumatic drug within 6 months of symptom onset. Conclusion: Approximately 1 in 3 referrals to rheumatologists were for a systemic inflammatory rheumatic disease. We observed substantial delays to rheumatology consultations and variations in patterns of care that could be amenable to quality improvement interventions.
MeSH term(s)	Adult ; Aged ; Delayed Diagnosis/statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Ontario ; Referral and Consultation ; Retrospective Studies ; Rheumatic Diseases/diagnosis ; Rheumatic Diseases/epidemiology ; Rheumatologists ; Rheumatology/statistics & numerical data
Language	English
Publishing date	2017-01
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	645059-3
ISSN	2151-4658 ; 0893-7524 ; 2151-464X
ISSN (online)	2151-4658
ISSN	0893-7524 ; 2151-464X
DOI	10.1002/acr.22910
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Article ; Online: Improving stroke prevention therapy for patients with atrial fibrillation in primary care: protocol for a pragmatic, cluster-randomized trial.

Lee, Theresa M / Ivers, Noah M / Bhatia, Sacha / Butt, Debra A / Dorian, Paul / Jaakkimainen, Liisa / Leblanc, Kori / Legge, Dan / Morra, Dante / Valentinis, Alissia / Wing, Laura / Young, Jacqueline / Tu, Karen

Implementation science : IS

2016 Volume 11, Issue 1, Page(s) 159

Abstract: Background: The prevalence of atrial fibrillation (AF) is growing as the population ages, and at least 15% of ischemic strokes are attributed to AF. However, many high-risk AF patients are not offered guideline-recommended stroke prevention therapy due ... ...

Abstract	Background: The prevalence of atrial fibrillation (AF) is growing as the population ages, and at least 15% of ischemic strokes are attributed to AF. However, many high-risk AF patients are not offered guideline-recommended stroke prevention therapy due to a variety of system, provider, and patient-level barriers. Methods: We will conduct a pragmatic, cluster-randomized controlled trial randomizing primary care clinics to test a "toolkit" of quality improvement interventions in primary care. In keeping with the recommendations of the chronic care model to simultaneously activate patients and facilitate proactive care by providers, the toolkit includes provider-focused strategies (education, audit and feedback, electronic decision support, and reminders) plus patient-directed strategies (educational letters and reminders). The trial will include two feedback cycles at baseline and approximately 6 months and a final data collection at approximately 12 months. The study will be powered to show a difference of 10% in the primary outcome of proportion of patients receiving guideline-recommended stroke prevention therapy. Analysis will follow the intention-to-treat principle and will be blind to treatment allocation. Unit of analysis will be the patient; models will use generalized estimating equations to account for clustering at the clinical level. Discussion: Stroke prevention therapy using anticoagulation in patients with AF is known to reduce strokes by two thirds or more in clinical trials, but most studies indicate under-use of this treatment in real-world practice. If the toolkit successfully improves care for patients with AF, stakeholders will be engaged to facilitate broader application to maximize the potential to improve patient outcomes. The intervention toolkit tested in this project could also provide a model to improve quality of care for other chronic cardiovascular conditions managed in primary care. Trial registration: ClinicalTrials.gov ( NCT01927445 ). Registered August 14, 2014 at https://clinicaltrials.gov/ .
Language	English
Publishing date	2016-12-03
Publishing country	England
Document type	Journal Article
ISSN	1748-5908
ISSN (online)	1748-5908
DOI	10.1186/s13012-016-0523-2
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Article: Wait times to rheumatology care for patients with rheumatic diseases: a data linkage study of primary care electronic medical records and administrative data.

Widdifield, Jessica / Bernatsky, Sasha / Thorne, J Carter / Bombardier, Claire / Jaakkimainen, R Liisa / Wing, Laura / Paterson, J Michael / Ivers, Noah / Butt, Debra / Lyddiatt, Anne / Hofstetter, Catherine / Ahluwalia, Vandana / Tu, Karen

CMAJ open

2016 Volume 4, Issue 2, Page(s) E205–12

Abstract: Background: The Wait Time Alliance recently established wait time benchmarks for rheumatology consultations in Canada. Our aim was to quantify wait times to primary and rheumatology care for patients with rheumatic diseases.: Methods: We identified ... ...

Abstract	Background: The Wait Time Alliance recently established wait time benchmarks for rheumatology consultations in Canada. Our aim was to quantify wait times to primary and rheumatology care for patients with rheumatic diseases. Methods: We identified patients from primary care practices in the Electronic Medical Record Administrative data Linked Database who had referrals to Ontario rheumatologists over the period 2000-2013. To assess the full care pathway, we identified dates of symptom onset, presentation in primary care and referral from electronic medical records. Dates of rheumatologist consultations were obtained by linking with physician service claims. We determined the duration of each phase of the care pathway (symptom onset to primary care encounter, primary care encounter to referral, and referral to rheumatologist consultation) and compared them with established benchmarks. Results: Among 2430 referrals from 168 family physicians, 2015 patients (82.9%) were seen by 146 rheumatologists within 1 year of referral. Of the 2430 referrals, 2417 (99.5%) occurred between 2005 and 2013. The main reasons for referral were osteoarthritis (32.4%) and systemic inflammatory rheumatic diseases (30.6%). Wait times varied by diagnosis and geographic region. Overall, the median wait time from referral to rheumatologist consultation was 74 (interquartile range 27-101) days; it was 66 (interquartile range 18-84) days for systemic inflammatory rheumatic diseases. Wait time benchmarks were not achieved, even for the most urgent types of referral. For systemic inflammatory rheumatic diseases, most of the delays occurred before referral. Interpretation: Rheumatology wait times exceeded established benchmarks. Targeted efforts are needed to promote more timely access to both primary and rheumatology care. Routine linkage of electronic medical records with administrative data may help fill important gaps in knowledge about waits to primary and specialty care.
Language	English
Publishing date	2016-05-11
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2701622-5
ISSN	2291-0026
ISSN	2291-0026
DOI	10.9778/cmajo.20150116
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Article ; Online: Validation of infant immunization billing codes in administrative data.

Schwartz, Kevin L / Tu, Karen / Wing, Laura / Campitelli, Michael A / Crowcroft, Natasha S / Deeks, Shelley L / Wilson, Sarah E / Wilson, Kumanan / Gemmill, Ian / Kwong, Jeffrey C

Human vaccines & immunotherapeutics

2015 Volume 11, Issue 7, Page(s) 1840–1847

Abstract: Ontario has a single payer provincial health insurance program. Administrative data may provide a potentially robust source of information for post-marketing vaccine studies. Vaccine-specific immunization billing codes were introduced in 2011. Our ... ...

Abstract	Ontario has a single payer provincial health insurance program. Administrative data may provide a potentially robust source of information for post-marketing vaccine studies. Vaccine-specific immunization billing codes were introduced in 2011. Our objective was to validate Ontario's universal health care administrative datasets to assess infant immunization status. Electronic medical record data from the Electronic Medical Record Administrative data Linked Database (EMRALD) was used as the reference standard to calculate performance characteristics of the Ontario Health Insurance Plan (OHIP) database vaccine-specific and general immunization codes for 4 primary infant immunizations: diphtheria, tetanus, acellular pertussis, inactivated polio, Haemophilus influenzae type B (DTaP-IPV-Hib) combination vaccine, pneumococcal conjugate vaccine, measles, mumps, rubella (MMR) vaccine, and meningococcal conjugate serogroup C vaccine. OHIP billing claims had specificity ranging from 81% to 92%, sensitivity 70% to 83%, positive predictive value (PPV) 97% to 99%, and negative predictive value (NPV) 13% to 46% for identifying the various specific vaccines in administrative data. For cohorts vaccinated in the new code introduction phase, using both the vaccine-specific and general codes had higher sensitivity than the vaccine-specific codes alone. In conclusion, immunization billing claims from administrative data in Ontario had high specificity and PPV, moderate sensitivity, and low NPV. This study identifies some of the applications of utilizing administrative data for post-marketing vaccine studies. However, limitations of these data decrease their utility for measuring vaccine coverage and effectiveness. Therefore, the establishment of a comprehensive and linkable immunization registry should be a provincial priority.
MeSH term(s)	Adolescent ; Adult ; Child ; Child, Preschool ; Databases, Factual ; Electronic Health Records ; Humans ; Immunization/economics ; Immunization/statistics & numerical data ; Infant ; Infant, Newborn ; Mothers ; National Health Programs/economics ; Ontario ; Physicians ; Product Surveillance, Postmarketing ; Reproducibility of Results ; Socioeconomic Factors ; Universal Coverage/economics ; Vaccination/economics ; Vaccination/statistics & numerical data ; Vaccines/adverse effects ; Vaccines/therapeutic use ; Young Adult
Chemical Substances	Vaccines
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.1080/21645515.2015.1043499
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Article: Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells.

Liu, Hong / Cheng, Dong / Weichel, Alyssa K / Osipo, Clodia / Wing, Laura K / Chen, Bin / Louis, Teresa E / Jordan, V Craig

International journal of oncology

2006 Volume 29, Issue 5, Page(s) 1237–1246

Abstract: The selective ER downregulator, fulvestrant, is currently approved as a second line endocrine therapy after onset of resistance to prior antiestrogen therapy in postmenopausal breast cancer patients. Resistance to antihormonal therapies is common and, ... ...

Abstract	The selective ER downregulator, fulvestrant, is currently approved as a second line endocrine therapy after onset of resistance to prior antiestrogen therapy in postmenopausal breast cancer patients. Resistance to antihormonal therapies is common and, therefore, we anticipate that fulvestrant-resistance will occur as well. The current study was undertaken to investigate the underlying molecular changes after fulvestrant-resistance and find new therapeutic targets and agents for fulvestrant-resistant breast cancer cells. We developed a unique fulvestrant-resistant cell line (MCF-7/F), derived from MCF-7 estrogen receptor alpha (ERalpha)-positive human breast cancer cells, by culturing them in 1 microM fulvestrant containing medium for approximately 18 months. MCF-7/F cells became irreversibly ERalpha negative as withdrawal of fulvestrant did not alter the ERalpha-negative phenotype, determined by real-time PCR, Western blot analysis, and ERE-luciferase transfection assays. MCF-7/F cells grew in a hormone-independent manner. Interestingly, MCF-7/F cells overexpressed both epidermal growth factor receptor (EGFR) and breast cancer resistant protein (BCRP). Gefitinib, a specific EGFR tyrosine kinase inhibitor, preferentially inhibited the growth of MCF-7/F cells relative to MCF-7 cells by inhibiting both MAPK44/42 and Akt phosphorylation. MCF-7/F cells became less sensitive to chemotherapeutic agents such as mitoxantrone. Moreover, fumitremorgin C, a specific BCRP inhibitor, significantly increased the efficacy of mitoxantrone in MCF-7/F cells. Gefitinib increased the inhibitory effect of mitoxantrone on cell growth. Similarly, fumitremorgin C increased the inhibitory effect of gefitinib on cell growth, suggesting that there is a bidirectional crosstalk between EGFR and BCRP. More importantly, these results provide a molecular basis for using gefitinib, BCRP inhibitors, and chemotherapeutic agents as combination therapy approaches in fulvestrant-resistant breast cancer.
MeSH term(s)	ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters/antagonists & inhibitors ; ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/metabolism ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/drug effects ; Estradiol/analogs & derivatives ; Estradiol/therapeutic use ; Estrogen Receptor alpha/analysis ; Female ; Humans ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Mitoxantrone/agonists ; Mitoxantrone/therapeutic use ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Phosphorylation/drug effects ; Piperazines/pharmacology ; Piperazines/therapeutic use ; Proto-Oncogene Proteins c-akt/metabolism ; Quinazolines/pharmacology ; Quinazolines/therapeutic use
Chemical Substances	ABCG2 protein, human ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; Estrogen Receptor alpha ; Neoplasm Proteins ; Piperazines ; Quinazolines ; demethoxyfumitremorgin C ; fulvestrant (22X328QOC4) ; Estradiol (4TI98Z838E) ; Mitoxantrone (BZ114NVM5P) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24) ; gefitinib (S65743JHBS)
Language	English
Publishing date	2006-11
Publishing country	Greece
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1154403-x
ISSN	1019-6439
ISSN	1019-6439
Database	MEDical Literature Analysis and Retrieval System OnLINE

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