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Article ; Online: On Framing the Research Question and Choosing the Appropriate Research Design.

Parfrey, Patrick S / Ravani, Pietro

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2249, Page(s) 1–16

Abstract: Clinical epidemiology is the science of human disease investigation with a focus on diagnosis, prognosis, and treatment. The generation of a reasonable question requires definition of patients, interventions, controls, and outcomes. The goal of research ... ...

Abstract	Clinical epidemiology is the science of human disease investigation with a focus on diagnosis, prognosis, and treatment. The generation of a reasonable question requires definition of patients, interventions, controls, and outcomes. The goal of research design is to minimize error, ensure adequate samples, measure input and output variables appropriately, consider external and internal validities, limit bias, and address clinical as well as statistical relevance. The hierarchy of evidence for clinical decision-making places randomized controlled trials (RCT) or systematic review of good-quality RCTs at the top of the evidence pyramid. Prognostic and etiologic questions are best addressed with longitudinal cohort studies.
MeSH term(s)	Biomedical Research/methods ; Clinical Decision-Making ; Epidemiologic Studies ; Evidence-Based Medicine/methods ; Humans ; Longitudinal Studies ; Prognosis ; Randomized Controlled Trials as Topic ; Research Design ; Systematic Reviews as Topic
Language	English
Publishing date	2021-04-19
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1138-8_1
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Article ; Online: Longitudinal Studies 3: Data Modeling Using Standard Regression Models and Extensions.

Ravani, Pietro / Barrett, Brendan J / Parfrey, Patrick S

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2249, Page(s) 125–165

Abstract: In longitudinal studies, the relationship between exposure and disease can be measured once or multiple times while participants are monitored over time. Traditional regression techniques are used to model outcome data when each epidemiological unit is ... ...

Abstract	In longitudinal studies, the relationship between exposure and disease can be measured once or multiple times while participants are monitored over time. Traditional regression techniques are used to model outcome data when each epidemiological unit is observed once. These models include generalized linear models for quantitative continuous, discrete, or qualitative outcome responses, and models for time-to-event data. When data come from the same subjects or group of subjects, observations are not independent and the underlying correlation needs to be addressed in the analysis. In these circumstances, extended models are necessary to handle complexities related to clustered data, and repeated measurements of time-varying predictors and/or outcomes.
MeSH term(s)	Adult ; Age Factors ; Female ; Humans ; Linear Models ; Longitudinal Studies ; Male ; Middle Aged ; Models, Statistical ; Regression Analysis ; Research Design ; Survival Analysis ; Young Adult
Language	English
Publishing date	2021-04-19
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1138-8_8
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Article ; Online: Longitudinal Studies 2: Modeling Data Using Multivariate Analysis.

Ravani, Pietro / Barrett, Brendan J / Parfrey, Patrick S

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2249, Page(s) 103–124

Abstract: Statistical models are used to study the relationship between exposure and disease while accounting for the potential role of other factors' impact upon outcomes. This adjustment is useful to obtain unbiased estimates of true effects or to predict future ...

Abstract	Statistical models are used to study the relationship between exposure and disease while accounting for the potential role of other factors' impact upon outcomes. This adjustment is useful to obtain unbiased estimates of true effects or to predict future outcomes. Statistical models include a systematic and an error component. The systematic component explains the variability of the response variable as a function of the predictors and is summarized in the effect estimates (model coefficients). The error element of the model represents the variability in the data unexplained by the model and is used to build measures of precisions around the point estimates (Confidence Intervals).
MeSH term(s)	Humans ; Longitudinal Studies ; Models, Statistical ; Multivariate Analysis ; Regression Analysis
Language	English
Publishing date	2021-04-19
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1138-8_7
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Article: Multifactor dimensionality reduction method identifies novel SNP interactions in the WNT protein interaction networks that are associated with recurrence risk in colorectal cancer.

Curtis, Aaron A / Yu, Yajun / Carey, Megan / Parfrey, Patrick / Yilmaz, Yildiz E / Savas, Sevtap

Frontiers in oncology

2023 Volume 13, Page(s) 1122229

Abstract: Background: Interactions among genetic variants are rarely studied but may explain a part of the variability in patient outcomes.: Objectives: In this study, we aimed to identify 1 to 3 way interactions among SNPs from five Wnt protein interaction ... ...

Abstract	Background: Interactions among genetic variants are rarely studied but may explain a part of the variability in patient outcomes. Objectives: In this study, we aimed to identify 1 to 3 way interactions among SNPs from five Wnt protein interaction networks that predict the 5-year recurrence risk in a cohort of stage I-III colorectal cancer patients. Methods: 423 patients recruited to the Newfoundland Familial Colorectal Cancer Registry were included. Five Wnt family member proteins (Wnt1, Wnt2, Wnt5a, Wnt5b, and Wnt11) were selected. The BioGRID database was used to identify the proteins interacting with each of these proteins. Genotypes of the SNPs located in the interaction network genes were retrieved from a genome-wide SNP genotype data previously obtained in the patient cohort. The GMDR 0.9 program was utilized to examine 1-, 2-, and 3-SNP interactions using a 5-fold cross validation step. Top GMDR 0.9 models were assessed by permutation testing and, if significant, prognostic associations were verified by multivariable logistic regression models. Results: GMDR 0.9 has identified novel 1, 2, and 3-way SNP interactions associated with 5-year recurrence risk in colorectal cancer. Nine of these interactions were multi loci interactions (2-way or 3-way). Identified interaction models were able to distinguish patients based on their 5-year recurrence-free status in multivariable regression models. The significance of interactions was the highest in the 3-SNP models. Several of the identified SNPs were eQTLs, indicating potential biological roles of the genes they were associated with in colorectal cancer recurrence. Conclusions: We identified novel interacting genetic variants that associate with 5-year recurrence risk in colorectal cancer. A significant portion of the genes identified were previously linked to colorectal cancer pathogenesis or progression. These variants and genes are of interest for future functional and prognostic studies. Our results provide further evidence for the utility of GMDR models in identifying novel prognostic biomarkers and the biological importance of the Wnt pathways in colorectal cancer.
Language	English
Publishing date	2023-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1122229
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Article: Examining SNP-SNP interactions and risk of clinical outcomes in colorectal cancer using multifactor dimensionality reduction based methods.

Curtis, Aaron / Yu, Yajun / Carey, Megan / Parfrey, Patrick / Yilmaz, Yildiz E / Savas, Sevtap

Frontiers in genetics

2022 Volume 13, Page(s) 902217

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2022-08-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2022.902217
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Article ; Online: Temporal Trends in Hemoglobin, Use of Erythropoiesis Stimulating Agents, and Major Clinical Outcomes in Incident Dialysis Patients in Canada.

Canney, Mark / Birks, Peter / Shao, Selena / Parfrey, Patrick / Djurdjev, Ognjenka / Levin, Adeera

Kidney international reports

2021 Volume 6, Issue 4, Page(s) 1130–1140

Abstract: Introduction: Several jurisdictions have adopted a more conservative approach to anemia in patients receiving dialysis amid safety concerns from target hemoglobin studies. It is largely unknown if this has contributed to a change in clinical outcomes.!## ...

Abstract	Introduction: Several jurisdictions have adopted a more conservative approach to anemia in patients receiving dialysis amid safety concerns from target hemoglobin studies. It is largely unknown if this has contributed to a change in clinical outcomes. Methods: A national registry was used to identify 35,945 adult patients who initiated and were maintained on dialysis for ≥90 days in Canada from January 2007 to December 2015. Outcomes were ascertained until March 2017 via linkage with hospital discharge diagnoses. Cox proportional hazards models were used to investigate the association between the era of dialysis initiation and the primary composite outcome (acute myocardial infarction [AMI], stroke, or mortality). Results: The mean hemoglobin at dialysis initiation decreased from 102.9 g/l in 2007 to 95.5 g/l in 2015, corresponding with a higher prevalence of hemoglobin <80 g/l (8% to 17%) and a reduction in erythropoiesis stimulating agent (ESA) use (49% to 44%). After multivariable adjustment, Era 3 (2013-2015) was associated with an 8% relative risk reduction in the primary outcome compared with Era 1 (2007-2009) (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.88-0.96), a 10% relative reduction in mortality (HR 0.90, 95% CI 0.85-0.94) but no significant change in AMI or stroke. In a model without era, neither hemoglobin nor ESA use was an independent predictor of outcome. Conclusion: There have been modest declines in average hemoglobin values and ESA use among incident dialysis patients in Canada with no change in major cardiovascular outcomes. Patient survival has improved over time, likely for reasons other than anemia management.
Language	English
Publishing date	2021-01-05
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2020.12.022
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Article ; Online: A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer.

Yu, Yajun / Werdyani, Salem / Carey, Megan / Parfrey, Patrick / Yilmaz, Yildiz E / Savas, Sevtap

Molecular oncology

2021 Volume 15, Issue 12, Page(s) 3329–3347

Abstract: ... A common SNP (WBP11-rs7314075) was associated with disease-specific survival with P-value of 3.2 × 10 ...

Abstract	We aimed to examine the associations of a genome-wide set of single nucleotide polymorphisms (SNPs) and 254 copy number variations (CNVs) and/or insertion/deletions (INDELs) with clinical outcomes in colorectal cancer patients (n = 505). We also aimed to investigate whether their associations changed (e.g., appeared, diminished) over time. Multivariable Cox proportional hazards and piece-wise Cox regression models were used to examine the associations. The Cancer Genome Atlas (TCGA) datasets were used for replication purposes and to examine the gene expression differences between tumor and nontumor tissue samples. A common SNP (WBP11-rs7314075) was associated with disease-specific survival with P-value of 3.2 × 10
MeSH term(s)	Colorectal Neoplasms/pathology ; DNA Copy Number Variations/genetics ; DNA-Binding Proteins/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; RNA Splicing Factors/genetics
Chemical Substances	DNA-Binding Proteins ; RNA Splicing Factors ; WBP11 protein, human
Language	English
Publishing date	2021-08-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.13067
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Article ; Online: Manipulation of the seagrass-associated microbiome reduces disease severity.

Graham, Olivia J / Adamczyk, Emily M / Schenk, Siobhan / Dawkins, Phoebe / Burke, Samantha / Chei, Emily / Cisz, Kaitlyn / Dayal, Sukanya / Elstner, Jack / Hausner, Arjun Lev Pillai / Hughes, Taylor / Manglani, Omisha / McDonald, Miles / Mikles, Chloe / Poslednik, Anna / Vinton, Audrey / Wegener Parfrey, Laura / Harvell, C Drew

Environmental microbiology

2024 Volume 26, Issue 2, Page(s) e16582

Abstract: Host-associated microbes influence host health and function and can be a first line of defence against infections. While research increasingly shows that terrestrial plant microbiomes contribute to bacterial, fungal, and oomycete disease resistance, no ... ...

Abstract	Host-associated microbes influence host health and function and can be a first line of defence against infections. While research increasingly shows that terrestrial plant microbiomes contribute to bacterial, fungal, and oomycete disease resistance, no comparable experimental work has investigated marine plant microbiomes or more diverse disease agents. We test the hypothesis that the eelgrass (Zostera marina) leaf microbiome increases resistance to seagrass wasting disease. From field eelgrass with paired diseased and asymptomatic tissue, 16S rRNA gene amplicon sequencing revealed that bacterial composition and richness varied markedly between diseased and asymptomatic tissue in one of the two years. This suggests that the influence of disease on eelgrass microbial communities may vary with environmental conditions. We next experimentally reduced the eelgrass microbiome with antibiotics and bleach, then inoculated plants with Labyrinthula zosterae, the causative agent of wasting disease. We detected significantly higher disease severity in eelgrass with a native microbiome than an experimentally reduced microbiome. Our results over multiple experiments do not support a protective role of the eelgrass microbiome against L. zosterae. Further studies of these marine host-microbe-pathogen relationships may continue to show new relationships between plant microbiomes and diseases.
MeSH term(s)	RNA, Ribosomal, 16S/genetics ; Stramenopiles/genetics ; Zosteraceae/genetics ; Zosteraceae/microbiology ; Microbiota/genetics ; Plant Leaves/microbiology ; Bacteria/genetics
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2024-01-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2020213-1
ISSN	1462-2920 ; 1462-2912
ISSN (online)	1462-2920
ISSN	1462-2912
DOI	10.1111/1462-2920.16582
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Article ; Online: On framing the research question and choosing the appropriate research design.

Parfrey, Patrick S / Ravani, Pietro

Methods in molecular biology (Clifton, N.J.)

2015 Volume 1281, Page(s) 3–18

Abstract	Clinical epidemiology is the science of human disease investigation with a focus on diagnosis, prognosis, and treatment. The generation of a reasonable question requires definition of patients, interventions, controls, and outcomes. The goal of research design is to minimize error, to ensure adequate samples, to measure input and output variables appropriately, to consider external and internal validities, to limit bias, and to address clinical as well as statistical relevance. The hierarchy of evidence for clinical decision-making places randomized controlled trials (RCT) or systematic review of good quality RCTs at the top of the evidence pyramid. Prognostic and etiologic questions are best addressed with longitudinal cohort studies.
MeSH term(s)	Evidence-Based Medicine/methods ; Humans ; Longitudinal Studies ; Randomized Controlled Trials as Topic/methods ; Research Design
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-2428-8_1
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Article: Family physician referral rates for lumbar spine computed tomography in Newfoundland and Labrador: a cross-sectional analysis using routinely collected data.

Logan, Gabrielle S / Copsey, Bethan / Etchegary, Holly / Parfrey, Patrick / Mahoney, Krista / Hall, Amanda

CMAJ open

2020 Volume 8, Issue 1, Page(s) E56–E59

Abstract: Background: Reducing computed tomography (CT) examinations of the lumbar spine is one of Choosing Wisely Canada's initial top 10 recommendations. This study's objective was to report the age- and-sex standardized rates of lumbar spine CT ordered by ... ...

Abstract	Background: Reducing computed tomography (CT) examinations of the lumbar spine is one of Choosing Wisely Canada's initial top 10 recommendations. This study's objective was to report the age- and-sex standardized rates of lumbar spine CT ordered by family physicians in 1 health region in Newfoundland and Labrador. Methods: We conducted a retrospective study using local health data from Meditech, an electronic health record system, from 2013 to 2016 for the Eastern Health Region of Newfoundland and Labrador, the largest health region in the province. Records were included if the referral was for an adult aged 20 years or more, and CT was ordered by a family physician. Lumbar spine CT rates were contextualized with age- and sex-stratified estimates. Population estimates were provided by the Newfoundland and Labrador Centre for Health Information to calculate age- and sex-standardized rates per 100 000 people. We calculated rate ratios to test for statistical significance in differences in rates between years. Results: A total of 14 370 records were examined. The age- and sex-standardized rates of lumbar spine CT per 100 000 were 1225 in 2013, 1393 in 2014, 1556 in 2015 and 1395 in 2016. The rate ratio was 1.137 (95% confidence interval [CI] 1.084-1.194) for the comparison between 2014 and 2013, 1.117 (95% CI 1.067-1.169) between 2015 and 2014, and 0.896 (95% CI 0.857-0.938) between 2016 and 2015. Interpretation: The age- and sex-standardized rates suggest that there was a steady rate of lumbar spine CT examinations being ordered by family physicians in Newfoundland and Labrador in 2013-2016. Although all rate ratios were statistically significant, the magnitude of the difference between years is likely not clinically relevant. These rates are important because they serve as a benchmark for future initiatives to reduce unnecessary referrals for lumbar spine CT.
MeSH term(s)	Adult ; Age Factors ; Aged ; Cross-Sectional Studies ; Female ; Health Care Surveys ; Humans ; Lumbar Vertebrae/diagnostic imaging ; Male ; Middle Aged ; Newfoundland and Labrador/epidemiology ; Physicians, Family ; Primary Health Care/statistics & numerical data ; Referral and Consultation/statistics & numerical data ; Sex Factors ; Tomography, X-Ray Computed ; Young Adult
Language	English
Publishing date	2020-01-28
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2701622-5
ISSN	2291-0026
ISSN	2291-0026
DOI	10.9778/cmajo.20190076
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