Back to Journals » OncoTargets and Therapy » Volume 8

Using an innovative multiple regression procedure in a cancer population (Part I): detecting and probing relationships of common interacting symptoms (pain, fatigue/weakness, sleep problems) as a strategy to discover influential symptom pairs and clusters

Authors Francoeur R

Received 18 April 2014

Accepted for publication 9 June 2014

Published 22 December 2014 Volume 2015:8 Pages 45—56


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Richard B Francoeur1,2

1School of Social Work and the Center for Health Innovation, Adelphi University, Garden City, NY, USA; 2Center for the Psychosocial Study of Health and Illness, Columbia University, New York, NY, USA

Background: The majority of patients with advanced cancer experience symptom pairs or clusters among pain, fatigue, and insomnia. Improved methods are needed to detect and interpret interactions among symptoms or diesease markers to reveal influential pairs or clusters. In prior work, I developed and validated sequential residual centering (SRC), a method that improves the sensitivity of multiple regression to detect interactions among predictors, by conditioning for multicollinearity (shared variation) among interactions and component predictors.
Materials and methods: Using a hypothetical three-way interaction among pain, fatigue, and sleep to predict depressive affect, I derive and explain SRC multiple regression. Subsequently, I estimate raw and SRC multiple regressions using real data for these symptoms from 268 palliative radiation outpatients.
Results: Unlike raw regression, SRC reveals that the three-way interaction (pain × fatigue/weakness × sleep problems) is statistically significant. In follow-up analyses, the relationship between pain and depressive affect is aggravated (magnified) within two partial ranges: 1) complete-to-some control over fatigue/weakness when there is complete control over sleep problems (ie, a subset of the pain–fatigue/weakness symptom pair), and 2) no control over fatigue/weakness when there is some-to-no control over sleep problems (ie, a subset of the pain–fatigue/weakness–sleep problems symptom cluster). Otherwise, the relationship weakens (buffering) as control over fatigue/weakness or sleep problems diminishes.
Conclusion: By reducing the standard error, SRC unmasks a three-way interaction comprising a symptom pair and cluster. Low-to-moderate levels of the moderator variable for fatigue/weakness magnify the relationship between pain and depressive affect. However, when the comoderator variable for sleep problems accompanies fatigue/weakness, only frequent or unrelenting levels of both symptoms magnify the relationship. These findings suggest that a countervailing mechanism involving depressive affect could account for the effectiveness of a cognitive behavioral intervention to reduce the severity of a pain, fatigue, and sleep disturbance cluster in a previous randomized trial.

Keywords: depression, moderated regression, multicollinearity, sickness behavior, statistical interaction, symptom cluster

Erratum for this paper has been published.

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Readers of this article also read:

Preparation and clinical evaluation of nano-transferosomes for treatment of erectile dysfunction

Ali MFM, Salem HF, Abdelmohsen HF, Attia SK

Drug Design, Development and Therapy 2015, 9:2431-2447

Published Date: 29 April 2015

Protective effect of gonadotropin-releasing hormone analog on the ovarian reserve in rats receiving cyclophosphamide treatment

Gui T, Yuan GW, Shen K, Cao DY, Yang JX, Wu M, Lang JH

OncoTargets and Therapy 2015, 8:661-667

Published Date: 23 March 2015

Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles

Di Bucchianico S, Fabbrizi MR, Cirillo S, Uboldi C, Gilliland D, Valsami-Jones E, Migliore L

International Journal of Nanomedicine 2014, 9:2191-2204

Published Date: 8 May 2014

Umbilical cord mesenchymal stem cells labeled with multimodal iron oxide nanoparticles with fluorescent and magnetic properties: application for in vivo cell tracking

Sibov TT, Pavon LF, Miyaki LA, Mamani JB, Nucci LP, Alvarim LT, Silveira PH, Marti LC, Gamarra LF

International Journal of Nanomedicine 2014, 9:337-350

Published Date: 8 January 2014

A characteristic optic disc appearance associated with myopia in subjects with Graves' ophthalmopathy and in subjects with primary open-angle glaucoma

Yamazaki S, Inoue R, Tsuboi T, Kozaki A, Inoue T, Inoue T, Inoue Y

Clinical Ophthalmology 2013, 7:47-53

Published Date: 7 January 2013

Eribulin mesylate as a microtubule inhibitor for treatment of patients with metastatic breast cancer

Muñoz-Couselo E, Pérez-García J, Cortés J

OncoTargets and Therapy 2011, 4:185-192

Published Date: 14 November 2011

Acute visual loss and intraocular hemorrhages associated with endoscopic spinal surgery

Marilita M Moschos, Alexandros Rouvas, Alexios Papaspirou, Michael Apostolopoulos

Clinical Ophthalmology 2008, 2:937-939

Published Date: 5 December 2008