Statistical Methods for Health Care Research

Summary Background The body of evidence related to breast-cancer-related lymphoedema incidence and risk factors has substantially grown and improved in quality over the past decade. We assessed the incidence of unilateral arm lymphoedema after breast cancer and explored the evidence available for lymphoedema risk factors. Methods We searched Academic Search Elite, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials (clinical trials), and Medline for research articles that assessed the incidence or prevalence of, or risk factors for, arm lymphoedema after breast cancer, published between Jan 1, 2000, and June 30, 2012. We extracted incidence data and calculated corresponding exact binomial 95% CIs. We used random effects models to calculate a pooled overall estimate of lymphoedema incidence, with subgroup analyses to assess the effect of different study designs, countries of study origin, diagnostic methods, time since diagnosis, and extent of axillary surgery. We assessed risk factors and collated them into four levels of evidence, depending on consistency of findings and quality and quantity of studies contributing to findings. Findings 72 studies met the inclusion criteria for the assessment of lymphoedema incidence, giving a pooled estimate of 16·6% (95% CI 13·6–20·2). Our estimate was 21·4% (14·9–29·8) when restricted to data from prospective cohort studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2 years after diagnosis or surgery of breast cancer (24 studies with time since diagnosis or surgery of 12 to Interpretation Our findings suggest that more than one in five women who survive breast cancer will develop arm lymphoedema. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to reduce the individual and public health burden of this disabling and distressing disorder. Funding The National Breast Cancer Foundation, Australia.

Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis

In certain surfactant solutions, such as aqueous cetyltrimethylammonium bromide (CTAB) in 0.1 M KBr, the amphiphiles are found to assemble reversibly into long, flexible worm-like micelles. Above a few per cent surfactant, these form an entangled viscoelastic fluid, reminiscent of a polymer solution. The authors review some recent experimental and theoretical progress concerning the equilibrium statistics and dynamics of these systems, which differ from normal polymer solutions in that the chains can break and reform reversibly.

http://iopscience.iop.org/article/10.1088/0953-8984/2/33/001/pdf

Statics and dynamics of worm-like surfactant micelles

The purpose of the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline is to provide recommendations to assist primary care and other clinicians in the care of female adult survivors of breast cancer. A systematic review of the literature was conducted using PubMed through April 2015. A multidisciplinary expert workgroup with expertise in primary care, gynecology, surgical oncology, medical oncology, radiation oncology, and nursing was formed and tasked with drafting the Breast Cancer Survivorship Care Guideline. A total of 1,073 articles met inclusion criteria; and, after full text review, 237 were included as the evidence base. Patients should undergo regular surveillance for breast cancer recurrence, including evaluation with a cancer-related history and physical examination, and should be screened for new primary breast cancer. Data do not support performing routine laboratory tests or imaging tests in asymptomatic patients to evaluate for breast cancer recurrence. Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle, monitor for post-treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine therapy. Recommendations provided in this guideline are based on current evidence in the literature and expert consensus opinion. Most of the evidence is not sufficient to warrant a strong evidence-based recommendation. Recommendations on surveillance for breast cancer recurrence, screening for second primary cancers, assessment and management of physical and psychosocial long-term and late effects of breast cancer and its treatment, health promotion, and care coordination/practice implications are made.This guideline was developed through a collaboration between the American Cancer Society and the American Society of Clinical Oncology and has been published jointly by invitation and consent in both CA: A Cancer Journal for Clinicians and Journal of Clinical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Cancer Society or the American Society of Clinical Oncology.

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American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline

Background: Lymphedema is a chronic, debilitating condition that has traditionally been seen as refractory or incurable. Recent years have brought new advances in the study of lymphedema pathophysiology. as well as diagnostic and therapeutic tools that are changing this perspective. Objective: To provide a systematic approach to evaluating and managing patients with lymphedema. Methods: We performed MEDLINE searches of the English-language literature (1966 to March 2006) using the terms lymphedema, breast cancer-associated lymphedema, lymphatic complications, lymphatic imaging, decongestive therapy, and surgical treatment of lymphedema. Relevant bibliographies and International Society of Lymphology guidelines were also reviewed. Results: In the United States, the populations primarily affected by lymphedema are patients undergoing treatment of malignancy, particularly women treated for breast cancer. A thorough evaluation of patients presenting with extremity swelling should include identification of prior surgical or radiation therapy for malignancy, as well as documentation of other risk factors for lymphedema, such as prior trauma to or infection of the affected limb. Physical examination should focus on differentiating signs of lymphedema from other causes of systemic or localized swelling. Lymphatic dysfunction can be visualized through lymphoscintigraphy; the diagnosis of lymphedema can also be confirmed through other imaging modalities, including CT or MRI. The mainstay of therapy in diagnosed cases of lymphedema involves compression garment use, as well as intensive bandaging and lymphatic massage. For patients who are unresponsive to conservative therapy; several surgical options with varied proven efficacies have been used in appropriate candidates, including excisional approaches, microsurgical lymphatic anastomoses, and circumferential suction-assisted lipectomy, an approach that has shown promise for long-term relief of symptoms. Conclusions: The diagnosis of lymphedema requires careful attention to patient risk factors and specific findings on physical examination. Noninvasive diagnostic tools and lymphatic imaging can be helpful to confirm the diagnosis of lymphedema or to address a challenging clinical presentation. Initial treatment with decongestive lymphatic therapy can provide significant improvement in patient symptoms and volume reduction of edematous extremities. Selected patients who are unresponsive to conservative therapy can achieve similar outcomes with surgical intervention, most promisingly suction-assisted lipectomy. (Less)

Lymphedema: a comprehensive review.

OBJECTIVE: The aim of this study was to evaluate the feasibility and effect of a water-based exercise program on lymphedema status and shoulder range of motion among women with breast cancer-related lymphedema. DESIGN: This was a single-blinded, randomized controlled pilot trial. Twenty-nine eligible breast cancer survivors (median, 10 yrs after surgery) with arm lymphedema (median, 21% interlimb difference) were included and randomized into the intervention (n = 15) or control (n = 14) group. Twenty-five participants completed the study. The intervention was at least twice-weekly water-based exercise for 8 wks, initially supervised but performed independently during the study period. Outcomes of interest were feasibility as measured by retention and adherence; lymphedema status as measured by optoelectronic perometry, bioimpedance spectroscopy, and tissue dielectric constant; and shoulder range of motion as measured by goniometer. RESULTS: Four participants were not measured at postintervention and were not included in the analysis (retention). Four participants in the intervention group did not perform the minimum water-based exercise criteria set (adherence). No effect was found on lymphedema status. Compared with the control group, median range of motion change for flexion was 6 (1-10) degrees (P < 0.001) and 6 (0-15.5) degrees (P = 0.07) for external rotation.A clinically relevant increase in the intervention group was found for 36% in flexion (P ≤ 0.05) and 57% in external rotation (P ≤ 0.05) compared with controls. CONCLUSIONS: This study shows that water-based exercise is feasible for breast cancer survivors with arm lymphedema and that shoulder range of motion can be improved years after cancer treatment has been completed. (Less)

Water-Based Exercise for Patients with Chronic Arm Lymphedema: A Randomized Controlled Pilot Trial.

Physical activity is of great benefit to women treated for breast cancer and can even be vital. The aim of this qualitative study was to describe how women treated for breast cancer experience physical activity after surgery. Twelve women, strategically selected according to hospital, age and length of time since surgery, took part in a semi-structured interview. A qualitative method with a phenomenographic approach was used. The result indicates that the incentive to remain or return to a normal physical condition is an important motive for physical activity after breast cancer surgery. The experience of physical activity was, from the women's perspective, expressed in (i) compliance to instructions and need for support, (ii) struggle to get back to normal and fear of negative side-effects, (iii) a wish to stay normal and not allow limitations and (iv) getting control of the situation with new strategies. In conclusion, instructions and motivation are important in starting up and/or continuing physical activity after breast cancer treatment. While in considering the vital benefits of physical activity for breast cancer patients healthcare professionals, and in particular physiotherapists, must be aware of the need for information and the patients' motive for exercise and physical activity to be able to guide and encourage them individually. The professionals must also understand the need for empowerment for these women to take control over their lives and to allow the limitations that eventually occur.

Women's experience of physical activity following breast cancer treatment.

The purpose of this study was to reduce the 188-item Swedish Lymphedema Quality of Life Inventory (SLQOLI) to an abbreviated, clinically useful version (phase 1) and to test it for reliability and validity (phase 2). In phase 1 correlation analysis, factor analysis, content validity assessment and expert panels were used to reduce the number of items in SLQOLI to 45 items, which was named, Lymphedema Quality of Life Inventory (LyQLI). In phase 2, LyQLI was sent to 200 patients with lymphedema. 126 patients completed the questionnaire twice to determine stability of the instrument over time. SF-36 was sent to the patients once, correlations between the three domains in LyQLI and the two sum scores Physical Health (PCS) and Mental Health (MCS) in SF-36 were used to assess concurrent validity. The 188-item SLQOLI was reduced to 45-item LyQLI. Four domains were reduced to three: physical, psychosocial and practical. Reliability estimates using ICC for the physical and psychosocial domains were 0.88 (p < 0.01) and 0.87 (p < 0.01), for the practical domain 0.87 (p < 0.01). Cronbach’s alpha coefficients for the three domains were 0.88, 0.92 and 0.88, respectively. The physical domain correlated highly significantly with PCS, psychosocial highly significantly with MCS and practical equally highly significantly to both PCS and MCS. Using skewness coefficients, small floor effects in the items were found. The shorter LyQLI demonstrated good reliability and validity with potential use to assess quality of life in clinic settings and in further cross-sectional studies of patients with lymphedema.

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Lymphedema Quality of Life Inventory (LyQLI)-Development and investigation of validity and reliability.

lower limb lymphedema : experiences and perceptions of cancer patients in the late palliative stage

Lower limb lymphedema: experiences and perceptions of cancer patients in the late palliative stage.

Objective: To evaluate the feasibility and effect of a water-based exercise (WBE) program on lymphedema status and shoulder range of motion (ROM) among women with breast cancer related lymphedema.

Design: Single-blinded, randomized controlled pilot trial. Twenty-nine eligible breast cancer survivors (median 10 years after surgery) with arm lymphedema (median 21% inter limb difference) were included and randomized into intervention (n= 15) or control (n=14). Twenty-five participants completed the study. The intervention was at least twice weekly WBE for 8 weeks; supervised initially but performed independently during the study period. Outcomes of interest were feasibility as measured by retention and adherence, lymphedema status as measured by optoelectronic perometry, bioimpedance spectroscopy and tissue dielectric constant, and shoulder range of motion (ROM) as measured by goniometer.

Results: Four participants were not measured at post-intervention and were not included in the analysis (retention). Four participants in the intervention group did not perform the minimum WBE criteria set (adherence). No effect was found on lymphedema status. Compared to the control group, median ROM change for flexion was 6 (1-10) degrees (p<0.001) and 6 (0-15.5) degrees (p=0,07) for external rotation. Clinically relevant increase in the intervention group was found for 36% in flexion (p≤0.05) and (57%) in external rotation (p≤0.05) compared to controls.

Conclusions: This study shows WBE is feasible for breast cancer survivors with arm lymphedema and that shoulder ROM can be improved years after cancer treatment has been completed.

Karin Johansson

Papers

Water-Based Exercise for Patients with Chronic Arm Lymphedema: A Randomized Controlled Pilot Trial.

Women's experience of physical activity following breast cancer treatment.

Lymphedema Quality of Life Inventory (LyQLI)-Development and investigation of validity and reliability.

Lower limb lymphedema: experiences and perceptions of cancer patients in the late palliative stage.

Water-based exercise for patients with chronic arm lymphedema : a randomized controlled pilot trial