Use of HbA1c in the Diagnosis of Diabetes in Adolescents

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Use of HbA1c in the Diagnosis of Diabetes in Adolescents

Study Overview

Objective. To examine the screening practices of family practitioners (FPs) and pediatricians for type 2 diabetes (T2D) in adolescents.

Design. Cross-sectional study.

Setting and participants. The researchers randomly sampled 700 pediatricians and 700 FPs who participated in direct patient care using the American Medical Association Physician Masterfile using a mail survey. Exclusion criteria included providers who were residents, hospital staff, retirees, or employed by federally owned medical facilities, certified with a subspecialty, or over age 70.

Main outcome measures. Providers were given a hypothetical case of an obese, female, teenaged patient with concurrent associated risk factors for T2D (family history of T2D, minority race, signs of insulin resistance) and asked what initial screening tests they would order. Respondents were then informed of the updated American Diabetes Association (ADA) guidelines that added hemoglobin A1c as a screening test to diagnose diabetes. The survey then asked if knowing this change in recommendation has changed or will change their screening practices in adolescents.

Main results. 1400 surveys were mailed. After 2 were excluded due to mailing issues, 52% of providers provided responses. Of these, 129 providers reported that they did not care for adolescents (age 10–17), resulting in 604 providers in the final sample, 398 pediatricians and 335 FPs.

The vast majority (92%) said they would screen the hypothetical case for diabetes, with most initially ordering a fasting test (fasting plasma glucose or 2-hour glucose tolerance test) (63%) or A1c test (58%). Of the 58% who planned to order HbA1c, only 35% ordered it in combination with a fasting test. HbA1c was significantly more likely to be ordered by pediatricians than by FPs (P = 0.001). After being presented with the new guidelines, 84% said then would now order HbA1c, a 27% increase.

Conclusion. In response to information about the new guidelines, providers were more likely to order A1c as part of initial testing. Due to the lower test performance in children and increased cost of the test, the use of HbA1c without fasting tests may result in missed diagnosis of T2D in adolescents as well as increased health care costs.

Commentary

Rates of childhood obesity continue to rise throughout the United States. Obese children are at risk for numerous comorbidities such as hypertension, hyperlipidemia, and T2D [1,2]. It is important for providers to use effective screening tools for risk assessment of prediabetes/T2DM in children.

The standard tests for diagnosing diabetes are the fasting plasma glucose test and the 2-hour plasma glucose test. While accurate, these tests are not convenient. In 2010, the ADA added an easier method of testing for T2D: an HbA1c, with results greater than or equal to 6.5% indicating diabetes [3]. However, this recommendation is controversial, given studies suggesting that HbA1c is not as reliable in children as it is in adults [4–6]. The ADA itself acknowledges that there are limited data in the pediatric population.

In this study, most providers were unaware of the 4-year-old revised guidelines offering the A1c option but are planning to apply the guidelines going forward. According to the study, this would result in a 27% increase in providers utilizing HbA1c.

Should increased uptake of A1c as an initial screening test be a concern? Using it in combination with other tests may be useful for assessing which adolescents will need further testing [3–6]. Additionally, by starting with a test that can be performed in the office with no regard to fasting time, it is possible that more cases of T2D will be found by primary care providers treating adolescents.

A weakness of the study is the potential for response bias related to mailed surveys. An additional weakness is that the researchers utilized only 1 hypothetical situation. Providing additional hypothetical situations may have allowed for further understanding of screening practices. The investigators also did not include nurse practitioners or physician assistants in their sample, a growing percentage of whom may care for adolescent populations at risk for T2D or be primary referral sources.

Applications for Clinical Practice

Providers can use HbA1c to screen for diabetes in nonfasting adolescents at risk for diabetes. While the test may not be as accurate in pediatric patients, utilizing HbA1C as directed by the ADA may aid in diagnosing patients that may otherwise miss follow-up appointments to complete a fasting test.

                                                                                                                                                                                           —Jennifer L. Nahum, MSN, CPNP-AC, PPCNP-BC, and Allison Squires, PhD, RN

References

1. Freedman DS, Dietz WH, Srinivasan SR, Berenson GS. The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics 1999;103(6 Pt 1):1175–82.

2. Pinhas-Hamiel O, Dolan LM, Daniels SR, Standiford D, Khoury PR, Zeitler P. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr 1996;128(5 Pt 1):608–15.

3. American Diabetes Association. Type 2 diabetes in children and adolescents. Pediatrics 2000 Mar;105(3 Pt 1):671–80.

4. Lee JM, Gebremariam A, Wu EL, et al. Evaluation of nonfasting tests to screen for childhood and adolescent dysglycemia. Diabetes Care 2011;34:2597–602.

5. Nowicka P, Santoro N, Liu H, et al. Utility of hemoglobin A(1c) for diagnosing prediabetes and diabetes in obese children and adolescents. Diabetes Care 2011;34:1306–11.

6. Lee JM, Wu EL, Tarini B, et al Diagnosis of diabetes using hemoglobin A1c: should recommendations in adults be extrapolated to adolescents? J Pediatr 2011;158:947–952.

Issue
Journal of Clinical Outcomes Management - July 2014, Vol. 21, No. 7
Publications
Topics
Sections

Study Overview

Objective. To examine the screening practices of family practitioners (FPs) and pediatricians for type 2 diabetes (T2D) in adolescents.

Design. Cross-sectional study.

Setting and participants. The researchers randomly sampled 700 pediatricians and 700 FPs who participated in direct patient care using the American Medical Association Physician Masterfile using a mail survey. Exclusion criteria included providers who were residents, hospital staff, retirees, or employed by federally owned medical facilities, certified with a subspecialty, or over age 70.

Main outcome measures. Providers were given a hypothetical case of an obese, female, teenaged patient with concurrent associated risk factors for T2D (family history of T2D, minority race, signs of insulin resistance) and asked what initial screening tests they would order. Respondents were then informed of the updated American Diabetes Association (ADA) guidelines that added hemoglobin A1c as a screening test to diagnose diabetes. The survey then asked if knowing this change in recommendation has changed or will change their screening practices in adolescents.

Main results. 1400 surveys were mailed. After 2 were excluded due to mailing issues, 52% of providers provided responses. Of these, 129 providers reported that they did not care for adolescents (age 10–17), resulting in 604 providers in the final sample, 398 pediatricians and 335 FPs.

The vast majority (92%) said they would screen the hypothetical case for diabetes, with most initially ordering a fasting test (fasting plasma glucose or 2-hour glucose tolerance test) (63%) or A1c test (58%). Of the 58% who planned to order HbA1c, only 35% ordered it in combination with a fasting test. HbA1c was significantly more likely to be ordered by pediatricians than by FPs (P = 0.001). After being presented with the new guidelines, 84% said then would now order HbA1c, a 27% increase.

Conclusion. In response to information about the new guidelines, providers were more likely to order A1c as part of initial testing. Due to the lower test performance in children and increased cost of the test, the use of HbA1c without fasting tests may result in missed diagnosis of T2D in adolescents as well as increased health care costs.

Commentary

Rates of childhood obesity continue to rise throughout the United States. Obese children are at risk for numerous comorbidities such as hypertension, hyperlipidemia, and T2D [1,2]. It is important for providers to use effective screening tools for risk assessment of prediabetes/T2DM in children.

The standard tests for diagnosing diabetes are the fasting plasma glucose test and the 2-hour plasma glucose test. While accurate, these tests are not convenient. In 2010, the ADA added an easier method of testing for T2D: an HbA1c, with results greater than or equal to 6.5% indicating diabetes [3]. However, this recommendation is controversial, given studies suggesting that HbA1c is not as reliable in children as it is in adults [4–6]. The ADA itself acknowledges that there are limited data in the pediatric population.

In this study, most providers were unaware of the 4-year-old revised guidelines offering the A1c option but are planning to apply the guidelines going forward. According to the study, this would result in a 27% increase in providers utilizing HbA1c.

Should increased uptake of A1c as an initial screening test be a concern? Using it in combination with other tests may be useful for assessing which adolescents will need further testing [3–6]. Additionally, by starting with a test that can be performed in the office with no regard to fasting time, it is possible that more cases of T2D will be found by primary care providers treating adolescents.

A weakness of the study is the potential for response bias related to mailed surveys. An additional weakness is that the researchers utilized only 1 hypothetical situation. Providing additional hypothetical situations may have allowed for further understanding of screening practices. The investigators also did not include nurse practitioners or physician assistants in their sample, a growing percentage of whom may care for adolescent populations at risk for T2D or be primary referral sources.

Applications for Clinical Practice

Providers can use HbA1c to screen for diabetes in nonfasting adolescents at risk for diabetes. While the test may not be as accurate in pediatric patients, utilizing HbA1C as directed by the ADA may aid in diagnosing patients that may otherwise miss follow-up appointments to complete a fasting test.

                                                                                                                                                                                           —Jennifer L. Nahum, MSN, CPNP-AC, PPCNP-BC, and Allison Squires, PhD, RN

Study Overview

Objective. To examine the screening practices of family practitioners (FPs) and pediatricians for type 2 diabetes (T2D) in adolescents.

Design. Cross-sectional study.

Setting and participants. The researchers randomly sampled 700 pediatricians and 700 FPs who participated in direct patient care using the American Medical Association Physician Masterfile using a mail survey. Exclusion criteria included providers who were residents, hospital staff, retirees, or employed by federally owned medical facilities, certified with a subspecialty, or over age 70.

Main outcome measures. Providers were given a hypothetical case of an obese, female, teenaged patient with concurrent associated risk factors for T2D (family history of T2D, minority race, signs of insulin resistance) and asked what initial screening tests they would order. Respondents were then informed of the updated American Diabetes Association (ADA) guidelines that added hemoglobin A1c as a screening test to diagnose diabetes. The survey then asked if knowing this change in recommendation has changed or will change their screening practices in adolescents.

Main results. 1400 surveys were mailed. After 2 were excluded due to mailing issues, 52% of providers provided responses. Of these, 129 providers reported that they did not care for adolescents (age 10–17), resulting in 604 providers in the final sample, 398 pediatricians and 335 FPs.

The vast majority (92%) said they would screen the hypothetical case for diabetes, with most initially ordering a fasting test (fasting plasma glucose or 2-hour glucose tolerance test) (63%) or A1c test (58%). Of the 58% who planned to order HbA1c, only 35% ordered it in combination with a fasting test. HbA1c was significantly more likely to be ordered by pediatricians than by FPs (P = 0.001). After being presented with the new guidelines, 84% said then would now order HbA1c, a 27% increase.

Conclusion. In response to information about the new guidelines, providers were more likely to order A1c as part of initial testing. Due to the lower test performance in children and increased cost of the test, the use of HbA1c without fasting tests may result in missed diagnosis of T2D in adolescents as well as increased health care costs.

Commentary

Rates of childhood obesity continue to rise throughout the United States. Obese children are at risk for numerous comorbidities such as hypertension, hyperlipidemia, and T2D [1,2]. It is important for providers to use effective screening tools for risk assessment of prediabetes/T2DM in children.

The standard tests for diagnosing diabetes are the fasting plasma glucose test and the 2-hour plasma glucose test. While accurate, these tests are not convenient. In 2010, the ADA added an easier method of testing for T2D: an HbA1c, with results greater than or equal to 6.5% indicating diabetes [3]. However, this recommendation is controversial, given studies suggesting that HbA1c is not as reliable in children as it is in adults [4–6]. The ADA itself acknowledges that there are limited data in the pediatric population.

In this study, most providers were unaware of the 4-year-old revised guidelines offering the A1c option but are planning to apply the guidelines going forward. According to the study, this would result in a 27% increase in providers utilizing HbA1c.

Should increased uptake of A1c as an initial screening test be a concern? Using it in combination with other tests may be useful for assessing which adolescents will need further testing [3–6]. Additionally, by starting with a test that can be performed in the office with no regard to fasting time, it is possible that more cases of T2D will be found by primary care providers treating adolescents.

A weakness of the study is the potential for response bias related to mailed surveys. An additional weakness is that the researchers utilized only 1 hypothetical situation. Providing additional hypothetical situations may have allowed for further understanding of screening practices. The investigators also did not include nurse practitioners or physician assistants in their sample, a growing percentage of whom may care for adolescent populations at risk for T2D or be primary referral sources.

Applications for Clinical Practice

Providers can use HbA1c to screen for diabetes in nonfasting adolescents at risk for diabetes. While the test may not be as accurate in pediatric patients, utilizing HbA1C as directed by the ADA may aid in diagnosing patients that may otherwise miss follow-up appointments to complete a fasting test.

                                                                                                                                                                                           —Jennifer L. Nahum, MSN, CPNP-AC, PPCNP-BC, and Allison Squires, PhD, RN

References

1. Freedman DS, Dietz WH, Srinivasan SR, Berenson GS. The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics 1999;103(6 Pt 1):1175–82.

2. Pinhas-Hamiel O, Dolan LM, Daniels SR, Standiford D, Khoury PR, Zeitler P. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr 1996;128(5 Pt 1):608–15.

3. American Diabetes Association. Type 2 diabetes in children and adolescents. Pediatrics 2000 Mar;105(3 Pt 1):671–80.

4. Lee JM, Gebremariam A, Wu EL, et al. Evaluation of nonfasting tests to screen for childhood and adolescent dysglycemia. Diabetes Care 2011;34:2597–602.

5. Nowicka P, Santoro N, Liu H, et al. Utility of hemoglobin A(1c) for diagnosing prediabetes and diabetes in obese children and adolescents. Diabetes Care 2011;34:1306–11.

6. Lee JM, Wu EL, Tarini B, et al Diagnosis of diabetes using hemoglobin A1c: should recommendations in adults be extrapolated to adolescents? J Pediatr 2011;158:947–952.

References

1. Freedman DS, Dietz WH, Srinivasan SR, Berenson GS. The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics 1999;103(6 Pt 1):1175–82.

2. Pinhas-Hamiel O, Dolan LM, Daniels SR, Standiford D, Khoury PR, Zeitler P. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr 1996;128(5 Pt 1):608–15.

3. American Diabetes Association. Type 2 diabetes in children and adolescents. Pediatrics 2000 Mar;105(3 Pt 1):671–80.

4. Lee JM, Gebremariam A, Wu EL, et al. Evaluation of nonfasting tests to screen for childhood and adolescent dysglycemia. Diabetes Care 2011;34:2597–602.

5. Nowicka P, Santoro N, Liu H, et al. Utility of hemoglobin A(1c) for diagnosing prediabetes and diabetes in obese children and adolescents. Diabetes Care 2011;34:1306–11.

6. Lee JM, Wu EL, Tarini B, et al Diagnosis of diabetes using hemoglobin A1c: should recommendations in adults be extrapolated to adolescents? J Pediatr 2011;158:947–952.

Issue
Journal of Clinical Outcomes Management - July 2014, Vol. 21, No. 7
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Does Bioelectrical Impedance Analysis Provide a Reliable Diagnosis of Secondary Lymphedema in Breast Cancer Patients?

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Does Bioelectrical Impedance Analysis Provide a Reliable Diagnosis of Secondary Lymphedema in Breast Cancer Patients?

Study Overview

Objective. To evaluate the reliability, sensitivity, and specificity of bioelectrical impedance analysis (BIA) in the diagnosis of secondary lymphedema.

Design. Cross-sectional study utilizing test-retest method

Setting and participants. The researchers used a purposeful sampling technique to recruit women between 2010 and 2011 from a metropolitan cancer center and communities in the New York City metropolitan area. Participants included women who were 18 years of age or older and able to read and write in English. Exclusion criteria included patients with bilateral breast disease, recurrent cancer, artificial limb, knee, or hip, and kidney or heart failure. Study participants were divided into 3 groups: breast cancer survivors with lymphedema, those at risk for lymphedema, and healthy adult women (no history of breast cancer or lymphedema). Women in the at risk category had to have completed surgical treatment, chemotherapy and/or radiation within the 5 years prior to the study enrollment.

Measurements. Patient’s arms were measured by the same 2 researchers using sequential circumferential measurements. BIA was measured in all patients with the ImpXCA (Impedimed Inc, Pittsford, NY), an FDA-approved device that measures impedance and resistance of the extracellular fluid. The ImpXCA utilizes a scale to correlate BIA to an L-Dex (lymphedema index) ratio; –10 to +10 defines the normal range of L-Dex values for a patient without lymphedema. Measurements were taken at 5-minute increments for a total of 3 times at the same visit to test for stability of BIA.

Main results. 250 patients were in the sample: 42 with known lymphedema, 148 at risk for lymphedema, and 60 healthy female adults. L-Dex ratios ranged from –9.7 to 7.7 in the healthy population, –9.6 to 36.9 in the at risk group, and 0.9 to 115 in the group with lymphedema. Mean L-Dex ratios were significantly different between the healthy and lymphedema groups (P < 0.001) and the at risk and lymphedema groups (P < 0.001). There was no difference between the at risk and healthy groups (= 0.85). Utilizing an L-Dex ratio cutoff of 7.1 provided 80% sensitivity and 90% specificity in the diagnosis of secondary lymphedema.

Reliability and reproducibility of BIA by ImpXCA using the L-Dex ratio was assessed using a test-retest method. Intra-class correlation coefficients (ICC) provided strong stability for the repeated measurements in the healthy group, with ICC = 0.99 (95% CI, 0.99–0.99), and in the at risk group, with ICC = 0.99 (95% CI, 0.99–0.99). There was also fair agreement in the repeated measurements in the lymphedema group, with ICC = 0.69 (95% CI, 0.58-0.82). All of these findings were statistically significant (P < 0.001).

Conclusion. The L-Dex ratio is reliable and reproducible and may be helpful in distinguishing women with lymphedema from those without lymphedema. BIA in conjunction with other tools, such as self-report of symptoms, circumferential measurements, and clinical observation, may have a role in diagnosing lymphedema.

Commentary

The first year and a half following surgical treatment for breast cancer is when providers tend to diagnose the initial onset of lymphedema [1]. Many women, however, go undiagnosed until the illness has progressed. Earlier treatment has the potential to improve patient outcomes [2]. Although awareness of secondary lymphedema among breast cancer survivors has increased over the past 10 years, the diagnosis remains difficult and the development of effective diagnostic tools continues to challenge health care providers.

The current gold standard for diagnosis is the water displacement method where the affected and unaffected extremities are each placed into a tank of water, and the displaced water is measured [3]. Greater than a 200 mL discrepancy between arms is used to make a diagnosis of lymphedema. While useful, this measurement is messy and difficult to set up, and thus underutilized. Many providers have turned to circumferential measurements as their primary method to diagnose and monitor lymphedema [4]. However, this method may miss patients in the earlier stages of lymphedema, since it measures the size of limbs rather than changes in the tissue. Without a definitive test to diagnose lymphedema, researchers and health care providers continue to search for the most accurate, reliable, and feasible means to assist in the diagnosis.

This cross-sectional study suggests that L-Dex can be helpful in detecting lymphedema. A weakness of the study is that the investigators did not compare the results of BIA to the current gold standard of water displacement, but rather to circumferential measurement. In addition, while all results were reproducible, the difference between groups was notable in terms of age and body mass index, making it difficult to generalize to all patients at risk for lymphedema or differentiate results by those same variables. Although having the same 2 investigators obtain circumferential tape measurements is preferable to having multiple investigators do so, such measurements are still at risk for human error.

BIA shows promise as a diagnostic tool. Future studies should include healthy patients with characteristics similar to those of at risk patients and lymphedema patients. Efforts also could be directed towards determining whether combining BIA with other methods, such as self-report, circumferential measurements, and close observation, may offer greater sensitivity and specificity than one method alone.

Applications for Clinical Practice

Secondary lymphedema is a common complication caused by surgical treatment of breast cancer. Early treatment is linked to a decrease in debilitating factors such as immobility of affected joints, skin changes, and risk for infection. Measurement of extracellular fluid utilizing L-Dex ratios produces reliable and repeatable results in the assessment for lymphedema. Paired with additional tools and resources it may be helpful in making a diagnosis, which is normally difficult in its earliest stages. The early diagnosis of secondary lymphedema may allow for improved quality of life for survivors of breast cancer.

—Jennifer L. Nahum, MSN, CPNP-AC, PPCNP-BC, and Allison Squires, PhD, RN

References

1. Czerniec SA, Ward LC, Lee MJ, et al. Segmental measurement of breast cancer-related arm lymphoedema using perometry and bioimpedance spectroscopy. Support Care Cancer. 2011;19:703–10.

2. Damstra RJ, Voesten HG, van Schelven WD, van der Lei B. Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature. Breast Cancer Res Treat 2009;113:199–206.

3. Brorson H, Höijer P. Standardised measurements used to order compression garments can be used to calculate arm volumes to evaluate lymphoedema treatment. Plast Surg Hand Surg 2012;46:410–5.

4. Langbecker D, Hayes SC, Newman B, Janda M. Treatment for upper-limb and lower-limb lymphedema by professionals specializing in lymphedema care. Eur J Cancer Care (Engl). 2008;17:557–64.

Issue
Journal of Clinical Outcomes Management - February 2014, VOL. 21, NO. 2
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Study Overview

Objective. To evaluate the reliability, sensitivity, and specificity of bioelectrical impedance analysis (BIA) in the diagnosis of secondary lymphedema.

Design. Cross-sectional study utilizing test-retest method

Setting and participants. The researchers used a purposeful sampling technique to recruit women between 2010 and 2011 from a metropolitan cancer center and communities in the New York City metropolitan area. Participants included women who were 18 years of age or older and able to read and write in English. Exclusion criteria included patients with bilateral breast disease, recurrent cancer, artificial limb, knee, or hip, and kidney or heart failure. Study participants were divided into 3 groups: breast cancer survivors with lymphedema, those at risk for lymphedema, and healthy adult women (no history of breast cancer or lymphedema). Women in the at risk category had to have completed surgical treatment, chemotherapy and/or radiation within the 5 years prior to the study enrollment.

Measurements. Patient’s arms were measured by the same 2 researchers using sequential circumferential measurements. BIA was measured in all patients with the ImpXCA (Impedimed Inc, Pittsford, NY), an FDA-approved device that measures impedance and resistance of the extracellular fluid. The ImpXCA utilizes a scale to correlate BIA to an L-Dex (lymphedema index) ratio; –10 to +10 defines the normal range of L-Dex values for a patient without lymphedema. Measurements were taken at 5-minute increments for a total of 3 times at the same visit to test for stability of BIA.

Main results. 250 patients were in the sample: 42 with known lymphedema, 148 at risk for lymphedema, and 60 healthy female adults. L-Dex ratios ranged from –9.7 to 7.7 in the healthy population, –9.6 to 36.9 in the at risk group, and 0.9 to 115 in the group with lymphedema. Mean L-Dex ratios were significantly different between the healthy and lymphedema groups (P < 0.001) and the at risk and lymphedema groups (P < 0.001). There was no difference between the at risk and healthy groups (= 0.85). Utilizing an L-Dex ratio cutoff of 7.1 provided 80% sensitivity and 90% specificity in the diagnosis of secondary lymphedema.

Reliability and reproducibility of BIA by ImpXCA using the L-Dex ratio was assessed using a test-retest method. Intra-class correlation coefficients (ICC) provided strong stability for the repeated measurements in the healthy group, with ICC = 0.99 (95% CI, 0.99–0.99), and in the at risk group, with ICC = 0.99 (95% CI, 0.99–0.99). There was also fair agreement in the repeated measurements in the lymphedema group, with ICC = 0.69 (95% CI, 0.58-0.82). All of these findings were statistically significant (P < 0.001).

Conclusion. The L-Dex ratio is reliable and reproducible and may be helpful in distinguishing women with lymphedema from those without lymphedema. BIA in conjunction with other tools, such as self-report of symptoms, circumferential measurements, and clinical observation, may have a role in diagnosing lymphedema.

Commentary

The first year and a half following surgical treatment for breast cancer is when providers tend to diagnose the initial onset of lymphedema [1]. Many women, however, go undiagnosed until the illness has progressed. Earlier treatment has the potential to improve patient outcomes [2]. Although awareness of secondary lymphedema among breast cancer survivors has increased over the past 10 years, the diagnosis remains difficult and the development of effective diagnostic tools continues to challenge health care providers.

The current gold standard for diagnosis is the water displacement method where the affected and unaffected extremities are each placed into a tank of water, and the displaced water is measured [3]. Greater than a 200 mL discrepancy between arms is used to make a diagnosis of lymphedema. While useful, this measurement is messy and difficult to set up, and thus underutilized. Many providers have turned to circumferential measurements as their primary method to diagnose and monitor lymphedema [4]. However, this method may miss patients in the earlier stages of lymphedema, since it measures the size of limbs rather than changes in the tissue. Without a definitive test to diagnose lymphedema, researchers and health care providers continue to search for the most accurate, reliable, and feasible means to assist in the diagnosis.

This cross-sectional study suggests that L-Dex can be helpful in detecting lymphedema. A weakness of the study is that the investigators did not compare the results of BIA to the current gold standard of water displacement, but rather to circumferential measurement. In addition, while all results were reproducible, the difference between groups was notable in terms of age and body mass index, making it difficult to generalize to all patients at risk for lymphedema or differentiate results by those same variables. Although having the same 2 investigators obtain circumferential tape measurements is preferable to having multiple investigators do so, such measurements are still at risk for human error.

BIA shows promise as a diagnostic tool. Future studies should include healthy patients with characteristics similar to those of at risk patients and lymphedema patients. Efforts also could be directed towards determining whether combining BIA with other methods, such as self-report, circumferential measurements, and close observation, may offer greater sensitivity and specificity than one method alone.

Applications for Clinical Practice

Secondary lymphedema is a common complication caused by surgical treatment of breast cancer. Early treatment is linked to a decrease in debilitating factors such as immobility of affected joints, skin changes, and risk for infection. Measurement of extracellular fluid utilizing L-Dex ratios produces reliable and repeatable results in the assessment for lymphedema. Paired with additional tools and resources it may be helpful in making a diagnosis, which is normally difficult in its earliest stages. The early diagnosis of secondary lymphedema may allow for improved quality of life for survivors of breast cancer.

—Jennifer L. Nahum, MSN, CPNP-AC, PPCNP-BC, and Allison Squires, PhD, RN

Study Overview

Objective. To evaluate the reliability, sensitivity, and specificity of bioelectrical impedance analysis (BIA) in the diagnosis of secondary lymphedema.

Design. Cross-sectional study utilizing test-retest method

Setting and participants. The researchers used a purposeful sampling technique to recruit women between 2010 and 2011 from a metropolitan cancer center and communities in the New York City metropolitan area. Participants included women who were 18 years of age or older and able to read and write in English. Exclusion criteria included patients with bilateral breast disease, recurrent cancer, artificial limb, knee, or hip, and kidney or heart failure. Study participants were divided into 3 groups: breast cancer survivors with lymphedema, those at risk for lymphedema, and healthy adult women (no history of breast cancer or lymphedema). Women in the at risk category had to have completed surgical treatment, chemotherapy and/or radiation within the 5 years prior to the study enrollment.

Measurements. Patient’s arms were measured by the same 2 researchers using sequential circumferential measurements. BIA was measured in all patients with the ImpXCA (Impedimed Inc, Pittsford, NY), an FDA-approved device that measures impedance and resistance of the extracellular fluid. The ImpXCA utilizes a scale to correlate BIA to an L-Dex (lymphedema index) ratio; –10 to +10 defines the normal range of L-Dex values for a patient without lymphedema. Measurements were taken at 5-minute increments for a total of 3 times at the same visit to test for stability of BIA.

Main results. 250 patients were in the sample: 42 with known lymphedema, 148 at risk for lymphedema, and 60 healthy female adults. L-Dex ratios ranged from –9.7 to 7.7 in the healthy population, –9.6 to 36.9 in the at risk group, and 0.9 to 115 in the group with lymphedema. Mean L-Dex ratios were significantly different between the healthy and lymphedema groups (P < 0.001) and the at risk and lymphedema groups (P < 0.001). There was no difference between the at risk and healthy groups (= 0.85). Utilizing an L-Dex ratio cutoff of 7.1 provided 80% sensitivity and 90% specificity in the diagnosis of secondary lymphedema.

Reliability and reproducibility of BIA by ImpXCA using the L-Dex ratio was assessed using a test-retest method. Intra-class correlation coefficients (ICC) provided strong stability for the repeated measurements in the healthy group, with ICC = 0.99 (95% CI, 0.99–0.99), and in the at risk group, with ICC = 0.99 (95% CI, 0.99–0.99). There was also fair agreement in the repeated measurements in the lymphedema group, with ICC = 0.69 (95% CI, 0.58-0.82). All of these findings were statistically significant (P < 0.001).

Conclusion. The L-Dex ratio is reliable and reproducible and may be helpful in distinguishing women with lymphedema from those without lymphedema. BIA in conjunction with other tools, such as self-report of symptoms, circumferential measurements, and clinical observation, may have a role in diagnosing lymphedema.

Commentary

The first year and a half following surgical treatment for breast cancer is when providers tend to diagnose the initial onset of lymphedema [1]. Many women, however, go undiagnosed until the illness has progressed. Earlier treatment has the potential to improve patient outcomes [2]. Although awareness of secondary lymphedema among breast cancer survivors has increased over the past 10 years, the diagnosis remains difficult and the development of effective diagnostic tools continues to challenge health care providers.

The current gold standard for diagnosis is the water displacement method where the affected and unaffected extremities are each placed into a tank of water, and the displaced water is measured [3]. Greater than a 200 mL discrepancy between arms is used to make a diagnosis of lymphedema. While useful, this measurement is messy and difficult to set up, and thus underutilized. Many providers have turned to circumferential measurements as their primary method to diagnose and monitor lymphedema [4]. However, this method may miss patients in the earlier stages of lymphedema, since it measures the size of limbs rather than changes in the tissue. Without a definitive test to diagnose lymphedema, researchers and health care providers continue to search for the most accurate, reliable, and feasible means to assist in the diagnosis.

This cross-sectional study suggests that L-Dex can be helpful in detecting lymphedema. A weakness of the study is that the investigators did not compare the results of BIA to the current gold standard of water displacement, but rather to circumferential measurement. In addition, while all results were reproducible, the difference between groups was notable in terms of age and body mass index, making it difficult to generalize to all patients at risk for lymphedema or differentiate results by those same variables. Although having the same 2 investigators obtain circumferential tape measurements is preferable to having multiple investigators do so, such measurements are still at risk for human error.

BIA shows promise as a diagnostic tool. Future studies should include healthy patients with characteristics similar to those of at risk patients and lymphedema patients. Efforts also could be directed towards determining whether combining BIA with other methods, such as self-report, circumferential measurements, and close observation, may offer greater sensitivity and specificity than one method alone.

Applications for Clinical Practice

Secondary lymphedema is a common complication caused by surgical treatment of breast cancer. Early treatment is linked to a decrease in debilitating factors such as immobility of affected joints, skin changes, and risk for infection. Measurement of extracellular fluid utilizing L-Dex ratios produces reliable and repeatable results in the assessment for lymphedema. Paired with additional tools and resources it may be helpful in making a diagnosis, which is normally difficult in its earliest stages. The early diagnosis of secondary lymphedema may allow for improved quality of life for survivors of breast cancer.

—Jennifer L. Nahum, MSN, CPNP-AC, PPCNP-BC, and Allison Squires, PhD, RN

References

1. Czerniec SA, Ward LC, Lee MJ, et al. Segmental measurement of breast cancer-related arm lymphoedema using perometry and bioimpedance spectroscopy. Support Care Cancer. 2011;19:703–10.

2. Damstra RJ, Voesten HG, van Schelven WD, van der Lei B. Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature. Breast Cancer Res Treat 2009;113:199–206.

3. Brorson H, Höijer P. Standardised measurements used to order compression garments can be used to calculate arm volumes to evaluate lymphoedema treatment. Plast Surg Hand Surg 2012;46:410–5.

4. Langbecker D, Hayes SC, Newman B, Janda M. Treatment for upper-limb and lower-limb lymphedema by professionals specializing in lymphedema care. Eur J Cancer Care (Engl). 2008;17:557–64.

References

1. Czerniec SA, Ward LC, Lee MJ, et al. Segmental measurement of breast cancer-related arm lymphoedema using perometry and bioimpedance spectroscopy. Support Care Cancer. 2011;19:703–10.

2. Damstra RJ, Voesten HG, van Schelven WD, van der Lei B. Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature. Breast Cancer Res Treat 2009;113:199–206.

3. Brorson H, Höijer P. Standardised measurements used to order compression garments can be used to calculate arm volumes to evaluate lymphoedema treatment. Plast Surg Hand Surg 2012;46:410–5.

4. Langbecker D, Hayes SC, Newman B, Janda M. Treatment for upper-limb and lower-limb lymphedema by professionals specializing in lymphedema care. Eur J Cancer Care (Engl). 2008;17:557–64.

Issue
Journal of Clinical Outcomes Management - February 2014, VOL. 21, NO. 2
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Journal of Clinical Outcomes Management - February 2014, VOL. 21, NO. 2
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Does Bioelectrical Impedance Analysis Provide a Reliable Diagnosis of Secondary Lymphedema in Breast Cancer Patients?
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