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The past 12 months have been busy ones for the United States Preventive Services Task Force (USPSTF), which issued 34 new recommendations since our last Practice Alert on the group’s activity a year ago. Some recommendations address controversial topics, such as cholesterol screening, and several others—on topics such as prostate cancer screening and acceptable tests for detecting colorectal cancer—differ from those of such prominent groups as the American Cancer Society (ACS).
TABLE 1 provides a breakdown of the 5 categories of USPSTF recommendations (A, B, C, D, I). We’ll start with recent D recommendations (TABLE 2), services the Task Force recommends against, to emphasize that some preventive measures—even if they are widely touted—either provide no benefit or cause more harms than benefits.
TABLE 1
USPSTF recommendation categories
A Recommendation: The Task Force recommends the service. There is high certainty that the net benefit is substantial. |
B Recommendation: The Task Force recommends this service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. |
C Recommendation: The Task Force recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small. |
D Recommendation: The Task Force recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. |
I Statement: The Task Force concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. |
TABLE 2
The USPSTF recommends AGAINST
|
What not to do
The most notable new D recommendations advise against screening men ≥75 years of age for prostate cancer and against screening for colorectal cancer after age 85. The Task Force also recommends against routine screening for colorectal cancer after age 75, although individual patient considerations may influence your decision about this screen for patients between ages 76 and 85. Bear in mind that the benefits of early detection of colon cancer decline after age 75 because of the time lag between early intervention and benefit and because of competing causes of morbidity and mortality.1
Cancer screening controversies. The recommendations for an age cutoff for prostate and colon cancer screening differ from those of the ACS, which lists no age cutoff for screening for either condition.2 In fact, the Task Force does not recommend screening for prostate cancer at all. Its rationale is that before age 75, the evidence is insufficient to evaluate benefits and harms, and after 75 there is good evidence that screening does more harm than good. The ACS no longer recommends routine prostate cancer screening, but does say that when a patient leaves the decision to the physician, screening should be performed.
Thumbs down on these, too. The Task Force now recommends against using spirometry to screen for chronic obstructive pulmonary disease and against using aspirin for preventing stroke in women <55 years and myocardial infarction (MI) in men <45 years. (See below for a fuller discussion of aspirin as a preventive measure.) The Task Force also recommends against screening for asymptomatic bacteriuria in men and nonpregnant women.
Recommended interventions
Now for the preventive interventions the USPSTF advises you to perform. They include:
Prescribing low-dose aspirin. The most complicated positive recommendations are those for low-dose aspirin to prevent MI in men and stroke in women. Aspirin is effective in preventing these conditions, but carries the risk of major gastrointestinal (GI) bleeding and cerebral hemorrhage. For younger patients, as we’ve seen in the previous section, the Task Force finds the risks of prophylactic low-dose aspirin therapy outweigh the benefits. But for older patients (men between the ages of 45 and 79 years and women ages 55-79), aspirin is recommended when the potential benefit of reducing the incidence of MI in men and stroke in women outweigh the harms. To assist clinicians in weighing the potential benefits and harms, the USPSTF provides a link to a coronary heart disease risk calculator, as well as several tables comparing numbers of prevented heart attacks for men and strokes for women by age and risk category, as well as risks of bleeding complications.3
Screening for hypercholesterolemia. The Task Force’s recommendations for dyslipidemia screening differ markedly from those of the American Heart Association and the Final Report of the National Cholesterol Education Program (NCEP) Expert Panel, which recommend routine screening for all adults starting at age 20 with no age cutoff.4 The USPSTF recommends deferring screening until patients are older, except for those at increased risk of coronary heart disease. This controversy was described in a 2008 Practice Alert.5
Screening for diabetes. The only asymptomatic patients the Task Force recommends screening for diabetes are those with a sustained blood pressure of more than 135/80 mm Hg, treated or untreated. The American Diabetes Association (ADA) would cast a wider net, recommending that you consider screening for prediabetes or diabetes in those ≥45 years of age, particularly in those with a body mass index of ≥25 kg/m2, and in overweight patients <45 years of age who have another risk factor for diabetes.6
Screening for colorectal cancer. The Task Force recommends screening adults starting at age 50 until age 75, using fecal occult blood testing, sigmoidoscopy, or colonoscopy. The ACS also recommends these screening modalities, but adds CT colonography and fecal DNA testing to the list of acceptable methods. The USPSTF found insufficient evidence to evaluate the benefits and harms of these newer tests and expressed concern over the high rate of incidental findings and the unknown long-term effects of radiation from CT colonography.
Screening adolescents. The Task Force is in favor of screening teenagers for major depressive disorder (MDD), as long as systems are in place to provide accurate diagnosis, therapy, and follow-up. High-intensity behavioral counseling for sexually active teens and adults at risk is also endorsed for the prevention of sexually transmitted infections. In both areas, however, the Task Force recognizes that adequately addressing these issues will require more than brief office- or clinic-based interventions.
Caring for pregnant women and newborns. According to the USPSTF, pregnant women should be screened for asymptomatic bacteriuria, advised to take a daily folic acid supplement, counseled about tobacco use, and encouraged to breastfeed. Newborns should be screened for congenital hypothyroidism, phenylketonuria, and hearing loss. These most recent A and B recommendations from the USPSTF are summarized in TABLE 3.
TABLE 3
The USPSTF recommends FOR
CARDIOVASCULAR DISEASE PREVENTION |
|
CANCER SCREENING |
|
PREGNANCY |
|
NEWBORNS |
|
ADOLESCENTS |
|
Not proven
When evidence is not available, some organizations are willing to issue guidelines based on expert opinion or consensus. Not so the USPSTF. When the Task Force members find current evidence is not sufficient to make a judgment, they put the intervention into Category I, for Insufficient. The new I recommendations range from aspirin to prevent MI and stroke in those ≥80 years to screening children for MDD and performing whole body skin examinations to detect early manifestations of skin cancer. The new I recommendations are listed in TABLE 4.
TABLE 4
Evidence is INSUFFICIENT to recommend for or against
|
What’s the take-home message?
All of these recent Task Force decisions add substantially to the full set of Task Force recommendations, which can be found at www.ahrq.gov/CLINIC/uspstfix.htm. Given the large number of level A and B recommendations from the Task Force, clinicians are faced with the dilemma of limited time to accomplish all the recommendations. It is reasonable to concentrate on the positive recommendations and avoid performing the interventions recommended against. The interventions in the “I” category are not as clear-cut and clinicians will continue to struggle with them, particularly when other professional organizations recommend them.
CORRESPONDENCE
Doug Campos-Outcalt, MD, MPA, 550 E. Van Buren, Phoenix, AZ 85004; [email protected].
1. US Preventive Services Task Force. Screening for colorectal cancer. October 2008. Available at: www.ahrq.gov/clinic/uspstf/uspscolo.htm. Accessed June 3, 2009.
2. American Cancer Society guidelines for early detection of cancer. Last revised May 21, 2009. Available at: http://www.cancer.org/docroot/PED/content/PED_2_3X_ACS_Cancer_Detection_Guidelines_36.asp?sitearea=PED. Accessed June 3, 2009.
3. US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: recommendation statement. March 2009. Available at: http://www.ahrq.gov/clinic/uspstf09/aspirincvd/aspcvdrs.htm. Accessed June 3, 2009.
4. National Cholesterol Education Program. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106:3143-3421.Available at: http://circ.ahajournals.org/cgi/content/full/106/25/3143. Accessed June 3, 2009.
5. Campos-Outcalt D. USPSTF scales back approach to lipid screening for women. J Fam Pract. 2008;57:740-742.
6. American Diabetes Association. Standards of medical care in diabetes—2008. Diabetes Care. 2008;31(suppl 1):S12-S54.
The past 12 months have been busy ones for the United States Preventive Services Task Force (USPSTF), which issued 34 new recommendations since our last Practice Alert on the group’s activity a year ago. Some recommendations address controversial topics, such as cholesterol screening, and several others—on topics such as prostate cancer screening and acceptable tests for detecting colorectal cancer—differ from those of such prominent groups as the American Cancer Society (ACS).
TABLE 1 provides a breakdown of the 5 categories of USPSTF recommendations (A, B, C, D, I). We’ll start with recent D recommendations (TABLE 2), services the Task Force recommends against, to emphasize that some preventive measures—even if they are widely touted—either provide no benefit or cause more harms than benefits.
TABLE 1
USPSTF recommendation categories
A Recommendation: The Task Force recommends the service. There is high certainty that the net benefit is substantial. |
B Recommendation: The Task Force recommends this service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. |
C Recommendation: The Task Force recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small. |
D Recommendation: The Task Force recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. |
I Statement: The Task Force concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. |
TABLE 2
The USPSTF recommends AGAINST
|
What not to do
The most notable new D recommendations advise against screening men ≥75 years of age for prostate cancer and against screening for colorectal cancer after age 85. The Task Force also recommends against routine screening for colorectal cancer after age 75, although individual patient considerations may influence your decision about this screen for patients between ages 76 and 85. Bear in mind that the benefits of early detection of colon cancer decline after age 75 because of the time lag between early intervention and benefit and because of competing causes of morbidity and mortality.1
Cancer screening controversies. The recommendations for an age cutoff for prostate and colon cancer screening differ from those of the ACS, which lists no age cutoff for screening for either condition.2 In fact, the Task Force does not recommend screening for prostate cancer at all. Its rationale is that before age 75, the evidence is insufficient to evaluate benefits and harms, and after 75 there is good evidence that screening does more harm than good. The ACS no longer recommends routine prostate cancer screening, but does say that when a patient leaves the decision to the physician, screening should be performed.
Thumbs down on these, too. The Task Force now recommends against using spirometry to screen for chronic obstructive pulmonary disease and against using aspirin for preventing stroke in women <55 years and myocardial infarction (MI) in men <45 years. (See below for a fuller discussion of aspirin as a preventive measure.) The Task Force also recommends against screening for asymptomatic bacteriuria in men and nonpregnant women.
Recommended interventions
Now for the preventive interventions the USPSTF advises you to perform. They include:
Prescribing low-dose aspirin. The most complicated positive recommendations are those for low-dose aspirin to prevent MI in men and stroke in women. Aspirin is effective in preventing these conditions, but carries the risk of major gastrointestinal (GI) bleeding and cerebral hemorrhage. For younger patients, as we’ve seen in the previous section, the Task Force finds the risks of prophylactic low-dose aspirin therapy outweigh the benefits. But for older patients (men between the ages of 45 and 79 years and women ages 55-79), aspirin is recommended when the potential benefit of reducing the incidence of MI in men and stroke in women outweigh the harms. To assist clinicians in weighing the potential benefits and harms, the USPSTF provides a link to a coronary heart disease risk calculator, as well as several tables comparing numbers of prevented heart attacks for men and strokes for women by age and risk category, as well as risks of bleeding complications.3
Screening for hypercholesterolemia. The Task Force’s recommendations for dyslipidemia screening differ markedly from those of the American Heart Association and the Final Report of the National Cholesterol Education Program (NCEP) Expert Panel, which recommend routine screening for all adults starting at age 20 with no age cutoff.4 The USPSTF recommends deferring screening until patients are older, except for those at increased risk of coronary heart disease. This controversy was described in a 2008 Practice Alert.5
Screening for diabetes. The only asymptomatic patients the Task Force recommends screening for diabetes are those with a sustained blood pressure of more than 135/80 mm Hg, treated or untreated. The American Diabetes Association (ADA) would cast a wider net, recommending that you consider screening for prediabetes or diabetes in those ≥45 years of age, particularly in those with a body mass index of ≥25 kg/m2, and in overweight patients <45 years of age who have another risk factor for diabetes.6
Screening for colorectal cancer. The Task Force recommends screening adults starting at age 50 until age 75, using fecal occult blood testing, sigmoidoscopy, or colonoscopy. The ACS also recommends these screening modalities, but adds CT colonography and fecal DNA testing to the list of acceptable methods. The USPSTF found insufficient evidence to evaluate the benefits and harms of these newer tests and expressed concern over the high rate of incidental findings and the unknown long-term effects of radiation from CT colonography.
Screening adolescents. The Task Force is in favor of screening teenagers for major depressive disorder (MDD), as long as systems are in place to provide accurate diagnosis, therapy, and follow-up. High-intensity behavioral counseling for sexually active teens and adults at risk is also endorsed for the prevention of sexually transmitted infections. In both areas, however, the Task Force recognizes that adequately addressing these issues will require more than brief office- or clinic-based interventions.
Caring for pregnant women and newborns. According to the USPSTF, pregnant women should be screened for asymptomatic bacteriuria, advised to take a daily folic acid supplement, counseled about tobacco use, and encouraged to breastfeed. Newborns should be screened for congenital hypothyroidism, phenylketonuria, and hearing loss. These most recent A and B recommendations from the USPSTF are summarized in TABLE 3.
TABLE 3
The USPSTF recommends FOR
CARDIOVASCULAR DISEASE PREVENTION |
|
CANCER SCREENING |
|
PREGNANCY |
|
NEWBORNS |
|
ADOLESCENTS |
|
Not proven
When evidence is not available, some organizations are willing to issue guidelines based on expert opinion or consensus. Not so the USPSTF. When the Task Force members find current evidence is not sufficient to make a judgment, they put the intervention into Category I, for Insufficient. The new I recommendations range from aspirin to prevent MI and stroke in those ≥80 years to screening children for MDD and performing whole body skin examinations to detect early manifestations of skin cancer. The new I recommendations are listed in TABLE 4.
TABLE 4
Evidence is INSUFFICIENT to recommend for or against
|
What’s the take-home message?
All of these recent Task Force decisions add substantially to the full set of Task Force recommendations, which can be found at www.ahrq.gov/CLINIC/uspstfix.htm. Given the large number of level A and B recommendations from the Task Force, clinicians are faced with the dilemma of limited time to accomplish all the recommendations. It is reasonable to concentrate on the positive recommendations and avoid performing the interventions recommended against. The interventions in the “I” category are not as clear-cut and clinicians will continue to struggle with them, particularly when other professional organizations recommend them.
CORRESPONDENCE
Doug Campos-Outcalt, MD, MPA, 550 E. Van Buren, Phoenix, AZ 85004; [email protected].
The past 12 months have been busy ones for the United States Preventive Services Task Force (USPSTF), which issued 34 new recommendations since our last Practice Alert on the group’s activity a year ago. Some recommendations address controversial topics, such as cholesterol screening, and several others—on topics such as prostate cancer screening and acceptable tests for detecting colorectal cancer—differ from those of such prominent groups as the American Cancer Society (ACS).
TABLE 1 provides a breakdown of the 5 categories of USPSTF recommendations (A, B, C, D, I). We’ll start with recent D recommendations (TABLE 2), services the Task Force recommends against, to emphasize that some preventive measures—even if they are widely touted—either provide no benefit or cause more harms than benefits.
TABLE 1
USPSTF recommendation categories
A Recommendation: The Task Force recommends the service. There is high certainty that the net benefit is substantial. |
B Recommendation: The Task Force recommends this service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. |
C Recommendation: The Task Force recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small. |
D Recommendation: The Task Force recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. |
I Statement: The Task Force concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. |
TABLE 2
The USPSTF recommends AGAINST
|
What not to do
The most notable new D recommendations advise against screening men ≥75 years of age for prostate cancer and against screening for colorectal cancer after age 85. The Task Force also recommends against routine screening for colorectal cancer after age 75, although individual patient considerations may influence your decision about this screen for patients between ages 76 and 85. Bear in mind that the benefits of early detection of colon cancer decline after age 75 because of the time lag between early intervention and benefit and because of competing causes of morbidity and mortality.1
Cancer screening controversies. The recommendations for an age cutoff for prostate and colon cancer screening differ from those of the ACS, which lists no age cutoff for screening for either condition.2 In fact, the Task Force does not recommend screening for prostate cancer at all. Its rationale is that before age 75, the evidence is insufficient to evaluate benefits and harms, and after 75 there is good evidence that screening does more harm than good. The ACS no longer recommends routine prostate cancer screening, but does say that when a patient leaves the decision to the physician, screening should be performed.
Thumbs down on these, too. The Task Force now recommends against using spirometry to screen for chronic obstructive pulmonary disease and against using aspirin for preventing stroke in women <55 years and myocardial infarction (MI) in men <45 years. (See below for a fuller discussion of aspirin as a preventive measure.) The Task Force also recommends against screening for asymptomatic bacteriuria in men and nonpregnant women.
Recommended interventions
Now for the preventive interventions the USPSTF advises you to perform. They include:
Prescribing low-dose aspirin. The most complicated positive recommendations are those for low-dose aspirin to prevent MI in men and stroke in women. Aspirin is effective in preventing these conditions, but carries the risk of major gastrointestinal (GI) bleeding and cerebral hemorrhage. For younger patients, as we’ve seen in the previous section, the Task Force finds the risks of prophylactic low-dose aspirin therapy outweigh the benefits. But for older patients (men between the ages of 45 and 79 years and women ages 55-79), aspirin is recommended when the potential benefit of reducing the incidence of MI in men and stroke in women outweigh the harms. To assist clinicians in weighing the potential benefits and harms, the USPSTF provides a link to a coronary heart disease risk calculator, as well as several tables comparing numbers of prevented heart attacks for men and strokes for women by age and risk category, as well as risks of bleeding complications.3
Screening for hypercholesterolemia. The Task Force’s recommendations for dyslipidemia screening differ markedly from those of the American Heart Association and the Final Report of the National Cholesterol Education Program (NCEP) Expert Panel, which recommend routine screening for all adults starting at age 20 with no age cutoff.4 The USPSTF recommends deferring screening until patients are older, except for those at increased risk of coronary heart disease. This controversy was described in a 2008 Practice Alert.5
Screening for diabetes. The only asymptomatic patients the Task Force recommends screening for diabetes are those with a sustained blood pressure of more than 135/80 mm Hg, treated or untreated. The American Diabetes Association (ADA) would cast a wider net, recommending that you consider screening for prediabetes or diabetes in those ≥45 years of age, particularly in those with a body mass index of ≥25 kg/m2, and in overweight patients <45 years of age who have another risk factor for diabetes.6
Screening for colorectal cancer. The Task Force recommends screening adults starting at age 50 until age 75, using fecal occult blood testing, sigmoidoscopy, or colonoscopy. The ACS also recommends these screening modalities, but adds CT colonography and fecal DNA testing to the list of acceptable methods. The USPSTF found insufficient evidence to evaluate the benefits and harms of these newer tests and expressed concern over the high rate of incidental findings and the unknown long-term effects of radiation from CT colonography.
Screening adolescents. The Task Force is in favor of screening teenagers for major depressive disorder (MDD), as long as systems are in place to provide accurate diagnosis, therapy, and follow-up. High-intensity behavioral counseling for sexually active teens and adults at risk is also endorsed for the prevention of sexually transmitted infections. In both areas, however, the Task Force recognizes that adequately addressing these issues will require more than brief office- or clinic-based interventions.
Caring for pregnant women and newborns. According to the USPSTF, pregnant women should be screened for asymptomatic bacteriuria, advised to take a daily folic acid supplement, counseled about tobacco use, and encouraged to breastfeed. Newborns should be screened for congenital hypothyroidism, phenylketonuria, and hearing loss. These most recent A and B recommendations from the USPSTF are summarized in TABLE 3.
TABLE 3
The USPSTF recommends FOR
CARDIOVASCULAR DISEASE PREVENTION |
|
CANCER SCREENING |
|
PREGNANCY |
|
NEWBORNS |
|
ADOLESCENTS |
|
Not proven
When evidence is not available, some organizations are willing to issue guidelines based on expert opinion or consensus. Not so the USPSTF. When the Task Force members find current evidence is not sufficient to make a judgment, they put the intervention into Category I, for Insufficient. The new I recommendations range from aspirin to prevent MI and stroke in those ≥80 years to screening children for MDD and performing whole body skin examinations to detect early manifestations of skin cancer. The new I recommendations are listed in TABLE 4.
TABLE 4
Evidence is INSUFFICIENT to recommend for or against
|
What’s the take-home message?
All of these recent Task Force decisions add substantially to the full set of Task Force recommendations, which can be found at www.ahrq.gov/CLINIC/uspstfix.htm. Given the large number of level A and B recommendations from the Task Force, clinicians are faced with the dilemma of limited time to accomplish all the recommendations. It is reasonable to concentrate on the positive recommendations and avoid performing the interventions recommended against. The interventions in the “I” category are not as clear-cut and clinicians will continue to struggle with them, particularly when other professional organizations recommend them.
CORRESPONDENCE
Doug Campos-Outcalt, MD, MPA, 550 E. Van Buren, Phoenix, AZ 85004; [email protected].
1. US Preventive Services Task Force. Screening for colorectal cancer. October 2008. Available at: www.ahrq.gov/clinic/uspstf/uspscolo.htm. Accessed June 3, 2009.
2. American Cancer Society guidelines for early detection of cancer. Last revised May 21, 2009. Available at: http://www.cancer.org/docroot/PED/content/PED_2_3X_ACS_Cancer_Detection_Guidelines_36.asp?sitearea=PED. Accessed June 3, 2009.
3. US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: recommendation statement. March 2009. Available at: http://www.ahrq.gov/clinic/uspstf09/aspirincvd/aspcvdrs.htm. Accessed June 3, 2009.
4. National Cholesterol Education Program. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106:3143-3421.Available at: http://circ.ahajournals.org/cgi/content/full/106/25/3143. Accessed June 3, 2009.
5. Campos-Outcalt D. USPSTF scales back approach to lipid screening for women. J Fam Pract. 2008;57:740-742.
6. American Diabetes Association. Standards of medical care in diabetes—2008. Diabetes Care. 2008;31(suppl 1):S12-S54.
1. US Preventive Services Task Force. Screening for colorectal cancer. October 2008. Available at: www.ahrq.gov/clinic/uspstf/uspscolo.htm. Accessed June 3, 2009.
2. American Cancer Society guidelines for early detection of cancer. Last revised May 21, 2009. Available at: http://www.cancer.org/docroot/PED/content/PED_2_3X_ACS_Cancer_Detection_Guidelines_36.asp?sitearea=PED. Accessed June 3, 2009.
3. US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: recommendation statement. March 2009. Available at: http://www.ahrq.gov/clinic/uspstf09/aspirincvd/aspcvdrs.htm. Accessed June 3, 2009.
4. National Cholesterol Education Program. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106:3143-3421.Available at: http://circ.ahajournals.org/cgi/content/full/106/25/3143. Accessed June 3, 2009.
5. Campos-Outcalt D. USPSTF scales back approach to lipid screening for women. J Fam Pract. 2008;57:740-742.
6. American Diabetes Association. Standards of medical care in diabetes—2008. Diabetes Care. 2008;31(suppl 1):S12-S54.