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imported>Robert Badgett
(Isosorbide dinitrate and hydralazine combination treatment - Added AHA statement about A-HeFT)
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====Isosorbide dinitrate and hydralazine combination treatment====
====Isosorbide dinitrate and hydralazine combination treatment====
Isosorbide dinitrate and hydralazine combination treatment reduces mortality in African-American patients with [[New York Heart Association Functional Classification|functional class]] III or IV heart failure.<ref name="pmid15533851">{{cite journal |author=Taylor AL, Ziesche S, Yancy C, ''et al'' |title=Combination of isosorbide dinitrate and hydralazine in blacks with heart failure |journal=N. Engl. J. Med. |volume=351 |issue=20 |pages=2049–57 |year=2004 |pmid=15533851|url=http://content.nejm.org/cgi/content/full/351/20/2049 |doi=10.1056/NEJMoa042934}}</ref> The U.S. Food and Drug Administration has approved the drug BiDil for African Americans<ref name="pmid17200223">{{cite journal |author=Temple R, Stockbridge NL |title=BiDil for heart failure in black patients: The U.S. Food and Drug Administration perspective |journal=Ann. Intern. Med. |volume=146 |issue=1 |pages=57–62 |year=2007 |pmid=17200223 |doi=|url=http://www.annals.org/cgi/content/full/146/1/57}}</ref> which has created controversy<ref name="pmid17200222">{{cite journal |author=Bibbins-Domingo K, Fernandez A |title=BiDil for heart failure in black patients: implications of the U.S. Food and Drug Administration approval |journal=Ann. Intern. Med. |volume=146 |issue=1 |pages=52–6 |year=2007 |pmid=17200222 |doi=|url=http://www.annals.org/cgi/content/full/146/1/52}}</ref> for reasons including the approval helped the manufacturer, NitroMed, add a second race-related patent that extended protection for BiDil for 13 years<ref name="pmid17679713">{{cite journal |author=Kahn JD |title=BiDil for heart failure in black patients |journal=Ann. Intern. Med. |volume=147 |issue=3 |pages=215; author reply 215–6 |year=2007 |pmid=17679713 |doi=|url=http://www.annals.org/cgi/content/full/147/3/215}}</ref>.
Isosorbide dinitrate and hydralazine combination treatment reduces mortality in African-American patients with [[New York Heart Association Functional Classification|functional class]] III or IV heart failure according to the A-HeFT [[randomized controlled trial]].<ref name="pmid15533851">{{cite journal |author=Taylor AL, Ziesche S, Yancy C, ''et al'' |title=Combination of isosorbide dinitrate and hydralazine in blacks with heart failure |journal=N. Engl. J. Med. |volume=351 |issue=20 |pages=2049–57 |year=2004 |pmid=15533851|url=http://content.nejm.org/cgi/content/full/351/20/2049 |doi=10.1056/NEJMoa042934}}</ref> The U.S. Food and Drug Administration has approved the drug BiDil for African Americans<ref name="pmid17200223">{{cite journal |author=Temple R, Stockbridge NL |title=BiDil for heart failure in black patients: The U.S. Food and Drug Administration perspective |journal=Ann. Intern. Med. |volume=146 |issue=1 |pages=57–62 |year=2007 |pmid=17200223 |doi=|url=http://www.annals.org/cgi/content/full/146/1/57}}</ref> which has created controversy<ref name="pmid17200222">{{cite journal |author=Bibbins-Domingo K, Fernandez A |title=BiDil for heart failure in black patients: implications of the U.S. Food and Drug Administration approval |journal=Ann. Intern. Med. |volume=146 |issue=1 |pages=52–6 |year=2007 |pmid=17200222 |doi=|url=http://www.annals.org/cgi/content/full/146/1/52}}</ref> for reasons including the approval helped the manufacturer, NitroMed, add a second race-related patent that extended protection for BiDil for 13 years<ref name="pmid17679713">{{cite journal |author=Kahn JD |title=BiDil for heart failure in black patients |journal=Ann. Intern. Med. |volume=147 |issue=3 |pages=215; author reply 215–6 |year=2007 |pmid=17679713 |doi=|url=http://www.annals.org/cgi/content/full/147/3/215}}</ref>.


Whether the benefit to African-Americans is more than occurs for Anglo patients is unclear, but is suggested by two controversial<ref name="pmid17679712b">{{cite journal |author=Bibbins-Domingo K, Fernandez A |title=BiDil for heart failure in black patients |journal=Ann. Intern. Med. |volume=147 |issue=3 |pages=215–6 |year=2007 |pmid= |doi=|url=http://www.annals.org/cgi/content/full/147/3/215-a}}</ref><ref name="pmid17679712">{{cite journal |author=Bibbins-Domingo K, Fernandez A |title=BiDil for heart failure in black patients |journal=Ann. Intern. Med. |volume=147 |issue=3 |pages=214–5; author reply 215–6 |year=2007 |pmid=17679712 |doi=|url=http://www.annals.org/cgi/content/full/147/3/214}}</ref> post-hoc analyses<ref name="pmid10496190">{{cite journal |author=Carson P, Ziesche S, Johnson G, Cohn JN |title=Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group |journal=J. Card. Fail. |volume=5 |issue=3 |pages=178–87 |year=1999 |pmid=10496190 |doi=10.1016/S1071-9164(99)90001-5}}</ref> of subgroups in the earlier  V-HeFT-1<ref name="pmid3520315">{{cite journal |author=Cohn JN, Archibald DG, Ziesche S, ''et al'' |title=Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study |journal=N. Engl. J. Med. |volume=314 |issue=24 |pages=1547–52 |year=1986 |pmid=3520315 |doi=}}</ref> and V-HeFT-2<ref name="pmid2057035">{{cite journal |author=Cohn JN, Johnson G, Ziesche S, ''et al'' |title=A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure |journal=N. Engl. J. Med. |volume=325 |issue=5 |pages=303–10 |year=1991 |pmid=2057035 |doi=}}</ref>
Whether the benefit to African-Americans is more than occurs for Anglo patients is unclear, but is suggested by two controversial<ref name="pmid17679712b">{{cite journal |author=Bibbins-Domingo K, Fernandez A |title=BiDil for heart failure in black patients |journal=Ann. Intern. Med. |volume=147 |issue=3 |pages=215–6 |year=2007 |pmid= |doi=|url=http://www.annals.org/cgi/content/full/147/3/215-a}}</ref><ref name="pmid17679712">{{cite journal |author=Bibbins-Domingo K, Fernandez A |title=BiDil for heart failure in black patients |journal=Ann. Intern. Med. |volume=147 |issue=3 |pages=214–5; author reply 215–6 |year=2007 |pmid=17679712 |doi=|url=http://www.annals.org/cgi/content/full/147/3/214}}</ref> post-hoc analyses<ref name="pmid10496190">{{cite journal |author=Carson P, Ziesche S, Johnson G, Cohn JN |title=Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group |journal=J. Card. Fail. |volume=5 |issue=3 |pages=178–87 |year=1999 |pmid=10496190 |doi=10.1016/S1071-9164(99)90001-5}}</ref> of subgroups in the earlier  V-HeFT-1<ref name="pmid3520315">{{cite journal |author=Cohn JN, Archibald DG, Ziesche S, ''et al'' |title=Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study |journal=N. Engl. J. Med. |volume=314 |issue=24 |pages=1547–52 |year=1986 |pmid=3520315 |doi=}}</ref> and V-HeFT-2<ref name="pmid2057035">{{cite journal |author=Cohn JN, Johnson G, Ziesche S, ''et al'' |title=A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure |journal=N. Engl. J. Med. |volume=325 |issue=5 |pages=303–10 |year=1991 |pmid=2057035 |doi=}}</ref>
In response to the results of the A-HeFT study, the [[American Heart Association]] [[clinical practice guideline]]s state "the effect of this combination of isosorbide dinitrate and hydralazine in other patients with HF who are undergoing standard therapy is not known because the population studied was limited to blacks, but there is no reason to believe that this benefit is limited to blacks."<ref name="pmid16160202"/>


===Noninvasive positive pressure ventilation===
===Noninvasive positive pressure ventilation===

Revision as of 10:01, 22 January 2008

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Congestive heart failure is defined as "defective cardiac filling and/or impaired contraction and emptying, resulting in the heart's inability to pump a sufficient amount of blood to meet the needs of the body tissues or to be able to do so only with an elevated filling pressure".[1]

Classification

Systolic dysfunction

Diastolic dysfunction

Diagnosis

History and physical examination

Hemodynamic Profiles
Congestion†?
(jugular venous distention and
radiographic redistribution)[2]
No Yes
Hypoperfusion‡?
(proportional pulse pressure < 25%[3][4],
cool extremities[5])		 No Warm and dry
(46% mortality at one year)		 Warm and wet
Yes Cold and dry Cold and wet
(33% mortality at one year[4])
Notes:

Adapted from Figure 1 of Nohria et al.[6]
† Congestion is defined as pulmonary capillary wedge pressure of 20 mm Hg or more[4]
‡ Hypoperfusion is defined as cardiac index of 1.8 L/min/m2.[4] This is associated with elevate lactate.[5]

The best findings for detecting increased filling pressure are jugular venous distention and radiographic redistribution. The best findings for detecting systolic dysfunction are abnormal apical impulse, radiographic cardiomegaly, and q waves or left bundle branch block on an electrocardiogram. [2]

The history and physical examination can also be used for patients with advanced heart failure to place the patient into a hemodynamic profile to guide management.[6][4][5] Patients in the "cold and wet" category may need to "warm up in order to dry out" by stopping beta-blockers and ACE inhibitors.[6]

Echocardiogram

The fractional shortening can estimate the left ventricular ejection fraction.[7][8][9]

Treatment

Medications

Race-based therapeutics?
The controversial approval[10] by the U.S. Food and Drug Administration of the drug NitroMed has led to the concept of race-based therapeutics.[11] Presumably, pharmacogenomics will lead to individualized drug treatment; until then the use of race may be a proxy of pharmacogenomic variations.
Angiotensin-converting enzyme inhibitors
There is conflicting evidence whether ACE inhibitors are as effective in African-American patients as in Anglo patients.[12][13]
Beta-blockers
There is conflicting evidence whether beta-blockers are as effective in African-American patients as in Anglo patients.[12]
Isosorbide dinitrate and hydralazine combination
Isosorbide dinitrate and hydralazine combination treatment reduces mortality in African-American patients with functional class III or IV heart failure.[14] Whether this benefit is more than occurs for Anglo patients is unclear, but is suggested by two controversial[15][16] post-hoc analyses[17] of subgroups in the earlier V-HeFT-1[18] and V-HeFT-2[19] randomized controlled trials (see randomized controlled trials for details about post-hoc and subgroup analyses).


Angiotensin-converting enzyme inhibitors

Angiotensin-converting enzyme inhibitors (ACE inhibitors) should not be used if:[20]

  • Baseline serum potassium is < 5.5 mmol per liter.
  • No prior life-threatening adverse reactions (angioedema or anuric renal failure) during previous exposure to the drug
  • They are not pregnant
  • Systolic blood pressure less than 80 mm Hg
  • Serum levels of creatinine greater than 3 mg per dL
  • Bilateral renal artery stenosis is not present

There is conflicting evidence whether ACE inhibitors are as effective in African-American patients as in Anglo patients.[12][13]

Angiotensin-converting enzyme inhibitors combined with angiotensin-receptor blockers

This combination should be avoided due to increased azotemia, hyperkalemia, and symptomatic hypotension.[21]

Beta-blockers

There is conflicting evidence whether beta-blockers are as effective in African-American patients as in Anglo patients.[12]

Aldosterone antagonists

Aldosterone antagonists, initial dose of spironolactone 12.5 mg or eplerenone 25 mg, may be used as long as:[20]

  • Serum creatinine 1.6 mg per dL or less and glomerular filtration rate or creatinine clearance exceeds 30 mL per minute.
  • Baseline serum potassium is < 5.0 mEq per liter

Risk of hyperkalemia is increased if the following drugs are used:[20]

  • Higher doses of ACE inhibitors (captopril greater than or equal to 75 mg daily; enalapril or lisinopril greater than or equal to 10 mg daily).
  • Nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors
  • Potassium supplements

After starting aldosterone antagonists:[20]

  • Potassium levels and renal function should be checked in 3 days
  • Potassium levels and renal function should be checked at 1 week
  • Potassium levels and renal function should be checked monthly for the first 3 months.
  • Diarrhea or other causes of dehydration should be addressed emergently

Isosorbide dinitrate and hydralazine combination treatment

Isosorbide dinitrate and hydralazine combination treatment reduces mortality in African-American patients with functional class III or IV heart failure according to the A-HeFT randomized controlled trial.[14] The U.S. Food and Drug Administration has approved the drug BiDil for African Americans[22] which has created controversy[10] for reasons including the approval helped the manufacturer, NitroMed, add a second race-related patent that extended protection for BiDil for 13 years[23].

Whether the benefit to African-Americans is more than occurs for Anglo patients is unclear, but is suggested by two controversial[15][16] post-hoc analyses[17] of subgroups in the earlier V-HeFT-1[18] and V-HeFT-2[19]

In response to the results of the A-HeFT study, the American Heart Association clinical practice guidelines state "the effect of this combination of isosorbide dinitrate and hydralazine in other patients with HF who are undergoing standard therapy is not known because the population studied was limited to blacks, but there is no reason to believe that this benefit is limited to blacks."[20]

Noninvasive positive pressure ventilation

Noninvasive positive pressure ventilation (NPP) can help treat acute cardiac pulmonary edema according to a meta-analyses of randomized controlled trials.[24][25] Among the different modes of NPPV, CPAP may be slightly better than BiPAP.[25] It is not clear that NPPV helps patients with normal partial pressures of carbon dioxide.[26]

Implantable devices

Several implantable devices may help long term treatment; however, it is not clear that implantable cardioverter-defibrillators (ICD) add benefit over cardiac resynchronisation therapy (CRT).[27]

Cardiac resynchronization therapy

According to a systematic review, cardiac resynchronization therapy (CRT), which is biventricular pacing, can reduce morbiity and mortality if the ejection fraction is less than 35%.[28] 30 patients must be treated to avoid one death (number needed to treat is 30). Cardiac resynchronization should only be used for patients with a QRS duration of at least 120 msec.[29]

Implantable cardioverter-defibrillator

Implantable cardioverter-defibrillators (ICD) can reduce mortality in patients who have an ejection fraction of less than 35%.[30]

Left ventricular assist devices

Left ventricular assist devices (LVADs) may be an option for patients with end stage heart failure.[31]

Prognosis

Mortality can be predicted with the The Seattle Heart Failure Model.[32] The model can show the affect of interventions on prognosis. The model is available online at http://depts.washington.edu/shfm/.

References

  1. ↑ National Library of Medicine. Heart Failure, Congestive. Retrieved on 2007-10-19.
  2. ↑ 2.0 2.1 Badgett RG, Lucey CR, Mulrow CD (1997). "Can the clinical examination diagnose left-sided heart failure in adults?". JAMA 277 (21): 1712-9. PMID 9169900. [e]
  3. ↑ Stevenson LW, Perloff JK (1989). "The limited reliability of physical signs for estimating hemodynamics in chronic heart failure". JAMA 261 (6): 884–8. PMID 2913385. [e]
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Shah MR, Hasselblad V, Stinnett SS, et al (2001). "Hemodynamic profiles of advanced heart failure: association with clinical characteristics and long-term outcomes". J. Card. Fail. 7 (2): 105–13. DOI:10.1054/jcaf.2001.24131. PMID 11420761. Research Blogging.
  5. ↑ 5.0 5.1 5.2 Kaplan LJ, McPartland K, Santora TA, Trooskin SZ (2001). "Start with a subjective assessment of skin temperature to identify hypoperfusion in intensive care unit patients". The Journal of trauma 50 (4): 620–7; discussion 627–8. PMID 11303155. [e]
  6. ↑ 6.0 6.1 6.2 Nohria A, Lewis E, Stevenson LW (2002). "Medical management of advanced heart failure". JAMA 287 (5): 628–40. PMID 11829703. [e]
  7. ↑ Tortoledo FA, Fernandez GC, Quinones MA (1983). "An accurate and simplified method to calculate angiographic left ventricular ejection fraction". Catheterization and cardiovascular diagnosis 9 (4): 357-62. PMID 6627386. [e]
  8. ↑ Quinones MA, Waggoner AD, Reduto LA, et al (1981). "A new, simplified and accurate method for determining ejection fraction with two-dimensional echocardiography". Circulation 64 (4): 744-53. PMID 7273375. [e]
  9. ↑ Erbel R, Schweizer P, Krebs W, Meyer J, Effert S (1984). "Sensitivity and specificity of two-dimensional echocardiography in detection of impaired left ventricular function". Eur. Heart J. 5 (6): 477-89. PMID 6745290. [e]
  10. ↑ 10.0 10.1 Bibbins-Domingo K, Fernandez A (2007). "BiDil for heart failure in black patients: implications of the U.S. Food and Drug Administration approval". Ann. Intern. Med. 146 (1): 52–6. PMID 17200222. [e]
  11. ↑ Bloche MG (2004). "Race-based therapeutics". N. Engl. J. Med. 351 (20): 2035–7. DOI:10.1056/NEJMp048271. PMID 15533852. Research Blogging.
  12. ↑ 12.0 12.1 12.2 12.3 Shekelle PG, Rich MW, Morton SC, et al (2003). "Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials". J. Am. Coll. Cardiol. 41 (9): 1529–38. PMID 12742294. [e]
  13. ↑ 13.0 13.1 Exner DV, Dries DL, Domanski MJ, Cohn JN (2001). "Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction". N. Engl. J. Med. 344 (18): 1351–7. PMID 11333991. [e]
  14. ↑ 14.0 14.1 Taylor AL, Ziesche S, Yancy C, et al (2004). "Combination of isosorbide dinitrate and hydralazine in blacks with heart failure". N. Engl. J. Med. 351 (20): 2049–57. DOI:10.1056/NEJMoa042934. PMID 15533851. Research Blogging.
  15. ↑ 15.0 15.1 Temple R, Stockbridge NL (2007). "BiDil for heart failure in black patients". Ann. Intern. Med. 147 (3): 215–6. [e] Cite error: Invalid <ref> tag; name "pmid17679712b" defined multiple times with different content
  16. ↑ 16.0 16.1 Bibbins-Domingo K, Fernandez A (2007). "BiDil for heart failure in black patients". Ann. Intern. Med. 147 (3): 214–5. PMID 17679712. [e] Cite error: Invalid <ref> tag; name "pmid17679712" defined multiple times with different content
  17. ↑ 17.0 17.1 Carson P, Ziesche S, Johnson G, Cohn JN (1999). "Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group". J. Card. Fail. 5 (3): 178–87. DOI:10.1016/S1071-9164(99)90001-5. PMID 10496190. Research Blogging.
  18. ↑ 18.0 18.1 Cohn JN, Archibald DG, Ziesche S, et al (1986). "Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study". N. Engl. J. Med. 314 (24): 1547–52. PMID 3520315. [e]
  19. ↑ 19.0 19.1 Cohn JN, Johnson G, Ziesche S, et al (1991). "A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure". N. Engl. J. Med. 325 (5): 303–10. PMID 2057035. [e]
  20. ↑ 20.0 20.1 20.2 20.3 20.4 Hunt SA, Abraham WT, Chin MH, et al (2005). "ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society". Circulation 112 (12): e154–235. DOI:10.1161/CIRCULATIONAHA.105.167586. PMID 16160202. Research Blogging. National Guidelines Clearinghouse
  21. ↑ Phillips CO, Kashani A, Ko DK, Francis G, Krumholz HM (2007). "Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials". Arch. Intern. Med. 167 (18): 1930–6. DOI:10.1001/archinte.167.18.1930. PMID 17923591. Research Blogging.
  22. ↑ Temple R, Stockbridge NL (2007). "BiDil for heart failure in black patients: The U.S. Food and Drug Administration perspective". Ann. Intern. Med. 146 (1): 57–62. PMID 17200223. [e]
  23. ↑ Kahn JD (2007). "BiDil for heart failure in black patients". Ann. Intern. Med. 147 (3): 215; author reply 215–6. PMID 17679713. [e]
  24. ↑ Peter JV, Moran JL, Phillips-Hughes J, Graham P, Bersten AD (2006). "Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis". Lancet 367 (9517): 1155–63. DOI:10.1016/S0140-6736(06)68506-1. PMID 16616558. Research Blogging.
  25. ↑ 25.0 25.1 Masip J, Roque M, Sánchez B, Fernández R, Subirana M, Expósito JA (2005). "Noninvasive ventilation in acute cardiogenic pulmonary edema: systematic review and meta-analysis". JAMA 294 (24): 3124–30. DOI:10.1001/jama.294.24.3124. PMID 16380593. Research Blogging.
  26. ↑ Nava S, Carbone G, DiBattista N, et al (2003). "Noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial". Am. J. Respir. Crit. Care Med. 168 (12): 1432–7. DOI:10.1164/rccm.200211-1270OC. PMID 12958051. Research Blogging.
  27. ↑ Lam SK, Owen A (2007). "Combined resynchronisation and implantable defibrillator therapy in left ventricular dysfunction: Bayesian network meta-analysis of randomised controlled trials". BMJ 335 (7626): 925. DOI:10.1136/bmj.39343.511389.BE. PMID 17932160. Research Blogging.
  28. ↑ McAlister FA, Ezekowitz J, Hooton N, et al (2007). "Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review". JAMA 297 (22): 2502–14. DOI:10.1001/jama.297.22.2502. PMID 17565085. Research Blogging. ACPJC summary
  29. ↑ Beshai JF, Grimm RA, Nagueh SF, et al (2007). "Cardiac-Resynchronization Therapy in Heart Failure with Narrow QRS Complexes". DOI:10.1056/NEJMoa0706695. PMID 17986493. Research Blogging.
  30. ↑ Bardy GH, Lee KL, Mark DB, et al (2005). "Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure". N. Engl. J. Med. 352 (3): 225–37. DOI:10.1056/NEJMoa043399. PMID 15659722. Research Blogging.
  31. ↑ Delgado RM, Radovancevic B (2007). "Symptomatic relief: left ventricular assist devices versus resynchronization therapy". Heart failure clinics 3 (3): 259–65. DOI:10.1016/j.hfc.2007.05.004. PMID 17723934. Research Blogging.
  32. ↑ Levy WC, Mozaffarian D, Linker DT, et al (2006). "The Seattle Heart Failure Model: prediction of survival in heart failure". Circulation 113 (11): 1424–33. DOI:10.1161/CIRCULATIONAHA.105.584102. PMID 16534009. Research Blogging.
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