Dabigatran: Difference between revisions
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Dabigatran was approved for use by the [http://www.emea.europa.eu European Medicines Agency] in 2009 for "to prevent the formation of blood clots in the veins in adults who have had an operation to replace a hip or knee."<ref>Anonymous (2009) [http://www.emea.europa.eu/humandocs/Humans/EPAR/pradaxa/pradaxa.htm EPARs for authorised medicinal products for human use] European Medicines Agency</ref> | Dabigatran was approved for use by the [http://www.emea.europa.eu European Medicines Agency] in 2009 for "to prevent the formation of blood clots in the veins in adults who have had an operation to replace a hip or knee."<ref>Anonymous (2009) [http://www.emea.europa.eu/humandocs/Humans/EPAR/pradaxa/pradaxa.htm EPARs for authorised medicinal products for human use] European Medicines Agency</ref> | ||
Under the trade name Pradaxa (Boehringer Ingelheim), Dabigatran was approved by the [[Food and Drug Administration]] in the [[United States]], in October 2010, <ref>{{citation | Under the trade name Pradaxa (Boehringer Ingelheim), Dabigatran was approved by the [[Food and Drug Administration]] in the [[United States of America]], in October 2010, <ref>{{citation | ||
| url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm230241.htm | | url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm230241.htm | ||
| date = 19 October 2010 | | date = 19 October 2010 | ||
| Line 12: | Line 12: | ||
| publisher = Food and Drug Administration}}</ref> "for the prevention of stroke and blood clots in patients with abnormal heart rhythm (atrial fibrillation)." | | publisher = Food and Drug Administration}}</ref> "for the prevention of stroke and blood clots in patients with abnormal heart rhythm (atrial fibrillation)." | ||
==Pharmacology== | ==Pharmacology== | ||
===Administration=== | ===Administration=== | ||
Dabigatran is given orally and reaches peak plasma concentrations within 0.5-2 hours.<ref name="pmid18956996">{{cite journal| author=Baetz BE, Spinler SA| title=Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases. | journal=Pharmacotherapy | year= 2008 | volume= 28 | issue= 11 | pages= 1354-73 | pmid=18956996 | Dabigatran is given orally and reaches peak plasma concentrations within 0.5-2 hours.<ref name="pmid18956996">{{cite journal| author=Baetz BE, Spinler SA| title=Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases. | journal=Pharmacotherapy | year= 2008 | volume= 28 | issue= 11 | pages= 1354-73 | pmid=18956996 | ||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=18956996 | doi=10.1592/phco.28.11.1354 }} < | | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=18956996 | doi=10.1592/phco.28.11.1354 }}</ref> | ||
====Withholding before procedures==== | |||
According to the U.S. [[Food and Drug Administration]]:<ref>{{cite web |url= http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=40084#Section_2.4 |title=DailyMed: About DailyMed |first= |last= |work=dailymed.nlm.nih.gov |year=2011 [last update] |accessdate=July 25, 2011}}</ref> | |||
* 1 to 2 days if [[creatinine clearance]] ≥50 mL/min | |||
* 3 to 5 days if [[creatinine clearance]] <50 mL/min | |||
In addition, the FDA states: "Consider longer times for patients undergoing major surgery, spinal puncture, or placement of a spinal or epidural catheter or port, in whom complete hemostasis may be required." Other experts provide recommendations depdning on the anticipated procedure and degree of renal function.<ref name="pmid20858185">{{cite journal| author=Douketis JD| title=Pharmacologic properties of the new oral anticoagulants: a clinician-oriented review with a focus on perioperative management. | journal=Curr Pharm Des | year= 2010 | volume= 16 | issue= 31 | pages= 3436-41 | pmid=20858185 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20858185 }} </ref> | |||
===Distribution=== | ===Distribution=== | ||
| Line 27: | Line 29: | ||
===Excretion=== | ===Excretion=== | ||
Dabigatran is renally excreted. | Dabigatran is renally excreted and patients with estimated [[creatinine clearance]] of less than 30 ml per minute have been excluded from major trials.<ref name="pmid19717844">{{cite journal| author=Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A et al.| title=Dabigatran versus warfarin in patients with atrial fibrillation. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 12 | pages= 1139-51 | pmid=19717844 | doi=10.1056/NEJMoa0905561 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19717844 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20083817 Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-2] </ref><ref name="pmid19966341">{{cite journal| author=Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H et al.| title=Dabigatran versus warfarin in the treatment of acute venous thromboembolism. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 24 | pages= 2342-52 | pmid=19966341 | doi=10.1056/NEJMoa0906598 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19966341 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20404376 Review in: Ann Intern Med. 2010 Apr 20;152(8):JC4-7] </ref> | ||
===Toxicity=== | ===Toxicity=== | ||
According to the manufacturer, "Pradaxa 150 mg resulted in a higher rate of major GI bleeds and any GI bleeds compared to warfarin...The risk of myocardial infarction was numerically greater in patients who received PRADAXA 150 mg than in those who received warfarin."<ref>{{citation | url = http://www.pradaxapro.com/ | publisher = Boehringer Ingelheim | title = Pradaxa (dabigatran) for healthcare professionals }}</ref><ref name="pmid19717844" /> | |||
"Dabigatran is associated with an increased risk of MI or ACS in a broad spectrum of patients when tested against different controls". <ref name="pmid22231617">{{cite journal| author=Uchino K, Hernandez AV| title=Dabigatran Association With Higher Risk of Acute Coronary Events: Meta-analysis of Noninferiority Randomized Controlled Trials. | journal=Arch Intern Med | year= 2012 | volume= | issue= | pages= | pmid=22231617 | doi=10.1001/archinternmed.2011.1666 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22231617 }} </ref> | |||
[[Drug toxicity]] includes elevation in [[liver function test]]s.<ref name="pmid18956996">{{cite journal| author=Baetz BE, Spinler SA| title=Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases. | journal=Pharmacotherapy | year= 2008 | volume= 28 | issue= 11 | pages= 1354-73 | pmid=18956996 | [[Drug toxicity]] includes elevation in [[liver function test]]s.<ref name="pmid18956996">{{cite journal| author=Baetz BE, Spinler SA| title=Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases. | journal=Pharmacotherapy | year= 2008 | volume= 28 | issue= 11 | pages= 1354-73 | pmid=18956996 | ||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=18956996 | doi=10.1592/phco.28.11.1354 }}</ref> | | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=18956996 | doi=10.1592/phco.28.11.1354 }}</ref> | ||
[[Drug toxicity]] includes elevation in [[intracranial hemorrhage]] among patients over 75 years of age.<ref name="pmid21576658">{{cite journal| author=Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J et al.| title=Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. | journal=Circulation | year= 2011 | volume= 123 | issue= 21 | pages= 2363-72 | pmid=21576658 | doi=10.1161/CIRCULATIONAHA.110.004747 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21576658 }} </ref> | |||
If bleeding occurs, the half life is short. If needed, recombinant [[coagulation]] factor VIIa or [[hemodialysis]] can be used.<ref name="pmid21324629">{{cite journal| author=American College of Cardiology Foundation. American Heart Association Task Force on Practice Guidelines. Wann LS, Curtis AB, Ellenbogen KA, Estes NA et al.| title=2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran). | journal=J Am Coll Cardiol | year= 2011 | volume= | issue= | pages= | pmid=21324629 | doi=10.1016/j.jacc.2011.01.010 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21324629 }} </ref> | If bleeding occurs, the half life is short. If needed, recombinant [[coagulation]] factor VIIa or [[hemodialysis]] can be used.<ref name="pmid21324629">{{cite journal| author=American College of Cardiology Foundation. American Heart Association Task Force on Practice Guidelines. Wann LS, Curtis AB, Ellenbogen KA, Estes NA et al.| title=2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran). | journal=J Am Coll Cardiol | year= 2011 | volume= | issue= | pages= | pmid=21324629 | doi=10.1016/j.jacc.2011.01.010 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21324629 }} </ref> | ||
==Clinical uses== | ==Clinical uses== | ||
According to the [[United States]] [[Food and Drug Administration]], dabigatran is indicated to: | According to the [[United States of America]] [[Food and Drug Administration]], dabigatran is indicated to: | ||
* "reduce the risk of stroke and systemic embolism in patients with non-valvular [[atrial fibrillation]]" | * "reduce the risk of stroke and systemic embolism in patients with non-valvular [[atrial fibrillation]]" | ||
===Atrial fibrillation=== | ===Atrial fibrillation=== | ||
{| class="wikitable" align="right" | {| class="wikitable" align="right" | ||
|+ [[Dabigatran]] versus [[warfarin]] for [[atrial fibrillation]]<ref name="pmid19717844" | |+ [[Dabigatran]] versus [[warfarin]] for [[atrial fibrillation]]<ref name="pmid19717844" /> | ||
! rowspan="2"|Intervention!! colspan="3"|Outcomes | ! rowspan="2"|Intervention!! colspan="3"|Outcomes | ||
|- | |- | ||
| Line 55: | Line 62: | ||
|colspan="4"|† p < 0.05 as compared to warfarin group | |colspan="4"|† p < 0.05 as compared to warfarin group | ||
|} | |} | ||
In 2009, dabigatran was compared to [[warfarin]] in the RE-LY [[randomized controlled trial]] for the treatment of [[atrial fibrillation]].<ref name="pmid19717844">{{cite journal| author= | In 2009, dabigatran was compared to [[warfarin]] in the RE-LY [[randomized controlled trial]] for the treatment of [[atrial fibrillation]].<ref name="pmid19717844" /> | ||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id= | |||
Dabigatran's may not be more effective than warfarin when patient's with warfarin's time in therapeutic range (TTR) is greater than 57% by the linear interpolation method.<ref name="pmid20801496">{{cite journal| author=Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG et al.| title=Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. | journal=Lancet | year= 2010 | volume= 376 | issue= 9745 | pages= 975-83 | pmid=20801496 | doi=10.1016/S0140-6736(10)61194-4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20801496 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21242360 Review in: Ann Intern Med. 2011 Jan 18;154(2):JC1-6] </ref> | |||
Dabigatran may be cost effective for atrial fibrillation.<ref name="pmid21041570">{{cite journal| author=Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS et al.| title=Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. | journal=Ann Intern Med | year= 2011 | volume= 154 | issue= 1 | pages= 1-11 | pmid=21041570 | doi=10.1059/0003-4819-154-1-201101040-00289 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21041570 }} </ref> | Dabigatran may be cost effective for atrial fibrillation.<ref name="pmid21041570">{{cite journal| author=Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS et al.| title=Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. | journal=Ann Intern Med | year= 2011 | volume= 154 | issue= 1 | pages= 1-11 | pmid=21041570 | doi=10.1059/0003-4819-154-1-201101040-00289 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21041570 }} </ref> | ||
| Line 78: | Line 86: | ||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}}[[Category:Suggestion Bot Tag]] | ||
Latest revision as of 06:01, 4 August 2024
In medicine, dabigatran is an anticoagulant that is a direct thrombin inhibitor[1] Like warfarin, dabigatran is given orgally, but unlike warfarin dabigatran is administered in fixed doses without the need for coagulation monitoring.
History
Dabigatran was approved for use by the European Medicines Agency in 2009 for "to prevent the formation of blood clots in the veins in adults who have had an operation to replace a hip or knee."[2]
Under the trade name Pradaxa (Boehringer Ingelheim), Dabigatran was approved by the Food and Drug Administration in the United States of America, in October 2010, [3] "for the prevention of stroke and blood clots in patients with abnormal heart rhythm (atrial fibrillation)."
Pharmacology
Administration
Dabigatran is given orally and reaches peak plasma concentrations within 0.5-2 hours.[4]
Withholding before procedures
According to the U.S. Food and Drug Administration:[5]
- 1 to 2 days if creatinine clearance ≥50 mL/min
- 3 to 5 days if creatinine clearance <50 mL/min
In addition, the FDA states: "Consider longer times for patients undergoing major surgery, spinal puncture, or placement of a spinal or epidural catheter or port, in whom complete hemostasis may be required." Other experts provide recommendations depdning on the anticipated procedure and degree of renal function.[6]
Distribution
Metabolism
Excretion
Dabigatran is renally excreted and patients with estimated creatinine clearance of less than 30 ml per minute have been excluded from major trials.[7][8]
Toxicity
According to the manufacturer, "Pradaxa 150 mg resulted in a higher rate of major GI bleeds and any GI bleeds compared to warfarin...The risk of myocardial infarction was numerically greater in patients who received PRADAXA 150 mg than in those who received warfarin."[9][7]
"Dabigatran is associated with an increased risk of MI or ACS in a broad spectrum of patients when tested against different controls". [10]
Drug toxicity includes elevation in liver function tests.[4]
Drug toxicity includes elevation in intracranial hemorrhage among patients over 75 years of age.[11]
If bleeding occurs, the half life is short. If needed, recombinant coagulation factor VIIa or hemodialysis can be used.[12]
Clinical uses
According to the United States of America Food and Drug Administration, dabigatran is indicated to:
- "reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation"
Atrial fibrillation
| Intervention | Outcomes | ||
|---|---|---|---|
| Stroke or systemic embolism | Major bleeding | Mortality | |
| Dabigatran 110 mg twice daily | 1.53% | 2.71%† | 3.75% |
| Dabigatran 150 mg twice daily | 1.11%† | 3.11% | 3.64% |
| Warfarin | 1.69% | 3.36% | 4.13% |
| † p < 0.05 as compared to warfarin group | |||
In 2009, dabigatran was compared to warfarin in the RE-LY randomized controlled trial for the treatment of atrial fibrillation.[7]
Dabigatran's may not be more effective than warfarin when patient's with warfarin's time in therapeutic range (TTR) is greater than 57% by the linear interpolation method.[13]
Dabigatran may be cost effective for atrial fibrillation.[14]
Deep venous thrombosis
Dabigatran given 150 mg orally twice a day was as effective as warfarin for the treatment of deep venous thrombosis in the RE-COVER randomized controlled trial.[15]
External links
The most up-to-date information about Dabigatran and other drugs can be found at the following sites.
- Dabigatran - FDA approved drug information (drug label) from DailyMed (U.S. National Library of Medicine).
- Dabigatran - Drug information for consumers from MedlinePlus (U.S. National Library of Medicine).
- Dabigatran - Detailed information from DrugBank.
References
- ↑ Anonymous (2024), Dabigatran (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2009) EPARs for authorised medicinal products for human use European Medicines Agency
- ↑ FDA approves Pradaxa to prevent stroke in people with atrial fibrillation, Food and Drug Administration, 19 October 2010
- ↑ 4.0 4.1 Baetz BE, Spinler SA (2008). "Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases.". Pharmacotherapy 28 (11): 1354-73. DOI:10.1592/phco.28.11.1354. PMID 18956996. Research Blogging.
- ↑ DailyMed: About DailyMed. dailymed.nlm.nih.gov (2011 [last update]). Retrieved on July 25, 2011.
- ↑ Douketis JD (2010). "Pharmacologic properties of the new oral anticoagulants: a clinician-oriented review with a focus on perioperative management.". Curr Pharm Des 16 (31): 3436-41. PMID 20858185. [e]
- ↑ 7.0 7.1 7.2 7.3 Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A et al. (2009). "Dabigatran versus warfarin in patients with atrial fibrillation.". N Engl J Med 361 (12): 1139-51. DOI:10.1056/NEJMoa0905561. PMID 19717844. Research Blogging. Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-2
- ↑ Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H et al. (2009). "Dabigatran versus warfarin in the treatment of acute venous thromboembolism.". N Engl J Med 361 (24): 2342-52. DOI:10.1056/NEJMoa0906598. PMID 19966341. Research Blogging. Review in: Ann Intern Med. 2010 Apr 20;152(8):JC4-7
- ↑ Pradaxa (dabigatran) for healthcare professionals, Boehringer Ingelheim
- ↑ Uchino K, Hernandez AV (2012). "Dabigatran Association With Higher Risk of Acute Coronary Events: Meta-analysis of Noninferiority Randomized Controlled Trials.". Arch Intern Med. DOI:10.1001/archinternmed.2011.1666. PMID 22231617. Research Blogging.
- ↑ Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J et al. (2011). "Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial.". Circulation 123 (21): 2363-72. DOI:10.1161/CIRCULATIONAHA.110.004747. PMID 21576658. Research Blogging.
- ↑ American College of Cardiology Foundation. American Heart Association Task Force on Practice Guidelines. Wann LS, Curtis AB, Ellenbogen KA, Estes NA et al. (2011). "2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran).". J Am Coll Cardiol. DOI:10.1016/j.jacc.2011.01.010. PMID 21324629. Research Blogging.
- ↑ Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG et al. (2010). "Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial.". Lancet 376 (9745): 975-83. DOI:10.1016/S0140-6736(10)61194-4. PMID 20801496. Research Blogging. Review in: Ann Intern Med. 2011 Jan 18;154(2):JC1-6
- ↑ Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS et al. (2011). "Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation.". Ann Intern Med 154 (1): 1-11. DOI:10.1059/0003-4819-154-1-201101040-00289. PMID 21041570. Research Blogging.
- ↑ Schulman, Sam; Clive Kearon, Ajay K. Kakkar, Patrick Mismetti, Sebastian Schellong, Henry Eriksson, David Baanstra, Janet Schnee, Samuel Z. Goldhaber, the RE-COVER Study Group (2009-12-06). "Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism". N Engl J Med: NEJMoa0906598. DOI:10.1056/NEJMoa0906598. Retrieved on 2009-12-06. Research Blogging.