Outcome measures for the hand study depend on approval of cream or dextrose. If dextrose we may go back to measurement of joint size.
Methylene Blue: Stains all soft tissue but not bone. Intense and capable of staining surface cartilage buds. H&E: Standard initial testing for cellular nature, number and orientation. Organized cartilage will have columnar orientation and degenerative cartilage will appear sporadic and clumped. Least useful but required for complete results. Saff O: In DJD not much activity since cells are dying. In regeneration MPS activity is high. Mechanical Properties: Lanny has other scientific support for durability in publications for regrown cartilage.
I adjusted the volume based on our confirmation today that ACD collects between 8-8.5 ml of whole blood per tube here on the West coast. Higher elevations will get less. I was not able to re-arrange the boxes to allow for 8 0.75 ml from 3 tubes boxes. I think that the 0.75 ml extraction works very well in our course, and we have settled on it as our benchmark. So there are two blood draws of 12 tubes each, and 8 attempts at concentrations total. You could call this 4 trials.
12 aaom reeves workshop april 20 research in practice
IntroducingResearch Into Your OrthopedicMedicine Practice AAOM 29th Annual Conference April 18-21 2012 K. Dean Reeves, M.D. Clinical Associate Professor University of Kansas
HSC Application and On-LineAnnouncement •Choose HSC •Protocol •Consent •Privacy Form •Phone Screening •Advertising •Send Application •HSC Approval •Clinicaltrials.org
From Enrollment To Publication •Enroll 6-24 Mo •Follow 1-2 Yr •Submit/hear back 3 Mo •Resubmit/hear back 3 mo •Correct Proof 1 mo •Publication 3 mo
From Preliminary Idea to Literature Review O T K T T C C H H● = Completed S T N M M A A A AN = Not applicable D P C J J U U N N R A D D D D P R R B R H B H R R G O O O K A I O O UCommon ● ● ● ● ● ● ● ● ●Function Impairing ● N ● ● ● ● ● ● ●Clear Rx ● ● ● ● ● ● ● ● ●AdvantagesFast ● ● ● ● ● ● ● ● ●Powerful ● ● ● ● ● ● ● ● ●Purpose Statement ● ● ● ● ● ● ● ● ●Literature Review ● ● ● ● ● ● ● ● ●
Pre-Site Choice: Practical Considerations O T K T T C C H H● = Completed S T N M M A A A AN = Not applicable D P C J J U U N N R A D D D D P R R B R H B H R R G O O O K A I O O UPreliminary Team ● ● ● ● ● ● ● ● ●Outcome Measures ● ● ● ● ● ● ●Power Analysis ● ● ● ● ● ● ● ● ●Precise Hypotheses ● ● ● ● ● ● ●Cost Estimates ● ● ● ● ● ● ●Site Choice(s) ● ● ● ● ● ● ●
HSC Application and On-Line Announcement O T K T T C C H H● = Completed S T N M M A A A AN = Not applicable D P C J J U U N N R A D D D D P R R B R H B H R R G O O O K A I O O UChoose HSC ● ● ● ● ● ● ●Protocol ● ● ● ● ● ● ●Consent ● ● ● ● ● ● ●Privacy Form ● ● ● ● ● ● ●Phone Screen ● ● ● ● ● ● ●Advertising ● ● ● ● ● ● ●Send Application ● ● ●HSC Approval ● ●Clinicaltrials.org ● ●
From Enrollment to Publication O T K T T C C H HTime To Publication S T N M M A A A AFrom Enrollment D P C J J U U N N27 mo – 57 mo R A D D D D P R R B R H B H R R G O O O K A I O O UEnroll 6-24 mo ●Follow 1-2 yr ●Submit 2 mo ●Resubmit 2 mo ●Resubmit 2 mo ●Correct Proof 1 mo ●Publication 2 mo ●
Post Exercise RCT Dextrose Cream• Location: Vancouver• Primary Investigatory: Helene Bertrand• Status: Preparing for May 6, 2012 (Vancouver Marathon)
Dextrose vs Vehicle Cream for Post Marathon Pain Leg pain > 5/10 Post Marathon Willing to apply cream three times daily? If yes, Randomize. Treat both sides if opposite side has pain. Gather data on each leg that has pain > 5/10. 20 20 Dextrose + Vehicle Cream Vehicle Cream Only for 5 days BID-TID for 5 days E mail Data collection of AM NRS daily X 5 days. At end of 5 days a 7 point Likert Scale response will be requested to the questions “I plan to use a cream like this in the future?” 1 month recheck for any potential side effects. Comfortable running distance at 1 month
Arthroscopic Study Cartilage Growth• Location: Rosario• Primary Investigator: Gaston Topol• Status: 1st group of 6 with 12.5% dextrose completed. 2nd group of 6 underway with 25% dextrose.
Knee OA: Double Arthroscopy Protocol Arthroscopy #1 Then wait until return to baseline symptoms Injection of 12.5% dextrose @ 0, 1, 2, 3, 4, and 5 month. (25% for 2nd group) (9 ml with HRUS guidance) Use medial lift in 2nd group) Arthroscopy #2 at 6 Mo Follow for 1 Year with Injection every 2-3 Months if symptomatic
Data Gathering 1st 0 6 Mo Arth MoWOMAC X XWalking Pain X XWalking Distance X XExtension Lack X XTotal flexion X XArthroscopic Video Pre/post MB X XBiopsy of growth area for cartilage Xquality.
Histological Investigations• Methylene Blue: Shows cartilage buds.• Hematoxin and Eosin Staining: Column orientation (organized cartilage) vs sporadic clumped (degenerative cartilage)• Saff O: Mucopolysaccharide (MPS) activity measure. Pale in OA (dying cartilage). Red with regeneration .• Polarized light: Fibrocartilage shows fibers distinctly. Hyaline cartilage shows glassy appearance. (No fibers)• Collagen typing: type 1 in fibrous tissue; type II in both fibrous and hyaline cartilage. Not essential but orthopedic community will enquire.• Mechanical properties: Not possible on small biopsy and not expected.
Finger OA RCT: Dextrose Cream• Location: Guadalajara, Buenos Aires• Potential Primary Investigators: David de la Mora, Irene Briseno, Gonzalo Yamauchi.• Status: Cream approval issues blocking HSC approval in 1 site. Pre-HSC submission in 2nd.
Finger OA: Dextrose vs Xanthan Gum 3 months of bilateral finger pain (Minimum 6/10) + At least one painful joint on fingers 2-5 + No finger “sticking”/No Painful flexor nodule + No worse pain in other areas + Inflammatory arthritis lab testing negative 15 Nighttime with gloves 15Dextrose + Vehicle Cream Xanthan Gum + Vehicle Cream 3 Mo Data (Grip Pain + AUSCAN) Dextrose + Vehicle Cream 12 Mo Data (Grip Pain + AUSCAN) 24 Month Data? (Repeat X-Ray, Grip Pain, AUSCAN
Randomized Comparison of Immediate Analgesic Effects of 5% Dextrose in Water vs Normal Saline and 1 Year Outcome Data of 5% Dextrose administration.
NRS Pain + ODI 2.0 at 0 Months #15 #15 10 ml D5W Caudal 10 ml NS CaudalNRS Pain 15 min, 2 hrs, 4 hrs, 48 hrs Unblinded@ 48 hrs, Then 10 ml D5W if Not Received90% or more reduction in Pain 15 minutes after Caudal D5W Y N D5W @ 2, 4, and 6 weeks and PRN. Offer Continued 90% Reduction in Pain 15 N Other Minutes Post Injection? Rx Y NRS Pain + ODI 2.0 at 3 and 12 Months
Dextrose TMJ Study• Location: Buenos Aires, Hong Kong• Primary Investigator: Miguel Zarate, Ricardo Frusso, Stanley Lam.• Status: Near HSC approval. Delay prior to HSC submission. Pilot completed
RCT of Dextrose vs Lidocaine Injection for TMD Facial Pain > 5/10 + Jaw symptoms > 5/10 + Exam for Obvious Dental Issues? Symptoms referable to jaw after exam? If Yes, Randomize.Treat both sides if opposite side has pain or jaw dysfunction, but gather data on the worst side 5 5 Dex 20%/Lido .2% 1ml Water/Lido .2% 1 ml @ 0, 1, and 2 mo @ 0, 1, and 2 mo. PRN Injection 6 Month Data Collection PRN Injection 1 Year Data
Pilot Results: NRS Scale Changes 0 to 6 Months For Dextrose (D) vs Lidocaine (L)
P Values for 10 Subject Study: 0 to 6 Months• Multivariate analysis Dextrose Vs Lidocaine: Dextrose better (p = .049)• Univariate analysis Dextrose vs Lidocaine Dextrose better in pain improvement (p = .013 Dextrose better in function improvement (p = .020)
PRP: Efficacy of Novice Teaching 25 tubes (196 ml total blood draw) FROM each novice preparer 12 Tubes for AM 12 Tubes for PM 1 tube for “Close Supervision” “Intermittent Input” baseline trials trials testing 6 Tubes 6 Tubes Trial 1 Trial 1 0.75 0.75 0.75 0.75 ml ml ml ml from from from from 3 3 3 3 tubes tubes tubes tubes0.75 0.75 0.75 0.75ml ml ml mlfrom from from from3 3 3 3tubes tubes tubes tubes
ACL Laxity Correction• Partial ACL tear by MRI + No symptoms opposite knee• KT-2000 confirms 2 mm or greater side to side anterior displacement difference with legs in neutral rotation. • 9 ml 25% Dex. Inj. • Delayed @ 0, 1, and 2 mo Treatment with HRUS • Blinded 3 month KT-1000 ADD.• Inject at 3 months and • Inject at 3, 4, 5 and 6 then PRN symptoms at months and PRN at 6, and 9 months 9 months. Blinded 12 month KT-1000 ADD