Forum Replies Created
-
AuthorPosts
-
In Australia the forecast was for a 230% increase in the death rate over the next 15 years.
Worldwide we are running at 500,000 deaths a year, so without action that’s on a trajectory towards exceeding a million preventable deaths per annum over the next decade.
The USA invaded Iraq on the pretext of it having Weapons of Mass Destruction but seems powerless to control the behaviour of its own corporate citizens, but then again Gilead are incorporated in Ireland for tax reasons.
http://www.bloomberg.com/research/stocks/private/snapshot.asp?privcapid=22613423
YMMV
Daclatasvir is active against L31M mutation. Ledipasvir is not, so Daclatasvir is better.
12 weeks + Riba is only one change – 2 changes would be better – Daclatasvir or 24 weeks (or both).
Resistance Profiles:
- Ledipasvir: M28T, Q30R, L31M, H58D, Y93H
- Daclatasvir: M28T, Q30R, H58D, Y93H
YMMV
Assuming that the patients were taking their medication daily, and that their medication was good quality, and that it’s not a <15 detected (because this may SVR - Tina here was <15 DET at EOT, UND @ SVR2 and UND @ SVR4)
Virological breakthrough happens when the patient's remaining HCV virus is not efficiently killed by the medications being taken and can continue to grow in their presence.
Resistant mutants are not created by taking DAAs. They are created because the HCV replication process does not reliably produce accurate copies of the original RNA genetic code. Most of these inaccurate copies (mutants) produce nonfunctional, or poorly functional viruses, however some may be resistant to drugs.
When we give drugs all the other HCV gets killed, and like weeds in a garden the mutants now have a chance to grow.
Although Sofosbuvir resistance is rare it is possible. In the original dose scoping trial for Sofosbuvir a dose of 200 mg suppressed virus on treatment to < LLOQ for 100% , but at EOT only 94% were still < LLOQ. SVR was 90%. On the dose of 400 mg on treatment and EOT were 100%. Interestingly SVR was only 1% higher - 91% The next step for patients who have relapsed depends on how sick they are. If they are not sick careful consideration should be given to waiting - as more people fail DAAs we learn more. If they are sick and must be treated urgently: 1b - Sof+Dac+/-Riba, Sof+Dac+Simeprevir or Viekira Pak would be reasonable options 2 - Sof+Dac+/-Riba, Sof+Dac+Simeprevir would be a reasonable options (note that the total reported trials for Sof+Dac in GT2 are 49/53 although I have some unpublished data that will increase those numbers) Note that Simprevir is active against all but GT3 - http://www.catie.ca/en/treatmentupdate/treatmentupdate-191/anti-hcv-agents/simeprevir-and-different-strains-hcv (GT1 is not mentioned but it is in the guidelines for GT1 with Sof)
In broad terms for retreatment we would pick at least one, probably 2, and maybe all 3 of:
1) Use different drug(s) - the resistance profile for each varies a bit
2) Treat for longer
3) Add something extra - (proven) Riba, Simeprevir (not GT3), or (experimental) Chlorcyclizine
YMMV
No it won’t make any difference but for peace of mind pm me your address and I will make one arrive.
YMMV
If you urinary infection is not getting better you are taking the wrong antibiotic.
With an acute UTI – when I do not have culture and sensitivity results – I randomly pick from Amoxil, Keflex and Trimethoprim knowing there is about a 30% resistance rate to each. If it does not work I change, and that is usually before the sensitivity results are back.
YMMV
Strangely his full blood test doesn’t have a platelet count or I would have used the tool.
Are you sure it’s not buried in there somewhere. I’ve seen Hb only but never seen a Full Blood Count without Platelets, that would be like the “Glass 1/2 Full Blood Count” or worse still if you drink a bit “The Claytons Full Blood Count”
YMMV
Can anyone tell me what the ALT/AST ratio suggests?
Normally the AST is less than the ALT.
When the AST is higher than the ALT it suggests (but does not prove) advanced fibrosis/cirrhosis. It is not a good sign.
It is calculated as AST/ALT so is > 1 (bad) when AST > ALT
The APRI score is better than the AST/ALT ratio. It is calculated from AST and Platelets. You can use the APRI calculator in our decision support tool at http://fixhepc.com/hcv (this also does AST/ALT)
If his platelets are anything less than 200 he will have an APRI of > 1 which suggests advanced fibrosis.
YMMV
Not long now Ariel……EOT bloods will pick you up!!!! I wasn’t tired towards EOT but as you know anxiety certainly settled in for a while just before and after EOT. Your road has been much longer than mine and physically you have battled much more than me but you have always lifted my spirits with your posts and beautiful photos. Hope you enjoyed your Nanna Nap
YMMV
Yes, it’s probably not a bad idea but unless you were one of those asymptomatic people with normal liver functions if you did relapse you would expect to feel sick and this to be obvious on your liver function tests.
After SVR24 maybe check it in a year to satisfy paranoia and declare yourself cured beyond all reasonable doubt.
YMMV
Hi Ken,
With any luck it should not matter. With a single dose to famotidine (not a PPI but like a PPI in action) primed dogs the AUC (Area Under The Curve) was about 50% less than without the antacid. Lower AUC means less drug means lower blood levels, however……
The 1/2 life (time taken to get rid of 1/2 the dose) of Ledipasvir is ~ 48 hours so once it’s in it hangs around for quite a while. That means what happens on any given day has very little impact on the steady state blood levels, and these levels were calculated to have a safety margin over the minimum requirement.
Say you took a PPI for 1/3 of your treatment, and this reduced absorbtion by 50% on those days. Overall that is only a 1/6th ie 17% average reduction.
Somebody who is 17% heavier than you already suffers from a 17% reduction in mg/kg concentration.
We know we don’t need to adjust the dose in large people so we can intuit that the base dose is well and truly enough, so don’t panic!
YMMV
So do you recommend being tested at 24 weeks as well and 4 & 12?
YMMV
As a pilot only two bad things can happen to you and one of them will.
- One day you will walk out to the aircraft knowing that it is your last flight in an aeroplane
- One day you will walk out to the airplane not knowing that it is your last flight in an aeroplane
YMMV
And continuing the aviation theme, what are the 3 most useless things to a pilot:
- Runway behind
- Altitude above
- Fuel in the truck
And of course the classic: “The only time you have too much fuel in an aeroplane is when you’re on fire”
YMMV
Do you know the difference between a good landing and a great landing?
A good landing is any landing you can walk away from
A great landing is when you can use the aeroplane for its intended purpose again….
YMMV
-
AuthorPosts