Clinical Question of the Day Pilot Thread 4/18-4/19

[gotdrugs]

No one has 100% completely perfect answer... I certainly don't.

Somebody needs to take a screenshot of this quote.

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[Praziquantel86]

I got an interesting clinical question for you wizards! (too busy to answer yours i know im lazy).. I made a hypothetical clinical case based on the question in mind, but if you like, you can skip to bottom to get to the actual clinical question.

Patient is recovering hospital from acute renal failure due to a pre-renal insult, but has CKD stage to the point where their day to day crcl is 18. For whatever reason (lets say acute hospital related infection and bacteremia develops), they will be in the hospital long term (1-2 weeks) and needing VTE prophy ( hx of vte, current sepsis/bacteremia, ie they absolutely NEED VTE prophy). Initial choice is heparin SC. They develop HIT (confirmed) and you treat successfully short term with argatroban to the appropriate APTT indicator until their platelets go back up. After the platelets normalize, what do yo udo next, since heparin , lmwh, and fondaparinux are all contraindicated.



TL;DR version

Patient has ABSOLUTE need of VTE prophy, but is in ARF , CrCl=18 , HIT develops within days of hospital admission and is confirmed and treated with argatroban. Now that platelet count is normal, what do you use for VTE prophylaxis, given that heparin, LMWH, and fondaparinux all seem like inappropriate choices?

Would you continue DTI ? Start oral anticoagulation or antiplatelet therapy short term? Go with some oddball option?

I'll answer your question with a question - what level of anticoagulation does the patient need at this point? And for how long? This is for all the young'uns out there.

 

[type b pharmD]

I'll answer your question with a question - what level of anticoagulation does the patient need at this point? And for how long? This is for all the young'uns out there.

What do you mean by what level? ?

Prophylaxis is clearly indicated due to advanced age (forgot to put this in the case),prolonged immobility, bacteremia, and history of VTE.

For duration I would say for the duration of the hospital stay, or until infection resolves and patient is mobile. No clear indication for long term therapy.

 

[gotdrugs]

I'll answer your question with a question - what level of anticoagulation does the patient need at this point? And for how long? This is for all the young'uns out there.

His case is regarding HIT, not HITT. So what you are driving at is debatable.

 

[type b pharmD]

His case is regarding HIT, not HITT. So what you are driving at is debatable.

Yeah my original thoughts were , no HITT but definite coagulable state. But my question may be bolstered by having HITT in the picture, and off the top of my head I believe the person may need several months of anti-coag at that point and would be good to put on warfarin anyway. Just guessin here.

 

[Praziquantel86]

What do you mean by what level? ?

Prophylaxis is clearly indicated due to advanced age (forgot to put this in the case),prolonged immobility, bacteremia, and history of VTE.

For duration I would say for the duration of the hospital stay, or until infection resolves and patient is mobile. No clear indication for long term therapy.

By level I mean intensity of anticoagulation (therapeutic, prophylactic, something else).

His case is regarding HIT, not HITT. So what you are driving at is debatable.

But is there a difference in the way you treat HIT vs. HITT? What percentage of patients with HIT develop thrombosis without treatment? And in what time frame?

 

[type b pharmD]

By level I mean intensity of anticoagulation (therapeutic, prophylactic, something else).



But is there a difference in the way you treat HIT vs. HITT? What percentage of patients with HIT develop thrombosis without treatment? And in what time frame?

I believe it is 50% or greater will develop thrombosis. And man, your question just made me have to go look back at the literature again

edit: Warfarin is clearly indicated if thrombosis has developed, and should be used for 6 months... Still doesnt answer my question about short term treatment though.

 

[gotdrugs]

But is there a difference in the way you treat HIT vs. HITT? What percentage of patients with HIT develop thrombosis without treatment? And in what time frame?

Yep, the numbers you are thinking of in your head are regarding the acute timeframe regarding treatment(or lack of) with DTIs, not long-term. - why do you think CHEST has always specifically avoided this question? Because there is no clear answer at all.

Sorry, but you are barking up the wrong tree trying to pimp me with questions on this disease state.

BTW just for clarification- I would use warfarin, but not for as long as you are probably thinking and it's still not a black/white answer.

 

[Praziquantel86]

Yep, the numbers you are thinking of in your head are regarding the acute timeframe regarding treatment(or lack of) with DTIs, not long-term. - why do you think CHEST has always specifically avoided this question? Because there is no clear answer at all.

Sorry, but you are barking up the wrong tree trying to pimp me with questions on this disease state.

I'm not pimping you...just trying to generate conversation. And I know the guidelines don't address the situation, because yes, there has never been a good answer to this question.

So what is your time frame for cessation of full-dose anticoagulation? I think the literature supports a specific cutoff point, in addition to the underlying pathophysiology making sense.

 

[gotdrugs]

So what is your time frame for cessation of full-dose anticoagulation? I think the literature supports a specific cutoff point, in addition to the underlying pathophysiology making sense.

Define "the literature" if you mean "the literature" as in experts or a consensus view or a "gold standard" randomized controlled trial? If so, you are sadly mistaken. If by "literature" you mean a random article or two you or one of your preceptors pulled that will have a relatively poor trial design (or not even a trial at all, but case series or the such), sure you can show me something where those particular authors set a cutoff point in the hopes of making a name for themselves. You will find some articles that give a cut-off point, but it's not clearly defined or well-studied. It's arbitrary.

I would recommend 30 days of overall anticoagulation therapy (including the DTI portion), but that's somewhat arbitrary from reviews I've conducted and research I've conducted myself. And that's not an answer I'm always comfortable with.

All the "literature" regarding "a specific cutoff point" is very weak evidence.

Hence the debate.

So it comes down to as you were saying, what level of anticoagulation is appropriate for the patient. Not every patient is an appropriate candidate for 30 days of anticoagulation therapy in isolated HIT.

So to answer your question - I would absolutely treat HIT differently than HITT. (duration of anticoagulation)

EDIT: One last thing you should think of in your budding career is the following........what are the bleeding rates of giving warfarin for 30 days, 90 days, 180 days? Esp in the setting of isolated HIT? What's the literature-supported benefit? To really get all devils advocate up in here, let's say you say that you give a patient long-term anticoagulation therapy for isolated HIT (from your initial posts, I'm going to assume in your mind you think they warrant 3 to 6 months of therapy) and that patient gets a bleed. How much fun do you think a malpractice attorney would have with that case? You would be surprised.

 

[Praziquantel86]

Define "the literature" if you mean "the literature" as in experts or a consensus view? If so, you are sadly mistaken. You will find some articles that give a cut-off point, but it's not clearly defined or well-studied. It's arbitrary.

I would recommend 30 days of overall anticoagulation therapy (including the DTI portion), but that's somewhat arbitrary from reviews I've conducted and research I've conducted myself.

All the "literature" regarding "a specific cutoff point" is very weak evidence.

Hence the debate.

So it comes down to as you were saying, what level of anticoagulation is appropriate for the patient. Not every patient is an appropriate candidate for 30 days of anticoagulation therapy in isolated HIT.

So to answer your question - I would absolutely treat HIT differently than HITT. (duration of anticoagulation)

The "literature" isn't guideline-based, I'm referring to the few studies that have actually looked at this. My arbitrary reviews reviews have also pointed me to the 30 day cutoff - which is what I use in practice.

I disagree with the differentiation between HIT and HITT though - I believe they're one in the same (unless you're talking "Type 1" and "Type 2", but I don't think you are). The underlying pathophysiology is the same, and we have no clinical way of differentiating who will and will not progress to thrombosis.

The ultimate duration of anticoagulation depends on the underlying condition - but I wouldn't go less than 30 days in the majority of cases. To me, the risk of subsequent thrombosis is the most pressing issue.

ETA: In response to your Devil's advocacy - I'm not supporting 3 - 6 months of anticoagulation by any means, unless the underlying condition (e.g., non-provoked PE) would support that duration. In this patient, I would probably acutely treat for 30 days and then switch to prophylaxis if warranted. And malpractice lawyers would have a field day in either event if they really wanted to, so they wouldn't sway me one way or another.

 

[gotdrugs]

The "literature" isn't guideline-based, I'm referring to the few studies that have actually looked at this. My arbitrary reviews reviews have also pointed me to the 30 day cutoff - which is what I use in practice.

I disagree with the differentiation between HIT and HITT though - I believe they're one in the same (unless you're talking "Type 1" and "Type 2", but I don't think you are). The underlying pathophysiology is the same, and we have no clinical way of differentiating who will and will not progress to thrombosis.

The ultimate duration of anticoagulation depends on the underlying condition - but I wouldn't go less than 30 days in the majority of cases. To me, the risk of subsequent thrombosis is the most pressing issue.

See my post, I didn't say guidelines, I say strong evidence. It's not out there. Trust me.

You are contradicting yourself. You are saying you would treat HIT for 30 days. You should be treating HITT for longer than that.

 

[gotdrugs]

ETA: In response to your Devil's advocacy - I'm not supporting 3 - 6 months of anticoagulation by any means, unless the underlying condition (e.g., non-provoked PE) would support that duration. In this patient, I would probably acutely treat for 30 days and then switch to prophylaxis if warranted. And malpractice lawyers would have a field day in either event if they really wanted to, so they wouldn't sway me one way or another.

Actually, not really, unless you picked a piss-poor candidate for warfarin or majorly screwed up, you have PLENTY of evidence to support treating in HITT for that timeframe. Little crappy evidence at best in HIT.

 

[Praziquantel86]

See my post, I didn't say guidelines, I say strong evidence. It's not out there. Trust me.

You are contradicting yourself. You are saying you would treat HIT for 30 days. You should be treating HITT for longer than that.

You said expert consensus, which to me means guidelines. There was a bit edited in after that which I didn't see in my initial post. There are a few observational studies which I base my opinions on - not random articles my preceptors pulled. I agree, it's not the best evidence, and no, the authors do not point to a specific cutoff. I, however, do believe they support a cutoff.

And I am not contradicting myself. What I was getting at was the treatment of HIT in and of itself, which requires therapeutic anticoagulation for a period of time beyond the acute platelet recovery (my 30 day cutoff). Thrombosis should be treated as such, although the guidelines do not have a clear duration - however, it's probably reasonable to treat as a provoked VTE in that case. So yes, beyond 30 days to 3 - 6 months.

I think there's some circular logic going on between the two of us, and I'm not entirely sure we disagree on treatment.

 

[gotdrugs]

You said expert consensus, which to me means guidelines.

And I am not contradicting myself. What I was getting at was the treatment of HIT in and of itself, which requires therapeutic anticoagulation for a period of time beyond the acute platelet recovery (my 30 day cutoff). Thrombosis should be treated as such, although the guidelines do not have a clear duration - however, it's probably reasonable to treat as a provoked VTE in that case. So yes, perhaps beyond 30 days.

Sorry, when I did my edit, I added the "good" evidence part. There isn't any.

Not to get all semantics here, in a way you disagree with my differentiation of HIT and HITT, but you then say they same things I do regarding duration of treatment - hence you are differentiating too.

 

[gotdrugs]

BTW - to play devils advocate again, re-read the initial post regarding this debate. What factors for this patient make warfarin a little bit more questionable?

 

[Praziquantel86]

Sorry, when I did my edit, I added the "good" evidence part. There isn't any.

Not to get all semantics here, in a way you disagree with my differentiation of HIT and HITT, but you then say they same things I do regarding duration of treatment - hence you are differentiating too.

That is true - I think where I disagreed was during the initial treatment phase (not withstanding the thrombosis part). I think every patient requires a minimum duration of full anticoagulation, regardless of platelet recovery. And that is what I often see missed - platelets bounce back, switch to prophylaxis. Which I don't think is appropriate.

My apologies for the misunderstanding.

 

[gotdrugs]

Coagulopathies, mechanical ventilation

Cook's criteria, and what I believe also.

However, there is at least one disease state outside of those that is a quality measure that you add SUP.

It's not an easy answer to find, but will be impressed if someone does.

 

[gotdrugs]

That is true - I think where I disagreed was during the initial treatment phase (not withstanding the thrombosis part). I think every patient requires a minimum duration of full anticoagulation, regardless of platelet recovery. And that is what I often see missed - platelets bounce back, switch to prophylaxis. Which I don't think is appropriate.

My apologies for the misunderstanding.

Personally, in most cases, I agree with you, but you do realize we could very well be "wrong."

And even that said as to what I have been alluding to, I don't think every isolated HIT patient is warranted the risk of even 30 days of warfarin. The patient scenario presented gives a couple of factors that make warfarin a little tricky. (i.e. increased bleeding risk)

 

[gotdrugs]

QUESTION FOR 4/19

In which patients is stress ulcer prophylaxis actually indicated? Our medical interns can never get this right.

Follow-up question - do PPI increase or decrease your risk of VAP?

 

[Praziquantel86]

Personally, in most cases, I agree with you, but you do realize we could very well be "wrong."

And even that said as to what I have been alluding to, I don't think every isolated HIT patient is warranted the risk of even 30 days of warfarin. The patient scenario presented gives a couple of factors that make warfarin a little tricky. (i.e. increased bleeding risk)

Definitely noted - very few things are cut and dry (unless its a CMS metric). I wouldn't use warfarin in that patient, but I'll leave that to the students to debate.

Cook's criteria, and what I believe also.

However, there is at least one disease state outside of those that is a quality measure that you add SUP.

It's not an easy answer to find, but will be impressed if someone does.

There were a few missing in there, I thought.

 

[rxlea]

Follow-up question - do PPI increase or decrease your risk of VAP?

>>>Numerous randomized trials, using different doses
and various study populations, have provided controversial results
on the benefits of specific stress bleeding prophylaxis agents
in relation to the increased risk of VAP.

LOL I told you those guidelines were a page turner

EDIT:

Stress bleeding prophylaxis, transfusion, and hyperglycemia.

1. Comparative data from randomized trials suggest a trend
toward reduced VAP with sucralfate, but there is a slightly
higher rate of clinically significant gastric bleeding, compared
with H2 antagonists. If needed, stress bleeding prophylaxis
with either H2 antagonists or sucralfate is acceptable
(Level I).

 

[gotdrugs]

There were a few missing in there, I thought.

Depends on how you were taught and what you want to believe.

The "gold standard" trial by Cook back in the 90's showed exactly 2 independent risk factors for clinically significant stress-ulcer bleeding: Mechanical ventilation >48 hours and coagulopathy (which if memory serves for purposes of her student she defined as INR >1.5 but I could be wrong on that part, but regardless most clinicians extrapolate to all coagulopathies). There has not been any other study as well designed before or since.

All other "indications" (such as steroids, etc) that you will see out there (including our own ASHP guidelines in the late 90's) come from much lesser quality evidence. However, they are still used by some clinicians/institutions in varying degrees.

 

[gotdrugs]

>>>Numerous randomized trials, using different doses
and various study populations, have provided controversial results
on the benefits of specific stress bleeding prophylaxis agents
in relation to the increased risk of VAP.

LOL I told you those guidelines were a page turner

EDIT:

Stress bleeding prophylaxis, transfusion, and hyperglycemia.

1. Comparative data from randomized trials suggest a trend
toward reduced VAP with sucralfate, but there is a slightly
higher rate of clinically significant gastric bleeding, compared
with H2 antagonists. If needed, stress bleeding prophylaxis
with either H2 antagonists or sucralfate is acceptable
(Level I).

SInce you are really working at this - I'll throw you a bone, start looking for the outcomes of "ventilator bundles" and the components.

 

[gotdrugs]

BTW - back on hyponatremia.

IV conivaptan is an option.

The vaptans also run the risk of overcorrection.

In acutely symptomatic situations (i.e. seizures/coma) yes, the use of hypertonic saline is absolutely justified in those cases.

 

[bananaface]

So much for question of the day.

 

[owlegrad]

So much for question of the day.

A new thread for each question would make it easier to follow. Just saying.

 

[Its Z]

So much for question of the day.

I vote to have a separate pharmacy forum for healthcare system practice.

 

[Its Z]

A new thread for each question would make it easier to follow. Just saying.

Yup

 

[rxlea]

Yup

I vote that you start tomorrow's with the title Question of the Day 4/20 -blahblahblah?

 

[rxlea]

I vote to have a separate pharmacy forum for healthcare system practice.

Then we would need one for CVS vs. Walgreens (...and PBMs too) ...

 

[Its Z]

Then we would need one for CVS vs. Walgreens (...and PBMs too) ...

No we don't. Call it "Retail" and it's done.

It's not like we're going to have each forum for MD Anderson, NYU Med Center, Fletcher Allen, Mt Sinai, Cedars, etc..

 

[Eviscerate]

BTW - back on hyponatremia.

IV conivaptan is an option.

The vaptans also run the risk of overcorrection.

In acutely symptomatic situations (i.e. seizures/coma) yes, the use of hypertonic saline is absolutely justified in those cases.

Yes, from what I learned in a topic discussion I had, treatment is more justified if it happens acutely (onset occurs in < 3 days, versus chronic hyponatremia) and if it is symptomatic (which usually occurs when Na is <120, and symptoms include headache, lethargy, confusion, seizure, etc). However, you do NOT want to correct it to normal in the next 48 hours. The service typically used demeclocycline, and hadn't used the vaptans yet, but I have seen it used in other institutions.

 

[gotdrugs]

However, you do NOT want to correct it to normal in the next 48 hours. .

. To be more specific, how fast is too fast? (i.e. how much of a rise is safe in 24hrs, 48 hrs) Sometimes in that timeframe, you can actually hit the "normal" range in 48 hours and still be safe depending on where you started.

 

[psychoandy]

We don't load vanco! All dosing is based on a hospital nomogram targeting a 10-15 trough for all indications. I wasn't a believer at first, but I think the literature that has come out in the last year, year and a half really fails to support higher troughs at this point.

I am not an ID superstar like you and Z, but what recent literature fails to support higher troughs? All I have read this year is the linezolid/vanc MRSA trial in CID, where vanc troughs weren't even therapeutic until somewhere between day 7 and day 9 of treatment. I would love to beef up my primary literature, been slacking the past couple months.

also fwiw, I usually evaluate and (mostly) recommend loading dose per IDSA guidelines whenever I cover the unit/ED or see vanco written stat on the floor. especially if they're younger.

 

[VCU07]

SInce you are really working at this - I'll throw you a bone, start looking for the outcomes of "ventilator bundles" and the components.

How about the link to c. Diff? What to do what to do...

 

[Eviscerate]

. To be more specific, how fast is too fast? (i.e. how much of a rise is safe in 24hrs, 48 hrs) Sometimes in that timeframe, you can actually hit the "normal" range in 48 hours and still be safe depending on where you started.

Hmm, was it 10 mEq/L/day?

 

[PharmDstudent]

I got an interesting clinical question for you wizards! (too busy to answer yours i know im lazy).. I made a hypothetical clinical case based on the question in mind, but if you like, you can skip to bottom to get to the actual clinical question.

Patient is recovering hospital from acute renal failure due to a pre-renal insult, but has CKD stage to the point where their day to day crcl is 18. For whatever reason (lets say acute hospital related infection and bacteremia develops), they will be in the hospital long term (1-2 weeks) and needing VTE prophy ( hx of vte, current sepsis/bacteremia, ie they absolutely NEED VTE prophy). Initial choice is heparin SC. They develop HIT (confirmed) and you treat successfully short term with argatroban to the appropriate APTT indicator until their platelets go back up. After the platelets normalize, what do yo udo next, since heparin , lmwh, and fondaparinux are all contraindicated.



TL;DR version

Patient has ABSOLUTE need of VTE prophy, but is in ARF , CrCl=18 , HIT develops within days of hospital admission and is confirmed and treated with argatroban. Now that platelet count is normal, what do you use for VTE prophylaxis, given that heparin, LMWH, and fondaparinux all seem like inappropriate choices?

Would you continue DTI (and break the bank?) ? Start oral anticoagulation or antiplatelet therapy short term? Go with some oddball option? Do you risk renal dosing of fonda?

Im intersted in knowing what you guys think would be the most effective real world option based on the costs and overall likelyhood of efficacy. Personally I would probably pick warfarin on gut instinct alone, but am unsure if this is effective for VTE prophy. (edit.. looked up some articles, warfarin is good VTE prophylaxis .. and is still my top choice pick, but is it the best for this patient?)

Renal Impairment and Anticoagulant Dosing

1.4.6. We recommend that renal function be considered when making decisions about the use and/or the dose of LMWH, fondaparinux, and other antithrombotic drugs that are cleared by the kidneys, particularly in elderly patients, patients with diabetes mellitus, and those at high risk for bleeding (Grade 1A). Depending on the circumstances, we recommend one of the following options in this situation: avoiding the use of an anticoagulant that bioaccumulates in the presence of renal impairment, using a lower dose of the agent, or monitoring the drug level or its anticoagulant effect (Grade 1B).
http://chestjournal.chestpubs.org/content/133/6_suppl/381S.full
circa 2008



Does anyone else have a Zosyn continuous infusion protocol?

 

[gotdrugs]

How about the link to c. Diff? What to do what to do...

Actually in a ventilated patient it's easy to know what to do. (Which is what we are talking about here).

 

[gotdrugs]

Hmm, was it 10 mEq/L/day?

You are partially correct.

 

[VCU07]

Renal Impairment and Anticoagulant Dosing

1.4.6. We recommend that renal function be considered when making decisions about the use and/or the dose of LMWH, fondaparinux, and other antithrombotic drugs that are cleared by the kidneys, particularly in elderly patients, patients with diabetes mellitus, and those at high risk for bleeding (Grade 1A). Depending on the circumstances, we recommend one of the following options in this situation: avoiding the use of an anticoagulant that bioaccumulates in the presence of renal impairment, using a lower dose of the agent, or monitoring the drug level or its anticoagulant effect (Grade 1B).
http://chestjournal.chestpubs.org/content/133/6_suppl/381S.full
circa 2008



Does anyone else have a Zosyn continuous infusion protocol?

is arixtra ci?

 

[Carboxide]

I got an interesting clinical question for you wizards! (too busy to answer yours i know im lazy).. I made a hypothetical clinical case based on the question in mind, but if you like, you can skip to bottom to get to the actual clinical question.

Patient is recovering hospital from acute renal failure due to a pre-renal insult, but has CKD stage to the point where their day to day crcl is 18. For whatever reason (lets say acute hospital related infection and bacteremia develops), they will be in the hospital long term (1-2 weeks) and needing VTE prophy ( hx of vte, current sepsis/bacteremia, ie they absolutely NEED VTE prophy). Initial choice is heparin SC. They develop HIT (confirmed) and you treat successfully short term with argatroban to the appropriate APTT indicator until their platelets go back up. After the platelets normalize, what do yo udo next, since heparin , lmwh, and fondaparinux are all contraindicated.



TL;DR version

Patient has ABSOLUTE need of VTE prophy, but is in ARF , CrCl=18 , HIT develops within days of hospital admission and is confirmed and treated with argatroban. Now that platelet count is normal, what do you use for VTE prophylaxis, given that heparin, LMWH, and fondaparinux all seem like inappropriate choices?

Would you continue DTI (and break the bank?) ? Start oral anticoagulation or antiplatelet therapy short term? Go with some oddball option? Do you risk renal dosing of fonda?

Im intersted in knowing what you guys think would be the most effective real world option based on the costs and overall likelyhood of efficacy. Personally I would probably pick warfarin on gut instinct alone, but am unsure if this is effective for VTE prophy. (edit.. looked up some articles, warfarin is good VTE prophylaxis .. and is still my top choice pick, but is it the best for this patient?)

Newer drugs are a good option here. I would continue with argatroban because (from the info we have) the patient is tolerating it at this point. Not best choice for short term therapy. Lovenox could be TRIED as it is not certain that HIT will reappear with it and risk in general is lower, but I think argatroban is more appropriate in this patient.

 

[psychoandy]

is arixtra ci?

That is technically correct...the best kind of correct. But you could counter that one could monitor antiXa levels.

 

[owlegrad]

That is technically correct...the best kind of correct.

Ha! Love this.

 

[PharmDstudent]

Newer drugs are a good option here. I would continue with argatroban because (from the info we have) the patient is tolerating it at this point. Not best choice for short term therapy. Lovenox could be TRIED as it is not certain that HIT will reappear with it and risk in general is lower, but I think argatroban is more appropriate in this patient.

And what about the cost?

That is technically correct...the best kind of correct. But you could counter that one could monitor antiXa levels.

I thought he said abcdefg?

 

[Carboxide]

And what about the cost?


I thought he said abcdefg?

Cost is definitely going to be high here, but I really don't see another option. We COULD try warfarin but it takes so long to kick in that I'm not sure it's a good option for this patient. The cost of readmitting the patient/extended hospital stay due to another case of HIT would be much more expensive than this drug for a few weeks, I think.

 

[joetrisman]

No cqod 4/21?

 

[rxlea]

No cqod 4/21?

start one

 

[Its Z]

No cqod 4/21?

Clinical every other day?

 

[rxlea]

Clinical every other day?

Yeah whatever works