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Dr. Bob is Robert Hsiung, MD,
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Posted by ed_uk on August 2, 2005, at 15:58:02
In reply to STUDY IN PROGRESS: haloperidol versus atypical APs, posted by ed_uk on August 2, 2005, at 15:42:07
Am J Psychiatry. 2005 May;162(5):947-53.
Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial.Schooler N, Rabinowitz J, Davidson M, Emsley R, Harvey PD, Kopala L, McGorry PD, Van Hove I, Eerdekens M, Swyzen W, De Smedt G; Early Psychosis Global Working Group.
Hurwich Professor, Bar Ilan University, Ramat Gan, Israel.
OBJECTIVE: The first episode of psychotic illness is a key intervention point. The initial experience with medication can affect willingness to accept treatment. Further, relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes. Thus, initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy. This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients. METHOD: First-episode psychosis patients (N=555, mean age=25.4 years) participated in a double-blind, randomized, controlled flexible-dose trial that compared risperidone (mean modal dose=3.3 mg) and haloperidol (mean modal dose=2.9 mg). The median treatment length was 206 days (maximum=1,514). RESULTS: Positive and Negative Syndrome Scale scores and Clinical Global Impression ratings improved significantly relative to baseline, with no significant differences between groups. Three-quarters of the patients achieved initial clinical improvement, defined as >20% reduction in total Positive and Negative Syndrome Scale score. However, among those who achieved clinical improvement, 42% of the risperidone group experienced a relapse compared with 55% of the haloperidol group. The median time to relapse was 466 days for risperidone-treated subjects and 205 days for those given haloperidol. These differences were statistically significant based on Kaplan-Meier survival analysis. Adverse effects distinguished the treatments: there were significantly more extrapyramidal signs and symptoms and adjunctive medication use in the haloperidol group and greater prolactin elevation in the risperidone group. There was less weight gain with haloperidol initially but no significant differences between groups at endpoint. CONCLUSIONS: Relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of first-episode psychosis patients. In the long term, risperidone prevents relapse in more patients and for a longer time and also induces less abnormal movements than haloperidol.
~ed
Posted by ed_uk on August 2, 2005, at 15:59:40
In reply to Re: Haloperidol (Haldol) » Declan, posted by ed_uk on July 30, 2005, at 17:02:36
I thought you might be interested in this.....
Neuropsychobiology. 2003;47(1):37-46.
Flupenthixol versus risperidone: subjective quality of life as an important factor for compliance in chronic schizophrenic patients.Hertling I, Philipp M, Dvorak A, Glaser T, Mast O, Beneke M, Ramskogler K, Saletu-Zyhlarz G, Walter H, Lesch OM.
Department of Psychiatry, University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
OBJECTIVE: The primary aim of this paper was to compare the effects of flupenthixol and risperidone on subjective quality of life and attitude towards medication in chronic schizophrenic patients with mainly negative symptoms. In a spectrum ranging from its typical end "haloperidol" to its atypical end "clozapine", flupenthixol has typical and atypical characteristics. METHODS: The effects of flupenthixol versus risperidone were investigated in a multicenter, double-blind trial, whereas subjective quality of life was assessed by means of the EuroQuol-Visual Analogue Scale and the patient satisfaction questionnaire. The attitude towards medication was assessed by means of the Drug Attitude Inventory-30 (DAI-30). RESULTS: Mean daily dose of study medication was 6.6 (SD 2.9) mg/day flupenthixol and 3.6 (SD 1.2) mg/day risperidone. Both groups showed a significant improvement regarding subjective quality of life and positive attitude towards medication. Especially the categories "control of their thoughts", concentration and "feeling better in general" ameliorated in both groups. In the flupenthixol group, the "ability to cope with stress", "feel more relaxed" and the "ability to achieve something" improved significantly more than in the risperidone group. CONCLUSIONS: (1) The spectrum of schizophrenia can be treated effectively with different neuroleptic treatments. (2) Flupenthixol especially improves the ability to cope with stress, the ability to achieve something and feeling more relaxed. (3) Subjective quality of life significantly increased with no difference between the groups.
~Ed
Posted by xbunny on August 2, 2005, at 18:31:27
In reply to A post for xbunny...., posted by ed_uk on August 2, 2005, at 15:59:40
> I thought you might be interested in this.....
thanks that is pretty interesting and its interesting to see flupenthixol represented as a atypical/typical crossover drug.
I was also interested by your discussion of haldol and dopamine receptor site occupation. Does the same hold true for flupenthixol or is it weaker? What does it really mean that say 70% of the receptor sites are occupied by the drug? What would happen if 100% were occupied? is there an optimal value? Oh and whilst I am asking questions, the TD thread got me wondering what are my chances of getting TD given that I take 6-9mg of flupenthixol and 20mg of pericyazine daily? Does the fact that I have been taking the flupenthixol for some years mean I am less likely to develop it? I was also wondering if theres any reason why I shouldnt take my flupenthixol as a single morning dose as I have been doing? does flupenthixol hang around long enough to build up and not require split doses like recommended in the leaflet? certainly I havent noticed any ill effects!Lots of questions tonight lol hope you are well.
Buns
Posted by ed_uk on August 3, 2005, at 15:16:08
In reply to Re: A post for xbunny.... » ed_uk, posted by xbunny on August 2, 2005, at 18:31:27
Hi Buns!
>Does the same hold true for flupenthixol or is it weaker?
Flupenthixol is said to be similar in antipsychotic potency to haloperidol. 6mg flupenthixol is said to be approximately 'equivalent' to 6mg haloperidol. However.......... no dose of flupenthixol is truly equivalent to haloperidol because flupenthixol and haloperidol have different receptor affinities. Haloperidol is a selective D2 antagonist whereas flupenthixol antagonises D1, D2 and (less so) 5-HT2 receptors.
>What does it really mean that say 70% of the receptor sites are occupied by the drug?
At any one time, 70% of D2 (dopamine type 2) receptors in the brain are occupied by a flupenthixol molecule. Flupenthixol binds to the D2 receptors but doesn't active the receptors like dopamine would. Flupenthixol simply 'sits' on the receptors and prevents them from being activated by dopamine ie. if flupenthixol is bound to a receptor, dopamine can't bind.
>What would happen if 100% were occupied?
Marked side effects would be present eg. dystonia, dysphoria, akathisia, parkinsonism, elevated prolactin levels.
>Does the fact that I have been taking the flupenthixol for some years mean I am less likely to develop it?
Since you can tolerate flupenthixol without taking an anticholinergic, the extrapyramidal side effects must be very mild. This is a good sign. The absence of EPS suggests that TD may be less likely to occur. Watch out for involuntary movements of the tongue, jaw and mouth. Fine (involuntary) movements of the tongue can be an early sign of TD.
>I was also wondering if theres any reason why I shouldnt take my flupenthixol as a single morning dose as I have been doing?
No, that's fine. Twice daily dosing is recommended initially but most people on long term maintenace treatment can take it as a single daily dose.
>..does flupenthixol hang around long enough to build up and not require split doses like recommended in the leaflet?
Yes, it has a long half-life - about 35 hours.
Kind regards
~Ed
Posted by ed_uk on August 3, 2005, at 16:36:30
In reply to Flupenthixol (Depixol) » xbunny, posted by ed_uk on August 3, 2005, at 15:16:08
Psychiatr Prax. 2003 May;30 Suppl 2:S94-6.
[Comparative effectiveness of flupenthixol and risperidone on negative symptoms of schizophrenia]
[Article in German]
Philipp M, Lesch OM, Schmauss M, Dose M, Glaser T.
Bezirkskrankenhaus Landshut, Prof.-Buchner-Strasse 22, 84034 Landshut.
The efficacy of flupentixol and risperidone were compared in a randomized double-blind study in 153 chronic schizophrenic patients. Flupentixol showed to be not inferior to risperidone concerning schizophrenic negative symptoms at week 8, 16 and 24. Positive symptoms and general psychopathology improved comparably, too. There was a trend in favor of flupentixol concerning the improvement of depressive symptoms and a trend in favor of risperidone concerning the improvement of preexisting parkinsonian symptoms. The study data justify to regard flupentixol as a "partial atypical" antipsychotic.
Fortschr Neurol Psychiatr. 2000 Apr;68 Suppl 1:S38-41.
[Flupenthixol--a partial atypical neuroleptic?]
[Article in German]
Kuhn KU, Meyer K, Maier W.
Klinik und Poliklinik fur Psychiatrie und Psychotherapie Rheinische Friedrich-Wilhelms-Universitat Bonn. k.u.kuehn@uni-bonn.de
There is no really clear-cut definition for "atypical" neuroleptics. The most convincing definition is draft by characterization of the receptor-binding profile. Most important are: the combined antagonism of D2 and 5-HT2 receptors, the preferential binding to D4 and D3 receptors and a balanced relation of D2 to D1 antagonism. Flupentixol fits into this description as well as some modern neuroleptics widely considered as "atypical" neuroleptics. Clinical criteria--like the absence of EPMS and the improvement of negative symptoms--offer no clear-cut distinction between "typical" and "atypical" neuroleptics, too, because some modern "atypical" neuroleptics lead--dose-dependent--to EPMS, and there is no proven efficacy for some atypical neuroleptics in the treatment of negative symptoms. So, neuroleptics are labelled "atypical" if there is a favourable relation between antipsychotic activity and the degree of EPMS, and if there is at least some efficacy in the treatment of negative symptoms. In this regard, Flupentixol has to be labelled at least a "partial atypical neuroleptic".
~ed
Posted by ed_uk on August 6, 2005, at 13:53:51
In reply to Haloperidol (Haldol), posted by ed_uk on July 29, 2005, at 15:57:15
Hi Zeugie!
I just found this..........
'I took a typical antipsychotic (Trilafon) many years ago. The problem as you mention was dosage: at one point I was on 48 mg a day and all I wanted to do was sleep. It probably had a 'calming' effect..........'
Wow, 48mg! That's a LOT! Probably far too much! Can you tell us more about how it affected you? How were you affected by lower doses?
Kind regards
~Ed
Posted by ed_uk on August 6, 2005, at 14:12:55
In reply to Re: Perphenazine (Trilafon) - to zeugma » ed_uk, posted by ed_uk on August 6, 2005, at 13:53:51
Posted by ed_uk on August 6, 2005, at 14:19:54
In reply to Re: Perphenazine (Trilafon) - to zeugma » ed_uk, posted by ed_uk on August 6, 2005, at 13:53:51
Hi Scott,
You mentioned in a previous post that you'd been on chlorpromazine (Thorazine), perphenazine (Trilafon) and fluphenazine (Prolixin).
Were you prescribed these drugs to treat acute mania? What doses did you take? Were they effective? Side effects?
~ed
Posted by zeugma on August 6, 2005, at 15:58:35
In reply to Re: Perphenazine (Trilafon) - to zeugma » ed_uk, posted by ed_uk on August 6, 2005, at 13:53:51
> Hi Zeugie!
hi Ed! Been a long time, huh? A crazy stretch of months- but then, there has been no stretch of my life longer than, say, five minutes that is truly otherwise...
>
> I just found this..........
>
> 'I took a typical antipsychotic (Trilafon) many years ago. The problem as you mention was dosage: at one point I was on 48 mg a day and all I wanted to do was sleep. It probably had a 'calming' effect..........'
>
> Wow, 48mg! That's a LOT! Probably far too much! Can you tell us more about how it affected you? How were you affected by lower doses?
>I had severe Parkinsonism, for which I was on a massive dose of benztropine (no 'dumb-drug' euphoria that I remember, alas). If I am normally one stage away from comatose, then Trilafon had me in a coma. It became increasingly difficult to stay awake as the dosage was increased, and the already huge quantities of coffee that I was drinking became proportionally ineffective as the dose the was raised. I believe that my constant requests to have the 'free time' I was allowed (I was in a hospital) to be spent in bed were interpreted by the staff as antisocial behavior, and so the dose went up, 'antisocial' symptoms presumably a sign of schizophrenia.
I did not like Trilafon at any dose. But I think that maybe if the dosage had not escalated so drastically that I might have been less miserable on it. I was lethargic and 'out of it' on trilafon at any dose, but then I am 'out of it' when not on stimulants anyway.
-best,
z
Posted by ed_uk on August 6, 2005, at 16:25:30
In reply to Re: Perphenazine (Trilafon) - to zeugma » ed_uk, posted by zeugma on August 6, 2005, at 15:58:35
Hi Z!
>Been a long time, huh?
It's great to have you back! :-D
>Perphenazine dose
The usual maximum dose for schizophrenia and acute mania is 24mg/day. I've heard of people benefiting from ~2-4mg/day for severe anxiety.
>I was in a hospital...
For depression? For what reason were you prescribed perphenazine? Just out of curiousity, how old were you at the time?
Kind regards
~Ed
PS. I wrote a post to you above - about ramelteon (Rozerem).
Posted by ed_uk on August 6, 2005, at 16:29:31
In reply to Re: Perphenazine (Trilafon) - to zeugma » ed_uk, posted by zeugma on August 6, 2005, at 15:58:35
Hi again Z!
Did you suffer from akathisia on perphenazine? Did benztropine help?
~Ed
Posted by SLS on August 7, 2005, at 8:51:17
In reply to Fluphenazine (Prolixin) - to SLS (Scott), posted by ed_uk on August 6, 2005, at 14:19:54
> Hi Scott,
>
> You mentioned in a previous post that you'd been on chlorpromazine (Thorazine), perphenazine (Trilafon) and fluphenazine (Prolixin).
>
> Were you prescribed these drugs to treat acute mania?The Prolixin and the Thorazine, yes. The perphenazine was given to me much earlier in my "career" to help deal with anxiety and derealization.
> What doses did you take?
I haven't a clue.
> Were they effective?
Generally speaking, they helped with the acute mania, but not as much as Depakote or Zyprexa.
> Side effects?
Thorazine produced some EPS. I was sticking my tongue out at everybody involuntarily in the hospital. How embarrasing. It really was an assault on my dignity.
- Scott
Posted by zeugma on August 7, 2005, at 9:59:08
In reply to Re: Perphenazine (Trilafon) - to zeugma » zeugma, posted by ed_uk on August 6, 2005, at 16:25:30
>
> The usual maximum dose for schizophrenia and acute mania is 24mg/day. I've heard of people benefiting from ~2-4mg/day for severe anxiety.I was severely anxious when entering the hospital.
>
> >I was in a hospital...
>
> For depression? For what reason were you prescribed perphenazine? Just out of curiousity, how old were you at the time?
>
age: 21. Perphenazine was the second drug prescribed, after molindone. I was retropsectively diagnosed with depression, but I think the initial diagnosis was schizophrenia. I think the clinicians thought I was delusional.-z
> Kind regards
>
> ~Ed
>
> PS. I wrote a post to you above - about ramelteon (Rozerem).i'll look at the ramelteon post as soon as I feel I can digest it- I had never heard of this drug.
-z
Posted by ed_uk on August 7, 2005, at 14:33:26
In reply to Re: Fluphenazine (Prolixin) - to SLS (Scott), posted by SLS on August 7, 2005, at 8:51:17
Hi Scott,
>> What doses did you take?
>I haven't a clue.Presumably the doses of Prolixin and Trilafon were quite low if you suffered a dystonia in response to Thorazine but not Prolixin or Trilafon.......... or perhaps the dose of Thorazine was quite high? Prolixin and Trilafon cause dystonias more frequently than Thorazine - at 'equivalent' doses.
~Ed
Posted by ed_uk on August 7, 2005, at 14:36:31
In reply to Re: Perphenazine (Trilafon) - to zeugma » ed_uk, posted by zeugma on August 7, 2005, at 9:59:08
Hi Z,
How were you affected by molindone? Have you taken any other APs?
>.....i'll look at the ramelteon post as soon as I feel I can digest it- I had never heard of this drug.
That's ok - read it when you've got the time (and energy).
Kind regards
~Ed
Posted by zeugma on August 8, 2005, at 18:44:13
In reply to Re: Perphenazine (Trilafon) - to zeugma » zeugma, posted by ed_uk on August 7, 2005, at 14:36:31
> Hi Z,
>
> How were you affected by molindone? Have you taken any other APs?
>I was not in a particularly receptive mode to pharmacological interventions when I was forced to sample molindone. I had had a harrowing experience with prozac not long before and was so naive (read: pre-Internet days) that I had no idea about the different classes of psych meds. I think perphenazine is more sedating, which 'calmed me down' enough to tolerate the drug minimally.
Perphenazine's sedation probably masked the akathisia that was (as best i recall) the reason for d/x'ing molindone, and I also developed intensified akathisia on Prozac. I have akathisia anyway, though less as I've gotten older and more lethargic.
> >.....i'll look at the ramelteon post as soon as I feel I can digest it- I had never heard of this drug.
>
> That's ok - read it when you've got the time (and energy).Time, energy, and focus. That third variable that is so essential and so elusive. I wrote this post on the bus,where focus was easier to come by, and am typing from memory. Focus..
-z
>
> Kind regards
>
> ~Ed
Posted by ed_uk on August 9, 2005, at 13:26:59
In reply to Re: Perphenazine (Trilafon) - to zeugma » ed_uk, posted by zeugma on August 8, 2005, at 18:44:13
Hi Z!
>prozac
I can't remember whether you've tried any other SSRIs. Perhaps you could try citalopram for your anxiety, starting at a very low dose - say 2.5mg.
>I wrote this post on the bus
You've got a good memory!
~Ed
Posted by zeugma on August 9, 2005, at 18:54:04
In reply to Re: Perphenazine (Trilafon) - to zeugma » zeugma, posted by ed_uk on August 9, 2005, at 13:26:59
> Hi Z!
>
> >prozac
>
> I can't remember whether you've tried any other SSRIs. Perhaps you could try citalopram for your anxiety, starting at a very low dose - say 2.5mg..hi Ed,
yes, that's the plan, if it comes to that- if I need further augmentation. I mentioned a good while ago that my pdoc gave me Lexapro samples in response to my suggestion about clomipramine. He told me 2.5 mg would be the place to start with those.
It's just that I have this feeling that more meds = multiplying s/x, and that my body is near its limit of reasonable toleration, with 100 mg nortriptyline, 200 mg Provigil, 30 mg buspirone, and 1 mg clonazepam daily. I'm substituting 30 mg Ritalin LA for the Provigil for the time being, because of an interaction with an antifungal, with reasonable results (I don't have to work long hours in the summer, so I can deal with Ritalin's ridiculous half-life as an annoyance).
As a matter of fact, my pdoc had to twist my arm to take buspirone, which is nearly side-effect free. And the buspirone does 'take the edge off'.
but yes, the plan is to take lex as the next AD, if needed. But I really don't want to take more meds.
by the way, my anxiety has improved after switching from Provigil to the low dose of Ritalin. I think the modafinil was building up in my system,due to the interaction with clotrimazole, causing it to become as anxiogenic as 60 mg Ritalin, if not more so. It suggests that 200 mg Provigil is my limit for anxiogenicity. Of course, being underdosed with a stim causes a horrible anxiety of its own, owing to the fact that I am in such a wretched haze. I think I'm finding a therapeutic window for stims, which is a good thing.
oh, and I tried Zoloft when it came out- AWFUL AWFUL AWFUL. I was in a nauseated fog.
-z
Posted by ed_uk on August 10, 2005, at 14:24:52
In reply to lex- and therapeutic window for stims » ed_uk, posted by zeugma on August 9, 2005, at 18:54:04
Hi Z!
>Lexapro (escitalopram)....
Too expensive. Try generic citalopram (Celexa) first!
>....It's just that I have this feeling that more meds = multiplying s/x.......
You don't take that many meds! A woman came to the pharmacy today with 5 (full) prescription forms - 25 drugs. This isn't uncommon.
>clotrimazole...
In the UK, clotrimazole only comes as a cream and a pessary. How are you taking it? - obviously not as a pessary LOL ;-)
>oh, and I tried Zoloft when it came out- AWFUL AWFUL AWFUL. I was in a nauseated fog.
Hmm. Definately start with a very low dose if you try citalopram!
~ed
Posted by zeugma on August 10, 2005, at 17:48:38
In reply to Re: lex- and therapeutic window for stims » zeugma, posted by ed_uk on August 10, 2005, at 14:24:52
> Hi Z!
>
> >Lexapro (escitalopram)....
>
> Too expensive. Try generic citalopram (Celexa) first!Ed, how dare you make that suggestion! Don't you know that single-isomer drugs are TWICE AS GOOD as the racemate, in every case? (just kidding)
>
> >....It's just that I have this feeling that more meds = multiplying s/x.......
>
> You don't take that many meds! A woman came to the pharmacy today with 5 (full) prescription forms - 25 drugs. This isn't uncommon.
>
It's not a phobia of taking too many meds. It's that no matter what I add to nortriptyline, buspirone, and clonazepam (which added together don't give me too many side effects, but also do nothing for sleepiness and ADHD) starts to feel like 'too much' before too long, whether it's increased anxiety, appetite suppression, dry mouth, or 'vaguely toxic' feeling (Provigil).
> >clotrimazole...
>
> In the UK, clotrimazole only comes as a cream and a pessary. How are you taking it? - obviously not as a pessary LOL ;-)
>
I don't think so ;-) It comes as a 'troche' (slowly dissolving tablet).> >oh, and I tried Zoloft when it came out- AWFUL AWFUL AWFUL. I was in a nauseated fog.
>
> Hmm. Definately start with a very low dose if you try citalopram!I would (but I insist on the single isomer if it bankrupts me!). I'm sure citalopram (ahem, escitalopram) is nothing like Zoloft- consider the differences between nortriptyline and atomoxetine. But I was told by the sleep doc that SSRI's can be disruptive to sleep, which corroborates my research.
speaking of which, do you have any thoughts on Focalin, the d-isomer of methylphenidate? An XR version just came out, and this report claims it has a duration of action of 12 hours:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16026226&query_hl=4
-z
Posted by ed_uk on August 11, 2005, at 14:36:08
In reply to only single isomers for me » ed_uk, posted by zeugma on August 10, 2005, at 17:48:38
Hi Z!
>Ed, how dare you make that suggestion!
:-O
>It's that no matter what I add.........
....but surely the side effects depend on *what* you add ;-)
>........do you have any thoughts on Focalin?
I've haven't come across many people who've tried it. I've read nothing that suggests it would be superior to MPH. I suspect it's just a money making device but I could be wrong!
>An XR version just came out........
I never knew that! I just found this.....
http://www.docguide.com/news/content.nsf/news/8525697700573E188525700E00431D54
Kind regards
~ed
Posted by alohashirt on August 11, 2005, at 21:04:45
In reply to Focalin XR » zeugma, posted by ed_uk on August 11, 2005, at 14:36:08
I'm hoping to Focalin XR next month and will happily give feedback.
When I tried Focalin I found that the effects were very similar to the same dose of Ritalin, if anything it made me even grouchier than Ritalin.I wonder if the XR technology is the same technology used for Metadate? I know it isn't as sophisticated as the Concerta technology which makes me suspect that its duration will be shorter. I have always found that the time the ADHD meds are effective is between 60% and 80% of the documented time.
Unfortunately the amphetamines then keep me awake for another four hours after they stop working.
Posted by ed_uk on August 12, 2005, at 1:18:42
In reply to Re: Focalin XR, posted by alohashirt on August 11, 2005, at 21:04:45
Hi!
Please report your experience with Focalin XR :-)
~Ed
Posted by Paulbwell on August 13, 2005, at 7:14:35
In reply to Re: Focalin XR » alohashirt, posted by ed_uk on August 12, 2005, at 1:18:42
> Hi!
>
> Please report your experience with Focalin XR :-)
>
> ~EdAfter having been on stimulants SR and IR, I suspect Focalin XR is a Dope compamy stradety to extend a patent and make $$$.
Cheers
Posted by ed_uk on August 13, 2005, at 8:02:05
In reply to Re: Focalin XR, posted by Paulbwell on August 13, 2005, at 7:14:35
>I suspect Focalin XR is a Dope compamy stradety to extend a patent and make $$$.
It's all about $$$ in the pharm industry!
~Ed
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