Friday, December 12, 2014

Reiseleiterlatein


Gewöhnlich reise ich ohne Reiseleitung. Jetzt hatte es sich aber so ergeben, dass ich zwei Reisen mit Reiseleitung gebucht hatte. Das hat Vorteile, wenn man keine Zeit findet, eine Reise selber zu organisieren. Die erste Reise hatte eine hervorragende Reiseleitung. Da war jemand, der Spaß daran hatte, sich Wissen anzueignen und aus diesem Schatz Wissen zu vermitteln. Bei der zweiten Reise war dies ganz anders; es gab Allgemeinplätze, Wiederholungen, Hinweise auf spätere Darstellungen von Fakten („Da kommen wir noch näher dazu.“), die dann aber ausblieben, und eine merkwürdige Diktion (anstatt „Ich war müde“ müsste es in dieser Diktion heißen: „natürlich war ich eigentlich ein bissel müde“). Dieser Reiseleiter gab eine Wertung ab und sagte dann, dass man es so wertfrei sehen müsse. Da es ärgerlich war, habe ich mir bereits unter #MussteAnhören auf Twitter Luft gemacht.

„Der Strand hat 25 km LuftLinie.“

„XXX ist eine Campus Universität; da ist alles über die Stadt verteilt.“ ( Ja, gerade das nicht!)

„Die sich nicht wieder aufraffelten.“ (Ich raff es nicht, eh, ich raffel es nicht.)

„Dass man die DuftStoffe auch sieht.“

„Das ein bissel dazu und dann schau mer mal.“

„Der Golfplatz ist aufgepäppelt worden.“

 „Hohe Schlagzahl“ – nein, nicht Rudern, beim BaumFällen spricht man eher von Einschlag.

„Natürlich hat man dann ja auch noch zum Teil eine große Landflucht.“

„Das ist dann sehr, sehr, sehr, sehr bitter dann auch.“ (Da erinnerte ich mich an „Spam, Spam, Spam, Spam, Ham & Spam“.)

„Das ist dann klar, aber bedeutsam.“

„Wir werden dann noch sehen, wie es aussieht.“

„Lange, lange Regenfälle über eine lange Zeit.“

„Wasser ist ein großes Thema, damals wie heute immer noch.“

„Mittag ist dann ein bissel später; das ist ja dann kein Problem.“

„Kein klassischer Klassizismus“.

„Wir haben hier 25% der Bevölkerung und 80% der WirtschaftsLeistung, deshalb haben wir hier einen Ballungsraum.“

„Das war ihm eben sehr, sehr, sehr suspekt.“

„Da haben die oberen Zehntausend ihre Karnevals- und Weihnachtsfeiern getätigt.“

„Das ist das Spannende an Südafrika; natürlich ist es Land, das sich erst langsam von der Apartheid erholt, das ist ganz klar. Da sollte man vorsichtig sein; natürlich gibt es hier Korruption.“

„Das ist zum Teil sehr marode mit der Energie.“

„Trotzdem ist es eigentlich ganz spannend, was so passiert in so einem Land.“

„Diese Landvermesser haben es neu-amerikanisch gemacht; die Claims wurden abgesteckt.“ (Zum SchachbrettMuster der Straßen von Johannesburg)

„Das waren letztlich die großen Gewinner dann auch.“

„Natürlich hat auch ein Nelson Mandela hier gewohnt. Natürlich hat auch er hinter Stacheldraht hier gewohnt. Das ist natürlich eben so.“

„Wichtig ist natürlich auch so, dass die Schwarzen nicht an der Wirtschaft teilgenommen haben.“

„Hoffentlich ist kein Bus da, aber wir sind ja früh dran. Das ist dann kein Problem.“

„1904. Ein Friedhof, der aus dieser Zeit stammend ist.“

„In der Ruhe liegt die Bürgerpflicht.“

„Das ein bissel dazu, damit wir ein bisschen vorbereitet sind.“

Ja. Gut. Jetzt kann man natürlich vielleicht ein bissel überlegen, ob Reiseleiterlatein nicht doch zum Teil ein bissel übertrieben ist. Aber schau mer mal. „Das ist dann klar, aber bedeutsam.“



Tuesday, December 9, 2014

Iguratimod at the ACR 2014 in Boston


I have already been interested in iguratimod (IGU) for a while. I’ve blogged on IGU for the first time 2 ½ years ago after the EULAR meeting in Berlin (2012). I had been a bit disappointed in 2013, when there had been only a Chinese cell study (Iguratimod inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells) at the 2013 EULAR meeting in Madrid. Earlier this year at the EULAR meeting in Paris IGU returned with three posters/studies. Please see below. Iguratimod already has been approved for the Japanese market (2012); see below. It is marketed under the brand names Careram® and KOLBET®.

Y. Kanayama and colleagues presented the following study [#1488]: “Clinical Efficacy of Add-on Iguratimod Therapy in Patients with Active Rheumatoid Arthritis Despite of Methotrexate - a Multicenter Registry.” It#s hard to tell, what this study is. I think, the authors aggregated data from existing studies and looked at 51 patients, who fulfilled the ACR/EULAR criteria for RA and didn’t respond to MTX. DAS had been reduced from 4.67 to 3.32 after 24 weeks, CDAI from 16.9 to 7.9. Remission rates were 33.3% for DAS and 27.5% for CDAI. Conclusion: “This study suggested that the new combination therapy of add-on IGU with MTX was effective in patients with active RA with inadequate response to MTX.”

Y. Hirano and colleagues presented another study [#1489]: “Influences of Disease Activity at the Initiation of Iguratimod, a Small Molecule Antirheumatic Drug, on Efficacy of Iguratimod in Patients with Rheumatoid Arthritis –a Multicenter Registry Study”. They looked at 79 patients. The study period also had been 24 weeks. In results we find: “The mean DAS28-CRP at 0, 4, 8, 12 and 24w was 4.99, 4.49, 4.29, 3.70 and 3.58 in HG [high disease activity group] and 3.24, 3.16, 2.76, 2.62 and 2.56 in MLG [moderate and low disease activity group]. DAS28-CRP was significantly decreased after 4w in HG and after 8w in MLG.” Conclusion: “This study suggests that IGU is one of the options not only in RA patients with high disease activity treated with insufficient MTX.”

T. Kondo and colleagues presented a third study [#1497]: “Efficacy and Safety of Iguratimod for Rheumatoid Arthritis.” They looked at 62 patients, who received 25 mg iguratimod during the first month and who were changed to a dosage of 50 mg afterwards. “DAS28-ESR and SDAI decreased significantly from 4.49_1.33 to 3.09_1.12 and from 18.5_10.9 to 7.44_7.11 in 24 weeks respectively (P_0.01).” “Adverse events were digestive symptom (n=6), liver dysfunction (n=3), nasal hemorrhage (n=2) and so on. There’s no severe adverse event.”  Conclusion: Iguratimod was well tolerable and may have a good cost effectiveness. So iguratimod be a new useful option as small molecule DMARDs for RA patients in a manner similar to tofacitinib.”

Sorry, as much as I want a new DMARD to treat patients with RA, who can’t receive biologics, these studies aren’t convincing and won’t be sufficient to get an approval by FDA or EMEA for iguratimod. The studies didn’t define primary endpoints, consisted of aggregated data, weren’t blinded or placebo controlled. Kondo’s conclusions are far fetched: “may have a good cost effectiveness” (cost effectiveness hadn’t been tested), “similar to tofacitinib” (hadn’t been tested against tofacitinib). And were is data on radiographic progression? As tofacitinib has been mentioned – radiographic progression was one of the critical points for not having yet optained approval by EMEA.

I’m still in favour of iguratimod, but the company has to sponsor better powered and designed studies. These studies have to include data on radiographic progression.

Links:


Sunday, November 9, 2014

Cranes


I've just come to hospital to do my work on a nice Sunday afternoon in November. Suddenly I've heard noise. No, the kindergarten wasn't having a festivity. I've heard thousands of cranes (not wild geese) cattering as they were crossing the hospital and Meerbusch to the Southwest. 
Here are some of the pictures, I've been able to take a couple of minutes ago.









The airport of Düsseldorf (DUS) is quite near and you can see an airplane starting

I had to correct this post as cranes were passing the hospital. It must have been a couple of thousands of birds flying in formation and in waves first across the hospital and then a little further to the South.

28.11.2016:
Today I've found by chance some other pictures, I've taken a couple of years ago. 



 


Friday, November 7, 2014

FreitagsGedichte / #KurzLyrik 07.11.2014

 

Im Nu
    im Nu
Hob sich
Ein Wind
UmWehte
Mich
Und Dich
Und ach!
    Entführt
Den Schleier

Spalten
    Scheite
Wurden
GeSpalten
Im Feuer
Flackern
Schatten auf
In den Spalten
    Und spaltete
Worte

Schärfe
    die Schärfe
Des Frosts
Schnitt tief
Ins Fleisch
Aber
Mehr
Schnitt
    Der Frost
Der Erinnerung

Sterne
    Sterne scheinen
Durchs Küchen-
Fenster
Die Nacht
Ist
Schwarz
Und es
    Wuchern
EisBlumen

Loipe
    neben der
Loipe
Drei Schritte
Im
TiefSchnee
Und dann
    Schweigt
Der Wald

Steppe
    der Wind
Hebt sich
In der
Steppe
Der Schritt
Ist mutig
    Kommt
Immer an

Mond
    der Mond
Ist in der
Mitte
Durch-
Geschnitten
Aber dann
    Strahlt er
Doch noch

Butter
    trafen sich
Beim Buttern
Vor den
GeHöften
Ja, ja
    So wars
Einmal

ZugVögel
    der stille
See
Sah sie
Als Spiegelung
Vom Boot aus
    Sie zogen
Gen Süden

Wunde
    Harz floß
Aus der
Wunde
GeSchnitten
Vom rück-
    Setzenden
Auto

Reusen
    sie haben
Reusen
AufGestellt
In der Stadt
Und fangen
Alle
    Die nichts
Kaufen

Ruine
    das halb
VerBrannte
Haus
Eine Ruine
Und doch
In ihr
Tanzen
    Nachts
Die Elfen

Grube
    tiefer
GeGraben
Aber die
Grube
Ist noch
Zu klein
    Und doch
So tief

Kraxeln
    im Urlaub
Finde ich
Immer
Noch
In die
    ZerKraxelten
Berge

Gold
    in der
Pfanne
Blieb
Nichts
Kein Gold
Kein Jubel
    Aber viel
Schweigen


Weitere #KurzLyrik:
.

 

Thursday, November 6, 2014

Fibromyalgia Breakthrough?


Did I miss something? Fibrolief is advertised as a breakthrough. “Clinical studies indicate that the ingredients in this formulation are highly effective at reducing the symptoms related to Fibromyalgia”. This is topped with claims that “for others” (who?) “ingredients have achieved”:
  * “Reduction of lower back pain, headaches, joint and muscle pain
  * Reduced inflammation
  * Improved energy levels
  * Increased mental clarity diminishing the effects of fibro fog
  * A full nights sleep without waking up groggy”
I'm not sure if these are legally called health claims; anyway that would be the duty of the FDA to decide. Theses claims, however, warrant a closer look at the ingredients.

Turmeric
There’s turmeric/curcumin in Fibrolief. Sorry, no study on PubMed – search has been done with this strategy: ("Curcuma"[Mesh] OR "Curcumin"[Mesh] OR "curcuminoid synthase, Curcuma longa" [Supplementary Concept] OR "turmeric extract" [Supplementary Concept]) AND "Fibromyalgia"[Mesh]. As fibromyalgia isn’t an inflammatory disease, why should turmeric work?

Boswellia
“Boswellia is a popular herb used for its benefits in fighting inflammation.” It doesn’t even work in arthritis.  And so sorry, nothing on PubMed, too.

White Willow Bark Extract
“White Willow Bark extract contains the active ingredient salicin which is a Cox-1 and Cox-2 inhibitor, and acts as an anti-inflammatory and also reduces pain by inhibiting prostaglandins.” That’s true, but … NSAIDs work like a key, which has to be but on a slot, the enzyme Cox-a or Cox-2. No matter whether you take salicin, aspirin or any other NSAID, you need the same number of key to lock the enzymes. Salicin is more toxic like aspirin, which is more toxic than naproxen, Diclofenac, ibuprofen or Cox-2-inhibitors. Salicin doesn’t work in fibromyalgia, which isn’t surprising as NSAIDs generally aren’t of much use in fibromyalgia. Please look here: http://www.ncbi.nlm.nih.gov/pubmed/19746561. One could cite a plethora of studies that proved the inefficacy of NSAIDs in fibromyalgia pain.

Celery Seed Extract
“Celery seed extract has been used as a pain reliever for arthritis, fibromyalgia and gout. It is known to help reduce muscle spasms and to alleviate painful gas and bloating. It is also known to aid in improving the painful symptoms of fibromyalgia sufferers by reducing inflammation.” How could symptoms of fibromyalgia be alleviated by reducing inflammation? And you guessed right, there’s no study on PubMed addressing fibromyalgia and celery seed extract.

Malic Acid/Malate
There has indeed be a study in 1995. IJ Russell and colleagues published: “Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study.” The study had been done in 24 patients, which is quite low. In results we are informed: “No clear treatment effect attributable to Super Malic was seen in the blinded, fixed low dose trial.” Conclusions: “These data suggest that Super Malic is safe and may be beneficial in the treatment of patients with FM. Future placebo-controlled studies should utilize up to 6 tablets of Super Malic bid and continue therapy for at least 2 months.” There have no further studies and may be is wishful thinking. The results didn’t show an effect.

Rhodiola Rosea
No study on rhodiola rosea and fibromyalgia. There is a study in mice on nociceptive pain: “Synergistic interactions between the antinociceptive effect of Rhodiola rosea extract and B vitamins in the mouse formalin test.” But pain in fibromyalgia is non-nociceptive!

Coenzyme Q10
“Coenzyme Q10 (CoQ10) A powerful Antioxidant”. There are studies going on, but in the last decade only small studies (N=5) or other pilot studies have been published. I don’t think that there’s the foundation for a breakthrough, but waiting for the result, especially for the dosing is a good idea.

Bacopa Monnieri
Nothing on fibromyalgia and bacopa monnieri.
SAM-e
“SAM-e is made from amino acid methionine and ATP. Studies have shown its effective for arthritis pain and shows both analgesic and anti-inflammatory properties.” I’ve already written about the futility of using SAM-e in fibromyalgia n this blog: http://rheumatologe.blogspot.de/2014/08/sam-e-and-fibromyalgia.html.

Magnesium
There is a deficiency in the general public. Eat a banana!

Vitamin D3
There also is a deficiency in the general public in vitamin D3. But in the US you already have lots of D3 fortified foods. And most people live 10° South of for instance Germany. Four times 3000 IU vitamin D3 per day might be an overdose.

Stabilized R-Alpha Lipoic Acid
Nothing on fibromyalgia and alpha lipoic acid on PubMed.

Zinc
There has been a Turkish study in 2008 seeing low levels of zinc in fibromyalgia patients, but there’s no study showing that substitution of zinc improves fibromyalgia.

Black Pepper Bioperine
Nothing on fibromyalgia and black pepper bioperine on PubMed.


The ingredients of Fibrolief aren’t convincing in reducing fibromyalgia symptoms. And Fibrolief is a dietary supplement, which hasn’t to show efficacy like a drug. But the producers should be careful with health claims. As you would spend around 750 US $ per year on Fibrolief, you should be pretty sure that it works. I would feel better with a scientific study on the effects of this product, but there is none. Would I buy Fibrolief? Nope! 

Wednesday, November 5, 2014

Leining, a novel cytotoxic T-lymphocyte antigen-4 fusion protein


I was a bit surprised to read about Leining, a novel cytotoxic T-lymphocyte antigen-4 fusion protein in patients with rheumatoid arthritis.
W. Fan and colleagues just published: “A randomized, double-blind, and placebo-controlled multicenter clinical trial of a novel cytotoxic T-lymphocyte antigen-4 fusion protein, Leining, in Chinese active rheumatoid arthritis patients with an inadequate response to methotrexate.” Conclusions: “Leining demonstrated clinically meaningful efficacy compared with placebo in Chinese patients with active RA despite MTX therapy. Administration of Leining in combination with MTX for 24 weeks was well tolerated.” Link: http://www.ncbi.nlm.nih.gov/pubmed/24671501.

There had been an article in Acta Pharmacologica Sinica in 2009: “Pharmacokinetics of CTLA4Ig fusion protein in healthy volunteers and patients with rheumatoid arthritis” by Y. Ma and colleagues – a phase 1 study! Conclusions: “Intravenous infusion of CTLA4Ig was well tolerated in healthy volunteers and patients with rheumatoid arthritis. CTLA4Ig exhibited linear pharmacokinetics over the dose range of 1 to 20 mg/kg in healthy volunteers. The pharmacokinetics in RA patients appeared to be similar to that in healthy volunteers. No system accumulation appeared upon repeated infusions of 10 mg/kg every 4 weeks.” Link: http://www.nature.com/aps/journal/v30/n3/abs/aps200913a.html.

Leining looks like a biosimilar to abatacept (Orencia) to me. In abatacept the extracellular domain of CTLA-4 and the Fc region of the immunoglobulin IgG1 are fused together. As I couldn’t find anything on it, I’ve contacted W. Fan and colleagues to tell us, whether Leining is a biosimilar to abatacept or what else it is. 

23.08.2016:
I've never reiceived an answer to my email, but I have looked into other sources. Leining is tested for Shanghai CP Guojian Pharmaceutical, who already has introduced Yisaipu, a biosimilar to etanercept. Leining is indeed planned as a biosimilar to abatacept, but four years later it still isn't approved or manufactured for sale. Since 1st of Dec. 2011 Leining holds a preregistration for rheumatoid arthritis in China. No new developments since then, at least none that left traces on the internet. (Links: http://adisinsight.springer.com/drugs/800039891 http://www.cpgj-pharm.com/Products.asp?id=7)

Monday, November 3, 2014

White Wedding in Central Asia


Since a visit to Guangzhou (广州), where I've watched the steady come and go of newly weds with their photographer from sitting at a Starbucks sipping at my coffee, I am interested in the phenomenon. And I've seen people taking white wedding photographs all over the world.


Lining up for photographs


A happy couple waiting for their turn


Doesn't this happy woman make your day?

 Needless to say I looked out, when and where couples were to be seen. Oh, Turkmenistan. I nearly forgot Turkmenistan. It's forbidden in Turkmenistan to take photographs of weddings, at least tourists aren't allowed to take pictures. Besides the streets of Ashgabat are as empty as a ghost town.

But already in Khiva, the first town I've visited in Uzbekistan, I could see, that white weddings are en vogue in Uzbekistan.



Wedding planning in Khiva


Wedding photography near Lyabi Hauz in Bukhara

Then it took a while until I chanced upon a white wedding, but I saw a couple in Tashkent, who was nice enough to let me take the photograph: it had been pitch dark and the flash wasn't as good as needed, I have to admit.


Wedding in Tashkent

In Kyrgyzstan couples go to Freedom Square (commemorating World War II) to place some flowers at the monument have their pictures taken.


Freedom Square with the Yurt


A couple with the photographer taking a video


You will notice that also the white wedding is established in the Muslim world, at least in Central Asia.