Hepatotoxicity by Drugs: The Most Common Implicated Agents.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Idiosyncratic drug-induced liver injury (DILI) is an underreported and underestimated adverse drug reaction. Information on the documented hepatotoxicity of drugs has recently been made available by a website that can be accessed in the public domain: LiverTox (http://livertox.nlm.nih.gov). According to critical analysis of the hepatotoxicity of drugs in LiverTox, 53% of drugs had at least one case report of convincing reports of liver injury. Only 48 drugs had more than 50 case reports of DILI. Amoxicillin-clavulanate is the most commonly implicated agent leading to DILI in the prospective series. In a recent prospective study, liver injury due to amoxicillin-clavulanate was found to occur in approximately one out of 2300 users. Drugs with the highest risk of DILI in this study were azathioprine and infliximab

Clostridium difficile infections. An increasing problem in westernized medicine [editorial]

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn Skoða/Opna(view/open)Clostridium difficile sýkingar (e. Clostridium difficile infections (CDI)) hafa verið þekkt heilsufarsvandamál í fleiri áratugi. Mikilvæg rannsóknarvinna hefur aukið þekkingu okkar á klínískum greiningaraðferðum, faraldsfræði og meðferð þessara iðrasýkinga. Tíðni CDI hefur farið vaxandi víðast hvar á Vesturlöndum og meinvirkari stofnar hafa komið fram. Faraldrar hafa einnig brotist út á mörgum stöðum í heiminum og fleiri alvarlegar sýkingar og aukin dánartíðni hafa fylgt í kjölfarið. Kostnaður heilbrigðiskerfisins hefur aukist að sama skapi sökum þessa. Afleiðingar CDI eru langvarandi spítalalegur vegna hvimleiðs niðurgangs, blóðsýkingar og lost í kjölfar hennar, ristilrof og brottnám ristils. Í byrjun þessa áratugar var lýst faröldrum í Quebec í Kanada af CDI þar sem tilfellum fjölgaði gífurlega ásamt fjölgun alvarlegra afleiðinga þessara sýkinga.1 Faraldrar þessir einkenndust af fjórum til fimm sinnum hærra nýgengi af CDI og aukinni dánartíðni frá 4,5% árið 1991 upp í 22% árið 2004.1 Faröldrum af þessu tagi hefur einnig verið lýst í Evrópu. Fjöldi CDI tilfella í Bandaríkjunum virðist sífellt fara vaxandi og á síðustu árum hefur verið áætlað að um 450.000-750.000 tilfelli eigi sér stað þar í landi á ári.2 Sterk tengsl á milli sýklalyfjanotkunar og CDI hefur verið þekkt áratugum saman en aukning af CDI tengd notkun prótónupumpuhemla hefur nýlega verið lýst.3-

Drug-induced liver injury

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn Skoða/Opna(view/open)Drug-induced liver injury (DILI) is a well known adverse reaction of many drugs. Direct toxic liver damage is associated with paracetamol toxicity whereas most other drugs causing liver damage have an unpredictable or idiosyncratic pattern of injury. Although idiosyncratic liver injury was initially thought to be dose independent, it has been shown that many drugs leading to idiosyncratic injury have a dose dependent component. Physicians need to bear in mind DILI in all patients who present with symptoms or signs of liver dysfunction. Clinically and histologically DILI can mimick any known liver disease and there are no pathognomonic histological features of DILI. The diagnosis is one of exclusion. In patients with a high clinical suspicion of DILI the causative drug need to be discontinued and patients with jaundice and/or coagulopathy have to be hospitalized and some cases considered for a liver transplantation. Bjornsson ES. Drug-induced liver injury. Icel J Med 2010; 96: 167-74 Key words: Drug-induced liver injury Correspondence: Einar S. Bjornsson, [email protected]ði af völdum lyfja er aukaverkun sem hefur tengst mörgum mismunandi lyfjum þótt sjaldgæf sé. Bein eitrunaráhrif tengjast of háum skömmtum af parasetamóli en flest önnur lyf sem orsaka lifrarskaða valda ófyrirsjáanlegum skaða. Þó að ófyrirsjáanlegur skaði hafi upphaflega verið talinn gerast óháð skammti hafa rannsóknir nýlega sýnt að lifrarskaði af þessu tagi getur í mörgum tilfellum verið háður skammti. Læknar verða að hafa lifrarskaða vegna lyfja í huga hjá öllum sjúklingum með afbrigðileg lifrarpróf eða einkenni um lifrarsjúkdóm. Skaðinn getur bæði klínískt og meinafræðilega líkst nánast öllum þekktum lifrarsjúkdómum og engin meinafræðileg auðkenni fyrirfinnast. Sjúkdómsgreiningin er útilokunargreining. Hjá sjúklingum sem taldir eru vera með lifrarskaða af völdum lyfja þarf að stöðva inntöku viðkomandi lyfja, og sjúklinga með gulu og/eða merki um lifrarbilun verður að leggja inn á spítala og í sumum tilfellum verður að íhuga lifrarígræðslu

Sudden Gains in Psychotherapy

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnMeð skyndiframförum (e. sudden gains) í sálrænni meðferð er átt við skyndilega og mikla lækkun á geðrænum einkennum skjólstæðings frá einum meðferðartíma til annars. Þessar skjótu framfarir fela oft í sér meira en helming þess heildarbata (t.d. lækkun einkenna á sjálfsmatskvarða) sem verður í meðferðinni. Einstaklingar sem sýna slíkar framfarir ná oft meiri árangri í meðferðinni en þeir sem sýna framfarir hægt og sígandi. Rannsóknir á skyndiframförum gætu því varpað ljósi á það hvernig sálræn meðferð leiðir helst til árangurs. Í þessari grein er veitt yfirlit um rannsóknir á skyndiframförum og rætt um þá aðferðafræðilegu annmarka sem hafa hrjáð þær. Gerður verður samanburður á skyndiframförum og öðrum algengum mynstrum í meðferð; snemmbúinni svörun (e. rapid early response) og þunglyndistoppum (e. depression spikes). Í lok greinar eru settar fram vangaveltur um hvaða lærdóma megi draga af þessum rannsóknum og hvernig best væri að rannsaka skyndiframfarirSudden gains in psychotherapy are characterized by large improvements between adjacent treatment sessions. Some studies have found that sudden gains account for the majority of participants´ total symptom improvements and that they predict better treatment outcomes. Research on sudden gains could provide important insights into the mechanisms of change in psychotherapy with implications for enhancing treatment effectiveness. However, research findings have been inconclusive as to why and how sudden gains occur. In this paper, we review research on sudden gains, discuss methodological shortcomings that have impeded sudden gains research and compare sudden gains to other common change patterns; rapid early response and depression spikes. In conclusion, we offer suggestions for future research on sudden gains

Secondary sclerosing cholangitis in critically ill patients: current perspectives.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesSecondary sclerosing cholangitis (SSC) is a term used for a group of chronic cholestatic disease affecting the intra- and/or extrahepatic biliary tree with inflammation and progressive stricture formation, which can lead to biliary cirrhosis. A newly recognized form of SSC is secondary sclerosing cholangitis in critically ill patients (SSC-CIP). Pathogenesis is believed to involve ischemic injury of intrahepatic bile ducts associated with prolonged hypotension, vasopressors administration, and/or mechanical ventilation in patients treated in the intensive care unit (ICU). Patients diagnosed with SSC-CIP have no prior history of liver disease and no known pathologic process or injury responsible for bile duct obstruction prior to ICU treatment. Reasons leading to ICU treatment are many including multitrauma, burn injury, cardiac surgery, severe pneumonia, other infections, or bleeding after abdominal surgery. Patients have in common prolonged ICU admission. SSC-CIP is associated with rapid progression to liver cirrhosis and poor survival with limited treatment options except a liver transplantation. Transplant-free survival is around 17-40 months, which is lower than in other SSC patients. During the initial stages of the disease, the clinical symptoms and biochemical profile are not specific and easily missed. Biliary casts formation may be considered pathognomonic for SSC-CIP since most patients have them in early stages of the disease. Increased awareness and early detection of the disease and its complications is considered to be crucial to improve the poor prognosis

Energy Injection Episodes in Gamma Ray Bursts: The Light Curves and Polarization Properties of GRB 021004

Several GRB afterglow light curves deviate strongly from the power law decay observed in most bursts. We show that these variations can be accounted for by including refreshed shocks in the standard fireball model previously used to interpret the overall afterglow behavior. As an example we consider GRB 021004 that exhibited strong light curve variations and has a reasonably well time-resolved polarimetry. We show that the light curves in the R-band, X-rays and in the radio can be accounted for by four energy injection episodes in addition to the initial event. The polarization variations are shown to be a consequence of the injections.Comment: 4 pages, 2 figures. To appear in ApJ

Severe cholestatic hepatitis due to large vessel vasculitis: report of two cases

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesGiant cell arteritis (GCA) is a vasculitis of medium and large sized vessels that occurs most often in people > 50 years of age with associated symptoms of fever, weight loss, headache and jaw claudication. Polymyalgia rheumatica (PMR), which is characterized by aching and stiffness in the shoulders, hip girdle, neck and torso, is intimately associated with GCA, and evidence suggests that GCA and PMR are two phases of the same disease. The occurrence of liver enzyme abnormalities in either of these conditions is rare. Furthermore, as these conditions occur most commonly in the elderly population who may be subject to polypharmacy, patients with elevated aminotransferases due to underlying GCA/PMR may mistakenly have their abnormal liver function tests attributed to drug-induced liver injury. Given the potential complications of these diseases if left untreated, including ischemic stroke and blindness, early recognition and treatment are critical. We report two patients who developed severe cholestatic liver enzyme elevation, which had been initially attributed to drug toxicity, but was ultimately caused by large vessel vasculitis, specifically GCA and PMR

Mortality associated with drug-induced liver injury (DILI)

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked File