Hepatitis C

Hepatitis C is an increasingly common disease. Up to 90% of patients who have injected illicit drugs and between 7% and 10% of individuals who received blood or blood products prior to 1992 test positive for hepatitis C. Other risk factors include: 1) history of multiple sexual partners (though hepatitis C is much less readily transmittable sexually than the hepatitis B virus); 2) chronic hemodialysis treatment; 3) being the child of a hepatitis C positive woman; 4) tattoos or body piercings; and 5) needle stick accidents. Hepatitis C should also be suspected in anyone with unexplained elevated serum alanine aminotransferase (ALT) levels or signs of liver disease, such as jaundice or hepatomegaly.
Acute hepatitis C infection often does not come to clinical attention. Patients may experience nonspecific symptoms such as malaise, abdominal pain, and nausea. A few have jaundice. Acute hepatitis C infection progresses to chronic hepatitis C in approximately 75% of patients. It is chronic hepatitis C that is of chief concern to psychiatrists, especially those who work with chemically dependent populations.
The screening test for hepatitis C is the ELISA test for antibody to the hepatitis C virus (anti-HVC), which can sometimes give false-positive results. The confirmatory test is HCV RNA, which can distinguish between past and active infection. The recombinant immunoblot assay is no longer commonly used as a confirmatory test.
Patients with hepatitis C should be referred to an internist or GI specialist for further assessment, which in selected cases may include liver biopsy. Liver biopsy can be helpful in determining if the patient is likely to progress to cirrhosis, which occurs in about 20% of individuals with chronic hepatitis C, typically over a period of 20-40 years.

Treatment of hepatitis C is an evolving field. All patients with hepatitis C should be advised to abstain from alcohol, which accelerates the progression to cirrhosis and reduces the response to HCV treatments. Prime candidates for drug therapy include patients with persistently elevated ALT readings, detectable HCV RNA levels, and appropriate liver biopsy results [“liver biopsy results (if available) that show portal or bridging fibrosis or at least moderate inflammation or necrosis”]2. For those patients who are candidates for drug therapy, the current standard regime is weekly subcutaneous pegylated interferon alpha plus oral ribavarin for six to twelve months, depending on HCV genotype. The response rate is approximately 50% but varies depending on HCV genotype. Common side effects of ribavarin include hemolytic anemia, fatigue, irritability, and rash. Side effects of interferon include fatigue, flu-like syndrome, nausea, headaches, and depression. Suicidal ideation and suicide attempts have also been reported. Selective serotonin reuptake inhibitors have been used to treat interferon associated depression. If psychiatric side effects are severe, antiviral treatment may need to be discontinued.

REFERENCES
1. American College of Physicians. PIER (Physician’s Information and Education Resource) module for Hepatitis C. Available online at http://pier.acponline.org/physicians/diseases/d163/d163-pdf.html
2. Park JS, Dieterich DT. Chronic Hepatitis C: Latest Diagnosis and Treatment Guidelines. ConsultantLive.com 2006. Available online at http://consultantlive.com/article/showArticle.jhtml?articleID=184429289

Calculus

This newspaper article reminds me of my days of high school calculus:
The Onion
Calculus Problem Hits Too Close To Home
April 26, 2006 Issue 42•17
PULLMAN, WA–The analysis of formulae derived from the fundamental theorem of calculus had a profound and seemingly personal impact on Washington State University freshman Barry Feldman on Monday, teaching assistants in Feldman's differential calculus section reported. "There was something about having to consider multiple rates of change and their effect on one another that really struck a nerve with Barry. I've never seen a student flinch so violently at terms like 'increasingly negative curves' or 'derivatives,'" TA Melanie Peppers said. "As uneasy as the unresolved equation seemed to make Barry feel, the prospect of eventually arriving at a solution for it actually appeared to upset him more." Feldman was recently the subject of gossip among the faculty after he interrupted a lecture on increasing-tensor calculus by screaming that "enough is enough" and asking if the professor would "please just change the subject."

Medical Porn

From Medscape:
NEW YORK (Reuters Health) Apr 17 - A study suggests that dermatology images available online are sometimes being used pruriently. Moreover, pornography and fetish websites seem to be a major source of referral, researchers report in the April issue of the Journal of the American Academy of Dermatology.
The thought that DermAtlas, a searchable archive of clinical photography, was being misused first occurred to the curators when they noticed a marked jump in queries for images containing genital sites.
The bulk of searches -- 62% -- involved queries for a specific diagnosis. Of these, 12% involved a genital site. Of the 11% of requests for an anatomic site, 37% involved a genital site. Twelve percent of the 10,000 free text queries were for images containing a genital site.
In searches that specified both an age group and an anatomic site, images involving children were 48% more likely to be requested than those involving an adult.
An analysis of the top 43 referring sites to DermAtlas revealed that 9 (21%) were pornographic/fetish sites. However, these sites only accounted for 14.3% of all 141,285 referrals.
The authors conclude that "Developers of online clinical image libraries containing potentially sensitive health information on topics such as sexuality and anatomy must be aware of issues beyond technical and domain knowledge."
No, I will not provide a link to the DermAtlas.

Resident Work Hours

Several bloggers, including Kevin,MD link to the Time Cover Story, "What Doctors Hate About Hospitals".
Part of the cover story discussest the relatively new 80-hour work week regulations for residents:
Studies showed that long work hours increased stress, depression, pregnancy-related complications, car wrecks and damage to residents' morale and personal life. So now residents' hours are limited to 80-hr. workweeks averaged over a month, in shifts that are limited to 24 hours of patient care, with at least 1 day off in 7. Remaining on call in the hospital is limited to every third night.
The reforms made intuitive sense; but the unintended result, older doctors warn, is a 9-to-5 mentality that detaches the doctor from the patient. They fear that young doctors don't get the experience they need or build the instincts and muscle memory from performing procedures so many times that they can do them in their sleep. Even the residents may agree: in a 2006 study in the American Journal of Medicine, both residents and attending physicians reported that they thought the risk of bad things happening because of fragmentation of care was greater than the risk from fatigue due to excess work hours. Other residents say that while they may feel more rested, they sense that they are not learning as much or as fast as they need to.
So, residents are now more rested, but care is more fragmented. I don't think anyone can conclusively state whether the new system currently improves or worsens care in teaching hospitals.
What will happen 20 years from now, when the majority of practicing physicians have trained under the new system??
"I know that I will not like it 20 years from now when I'm 68 and having to be taken care of by these guys," says Dr. Paul Shekelle, a professor of medicine at UCLA. "It's all shift work now. When 5 o'clock comes, whatever it is they're doing, they just sign it all out to the 5 o'clock person. It's eroding the sense of duty, or commitment to being the person responsible for a patient's care."

New Clozaril Monitoring Requirements

A requirement for absolute neutrophil count (ANC) has been added to the baseline requirements for clozapine therapy; patients must have both WBC and ANC in the normal range (3500/mm3 and 2000/mm3 or greater, respectively). ANC must be determined and reported along with each WBC.
A monthly monitoring schedule may only be initiated after 1 year (6 months weekly, 6 months every 2 weeks) of WBCs and ANCs in the normal range.
Because of the increased risk for agranulocytosis in patients rechallenged with clozapine after recovery from an initial episode of moderate leukopenia (WBC range, <3000/mm3 and 2000/mm3 or higher, and/or ANC range, <1500/mm3 and 1000/mm3 or higher), these patients now require weekly monitoring of WBC and ANC for a period of 12 months.
Complete information regarding changes in monitoring frequency after interruption of therapy is available at: http://www.fda.gov/medwatch/safety/2006/Clozaril_2005-19.pdf.
For patients whose WBC is currently being monitored on a weekly or biweekly basis according to the previous schedule, ANC reporting is required from this point on. Patients may continue on their monitoring schedule and 6-month transition to biweekly or monthly monitoring if WBC and ANC remain in the normal range.
Healthcare providers are required to submit all WBC and ANC values to the Clozaril National Registry during treatment and until values reach the normal range after discontinuation of clozapine in nonrechallengeable patients (WBC, <2000/mm3 and/or ANC, <1000/mm3).
The FDA also warned of the increased risk for death associated with off-label use of clozapine in elderly patients with dementia-related psychosis.
The warning was based on an analysis of data from 17 placebo-controlled, 10-week trials showing that use of olanzapine, aripiprazole, risperidone, and quetiapine in 5106 elderly patients with dementia-related behavioral disorders was associated with an increased risk for mortality compared with placebo (4.5% vs 2.6%).
Because the 1.6- to 1.7-fold increase in death risk was linked to medications from all 3 classes of atypical antipsychotic medications, it is considered by the FDA to be a class effect.
In addition, the FDA advised that use of clozapine is now contraindicated in patients with paralytic ileus, a condition previously listed as a potential adverse event in the labeling. The change was based on a review and evaluation of data from global postmarketing safety and clinical trial databases.
The postmarketing safety database also included reports of hypercholesterolemia and/or hypertriglyceridemia in patients receiving clozapine. Moreover, database and literature data indicate that concomitant use of citalopram results in significantly increased clozapine blood concentrations, potentially resulting in adverse effects.
Clozapine is indicated for the treatment of severely ill patients with schizophrenic who fail to respond adequately to standard therapy and for reducing the risk for recurrent suicidal behavior in at-risk patients with schizophrenia or schizoaffective disorder.
The above is taken from Medscape.com.
I hadn't heard of the citalopram (Celexa)-clozapine drug interaction before.
A quick Pub Med search reveals these 2 relevant articles:
1.
Int Clin Psychopharmacol. 1998 Jan;13(1):19-21.
Co-administration of citalopram and clozapine: effect on plasma clozapine levels.Taylor D, Ellison Z, Ementon Shaw L, Wickham H, Murray R.Bethlem & Maudsley NHS Trust, London, UK.Antidepressants are frequently used in the treatment of depressive symptoms associated with schizophrenia. In patients taking clozapine, choice of antidepressant is complicated by additive pharmacodynamic effects and by pharmacokinetic interactions. We predicted that citalopram would not elevate plasma clozapine levels when the two drugs were co-administered because it does not inhibit the relevant enzyme systems. In this preliminary study of five patients given citalopram and clozapine there was no overall change in mean clozapine levels. Based on this limited evidence, citalopram might be the antidepressant of choice in patients taking clozapine.
2.
J Clin Psychiatry. 2000 Apr;61(4):301-2.
Citalopram and clozapine: potential drug interaction.Borba CP, Henderson DC.Publication Types:
Case Reports
Letter No abstract available.
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Does anyone have anymore info about the Celexa/Clozaril drug interaction???