Health posts

March 18, 2010
08:12 PM
5 views

Germs in Tobacco

Bacteria found in major cigarette brands.
It’s not enough that smoking causes all manner of cardiopulmonary complications, or that more than 3,000 chemicals and heavy metals have been identified as additives. Now comes evidence that tobacco particles extracted from cigarettes contain markers for hundreds of known bacteria. Lung infections in some smokers may be caused by germs on shredded tobacco, rather than the act of smoking itself.
According to a report by Janet Raloff in Science News, Amy Sapkota and a team of researchers at the University of Maryland screened tobacco flakes from cigarettes for bacterial DNA using known markers. In an online paper for Environmental Health Perspectives, the scientists explored the bacterial metagenomics of cigarettes using standard cloning and sequencing processes. The team provided evidence for the presence of Campylobacter (a cause of food poisoning), E. coli, several Staphylococcus varieties, as well as a number of bacteria, such as Clostridium, which is directly associated with pneumonia and other infections. Fifteen different classes of bacteria in all, with no significant variation from one cigarette brand to another.
The time has come, Sapkota and coworkers conclude, “ to further our understanding of the bacterial diversity of cigarettes,” given the more than 1 billion smokers worldwide. Smoking is now recognized as a risk factor for a basketful of respiratory illnesses, including influenza, asthma, bacterial pneumonia, and interstitial lung disease. In light of this, the authors have advanced their study as solid evidence that “cigarettes themselves could be the direct source of exposure to a wide array of potentially pathogenic microbes among smokers and other people exposed to secondhand smoke.”
In 2008, researcher John Pauly and coworkers at the Roswell Park Cancer Institute in Buffalo, New York, helped provide early evidence by conducting a tobacco flake assay and publishing the results in the journal Tobacco Control. The scientists opened a package of cigarettes “within the sterile environment of a laminar flow hood. A single flake of tobacco was collected randomly and aseptically from the middle of the cigarette column and placed onto the surface of a blood agar plate. The test cigarettes included eight different popular brands, and these were from three different tobacco companies.”
And the results? “After 24 hours of incubation at 37 degrees C, the plates showed bacterial growth for tobacco from all brands of cigarettes. Further, more than 90% of the individual tobacco flakes of a given brand grew bacteria.” Pauly believes that “the results of these studies predict that diverse microbes and microbial toxins are carried by tobacco microparticulates that are released from the cigarette during smoking, and carried into mainstream smoke that is sucked deep into the lung.”

In a recent study published in Immunological Research , Pauly and others expanded on their findings, writing that “Cured tobacco in diverse types of cigarettes is known to harbor a plethora of bacteria (Gram-positive and Gram-negative), fungi (mold, yeast), spores, and is rich in endotoxin (lipopolysaccharide).” This time out, the researchers conclude that “lung inflammation of long-term smokers may be attributed in part to tobacco-associated bacterial and fungal components that have been identified in tobacco and tobacco smoke.”
Cigarette manufacturers already use antibacterial washes during the curing process in order to reduce infection by fungi and bacteria.
If the findings are sound, they could place the argument over secondhand smoke in a vastly different light—cigarettes smoke may be taking the rap for respiratory infections cause by extant bacteria. With smoking rates in the U.S. holding at a steady 21 percent of the population, the issue is not trivial.
Graphics Credit: http://commons.wikimedia.org/
Sapkota, A., Berger, S., & Vogel, T. (2009). Human Pathogens Abundant in the Bacterial Metagenome of Cigarettes Environmental Health Perspectives, 118 (3), 351-356 DOI: 10.1289/ehp.0901201
Pauly, J., Smith, L., Rickert, M., Hutson, A., & Paszkiewicz, G. (2009). Review: Is lung inflammation associated with microbes and microbial toxins in cigarette tobacco smoke? Immunologic Research, 46 (1-3), 127-136 DOI: 10.1007/s12026-009-8117-6

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Sapkota, A., Berger, S., & Vogel, T. (2009) Human Pathogens Abundant in the Bacterial Metagenome of Cigarettes. Environmental Health Perspectives, 118(3), 351-356. DOI: 10.1289/ehp.0901201

Pauly, J., Smith, L., Rickert, M., Hutson, A., & Paszkiewicz, G. (2009) Review: Is lung inflammation associated with microbes and microbial toxins in cigarette tobacco smoke?. Immunologic Research, 46(1-3), 127-136. DOI: 10.1007/s12026-009-8117-6

March 18, 2010
04:25 PM
14 views

Death by human stampede

by Tom Rees in Epiphenom

Over the past 30 years, stampedes have killed at least 7,000 people and injured another 14,000. That's the conclusion that Edbert Hsu (Johns Hopkins Medical Institutions) and colleagues reached after a painstaking trawl of news reports in the world's English-language media.The real toll is probably even higher, of course, but the data were enough to allow Hsu to work out the characteristics of the most lethal stampedes. They found reports on 215 stampedes, of which 49 occurred at sporting events, 25 at musical events, 38 were political and 41 were religious. The rest (totalling 60) were due to a mixed bag of causes and were mostly spontaneous.And the award for the most lethal type of stampede goes to... religious ones! In simple terms of the number of fatalities per stampede, religious events come out over double that of their closest rival.The simple comparison is not a very fair, however. Religious stampedes take place in different parts of the world (often in the Middle East, which is the most dangerous place to be in a stampede), often in low income nations (also very dangerous), and often outdoors (slightly more dangerous than indoor stampedes).But even when you take all this into account, religious stampedes still come out on top of the lethality stakes - but sporting stampedes are so close as to make it a photo finish.There's one other factor that contributes to the lethality of a stampede, and that's the size of the crowd. Unfortunately, Hsu was only able to determine the size of the crowd in 130 cases.But even taking into account crowd size, religious stampedes are still pretty dangerous. When you look at fatality rate (i.e. deaths per crowd member), they're 6 times riskier than stampedes at sporting events.But with with crowd size taken into account, religious stampedes drop into third place. The riskiest kind of stampede by a long way are the spontaneous ones (because of the lack of crowd control), followed by political ones.The explanation for all this is fairly simple. Religion is the one event that brings together truly massive crowds, often in settings that are poorly controlled.One of the most lethal stampedes in recent history occurred in Iraq in 2005, when nearly 1000 people died when fears of a suicide attack sparked panic. In the same year, over 250 died (out of a crowd of 400,000) when Hindu worshippers set fire to shops.But the biggest contributor is the annual Hajj, which these days draws crowds in excess of 2 million. Five of the biggest stampedes in the past100 years occurred in Mina Valley, Saudi Arabia, during the Hajj.Over the past 3 decades, nearly 3,000 people have been killed in stampedes during the Hajj - the last big disaster being in 2006. With crowds that big, I suppose the surprise is that there are so few casualties!Hsieh, Y., Ngai, K., Burkle, F., & Hsu, E. (2009). Epidemiological Characteristics of Human Stampedes Disaster Medicine and Public Health Preparedness, 3 (4), 217-223 DOI: 10.1097/DMP.0b013e3181c5b4ba This article by Tom Rees was first published on Epiphenom. It is licensed under Creative Commons.

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Hsieh, Y., Ngai, K., Burkle, F., & Hsu, E. (2009) Epidemiological Characteristics of Human Stampedes. Disaster Medicine and Public Health Preparedness, 3(4), 217-223. DOI: 10.1097/DMP.0b013e3181c5b4ba

March 18, 2010
12:19 AM
16 views

Palliative Care in Cancer Centers - Horses of many different colors

by Christian Sinclair, MD in Pallimed: a Hospice & Palliative Medicine Blog

The third Palliative Care related article released for St. Patrick's (Palladius) day is a article that speaks to what many of us in the field know already:

Palliative Care is a chameleon: it looks different depending on the background of the institution.
But as the editor-in-chief of the Lancet has said: "It is not true, until it is published." Well JAMA has published a little bit of truth with the article: "Availability and Integration of Palliative Care at US Cancer Centers." We have already known from CAPC data about a variability in access among states. This data helps underscore the variability in palliative care services, staffing, education and research at major cancer centers in the US.
I won't belabor the data here as it is relayed well in the abstract. But a few things impressed me about the study. It made a strong effort to differentiate between the simple question of 'Do you have a palliative care program?' which in a few institutions I have seen consists of a well stocked brochure rack and a single staff member (usually a nurse) who has 20 other job responsibilities that are prioritized by the administration above palliative care. Instead the authors focused on the structure, process and outcomes (also known as a Donabedian tripartite division, but of course you already knew that.)

Also a question to cancer center executive about barriers to palliative care seemed to be somewhat contradictory to other findings. Thee highest rated barriers (around 50-60%) were:
limited institutional budgets
poor reimbursement
limited trained palliative care staff
despite 89% of cancer centers surveyed claiming to have palliative care programs. And conversely very few center executives (less than 10%) reported the following as barriers:
limited palliative care needs
lack of evidence for palliative care
palliative care may increase mortality
palliative care may affect national rating
palliative care available but not utilized

So if I understand this right, 89% of cancer center executives have palliative care programs with staff who get paid from the budget but the around 60% feel the biggest barrier to getting palliative care access is that there is no budget/reimbursement or staff?

Couldn't be the culture of cure (see the media study), or the fact they are a tertiary referral center focused on the 'save'? Or the drive to get more patients enrolled in experimental drug trials which is a major source of funding/prestige? Or that palliative care may still not be well integrated into the culture?

I'm merely speculating here, but I think there is a juicy qualitative/anthropological study in this data.

One last thing...only 57% of NCI Cancer Centers had board certified palliative medicine physicians. And the data was collected in 2009. Come on people get board certified in hospice and pallaitive medicine this fall.

(Image from Funnycancershirts.com)

David Hui, MD, MSc, Ahmed Elsayem, MD, Maxine De La Cruz, MD, Ann Berger, MD, Donna S. Zhukovsky, MD, Shana Palla, MS, Avery Evans, Nada Fadul, MD J. Lynn Palmer, PhD; Eduardo Bruera, MD (2010). Availability and Integration of Palliative Care at US Cancer Centers JAMA, 303 (11), 1054-1061

... Read more »

David Hui, MD, MSc, Ahmed Elsayem, MD, Maxine De La Cruz, MD, Ann Berger, MD, Donna S. Zhukovsky, MD, Shana Palla, MS, Avery Evans, Nada Fadul, MD, & J. Lynn Palmer, PhD; Eduardo Bruera, MD. (2010) Availability and Integration of Palliative Care at US Cancer Centers. JAMA, 303(11), 1054-1061. info:/

March 17, 2010
11:52 PM
23 views

Cancer Reporting in the Media - Guess what they report on?

by Christian Sinclair, MD in Pallimed: a Hospice & Palliative Medicine Blog

Image via WikipediaSt. Patrick's day is good for celebrating your Irish heritage or fondness for food coloring, but it may have a new tradition, the release of major Palliative Care articles. Three major articles came out this week. Today JAMA published "Availability and Integration of Palliative Care at US Cancer Centers", yesterday the Archives of Internal Medicine released "Cancer and the Media: How Does the News Report on Treatment and Outcomes?" and on the 15th CMAJ released "Why do patients with cancer visit the emergency department near the end of life?"

(And all apparently with open access free pdf's!)

Today we are going to review all three (in separate posts JAMA review here, CMAJ review here)!

So why the St. Patrick's day logjam of articles? Some may say it is mere coincidence, but I think there may be some meta-meaning here. By the power of Grayskull Wikipedia I found that St. Patrick is very likely two different people, one of which is named Palladius...very similar to 'palliative'...which is why I am sure the editors of these three journals got together to plan this bounty of articles. (I guess the New England Journal of Medicine missed the conference call). We will see if next year the same thing happens. Enough conspiracy talk...

This study by Fischman, Have and Casarett shines a light on the bias present in the media towards the 'fight' against cancer. The researchers looked at 8 newspapers (Chicago Sun-Times, Chicago Tribune, Daily-Herald Chicago, New York Daily, New York Post, New York Times, Philadelphia Daily News , Philadelphia Inquirer) and 5 magazines (Newsweek, Parade, People, Redbook, Time). (What no Washington Post or Cosmo?)

The main points in the articles that were coded if they were mentioned were:
Survival
Mortality
Aggressive/curative
Treatment failures
Adverse events
Palliative focus

The researchers found a very significant bias towards reporting cures/survivors (32%) over deaths (8%) and sadly only 2% that mentioned both. Also they found that adverse events and treatment failures were rarely reported (both less than 30%).

And of course the result you have been waiting for, 11 articles out of 436 (3%) mentioned aggressive and pallaitive measures and only 2 (two, dos, deux, zwei!) of the articles focused exclusively on end of life care exclusively. Well the researches only searched from 2005-7 and so they missed the whole past year of New York Times articles we have been writing about. Still it is shocking in 'cancer focused' articles only 0.5% mention end-of-life care exclusively?!

Pallimed was initially focused on EBM style analysis of palliative care articles, but we have expanded our scope to report on palliative care in the media also, and this study justifies the importance of getting the story about good palliative care into the main media news cycles. It is not just enough that there are articles about cancer treatments (mainly read by cancer patients and their families) or articles about hospice or palliative care programs (read by hospice and palliative care staff and families with hospice experience.) We need articles that combine the two so people are equally exposed to the balance of treatments that exist out there. Few patients or families facing cancer diagnoses will choose to read the 'hospice is valuable' headline when juxtaposed with a 'new cancer treatment' headline.

But it is important to understand the view of the journalist and editors as well. 'New cancer treatment' headlines may sell more copies than 'hospice is valuable' headlines. Also a new treatment being available is news because it is new, different, interesting. Having articles about how people have poor survival with a cancer diagnosis is not new, different or interesting. Palliative care and hospice organizations need to make sure the journalists and editors hear the great stories we see every day in our work. The human interest perspective is very powerful. Some hospices are better at connecting with the media than others. Maybe it was time we all had a lesson in how to best interact professionally with the media.

For reference I have uploaded a slidedeck I gave at the NHPCO conference in 2007 titled: Working With the Media: How to Reach the Widest Audience Possible. It is embedded below.

View more presentations from Christian Sinclair, MD.If you know of any other good media resources for medical professionals please comment below. Hospice Foundation of America also posted about this today.

Fishman, J., Ten Have, T., & Casarett, D. (2010). Cancer and the Media: How Does the News Report on Treatment and Outcomes? Archives of Internal Medicine, 170 (6), 515-518 DOI: 10.1001/archinternmed.2010.11

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Fishman, J., Ten Have, T., & Casarett, D. (2010) Cancer and the Media: How Does the News Report on Treatment and Outcomes?. Archives of Internal Medicine, 170(6), 515-518. DOI: 10.1001/archinternmed.2010.11

March 17, 2010
09:42 PM
29 views

Genetics of Alcoholism

by Allison in Dormivigilia

A recent paper in PNAS identified many single-nucleotide polymorphisms and environmental factors, such multiple drug abuse, tied to alcoholism... Read more »

Bierut LJ, Agrawal A, Bucholz KK, Doheny KF, Laurie C, Pugh E, Fisher S, Fox L, Howells W, Bertelsen S.... (2010) A genome-wide association study of alcohol dependence. Proceedings of the National Academy of Sciences of the United States of America. PMID: 20202923

March 17, 2010
09:40 PM
27 views

Epidemiology of Human Prion Diseases in the U.S.

by Brian Appleby in CJD Blogger

In January 2010, members of the Centers for Disease Control and Prevention published an article in PLoS One regarding epidemiological data of human prion diseases in the United States. To those who have attended prion meetings in past couple of years, this is not new data as it has been presented before. The study examines the incidence of classical CJD and variant CJD (vCJD) within the U.S. between 1979-2008 and examines some basic demographic features of this population. The data were collected using a variety of different methods. From 1979-2006, data were collected from death certificates of U.S. residents and through alternative surveillance mechanisms from 1996-2008. These other surveillance efforts as of 6/1/2009 include collaboration with state health authorities and of directly reported or indirectly reported cases of possible vCJD. From 1999 onwards, text of death certificates were examined for CJD-related terms using SuperMICAR (Mortality Medical Indexing, Classification, and Retrieval system). The study uses the annual death rate to estimate the incidence of CJD (defined as the number of new cases per year) since the majority of cases have an illness duration of less than one year. From 1979-2006, the mean annual number of reported deaths secondary to CJD was 247 (range 172-304). The annual age-adjusted incidence of CJD was estimated at 0.97 per million individuals. In individuals older than 64 years of age, the incidence of CJD was estimated to be 4.8 per million individuals. The vast majority of deaths due to CJD were reported in whites (94.6%), resulting in an age-adjusted incidence for blacks of 0.4 per million individuals. Three deaths due to vCJD have been reported since 2004, all of which were determined to have acquired infection from outside of the U.S. In summary, this study estimates the incidence of CJD in the U.S. to be approximately 1 per million individuals, which is in accordance with data from other countries. The authors also describe a striking disparity between the incidence of CJD in whites and blacks. There are several limitations to this study, including but not limited to the various methods used for surveillance at different points in time and the reliance on reported data that may not have been uniformly reported across the country. Holman, R., Belay, E., Christensen, K., Maddox, R., Minino, A., Folkema, A., Haberling, D., Hammett, T., Kochanek, K., Sejvar, J., & Schonberger, L. (2010). Human Prion Diseases in the United States PLoS ONE, 5 (1) DOI: 10.1371/journal.pone.0008521 del.icio.us Tags: Creutzfeldt-Jakob disease,CJD,vCJD,epidemiology,research... Read more »

Holman, R., Belay, E., Christensen, K., Maddox, R., Minino, A., Folkema, A., Haberling, D., Hammett, T., Kochanek, K., Sejvar, J.... (2010) Human Prion Diseases in the United States. PLoS ONE, 5(1). DOI: 10.1371/journal.pone.0008521

March 17, 2010
12:05 PM
49 views

Painting lines on the playground - easiest physical activity intervention. EVER.

by Travis Saunders, MSc in Obesity Panacea

In most developed nations, kids get far less physical activity than they did just a few generations ago. Given the strong links between physical inactivity and health risk (and given that we're now seeing "adult" diseases like heart disease and type 2 diabetes in children and teenagers), this has become a very real public health concern. Unfortunately, when it comes to increasing childhood physical activity levels, people often want to reinvent the wheel. For example, many people are enthralled with the Nintendo Wii as a means of increasing childhood physical activity - even though it is expensive, and the evidence supporting it is weak at best. At the same time, evidence continues to accumulate in support of simple, inexpensive interventions for increasing childhood physical activity. Today I'd like to briefly look at one of the simplest possible ways of increasing childhood physical activity levels - painting lines on a schoolyard playground.... Read more »

STRATTON, G., & MULLAN, E. (2005) The effect of multicolor playground markings on children's physical activity level during recess. Preventive Medicine, 41(5-6), 828-833. DOI: 10.1016/j.ypmed.2005.07.009

March 17, 2010
05:32 AM
31 views

Mmm... Food-Induced Seizures

by Neuroskeptic in Neuroskeptic

In a tasty new paper, British neurologists Kate El Bouzidi et al report on the case of a woman who suffered epileptic seizures whenever she saw, or tasted, food:A 44-year-old right-handed woman was walking in the Scottish highlands. Upon unwrapping her lunch, she had a focal seizure with witnessed onset on the right side of the face and secondary generalization... She was airlifted to hospital. Three weeks later, the smell of food triggered another seizure and she was admitted to the neurology unit...Even hospital fare was able to provoke the attacks:The next morning, the patient had a simple partial seizure after eating a spoonful of porridge. Thereafter, most meals triggered seizures, as did other food-related stimuli such as being offered a piece of cake, seeing her visitors pass around food at her bedside, and smelling the hospital dinner trolley.Anti-convulsant drugs failed to control the seizures. An MRI scan revealed an abnormal mass and electrode recordings from the surface of the brain confirmed that the seizure activity was starting nearby. The mass was surgically removed - it turned out to have been a grade IV glioblastoma cancer - which put an end to the seizures, although sadly we're told that the surgery was "subtotal" i.e. they weren't able to remove the tumour entirely.The authors note that eating-induced seizures have been reported hundreds of times, most commonly in India and Sri Lanka, curiously enough, but this is the first known case in which merely seeing or thinking about food was also a trigger. Why it happens is a mystery: presumably, neural activation in response to the taste or smell of food somehow spills over into the epileptic focus... but the details are sketchy.In this case, seizures were specifically triggered by food-related stimuli in the context of hunger. The finding of a seizure focus in the left frontal operculum, adjacent to the tumor, is consistent with the hypothesis that activation of this region by appetite triggered seizure activity that then propagated to the surrounding cortex and was manifest clinically as a motor seizure.El Bouzidi K, Duncan S, Whittle IR, & Butler CR (2010). Lesional reflex epilepsy associated with the thought of food. Neurology, 74 (7), 610-2 PMID: 20157165... Read more »

El Bouzidi K, Duncan S, Whittle IR, & Butler CR. (2010) Lesional reflex epilepsy associated with the thought of food. Neurology, 74(7), 610-2. PMID: 20157165

March 16, 2010
09:43 AM
18 views

Editorial Support, CME, and the Primary Care Companion

by CL Psych in Clinical Psychology & Psychiatry

By now, everyone who has been paying attention should know that a journal article which lists "editorial support" is an article that was ghostwritten. Yet the average reader of these articles is apparently uninformed enough to not care. Why else would so many articles get published which feature "editorial support provided by [insert name of ghostwriter here]." One my my favorite journals, under the "so bad, it's good" category, is the Primary Care Companion to the Journal of Clinical Psychiatry. Good articles certainly make their way into the journal, perhaps by accident, but the journal can always be counted on to provide a steady supply of utter garbage.Here's the acknowledgements section from one recent piece in the journal: "Editorial support was provided by George Rogan, MSc, Phase Five Communications Inc, New York, New York. Mr. Rogan reports no other financial affiliations relevant to the subject of this article." And in case you're wondering, "Funding for editorial support was provided by Bristol-Myers Squibb." If you've somehow guessed that this is an advertorial for Abilify, you win. Other ghostwritten pieces of fluff paid for by BMS include an article discussing the safety profile of Abilify in depression. It states that "In conclusion, this post hoc analysis extends previous findings demonstrating that aripiprazole is safe and generally well tolerated as an augmentation strategy to standard ADT in patients with MDD with a history of an inadequate response to antidepressant medication." But Abilify caused akathisia in a quarter of patients - I think that's a problem.But wait... there's more. An article based on data from two trials, which showed (allegedly) that Seroquel improves anxiety in patients with bipolar disorder. This piece also acknowledges that it was ghostwritten. And we know that AstraZeneca, manufacturer of Seroquel, has cooked the books on Seroquel in the past. Feel free to look through the journal every month and have a giggle at some of the ridiculous pieces that make their way into print. CMEYou can get your continuing medical education (CME) from the Primary Care Companion as well. One particularly awesome piece of medical wisdom pimped Abilify educated physicians about the best ways to manage resistant depression. This one is a beauty. It was supported by cash from BMS, which features prominently in the "treat aggressively" message of the piece. The article features none other than Michael Thase as the leading discussant. The same guy who was the leading author on a paper which allegedly showed the wonders of Abilify for depression - despite the pesky fact that patients said it didn't work. Back to the CME.. Thase starts off by stating that only a third of patients achieve remission of depressive symptoms during treatment. Given that Abilify is being marketed for treatment-resistant depression, this is a perfect way to start off this infomercial educational piece. He adds that failure to achieve remission increases the risk of suicide and puts people at risk for more depression, worse psychiatric outcomes, and all sorts of other bad things. So we better get rid of all symptoms of depression. Thase suggests that clinicians should closely monitor patients to see if their symptoms are remitting. In particular, "Relying on the global statement “I’m definitely better” from the patient overlooks persistent, minor, or residual symptoms. Dr Thase recommended using a standardized symptom assessment measure and keeping track of the patient’s levels of symptom burden." So even if the patient says he or she is much better, don't believe it. Have the patient fill out rating scales and if any symptoms at any level are present, keep treating. In Thase's words, "If the current treatment is well tolerated and the individual has made significant symptom improvement but is still experiencing residual symptoms, then it may be necessary to adjust the treatment dose, add another medication, or combine pharmacotherapy and psychotherapy." Note that adding psychotherapy comes after adding another medication.Then a series of other objective, expert psychiatrists chime in. Dr. Gaynes offers his wisdom, which includes "Dr Gaynes concluded that incomplete remission requires aggressive identification and management." Don't be afraid - be aggressive. The unspoken message: Hey, using an antipsychotic like Abilify for depression may seem freakin' crazy. But don't worry, you need to be aggressive. Dr. Trivedi then comments about using rating scales to measure side effects. I don't have much to say about his section, but things get worse momentarily...Dr. Papakostas then checks in. "A meta-analysis of randomized, double-blind, placebo controlled studies found that augmentation of various antidepressants with the atypical antipsychotic agents olanzapine, risperidone, and quetiapine was more efficacious than adjunctive placebo therapy. In addition, Dr Papakostas noted that the atypical antipsychotic aripiprazole was recently approved by the US Food and Drug Administration (FDA) for use as an adjunctive therapy to antidepressants in MDD. Augmenting with atypical antipsychotics has so far been the best studied strategy for managing treatment-resistant depression, said Dr Papakostas." Dr. P was the coauthor of a meta-analysis that provided "considerable evidence" regarding the wonders of antipsychotic therapy for depression. The only problem was that the analysis actually did not find convincing evidence that the drugs were particularly effective, which I discussed in December 2009.Next comes Dr. Shelton. Time to be aggressive, again: "Thus, said Dr Shelton, the long-term management of depression should be viewed in the context of acute treatment and the need for early aggressive management to get the patient as well as possible." Be aggressive by adding Abilify to the antidepressant regimen. If not, your patient won't achieve full remission and will suffer needlessly... "Dr Shelton advised clinicians to be aggressive in treatment and stay active over time, asking themselves if everything hashonestly been done to help the patient." Psychotherapy is given a brief mention in this section, but let's face it -- most physicians think of "be aggressive" as upping the dosage and/or adding medications - not as "let's be aggressive by adding psychotherapy."Then there's the exam at the end. Write up your answers, mail them in, and get your medical education credit. Here's one of the questions...3. Scores on both patient- and clinician-rated scales found that Ms B is still experiencing residual depressive symptoms. You optimize her current SSRI dose, which produces some improvement. She has not reported any problems with side effects. What course of action to improve her outcome has the most comprehensive efficacy data?a. Increase the dose of her current SSRI againb. Augment her current SSRI with another SSRIc. Switch her to a serotonin-norepinephrine reuptake inhibitord. Augment her current SSRI with an atypical antipsychoticIf you guessed that D is the correct answer, you're one step closer to CME credit. And one step closer to writing a prescription for Abilify despite the fact that it is as likely to induce akathisia as to induce remission of depressive symptoms. Or that its advantage over placebo is small on several measures and nonexistent on a patient-rated measure of depression. But D is still the "correct" answer.The offending educational piece is cited below:... Read more »

Thase, M., Gaynes, B., Papakostas, G., Shelton, R., & Trivedi, M. (2009) Tackling Partial Response to Depression Treatment. The Primary Care Companion to The Journal of Clinical Psychiatry, 11(4), 155-162. DOI: 10.4088/PCC.8133ah3c

March 16, 2010
06:00 AM
40 views

A healthy life leads to a healthy sex life

by Helen Jaques in In Sickness and In Health

Being in good or excellent health increases the quality and quantity of sex for middle aged and older people, according to a big study that delved into the sex lives of 6,000 American adults aged 25-85. Plus being fit can keep you sexually active into a ripe old age, unlike your unhealthy peers.
The study also [...]... Read more »

Lindau, S., & Gavrilova, N. (2010) Sex, health, and years of sexually active life gained due to good health: evidence from two US population based cross sectional surveys of ageing. BMJ, 340(mar09 2). DOI: 10.1136/bmj.c810

Health

March 16, 2010
05:30 AM
57 views

Don't eat on a full brain

by Yoni Freedhoff in Weighty Matters

Here's a interesting study. Simple experimental design. Take 165 undergraduate students and enroll them in a study you tell them is about memory and where as part of their reward for inclusion, they'll be given a snack. Ask half of them to memorize a 2 digit number and the other half a 7 digit number and once they've memorized their numbers ask them to go into a second room where they are faced with their snack choice - either a piece of chocolate cake or a cup of fruit salad. Track choice and then follow up with an exploration of the students' perceived reasons for making the choice.The results?63% of the students who were trying to remember the 7 digit number chose the cake compared with only 42% of those trying to remember the 2 digit number. Students who chose the cake reported a stronger emotional decision making drive while those who chose the fruit salad reporter a stronger cognitive drive.Researchers hypothesized that the difference was explicable on the basis of the 7 digit memory group having "lower levels of processing resources" with much of their cognitive brain power being spent on trying to remember their 7 digit number.Moral of the story?Don't eat on a full brain.Shiv, B., & Fedorikhin, A. (1999). Heart and Mind in Conflict: the Interplay of Affect and Cognition in Consumer Decision Making Journal of Consumer Research, 26 (3), 278-292 DOI: 10.1086/209563

... Read more »

Shiv, B., & Fedorikhin, A. (1999) Heart and Mind in Conflict: the Interplay of Affect and Cognition in Consumer Decision Making. Journal of Consumer Research, 26(3), 278-292. DOI: 10.1086/209563

March 16, 2010
03:28 AM
45 views

Chocolate Against Stress

by Dr Shock in Dr Shock MD PhD

40 grams of dark chocolate per day reduces the urinary excretion of the stress hormone cortisol and it almost normalizes the stress related differences in energy metabolism and gut microbial activities between participants with low and high anxiety traits.
You are what you eat, it has been described how dietary preferences is associated with metabolic processes [...]

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Martin, F., Rezzi, S., Peré-Trepat, E., Kamlage, B., Collino, S., Leibold, E., Kastler, J., Rein, D., Fay, L., & Kochhar, S. (2009) Metabolic Effects of Dark Chocolate Consumption on Energy, Gut Microbiota, and Stress-Related Metabolism in Free-Living Subjects. Journal of Proteome Research, 8(12), 5568-5579. DOI: 10.1021/pr900607v

March 15, 2010
05:00 PM
31 views

The Drosophila Circadian Clock

by Allison in Dormivigilia

Today, we had a guest seminar speaker, Dr. Bridget Lear, who presented us with the molecular regulation of circadian locomotor activity in the Drosophila. By deleting several of specific genes and interfering with the kinetics of specific ion channels, Bridget is able to modify, and in most cases, eradicate organized circadian locomotor activity... Read more »

Lear, B., Lin, J., Keath, J., McGill, J., Raman, I., & Allada, R. (2005) The Ion Channel Narrow Abdomen Is Critical for Neural Output of the Drosophila Circadian Pacemaker. Neuron, 48(6), 965-976. DOI: 10.1016/j.neuron.2005.10.030

March 15, 2010
12:17 PM
29 views

Fumbling the Communication Baton in Patient Hand-offs

by Rob Mitchum in ScienceLife

As you may have gathered from various television dramas, medical residents work insane hours. A typical shift “on call” often means 30 straight hours on duty at the hospital, mostly spent on the time-intensive process of admitting new patients. People outside the medical profession often ask why such marathon shifts are necessary, and express surprise [...]... Read more »

Chang, V., Arora, V., Lev-Ari, S., D'Arcy, M., & Keysar, B. (2010) Interns Overestimate the Effectiveness of Their Hand-off Communication. PEDIATRICS, 125(3), 491-496. DOI: 10.1542/peds.2009-0351

March 15, 2010
09:50 AM
38 views

Tumour associated macrophages and survival in Hodgkins Lymphoma

by Sally Church in Pharma Strategy Blog

While reading my pile of mail on Friday, I realised that an interesting paper on Hodgkins Lymphoma (HL) appeared in the current edition of the New England Journal of Medicine (full reference below). The basics of the paper are that...... Read more »

Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD.... (2010) Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. The New England journal of medicine, 362(10), 875-85. PMID: 20220182

DeVita, V., & Costa, J. (2010) Toward a Personalized Treatment of Hodgkin's Disease. New England Journal of Medicine, 362(10), 942-943. DOI: 10.1056/NEJMe0912481

Kunisch, E. (2004) Macrophage specificity of three anti-CD68 monoclonal antibodies (KP1, EBM11, and PGM1) widely used for immunohistochemistry and flow cytometry. Annals of the Rheumatic Diseases, 63(7), 774-784. DOI: 10.1136/ard.2003.013029

March 15, 2010
06:30 AM
39 views

Should scientists be in control?

by Björn Brembs in bjoern.brembs.blog

The cliché scientist is often portrayed as the laborious worker slogging away days and nights in the lab. In contrast, the cliché for musicians or artists often comprises a bohemian lifestyle, full of parties, drugs and the occasional spurts of genius and frantic artistic expression. Reality, as always, is somewhere in-between. Artists need to work hard and laboriously to get something finished before the concert, recording or exhibition and scientists need to be creative and invest a lot of thought and effort into devising the new hypothesis or the clincher experiment. In his highly readable autobiography "Physics and Beyond" Werner Heisenberg of uncertainty-principle fame tells us that, when stuck with a complicated problem, he would have to leave the institute and spend time in nature, away from everything, waiting for the creative idea to solve the problem. In today's publish-or-perish scientific culture, such behavior is a young scientist's doom. Heisenberg received his Nobel Prize at the age of 31, an age where today's scientists barely get around towards their first or second postdoc and a tenured faculty position is still about a decade away, on average.It's been known for a very long time that creativity requires a so-called 'relaxed field', meaning an absence of outside stressor distracting from the thought processes at hand. I've written before about neurobiological research uncovering the biological basis for this requirement. Today I listened to a podcast from Radio National on the "Powerful Biology of Stress", which reminded me of that post. In the podcast, Bruce McEwen, one of the researchers the host, Natasha Mitchell, interviewed, mentioned research of one of his graduate students, Connor Liston. Connor Liston had conducted a series of experiments in rats which showed that when the animal, the rat, is challenged with a complex task in which it has to shift the meaning of cues that predict where a food reward is, if the task is difficult, having either a lesion of the prefrontal cortex which other people did, or chronic stress, reduces mental flexibility. Their ability to shift is not totally gone, it's just much slower and less efficient. Confirming much previous work, chronic stress reduces mental flexibility in rats and lesion studies pointed towards the prefrontal cortex. Connor Liston found that in the prefrontal cortex, under chronic stress these neurons are shrinking, the dendrites are shrinking and they're losing connections. So they are losing a very important input—it's a reversible process, if you stop the stress it will grow back. Chronic stress leads to dendritic pruning in the medial prefrontal cortex, which probably accounts for the loss in flexibility. So far, this research is interesting, but still on the level of the rat model system. How would this research translate into humans under chronic stress? Just over one year ago, Connor Liston published a study in PNAS about chronic stress in medical students who were preparing for their board exams. he used something called the perceived stress scale, which actually asks you questions about how much in control of your life you are in and what things are causing you to be stressed out. What he also did was to develop a human task which was very much like what he did with the rats, and they used functional brain imaging to define a circuit that was activated by this task. They could observe this circuit in these stressed students and they found that the more stressed out, the less efficient was the circuit, and they also showed an impairment on this behavioural task. While dendritic pruning cannot easily be studied in live human beings, it is tempting to speculate that also in humans this process takes place in our prefrontal cortex under chronic stress and causes you to fail in behavioral tests which require mental flexibility.This kind of research shows that not only were the old reports which connected creativity with what people at the time called 'a relaxed field' correct, we are now finding out what the neurobiological basis of this connection is. This research also demonstrates even more clearly how detrimental a stressful environment is for scientists: lacking the mental flexibility to think out of the box, to distance yourself from the problem at hand to maybe find the ingenious solution, stress postpones the progress of science. Forcing scientists into habits and grunt work, stress pushes science into dead ends and wasteful spending. Today, scientists finish their PhDs when they're just about to turn 30 and receive their first own grant in their 40s. During this decade, they live on short-term contracts and any failure to publish could mean the end of a life in science. For many 40-somethings, having been scientists for all their lives, never seen a company from the inside, a dry spell at any time in their career may mean the end to any middle-class life, with salaries being so low that no large savings would ever accrue. I'm not aware of any study investigating the reversibility of dendritic pruning after a decade of existential stress, but I'm willing to hazard a guess that a scientist's most formative years are not being used to their full potential by our current system and may even be detrimental for the final decades of a scientist's work. It is also conceivable that such existential stress incentivizes fraud and other misconduct in scientists who under normal circumstances would never be prone to such behavior.Interesting for my own research is the aspect that the critical factor deciding what is considered stress in these neurobiological studies, was whether or not the rats or humans had any control over their circumstances (restraint in rats and the exams in humans). My own research focuses on how the brain learns to control its circumstances and how it detects whether it is in control or not. Maybe one day my own research will contribute to a better understanding of how to contstruct a professional work-environment that fosters science, instead of stifling it.Liston, C., McEwen, B., & Casey, B. (2009). Psychosocial stress reversibly disrupts prefrontal processing and attentional control Proceedings of the National Academy of Sciences, 106 (3), 912-917 DOI: 10.1073/pnas.0807041106Radley, J. et al. (2005). Repeated Stress Induces Dendritic Spine Loss in the Rat Medial Prefrontal Cortex Cerebral Cortex, 16 (3), 313-320 DOI: 10.1093/cercor/bhi104... Read more »

Liston, C., McEwen, B., & Casey, B. (2009) Psychosocial stress reversibly disrupts prefrontal processing and attentional control. Proceedings of the National Academy of Sciences, 106(3), 912-917. DOI: 10.1073/pnas.0807041106

Radley, J. (2005) Repeated Stress Induces Dendritic Spine Loss in the Rat Medial Prefrontal Cortex. Cerebral Cortex, 16(3), 313-320. DOI: 10.1093/cercor/bhi104

March 15, 2010
05:52 AM
68 views

How to Stop Smoking

by Neuroskeptic in Neuroskeptic

1. Don't smoke.2. See 1.This is essentially what Simon Chapman and Ross MacKenzie suggest in a provocative PloS Medicine paper, The Global Research Neglect of Unassisted Smoking Cessation: Causes and Consequences.Their point is deceptively simple: there is lots of research looking at drugs and other treatments to help people quit smoking tobacco, but little attention is paid to people who quit without any help, despite the fact that the majority (up to 75%) of quitters do just that. This is good news for the pharmaceutical industry and others who sell smoking-cessation aids, but it's not clear that it's good for public health.As they put it,despite the pharmaceutical industry’s efforts to promote pharmacologically mediated cessation and numerous clinical trials demonstrating the efficacy of pharmacotherapy, the most common method used by most people who have successfully topped smoking remains unassisted cessation ... Tobacco use, like other substance use, has become increasingly pathologised as a treatable condition as knowledge about the neurobiology, genetics, and pharmacology of addiction develops. Meanwhile, the massive decline in smoking that occurred before the advent of cessation treatment is often forgotten.Debates over drugs, or other treatments, tend to revolve around the question of whether they work: is this drug better than placebo for this disorder? Chapman and MacKenzie point out that even to frame an issue in these terms is to concede a lot to the medical or pathological approach, which may not be a good idea. Before asking, do the drugs work? We should ask, what have drugs got to do with this?Their argument is not that drugs never help people to quit; nor are they saying that tobacco isn't addictive, or that there is no neurobiology of addiction. Rather, they are saying that the biology is only one aspect of the story. The importance of drugs (and other stop-smoking aids like CBT), and the difficulty of quitting, is systematically exaggerated by the medical literature...Of the 662 papers [about "smoking cessation" published in 2007 or 2008], 511 were studies of cessation interventions. The other 118 were mainly studies of the prevalence of smoking cessation in whole or special populations. Of the intervention papers, 467 (91.4%) reported the effects of assisted cessation and 44 (8.6%) described the impact of unassisted cessation (Figure 1).... Of the papers describing cessation trends, correlates, and predictors in populations, only 13 (11%) contained any data on unassisted cessation.And although pharmaceutical industry funding of research plays a part in this, the fact that medical science tends to focus on treatments rather than on untreated individuals is unsurprising since this is fundamentally how science works:Most tobacco control research is undertaken by individuals trained in positivist scientific traditions. Hierarchies of evidence give experimental evidence more importance than observational evidence; meta-analyses of randomized controlled trials are given the most weight. Cessation studies that focus on discrete proximal variables such as specific cessation interventions provide ‘‘harder’’ causal evidence than those that focus on distal, complex, and interactive influences that coalesce across a smoker’s lifetime to end in cessation.Overall, it's an excellent paper and well worth a read in full (it's short and it's open access). Of course, it is itself only one side of the story and many in the tobacco control community will find it controversial. But I think Chapman and MacKenzie's is a point that needs to be made, and point applies to other areas of medicine, especially, although not exclusively, to mental health. This week, British social care charity Together told us thatSix out of ten of people have had at least one time in their life where they have found it difficult to cope mentally... stress (70%), anxiety (59%) and depression (55%) were the three most common difficulties encountered by the publicWhich was not still not quite as good as rivals Turning Point who last month saidThree quarters of people in the UK experience depression occasionally or regularly yet only a third seek helpThese were opinion surveys, not real peer-reviewed science, but they might as well have been: the best available science says that if you go and ask people, 50-70% of the population report suffering at least one diagnosable DSM-IV mental disorder in their lifetime, and that the majority receive no treatment at all. This leads to papers in major journals such as this one warning that "Depression Care in the United States" is "Too Little for Too Few."But we don't know whether these tens of millions of cases of untreated "mental illness" should be treated, because there is basically no research looking at what happens to such people without treatment. On the other hand, the very fact that they aren't treated, and yet manage to hold down jobs, relationships and so forth, suggests that the situation is not so bad.Of course we must never forget that depression and anxiety can be crippling diseases, but fortunately, such cases are at least comparatively rare. By using the word "depression" to cover everything from waking-up-at-4-am-in-a-suicidal-panic-melancholia to feeling-a-bit-miserable-because-something-bad-just-happened, it's easy to forget that while clinical depression is a serious matter, feeling a bit miserable is normal and resolves without any help 99% of the time. Even though there are no published scientific studies proving this, because it's not the kind of thing scientists study.Incidentally, this issue is a good reminder that there's no one big bad conspiracy behind everything. With smoking, Big Tobacco find themselves in direct opposition to Big Pharma, like in From Dusk Till Dawn when the psychopaths fight the vampires. With depression, the people who are quickest to decry the widespread use of antidepressants often seem to be the ones who are most keen on the idea that depression is common and under-treated, perhaps because it allows them to recommend their own favorite psychotherapy. Big Pharma hands the baton to Big Couch in the race to medicalize life.Chapman S, & MacKenzie R (2010). The global research neglect of unassisted smoking cessation: causes and consequences. PLoS medicine, 7 (2) PMID: 20161722... Read more »

Chapman S, & MacKenzie R. (2010) The global research neglect of unassisted smoking cessation: causes and consequences. PLoS medicine, 7(2). PMID: 20161722

March 15, 2010
03:33 AM
46 views

The Neuroscience of Anorexia Nervosa

by Dr Shock in Dr Shock MD PhD

One of the most striking features of those suffering from anorexia nervosa is their perception of their bodies. You can put them in front of a mirror and they will still tell you they’re to fat when in fact they’re skinny. A recent publication in Nature Proceedings has an explanation.
This explanation is based on the [...]

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Riva, Guiseppe. (2010) Neuroscience and Eating Disorders: The role of the medial-temporal lobe. Nature Proceedings. info:/

March 14, 2010
02:59 PM
42 views

The Cocaine Conundrum

by Dirk Hanson in Addiction Inbox

Effective treatment remains elusive.
For addiction to cocaine, amphetamine, and other stimulants, the treatment picture has been complicated by the lack of any truly significant anti-craving medications. (See post, “No Pill for Stimulant Addiction"). The National Institute on Drug Abuse (NIDA) has yet to approve any medications for the treatment of either cocaine or amphetamine addiction.
Take the case of cocaine. Partly the problem stems from the direct effect cocaine has on dopamine transmission. The hunt for a pharmaceutical approach to blunt that effect is complicated by the problematic nature of dopamine receptors. Dopamine antagonist drugs like the antipsychotic drug haloperidol do not always block the stimulant rush. And their side effects, such as lethargy, emotional blunting, and tardive dyskinesia, make them unsuitable for ongoing addiction therapy. Conversely, some drugs that act as dopamine agonists turn out to be addictive in their own right. Many designer drugs are like that.
Because of all this, different approaches may be needed. The direct ride to the pleasure pathway provided by stimulants makes it difficult to tamper selectively with their effects. An antibody that would reduce cocaine consumption and sop up cocaine molecules in the brain, a kind of vaccine against cocaine, is one approach being pursued (See post, “Cocaine Vaccine Hits Snag”).
But other avenues of attack are being exploited. Scientists in NIDA’s Intramural Research Program are testing compounds that target certain proteins known as dopamine transporters. Transporters move dopamine molecules in and out of the synaptic gap between neurons in the brain. Interfering with that transportation system is another way of altering dopamine uptake, and it represents one active avenue of approach to the treatment of cocaine addiction.
The researchers tested Benztropine Mesylate (BZT), brand name Cogentin, one of a class of drugs known as anticholinergic suppressants commonly used in the management of Parkinson’s disease. What exactly does benztropine do? It possesses both anticholinergic (acetylcholine-blocking) and antihistaminic effects. It has chemical similarities to atropine, which is used for Parkinson’s and for heart disease.
To begin with, the researchers wanted to establish that benztropine itself is non-addictive. By substituting different BZT analogs for cocaine during self-administration testing, “two of the three BZT analogs that were tested significantly reduced drug self-administration… which indicates that those BZT analogs themselves have low potential for abuse.”

Next, the cocaine-addicted rats were given different BZT analogs before they got their cocaine. “When given before rats had access to cocaine in the self-administration chambers,” the researchers reported in the Journal of Pharmacology and Experimental Therapeutics, “two BZT analogs also significantly reduced the number of times the rats would press a lever to receive cocaine.” Monoamine uptake inhibitors were used as a control. The authors conclude that “these compounds are promising candidates for the development of medications for cocaine addiction.”
Hiranita, T., Soto, P., Newman, A., & Katz, J. (2009). Assessment of Reinforcing Effects of Benztropine Analogs and Their Effects on Cocaine Self-Administration in Rats: Comparisons with Monoamine Uptake Inhibitors Journal of Pharmacology and Experimental Therapeutics, 329 (2), 677-686 DOI: 10.1124/jpet.108.145813
Photo credit: http://www.drugabuse.gov... Read more »

Hiranita, T., Soto, P., Newman, A., & Katz, J. (2009) Assessment of Reinforcing Effects of Benztropine Analogs and Their Effects on Cocaine Self-Administration in Rats: Comparisons with Monoamine Uptake Inhibitors. Journal of Pharmacology and Experimental Therapeutics, 329(2), 677-686. DOI: 10.1124/jpet.108.145813

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